Objective To evaluate the anticoagulation efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in patients with high-risk atrial fibrillation (AF) undergoing transcatheter aortic valve implantation (TAVI). Methods A computer-based search was conducted on PubMed, EMbase, The Cochrane Library, CNKI, SinoMed, and VIP databases to identify studies on the application of NOACs and VKAs in high-risk AF patients after TAVI. The search period was from database inception to January 2023. The quality of the included studies was assessed using the Cochrane risk assessment tool and the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using RevMan 5.4 software. Results A total of 7 studies involving 24 592 patients were included. The meta-analysis results showed that compared to patients using VKAs, those treated with NOACs had a significantly lower risk of all-cause mortality [RR=0.74, 95%CI (0.58, 0.94), P=0.01]. Subgroup analysis indicated that when the follow-up period was less than 1 year, there was no significant difference in all-cause mortality between the NOAC and VKA groups [RR=0.57, 95%CI (0.17, 1.88), P=0.35]; however, when the follow-up period was ≥1 year, the VKA group had a higher all-cause mortality rate than the NOAC group, with a statistically significant difference [RR=0.73, 95%CI (0.57, 0.95), P=0.02]. No significant differences were found between the two groups regarding early stroke [RR=0.50, 95%CI (0.19, 1.28), P=0.15], stroke during follow-up [RR=1.04, 95%CI (0.88, 1.22), P=0.64], bleeding [RR=0.94, 95%CI (0.73, 1.21), P=0.61], major or life-threatening bleeding [RR=0.80, 95%CI (0.49, 1.31), P=0.38], or acute kidney injury [RR=0.51, 95%CI (0.16, 1.59), P=0.24]. Conclusion Compared to VKAs, the use of NOACs in patients with high-risk AF undergoing TAVI may reduce the risk of all-cause mortality, especially during long-term anticoagulation therapy, potentially offering greater benefits. However, further evidence from randomized controlled trials is needed to confirm these findings.

Objective:To explore the improvement of the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection and conduct safety tests including abnormal toxicity test,allergic reaction test,hemolysis and coagulation test.Methods:Ginkgo Leaf Extract and Dipyridamole Injection from 3 different manufactures(A,B and C)were tested respectively through abnormal toxicity test and acute toxicity test in mice,active systemic anaphylaxis test in guinea pigs and hemolysis test in vitro.Five mice were used in each batch for abnormal toxicity test according to the abnormal toxicity test method in general notice of the Chinese Pharmacopoeia 2020 Volume Ⅳ(1141),and 50 mice were selected in each batch for acute toxicity test to determine the median lethal dose(LD50)or maximum tol-erable dose(MTD)of Ginkgo Leaf Extract and Dipyridamole Injection,which were used to establish the method of abnormal toxicity experiment.The anaphylaxis of Ginkgo Leaf Extract and Dipyridamole Injection was evaluated by active systemic anaphylaxis test in guinea pigs,which was used to establish the method of allergic test.The hemoly-sis test of Ginkgo Leaf Extract and Dipyridamole Injection was studied by conventional tube method in vitro(macro-scopic observation)and improved hemolysis method in vitro(spectrophotometric method),which were used to establish the method of hemolysis and coagulation test.Results:① In manufacture A,the results of abnormal toxicity test were showed that LD50 was20.8 mL·kg-1and MTD was 16.5 mL·kg-1.No death or abnormal reac-tions were observed in mice tested for abnormal toxicity of 2 manufactures(B and C),and MTD was 50 and 40 mL·kg-1,respectively.②The no-observed-adverse-effect dose of Ginkgo Leaf Extract and Dipyridamole Injec-tion from 3 manufactures to guinea pig intravenous was 0.83 mL·kg-1,and no allergic reaction symptoms were observed when Ginkgo Leaf Extract and Dipyridamole Injection was diluted 4 times to challenge the sensitized guinea pigs(equivalent to human clinical dosage).③Differences were observed in the hemolytic effects of Ginkgo Leaf Extract and Dipyridamole Injection from 3 manufactures,but no obvious hemolytic reaction occurred when it was diluted 1.2 times(equivalent to 5%of the maximum clinical concentration).Conclusion:It is recommended to add abnormal toxicity test,allergic reaction test,hemolysis and coagulation test in the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection as safety test items to control the risk.The proposed method is diluting Ginkgo Leaf Extract and Dipyridamole Injection by 5 times,4 times and 1.2 times to perform abnormal toxicity test,allergic reaction test,hemolysis test and coagulation test respectively.

Objective:To analyze the value of marginal donor livers in liver transplantation for patients with acute-on-chronic liver failure (ACLF).Methods:Clinical data of 58 patients with ACLF undergoing liver transplantation at the First Affiliated Hospital of Guangxi Medical University from January 2020 to June 2023 were retrospectively analyzed, including 33 males and 25 females, aged (40.4±14.4) years. According to the source of donor (marginal or standard), recipients were divided into the marginal group ( n=28), and standard group ( n=30). The preoperative model for end-stage liver disease (MELD) score, cold/warm ischemia time, intraoperative blood loss, postoperative tracheal intubation time, intensive care unit (ICU) stay, liver function, renal function, coagulation function, postoperative complications, and survival situation were compared between the groups. Results:The MELD score, cold/warm ischemia time, intraoperative blood loss, postoperative tracheal intubation time, length of ICU stay, alanine transaminase, aspartate transaminase, total bilirubin, serum creatinine, blood urea nitrogen, estimated glomerular filtration rate, fibrinogen, postoperative infection, primary graft nonfunction, biliary complications, and vascular complications were compared between the groups (all P>0.05). The incidence of delayed graft function (DGF) recovery was 28.6%(8/28) in marginal group, higher than that in standard group 6.7%(2/30) ( χ2=5.13, P=0.038). The one-year cumulative survival rates were 89.3% and 93.3% in marginal group and standard group, respectively ( P=0.580). Conclusion:The therapeutic effect of marginal donor liver in ACLF recipients is comparable to that of standard donor liver. The incidence of DGF is higher in recipients with marginal donor liver.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective:To explore the improvement of the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection and conduct safety tests including abnormal toxicity test,allergic reaction test,hemolysis and coagulation test.Methods:Ginkgo Leaf Extract and Dipyridamole Injection from 3 different manufactures(A,B and C)were tested respectively through abnormal toxicity test and acute toxicity test in mice,active systemic anaphylaxis test in guinea pigs and hemolysis test in vitro.Five mice were used in each batch for abnormal toxicity test according to the abnormal toxicity test method in general notice of the Chinese Pharmacopoeia 2020 Volume Ⅳ(1141),and 50 mice were selected in each batch for acute toxicity test to determine the median lethal dose(LD50)or maximum tol-erable dose(MTD)of Ginkgo Leaf Extract and Dipyridamole Injection,which were used to establish the method of abnormal toxicity experiment.The anaphylaxis of Ginkgo Leaf Extract and Dipyridamole Injection was evaluated by active systemic anaphylaxis test in guinea pigs,which was used to establish the method of allergic test.The hemoly-sis test of Ginkgo Leaf Extract and Dipyridamole Injection was studied by conventional tube method in vitro(macro-scopic observation)and improved hemolysis method in vitro(spectrophotometric method),which were used to establish the method of hemolysis and coagulation test.Results:① In manufacture A,the results of abnormal toxicity test were showed that LD50 was20.8 mL·kg-1and MTD was 16.5 mL·kg-1.No death or abnormal reac-tions were observed in mice tested for abnormal toxicity of 2 manufactures(B and C),and MTD was 50 and 40 mL·kg-1,respectively.②The no-observed-adverse-effect dose of Ginkgo Leaf Extract and Dipyridamole Injec-tion from 3 manufactures to guinea pig intravenous was 0.83 mL·kg-1,and no allergic reaction symptoms were observed when Ginkgo Leaf Extract and Dipyridamole Injection was diluted 4 times to challenge the sensitized guinea pigs(equivalent to human clinical dosage).③Differences were observed in the hemolytic effects of Ginkgo Leaf Extract and Dipyridamole Injection from 3 manufactures,but no obvious hemolytic reaction occurred when it was diluted 1.2 times(equivalent to 5%of the maximum clinical concentration).Conclusion:It is recommended to add abnormal toxicity test,allergic reaction test,hemolysis and coagulation test in the quality standard of Ginkgo Leaf Extract and Dipyridamole Injection as safety test items to control the risk.The proposed method is diluting Ginkgo Leaf Extract and Dipyridamole Injection by 5 times,4 times and 1.2 times to perform abnormal toxicity test,allergic reaction test,hemolysis test and coagulation test respectively.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.

Objective:To analyze the value of marginal donor livers in liver transplantation for patients with acute-on-chronic liver failure (ACLF).Methods:Clinical data of 58 patients with ACLF undergoing liver transplantation at the First Affiliated Hospital of Guangxi Medical University from January 2020 to June 2023 were retrospectively analyzed, including 33 males and 25 females, aged (40.4±14.4) years. According to the source of donor (marginal or standard), recipients were divided into the marginal group ( n=28), and standard group ( n=30). The preoperative model for end-stage liver disease (MELD) score, cold/warm ischemia time, intraoperative blood loss, postoperative tracheal intubation time, intensive care unit (ICU) stay, liver function, renal function, coagulation function, postoperative complications, and survival situation were compared between the groups. Results:The MELD score, cold/warm ischemia time, intraoperative blood loss, postoperative tracheal intubation time, length of ICU stay, alanine transaminase, aspartate transaminase, total bilirubin, serum creatinine, blood urea nitrogen, estimated glomerular filtration rate, fibrinogen, postoperative infection, primary graft nonfunction, biliary complications, and vascular complications were compared between the groups (all P>0.05). The incidence of delayed graft function (DGF) recovery was 28.6%(8/28) in marginal group, higher than that in standard group 6.7%(2/30) ( χ2=5.13, P=0.038). The one-year cumulative survival rates were 89.3% and 93.3% in marginal group and standard group, respectively ( P=0.580). Conclusion:The therapeutic effect of marginal donor liver in ACLF recipients is comparable to that of standard donor liver. The incidence of DGF is higher in recipients with marginal donor liver.

Objective To establish a method for bacterial endotoxin test of flumazenil bulk drug.Methods According to the bacterial endotoxin test(BET)method in general rule 1143 in the Chinese Pharmacopoeia(2020 Edition,VolumeⅣ),flumazenil was dissolved with dimethyl sulfoxide(DMSO)and diluted with BET water.The gel-clot method and kinetic turbidimetric assay were used to carry out the interference test and endotoxin recovery test.Results Flumazenil was dissolved with DMSO to 10 mg·mL-1,and then diluted 100 times or more by BET water,which has no interference effects on the bacterial endotoxin test.Conclusion The BET method established in this study can be used to control the quality of flumazenil by performing bacterial endotoxin tests.

Chemogenetic technology is a receptor-ligand system that regulates cell viability and function by changing receptor specificity and affinity, and it achieves precise neuronal regulation by specifically regulating neurons and neural circuits. At present, this technique is widely used in the study of neural circuits. This article briefly describes the application and progress of chemogenetic technology in the study of depression neural circuits, reviews the application of chemogenetic technology in several brain regions closely related to depression, such as ventral tegmental area, nucleus accumbens, prefrontal cortex, hippocampus and lateral habenula, and discusses the potential and challenges of chemogenetic technology as a technology for precise regulation of neural activity in future research, in order to provide reliable ideas and directions for chemogenetic technology in the study of depression neural circuits.

Objective:To investigate the effect of BOPPPS teaching model combined with virtual simulation technologyin the teaching of Prevention and treatment of Major Infectious Diseases,in order to explore innovative teaching model and provide evidence for improving students'comprehensive ability to deal with major infectious disease events.Methods:Undergraduates from three classes of preventive medicine major in a medical university were selected as the research objects.One class was given the new teaching model,and the other two classes were given the traditional teaching model.The total scores,the theoretical score and the skill score were compared between the two groups.Results:A total of 141 students participated in the survey,49 students in the new teaching model group,and 92 students in the traditional teaching model group.The results showed that compared with the traditional model group,the total score,the theoretical score,the skill score of the new model group was significantly higher(P＜0.01).However,there was no significant difference between male and female students in each group(P＞0.05).Conclusions:Compared with the traditional teaching model,the students in the new teaching model has a good teaching effect,which can improve the students'theoretical knowledge level,cultivate the students'emergency response ability,and improve the students'comprehensive ability of discovery,analysis and solution.Boys and girls have the same acceptance of the two teaching models,and gender does not affect the teaching effect.