Background: and Purpose Acute ischemic stroke (AIS) is a leading cause of disability worldwide. While intravenous thrombolysis is recommended within 4.5 hours of last known well (LKW) time, many patients present beyond this window. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating tenecteplase (TNK) administration in AIS patients within 4.5 to 24 hours of LKW. The primary outcomes assessed functional independence and ordinal modified Rankin Scale (mRS) shift at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Results: Three RCTs were included, comprising 1,054 patients (532 TNK and 522 standard medical therapy) with a mean age of 69 years, 59% males, and median baseline National Institutes of Health Stroke Scale score of 10.5. TNK treatment was associated with mRS 0–2 at 90 days (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.04–1.70, P=0.023), indicating a 33% higher likelihood of achieving functional independence. However, the ordinal mRS shift showed no significant difference (standardized mean difference: 0.01, 95% CI: -0.37–0.39, P=0.09). Safety outcomes indicated no difference in the rates of sICH (OR: 2.07, 95% CI: 0.86–5.00, P=0.1), and no difference in 90-day mortality (OR: 1.08, 95% CI: 0.76–1.53, P=0.67). Conclusion This meta-analysis suggests TNK might be safe and effective for selected AIS patients in the 4.5- to 24-hour time window, offering improved functional outcomes without a significant increase in hemorrhagic complications.

Background: and Purpose Acute ischemic stroke (AIS) is a leading cause of disability worldwide. While intravenous thrombolysis is recommended within 4.5 hours of last known well (LKW) time, many patients present beyond this window. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating tenecteplase (TNK) administration in AIS patients within 4.5 to 24 hours of LKW. The primary outcomes assessed functional independence and ordinal modified Rankin Scale (mRS) shift at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Results: Three RCTs were included, comprising 1,054 patients (532 TNK and 522 standard medical therapy) with a mean age of 69 years, 59% males, and median baseline National Institutes of Health Stroke Scale score of 10.5. TNK treatment was associated with mRS 0–2 at 90 days (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.04–1.70, P=0.023), indicating a 33% higher likelihood of achieving functional independence. However, the ordinal mRS shift showed no significant difference (standardized mean difference: 0.01, 95% CI: -0.37–0.39, P=0.09). Safety outcomes indicated no difference in the rates of sICH (OR: 2.07, 95% CI: 0.86–5.00, P=0.1), and no difference in 90-day mortality (OR: 1.08, 95% CI: 0.76–1.53, P=0.67). Conclusion This meta-analysis suggests TNK might be safe and effective for selected AIS patients in the 4.5- to 24-hour time window, offering improved functional outcomes without a significant increase in hemorrhagic complications.

Background: and Purpose Acute ischemic stroke (AIS) is a leading cause of disability worldwide. While intravenous thrombolysis is recommended within 4.5 hours of last known well (LKW) time, many patients present beyond this window. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating tenecteplase (TNK) administration in AIS patients within 4.5 to 24 hours of LKW. The primary outcomes assessed functional independence and ordinal modified Rankin Scale (mRS) shift at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Results: Three RCTs were included, comprising 1,054 patients (532 TNK and 522 standard medical therapy) with a mean age of 69 years, 59% males, and median baseline National Institutes of Health Stroke Scale score of 10.5. TNK treatment was associated with mRS 0–2 at 90 days (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.04–1.70, P=0.023), indicating a 33% higher likelihood of achieving functional independence. However, the ordinal mRS shift showed no significant difference (standardized mean difference: 0.01, 95% CI: -0.37–0.39, P=0.09). Safety outcomes indicated no difference in the rates of sICH (OR: 2.07, 95% CI: 0.86–5.00, P=0.1), and no difference in 90-day mortality (OR: 1.08, 95% CI: 0.76–1.53, P=0.67). Conclusion This meta-analysis suggests TNK might be safe and effective for selected AIS patients in the 4.5- to 24-hour time window, offering improved functional outcomes without a significant increase in hemorrhagic complications.

OBJECTIVE To observe the changes of cardiac function,local inflammation level and macrophage M2 polarization in mice with acute myocardial infarction(AMI after electroacupuncture preconditioning at the Neiguan point,and to explore the possible mechanisms from the perspective of regulating the DNA-PK/Rictor/Myc signaling pathway.METHODS Male C57BL/6J mice were randomly divided into sham group,model group and electroacupuncture group,with 10 mice in each group.The electroacupuncture group received bilateral electroacupuncture interventions at the Neiguan points,sparse-dense wave,2/15 Hz,1 mA,20 min/time,once a day for 3 consecutive days,and AMI models were performed 0.5 h after the electroacupuncture interventions.The myocardial ischemia model was prepared by ligating the left anterior descending branch.Echocardiography was used to detect cardiac ejection frac-tion(EF and fractional shortening(FS to evaluate cardiac function;HE and TUNEL staining were used to observe the pathological morphology of myocardium and apoptosis of cardiomyocytes,and immunohistochemistry and ELISA were used to detect IL-1β,TNF-α and NLRP3 in infarcted myocardium and peripheral blood to evaluate the level of inflammation;flow cytometry was used to detect cardiac macrophage polarization status,and Western blot method to detect the protein expression levels of DNA-PK,p-DNA-PK,Rictor and Myc in infarcted myocardium.RESULTS Compared with the sham group,the model group showed significantly lower EF and FS(P<0.000 1,significant inflammatory cell infiltration,significantly higher cardiomyocyte apoptotic index(P<0.001,up-regulated expression of IL-1β,NLRP3 and TNF-α in the myocardium and serum(P<0.01,P<0.001,a significant increase in the percentage of macrophages(P<0.001,a decrease in the percentage of cardiac M2-type macrophages(P<0.000 1,and a significant decrease in the expression levels of p-DNA-PK,Rictor and Myc proteins in myocardium(P<0.05,P<0.000 1.Compared with the model group,EF and FS were significantly higher in the electroacupuncture group(P<0.000 1,inflammatory cell infiltration was re-duced,cardiomyocyte apoptotic index was decreased(P<0.01,and the expression of IL-1β,NLRP3 and TNF-α was down-regula-ted in myocardium and serum(P<0.05,P<0.01,P<0.001;the macrophage percentage was decreased(P<0.05,cardiac M2-type macrophage percentage was increased(P<0.01,and p-DNA-PK,Rictor and Myc protein expression was enhanced in myocardium(P<0.05,P<0.01,P<0.000 1.CONCLUSION Electroacupuncture preconditioning may promote macrophage M2 polarization,attenuate local inflammation,and reduce cardiomyocyte apoptosis by modulating the DNA-PK/Rictor/Myc signaling pathway,thus im-proving cardiac function and achieving myocardial protective effects.

Gastric cancer is a common tumor of the gastrointestinal tract, and the global trend in morbidity and mortality are not encouraging. Especially in advanced gastric cancer, patient survival outcome is an essential clinical concern and a vital outcome indicator in clinical outcome assessment. This article reviews the definition of clinical outcome assessment and the measurement tools that can be applied in gastric cancer patients, describes the detailed classification of clinical outcome assessment tools, and reviews the current status of the application of clinical outcome assessment in gastric cancer, analyzing the effects and shortcomings of its application, to provide a reference for the clinical staff in choosing the appropriate tools, and assisting in the comprehensive and holistic assessment of clinical outcomes for the promotion of the development of precision medicine.

ObjectiveTo investigate the induction of ferroptosis by polyphyllin Ⅱ （PPⅡ） in hepatocellular carcinoma HepG2 cells and its underlying mechanism. MethodThe effect of PPⅡ （0， 1.5， 3.0， 4.5， 6.0， 9.0， 18.0 mg·L^-1） on the in vitro proliferation of HepG2 cells was assessed using the methyl thiazolyl tetrazolium （MTT） assay. Colony formation ability of HepG2 cells was evaluated through a colony formation assay. Cell migration ability was assessed via a scratch assay. Lactate dehydrogenase （LDH） content in HepG2 cells was measured using a kit. Reactive oxygen species （ROS） levels in HepG2 cells were observed using a fluorescence inverted microscope. Malondialdehyde （MDA）， glutathione （GSH）， and free Fe²⁺ content in HepG2 cells were detected using respective kits. The mitochondrial ultrastructure in HepG2 cells was observed by transmission electron microscopy. The expression of ferroptosis-related proteins p53， solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， and transferrin receptor 1 （TFR1） in HepG2 cells was detected using Western blot. ResultCompared with the control group， the PPⅡ treatment groups showed significantly decreased survival rate of HepG2 cells in a dose-dependent manner （P<0.01）， significantly reduced number of cell colonies （P<0.01）， significantly shortened scratch healing distance， inverse correlation of the migration distance with drug concentration （P<0.01）， significantly increased LDH leakage in cells （P<0.01）， significantly enhanced relative fluorescence intensity of intracellular ROS， and significantly increased accumulation of lipid peroxide MDA （P<0.01）， decreased intracellular GSH content with increasing drug concentration （P<0.01）， and significantly enhanced fluorescence intensity of FeRhoNox-1 in cells （P<0.01）. Moreover， cells exhibited vacuolation， and mitochondria showed significant shrinkage with reduced or even disappeared cristae. Compared with the results in the control group， the expression of p53， ACSL4， and TFR1 proteins significantly increased， while the expression of SLC7A11 and GPX4 proteins significantly decreased in the PPⅡ treatment groups （P<0.05）. ConclusionIn summary， PPⅡ induces ferroptosis in HepG2 cells by regulating the p53/SLC7A11/GPX4 signaling axis， promoting ACSL4 expression and Fe³⁺ uptake， leading to an imbalance in the antioxidant system.

Gastric cancer is a common tumor of the gastrointestinal tract, and the global trend in morbidity and mortality are not encouraging. Especially in advanced gastric cancer, patient survival outcome is an essential clinical concern and a vital outcome indicator in clinical outcome assessment. This article reviews the definition of clinical outcome assessment and the measurement tools that can be applied in gastric cancer patients, describes the detailed classification of clinical outcome assessment tools, and reviews the current status of the application of clinical outcome assessment in gastric cancer, analyzing the effects and shortcomings of its application, to provide a reference for the clinical staff in choosing the appropriate tools, and assisting in the comprehensive and holistic assessment of clinical outcomes for the promotion of the development of precision medicine.

Objective:To explore the immune and angiogenesis-related genes in aortic valve stenosis(AS)and potential therapeutic targets, based on bioinformatics and machine learning analysis.Methods:AS data sets from the Gene Expression Omnibus(GEO), immune-related genes from the ImmPort database, and angiogenesis-related genes from the Genecards database and MsigDB were downloaded and combined to determine differentially expressed immune and angiogenesis-related genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analyses were performed.Protein-protein interaction(PPI)was analyzed by using STRING database.The key biomarkers were identified by two machine learning methods including Least Absolute Shrinkage Selection Operator(LASSO)and Support Vector Machine Recursive Feature Elimination(SVM-RFE), validated in training data set and verification data set by receiver operating characteristic curve(ROC), and analyzed by Gene Set Enrichment Analysis(GSEA).The subtypes of immune infiltrating cells were analyzed by CIBERSORT.Based on starBase, miRDB, miRWalk and hTFtarget databases, the mRNA-miRNA-TF was constructed.Finally, Potential therapeutic targets and drugs were analyzed through the CTD database.Results:A total of 90 DEGs related to AS, immune, and angiogenesis were obtained.Enrichment analysis found that DEIRGs were mainly related to immune regulation and cell cycle regulation, such as "leukocyte migration" , "cell chemotaxis" and "cytokine-cytokine receptor interaction" .84 related proteins and 548 interactions were obtained by PPI analysis.Two key biomarkers SecretograninⅡ(SCG2)and Tenascin-C(TNC)were identified by machine learning, which showed high diagnostic value for AS by ROC.SCG2 and TNC are mainly involved in the immune regulation by Enrichment analysis.The infiltration level of macrophage M0 in AS group was significantly higher than that in control group by CIBERSORT analysis.The correlation between macrophage M0 and macrophage M2 and SCG2 was the highest.879 mRNA-miRNA-TF, 253 potential therapeutic agents and 299 relationships were obtained.Conclusions:The key biomarkers, immune characteristics and potential therapeutic targets obtained from the research play a vital role in exploring the pathophysiological progress and new therapeutic strategies of AS.

【Objective】 To investigate the serological and molecular characteristics of HBsAg+ /HBV DNA non-reactive (NR) infections. 【Methods】 Samples tested as HBsAg+ and HBV DNA NR were confirmed by individual NAT repeat testing, viral particle concentration by PEG precipitation combined with in-house nested PCR and real-time quantitative PCR, anti-HBc testing, and HBsAg quantification. HBV sequences were compared with those from donors with chronic and occult infection as controls. 【Results】 A total of 792 195 samples were screened between January 2011 and December 2020, of which 53 (1: 14 947) were confirmed HBsAg+ /HBV DNA NR. HBV DNA was detected further in five (9.4%) samples; three S sequences and four Pre Core/Core sequences were obtained. Unique amino acid substitutions (P130T, P135Q/S, R151Q, G153S and S155F) were found in the Core protein that may affect virus packaging and replication. 【Conclusion】 Extremely low HBV DNA level was detected in plasmas of HBsAg+ /HBV DNA NR donors. Barely detectable HBV DNA might be associated with unusual mutations in the Pre Core/Core protein affecting viral replication. More sensitive HBV DNA and/or HBsAg assays may be considered to further reduce the potential HBV transfusion-transmission residual risk.

Objective:To explore the efficacy and safety of in-class transition from proteasome inhibitor bortezomib to ixazomib in the treatment of newly-treated patients with multiple myeloma (MM).Methods:The clinical data of 63 newly-treated MM patients in Shenzhen Second People's Hospital from January 2018 to December 2020 were retrospectively analyzed. They were divided into transition group (23 cases) and bortezomib group (40 cases). Both groups were treated with bortezomib-containing regimen as the first-line treatment regimen. In case of intolerable adverse reactions, patients in the transition group were treated with ixazomib instead of bortezomib, while the patients in the bortezomib group did not undergo drug transition. The curative effect and progression-free survival (PFS) were compared between the two groups.Results:In the transition group, the overall response rate (ORR) before in-class transition was 95.7% (22/23), the rate of ≥ very good partial remission (VGPR) was 52.2% (12/23); the ORR after transition was 95.7% (22/23), and the rate of ≥ VGPR was 82.6% (19/23). In the bortezomib group, ORR was 90.0% (36/40), and the rate of ≥ VGPR was 72.5% (29/40). There was no significant difference in ORR and the rate of ≥VGPR between the two groups ( χ2 = 0.64, P=0.424; χ2 = 0.82, P = 0.364). The median number of cycles of PI therapy in the transition group was 9, and the median PFS time was not reached. The median number of cycles of PI therapy in the bortezomib group was 7.5, and the median PFS time was 30.0 months (95% CI 19.1-40.9 months), there was no significant difference in PFS between the two groups ( P = 0.275). In the bortezomib group, 12 patients discontinued bortezomib due to adverse reactions, the median PFS time was 20.0 months (95% CI 12.6-27.4 months), and the PFS of patients who discontinued PI in the transition group and the bortezomib group was compared, the difference was statistically significant ( P = 0.043). In the transition group, 21 patients (21/23, 91.3%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 13.0% (3/23); in the bortezomib group, 22 patients (22/40, 55.0%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 12.5% (5/40). Conclusions:For newly-treated MM patients, the transition from bortezomib to ixazomib can improve the depth of remission and reduce the recurrence caused by the discontinuation of PI.