ObjectiveTo investigate the effect of cerebellar intermittent theta-burst stimulation (iTBS) on postural control and fall risk in stroke patients. MethodsFrom October, 2024 to August, 2025, 45 stroke patients were recruited from Huadong Hospital Affiliated to Fudan University. They were randomly divided into control group (n = 15), group A (n = 15) and group B (n = 15). All the groups received conventional medication and rehabilitation. Group A was additionally administered iTBS over the ipsilesional primary motor cortex (M1), while group B received iTBS over the contralesional cerebellum, for three weeks. Before and after intervention, postural stability indexes (eyes open/closed), limits of stability, directional control score and reaction time were measured using Biodex Balance System, and they were assessed with Berg Balance Scale (BBS), Timed Up & Go Test (TUGT) and 10-meter walk test (10MWT). ResultsAfter intervention, significant group-time interaction effects were observed for eyes open/closed postural stability indexes, limits of stability, directional control score, reaction time, BBS score, TUGT and 10MWT (F > 23.487, P < 0.001). All the groups improved in all the indexes after intervention (P < 0.01). The eyes open/closed postural stability indexes, limits of stability, directional control score and reaction time were the best in group B, followed by group A, and the worst in the control group (P < 0.05), while BBS, TUGT and 10MWT were better in groups A and B than in the control group (P < 0.05). ConclusionCerebellar iTBS can effectively improve postural control disorders and reduce fall risk in stroke patients, and may be superior to M1 iTBS.

ObjectiveTo systematically evaluate the effect of intermittent theta burst stimulation (iTBS) on lower extremity motor function and balance function in patients with stroke. MethodsA systematic literature search was conducted in the Cochrane Library, Embase, PubMed, Web of Science, CNKI, SinoMed, Wanfang data and VIP from inception to February 19, 2025. Randomized controlled trials comparing iTBS with conventional rehabilitation or sham iTBS in patients with post-stroke lower extremity motor and balance dysfunction were included. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias Tool. Meta-analysis was performed using RevMan 5.4 and Stata 14.0. ResultsA total of 16 articles involving 647 patients were included. Meta-analysis showed that iTBS improved the Fugl-Meyer Assessment-Lower Extremities score (MD = 2.58, 95%CI 1.61 to 3.55, P < 0.001), Berg Balance Scale score (MD = 4.11, 95%CI 2.43 to 5.79, P < 0.001), Barthel Index score (MD = 4.95, 95%CI 0.97 to 8.92, P = 0.010) and motor-evoked potential (MEP) latency (MD = -1.42, 95%CI -2.54 to -0.30, P = 0.010). Subgroup analyses suggested that at subacute stage, cerebellar iTBS, more than ten treatment sessions, and 1 200 pulses per day may be more effective. ConclusioniTBS may improve lower extremity motor function and activities of daily living in patients with stroke, and shorten MEP latency, and it may also confer potential benefits in improving balance function in these patients.

BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

Sensorineural hearing loss (SNHL) is recognized as the most severe ototoxic complication following radiotherapy or chemoradiotherapy in patients with head and neck cancers (HNCs). It significantly impairs patients′ quality of life due to the lack of effective drugs. Although advances in radiotherapy techniques have played a crucial role in improving patients′ survival rates and protecting organs at risk, SNHL remains inevitable. This review presents the diagnosis, differential diagnosis, clinical manifestations, assessment criteria, pathogenesis, risk factors, and prophylactic/therapeutic strategies of SNHL, in order to provide novel insights for clinical diagnosis, treatment, and prevention.

Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.

Objective:To standardize the management of Investigator-Initiated Trials(IITs) and improve the quality of research projects, this study takes a tertiary hospital in Beijing as an example to analyze the key risk points in the implementation process of IITs and proposes countermeasures based on the issues identified during the management process.Methods:The study analyzed the IITs conducted at in the hospital from 2022 to 2023, focusing on 4 aspects: project classification evaluation and management (risk management), project implementation quality (process management), collaboration and support conditions(contract review and execution), and participant protection (medical ethics). It examined the key points and difficulties in project process management to standardize the quality management of IITs.Results:The implementation process management of IITs in medical institutions was an essential component for standardized clinical research management and an effective means to ensure the scientific nature of clinical research and the quality of data.Conclusions:Medical institutions should establish an effective and feasible IIT quality management system to comprehensively enhance the quality of IIT project, aiming to produce high-quality clinical research outcomes.

Objective To investigate the current status of knowledge,attitude,and practice(KAP)re-garding the clinical application of graduated compression stockings(GCS)for preventing venous thromboem-bolism(VTE)among medical staff and analyze its influencing factors.Methods Through convenience sam-pling,5 706 medical staff from 85 hospitals in Chongqing were surveyed using the"Questionnaire on KAP of Clinical Application of GCS for VTE Prevention"between March 16 and 30,2024.Univariate and multiple lin-ear stepwise regression analyses were conducted to explore influencing factors.Results The scores for knowl-edge,attitude,and practice in the clinical application of GCS for VTE prevention among healthcare workers were(37.77±10.56),(16.85±3.05),and(24.85±7.51),respectively.Age,highest education level,seniori-ty,department,whether they had received GCS application training,hospital level,whether the hospital passed the national venous thrombosis prevention center certification,and GCS procurement channels were influen-cing factors for knowledge scores.Professional title,whether they had received GCS application training,hos-pital level,and whether the hospital passed the national venous thrombosis prevention center certification were influencing factors for attitude scores.Gender,age,highest education level,seniority,department,whether they had received GCS application training,hospital level,whether the hospital passed the national venous thrombo-sis prevention center certification,and GCS procurement channels were influencing factors for behavior scores.Conclusion Healthcare workers'knowledge of clinical application of GCS for VTE prevention is at a medium level,their attitude toward clinical application is positive,and practical behaviors are basically in compliance with standards.Hospital managers should emphasize training and assessment on clinical application of GCS for healthcare workers,strengthen quality control in practical implementation,and ensure patients receive stand-ardized mechanical VTE prevention.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the abnormal expansion of CAG trinucleotide repeats in the Huntingtin gene (HTT) located on chromosome 4. It is transmitted in an autosomal dominant manner and is characterized by motor dysfunction, cognitive decline, and emotional disturbances. To date, there are no curative treatments for HD have been developed; current therapeutic approaches focus on symptom relief and comprehensive care through coordinated pharmacological and nonpharmacological methods to manage the diverse phenotypes of the disease. International clinical guidelines for the treatment of HD are continually being revised in an effort to enhance care within a multidisciplinary framework. Additionally, innovative gene and cell therapy strategies are being actively researched and developed to address the complexities of the disorder and improve treatment outcomes. This review endeavours to elucidate the current and emerging gene and cell therapy strategies for HD, offering a detailed insight into the complexities of the disorder and looking forward to future treatment paradigms. Considering the complexity of the underlying mechanisms driving HD, a synergistic treatment strategy that integrates various factors-such as distinct cell types, epigenetic patterns, genetic components, and methods to improve the cerebral microenvironment-may significantly enhance therapeutic outcomes. In the future, we eagerly anticipate ongoing innovations in interdisciplinary research that will bring profound advancements and refinements in the treatment of HD.
Huntington Disease/pathology* ; Humans ; Genetic Therapy/methods* ; Animals ; Huntingtin Protein/genetics* ; Cell- and Tissue-Based Therapy/methods*

Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC₅₀) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL^-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G₀/G₁ phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe²⁺, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals ; Humans ; Mice ; Antineoplastic Agents, Phytogenic ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cyclin D1/genetics* ; Cyclin-Dependent Kinase 4/genetics* ; DNA Damage/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Ferroptosis/drug effects* ; G1 Phase Cell Cycle Checkpoints/drug effects* ; Heme Oxygenase-1/genetics* ; Mice, Inbred BALB C ; Mice, Nude ; Plant Extracts/pharmacology* ; Stomach Neoplasms/physiopathology* ; Thymelaeaceae/chemistry* ; Up-Regulation/drug effects*