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.

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.

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*

AIM:Xiongshi Shiwei Wendan decoc-tion(SWD)comes from Xiong Jibai,a master of tra-ditional Chinese medicine,and has been widely used in the treatment of AS.ABCA1 is an important pathway for macrophages to export cholesterol and plays a protective role in the occurrence and development of AS.The purpose of this study was to study the effects of SWD on ABCA1 expression and cholesterol efflux through network pharmacol-ogy,molecular docking and in vitro experiments,and explore the pathway mechanism of promoting reverse cholesterol transport(RCT).METHODS:The active components of SWD drugs were screened by TCMSP and HERB databases,RCT targets were pre-dicted,the component-target network map was constructed,the PPI network was constructed and the GO and KEGG pathways were enriched and ana-lyzed by STRING database,and the key active com-ponents of SWD were selected for molecular dock-ing with ABCA1 protein and miR-33 by AutoDockVi-na.In vitro,RAW264.7 was used to establish foam cell model,oil red O staining,NBD-cholesterol staining and lentivirus overexpression cell miRNA-33 were used to study the effect of SWD on lipid accumulation and cholesterol outflow rate of RAW264.7 cells.Western blotting was used to de-tect the expression of ABCA1.RESULTS:According to network pharmacology,336 active components of SWD,267 targets of RCT and 46 targets of inter-section of RCT and SWD were obtained,which in-volved multiple signal pathways such as lipid and atherosclerosis.Molecular docking showed that the main active components had stable conforma-tion with ABCA1 and miR-33.In vitro experiment,it was found that the lipid content was significantly decreased(P＜0.01),the cholesterol outflow rate was significantly increased(P＜0.01)and the expres-sion of ABCA1 protein was up-regulated in SWD group(P＜0.01),but the expression of ABCA1 in miR-33 overexpression group was significantly de-creased(P＜0.01).CONCLUSION:SWD has the char-acteristics of multi-components and multi-targets,which can promote RCT and treat AS through miR-NA-33-ABCA1 pathway.

OBJECTIVE To evaluate the influence of gene polymorphism on plasma minimum concentration(cmin)of voriconazole(VRZ)in patients with invasive fungal infection.METHODS The Cochrane Library,Embase,PubMed,Web of Science,China Biomedical Literature Database,CNKI,VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms andcmin of VRZ from inception to April 2024.After screening the literature,extracting data,and evaluating the quality of the literature,meta-analysis was performed using R 4.3.2 software.RESULTS A total of 21 studies with 2 454 patients were included.The results of meta-analysis showed that the VRZ cmin of CYP2C19 IM and PM types was significantly higher than EM type,and the VRZ cmin of IM type was significantly lower than PM type(P＜0.01).The VRZ cmin of CYP2C9 rs1057910 AA type was significantly higher than AC/CC type,and that of CYP3A5 rs776746 CC type was significantly higher than TT type(P＜0.01).The VRZ cmin of POR rs10954732 GG type was significantly higher than GA and AA types,and that of POR rs1057868 CT type was significantly lower than TT type(P＜0.01).The VRZ cminof ABCB1 rs1045642 CC type was significantly higher than TT type(P＜0.05).The VRZ cmin of NR1I2 rs2472677 CT type was significantly higher than TT type,and rs7643645 AA type was significantly higher than AG type(P＜0.05).The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type,and the CT type was significantly lower than TT type(P＜0.01).CONCLUSIONS Mutant alleles in CYP2C19,CYP2C9 rs1057910,CYP3A5 rs776746,POR rs10954732,ABCB1 rs1045642 and NR1I2 rs7643645 can lead to a decrease in VRZ plasma concentration,and mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration.

Objective:To investigate the role of the Brock, Mayo, and PKUPH combined model in risk stratification of solitary pulmonary nodules (SPNs) in health check-up population.Methods:An ambispective cohort study was conducted on 668 eligible SPNs cases from the health management center in Chongqing General Hospital from June 2018 to June 2019. The exposure condition was prospectively followed or historically retrospected, and the clinical outcomes were prospectively followed. SPNs were classified into benign and malignant groups. Descriptive statistics and univariate analysis were performed to assess the differences in risk characteristics between two groups. Receiver operating characteristic (ROC) curve, clinical decision curve, and Hosmer-Lemeshow goodness-of-fit test were used to evaluate and compare the predictive performance, clinical utility, and calibration of the combined model versus individual Brock, Mayo, and PKUPH models.Results:Among the 668 SPNs cases, 82 (12.28%) were diagnosed as malignant. Age, sex, smoking history, extrapulmonary tumor history, diameter, upper lobe, clear border and spicule sign in the malignant group were significantly different from those in the benign group (all P<0.05). The combined model demonstrated superior predictive performance, clinical utility, and calibration compared to the best-performing individual Brock model [Area under the curve (AUC): 0.88 (95% CI: 0.84-0.92) vs 0.86 (95% CI: 0.82-0.91)]. Besides, multi-grade risk stratification enabled by the combined model was better than binary classification, with the malignant rate of the four risk levels were 0.60%, 4.62%, 14.58% and 56.07%, respectively. Conclusion:The combined model addresses the limitations of individual models in SPNs risk stratification for health examination populations, improving predictive performance, clinical utility, and calibration, while proposing a superior multi-grade risk stratification system.

Sj?gren syndrome(SS)is an immune disease mainly characterized by lymphocytes infiltrate in salivary and lacrimal glands,leading to glandular secretion disorders and dryness in the mouth and eyes.In recent years,clinical application of ultrasound elastography(USE)increased widespread,providing a new imaging method for diagnosis of SS.The research progresses of USE in SS were reviewed in this article.

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: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.