Pakistan journal of pharmaceutical sciencesYuan Gao, Lei Chi, Kun Gao, Yanning Liu, Mengdan Zhou
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint swelling, pain, cartilage destruction and bone erosion. Qingteng Waifu San is an external sinomenine-containing preparation, but its site-specific transdermal response requires disease-relevant evaluation. OBJECTIVES: To compare Zusanli (ST36)-site and adjacent non-acupoint transdermal application of Qingteng Waifu San in an ovalbumin/complete Freund's adjuvant-induced RA rabbit model and to evaluate formulation, neuropeptide, inflammatory, behavioural and histopathological outcomes. METHODS: Forty-eight New Zealand white rabbits were allocated into six groups (n=8 each): normal control, vehicle-only transdermal control, acupuncture, acupoint injection, ST36-site transdermal Qingteng Waifu San and adjacent non-acupoint transdermal Qingteng Waifu San. Gel appearance, pH, viscosity, spreadability, sinomenine content and high-performance liquid chromatography (HPLC) fingerprint similarity were assessed. Substance P (SP), calcitonin gene-related peptide (CGRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 beta (IL-1beta) were measured by enzyme-linked immunosorbent assay (ELISA). SP and CGRP messenger RNA (mRNA) were analysed by real-time polymerase chain reaction (PCR). Arthritis score, paw volume, mechanical withdrawal threshold and histopathological scores were assessed. RESULTS: The vehicle-only group showed RA-related changes compared with normal controls. ST36-site Qingteng Waifu San reduced arthritis score, paw volume, serum cytokines and histopathological injury scores and improved mechanical withdrawal threshold compared with vehicle-only control. SP and CGRP levels were higher after ST36 application than after adjacent non-acupoint application, indicating site-dependent neurocutaneous modulation. CONCLUSION: ST36-site transdermal Qingteng Waifu San produced stronger neuropeptide modulation and more favourable RA-related outcome profiles than adjacent non-acupoint application.
Journal of visualized experiments : JoVEMinjie Wang, Yifei Xu, Yuwen Zhang, Kangjing Wei, Haojing Wang, Yi Zhang, Hao Xu, Liqun Yang, Huashun Cui
Osteoarthritis is a chronic degenerative joint disease that commonly affects the knee and causes pain, swelling, stiffness, and functional limitation. Synovial inflammation and changes in periarticular muscles contribute to disease initiation and progression. Clinical evidence suggests that electroacupuncture may alleviate local inflammation and modulate cartilage metabolism. In this study, knee osteoarthritis was induced in mice by surgical destabilization of the medial meniscus. Outcomes were assessed using a multimodal protocol comprising the rotarod test, ultrasound, infrared thermography, magnetic resonance imaging, and histological staining. Joint cavity volume and skin temperature were monitored longitudinally, and endpoint magnetic resonance imaging and Safranin O-Fast Green staining were used to assess periarticular muscle signal changes and cartilage pathology. Electroacupuncture was associated with improved motor performance, reduced joint swelling, higher local skin temperature, less pronounced periarticular muscle signal changes on magnetic resonance images, and lower cartilage degeneration scores. These findings support the use of this multimodal protocol to assess electroacupuncture-associated outcomes in a preclinical mouse model.
Journal of visualized experiments : JoVEZhiqiang Huang, Bo Wang, Zhen Chen, Aiping Wang, Longhai Wang
Acute ischemic stroke is accompanied by systemic inflammation and intestinal microbial disturbance. This single-center, assessor-blinded randomized controlled trial tested whether standardized acupuncture plus modified Xiaoxuming Decoction, added to standard care, improved early neurological recovery and was associated with predefined gut and inflammatory biomarkers. Adults with imaging-confirmed acute ischemic stroke within 72 h and a National Institutes of Health Stroke Scale (NIHSS) score of 4-15 were randomized 1:1 to standard care or the combined intervention for 28 days, with 64 participants per group. The primary endpoint was day-28 NIHSS adjusted for baseline NIHSS, age, sex, reperfusion therapy, and onset-to-randomization time, with missing outcomes handled by 30-fold multiple imputation. Secondary and exploratory outcomes included the Barthel Index, day-90 modified Rankin Scale (mRS), adverse events, inflammatory markers, lipopolysaccharide (LPS), fecal microbial diversity, selected genera, and short-chain fatty acids. Multiple imputation analysis estimated a lower day-28 NIHSS score in the intervention group (adjusted difference: -1.30 points; 95% confidence interval: -2.36 to -0.24; P = 0.017). Day-28 Barthel Index was higher, whereas day-90 NIHSS, Barthel Index, and observed mRS 0-2 did not differ significantly. At day 28, the intervention group had higher Shannon diversity and fecal butyrate and lower interleukin-6 and LPS. Participant-level changes in butyrate, interleukin-6, LPS, and Shannon diversity were not significantly associated with NIHSS change; therefore, mediation analysis was not performed. No intervention-related serious adverse event was identified. The combined intervention was associated with modest early neurological improvement and selected biomarker differences, but the biological findings are exploratory and do not establish a causal brain-gut pathway.
Neurochemical researchTian Ma, Huating Zhou, Yabo Liu, Xianglin Cheng, Ming Li
Global population aging leads to a growing clinical demand for interventions against age-related cognitive decline (ARCD), including mild cognitive impairment (MCI, termed senescence-associated cognitive impairment [SACI] in this review)-a prodromal pathological stage preceding Alzheimer's disease (AD) and vascular dementia. Chronic microglia-mediated neuroinflammation, predominantly triggered by excessive NLRP3 inflammasome activation, acts as a key upstream mediator of hippocampal neuronal injury and gradual cognitive decline in preclinical aging models.Manual acupuncture and electroacupuncture (EA) exert reproducible neuroprotective effects against cognitive deficits, yet a comprehensive, multi-layered regulatory framework unifying NLRP3-centered molecular mechanisms of acupuncture remains absent from current literature. This review systematically summarizes NLRP3‑dependent pathological cascades in SACI and outlines four synergistic signaling axes through which acupuncture may modulate excessive NLRP3‑dependent inflammatory responses to potentially alleviate neurotoxic inflammatory injury.Persistent overactivation of the NLRP3 inflammasome triggers self-amplifying inflammatory feedback cycles in hippocampal tissue through four interrelated pathological processes: impaired autophagic clearance, disrupted mitochondrial homeostasis, persistent endoplasmic reticulum (ER) stress, and caspase-1/GSDMD-mediated neuronal pyroptosis.Acupuncture counteracts NLRP3-dependent neural injury through synergistic multi-target modulation: (1) activation of AMPK/mTOR signaling to restore defective autophagy; (2) suppression of the ROS-TXNIP cascade to block NLRP3 transcriptional priming and protein oligomerization; (3) phenotypic reprogramming of microglia from pro-inflammatory M1 toward anti-inflammatory M2 states; (4) inhibition of pyroptotic execution by blunting caspase-1 maturation and GSDMD proteolytic cleavage. Collectively, available pre‑clinical evidence suggests these signaling axes constitute a bidirectionally‑interconnected hypothetical protective network that may mitigate chronic neuroinflammation.A meta analysis integrating nine eligible randomized controlled trials (published 2015-2025) involving 614 participants was performed. After subject dropout, 599 participants completed the studies. Pooled analyses of heterogeneous acupuncture/electroacupuncture RCTs revealed that intervention was associated with short‑term improvements in MoCA and MMSE scores and reduction in peripheral pro‑inflammatory cytokine IL‑6. Pooled effect sizes were moderately larger in MCI subgroups compared with patients with early AD. Nevertheless, substantial methodological heterogeneity existed across included trials, and these short term observational findings cannot confirm durable disease modifying benefits.Severe methodological heterogeneity across existing trials-including inconsistent acupoint prescriptions, divergent EA stimulation parameters, and variable treatment cycles-impairs cross-study comparability and translational reproducibility. Herein, we synthesize high‑quality preclinical and clinical evidence to propose a provisional consensus‑oriented translational reference protocol for electroacupuncture, intended for standardized mechanistic research rather than routine clinical intervention.Collectively, the NLRP3 inflammasome constitutes a tractable therapeutic target for acupuncture-mediated SACI intervention. Acupuncture exerts pleiotropic neuroprotection by dampening NLRP3-dependent neuroinflammation, alongside complementary NLRP3-independent regulatory pathways. This review‑meta‑analysis provides preliminary translational theoretical evidence for a provisional electroacupuncture intervention framework targeting NLRP3‑mediated neuroinflammation in MCI and early‑AD. Future high‑quality, multi‑center RCTs are warranted to validate these preliminary findings.
MedicineYaheng Zhao, Xiaochuan Zhu, Lei Xie, Dongyi Yang, Jiabin Wang, Yangyang Liu, Tao Wu, Renyi Qian
BACKGROUND: Lower-extremity motor impairment after stroke is a major determinant of mobility limitation and persistent disability. Acupuncture is frequently used as an adjunct to conventional rehabilitation, but the magnitude and consistency of its effects on lower-limb recovery remain uncertain. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to December 31, 2025, without language restrictions. Randomized controlled trials evaluating needle-based acupuncture for poststroke lower-limb recovery were included. Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized trials version 2.0, and the certainty of evidence for the main outcomes was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Meta-analyses were conducted in Stata 18.0 using random-effects models, and treatment effects for continuous outcomes were pooled as standardized mean differences (SMDs) with Hedges g correction and 95% confidence intervals (CIs). Because fewer than 10 studies contributed to each outcome, formal funnel-plot asymmetry tests, including Egger test, were not performed; publication bias was considered qualitatively. RESULTS: Six trials met the inclusion criteria. Acupuncture was associated with improved lower-extremity motor function, as measured by the Fugl-Meyer Assessment Lower Extremity (SMD = 0.51, 95% CI = 0.32-0.71; I2 = 53.9%; low certainty). Balance assessed by the Berg Balance Scale also favored acupuncture but showed substantial heterogeneity (SMD = 0.96, 95% CI = 0.35-1.56; I2 = 91.5%; very low certainty). The Modified Barthel Index did not demonstrate a statistically significant benefit (SMD = 0.26, 95% CI = 0.16-0.68; I2 = 86.3%; very low certainty). The high heterogeneity for Berg Balance Scale and Modified Barthel Index indicates that these pooled estimates should be interpreted cautiously. CONCLUSION: Acupuncture may provide low-certainty incremental improvements in poststroke lower-extremity motor impairment. Evidence for balance and activities of daily living remains very uncertain because of substantial heterogeneity, limited sample size, and variability in acupuncture protocols and control conditions. Larger, prospectively registered, methodologically rigorous trials with standardized protocols, comparable rehabilitation dose, and clinically interpretable outcome reporting are needed.
This retrospective cohort study evaluated the clinical efficacy of adjunctive moxibustion combined with detoxification enema in patients with chronic kidney disease (CKD). Clinical data were retrospectively collected from patients with CKD treated between January 2020 and May 2024. All patients received losartan potassium (50 mg once daily) and general supportive care. The treatment group additionally received moxibustion combined with detoxification enema. Outcomes were assessed at baseline and after 60 days. The primary outcome was the change in measured creatinine clearance (Ccr), with renal function parameters and traditional Chinese medicine (TCM) symptom scores also evaluated. Ccr increased from 24.38 ± 7.21 mL/min/1.73 m2 to 32.16 ± 5.68 mL/min/1.73 m2 in the treatment group and from 26.15 ± 8.04 mL/min/1.73 m2 to 29.86 ± 6.29 mL/min/1.73 m2 in the comparison group. The baseline-adjusted between-group difference in post-treatment Ccr was 2.29 mL/min/1.73 m2 (95% CI, 0.31-4.27; p = 0.024), favoring the treatment group. Serum creatinine, blood urea nitrogen, uric acid, and TCM symptom scores also decreased after treatment. Adjunctive moxibustion, combined with a detoxification enema, was associated with improved short-term renal function and reduced TCM symptom scores. Prospective studies are needed to validate these findings.
Pakistan journal of pharmaceutical sciencesJiali Lou, Guoli Zhang, Wei Zhang, Ling Ye
BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is a medical emergency that can significantly impact patients' quality of life, often accompanied by anxiety and depression. Although pharmacotherapy is a common treatment, its effectiveness in improving both auditory and psychological outcomes remains limited. Acupuncture, especially electroacupuncture (EA), has shown potential in treating SSNHL and related affective disorders, but its adjunctive role with pharmacotherapy needs further investigation. OBJECTIVES: This randomized controlled trial aimed to evaluate the incremental benefits of adding EA to standard pharmacotherapy on audiological and psychological outcomes in patients with SSNHL accompanied by anxiety or depression. METHODS: A randomized controlled trial was conducted involving 78 SSNHL patients, divided equally into two groups: P group (n=39) and EA+P group (n=39). The EA+P group received additional EA therapy for 7 days besides the pharmacological treatments. Baseline demographics, pure tone audiometric thresholds (0.25, 0.5, 1, 2, 4, 8 kHz) and psychological scores (HAMD, HAMA) were recorded. Pre-treatment and post-treatment assessments were performed to evaluate changes in hearing thresholds and mental health outcomes. RESULTS: The EA+P group showed significant improvements at all frequencies (p < 0.001). Hearing gain was significantly greater in the EA+P group across all frequencies (p ≤ 0.044). Besides, the EA+P group demonstrated significant reductions in HAMD and HAMA scores (p < 0.001), whereas the P group showed no significant changes (p ≥ 0.051). CONCLUSIONS: Combined EA+P therapy significantly improves hearing recovery and reduces psychological symptom in SSNHL patients with anxiety and depression compared to drug treatment alone. This suggests a synergistic benefit of integrating acupuncture with conventional treatment.
Approximately 44% of cancer patients experience pain, with over 50% affected in advanced stages. Opioid therapy, though standard, carries significant side effects. Acupuncture, a traditional Chinese therapy, has shown potential in relieving cancer pain with minimal adverse reactions. This study used bibliometric methods to identify research hotspots and frontiers in acupuncture for cancer pain. Publications (2010-2025) were retrieved from the Web of Science Core Collection, PubMed, and Scopus. CiteSpace 6.4.R1 and VOSviewer 1.6.20 were used for bibliometric and thematic analysis, examining countries, institutions, authors, journals, co-cited references, and keywords. The literature selection process was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A total of 2,139 publications were included, showing an overall increasing trend. China led in publication volume; Memorial Sloan Kettering Cancer Center (MSK) was the most productive institution; J. Mao was the most productive author; and J Clin Oncol was the most cited journal. Core keywords included "acupuncture", "breast cancer", "pain", "quality of life", "management", "cancer pain", and "electroacupuncture". Cluster analysis generated 15 thematic clusters. Emerging themes included acupoint stimulation, complementary therapies, symptom management, integrative medicine, and clinical evaluation. This study maps 16-year trends in acupuncture for cancer pain, revealing collaborations, hotspots, and emerging directions to guide future research.
Zhongguo gu shang = China journal of orthopaedics and traumatologyMinglan Xu, Jun Shen, Pengfei Sun, Jianye Wang, Chi Zhao, Bingxin Kang, Xiaoxue Hu, Lianbo Xiao
OBJECTIVE: To explore clinical efficacy of applying giant needle electroacupuncture at different times in improving pain and joint function after total knee arthroplasty(TKA). METHODS: A total of 120 patients who underwent TKA from July 2022 to March 2023 were included. They were divided into preoperative electro-acupuncture group, postoperative electro-acupuncture group, and control group according to different intervention times of electro-acupuncture, and 38 patients in each group, 2 patients from each group were dropped out, resulting in a final inclusion of 114 patients. In preoperative electro-acupuncture group, there were 7 males and 31 females;aged from 60 to 80 years old with an average of (72.0±5.8) years old;electro-acupuncture was performed on Weishu acupoint (ST32), Zusanli acupoint (ST36), Yinlingquan acupoint (SP9), and Yanglingquan acupoint (GB34) of non-operated lower limbs at 1 day before operation, 30 min before anesthesia induction, and 1 to 3 days after operation. In postoperative electro-acupuncture group, there were 9 males and 29 females;aged from 60 to 80 years old with average of (71.6±6.7) years old;the same acupuncture points and parameters were treated 1 to 3 days after operation. In control group, there were 6 males and 32 females;aged from 60 to 80 years old with an average of (71.6±7.1) years old;and were received pseudo-electroacupuncture treatment. Pain was scored at rest and during movement respectively before operation and 4 to 7 days after operation by using numerical rating scale at rest (NRSR) and numerical rating scale with movement (NRSM), joint function was evaluated by active range of motion (AROM) of knee joint, Hospital for Special Surgery(HSS) knee score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: A total of 114 patients were followed up, with the follow-up period being 7 days after operation. There were no statistically significant differences in preoperative NRSR, NRSM, AROM, HSS, and WOMAC scores among three groups (P>0.05). There were statistically significant differences among three groups of NRSR and NRSM scores on the 4th to 7th day after operation (P<0.05). The comparison of AROM among three groups on the 7th day after operation showed statistically significant difference (P<0.05), while there was no statistically significant difference when comparing the data from 4 to 6 days after operation (P>0.05). The comparisons of HSS and WOMAC scores on the 7th day after operation among three groups showed statistically significant differences (P<0.05). NRSR scores of pre-electroacupuncture group on the 4th to 6th days after operation were 2.0(1.0, 2.3), 1.0(1.0, 2.0), and 1.0(1.0, 2.0) respectively, which were lower than those of post-electroacupuncture group 3.0(2.0, 4.0), 2.0(1.0, 3.0), 2.0(1.0, 2.0), and the differences were statistically significant (P<0.05). NRSM of preoperative electroacupuncture group on the 4th to 5th day after operation were 3.0(2.0, 3.0) and 2.0(1.0, 2.0), which were lower than those of postoperative electroacupuncture group 4.0(3.0, 5.0) and 3.0(2.0, 3.0), and the differences were statistically significant (P<0.05). HSS score of pre-electroacupuncture group on the 7th day after operation was (76.22±3.51), which was higher than that of post-electroacupuncture group (71.54±6.36), and the difference was statistically significant (P<0.05). WOMAC score of pre-electroacupuncture group on the 7th day after operation was(19.84±3.61), which was lower than that of post-electroacupuncture group (22.37±3.81), and the difference was statistically significant (P<0.05). CONCLUSION: The application giant needle electroacupuncture before operation could better alleviate acute pain after TKA and improve function of knee joint.
This paper systematically elaborates the theories of stress, biological resilience and hormesis. Mild low-dose stress induces organismic overcompensation via preconditioning, activates nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant, autophagy, DNA repair and other pathways, and presents an inverted U-shaped biphasic dose-response relationship. Preconditioning is categorized into local and remote types, which exerts long-term protective effects on systemic organs via metabolic reprogramming as well as neuro-humoral and immune pathways, with 2 distinct protective time windows (early and delayed). Numerous clinical trials have validated that remote ischemic preconditioning improves the prognosis of organ transplantation, stroke, hypertension and other diseases, yet its clinical application is limited by the requirement to predict injuries in advance. It proposes that somatic stimulation therapies including acupuncture, scraping and cupping act as mild stress-like interventions that fully conform to the six core characteristics of hormesis. By regulating oxidative stress, inflammatory response, mitochondrial function and DNA repair pathways, these therapies elevate systemic biological resilience, consistent with the evolutionary law that "mild stress confers benefits" and the traditional Chinese medicine health-preserving philosophy of tempering vitality through hardship as recorded in ancient texts. Acupuncture can be applied to perioperative care, chronic disorders, neurological diseases and full-life-cycle health management. Nevertheless, current research on acupuncture modulating resilience-related pathways remains insufficient, and in-depth exploration of its underlying basic mechanisms and clinical translation is still warranted.
OBJECTIVES: To analyze the characteristics of acupoint selection and stimulation parameters in randomized controlled trials (RCTs) of electroacupuncture for motor dysfunction after ischemic stroke. METHODS: The search was conducted in Chinese and English Databases, including China National Knowledge Infrastructure (CNKI), Wanfang, VIP, China Biomedical Literature Database, PubMed, Cochrane Library, Web of Science, and Embase, from the inceptions of these databases to December 31, 2025. RCTs of electroacupuncture for motor dysfunction after ischemic stroke in patients were included. Data on participant characteristics, the location or type of motor dysfunction, acupoint selection, and electroacupuncture stimulation parameters were extracted. Descriptive statistics and frequency analysis were used to summarize the distribution and characteristics of acupoints and stimulation parameters. Methodological quality assessment was performed to evaluate the included studies, and association rule analysis, hierarchical clustering, and network visualization were applied to identify structural patterns of high-frequency acupoint combinations. RESULTS: A total of 208 RCTs were included, involving 192 acupoints with a total use frequency of 1948. The main high-frequency acupoints were Quchi (LI11), Zusanli (ST36), Hegu (LI4), Waiguan (TE5), Jianyu (LI15), Yanglingquan (GB34), Shousanli (LI10) and Sanyinjiao (SP6). Acupoint selection varied to some extent in accordance with the location or type of motor dysfunction. For motor dysfunction in the upper limbs, Quchi (LI11), Hegu (LI4), Waiguan (TE5), Shousanli (LI10) and Jianyu (LI15) were commonly used, whereas for that in the lower limbs and feet, Zusanli (ST36), Yanglingquan (GB34), Sanyinjiao (SP6), Taichong (LR3) and Jiexi (ST41) were frequently selected. Association rule and cluster analysis suggested that the core acupoint group was primarily composed of Quchi (LI11), Hegu (LI4), Waiguan (TE5), LI10, and LI15 for the motor impairment of upper limbs；that for the motor impairment of lower limbs included ST36, GB34, SP6, ST41 and Xuanzhong (GB39). Regarding stimulation parameters of electroacupuncture, the low frequency and its variants were predominated, while dense-disperse and continuous waves were the common waveform types；current intensity and pulse width were mostly depended on "patient's tolerance" or "mild local muscle twitching". The duration of each treatment session was 30 minutes, treatment schedules were reported as once daily, 5 or 6 times per week, and the treatment course was ranged from 2 to 4 weeks. CONCLUSIONS: Among the included RCTs of electroacupuncture for motor dysfunction after ischemic stroke, acupoint selection is characterized as a certain of centrality, stability and diversity. The stimulation parameters of electroacupuncture exhibit significant heterogeneity and are not reported in accordance with the relevant guidelines. In the future, based on the clarification of different functional subtypes, it needs to enhance the quantification and standardized reporting of the intervention parameters of electroacupuncture, so as to improve inter-study comparability and protocol reproducibility.
Zhen ci yan jiu = Acupuncture researchWeili Dang, Lüyuan Liang, Yuxin Li, Xianghan Tan, Jialei Cao, Zhiyao Li, Saidan Liu, Bingxiang Ma
OBJECTIVES: To investigate the ameliorative effect of acupuncture at "Neiguan" (PC6) on behavioral deficits, hippocampal neuronal damage, and neuroinflammation in young rats with valproic acid (VPA)- induced autism spectrum disorder (ASD). METHODS: Pregnant SD rats were randomly divided into a control group and a model group. The ASD model was established by a single intraperitoneal injection of VPA (600 mg/kg) on gestational day 12.5. After birth, the offspring young rats were then randomly divided into control (CON), ASD model (model), sham-acupuncture (ASD+sham-Acu), acupuncture (ASD+Acu), solvent (DMSO) control (ASD+DMSO), and positive drug bumetanide (ASD+Bu) groups (n=9 in each group). Manual acupuncture (uniform reinforcing-reducing manipulation) was applied to bilateral PC6 of newborn rats for 30 min, once daily, 6 d a week, for 15 d (from the 7th day to the 21st day after birth). After acupuncture intervention, behavioral tests including the Morris water maze test, three-chamber social test, and self-grooming test were conducted. The hippocampal tissue was collected for observing changes of neuronal morphology and dendritic spine density by using hematoxylin-eosin and Golgi staining. The expression levels of synapse-related proteins postsynaptic density protein 95 (PSD95), glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT) and pyroptosis-related proteins NOD-like receptor protein 3 (NLRP3), gasdermin domain-N-terminal (GSDMD-NT) and cleaved Caspase-1 in the hippocampal tissue were detected by Western blot. The levels of hippocampal interleukin (IL)-1β, IL-18 and activity of LDH were measured by enzyme-linked immunosorbent assay. The level of hippocampal reactive oxygen species (ROS) were detected by using commercial kits. The activity of hippocampal Iba1-positive cell (microglia) was assessed by immunofluorescence staining, and the cell apoptosis was detected by TdT-mediated dUTP nick-end labeling staining. RESULTS: Compared with the CON group, the model group showed a significant increase in the escape latency of water maze test, self-grooming times, LDH activity, ROS level, IL-1β and IL-18 contents, expression of PSD95, NLRP3, ratios of GSDMD-NT/GSDMD and cleaved Caspase-1/pro-Caspase-1, number of Iba1-positive cells and the apoptosis rate (P<0.01, P<0.001), and a considerable decrease in the body mass, number of platform crossings and time spent in the target quadrant, social index and social preference, number of dendritic spine, and the expressions of GAD67 and VGAT proteins (P<0.05, P<0.01, P<0.001). In comparison with the model group, both the increased and decreased levels of all the indexes mentioned above were reversed in the ASD+Acu and ASD+Bu groups (P<0.05, P<0.01, P<0.001), and the effects of ASD+Acu were evidently superior to those of ASD+Bu in up-regulating the expressions of GAD67 and VGAT proteins (P<0.05), but inferior to those of ASD+Bu in shortening the escape latency, reducing ROS level, and down-regulating the protein expressions of PSD95 and NLRP3, ratio of cleaved Caspase-1/pro-Caspase-1, and apoptosis rate (P<0.05, P<0.01, P<0.001). The effects of acupuncture were evidently better than those of the sham acupuncture in increasing the body mass and number of platform crossings, shortening the escape latency, prolonging the time spent in the target quadrant, increasing the social index and social preference, reducing the self-grooming times, elevating the number of dendritic spine, and the expressions of GAD67 and VGAT proteins (P<0.05, P<0.01, P<0.001), and in down-regulating the LDH activity and ROS levels, IL-1β and IL-18 contents, and the expressions of PSD95 and NLRP3, ratios of GSDMD-NT/GSDMD and cleaved Caspase-1/pro-Caspase-1, Iba1-positive cell number, and the apoptosis rate (P<0.05, P<0.01, P<0.001). Similarly, in comparison with the ASD+DMSO group, the ASD+Bu group showed a significant improvement in the aforementioned behavioral and molecular biological indexes (P<0.05, P<0.01, P<0.001). CONCLUSIONS: Acupuncture at PC6 can improve social deficits, repetitive stereotyped behavior and cognitive impairment in VPA-induced ASD-like young rats, which may be related to its functions in alleviating hippocampal neuronal damage, regulating the balance of synaptic proteins, and inhibiting oxidative stress and NLRP3 inflammasome-mediated neuroinflammation.
Zhen ci yan jiu = Acupuncture researchHui Wang, Shuqing Li, Luyu Chai, Guihua Deng, Xu Zhou
OBJECTIVES: To evaluate the effectiveness, safety and compliance of heat-sensitive moxibustion self-management in community patients with essential hypertension. METHODS: A total of 120 patients with essential hypertension were recruited from three communities and randomly assigned at a 1∶1 ratio to either the intervention group (heat-sensitive moxibustion self-management combined with original antihypertensive regimen) or the control group (original antihypertensive regimen alone). In the intervention group, heat-sensitive moxibustion was applied to one main acupoint with the strongest moxibustion sensation selected from three main acupoints (Yongquan［KI1］, Baihui［GV20］, Shenque［CV8］) and one adjunct acupoint with the strongest moxibustion sensation selected from five adjunct acupoints (Quchi［LI11］, Zusanli［ST36］, Hegu［LI4］, Taichong［LR3］, Dazhui［GV14］). The treatment lasted approximately 30 minutes once daily, with flexible adjustment of frequency allowed. The intervention and follow-up period lasted 6 months. The primary outcome was the reduction in systolic blood pressure. Secondary outcomes included the reduction in diastolic blood pressure, antihypertensive effective rate, changes in antihypertensive medication dosage, traditional Chinese medicine (TCM) symptom score for hypertension, quality of life score measured by the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L), and incidence of new-onset cardiovascular and cerebrovascular events. Compliance with heat-sensitive moxibustion self-management and incidence of adverse events were also assessed. RESULTS: A total of 89.2% (107/120) of patients completed the 6-month follow-up. At the end of the 6-month intervention, the reduction in systolic blood pressure from baseline was significantly greater in the intervention group than in the control group (P<0.01), whereas no significant difference was observed in the change in diastolic blood pressure from baseline between the two groups. The antihypertensive effective rate was significantly higher in the intervention group than in the control group (P<0.05). The intervention group showed significantly greater improvements in the EQ-5D-5L overall health self-rating score, total TCM hypertension symptom score, and individual symptoms including headache, tinnitus and red eyes compared with the control group (P<0.01, P<0.05). All heat-sensitive moxibustion-related adverse events were mild. CONCLUSIONS: Heat-sensitive moxibustion self-management can reduce systolic blood pressure, improve antihypertensive effective rate, and alleviate hypertension-related symptoms and quality of life in community patients with essential hypertension, with favorable safety and compliance. These findings suggest that heat-sensitive moxibustion can be promoted as an adjunctive management strategy for essential hypertension in community settings.
Zhen ci yan jiu = Acupuncture researchYufei Wang, Jia Meng, Liujiao Huang
OBJECTIVES: To observe the effects of electroacupuncture (EA) intervention at different time points on cuproptosis-related proteins and Cu2+ levels in the ischemic penumbra of rats with cerebral ischemia-reperfusion injury (CIRI) after acute ischemic stroke (IS), so as to explore the mechanism by which acupuncture inhibits cuproptosis to improve neurological function in CIRI rats, as well as the therapeutic efficacy of intervention administered at different time windows. METHODS: SD rats were randomly divided into sham operation group, model group, 0 h acupuncture group, 24 h acupuncture group and 48 h acupuncture group, with 12 rats in each group. The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by Longa filament occlusion method. Rats in each EA group received 30 min of EA at "Baihui" (GV20) and "Fengfu" (GV16) at 0 h, 24 h and 48 h after reperfusion, respectively. Modified neurological severity score (mNSS) was used to evaluate the recovery of neurological deficit. 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was adopted to detect cerebral infarct volume. Colorimetric assay was performed to measure Cu2+ content in brain tissues of the ischemic penumbra. Real-time quantitative PCR and Western blot were used to detect the mRNA and protein expression of ferredoxin 1 (FDX1), dihydrolipoamide S-acetyltransferase (DLAT), lipoic acid synthetase (LIAS), and solute carrier family 31 member 1 (SLC31A1) in the ischemic penumbra. RESULTS: Compared with the sham operation group, the model group exhibited significantly elevated mNSS score, cerebral infarct volume, Cu2+ content in ischemic penumbra tissues, as well as increased mRNA and protein expression of DLAT and SLC31A1 (P<0.01)；meanwhile, the mRNA and protein expression of FDX1 and LIAS were markedly decreased (P<0.01). Compared with the model group, all acupuncture groups presented reduced mNSS score, cerebral infarct volume, Cu2+ level, together with down-regulated mRNA and protein expression of DLAT and SLC31A1 (P<0.01, P<0.05), and up-regulated mRNA and protein expression of FDX1 and LIAS (P<0.01, P<0.05). Compared with the 24 h acupuncture group and 48 h acupuncture group, the 0 h acupuncture group showed distinctly lower mNSS score, cerebral infarct volume, Cu2+ content, and weaker mRNA and protein expression of DLAT and SLC31A1 (P<0.05, P<0.01), accompanied by remarkably higher mRNA and protein expression of FDX1 and LIAS (P<0.01, P<0.05). The 24 h acupuncture group achieved better outcomes in cerebral infarct volume, Cu2+ content, and mRNA expression of DLAT, SLC31A1, FDX1 and LIAS relative to the 48 h acupuncture group (P<0.01, P<0.05). CONCLUSIONS: EA intervention can effectively suppress cuproptosis and alleviate cerebral injury in CIRI rats, and early EA intervention exerts superior efficacy in ameliorating neurological impairment after CIRI. The underlying mechanism may involve regulating the expression of FDX1, DLAT, LIAS and SLC31A1, reducing brain Cu2+ concentration, and thereby inhibiting neuronal cuproptosis.
Zhen ci yan jiu = Acupuncture researchZhaoxie Yu, Yao Wang, Yanan Li, L U Chunfeng, Junling Li, Xun Zhang, Zhipeng Feng, Feng Shen, Yanchun Wang
OBJECTIVES: To observe the effect of electroacupuncture (EA) on the cognitive ability, hypoxia-inducible factor-1 alpha (HIF-1α)/6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) signaling pathway and glycolytic function in the hippocampus of Alzheimer's disease (AD) model mice, so as to elucidate its potential mechanism underlying improvement of cognitive function. METHODS: Male APP/PS1 transgenic mice were used as the AD model and randomly divided into model, EA and EA plus dimethyloxaloylglycine (DMOG, antagonist of α-ketoglutarate cofactor and inhibitor of HIF prolylhydroxylase) groups (n=6 each). Age-matched C57BL/6J mice served as the control group (n=6). EA stimulation (2 Hz, 1 mA) was applied to bilateral "Shenshu"(BL23) and "Zusanli"(ST36), acupuncture was applied to "Baihui" (GV20) for 20 min, once every other day for 4 weeks. The mice in the EA+DMOG group was received intraperitoneal injection of DMOG (50 mg/kg) solution on the basis of EA starting from the 4th week. The mouse's cognitive function was evaluated by using Morris water maze and novel object recognition tests. Hematoxylin-eosin (H.E.) staining and immunohistochemistry were used to observe hippocampal neuronal morphology and β-amyloid (Aβ)1-42 deposition. The contents of pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA) in the hippocampal tissue were assayed using ELISA, and the activity of hippocampal hexokinase (HK) and content of lactic acid were detected using biochemical methods. Western blot was employed to detect the expression levels of hippocampal HIF-1α and PFKFB3 protein, and real-time quantitative PCR was employed to detect the expression levels of hippocampal HIF-1α, PFKFB3, HK, PKM2, and LDHA mRNAs. The immunofluorescence histochemistry technique was used to measure the fluorescence intensity of hippocampal LDHA. RESULTS: Compared with the control group, the model group showed significantly longer escape latency, fewer platform crossings and lower novel object recognition index (P<0.01). After EA intervention, the escape latency was evidently shorter, the platform crossings and the novel object recognition index were apparently increased in the EA group (P<0.01), suggesting an improvement of the recognition ability and learning-memory ability. Following administration of DMOG, the effects of EA in shortening the escape latency, and increasing the number of platform crossings and novel object recognition index were eliminated (P<0.01, P<0.05, compared with the EA group). In contrast to the control group, the model group had a considerable increase in the optical density of Aβ1-42, contents of PKM2, LDHA, lactate, and HK activity, expression levels of HIF-1α and PFKFB3 proteins and mRNAs, and HK, PKM2, LDHA mRNAs, and LDHA fluorescence density (P<0.01). Compared with the model group, the increased levels of Aβ1-42 optical density, contents of PKM2, LDHA, lactate and HK activity, expression levels of HIF-1α and PFKFB3 proteins and mRNAs, and HK, PKM2, LDHA mRNAs, and LDHA fluorescence density were all reversed in the EA group (P<0.01). In comparison with the EA group, the decreased levels of Aβ1-42 optical density, contents of PKM2, LDHA, lactate, and HK activity, expression levels of HIF-1α and PFKFB3 proteins and mRNAs, and HK, PKM2, LDHA mRNAs, and LDHA fluorescence intensity were reversed by EA+DMOG (P<0.01, P<0.05). HE staining showed swollen or disintegrated neuronal cell bodies in the hippocampal CA1 region, deepened nuclear staining and expanded intercellular space in the model group. In comparison with the model group, the EA group (not the EA+DMOG group) displayed relatively intact nuclei of neurons, mitigated swelling of cell body and reduction in the infiltration of inflammatory cells and uniform distribution of cells in the CA1 region. CONCLUSIONS: EA can significantly improve the cognitive function in AD model mice, which may be related to its function in inhibiting the hippocampal HIF-1α/PFKFB3 signaling pathway to reduce glycolytic enzyme activity and abnormal lactate accumulation.
Zhen ci yan jiu = Acupuncture researchJisheng Han, Haiting Jiang
On the occasion of the 50th anniversary of the founding of Acupuncture Research, this paper systematically reviews the milestone value of the journal in promoting the scientification, standardization, and internationalization of acupuncture-moxibustion medicine. Integrating the core research achievements of the authors' team over the past sixty-odd years-particularly the classic literature published in Acupuncture Research over the last half-century-this article deeply analyzes the development characteristics of modern acupuncture research in its transition from "empirical verification" to "mechanism-driven" science. Furthermore, it elucidates four core pathways for the high-quality development of the acupuncture research field： first, emphasizing the neurochemical principles of acupuncture analgesia to drive theoretical and technological innovation through heritage preservation； second, harnessing translational medicine as a developmental catalyst to integrate basic medicine and clinical medicine； third, spearheading the evolution of the "Clinical+X" paradigm via brain-computer interfaces； and fourth, prioritizing the standardization and internationalization of acupuncture research, while strengthening the building of multidisciplinary talent teams to enhance China's voice and leadership in the field of global acupuncture governance. Ultimately, this work provides a robust theoretical foundation and forward-looking horizons for constructing a modern acupuncture medical system with Chinese characteristics and advancing the cause of global health.
Zhen ci yan jiu = Acupuncture researchWenjing Huang, Shengyong Su, Tian Wang, Hong Su, Xinyu Huang, Xin Li, Guangmei Zheng, Lili Yin, Zhiyi Xu, Ying Huang, Gangliang Wei, Xiaoming Li
OBJECTIVES: To investigate the regulatory effect of electroacupuncture on Piezo1 protein in rats with cervical spondylotic radiculopathy (CSR) and its impact on the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathway, in order to explore the analgesic mechanism of electroacupuncture in treating CSR. METHODS: Male SD rats were randomly divided into sham-operation, model, electroacupuncture (EA), and EA+Yoda1 groups, with 10 rats in each group. The CSR model was established by a surgical procedure involving thread insertion into the vertebral canal. Rats in the EA group received electroacupuncture at bilateral "Hegu" (LI4) and "Taichong" (LR3) acupoints for 20 min per session, continuously for 7 days. Rats in the EA+Yoda1 group received an intraperitoneal injection of the Piezo1 agonist Yoda1 (1.5 mg/kg) before electroacupuncture treatment. Gait score, mechanical paw withdrawal threshold, and thermal paw withdrawal latency were measured before and after the electroacupuncture intervention. Pathological changes in the spinal cord tissue at the lesion site were observed using hematoxylin-eosin (HE) staining. The mRNA expression level of Piezo1 in the spinal cord was detected by qPCR. The expression of Piezo1 and calmodulin (CaM) in the spinal cord was detected by immunofluorescence double staining. The protein expression levels of CaM, neuronal nitric oxide synthase (nNOS), soluble guanylate cyclase (sGC), and PKG1 in the spinal cord were detected by Western blot. The content of cGMP in the spinal cord was measured by ELISA. The nitrite colorimetric method was used to determine the NO content in the spinal cord. RESULTS: Compared to the sham-operation group, the model group showed increased gait score (P<0.01), decreased mechanical withdrawal threshold, and shortened thermal withdrawal latency before intervention (P<0.01). After intervention, the model group exhibited significant increases in Piezo1 mRNA expression, Piezo1 and CaM immunofluorescence intensity and co-localization, protein expressions of CaM, nNOS, sGC and PKG1, as well as cGMP and NO contents in the spinal cord tissue (P<0.01). HE staining revealed shrunken neurons, deepened cytoplasmic staining, blurred nuclear-cytoplasmic boundaries, glial cell hyperplasia, increased cell density, and dilated microvessels with hemorrhage in the spinal cord of the model group. Compared to the model group, the electroacupuncture group showed decreased gait score (P<0.01), increased mechanical withdrawal threshold, and prolonged thermal withdrawal latency (P<0.01). Piezo1 mRNA expression, Piezo1 and CaM immunofluorescence intensity and co-localization, protein expressions of CaM, nNOS, sGC, PKG1, as well as cGMP and NO contents were all reduced (P<0.01). HE staining showed occasionally shrunken neurons in the electroacupuncture group, with reduced microvascular dilation and glial cell hyperplasia compared to the model group. Compared to the electroacupuncture group, the EA+Yoda1 group showed shortened thermal withdrawal latency (P<0.01), and increased Piezo1 mRNA expression, Piezo1 and CaM immunofluorescence intensity and co-localization, protein expressions of CaM, nNOS, sGC, PKG1, as well as cGMP and NO contents (P<0.05, P<0.01). HE staining revealed neuronal shrinkage, increased glial cell numbers, and some microvascular dilation with hemorrhage in the EA+Yoda1 group. CONCLUSIONS: Electroacupuncture can effectively alleviate pain in CSR rats, potentially by inhibiting Piezo1 protein activation and suppressing the NO/cGMP/PKG signaling pathway in the spinal cord to exert analgesic effects.
Zhen ci yan jiu = Acupuncture researchTingting Liang, Yu Zhao, Tianlang Wang, Jiahao Zhang, Xihan Wang, Xining Wang, Yifan Feng, Yue Guo, Yunxiao Liu, Yi Qu, Yanan Xue, Jidong Liu
OBJECTIVES: To clarify the pathway by which electroacupuncture (EA) at "Taichong" (LR3) and "Zusanli" (ST36) alleviates low-grade duodenal inflammation in functional dyspepsia (FD) rats via regulating the Hippo/Yes-associated protein (YAP) signaling pathway. METHODS: A total of 21 male SD rats were enrolled and randomly divided into the blank group, the model group, and the EA group (n = 7). The FD model was established through a combined induction strategy involving simultaneous administration of forced swimming, tail-clamping stimulation, and food restriction/overeating protocols, with continuous intervention lasting 21 days. Rats in the EA group received EA stimulation at LR3 and ST36, once daily for 20 min, 6 consecutive days followed by 1-day rest each course , with 2 courses administered in total. The general physical conditions and body weight of rats in each group were monitored throughout model establishment and treatment. Upon completion of intervention, the 3-h food intake, gastric emptying rate and small intestinal transit rate of rats were measured. HE staining was performed to observe pathological changes in duodenal mucosa. ELISA was adopted to detect serum content of motilin (MTL) and gastrin (GAS). Western blot was used to quantify the protein expressions of YAP, transcriptional coactivator with PDZ-binding motif (TAZ), phosphorylated (p)-YAP and p-TAZ in duodenal tissues. Immunohistochemistry was applied to determine the positive expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in duodenum. Immunofluorescence staining was conducted to detect the positive expression of Occludin and zonula occludens-1 (ZO-1) in duodenal tissues. Quantitative real-time PCR was utilized to test the mRNA expression levels of YAP, TAZ, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) in duodenum. TUNEL staining was carried out to assess the apoptotic rate of duodenal epithelial cells. RESULTS: Compared with the blank group, rats in the model group exhibited severe lethargy, manifested as narrowed eyes, curled recumbency, dry and messy fur, and loose stools；the body weight, 3-h food intake, gastric emptying rate and small intestinal transit rate were markedly decreased (P<0.05, P<0.01)；massive inflammatory infiltration was observed in the lamina propria of duodenal tissues；serum MTL and GAS concentrations were significantly reduced (P<0.01)；the protein expression ratios of p-YAP/YAP and p-TAZ/TAZ in duodenum were notably elevated (P<0.01)；the positive expression of IL-1β, IL-6 and TNF-α in duodenal tissues was up-regulated (P<0.01). The mean fluorescence intensity of Occludin and ZO-1 in duodenum was remarkably lowered (P<0.01). The mRNA level of Bax in duodenal tissues was significantly increased (P<0.01), while the mRNA expressions of YAP, TAZ and Bcl-2 were distinctly down-regulated (P<0.01). The apoptotic rate of intestinal epithelial cells was markedly higher (P<0.01). After EA intervention, relative to the model group, rats in the EA group showed improved mental state, enhanced locomotor activity, glossy fur and formed stools, the inflammatory infiltration in the duodenal lamina propria was alleviated, and all the indicators mentioned above were reversed (P<0.01, P<0.05). CONCLUSIONS: EA at LR3 and ST36 can effectively relieve symptoms of FD, improve the general physical status and suppress low-grade duodenal inflammation in FD rats. Its therapeutic mechanism may be associated with regulating the Hippo/YAP signaling pathway.
Zhen ci yan jiu = Acupuncture researchXuejia Li, Yongdan Li, Zhaolin Liu, Haiming Chen, Yuchao Chen, Huazhen Liu
OBJECTIVES: To investigate the therapeutic effect of electroacupuncture(EA) on mice with recurrent psoriasis, so as to explore its mechanism from the perspective of memory T cell differentiation and the tumor necrosis factor receptor-associated factor 2 (TRAF2)/nuclear factor-κB (NF-κB) signaling pathway. METHODS: BALB/c mice were divided into batches for establishment of recurrent psoriasis model and mechanism verification experiments. The recurrence experiment included blank control group, model group, EA group, methotrexate(MTX) group, and EA + MTX group. The verification experiment additionally set up EA + NF-κB inhibitor group and EA + NF-κB agonist group. The recurrent psoriasis model was induced by topical imiquimod (IMQ) application on the back skin. EA was applied at "Quchi" (LI11) and "Zusanli" (ST36) with sparse-dense wave, frequency of 2 Hz/30 Hz and intensity of 1 mA, once daily for 7 consecutive days, 15 min each time. Lesion changes were observed and psoriasis area and severity index (PASI) scores were evaluated. HE staining was adopted to observe histopathological alterations of lesional skin tissues. ELISA was used to detect the contents of interleukin (IL)-6, IL-17A and tumor necrosis factor α (TNF-α) in lesional skin tissues. Real-time quantitative PCR was performed to detect mRNA expressions of IL-15, C-X-C motif chemokine ligand (CXCL) 9, CXCL10 and C-X-C chemokine receptor 3 (CXCR3) in lesional skin tissue. Flow cytometry was applied to detect the proportions of CD8+ tissue-resident memory T cells (TRM) and CD4+ TRM in skin lesions. Western blot was used to test protein expression of phosphorylated NF-κB p65 (p-NF-κB p65), NF-κB p52, phosphorylated TRAF2 (p-TRAF2), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) in lesional skin tissues. RESULTS: Compared with the blank control group, the model group exhibited significantly increased PASI score, contents of IL-6, TNF-α and IL-17A, proportions of CD8+ TRM and CD4+ TRM, mRNA expressions of IL-15, CXCL9, CXCL10, CXCR3, as well as protein expressions of p-TRAF2, p-NF-κB p65 and NF-κB p52 (P<0.01, P<0.05). Compared with the model group, all above indicators were markedly reversed in the EA group and EA + MTX group (P<0.01, P<0.05, except for the proportion of CD4+ TRM). Except for the proportion of CD4+ TRM and IL-17A, the remaining indicators were significantly lower in the two EA-related groups than those in the MTX group (P<0.01, P<0.05). Compared with the EA group, the EA + MTX group showed further decreased proportion of CD8+CD103+ TRM, down-regulated mRNA expressions of CXCL9, CXCL10 and reduced p-NF-κB p65 protein expression (P<0.01, P<0.05). In verification experiments, compared with the model group, the EA group and EA + NF-κB inhibitor group presented obvious improvements in skin lesions, inflammatory factors, proportions of CD8+CD103+ TRM and CD4+ TRM, protein expressions of p-TRAF2, p-NF-κB p65, and mRNA levels of CXCL9, CXCL10, CXCR3 (P<0.01, P<0.05). Compared with the EA group, these indicators (except for PASI score) were further decreased in the EA + inhibitor group (P<0.01, P<0.05)；in the EA + agonist group, all these indicators were significantly elevated (P<0.01, P<0.05). CONCLUSIONS: EA can effectively alleviate symptoms of recurrent psoriasis. Its underlying mechanism may be related to inhibiting the activation of the TRAF2/NF-κB signaling pathway and specifically down-regulating the level of CD8+ memory T cells.
Zhen ci yan jiu = Acupuncture researchWenjing Kan, Aihong Yuan, Hudie Song, Min Ye, Jun Yang
OBJECTIVES: To investigate the regulatory effects of electroacupuncture (EA) intervention on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/forkhead box transcription factor O1 (FoxO1) signaling pathway and gluconeogenic function in liver tissue of type 2 diabetes mellitus (T2DM) model rats, so as to elucidate the possible mechanisms underlying EA improvement of blood glucose levels. METHODS: Male SD rats were fed with a high-fat diet combined with intraperitoneal injection of streptozotocin to establish T2DM model. The rats were randomly divided into model, EA, and EA + LY294002 groups, with 10 rats in each group；another 10 age-matched SD rats were selected as the control group. Rats in the EA group received EA intervention at "Zusanli" (ST36) and "Neiting" (ST44) as well as acupuncture at "Weiwanxiashu" (EX-B3), once daily for 15 min each time, 6 times a week, for 4 consecutive weeks. The EA + LY294002 group received intraperitoneal injection of the PI3K inhibitor LY294002 (10 mg/kg) in addition to the EA treatment once daily, with the same intervention period with the EA group. Random blood glucose was measured using a glucometer；body weight was measured with an electronic balance；HE staining was used to observe pathological changes in liver tissue；real-time quantitative PCR was used to detect the mRNA expression levels of PI3K, AKT, FoxO1, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase)；Western blot was used to detect the protein expression levels of PI3K, p-PI3K, AKT, p-AKT, FoxO1, PEPCK, and G6Pase. RESULTS: After treatment, compared with the control group, the model group showed significantly elevated random blood glucose levels (P<0.01), decreased body weight (P<0.01), severe liver tissue damage with enlarged hepatocytes and numerous fatty vacuoles, decreased mRNA expression levels of PI3K and AKT and reduced p-PI3K/PI3K and p-AKT/AKT protein expression ratios (P<0.01, P<0.05), and increased mRNA and protein expression levels of FoxO1, PEPCK, and G6Pase (P<0.01) in liver tissue. Compared with the model group, the EA group showed significantly decreased random blood glucose (P<0.01), increased body weight (P<0.01), improved liver pathological injury with reduced hepatocyte size and attenuated steatosis, significantly increased mRNA expression levels of PI3K and AKT and elevated p-PI3K/PI3K and p-AKT/AKT protein expression ratios (P<0.01), and decreased mRNA and protein expression levels of FoxO1, PEPCK, and G6Pase (P<0.01) in liver tissue. Compared with the EA group, the EA + LY294002 group showed elevated random blood glucose (P<0.01), decreased body weight (P<0.05), aggravated liver tissue injury, decreased mRNA expression levels of PI3K and AKT and reduced p-AKT/AKT protein expression ratio (P<0.01, P<0.05), and increased mRNA and protein expression levels of FoxO1, PEPCK, and G6Pase (P<0.01, P<0.05) in liver tissue. CONCLUSIONS: EA at EX-B3, ST36, and ST44 can significantly reduce blood glucose levels, increase body weight, and improve liver injury in T2DM rats. The underlying mechanism may involve activation of the hepatic PI3K/AKT/FoxO1 signaling pathway, which suppresses the expression of the downstream gluconeogenic key enzymes PEPCK and G6Pase, thereby reducing hepatic glucose output.
Zhen ci yan jiu = Acupuncture researchBinbin Zhou, Yongjun Chen, Yucen Xia
Depression is a complex systemic disease dominated by emotional disorders, whose occurrence and progression involve multiple pathological processes including imbalance of immune inflammatory response, disrupted metabolic homeostasis and abnormal neural plasticity. Recent studies indicate that a single mechanism cannot fully interpret the pathological characteristics of depression, and multi-system coupling dysfunction serves as a crucial biological basis. As a characteristic traditional Chinese medical therapy, acupuncture presents favorable efficacy in the prevention and treatment of depression, yet its action mechanism lacks a systematically integrated theoretical framework. Based on a systematic review of relevant studies on the antidepressant effect of acupuncture, this paper summarizes regulatory evidence of acupuncture on immune inflammation, oxidative stress, energy metabolism, neural plasticity and brain network from the immunity-metabolism-nerve coupling perspective. It mainly discusses the cross-system cascade regulation mediated by key molecular nodes and signaling pathways. Furthermore, it proposes that acupuncture may exert antidepressant effects by remodeling the dynamic balance of the immunity-metabolism-nerve network and restoring systemic homeostasis. This study aims to provide theoretical references for clarifying the systematic regulatory mechanism of acupuncture against depression and promoting its individualized clinical application.
Zhen ci yan jiu = Acupuncture researchJiaqi Chen, Wei Lin, Tao Yin, Yang Chen, Fang Zeng
Electroacupuncture (EA) shows marked clinical efficacy in the treatment of functional gastrointestinal disorders (FGIDs)； however, there is no consensus on optimal parameter selection. This review systematically summarizes recent evidence on six key EA parameters-acupoint selection, needling depth, stimulation frequency, current intensity, waveform, and stimulation duration/frequency-in the management of FGIDs. For gastric motility disorders, deep needling at Zhongwan (CV12), Zusanli (ST36), Neiguan (PC6), and Yintang (GV24+) are recommended. For intestinal dysmotility, deep needling at Tianshu (ST25), Quchi (LI11), Shangjuxu (ST37), and GV24+ are advised. Patients with functional dyspepsia or constipation may benefit from 2 Hz/100 Hz alternating frequency, intermittent waveform, and strong but tolerable current intensity with a needle retention of 20 min, once daily, 5 days per week for 4 consecutive weeks. By contrast, low-intensity stimulation is suggested for diarrhea-predominant FGIDs. Elucidating the optimal parameter combinations and their underlying mechanisms will facilitate dynamic optimization and precision-based recommendations for EA therapy, paving the way toward acupoint-technique synergy and ultimately enhancing the reliability and personalization of clinical outcomes.
Zhen ci yan jiu = Acupuncture researchYaohui Cui, Boya Chang, Huichao Xu, Haijun Wang, Laixi Ji
OBJECTIVES: To explore the mechanism by which moxibustion with seed-sized moxa cones improves colonic tissue damage by regulating the cuproptosis signaling pathway in mice with ulcerative colitis (UC). METHODS: Thirty male C57BL/6 mice were randomly and equally divided into a control group, a model group, and a seed-sized moxa cone moxibustion (moxibustion) group (n=10 per group) using a random number table. The UC model was established by feeding the mice with 3% dextran sulfate sodium (DSS) solution for 7 consecutive days. After successful establishment of the UC model, the mice of the moxibustion group received moxibustion at "Zhongwan" (CV12), bilateral "Tianshu" (ST25) and bilateral "Shangjuxu" (ST37) for 3 cones, once daily for 7 consecutive days. The disease activity index (DAI) was recorded, fecal occult blood assessed, colon length measured, and the serum contents of tumor necrosis factor α (TNF- α ), interleukin (IL)-1β, and IL-10 were determined by ELISA. Histopathological changes of the colon tissue were observed after HE staining, changes of colonic ultrastructure observed by using a transmission electron microscopy (TEM), and the mitochondrial membrane potential in the colonic epithelial cells measured after JC-1 staining. The reactive oxygen species (ROS) level was detected using flow cytometry, and the copper ion (Cu2+) content in the colon tissue was detected by colorimetry. The mRNA and protein expression levels of ferredoxin 1 (FDX1), dihydrolipoamide acetyltransferase (DLAT), dihydrolipoamide succinyltransferase (DLST), lipoic acid synthetase (LIAS), and heat-shock protein 70 (HSP70) in the colon tissue were detected by using quantitative real-time PCR and Western blot, separately. The immunofluorescence intensity of DLAT in the colon tissue was evaluated by immunofluorescence staining. RESULTS: Compared with the control group, the model group showed a significant increase in the DAI score, serum TNF-α and IL-1β contents, mitochondrial low-potential ratio, ROS level in colonic epithelial cells, Cu2+ content, and expressions of HSP70 mRNA and protein (P<0.01), and a considerable decrease in the colon length, serum IL-10, expression levels of FDX1, DLAT, DLST and LIAS mRNAs and proteins and immunofluorescence intensity of DLAT immunoactivity (P<0.01). In comparison with the model group, both the increased and decreased levels of the indexes mentioned above were all reversed in the moxibustion group (P<0.01, P<0.05). In addition, the fecal occult blood test was positive in the model group and weakly positive in the moxibustion group. Results of HE staining and TEM exhibited obvious damage of the intestinal mucosal epithelium with inflammatory cell infiltration, irregular mitochondrial morphology, varying degrees of swelling and vacuolization, and blurred or even broken and disappeared cristae structure in the model group；and alleviation in the pathological damage of colonic mucosal epithelium and inflammatory infiltration, improved internal structure of the colon epithelial cells, and reduction in the degree of mitochondrial swelling and vacuolization in the moxibustion group. CONCLUSIONS: Moxibustion with seed-sized moxa cones can alleviate symptoms and colonic tissue injury in UC mice, which may be associated with its functions in up-regulating the expressions of cuproptosis-related proteins and genes and improving mitochondrial function and oxidative stress.
Zhen ci yan jiu = Acupuncture researchRenzhen Zhang, Cui Ma, Tingting Dou, Li Li, Xuejiao Ma, Yuting Wei, Xingke Yan
Chronic pain is often accompanied by negative emotions such as anxiety, depression, and aversion, with structural and functional abnormalities in the limbic system serving as the key pathological basis for this comorbidity. Acupuncture can improve pain-related emotions by modulating multilevel neural centers within the limbic system. At the cortical level, acupuncture can restore the regulatory mechanism of the cortex over pain-related emotions by modulating the neural plasticity of the anterior cingulate cortex, medial cingulate cortex, prefrontal cortex, and insular cortex； at the subcortical level, acupuncture can act on the amygdala and hippocampus to block negative emotions induced by nociceptive information； at the diencephalic level, acupuncture can inhibit the generation of pain-related emotions by down-regulating the abnormal excitability of thalamic paraventricular nucleus neurons, thereby blocking the transmission of pain signals to the limbic system. From a hierarchical perspective of the limbic system, this review elucidated the mechanisms of acupuncture intervention in pain-related emotions, providing a theoretical foundation and reference for clinical research on acupuncture treatment of pain-related emotions.
INTRODUCTION: Knee osteoarthritis (KOA) is a prevalent chronic degenerative joint disorder that seriously affects mobility and quality of life in older adults. Pharmacological treatments such as celecoxib are commonly used for symptom relief, but their long-term use may be limited by adverse effects. Acupuncture has been widely used as a complementary non-pharmacological treatment for KOA and may help reduce pain and improve function; however, its onset of benefit may be relatively gradual. Combining acupuncture-related integrative therapy with celecoxib may provide more rapid symptom relief while potentially improving sustained clinical outcomes and reducing reliance on prolonged pharmacological treatment. This study aims to evaluate the comparative effectiveness and safety of acupuncture-related integrative therapy, celecoxib and their combination in patients with KOA in a multicentre randomised controlled trial. METHODS AND ANALYSIS: This is a multicentre, three-arm, parallel-group randomised controlled trial that will be conducted in three hospitals in Hunan Province, China. A total of 282 participants with KOA will be randomly assigned in a 1:1:1 ratio to receive acupuncture-related integrative therapy, celecoxib therapy or combined acupuncture-related integrative therapy and celecoxib for 4 weeks, with an additional 4-week follow-up period. The primary outcome is the change in Visual Analogue Scale score for activity-related knee pain from baseline to week 4. Secondary outcomes include the Western Ontario and McMaster Universities Osteoarthritis Index, clinical response rate, knee range of motion, 30-second chair-stand test, 40-metre fast-paced walk test and incidence of adverse events. Outcome assessments will be conducted at baseline, week 2, week 4 and week 8. Safety will be monitored throughout. Data will be analysed using the intention-to-treat principle. ETHICS AND DISSEMINATION: The study has been approved by the ethics committees of all centres (HN-LL-KY-2025-007-01, 2025-KY-019-01, 2025042705). The study findings will be disseminated through publication in peer-reviewed journals and presentations at national or international academic conferences. TRIAL REGISTRATION NUMBER: ITMCTR2026000093. Registered on 5 December 2025. The first participant was recruited on 27 February 2026.
BACKGROUND: Disorders of gut-brain interaction (DGBIs) affect approximately 25% of children worldwide and account for a substantial proportion of paediatric gastroenterology consultations. These conditions are associated with significant morbidity, including chronic pain, school absenteeism, anxiety and reduced quality of life. Current treatment options offer limited efficacy, particularly in paediatric populations. Acupuncture, a widely used complementary therapy, has shown promise in adult DGBIs; however, high-quality evidence in children is lacking. The Paediatric Gut-Brain Acupuncture Protocol aims to evaluate the efficacy and safety of acupuncture in paediatric patients with DGBIs. METHODS AND ANALYSIS: This randomised, participant-blinded and assessor-blinded sham-controlled trial will enrol 96 children aged 8-17 years with a diagnosis of DGBIs defined by Rome IV criteria. Participants will be randomised 1:1 to receive either standardised acupuncture or sham acupuncture one time per week for 8 weeks. The primary outcome is adequate pain relief, defined as a≥30% reduction in mean abdominal pain severity on the 11-point Numerical Rating Scale from baseline to follow-up at weeks 12-14. Secondary outcomes include change in mean abdominal pain severity, pain frequency, Rome IV diagnostic status, health-related quality of life, psychological well-being and safety. Outcomes will be assessed at baseline, weeks 4 and 8 during treatment and at post-treatment follow-up at weeks 12-14. Analyses will follow the intention-to-treat principle. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Children's Hospital of Orange County. Written informed consent and assent will be obtained from parents/guardians and participants, respectively. Findings will be disseminated through peer-reviewed publications and presentations at scientific conferences. TRIAL REGISTRATION NUMBER: NCT07435610.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in CancerHiroto Ishiki, Eriko Satomi, Hiromichi Matsuoka, Sayaka Arakawa, Naruaki Kawasaki, Yoko Horiguchi, Asuka Takahashi, Tatsuya Takagi, Shota Kobayashi, Shunsuke O…
BACKGROUND: Taxane-related chemotherapy-induced peripheral neuropathy (CIPN) is highly prevalent among breast cancer survivors and significantly impairs quality of life, yet established treatments are lacking. This study investigated the preliminary efficacy and safety of multimodal Japanese-style acupuncture and moxibustion (MJAM)-a program combining filiform needle acupuncture, non-insertive needle (Teishin) therapy, motion-style acupuncture, indirect moxibustion, hot pack application, and self-care instruction-for taxane-related CIPN. METHODS: In this single-center, single-arm study, we enrolled breast cancer survivors who had completed curative treatment for stage I-III breast cancer at least 3 months previously and who had moderate-to-severe taxane-related CIPN pain (BPI item 5 score of 4 or greater) at the time of enrollment. Participants received 12 weekly sessions of a standardized MJAM program. The primary endpoint was the change in Brief Pain Inventory (BPI) item 5 (average pain) from baseline to week 16. RESULTS: Between October 2022 and April 2024, 30 women (median age 58.0 years) were enrolled. Median time since chemotherapy completion was 2.47 years. Mean baseline BPI item 5 score was 5.3 (SD 1.7). Twenty-eight participants (93.3%) completed the treatment. Nine participants (30.0%) experienced mild (grade 1) adverse events. BPI item 5 scores significantly decreased over time. Changes from baseline were -0.1 (95%CI, -0.6 to 0.3; p = 0.56) at week 4, -0.7 (95%CI, -1.2 to -0.2; p = 0.008) at week 8, -1.1 (95%CI, -1.7 to -0.6; p = 0.0003) at week 12, and -1.2 (90%CI, -1.7 to -0.8; p < 0.0001) at week 16. CONCLUSIONS: MJAM was safe, feasible, and associated with a reduction in pain in breast cancer survivors with persistent taxane-related CIPN. A confirmatory randomized clinical trial is warranted. TRIAL REGISTRATION: UMIN-CTR UMIN000048478.
BACKGROUND: Type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) is strongly linked to disruption of cognition-supporting brain networks. Electroacupuncture (EA) has increasingly been examined as a nonpharmacological intervention targeting cognitive impairment; however, the longitudinal neurobiological patterns accompanying EA in T2DACD have not been fully characterized. In this exploratory pilot study, we evaluated alterations in resting-state functional connectivity (RSFC) across hippocampal subregions and default mode network (DMN) nodes in individuals with T2DACD. METHODS: For this exploratory, open-label, non-randomized, uncontrolled pilot investigation, we enrolled 20 individuals with T2DACD and 26 healthy controls (HCs). Longitudinal analyses included 15 participants who had usable post-treatment data. T2DACD was defined according to clinical type 2 diabetes mellitus criteria, and a Montreal Cognitive Assessment (MoCA) score <26. Patients underwent an 8-week Adjust Zang-fu and Arouse Spirit electroacupuncture (AZASE) intervention. Cognitive, emotional, metabolic, and seed-based resting-state functional magnetic resonance imaging (rs-fMRI) outcomes were evaluated. Clinical longitudinal analyses were carried out according to protocol, whereas imaging analyses were limited to participants with usable scans after treatment. RESULTS: At baseline, individuals with T2DACD showed lower MoCA scores than HCs and had poorer executive and working-memory outcomes. Among the 15 participants with complete longitudinal neuroimaging data, MoCA scores increased from 23.27 ± 1.71 to 26.07 ± 1.53 over the intervention period. Within-group alterations were observed for Flanker-conflict reaction time and accuracy, Stroop-conflict reaction time, 1-back reaction time, Self-Rating Anxiety Scale score, and Hamilton Depression Rating Scale score. Omnibus group analyses detected significant effects for the left anterior hippocampus-left angular gyrus connection and the left posterior hippocampus-right middle occipital gyrus connection. Post-treatment scans demonstrated reduced RSFC in several hippocampal-DMN and intra-DMN connections. The association between change in left anterior hippocampus-left angular gyrus RSFC and change in Stroop-conflict performance was no longer statistically significant after Bonferroni correction. For neuroimaging outcomes, cluster-level family-wise error (FWE) correction (p < 0.05) was applied to control for multiple comparisons; clinical outcomes are reported descriptively as hypothesis-generating findings. CONCLUSIONS: In this exploratory pilot study, we identified preliminary alterations in cognitive outcomes and hippocampal-DMN connections over an 8-week EA intervention in individuals with T2DACD. In view of the small sample size and the open-label, non-randomized, uncontrolled design, the findings should be interpreted as hypothesis-generating observations rather than definitive evidence of a specific causal treatment effect. Larger controlled studies will be needed to determine whether the observed neural and behavioral alterations are reproducible and clinically meaningful in practice. CLINICAL TRIAL REGISTRATION: No: ChiCTR2000040268, https://www.chictr.org.cn/hvshowproject.html?id=76145&v=1.3.
Chronic heart failure (CHF) is a leading global cause of cardiovascular mortality, driven by autonomic dysregulation and sympathetic overactivation. While electroacupuncture (EA) exerts cardioprotective effects via central neuromodulation, its specific molecular targets within the nucleus tractus solitarius (NTS), a key autonomic integration center, remain unclear. To investigate this, the CHF rat model was established via left anterior descending coronary artery ligation. Rats received EA at bilateral HT7 acupoints for seven consecutive days. Cardiac function and myocardial injury were evaluated using echocardiography, enzyme-linked immunosorbent assays, and histological staining. NTS neural activity was assessed via c-Fos immunofluorescence and in vivo electrophysiology. Molecular mechanisms were explored utilizing quantitative proteomics and bioinformatics, with core targets verified via quantitative PCR and Western blotting. EA improved left ventricular ejection fraction, mitigated myocardial fibrosis, and reduced serum heart failure markers. Concurrently, EA restored spontaneous neuronal firing rates, local field potential energy, and c-Fos expression within the NTS. Proteomic profiling identified 85 core differentially expressed proteins modulated by EA. Functional stratification of the 58 downregulated and 27 upregulated proteins revealed their respective participation in extracellular matrix organization and ATP-dependent chromatin remodeling. The stepwise screening approach, integrating topological network mapping, pathway enrichment, and tissue expression profiling, identified the transcription factor YY1 as a highly responsive candidate target. In vivo validation confirmed that EA upregulated YY1 expression. Overall, EA mitigated pathological cardiac remodeling and restored NTS neuronal activity. YY1 was identified as a candidate target associated with this central neuromodulation, providing molecular insight into the mechanisms underlying EA effects in CHF.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in CancerYu Song, Xinyu Zhou, Yao Luo, Hongying Guo, Ying Xia, Fang Ni, Shuang Geng
BACKGROUND: Fatigue is a prevalent symptom in lung cancer patients and adversely affects their health and quality of life. While some evidence suggests that Traditional Chinese Medicine (TCM)-based non-pharmacological therapies can effectively alleviate cancer-related fatigue (CRF), it remains unclear which therapy is most effective for managing CRF in this population. OBJECTIVE: To compare the effects of different TCM-based non-pharmacological therapies on reducing CRF in lung cancer patients. METHODS: We searched eight databases from their inception to 24 November 2025. Following literature screening, the quality of the included randomized controlled trials (RCTs) was assessed using the Cochrane Risk of Bias 2.0 tool. A network meta-analysis was conducted to evaluate the relative efficacy of the TCM-based non-pharmacological therapies. Statistical analyses were performed using STATA 18.0 software. RESULTS: A total of 32 RCTs involving eight TCM-based non-pharmacological therapies were included. The network meta-analysis results indicated that moxibustion (SMD = -2.56, 95% CI = -3.60 to -1.51) and auricular acupressure (SMD = -1.82, 95% CI = -3.61 to -0.03) were significantly more effective than usual care in improving CRF. Furthermore, moxibustion showed a significant advantage over qigong (SMD = -2.12, 95% CI = -3.58 to -0.65). CONCLUSION: Current evidence shows that moxibustion and auricular acupressure may be the most promising TCM-based non-pharmacological therapies for alleviating CRF in lung cancer patients, whereas qigong appears less effective. However, given the considerable risk of bias across the included studies, these conclusions require further validation through more rigorously designed, high-quality clinical trials.
BMJ openChen Zhou, Peisen Yuan, Jin Fang, Junhong Gao
OBJECTIVES: To evaluate the effectiveness and safety of electroacupuncture (EA), alone or combined with conventional therapy, for peripheral facial palsy. DESIGN: Systematic review and pairwise meta-analysis of randomised controlled trials. DATA SOURCES: PubMed, Embase.com, Web of Science Core Collection, the Cochrane Library, CNKI, Wanfang Data, VIP and SinoMed/CBM were searched from inception to 15 July 2026. ELIGIBILITY CRITERIA: Chinese-language or English-language randomised trials enrolling patients with peripheral facial palsy and comparing an EA-containing regimen with a control regimen were eligible when at least one prespecified clinical outcome was reported. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened studies, extracted data and assessed risk of bias using Cochrane RoB 1.0. Random-effects risk ratios (RRs) were used for cure and total effective rates, standardised mean differences (SMDs) for facial-function scales and a Mantel-Haenszel OR for adverse events. Control-comparator and end-of-treatment timing subgroups were explored, and certainty was assessed with Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: 10 trials involving 888 participants were included. Outcomes were assessed at the end of treatment: three trials within 3 weeks, three at about 1 month and four at unclear or course-based endpoints. EA-containing regimens may improve cure and total effective rates (cure: RR 1.37, 95% CI 1.13 to 1.67; I²=57.0%; total effective rate: RR 1.21, 95% CI 1.07 to 1.36; I²=81.6%). Three independent trials reported facial function (SMD 1.91, 95% CI 0.51 to 3.30; I²=94.4%). Two trials reported adverse events (OR 0.36, 95% CI 0.11 to 1.22; I²=0%). Comparator subgroup differences were exploratory because two comparator categories contained only one study each. Certainty was low for all outcomes. CONCLUSIONS: EA-containing regimens may improve short-term clinical response, but substantial heterogeneity, low-certainty evidence, variable comparators and limited follow-up preclude firm conclusions.
MedicineDa-Eun Yoon, Yoonjeong Seo, Heeyoung Moon, Shin Ho Kong, Changwoo Nam, Joowon Hwang, Karam Kim, Man-Heum Kwon, Hyun-Woo Jin, Yeonhee Ryu, In-Seon Lee, Younbyou…
In Traditional East Asian Medicine, acupoints are selected based on clinical symptoms and pattern identification. Since treatment plans target specific diseases and patterns, acupoints may be selected based on clinical indications or pattern-related considerations. This study aimed to examine the associations between acupoint use and deficiency-excess, cold-heat, and dryness-dampness pattern scores. Data were collected from the medical records of 423 outpatients with various pain disorders. Clinicians assigned semi-quantitative scores for deficiency-excess, cold-heat, and dryness-dampness on a -5 to +5 scale as part of the study assessment. Mean scores across the 3 pattern dimensions were calculated for the 30 most frequently prescribed acupoints, followed by hierarchical clustering. Two- to six-cluster solutions were compared using silhouette scores, and a five-cluster partition was retained for descriptive interpretation and further assessed for bootstrap stability. Across the 423 cases, ST36, LR3, and LI4 were the most commonly used acupoints for pain management. These 30 acupoints showed heterogeneous profiles across the 3 pattern dimensions. Hierarchical clustering provided an exploratory five-group representation, although no uniquely optimal cluster solution was identified. Commonly used acupoints showed heterogeneous profiles across clinician-assigned deficiency-excess, cold-heat, and dryness-dampness scores. These findings provide an exploratory description of pattern-related tendencies in real-world acupoint selection. Further prospective studies using standardized pattern assessment and adjustment for disease- and clinician-related factors are required to validate these associations.
Journal of visualized experiments : JoVEFengjiao Zhang, Lei Liu, Liangliang Wang, Dejun Chai, Bin Hu
Nonspecific low back pain (NLBP) is a prevalent condition associated with pain and functional limitation. This study evaluated the therapeutic efficacy and procedural feasibility of ultrasound-guided acupotomy combined with extracorporeal shock wave therapy (ESWT) compared with monotherapy approaches for NLBP. A total of 90 patients with NLBP were randomly allocated to three groups (n = 30 each). In the acupotomy group, trigger points within the lumbar erector spinae muscles were identified by palpation and treated using acupotomy. In the shock wave group, ESWT was applied to painful areas using an energy density of 0.10-0.20 mJ/mm2 at a frequency of 10 Hz. In the combined group, ESWT and acupotomy were performed sequentially under ultrasound guidance. Clinical outcomes were evaluated using the visual analog scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) scores before treatment and at a 2-month follow-up. Therapeutic efficacy was additionally assessed in accordance with the Traditional Chinese Medicine Syndrome Diagnosis and Efficacy Standard. Baseline scores were comparable among groups (p > 0.05). After treatment, the combined group demonstrated significantly lower VAS and ODI scores, higher JOA scores, and a higher overall effective rate (93.33%) compared with the monotherapy groups (p < 0.05). This study presents a structured protocol for combining ultrasound-guided acupotomy with ESWT for NLBP and demonstrates improved short-term clinical outcomes compared with monotherapy.
Clinical and experimental hypertension (New York, N.Y. : 1993)Jing Pang, Kunpeng Xia, Yihong Ma
BACKGROUND: Contemporary hypertension management increasingly emphasizes hypertension-mediated organ damage (HMOD) rather than blood pressure (BP) targets alone. Electroacupuncture (EA) has been studied mainly as a non-pharmacological antihypertensive intervention, but whether its reported organ-level effects reflect BP lowering or additional tissue-level mechanisms remains unclear. METHODS: This narrative mechanistic review synthesized preclinical and clinical literature from PubMed, Web of Science, Scopus and CNKI to organize EA-related evidence within a dual-pathway framework distinguishing BP-dependent from candidate BP-independent mechanisms across the brain, heart, kidney and vasculature. RESULTS: Preclinical evidence, mainly from spontaneously hypertensive rats, suggests that EA attenuates central sympathetic outflow, modulates brainstem-hypothalamic autonomic circuits, downregulates systemic and tissue renin-angiotensin-aldosterone system signaling, and reduces oxidative stress and inflammation. Organ-level evidence is graded moderate, and is the most developed of the four domains, for cardiac remodeling, including left ventricular hypertrophy and myocardial fibrosis; it is low-to-moderate for conduit-artery vascular changes and low for renal and cerebral effects. Across available studies, BP reduction and favorable organ-level changes occur together. No study has used BP-matched controls to isolate a BP-independent component, and no human trial with validated organ-specific HMOD endpoints was identified. CONCLUSION: Current evidence supports a hypothesis-generating dual-pathway framework in which EA-related organ effects may arise through BP-dependent mechanisms and candidate BP-independent tissue-level pathways. However, BP-independent organ protection remains unproven and requires BP-matched preclinical designs and sham-controlled human trials using validated HMOD surrogate endpoints.
Acupuncture and electroacupuncture (EA) are used for pain modulation, but the molecular events linking needling to analgesia remain incompletely defined. Purinergic signaling provides a biologically coherent framework because mechanical stimulation at acupoints releases extracellular adenosine triphosphate (ATP), which can activate P2X receptors and is subsequently metabolized into adenosine. Importantly, the receptor-level literature synthesized here is dominated by EA studies, whereas key local ATP-adenosine evidence derives from manual or traditional acupuncture. This review synthesizes evidence on purinergic mechanisms involved in acupuncture-related analgesia, with primary emphasis on EA modulation of P2X3, P2X4, and P2X7 receptors across dorsal root ganglion (DRG), spinal dorsal horn, and supraspinal cortical compartments, while distinguishing manual/traditional acupuncture evidence at the acupoint level. A narrative review with structured evidence mapping was conducted. The synthesis prioritizes mechanistic studies of manual/traditional acupuncture and EA in inflammatory, neuropathic, diabetic neuropathic, visceral, and cancer pain models, and integrates the limited available human data on acupoint adenosine signaling. Evidence is interpreted according to stimulation modality, receptor subtype, and anatomical compartment. The best-supported local pathway is the ATP-adenosine cascade: manual or traditional needling induces ATP release and CD39/CD73-mediated conversion to adenosine, activating anti-nociceptive adenosine A1 receptors (A1R). Most receptor-specific evidence, however, derives from EA. P2X3 receptors in nociceptive DRG neurons are the most consistently reproduced EA-associated target, with reduced receptor expression, membrane trafficking, and ATP-evoked currents. P2X4R-related evidence links EA analgesia with reduced spinal microglial activation, BDNF signaling, and central sensitization, but direct receptor-specific causal confirmation remains limited. P2X7R findings are compartment-specific and must be interpreted alongside EA stimulation parameters and the receptor's requirement for relatively high or sustained extracellular ATP exposure. Purinergic signaling offers a compelling mechanistic bridge between needling-based stimulation and pain relief. The receptor-level evidence is predominantly preclinical, male-biased, and EA-centred; manual acupuncture and EA should not be treated as mechanistically interchangeable. Human receptor-level studies, sex-balanced designs, standardized reporting of EA parameters, and direct causal interrogation of receptor function are needed before P2X modulation can be considered clinically validated.
OBJECTIVE: The aim of the study was to observe the changes in phosphorylated caveolin-1 (p-Cav-1) expression in the dorsal root ganglion (DRG) of rats with diabetic neuropathic pain (DNP) and to explore the interventional effect of electroacupuncture on Cav-1. METHODS: In experiment 1, DNP was induced by intraperitoneal streptozotocin (STZ). Fasting blood glucose (FBG), body weight, and paw withdrawal latency (PWL) to thermal stimuli were measured at baseline and on days 7, 14, and 21 post-STZ. p-Cav-1-positive cells in L4-L6 DRG were detected by immunofluorescence. In experiment 2, rats were divided into normal, STZ, and STZ+siRNA groups. From days 15-21, cav-1-siRNA or blank liposomes were administered intrathecally. FBG, body weight, and PWL were measured. In experiment 3, rats were divided into normal, STZ, and STZ+electroacupuncture groups. From days 15-21, electroacupuncture (2 Hz, 30 min daily) was applied at ST36 and BL60. The above indicators and p-Cav-1 expression were detected. RESULTS: In experiment 1, compared with the normal group, the DNP group showed increased FBG, decreased body weight (D7-D21), and shortened PWL (D14, D21). The number of p-Cav-1-positive neurons in DRG significantly increased in L4-L5 (D7) and L4-L6 (D14, D21). In experiment 2, after siRNA intervention, the PWL of the STZ + siRNA group was significantly prolonged compared with the DNP group. In experiment 3, after electroacupuncture intervention, the PWL of the STZ + electroacupuncture group was significantly prolonged compared with the DNP group (D21), and the expression of p-Cav-1-positive cells in DRG was significantly decreased compared with the STZ group. CONCLUSION: Upregulation of p-Cav-1 expression in DRG is involved in the development of DNP. Electroacupuncture can effectively alleviate hyperalgesia in DNP rats, and its mechanism may be related to the inhibition of p-Cav-1 expression in DRG.
Drug design, development and therapyJuan Du, Zimo Li, Shujun Chen, Xia Zheng, Yu Zhang, Xingwei Pu, Mingya Zhu, Xiang Hu
Endometriosis (EMs) is a chronic neuroinflammatory disorder prevalent in women of reproductive age characterized by heterogeneous clinical manifestations, while conventional Western therapies are limited by obvious adverse reactions and unsatisfactory long-term efficacy. In traditional Chinese medicine (TCM), endometriosis is categorized as "abdominal mass" and "dysmenorrhea", and qi stagnation and blood stasis is recognized as the core pathogenic basis. TCM exerts therapeutic effects on endometriosis mainly by suppressing NF-κB-mediated inflammatory cascades, modulating immune homeostasis, balancing sex hormone secretion and abnormal angiogenesis. Clinically, herbal compound prescriptions, acupuncture and combined TCM interventions can alleviate pelvic pain, shrink ectopic lesions and cut postoperative recurrence risks. Nevertheless, the clinical application of TCM is hindered by non-unified syndrome differentiation criteria and insufficient high-level mechanistic verification. This review concludes that TCM serves as a valuable adjunctive regimen for endometriosis management; however, standardized multi-omics mechanistic exploration, large-sample randomized controlled trials and integrated Chinese-Western therapeutic protocol optimization are urgently required to facilitate the standardized formulation and international recognition of TCM for endometriosis treatment.
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and GynaecologyWenxia Zhao, Jin Yang, Yufei Hou, Min Li
BACKGROUND: Complex Decongestive Therapy (CDT) is the non-operative standard for breast cancer-related lymphedema (BCRL), but many patients experience persistent subcutaneous stiffness, pain, and restricted mobility. This study systematically reviews the safety and clinical efficacy of Meridian Sinew Tuina (MST) protocols for BCRL. METHODS: Global and regional databases (PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP) were searched from inception to January 15, 2026, with alerts monitored through April 30, 2026. Randomised controlled trials (RCTs) evaluating MST (deep tissue mobilisation along the six-hand meridian sinew [Jingjin] lines via plucking, kneading, and pressing) were included. Two reviewers independently extracted data, evaluated risk of bias using Cochrane RoB 2, and assessed evidence certainty via GRADE using a random-effects model. RESULTS: Fifteen RCTs were included. For the primary anthropometric outcome, MST significantly reduced upper limb circumference compared to controls (SMD = 1.59; 95% CI: 1.44 to 1.74; Z = 20.81; p < 0.0001; I2=0.0%; N = 924; GRADE: Moderate certainty). The Clinical Response Efficacy Rate (≥ 30% swelling reduction and symptom relief) favoured MST (RR = 1.69; 95% CI: 1.54 to 1.87; Z = 10.62; p < 0.0001; I2=0.0%; N = 1,114; GRADE: Moderate certainty). Trial Sequential Analysis confirmed sample size sufficiency. For secondary outcomes (N = 924; GRADE: Low to Very Low certainty due to performance bias and clinical heterogeneity), MST showed favourable 3-month improvements in DASH functional scores (SMD = -1.81; 95% CI: -2.11 to -1.51; I2=45.1%), pain intensity (SMD = -2.44; 95% CI: -2.93 to -1.95; I2=50.4%), and quality of life (SMD = 1.04; 95% CI: 0.79 to 1.29; I2=0.0%). No serious adverse events occurred. CONCLUSIONS: MST protocols are associated with favourable short- and mid-term reductions in upper limb swelling. However, confidence is tempered by unblinded performance bias and control group variations. MST cannot be unconditionally recommended for standalone implementation but represents a promising, optional supportive adjunctive intervention within oncological rehabilitation.
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke AssociationJiayong Yao, Ce Zhang, Xiaohong Dai, Xueping Yu, Xiuhua Jia, Binglin Kuang, Jia Zheng, Lei Zheng, Wei Teng, Weiwei Yu, Mingyue Li, Wei Zou
BACKGROUND: Secondary brain injury following intracerebral hemorrhage (ICH) is largely driven by regulated cell death and neuroinflammation. Necroptosis, a form of programmed necrotic cell death mediated by the RIP1/RIP3/MLKL pathway, has emerged as a key contributor to tissue injury after ICH; however, effective strategies for its modulation remain limited. OBJECTIVE: This study aimed to determine whether RIP1/RIP3/MLKL-dependent necroptosis is functionally activated after ICH and to investigate whether scalp acupuncture (SA) modulates this pathway, using the necroptosis inhibitor necrostatin-1 (Nec-1) as a mechanistic comparator. METHODS: A total of 168 adult male Sprague-Dawley rats were randomly assigned to sham, ICH, SA + ICH, and Nec-1 + ICH groups. Neurological function, necroptotic cell death, ultrastructural alterations, necroptosis-related signaling molecules, inflammatory mediators, and brain edema were systematically evaluated using behavioral assessments, propidium iodide staining, immunofluorescence, transmission electron microscopy, Western blotting, RT-qPCR, ELISA, and wet/dry weight analysis. RESULTS: Following ICH, multiple independent assays consistently demonstrated marked activation of necroptosis in perihematomal brain tissue, including increased PI-positive cells, RIP1/RIP3 colocalization, mitochondrial structural disruption, and upregulation of RIP1, RIP3, MLKL, PGAM5, DRP1, and HMGB1. Both SA and Nec-1 significantly attenuated necroptosis-related signaling and were associated with improved neurological outcomes. Notably, compared with Nec-1, SA exerted stronger inhibitory effects on proinflammatory cytokine release and brain edema. CONCLUSION: These findings support a prominent role for RIP1/RIP3/MLKL-mediated necroptosis in secondary injury after ICH in male rats. SA effectively attenuates necroptosis-related signaling and associated neuroinflammation, highlighting its potential as a multimodal biological intervention. Given that only male animals were included, further studies incorporating female subjects are warranted to determine whether sex-specific differences influence necroptotic signaling or therapeutic responsiveness.
MedicineXueqin Yu, Minghua Yuan, Mengxin Yi, Hong Ding, Jun Huang, Wenbing Zou, Xiaoyan Yan
This study investigates the clinical efficacy of Knee Three Needles combined with ultra-short wave for knee osteoarthritis and its effects on different traditional Chinese medicine syndrome types. This retrospective, non-randomized cohort study enrolled 180 patients with knee osteoarthritis from June 2024 to June 2025. Patients were classified according to the rehabilitation protocols previously received into 3 groups (n = 60 each): Knee Three Needles (Group A), ultra-short wave (Group B), and combination therapy (Group C). All received basic treatment (education, exercises, and oral glucosamine hydrochloride). Group A received Knee Three Needles acupuncture (main points: bilateral Knee Eye, Liangqiu, and Xuehai; adjunct points based on syndrome). Group B received ultra-short wave therapy (nonthermal/microthermal, 20 minutes/session). Group C received both treatments. All interventions were administered once daily, with 10 sessions per course. Individual matching for age (±3 years) and body mass index (±1.5) was applied, with analysis of covariance correcting for baseline differences. Visual Analog Scale (rest/motion pain), Lysholm score, and knee range of motion (ROM) were assessed pre- and posttreatment. Baseline data were comparable among groups (P > .05). All groups showed significant posttreatment improvements in Visual Analog Scale, Lysholm score, and ROM (P < .001). Group C demonstrated significantly lower posttreatment rest pain (1.68 ± 0.95) and motion pain (2.95 ± 1.36) versus Groups A and B (P < .05), with superior pain reduction (P < .01). Lysholm score (80.26 ± 10.42) and improvement value (31.30 ± 10.68) in Group C were significantly higher than those in the other groups (P < .01). Flexion/extension improvements in Group C (18.32 ± 9.56°/5.19 ± 3.42°) also surpassed those in Groups A and B (P < .01). The total efficacy rate in Group C (93.3%) was significantly higher than that in Group A (83.3%) and that in Group B (78.3%; P < .05). Subgroup analysis revealed significantly greater Lysholm score improvements in Group C across Blood Stasis, Dampness, and Cold Predominance syndromes versus the monotherapy groups within the same syndrome types (P < .05 or P < .01). For Cold Predominance syndrome, the improvement in Group A (23.18 ± 9.24) exceeded that in Group B (18.28 ± 9.56). In this retrospective cohort, receipt of Knee Three Needles combined with ultra-short wave was associated with greater short-term improvements in pain, function, and ROM than either monotherapy. Because treatment allocation was non-randomized, these findings should be interpreted as associations rather than proof of causality or synergy.