ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion （CIRI） injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups： A sham operation group， a model group， Taohong Siwutang treatment groups （low dose， medium dose， and high dose）， ligustrazine phosphate tablet （LPT） group， and AG490 group. All groups， except for the sham operation group， underwent middle cerebral artery occlusion/reperfusion （MCAO/R） modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2，3，5-triphenyltetrazolium chloride （TTC） staining. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 （C3）， S100 calcium-binding protein A10 （S100A10）， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription 3 （STAT3）. Additionally， protein expression levels of vascular endothelial growth factor-A （VEGF-A） were assessed， and the mRNA expression levels of inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were evaluated. Glial fibrillary acidic protein （GFAP） and C3， S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly， VEGF expression levels were measured using enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham operation group， the model group showed a significant increase in cerebral infarction volume and neurological impairment （P<0.01）. C3 protein levels were elevated， while S100A10 levels were decreased. Pathway-related markers were significantly upregulated （P<0.05， P<0.01）， and VEGF-A protein levels were significantly reduced （P<0.01）. The mRNA expression of inflammatory factors was significantly upregulated （P<0.01）. Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity （P<0.01） and greatly decreased GFAP and S100A10 fluorescence intensity （P<0.01）. Additionally， VEGF content was significantly elevated （P<0.01）. Compared with the model group， medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment （P<0.01）. Groups treated with low， medium， and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels （P<0.01）. In the high-dose Taohong Siwutang and AG490 groups， both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated （P<0.05， P<0.01）， while S100A10 expression and VEGF-A protein levels were significantly increased （P<0.01）. Additionally， the mRNA expression levels of inflammatory factors were significantly reduced （P<0.01）. The co-localization fluorescence intensity of GFAP and C3 significantly decreased （P<0.01）， while that of GFAP and S100A10 greatly increased （P<0.01）. Furthermore， VEGF content exhibited a marked elevation （P<0.01）. ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway， promotion of A2-type astrocyte polarization， reduction of inflammatory factor release， and enhancement of VEGF production.

ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion （CIRI） injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups： A sham operation group， a model group， Taohong Siwutang treatment groups （low dose， medium dose， and high dose）， ligustrazine phosphate tablet （LPT） group， and AG490 group. All groups， except for the sham operation group， underwent middle cerebral artery occlusion/reperfusion （MCAO/R） modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2，3，5-triphenyltetrazolium chloride （TTC） staining. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 （C3）， S100 calcium-binding protein A10 （S100A10）， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription 3 （STAT3）. Additionally， protein expression levels of vascular endothelial growth factor-A （VEGF-A） were assessed， and the mRNA expression levels of inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were evaluated. Glial fibrillary acidic protein （GFAP） and C3， S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly， VEGF expression levels were measured using enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham operation group， the model group showed a significant increase in cerebral infarction volume and neurological impairment （P<0.01）. C3 protein levels were elevated， while S100A10 levels were decreased. Pathway-related markers were significantly upregulated （P<0.05， P<0.01）， and VEGF-A protein levels were significantly reduced （P<0.01）. The mRNA expression of inflammatory factors was significantly upregulated （P<0.01）. Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity （P<0.01） and greatly decreased GFAP and S100A10 fluorescence intensity （P<0.01）. Additionally， VEGF content was significantly elevated （P<0.01）. Compared with the model group， medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment （P<0.01）. Groups treated with low， medium， and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels （P<0.01）. In the high-dose Taohong Siwutang and AG490 groups， both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated （P<0.05， P<0.01）， while S100A10 expression and VEGF-A protein levels were significantly increased （P<0.01）. Additionally， the mRNA expression levels of inflammatory factors were significantly reduced （P<0.01）. The co-localization fluorescence intensity of GFAP and C3 significantly decreased （P<0.01）， while that of GFAP and S100A10 greatly increased （P<0.01）. Furthermore， VEGF content exhibited a marked elevation （P<0.01）. ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway， promotion of A2-type astrocyte polarization， reduction of inflammatory factor release， and enhancement of VEGF production.

OBJECTIVE To evaluate the effects of ivabradine on vascular endothelial function in patients with coronary artery disease. METHODS PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang Data， VIP and CBM databases were retrieved to collect randomized controlled trials （RCTs） about ivabradine （intervention group） versus placebo or β-blocker （control group） from the inception to Mar. 20th 2023. The meta-analysis was performed by using RevMan 5.4 software after literature screening， data extraction and quality evaluation. RESULTS A total of 12 RCTs were included， involving 1 206 patients. The results of meta-analysis showed that the levels of flow-mediated dilation （FMD） [MD＝1.71， 95%CI （0.96， 2.46）， P＜0.000 01] and nitric oxide （NO） [MD＝5.80， 95%CI （5.02， 6.59）， P＜0.000 01] in the intervention group were significantly higher than control group， while endothelin-1（ET-1） level was significantly lower than control group [MD＝－7.45， 95%CI （－8.42， －6.47）， P＜0.000 01]. There was no statistical significance in nitroglycerin-mediated dilation （NMD） level between 2 groups [MD＝0.13， 95%CI（－0.74， 1.00）， P＝0.77]. Subgroup analyses based on the different medications and intervention time in the control group showed better improvement in FMD level of patients receiving ivabradine， compared with placebo （P＜0.05）； compared with placebo and β-blocker， the level of NO in patients receiving ivabradine was improved significantly （P＜0.05）， while ET-1 level was decreased significantly （P＜0.05）. Regardless of the duration of the intervention， the levels of FMD， NO， and ET-1 in the intervention group were significantly improved compared to the control group （P＜0.01）， while the difference in NMD was not statistically significant （P＞0.05）. CONCLUSIONS Ivabradine can improve vascular endothelial function in patients with coronary artery disease.

Objectives:To assess the effectiveness and safety of ivabradine for the treatment of chronic heart failure in the context of the new quadruple combination. Methods:Clinical data of 656 chronic heart failure patients hospitalized in Nanjing Drum Tower Hospital from March 2021 to June 2022 were retrospectively collected,and the patients were divided into control group(n=361)and observation group(n=295)according to ivabradine use,and both groups were treated with the new quadruple drug therapy.Propensity score matching was performed,268 patients in the observation group and 268 patients in the control group were successfully matched.The effectiveness(primary endpoint was the composite endpoint of cardiovascular death and rehospitalisation for worsening heart failure within 1 year of discharge;secondary endpoints were rehospitalisation for worsening heart failure,all-cause rehospitalisation,cardiovascular death,and all-cause death)and safety outcome measures(including bradycardia,atrial fibrillation,blurred vision,renal impairment,and hypertension)were compared between the two groups at 1 year after treatment. Results:After matching,there were no statistically significant differences at baseline characteristics between the two groups.Kaplan-Meier survival curve showed that the occurrence rates of primary endpoints(P=0.031),readmission for worsening heart failure(P=0.020),and all-cause readmission(P=0.036)were lower in the observation group than in the control group.Multivariate Cox proportional hazard regression analysis showed that the occurrence rates of primary endpoint events(P=0.045)and readmission for heart failure worsening(P=0.028)were lower in the observation group than in the control group. Conclusions:The ivabradine use on top of the new quadruple therapy regimen in patients with chronic heart failure is beneficial to improve one-year prognosis with favorable safety profile.

Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.

Objective To explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5％.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P＜0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P＞0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.

Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*

Objective: To evaluate the safety of simultaneous administration of quadrivalent influenza split virion vaccine and 23-valent pneumococcal polysaccharide vaccine in adults aged 60 years and older. Methods: From November 2021 to May 2022, eligible participants aged 60 years and older were recruited in Taizhou City, Jiangsu Province, China, and a total of 2 461 participants were ultimately enrolled in this study. Each participant simultaneously received one dose of quadrivalent influenza split virion vaccine and one dose of 23-valent pneumococcal polysaccharide vaccine. The safety was observed within 28 days after vaccination. Safety information was collected through voluntary reporting and regular follow-ups. Results: All 2 461 participants completed the simultaneous administration of both vaccines and the safety follow-ups for 28 days after vaccination. The mean age of the participants was (70.66±6.18) years, with 54.61% (1 344) being male, and all participants were Han Chinese residents. About 22.51% (554) of the participants had underlying medical conditions. The overall incidence of adverse reactions within 0-28 days after simultaneous vaccination was 2.07% (51/2 461), mainly consisting of Grade 1 adverse reactions [1.83% (45/2 461)], with no reports of Grade 4 or higher adverse reactions or vaccine-related serious adverse events. The incidence of local adverse reactions was 0.98% (24/2 461), primarily presenting as pain at the injection site [0.93% (23/2 461)]. The incidence of systemic adverse reactions was 1.42% (35/2 461), with fever [0.85% (21/2 461)] being the main symptom. In the group with underlying medical conditions and the healthy group, their overall incidence of adverse reactions was 2.53% (14/554) and 1.94% (37/1 907), respectively. The incidence of local adverse reactions in the two groups was 1.62% (9/554) and 0.79% (15/1 907), respectively, and the incidence of systemic adverse reactions was 1.44% (8/554) and 1.42% (27/1 907), respectively, with no statistically significant differences between them (all P>0.05). Conclusion: It is safe for adults aged 60 years and older to receive quadrivalent influenza split virion vaccine and 23-valent pneumococcal polysaccharide vaccine at the same time.

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.