OBJECTIVE To systematically evaluate the efficacy and safety of tislelizumab in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Computerized searches were conducted in PubMed， Embase， the Cochrane Library， CNKI， Wanfang and other Chinese and English databases to collect randomized controlled trials （RCTs） on tislelizumab for advanced NSCLC. The search period was from the establishment of the databases to December 2024. After strictly screening the literature， extracting data and conducting quality evaluations in accordance with the inclusion and exclusion criteria， a meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 18 RCTs involving 2 337 patients were included， with 1 283 in the experimental group and 1 054 in the control group. The meta-analysis results showed that the objective response rate [RR＝1.61， 95%CI （1.48， 1.75）， P＜0.000 01]， disease control rate [RR＝1.21， 95%CI （1.13， 1.29）， P＜0.000 01]， progression free survival [HR＝0.55， 95%CI （0.45， 0.66）， P＜0.000 01]， and overall survival [HR＝0.78， 95%CI（0.62， 0.97）， P＝0.03] were significantly better in the experimental group than in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups [RR＝1.00， 95%CI （0.73， 1.37）， P＝1.00]； among the common adverse reactions， only the incidence of liver function impairment was significantly higher in the experimental group than in the control group [RR＝1.30， 95%CI （1.10， 1.54）， P＜0.01]. CONCLUSIONS Tislelizumab in combination with chemotherapy or targeted drugs significantly improves the efficacy in patients with advanced NSCLC without increasing the risk of adverse reactions overall. However， liver function should be closely monitored during treatment.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Objective:To explore the association of serum levels of 41 serum cytokines and growth factors with the risk of sero-negative rheumatoid arthritis(SNRA)by Mendelian randomization.Methods:Genetic instruments for 41 circulating cytokines and growth factors were determined from a genome-wide association study(GWAS)of 8 293 European participants.Summary statistics for the SNRA were obtained from the Finnish database,including 3 877 SNRA cases and 285 035 controls of European ancestry.All of the inverse variance weighted(IVW),weighted median method(WM)and MR-Egger regression were used for MR analysis,while the IVW method was considered as the main analysis.The sensitivity analysis included a heterogeneity test,horizontal pleiotropic test,and leave-one method test to determine the reliability of the MR results.Results:In the IVW method,TNF-α[OR=1.470,95%CI(1.1331～1.910),P=0.004],IP-10[OR=0.794,95%CI(0.660～0.955),P=0.015]and IL-2rα[OR=0.049,95%CI(0.856～0.999),P=0.049].Sensitivity analysis showed no heterogeneity and horizontal pleiotropy.Conclusion:TNF-α,IP-10 and IL-2rα are causally associated to SNRA.TNF-α increases the risk of SNRA,while IP-10 and IL-2rα reduce the risk of SNRA.

Network analysis serves as a critical methodological approach for enhancing the efficiency of health management in elderly patients with chronic diseases,demonstrating unique advantages in precisely identifying intervention targets.This article comprehensively reviews recent advancements in the application of network analysis for managing chronic conditions in older adults,systematically organizing research findings across 3 analytical dimensions:cross-sectional networks,dynamic networks,and individualized networks.The review aims to provide healthcare professionals with a robust theoretical foundation and methodological support for developing personalized health management strategies.

Objective To observe the value of nomogram of ultrasound combined with laboratory indexes for predicting axillary lymph node metastasis(ALNM)of stage cT1N0 breast invasive ductal carcinoma(IDC).Methods A total of 77 cases with pathologically diagnosed stage cT1N0 single breast IDC were retrospectively collected,including 23 cases with and 54 cases without ALNM.Univariate and multivariate binary logistic regression analysis were used to analyze clinical data,laboratory indicators and ultrasonic manifestations,then the independent predictors of ALNM of stage cT1N0 breast IDC were screened to establish laboratory indexes model,ultrasound model and combined model,respectively,and nomogram of the combined model was drawn.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive efficacy of each model.The consistency of results of combined model and actual results was analyzed using calibration curve.Decision curve analysis(DCA)was used to explore the clinical value of each model.Results Serum carbohydrate antigen 153(CA153)(OR=1.132),platelet-to-lymphocyte ratio(PLR)(OR=1.020)and echo attenuation behind the lesion on ultrasound(OR=8.789)were all independent predictors of ALNM in stage cT1N0 breast IDC(all P＜0.05),and the area under the curve(AUC)of laboratory indexes model,ultrasound model and combined model for predicting ALNM of stage cT1N0 breast IDC was 0.757,0.616 and 0.836,respectively.The consistency of the predicted results of combined model and actual results was good.When the threshold was higher than 0.15,the net benefit of combined model was higher than that of the other 2 models.Conclusion Nomogram of ultrasound combined with laboratory indexes could effectively predict ALNM of stage cT1N0 breast IDC.

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 explore the association of serum levels of 41 serum cytokines and growth factors with the risk of sero-negative rheumatoid arthritis(SNRA)by Mendelian randomization.Methods:Genetic instruments for 41 circulating cytokines and growth factors were determined from a genome-wide association study(GWAS)of 8 293 European participants.Summary statistics for the SNRA were obtained from the Finnish database,including 3 877 SNRA cases and 285 035 controls of European ancestry.All of the inverse variance weighted(IVW),weighted median method(WM)and MR-Egger regression were used for MR analysis,while the IVW method was considered as the main analysis.The sensitivity analysis included a heterogeneity test,horizontal pleiotropic test,and leave-one method test to determine the reliability of the MR results.Results:In the IVW method,TNF-α[OR=1.470,95%CI(1.1331～1.910),P=0.004],IP-10[OR=0.794,95%CI(0.660～0.955),P=0.015]and IL-2rα[OR=0.049,95%CI(0.856～0.999),P=0.049].Sensitivity analysis showed no heterogeneity and horizontal pleiotropy.Conclusion:TNF-α,IP-10 and IL-2rα are causally associated to SNRA.TNF-α increases the risk of SNRA,while IP-10 and IL-2rα reduce the risk of SNRA.

Objective To observe the value of nomogram of ultrasound combined with laboratory indexes for predicting axillary lymph node metastasis(ALNM)of stage cT1N0 breast invasive ductal carcinoma(IDC).Methods A total of 77 cases with pathologically diagnosed stage cT1N0 single breast IDC were retrospectively collected,including 23 cases with and 54 cases without ALNM.Univariate and multivariate binary logistic regression analysis were used to analyze clinical data,laboratory indicators and ultrasonic manifestations,then the independent predictors of ALNM of stage cT1N0 breast IDC were screened to establish laboratory indexes model,ultrasound model and combined model,respectively,and nomogram of the combined model was drawn.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive efficacy of each model.The consistency of results of combined model and actual results was analyzed using calibration curve.Decision curve analysis(DCA)was used to explore the clinical value of each model.Results Serum carbohydrate antigen 153(CA153)(OR=1.132),platelet-to-lymphocyte ratio(PLR)(OR=1.020)and echo attenuation behind the lesion on ultrasound(OR=8.789)were all independent predictors of ALNM in stage cT1N0 breast IDC(all P＜0.05),and the area under the curve(AUC)of laboratory indexes model,ultrasound model and combined model for predicting ALNM of stage cT1N0 breast IDC was 0.757,0.616 and 0.836,respectively.The consistency of the predicted results of combined model and actual results was good.When the threshold was higher than 0.15,the net benefit of combined model was higher than that of the other 2 models.Conclusion Nomogram of ultrasound combined with laboratory indexes could effectively predict ALNM of stage cT1N0 breast IDC.

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.

Network analysis serves as a critical methodological approach for enhancing the efficiency of health management in elderly patients with chronic diseases,demonstrating unique advantages in precisely identifying intervention targets.This article comprehensively reviews recent advancements in the application of network analysis for managing chronic conditions in older adults,systematically organizing research findings across 3 analytical dimensions:cross-sectional networks,dynamic networks,and individualized networks.The review aims to provide healthcare professionals with a robust theoretical foundation and methodological support for developing personalized health management strategies.