INTRODUCTION: Radical cystectomy (RC) is the standard therapy for muscle-invasive bladder cancer (MIBC) and refractory high-risk non-muscle-invasive bladder cancer (1-3). Single-port robot-assisted radical cystectomy (RARC) offers notable minimally invasive advantages (4-6), whereas conventional transperitoneal approaches are associated with intestinal and gastrointestinal complications (7). This study evaluated an optimized extraperitoneal single-port RARC with orthotopic neobladder reconstruction for improved surgical safety and clinical outcomes. MATERIALS AND METHODS: A 57-year-old male presented with three months of intermittent painless gross hematuria. Pelvic CT revealed a bladder mass. Preoperative biopsy confirmed high-grade urothelial carcinoma with muscularis propria invasion, and the patient received gemcitabine-cisplatin neoadjuvant chemotherapy before radical surgery. Preoperative MRI identified a 3.2×2.9×2.6 cm bladder lesion without extravesical invasion or lymphadenopathy. During the procedure, the patient was placed in a supine position with buttocks elevated. A 5-cm infraumbilical single incision was made for da Vinci Xi-assisted extraperitoneal RARC, and a single-port multichannel device was deployed through the incision. Robotic instruments including a 30° endoscope, monopolar scissors, bipolar forceps, and a robotic stapler were arranged in a chopstick configuration. Via the extraperitoneal approach, we mobilized the bilateral ureters, bilateral vas deferens, and umbilical artery, dissected the bladder lateral ligaments with vascular ligation, and established a sufficient extraperitoneal working space. Bladder and prostate dissection was performed along the perivesical avascular plane, with careful protection and precise hemostasis of the dorsal venous complex. Standard pelvic lymphadenectomy was concurrently conducted during radical resection of the bladder and prostate (8). A segment of ileum was then harvested to construct an orthotopic neobladder (9), followed by anastomosis with the bilateral ureters and urethral stump. RESULTS: Operative time was 400 minutes with 200 mL blood loss and no transfusion. No perioperative complications occurred, and the patient was discharged on postoperative day 6. Pathological diagnosis was pT2aN0M0 with negative surgical margins and negative lymph nodes. The 12-month follow-up showed no tumor recurrence, normal renal function, complete daytime continence, and mild nocturnal incontinence requiring one nightly pad. CONCLUSIONS: Extraperitoneal single-port RARC with orthotopic neobladder reconstruction is a feasible minimally invasive procedure for MIBC. The optimized infraumbilical single-incision technique preserves peritoneal integrity and avoids intestinal mobilization, effectively reducing abdominal complications. It achieves reliable oncological results and improves patients' postoperative continence and quality of life.

PubMed2027

Robot-Assisted Partial Nephrectomy in a High-Complexity Renal Tumor in a Horseshoe Kidney.

International braz j urol : official journal of the Brazilian Society of UrologyMarcos Tobias-Machado, Ricardo C Brianson, John Eder Gamarra Bravo, Alcedir Raiser, Eliney Faria

INTRODUCTION: Horseshoe kidney is an uncommon congenital fusion anomaly that can make renal tumor surgery especially challenging because of altered rotation, limited mobility, variable vascular supply, and an unpredictable collecting system (1-7). This video presents a robot-assisted partial nephrectomy for a high-complexity renal tumor in this setting. CASE PRESENTATION: A 33-year-old man, with ECOG 0 and no relevant comorbidities, was diagnosed with a 7.5-cm solid renal mass in the central posterior portion of the left moiety of a horseshoe kidney. The lesion had a RENAL score of 10p. Contrast-enhanced computed tomography and three-dimensional reconstruction were used to understand the relationship between the tumor, aberrant vessels, renal hilum, and collecting system, supporting the decision to attempt nephron-sparing surgery (5, 8). Surgical technique and results: The procedure was performed through a transperitoneal robotic approach with the patient in right lateral decubitus using the Da Vinci Si platform. Port placement followed a standard renal robotic configuration, with a paramedian supraumbilical camera port, three robotic working ports along a craniocaudal lateral axis, a caudal fourth-arm port, and two medial assistant ports for suction, exposure, and support during renorrhaphy. After exposure of the horseshoe kidney and left hilar dissection, two arterial branches and one renal vein were identified. Tumor excision was performed under vascular control, with 20 minutes of warm ischemia and no collecting system opening, followed by two-layer absorbable renorrhaphy with adjunctive hemostatic agents. The operative time was 150 minutes. No transfusion, conversion, drain placement, or relevant immediate complication occurred. The urinary catheter was removed after 24 hours, and the patient was discharged 72 hours after surgery. Pathology showed clear cell renal cell carcinoma, Fuhrman grade 3, pT2N0M0, with negative surgical margins. During 12 months of oncologic follow-up, renal function remained stable and semiannual imaging showed no evidence of recurrence. Contemporary video reports have also emphasized the feasibility of advanced robotic renal surgery and complex partial nephrectomy strategies in selected patients (9, 10). CONCLUSION: In a carefully selected patient, robot-assisted partial nephrectomy supported by three-dimensional planning was feasible for a complex renal tumor in a horseshoe kidney, with negative surgical margins, preserved renal function, and no recurrence during 12 months of follow-up.

PubMed2026

[THE ECONOMIC VIEW UPON MEDICAL CARE SUPPORT OF PATIENTS UNDER MYOCARDIUM INFARCTION IN MEDICAL ORGANIZATIONS OF VARIOUS LEVEL].

Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyD V Vankov, O V Obukhova, I A Deev, M A Ivanova

The diseases of circulatory system represent one of the main problems of the population health due to corresponding high morbidity and mortality and load on health care. The purpose of the study is to evaluate direct and indirect costs of medical care under acute coronary syndrome depending on level of medical organization. The study used content-analysis, statistical and analytical methods scientific publications on the research topic, copying of data from the medical documentation of the Vologda Regional Clinical Hospital for the period 2012-2021. The significant number of publications confirm that diseases of circulatory system develop due to multitude of risk factors. Also economic and medical effectiveness of timely applied medical care of diseases of the circulatory system is proved. It is demonstrated that medical care and cardiac rehabilitation under acute coronary syndrome are the most resource-wasteful types of medical care, while prevention of development of disease allows to save human, material and financial resources. In the medium perspective, economic damage under the worst scenario of development of disease when disability is set in makes up to about 400.000 rubles and in case of death of patient, more than five million rubles. Under acute coronary syndrome, medical, social and economic efficiency of emergency medical care is higher in medical organizations of the 3rd level. However, it is more economically advantageous to implement preventive measures.

PubMed2026

[THE EVALUATION OF EFFICIENCY OF REORGANIZATION OF MEDICAL CARE UNDER DISSEMINATED SCLEROSIS ON THE BASIS OF ANALYSIS OF DYNAMICS OF TREATMENT WITH MEDICATIONS ALTERING COURSE OF DISSEMINATED SCLEROSIS].

Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyM S Cherepianskii, A V Baranov, G O Penina

The multiple sclerosis is chronic autoimmune disease with high risk of disability. The effective management of this disease directly depends on the timely prescription and escalation of treatment with medications altering course of multiple sclerosis. The key factor in optimizing medical care is organization of specialized structures. The specialized Multiple Sclerosis Clinic was opened in the Komi Republic in the beginning of 2021. The purpose of the study is to assess dynamics of key indicators of medication therapy of multiple sclerosis during 2018-2024 and to determine impact of opening of Multiple Sclerosis Clinic on these indicators using methods of statistical analysis.

PubMed2026

[THE MODERN DEMOGRAPHIC CHANGES IN THE KYRGYZ REPUBLIC].

Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyG K Kanatbekova, O A Bolbachan, D D Ibraimova

The article presents results of analysis of medical demographic indicators of the Kyrgyz Republic in 2016-2024. The study was carried out concerning dynamics of population size, natality, mortality and migration processes based on statistical data from the National Statistical Committee and the Center of E-Health Care. The regional differences in demographic trends were revealed. The high natality is specific for Southern regions, while in Northern regions its steady decreasing was fixed. It is established that COVID-19 pandemic had short-term impact on mortality growth in 2020. Despite positive natural increase, its pace is decreasing that requires elaboration of state demographic policy and mechanisms stimulating natality, population health promotion and development of regional health care infrastructure. In 2022-2023 migration flows demonstrated positive balance that reflects changes in social economic priorities of population. The main motives for migration remain low wages, limited career opportunities and uncertainty about future. The obtained results confirm necessity of systematic approach to prognostication of demographic processes and development of measures stabilizing medical demographic situation in the Republic.

PubMed2026

[THE PREVENTIVE MEASURES OF AVERTING DEVELOPMENT OF OCCUPATION DISEASES OF SAILORS IN CONDITIONS OF EXTREME TEMPERATURES].

Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyM V Botnaryuk, Y A Lepekhina

The sailors more often than other professional groups are forced to work in extreme conditions associated with heat, humidity and low temperatures (passage of tropical and northern latitudes). Therefore, they are at risk of development of various diseases and the most dangerous are cardiovascular ones. Despite taken protective measures, the number of crew members of merchant marine vessel complaining on poor well-being continues to increase, including at the expense of disorders of heart and vascular functioning. With purpose to enhance measures preventing development of cardiovascular diseases that currently are not always detected during pre-voyage medical examination and result in health deterioration and lethal outcomes, the article proposes a number of practical recommendations. It is relevant to carry out genetic examination before starting voyage in order to identify risks of development of occupational diseases in sailors older than 40 years. To equip vessel with portable cardiograph will contribute to timely detection of physiological changes in heart functioning of of crew member and will reduce possibility of occurrence of life-threatening conditions. The issuing of voluntary medical insurance program will permit to apply more in-depth diagnostics with purpose to increase possibility to detect cardiovascular diseases at early stage.

PubMed2026

[THE STRUCTURAL AND DYNAMIC CHARACTERISTICS OF THE DISEASES OF BLOOD CIRCULATION ORGANS IN THE KYRGYZ REPUBLIC].

Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyA B Dzhanaliev, N K Kasiev, M Kulzhanov

The diseases of circulatory system continue to occupy leading positions in structure of morbidity and mortality of population, remaining one of key public health problems. The purpose of the study is to investigate dynamics of primary morbidity and prevalence of diseases of circulatory system by main nosological forms among adult and adolescent population of the Kyrgyz Republic in 2018-2024. The study used official data from the Center for E-Health Care that was analyzed using retrospective, statistical and comparative analytical methods. It was found that indicators of primary morbidity and prevalence were characterized by pronounced variability with greatest increase in 2022, against the background of decrease in 2020-2021, that may be due to changes in availability of medical care in period of COVID-19 pandemic. The highest levels of morbidity and prevalence were found for hypertension, coronary heart disease and cerebrovascular diseases. Some nosologies, including myocardial infarction and other peripheral vascular diseases, demonstrated sharp increase in indicators, suggesting changes in disease detection and health care seeking behavior of population. The obtained results confirm necessity to improve system of monitoring, prevention and early detection of cardiovascular diseases, especially among high-risk groups.

PubMed2026

Dynamic evolution, prediction and patient stratification of chemotherapy-induced neutropenia in a predominantly breast cancer cohort: A decision-support study for building a bundle care strategy.

Pakistan journal of pharmaceutical sciencesShuhui Dai, Xuanhe Zhang, Zhen Qiao, Liudan Li, Litong Ye

BACKGROUND: Chemotherapy-induced neutropenia (CIN) is a common dose-limiting toxicity in patients with solid tumors, often leading to infections, treatment delays, or dose reductions. However, studies on the dynamic patterns of CIN across multiple chemotherapy cycles and their prediction remain limited. OBJECTIVES: To longitudinally observe CIN evolution across two consecutive cycles, develop a predictive model for severe CIN in cycle 2 (T2) based on cycle 1 (T1) characteristics, and classify patients by early recovery capacity to form a personalized bundle care strategy. METHODS: This single-center retrospective cohort study using electronic medical record (EMR) data enrolled 138 patients with solid tumors (89.1% breast cancer) who received ≥2 chemotherapy cycles between January 1, 2015, and January 31, 2025, at Zhuhai Maternal and Child Health Care Hospital, China. Neutrophil kinetic parameters were collected for T1 and T2. A multivariable logistic regression model predicted grade 3-4 CIN in T2 using T1 variables, with internal bootstrap validation. K-means clustering based on T1 recovery patterns identified patient subgroups. RESULTS: Severe CIN incidence decreased from 88.0% in T1 to 42.7% in T2 (p<0.001); neutrophil nadir rebounded from 0.40 × 109/L (IQR: 0.10-0.70) in cycle 1 to 1.05 × 109/L (IQR: 0.50-1.80) in cycle 2 (p<0.001). The prediction model (age, T1 nadir, T1 days to nadir, T1 recovery duration) achieved a test AUC of 0.677 and an accuracy of 78.6%. Out of the 138 total patients, 120 with complete recovery data were utilized for clustering analysis, identifying three groups: rapid (n=21), similar (n=79) and slow (n=20). The slow-recovery group exhibited significantly higher rates of febrile neutropenia (25.0% vs. 10.1% and 4.8%, p=0.043) and chemotherapy delays (35.0% vs. 15.2% and 9.5%, p=0.021). CONCLUSION: CIN severity generally improves from first to second cycle, but with substantial inter-individual heterogeneity. A T1-based prediction model combined with recovery stratification can identify high-risk patients for personalized CIN management. Further validation in diverse populations is warranted.

PubMed2026

Amyloid-Like Immunoglobulin Deposition Neuropathy.

Journal of the peripheral nervous system : JPNSChrister Sawaya, Mark Fabian, Agustín Sancho Saldaña, Chinar Osman, Robert Hadden, Haider Katifi

BACKGROUND AND AIMS: Amyloid-like immunoglobulin deposition neuropathy is a rare cause of polyneuropathy, characterised by unique clinical and histological features in combination with proteomics that distinguish it from both amyloidosis and anti-MAG neuropathy. While light microscopic findings resemble amyloidosis with 'amyloid-like deposits', they are negative for Congo-red stain and have granular ultrastructure appearances under electron microscopy, unlike the characteristic fibrillary appearance of amyloid. METHODS: We present five cases of polyneuropathy associated with IgM paraprotein, without anti-MAG antibodies, with a distinctive phenotype: predominant neuropathic pain, skin changes or neuropathic ulcers, and a progressive distal sensory neuropathy. RESULTS: All patients demonstrated an axonal sensorimotor neuropathy and histopathology of 'amyloid-like' (Congo-red negative) material with predominant granular deposition on electron microscopy consistent with a combination of heavy and light chain deposition. Skin involvement demonstrated similar histological features, but there was no evidence of renal or cardiac involvement. Most patients had treatment for their underlying haematological disorder and subsequently had no further progression in their neuropathy. DISCUSSION: Amyloid-like immunoglobulin deposition neuropathy is a slowly progressive painful axonal polyneuropathy associated with paraproteinaemia. Diagnosis is made with biopsy and electron microscopy. Treatment targets the source of the paraproteins and controls disease progression, leading to favourable survival compared to AL amyloidosis.

PubMed2026

Bis-(di-4-phenyl-benzylaminethiocarbonyl)disulfide sensitizes ABCC2/ALDH3A1 overexpressing NSCLC cells to cisplatin.

Cancer biology & therapyJolanta Kryczka, Jakub Mateusz Kryczka, Łukasz Janczewski, Sho Shimida, Andrzej Frączyk, Beata Kolesińska, Joanna Boncela, Ewa Brzeziańska-…

BACKGROUND: Lung cancer presents complex etiopathology involving a mix of genetic predispositions and environmental factors. The best treatment modality is surgical resection. However, it becomes ineffective in the advanced metastatic stage. Thus, cisplatin-based chemotherapy, though restricted by an intrinsic and/or acquired chemo-resistant phenotype, remains the first-line therapy for advanced non-small-cell cancer (NSCLC). METHODS: Various tools were used to verify the mRNA expression and protein levels of ABC and ALDH proteins in patient-derived non-small-cell lung cancer (NSCLC) samples (GSE102287, GSE43580) and cell lines A549 and NCI-H158 (including their respective cisplatin-resistant variants) to verify the cisplatin-sensitizing abilities of newly synthesized bis-(di-4-phenyl-benzylaminethiocarbonyl)disulfide-non-toxic ALDH and ABCC2 inhibitors. RESULTS: We identified significant molecular differences in the expression levels of ABCC1, ABCC5, ABCC3, ALDH7A1, and ALDH3A1. Additionally, a fairly significant patient subgroup (Z-score > 1.5), characterized by ABCC2 and ALDH3A1 overexpression, was identified. Importantly, in vitro, ABCC2 and ALDH3A1 accompany the acquisition of cisplatin resistance in A549 cells. Bis-(di-4-phenyl-benzylaminethiocarbonyl)disulfide reverses cisplatin resistance in a cisplatin-resistant variant of A549 cells (via ALDH and ABCC2 inhibition) but not in NCI-H158 cells. CONCLUSIONS: Molecular categorization of NSCLC cancer is essential for predicting therapy outcomes, enabling the use of bis-(di-4-phenyl-benzylaminethiocarbonyl)disulfide as a cisplatin therapy enhancer for NSCLC patients' subpopulation with significant ABCC2 and ALDH3A1 overexpression.

PubMed2026

Fibrinogen-like protein 2-complement C3 interaction exacerbates tubular inflammation in acute kidney injury by elevating complement C3a levels.

Renal failureWenli Wan, Qun Yang, Jiayue Li, Shun Wu, Xueqing Hu, Zhenmin Ruan, Rui Wang, Zhaoyong Zhang, Xin Geng, YuXin Zhou, Qian Lu, Hongqi Ren

Renal tubular epithelial cells are among the earliest renal parenchymal cells to be injured in the context of acute kidney injury (AKI). Numerous studies have confirmed that fibrinogen-like protein 2 (FGL2) can regulate the occurrence and development of inflammation during disease progression. We found that FGL2 expression is elevated under AKI conditions. However, the role of FGL2 in AKI remains unclear. To elucidate the role of FGL2 in AKI, we employed lentiviral and adeno-associated virus for transfection in cellular and murine models. Furthermore, by leveraging datasets from the gene expression omnibus and gene set enrichment analysis databases, we identified the inflammation-related genes in AKI and predicted their interaction with FGL2. Both in vivo and in vitro studies showed that overexpression of FGL2 markedly increased complement C3a (C3a) levels and exacerbated inflammation and injury. In contrast, knockdown of FGL2 resulted in a marked decline in C3a levels, which not only conferred a substantial protective effect against hypoxia/reoxygenation-induced injury in tubular cells but also effectively alleviated kidney injury in mice. At the molecular level, FGL2 interacts with complement C3, leading to elevated C3a production. This stimulates the inflammatory response of renal tubular epithelial cells, thereby inducing tubular damage. Targeting FGL2 may hold potential prevention and treatment strategy for tubular injury in AKI.

PubMed2026

Hospital resource utilization in patients with generalized myasthenia gravis treated with nipocalimab: results from the VIVACITY-MG3 study.

Journal of medical economicsJohn Vissing, Geoffroy Coteur, Ibrahim Turkoz, Kavita Gandhi

AIMS: Generalized myasthenia gravis (gMG) is a rare, chronic autoimmune disorder with substantial healthcare resource utilization (HRU) and high economic burden. This study evaluated HRU, costs, and predictors of high-cost events in adults with gMG, using data from VIVACITY-MG3. METHODS: Post-hoc analyses used the primary efficacy dataset from VIVACITY-MG3, a randomized, double-blind, placebo-controlled study of nipocalimab and standard-of-care (SoC) versus placebo and SoC in seropositive adults with gMG. HRU endpoints included hospital admissions (HA), emergency department visits (EDV), and hospital days. Logistic regression analysis identified clinical and demographic HA/EDV predictors. Hospital costs per patient per year (PPPY) were estimated using United States (US) cost data from published sources and from a claims database, adjusted to 2024 US dollars. RESULTS: Among 153 patients, nipocalimab numerically reduced the proportion experiencing ≥1 all-cause (9.1% vs 15.8%) and gMG-related (3.9% vs 7.9%) HA/EDV events versus placebo. The incidence rate of HA/EDV events was 51% numerically lower with nipocalimab. Mean hospital stay duration was numerically shorter with nipocalimab for all-cause (8.4 vs 14.6 days) and gMG-related admissions (11.2 vs 17.6 days). All-cause and gMG-related hospital days per 100 patient-years were statistically significantly reduced by 60% and 68% with nipocalimab, respectively. Estimated cost offsets for reduced HRU were $10,860-$13,253 PPPY. Multivariate analysis identified worsening in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score and higher baseline Quantitative Myasthenia Gravis (QMG) respiratory total score as independent predictors. Patients switching from placebo to nipocalimab in the VIVACITY-MG3 open-label extension experienced a 64% reduction in hospital days PPPY. LIMITATIONS AND CONCLUSION: Study limitations include the post-hoc nature of the analysis and the relatively short study duration. Nipocalimab added to SoC significantly reduces overall HRU and associated costs in adults with gMG, particularly by lowering rates and severity of HA/EDV events. Clinical deterioration and high baseline disease severity independently predict high-cost events.

PubMed2026

Inhaled 3% hypertonic saline is associated with improved symptoms and microbiological stabilisation in antibiotic-naïve nontuberculous mycobacterial lung disease: A prospective study.

PulmonologyI-Hua Chen, Jia-Yih Feng, Chin-Chung Shu, Chih-Jung Chang, Yen-Han Tseng, Ping-Huai Wang, Sheng-Wei Pan

BACKGROUND: Evidence for hypertonic saline (HS) in nontuberculous mycobacterial lung disease (NTM-LD) remains limited, particularly during watchful waiting when non-antibiotic strategies are needed. We evaluated inhaled 3% HS as a potential adjunct in antibiotic-naïve NTM-LD. METHODS: In this prospective cohort study, antibiotic-naïve NTM-LD patients were enrolled between September 2024 and December 2025. Patients receiving daily inhaled 3% HS were compared with contemporaneous controls. Symptom burden (visual analog scale, 0-60) and sputum smear status at month 3 were analysed using generalised estimating equations. In vitro experiments assessed HS effects on Mycobacterium abscessus growth and macrophage function, including intracellular bacterial burden, viability, phagocytosis, and pro-inflammatory gene expression. RESULTS: Among 45 patients (HS: n = 22; control: n = 23), 3% HS was associated with a significant reduction in symptom burden from baseline (coefficient -4.40, 95% CI -6.43 to -2.37; p < 0.001) and a lower odds of sputum smear positivity at month 3 (odds ratio 0.15, 95% CI 0.03-0.64; p = 0.011) in adjusted analyses. In vitro, HS inhibited extracellular M. abscessus growth in a concentration-dependent manner. Pretreatment of macrophages with 3% HS reduced intracellular M. abscessus burden by 51% (p = 0.021) without impairing viability or phagocytosis, while upregulating pro-inflammatory gene expression, including TNF-α (p = 0.004), IL-6 (p = 0.030), and IL-1β (p = 0.058). CONCLUSIONS: In antibiotic-naïve NTM-LD, inhaled 3% HS was associated with improved symptom burden and reduced progression to sputum smear positivity. Complementary in vitro findings support both direct antimycobacterial effects and enhanced macrophage-mediated control, supporting HS as a biologically active adjunct during conservative management of NTM-LD.

PubMed2026

Research trends and hotspots of CAR-T cell therapy for acute lymphoblastic leukemia: A bibliometric analysis.

Human vaccines & immunotherapeuticsXiaolong Tian, Yingping Zhang, Chen Zhang, Dongdong Liu, Yanmin Ma

This study aims to analyze the global research patterns and emerging trends in CAR-T cell therapy for ALL through a bibliometric analysis. Publications were retrieved from the Web of Science Core Collection database. The bibliometric analysis utilized VOSviewer, CiteSpace, and the R package "bibliometrix" to visualize collaborations, keyword co-occurrences, and emerging research trends. A total of 844 articles from 253 journals by 6,459 authors across 44 countries were analyzed, showing an annual growth rate of 40.08%. The USA (372 articles, 38,065 citations) and China (275 articles, 5,636 citations) dominated research output. The University of Pennsylvania (353 articles), Memorial Sloan Kettering Cancer Center (170), and Children's Hospital of Philadelphia (131) were the most productive institutions, while Blood (41 articles) published the most articles. Stephan A. Grupp (38 articles, H-index = 30), Carl H. June (26 articles, H-index = 24), and Shannon L. Maude (25 articles, H-index = 20) were the most influential authors. Keyword analysis revealed five research clusters, including basic mechanisms, CAR design, population treatment integration, clinical outcomes, and toxicity management. Burst keyword analysis showed the evolution from basic science (2010-2013) to clinical translation (2014-2016), toxicity management (2017-2019), and recently to long-term outcomes and risk assessment (2020-2024), with "term follow-up" and "risk" as the only keywords with active bursts in 2024. This bibliometric analysis reveals that research on CAR-T therapy for ALL has progressed from foundational concepts to clinical implementation and now focuses on optimizing long-term outcomes and patient selection. Future research should prioritize biomarker development, next-generation CAR designs, and combination strategies to overcome persistence, toxicity, and resistance limitations in ALL treatment.

PubMed2026

Predictive modeling of fluid status in hemodialysis: model development and internal validation using the MONitoring dialysis outcomes (MONDO) global database.

Renal failureSheng-Han Yueh, Jochen Raimann, Bernard Canaud, Meijiao Zhou, Xiaoling Ye, Ariella Mermelstein, Jeroen Kooman, Frank van der Sande, Len Usv…

BACKGROUND: Optimized fluid management is crucial in dialysis care because extracellular volume overload drives adverse cardiovascular outcomes. At the same time, comorbidities such as inflammation and protein energy wasting lead to decreased muscle mass and intracellular water. Accurate assessment of total body water (TBW) and its extracellular water (ECW) and intracellular water (ICW) compartments is therefore essential to guide ultrafiltration, evaluate dialysis adequacy, and monitor patient risk. METHOD: Using adult patients from the MONitoring Dialysis Outcomes (MONDO) 2012 cohort, we developed predictive models to estimate fluid volume compartments based on demographic data, laboratory values, treatment parameters, and multi-frequency whole-body bioimpedance spectroscopy (BIS) measurements. Clinical features were aggregated over an up-to-90-day look-back window, yielding 18,600 patients and 162,479 dialysis treatments. eXtreme Gradient Boosting (XGBoost) models were trained and tested using patient-level splits, with parallel models built either incorporating or excluding prior BIS measurements. RESULTS: Models including BIS data showed excellent accuracy (R2 > 0.85), models excluding BIS features achieved inferior performance (R2 = 0.73-0.81). In models using BIS inputs, recent bioimpedance changes dominated feature importance. Models without BIS data relied primarily on urea distribution volume, age, and height. CONCLUSION: These findings indicate that fluid volume compartments can be reliably estimated from routinely collected clinical data and history BIS measurements, offering valuable support for interim assessment of fluid status between scheduled BIS measurements.

PubMed2026

Day-to-day variability in resting metabolic rate in strength athletes.

Journal of the International Society of Sports NutritionClaire Buechel, Kate Pumpa, Naroa Etxebarria, Luke Ashton, Michelle Minehan

BACKGROUND: Resting Metabolic Rate (RMR) is measured in sport settings for health monitoring and nutrition planning; however, interpreting repeated measures requires an understanding of typical day-to-day variability under habitual, free-living conditions. This study quantified intra-individual variability in RMR among weight-stable strength-trained athletes, examined the impact of data processing approaches, and established protocol-specific least significant change (LSC) thresholds under ecological conditions. METHODS: A repeated-measures design was used to quantify intra-individual variability in RMR in 13 weight-stable strength-trained athletes (8 male, 5 female). RMR was measured on five consecutive mornings using the Parvo Medics TrueOne 2400 metabolic cart with a Hans Rudolph mouthpiece under standardized conditions. Breath-by-breath data were processed using multiple cleaning approaches to evaluate their impact on RMR estimates, with the most reliable method retained for analysis. Intra-individual variability was quantified and used to derive protocol-specific LSC thresholds. RESULTS: Session averaging produced the lowest intra-individual variability in RMR (CV: 3.4 ± 1.4%) compared with alternative data cleaning approaches. Mean RMR was 26.9 ± 1.4 and 29.1 ± 1.7 kcal·kgFFM-1·day-1 in males and females, respectively. The group-level LSC was 2.9 ± 1.2 kcal·kgFFM-1·day-1 (10.4 ± 4.2%), representing the magnitude of change required to exceed expected within-subject variability under the conditions of this protocol. Fat-free mass (FFM) was positively associated with both absolute RMR and day-to-day variability, whereas prior-day training load and protein intake showed no clear association with RMR variability. CONCLUSIONS: Notable intra-individual variability occurs in repeated RMR measurements in strength-trained athletes under applied conditions. Meaningful interpretation of change requires protocol-specific reliability estimates to distinguish true physiological change from expected day-to-day variation. Session averaging improves measurement consistency and is recommended for mouthpiece-based indirect calorimetry systems. RMR should be interpreted relative to individual and context-specific variability rather than universal thresholds.

PubMed2026

Investigating and validating the molecular mechanisms of lipid metabolism regulation in myasthenia gravis development based on single-cell, bulk transcriptomics, and RT-qPCR.

AutoimmunityMeiqiu Chen, Fang Cai, Yawei Sun, Lanqing Peng, Cong Xia, Yifan Zhang

Myasthenia gravis (MG) is a complex autoimmune neuromuscular disorder, and the role of lipid metabolism dysregulation in MG pathogenesis remains unclear. This study aimed to investigate the molecular mechanisms of lipid metabolism regulation in myasthenia gravis development by integrating single-cell and bulk transcriptomic data. This study analyzed bulk RNA sequencing data from the GSE85452 dataset (13 MG patients and 12 healthy controls) and single-cell RNA sequencing data from the GSE227835 dataset (10 MG patients and 10 healthy controls). Differential expression analysis was performed, and weighted gene co-expression network analysis (WGCNA) was conducted to identify disease-related modules. Key genes were screened through the intersection of differentially expressed genes (DEGs), WGCNA hub genes, and lipid metabolism-related genes. Functional enrichment analysis, protein‒protein interaction (PPI) network construction, immune infiltration analysis, and regulatory network analysis were performed. Single-cell analysis was used to characterize cellular heterogeneity and intercellular communication features. A nomogram prediction model was constructed and internally validated using leave-one-out cross-validation (LOOCV). Potential therapeutic compounds were identified through drug prediction and molecular docking analysis. Furthermore, key genes were validated by RT-qPCR in an independent cohort of 5 MG patients and 5 healthy controls. A total of 823 DEGs and 13 co-expression modules were identified, of which 4 modules were significantly associated with MG. Twenty-one candidate genes were screened, and 2 key genes (IRS2 and ALDH2) were ultimately determined. IRS2 was significantly downregulated while ALDH2 was significantly upregulated in MG patients. The nomogram model based on key genes demonstrated excellent predictive performance (AUC = 0.897). Immune infiltration analysis showed increased regulatory T cells (Tregs) and decreased CD4+ memory activated T cells in MG patients. Single-cell analysis identified 10 major cell types. Cell‒cell communication analysis revealed dense interactions among CD4+ T cells, B cells, and CD14+ monocytes. Drug prediction identified metformin and cyclophosphamide as potential therapeutic candidates, and molecular docking confirmed favorable binding affinities. This integrative study generated the hypothesis that lipid metabolism dysregulation, potentially mediated by IRS2 and ALDH2, may contribute to immune dysfunction in MG pathogenesis. These findings provide preliminary insights into the molecular mechanisms underlying MG development and suggest potential diagnostic biomarkers and therapeutic targets. However, these results are hypothesis-generating, and clinical translation is contingent upon rigorous mechanistic validation through functional experiments, animal models, and larger multicenter clinical cohorts.

PubMed2026

Accuracy and safety of C-TST for tuberculosis infection: A clinical trial in Brazil.

PulmonologyMarcela Bhering, Carla Conceição, Martha Oliveira, Ana Paula Razal Dalvi, Marcelo Cordeiro-Santos, Adriana Rezende Moreira, Anna Cristina C…

BACKGROUND: Tuberculosis infection (TBI) diagnosis in BCG-vaccinated, high-burden settings remains challenging. RESEARCH QUESTION: We aimed to assess the sensitivity, specificity, and safety of the C-tuberculin skin test (C-TST), compared with PPD RT-23, for tuberculosis infection in BCG-vaccinated adults. STUDY DESIGN AND METHODS: Randomised, double-blind clinical trial in Brazil. Adults with pulmonary tuberculosis (PTB) and asymptomatic controls without known TB exposure or prior TB/TPT underwent C-TST, PPD RT-23, and QuantiFERON-TB Gold Plus (QFT-Plus). Skin tests were read by two strategies: (a) induration only or (b) induration or erythema, at a ≥5-mm cut-off. Sensitivity was assessed in PTB; specificity for C-TST and PPD RT-23 was estimated against QFT-Plus. Adverse events were monitored. RESULTS: Among 446 participants (141 PTB; 305 controls), at the 5-mm cut-off, C-TST showed lower sensitivity but higher specificity than PPD RT-23. With strategy (a) and (b), C-TST sensitivity was 0.67 and 0.68, specificity was 0.92 and 0.9, compared to 0.74 sensitivity and 0.78 specificity for PPD RT-23. Adverse events were more frequent in PTB: 12.1% (C-TST) and 6.4% (PPD RT-23); none were serious. CONCLUSION: In BCG‑vaccinated adults, C-TST showed a trade-off of higher specificity and lower sensitivity than PPD RT-23 at the 5-mm cut-off; and a favourable safety profile. Adding erythema to readings did not improve accuracy, suggesting that C-TST may be a useful alternative for programmatic TBI screening in high-burden settings. TRIAL REGISTRATION: Trial registry number RBR-7tn2ysw (https://ensaiosclinicos.gov.br/ registered on 25 January 2021).

PubMed2026

AI-guided data-driven kinetic modelling carbon quantum dot-enabled pH-responsive CMC/CeO2 nanocarriers for quercetin delivery and in vitro evaluation in lung cancer cells.

Artificial cells, nanomedicine, and biotechnologyNikoo Baghal Darbandi, Zeinab Rostami Dehka, Mehrab Pourmadadi, Salar Mohammadi Shabestari, Elham Hatami Monfared

This work reports the development and systematic evaluation of a carboxymethyl cellulose (CMC)-based nanocarrier system co-loaded with cerium oxide (CeO2) and carbon quantum dots (CQDs) for pH-responsive delivery of quercetin (QC) and in vitro evaluation in lung cancer cells. The nanocarriers were prepared using a water-in-oil-in-water (W/O/W) double emulsion approach, yielding spherical particles with an average size of approximately 134 nm and a high positive surface charge (+66 mV), indicative of favourable colloidal stability. FESEM analysis confirmed a uniform morphology and compact internal structure. The incorporation of CeO2 appears to reinforce the polymer matrix, contributing to improved drug encapsulation. The optimized formulation exhibited high encapsulation efficiency (88%) and drug loading capacity (47%), outperforming CeO2-free systems. In vitro release studies demonstrated a clear pH-dependent biphasic behaviour, with significantly faster release under pH 5.4 compared to physiological pH (7.4), reaching 98% and 58% after 96 h, respectively. Drug release followed the Higuchi model, suggesting diffusion-controlled kinetics, while the Korsmeyer-Peppas model indicated a non-Fickian mechanism. An AI-guided nonlinear modelling workflow was used to extract interpretable kinetic descriptors directly from experimental release data. Biological evaluation revealed enhanced anticancer activity against A549 cells, with viability reduced to 49.1%, while maintaining high biocompatibility towards L929 cells.

PubMed2026

Benralizumab effectiveness in a real-world Portuguese severe eosinophilic asthma population: BETREAT study.

PulmonologyCláudia Chaves Loureiro, Filipa Carriço, Ulisses Brito, Inês Belchior, Rosa-Anita Fernandes, Nuno Sousa, Ana Mendes, Carlos Loureiro, Cecíl…

BACKGROUND AND OBJECTIVES: Severe eosinophilic asthma (SEA) is often inadequately controlled. The BETREAT study evaluated the real-world effectiveness of benralizumab, an anti-IL-5 receptor monoclonal antibody, in Portugal, focusing on treatment persistence, asthma control, exacerbation rates, and quality of life (QoL). STUDY DESIGN AND METHODS: Retrospective, observational study including SEA adults who received benralizumab between July 2019 and October 2020 across 16 sites in Portugal. Data from electronic medical records were analysed over 24 months, with evaluations at 3, 6, 12, and 24 months after treatment initiation. Key outcomes included exacerbation rates, oral corticosteroid use, asthma and lung function, and QoL. RESULTS: Of the 74 patients (mean ± SD age 56 ± 11 years and 73.0% female), 66.2% were biologic-naïve. After initiating benralizumab, median eosinophil counts decreased to 0 cells/µL after 3 months. Exacerbation rates decreased from a mean annual rate of 3.12 at baseline to 0.48 by 24 months. Patient-reported asthma control and QoL improved, with ACT and CARAT scores reaching well-controlled levels in most patients by 24 months. Notably, 20.0% of patients achieved clinical remission by the end of the study. CONCLUSIONS: Benralizumab significantly improved SEA outcomes and contributed to clinical remission over a 24-month period, demonstrating potential for long-term disease control and QoL improvement.

PubMed2026

Bidirectional Mendelian randomization of childhood maltreatment and sleep-related phenotypes.

European journal of psychotraumatologyZheng Zhang, Ying Liu, Yuan Zhao

Background: Childhood maltreatment (CM) is associated with sleep disturbance, but observational findings may be affected by confounding, shared familial liability, and reverse-direction explanations. We conducted bidirectional two-sample Mendelian randomization (MR) to examine genetic evidence linking composite CM liability with six sleep-related phenotypes.Methods: Genetic instruments for CM were obtained from a large European-ancestry multi-cohort GWAS meta-analysis. CM was defined as a composite phenotype encompassing multiple abuse and neglect subtypes and ascertainment modes. Summary statistics for chronotype, daytime sleepiness (DS), insomnia symptoms, sleep apnea (SA), daytime napping (DN), and sleep duration (SD) were derived from large European-ancestry GWASs. Inverse-variance weighted MR was the primary method, with weighted median and MR-Egger sensitivity analyses. Benjamini-Hochberg correction was applied and reported as P(BH).Results: In forward MR, genetically proxied CM was associated with higher DS (OR = 1.04, 95% CI 1.01-1.07; P(BH) = 0.030), insomnia symptoms (OR = 1.08, 95% CI 1.01-1.15; P(BH) = 0.030), and DN (β = 0.07, 95% CI 0.03-0.09; P(BH) = 0.002). Little evidence was observed for chronotype, SA, or SD. In exploratory reverse-direction MR, genetic liability to DN (β = 0.16, 95% CI 0.05-0.27; P(BH) = 0.012) and insomnia symptoms (β = 0.21, 95% CI 0.07-0.35; P(BH) = 0.012) was associated with CM liability.Conclusions: This study provides suggestive genetic evidence linking composite CM liability with selected sleep-related phenotypes, particularly self-reported DS, insomnia symptoms, and DN. Reverse-direction findings may reflect shared genetic liability, gene-environment correlation, reporting-related mechanisms, or broader familial pathways rather than temporal effects of adult sleep traits on CM. Given modest effects and uneven sensitivity support, findings should be interpreted cautiously.

PubMed2026

Brain iron deposition mediates cognitive impairment in COPD: A possible imaging marker linking systemic inflammation to neurodegeneration.

PulmonologyQian Chen, Tianlu Teng, Wenyu Zhou, Yu Zhang, Jingting Sun, Ziyi Jing, Ling Wang, Xuejing Li, Lucas Becker, Huan Ye, Zhenghan Yang, Hongjia…

BACKGROUND: Cognitive impairment is a relatively prevalent comorbidity in chronic obstructive pulmonary disease (COPD), yet its neuropathological mechanism remains poorly understood. METHODS: We enrolled 48 stable COPD patients, categorized into cognitively normal (CogN, n = 22) and impaired (Cog, n = 26) groups based on Montreal Cognitive Assessment (MoCA) scores, along with 34 matched healthy controls. All participants underwent 3T MRI with quantitative susceptibility mapping (QSM) to quantify regional brain iron content. Group comparisons of whole-brain and region-of-interest susceptibility were performed. Mediation analysis was then used to test whether specific brain iron deposition mediates the relationship of both COPD status and peripheral inflammatory markers with cognitive performance. RESULTS: Cog patients showed increased total iron in the right cerebellum crus I, while CogN patients exhibited higher paramagnetic susceptibility (χpara) in the left orbitofrontal cortex (OFC), right precentral gyrus, and right brainstem. χpara in the left OFC and right brainstem were positively correlated with total MoCA, abstraction, and orientation scores. Mediation analysis demonstrated that χpara of the left OFC mediated the effects of both COPD status and systemic neutrophil counts on impaired abstraction. Additionally, right brainstem χpara mediated the relationship between COPD and deficits in orientation. CONCLUSIONS: COPD patients with cognitive impairment exhibited distinct patterns of brain iron deposition. Importantly, deposition in several key regions served as a potential mediator, linking both COPD and systemic inflammation to specific cognitive deficits. These preliminary findings suggest a possible association between brain iron accumulation and cognitive impairment in COPD, offering candidate neuroimaging markers for early identification. .

PubMed2026

Gut microbiota-nanoparticle interactions in Parkinson's disease: mechanistic insights and therapeutic perspective.

Artificial cells, nanomedicine, and biotechnologyLeila Kafshdooz, Reza Safaralizadeh

OBJECTIVE: This review introduces the 'nanomaterial-microbiome-brain interface' as a conceptual framework uniting three systems: gut microbiota, nanoparticles, and neurodegeneration. MAIN FINDINGS: We synthesize evidence showing that titanium dioxide, silver, and zinc oxide nanoparticles differentially alter microbial composition. These microbial shifts intersect with established gut-brain mechanisms, including short-chain fatty acid production and immune modulation, providing plausible pathways linking nanomaterial exposure to neurological outcomes. CONCLUSION: We propose the 'nanomaterial-microbiome-brain interface' as a novel conceptual framework with twofold relevance-serving both as a potential contributor to Parkinson's disease pathogenesis through unintentional environmental exposure, and as an underexplored avenue for therapeutic intervention. Critical knowledge gaps persist. Addressing these gaps will require integrated approaches that bridge nanomaterial research, microbiome science, and neurodegeneration studies.

PubMed2026

Lactobacillus johnsonii mediates the protective effects of pristimerin against ulcerative colitis and concomitant liver injury through remodeling hepatic lipid metabolism via LXRα-SCD1 axis.

Gut microbesYan Cheng, Zhanxuan E Wu, Ruoyue Huang, Qingmei Li, Dongmei Yan, Yuqi Chen, WeiFeng Zhu, Fei Li

Ulcerative colitis (UC) is a systemic disease that can involve multiple organs, and hepatobiliary diseases in UC patients are frequently observed. However, the pathogenesis of UC and its associated hepatobiliary complications remains elusive, and limited therapeutic options are available. This study revealed that disrupted hepatic lipid metabolism plays a pivotal role in driving the progression of UC and its extraintestinal hepatobiliary manifestations. Mechanistically, colitis-elevated circulating endogenous corticosterone (CORT) mediates the downregulation of hepatic LXRα-SCD1 signaling, resulting in diminished monounsaturated fatty acid (MUFA), reduced unsaturated lysophospholipids, and the accumulation of alkyl lysophospholipids, ceramide and hexosylceramide. These alterations contribute to liver lipotoxicity and, in turn, exacerbate colitis. A similar lipid profile is observed in UC patients. Importantly, pristimerin, a natural compound structurally similar to the star molecule celastrol, has been demonstrated to alleviate UC and concomitant liver injury by remodeling hepatic lipid metabolism in a microbiota-dependent manner. The gut commensal Lactobacillus johnsonii mediates the effects of PSM by activating hepatic LXRα-SCD1 signaling and increasing the potential anti-inflammation lipid species LPC20:2 and LPC20:3. This investigation suggests a novel therapeutic strategy for UC and associated liver injury based on the L. johnsonii-hepatic LXRα-SCD1 axis. This study also opens new avenues for mechanistic exploration of systemic diseases and therapeutic strategies of multi-organ comorbidity.

PubMed2026

Local governance and health equity: Practical reflections from Chinese crisis governance.

Global public healthTing Zhang, Ran Xu

This study examines mass testing in three Chinese cities since 2020 as a 'stress test' for local governance. It analyses the governance performance of Shenzhen, Nanjing and Wuxi in terms of efficiency, equity and community resilience. Using Melbourne's pandemic lockdown as a reference case, it discusses the underlying mechanisms linking different governance approaches to health equity outcomes. The study adopts a nested governance framework to examine how governance capacities and policy logics operate across different local contexts. The results indicate that Chinese cities can efficiently complete mass testing within a few days, but face pressures related to health equity and community resilience. Melbourne's lockdown governance emphasised participation and institutional transparency, but advanced policies at a relatively slower pace. This study recommends building a dynamic governance mechanism that better balances efficiency and equity.

PubMed2026

Predictive value of the uric acid to high-density cholesterol ratio (UHR) combined with intact parathyroid hormone for protein-energy wasting after incident hemodialysis: a multicenter study.

Renal failureJialing Rao, Yin Li, Wang Qian, Yunfang Zhang, Xianrui Dou, Huimin Cao, Zengchun Ye, Hui Peng

Protein-energy wasting (PEW) is common in incident hemodialysis patients and linked to poor outcomes. The uric acid/HDL-cholesterol ratio (UHR) and intact parathyroid hormone (iPTH) relate to metabolic, inflammatory, and nutritional disturbances, but their value for predicting PEW in incident hemodialysis is unclear. This retrospective multicenter study included 863 incident hemodialysis patients. PEW was defined according to the International Society of Renal Nutrition and Metabolism criteria. UHR and iPTH were evaluated using ROC analysis, multivariable logistic regression, and ten machine learning models. Restricted cubic spline, mediation, and trajectory analyses were performed, with SHAP for interpretability. PEW was identified in 59.2% of patients. Feature selection across four machine learning approaches consistently identified UHR, iPTH, and eGFR as key predictors. Higher baseline and cumulative UHR were independently associated with a lower risk of PEW. Trajectory analysis showed that both rapidly increasing and decreasing UHR patterns with higher mean levels were linked to the lowest PEW risk. Nonlinear associations were observed, with an inverted U-shaped relationship between UHR and PEW and an S-shaped relationship between iPTH and PEW. Mediation analysis indicated that iPTH accounted for approximately 10-13% of the association between UHR and PEW. Among all models, XGBoost achieved the best performance (AUC = 0.801). A web-based Shiny tool was developed for individualized PEW risk assessment. UHR and iPTH were associated with PEW risk within specific ranges. Machine learning models integrating these markers showed favorable predictive performance and may assist individualized risk assessment in clinical practice.

PubMed2026

Triptonide enhances DNA damage by inhibiting TRIP13‑mediated DNA repair and synergizes with bortezomib to suppress multiple myeloma.

International journal of oncologyFen He, Junjun Li, Lijun Peng, Hongyan Zhao, Maoyou Lu, Ruixin Gao, Siqi Wang, Yu Chen, Ruihan Tang, Zhengguo Li, Linlin Zhang, Xinyu Zhang…

Multiple myeloma (MM) is a malignant disorder of plasma cells. Combinations of bortezomib (BTZ) with other therapeutic agents remain the mainstay of MM treatment. However, the rising incidence of drug resistance among patients with MM underscores an urgent need for novel therapeutic strategies. The present study identified triptonide (TN), a small‑molecule monomer extracted from the traditional Chinese herb Tripterygium wilfordii Hook. f., as a synergistic agent that enhanced the anti‑MM activity of BTZ, following a screening of 198 compounds from a ubiquitination‑focused library. TN effectively inhibited cell proliferation, induced apoptosis, and reduced cell viability in MM cells. Furthermore, the synergistic anti‑MM effect between TN and BTZ was validated across MM cell lines, primary MM cells, and xenograft mouse models of MM. Mechanistic investigations revealed that TN synergizes with BTZ by enhancing DNA damage through the suppression of TRIP13‑mediated DNA repair pathways, including non‑homologous end joining and homologous recombination. Notably, TRIP13 knockdown attenuated TN‑induced DNA damage and apoptosis, and diminished the synergistic effect of TN and BTZ on MM cells. Collectively, TN represents a novel anti‑MM agent, and the combination of TN with BTZ constitutes a promising therapeutic strategy for the treatment of MM.

PubMed2026

A NANOBODY molecule that blocks MerTK ectodomain cleavage in vitro and in vivo.

mAbsLinde Duprez, Ayse Kilic, Hélène Bruwiere, Karim Fekir, Dennis Vlaeminck, Camille De Craene, Daan Geiregat, Kirsten Paesen, Lien Leutenez, …

The membrane receptor MerTK is critical for the resolution of inflammation and thus is of pharmacological interest. MerTK function is inhibited by the proteolytic cleavage of its extracellular domain leading to the formation of soluble Mer (sMer). We describe here the NANOBODY molecule A0445046C08 and its half-life-extended version A044500050. Both bound selectively to MerTK and blocked lipopolysaccharide-induced MerTK cleavage in primary macrophages without influencing ligand binding or kinase activity of MerTK. A044500050 reduced Zymosan-induced sMer levels in the peritoneal lavage fluid of a mouse model with sterile peritonitis. The study demonstrates that NANOBODY molecules can be generated that selectively inhibit ectodomain shedding and outlines a novel pharmacological approach for targeting membrane proteins where aberrant cleavage plays a pathogenic role.

PubMed2026

Analysis of tuberculosis and multiple diseases as co-morbidities: a narrative review.

Annals of medicineYaqi Sun, Kaixin Zhou, Wenhui Wang, Qian Gao, Yan Lin

BACKGROUND: Tuberculosis (TB) remains the leading cause of death from infectious diseases worldwide, and its control is increasingly complicated by chronic comorbidities. Diabetes mellitus (DM), human immunodeficiency virus (HIV) infection, chronic obstructive pulmonary disease (COPD), and lung cancer (LC) substantially affect TB susceptibility, diagnosis, treatment, and prognosis. METHODS: This narrative review summarizes evidence on the interactions between TB and DM, HIV infection, COPD, and LC. Relevant literature was identified through PubMed, Web of Science, and World Health Organization publications, focusing on studies published between 2001 and 2025. Priority was given to peer-reviewed original studies and reviews addressing immune mechanisms, diagnosis, and treatment. RESULTS: DM increases TB risk by impairing innate and adaptive immunity and complicates prevention, diagnosis, and treatment. HIV-1 weakens antimycobacterial defense through lymphocyte depletion, macrophage dysfunction, granuloma instability, and immune exhaustion, markedly increasing susceptibility to active TB. TB and COPD mutually aggravate pulmonary inflammation, oxidative stress, and structural lung damage, contributing to poor respiratory outcomes. Mycobacterium tuberculosis(M.tb) infection may also be associated with LC development through chronic inflammation, oxidative stress-related genomic instability, and oncogenic signaling. Overall, these comorbidities increase diagnostic difficulty, therapeutic complexity, and the risk of adverse outcomes. CONCLUSIONS: TB associated comorbidities remain a major challenge to global TB control. Understanding these interactions may support bidirectional screening, risk stratification, and integrated management. Although these conditions share immune dysregulation, chronic inflammation, and oxidative stress, they differ in dominant mechanisms, diagnostic challenges, and treatment priorities. Future research should prioritize biomarker discovery, mechanistic clarification, and multilevel prevention and control strategies.

PubMed2026

Association of CBC‑derived inflammation indices with prevalent CKD: a cross‑sectional analysis of a Chinese data set and NHANES.

Annals of medicineRuichao Feng, Yang Shao, Yuxin Zhao, Xiangfei Cui, Congcong Jiao, Hua Zhou

BACKGROUND: Given the established association between chronic kidney disease (CKD) and systemic inflammation, this study examined the relationships between complete blood count (CBC)-derived inflammatory markers and prevalent CKD. METHODS: Two data sets (Chinese clinical data, n = 4,518; NHANES 2017-2020, n = 7,724) are analyzed. Seven CBC‑derived inflammatory indices were calculated: SII, SIRI, NLR, dNLR, NMLR, MLR, and PLR. Each index was categorized into quartiles (Q1-Q4). Weighted logistic regression (for NHANES) and unweighted logistic regression (for the Chinese clinical data) were applied to estimate associations with CKD, with sequential adjustment for demographics, body mass index, and comorbidities. To control for multiple comparisons, false discovery rate (FDR) correction was applied. Furthermore, subgroup analysis, restricted cubic spline analysis and sensitivity analysis were also performed in this study. RESULTS: In the two fully adjusted models, the highest quartile (Q4) of SIRI, NLR, and NMLR was significantly associated with higher odds of prevalent CKD compared with Q1. After FDR correction, these associations remained significant in both cohorts: in the Chinese cohort, all padj < 0.001; in NHANES, padj = 0.028 for SIRI, 0.040 for NLR, and 0.041 for NMLR. Sensitivity analyses consistently supported the primary findings: excluding outliers, log2 transformation, and the alternative CKD definition yielded similar effect directions and significance levels. Heterogeneity was observed across subgroups, and restricted cubic splines revealed nonlinear dose‑response relationships (p for nonlinearity <0.05). CONCLUSIONS: Elevated SIRI, NLR, and NMLR are associated with prevalent CKD, suggesting systemic inflammation may play a role, yet prospective studies are required to establish temporality and causality.