Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

Aim To explore the role of Takeda G pro-tein-coupled receptor 5(TGR5)in the proliferation and migration of vascular smooth muscle cells(VSMCs)within the intimal layer of mice.Methods Mouse VSMCs were stimulated for proliferation and migration with PDGF-BB,followed by administration of INT-777 for activation of TGR5.CCK-8 assay and Ki-67 immunofluorescence staining were employed to eval-uate cell proliferation.The scratch assay was utilized to assess migration.Western blot analysis was conducted to monitor TGR5 protein expression.To further investi-gate the role of TGR5 in intimal hyperplasia in vivo,20 male wild-type C57BL/6J mice were randomly divided into four groups:sham group,carotid artery endothelial injury group,sham+UDCA(ursodeoxy-cholic acid,a TGR5 agonist)group,and carotid artery endothelial injury+UDCA group(n=5 in each group).After the establishment of endothelial injury model,mice were orally fed with regular maintenance feed containing 0.5％UDCA for 21 days.Subsequent-ly,samples were collected for Hematoxylin and Eosin(HE)staining to assess the neointimal hyperplasia.Immunofluorescence(IF)staining was used to exam-ine the proliferation of VSMCs within the carotid inti-ma.Results The specific activation of TGR5 marked-ly diminished cell viability,the proportion of Ki-67-positive cells,and slowed down the rate of wound-heal-ing.Notably,the specific activation of TGR5 increases the expression of UCP2 in cells and reduces the levels of reactive oxygen species(ROS).The inhibitory effect of TGR5 on VSMC proliferation and migration was neutralized upon the restoration of intracellular ROS level with H2O2.Activation of TGR5 was found to mitigate intimal thickening following carotid artery inju-ry.Conclusion TGR5 may inhibit the proliferation and migration of mouse VSMCs by attenuating intracel-lular oxidative stress.

Aim To explore the antimicrobial activity of a novel R-type phage tail-like bacteriocin(PTLB)secreted by Enterobacter cloacae SHAMU191747 a-gainst methicillin-resistant Staphylococcus aureus(MR-SA).Methods Antagonistic activity of E.cloacae SHAMU191747 against MRS A was detected by LB agar plate antagonistic test and LB broth micro-fermentation test.The crude extract of fermentation supernatant of E.cloacae SHAMU191747 was prepared by ultra-high-speed centrifugation and density gradient centrifuga-tion.The novel R-type PTLB in the crude extract was detected by transmission electron microscopy.The an-timicrobial activity of the crude extract against MRSA was verified by LB agar plate spot-seeding method.The molecular weight of the novel R-type PTLB was detected by SDS-PAGE electrophoresis.Results E.cloacae SHAMU191747 secreted a novel R-type PTLB,and had a strong antagonistic effect on MRSA.The no-vel R-type PTLB had a molecular weight of approxi-mately 35 ku and could efficiently kill MRSA.The physical dimensions of its tail-sheath-uncontracted functional molecules were(142.7±4.3)×(13.8±0.6)nm,and those of the tail-sheath-contracted non-functional molecules were(57.7±1.2)×(20.8±1.5)nm.Conclusions The novel R-type PTLB pro-duced by E.cloacae SHAMU191747 can efficiently kill MRSA,and has the potential to be developed into a novel antimicrobial drug with great prospects for clini-cal application.

Objective:To investigate protective effect of wogonin on myocardial ischemia/reperfusion(MI/R)injury in rats,and to analyze its potential mechanism.Methods:SD rats were randomly separated into sham operation group,MI/R group,trimetazi-dine group(10 mg/kg),wogonin low,medium and high doses groups(5,10,20 mg/kg),with 12 rars per group.MI/R model was established by ligation of left anterior descending coronary artery for 30 min and reperfusion for 24 h.Echocardiography was applied to detect cardiac function in rats,ELISA was applied to detect activities of serum lactate dehydrogenase(LDH),creatine kinase isoen-zyme(CK-MB)and levels of TNF-α,IL-6 and IL-1β in rats;TTC staining was applied to detect myocardial infarct size;HE staining was applied to detect myocardial histopathological changes;TUNEL staining was applied to detect apoptosis level of cardiomyocytes;immunohistochemistry(IHC)method was applied to detect expression of nuclear factor-κB(NF-κB)p65 in myocardial tissue;Western blot was applied to detect myocardial apoptosis and expressions of NF-κB/mitogen-activated protein kinase(MAPK)pathway-related proteins.Results:Compared with sham operation group,LVESD,LVEDD,serum CK-MB and LDH activities,levels of IL-6,IL-1β and TNF-α,myocardial infarction area percentage,myocardial cell apoptosis rate,protein level of Bax,expression of nuclear NF-κB p65,and Cleaved-Caspase-3/Caspase-3,p-P38 MAPK/P38 MAPK in MI/R group were obviously increased,EF,FS and pro-tein levels of Bcl-2 were obviously decreased(P<0.05),myocardial fibers were disordered,and a large number of inflammatory cells were infiltrated;compared with MI/R group,LVESD,LVEDD,serum CK-MB and LDH activities,levels of IL-6,IL-1β and TNF-α,myocardial infarction area percentage,myocardial cell apoptosis rate,protein level of Bax,expression of nuclear NF-κB p65,and Cleaved-Caspase-3/Caspase-3 and p-P38 MAPK/P38 MAPK in trimetazidine group and wogonin high,medium and low doses groups were obviously decreased,EF,FS and protein levels of Bcl-2 were obviously increased(P<0.05),myocardial inflammatory cell infil-tration and muscle fiber fragmentation were reduced in a dose-dependent manner.Conclusion:Wogonin may improve MI/R injury in rats by inhibiting NF-κB/MAPK signaling pathway,inhibiting inflammatory response and cardiomyocyte apoptosis.

Objective To construct models of viral transfection and hypoxia/reoxygenation induced cellular injury in adult mouse cardiomyocytes(AMCMs)isolated using a non-Langendorff method.Methods AMCMs were isolated,extracted,sedimented,and plated using a non-Langendorff method.The morphology and survival rate of the isolated cells were evaluated 2,24,48 and 72 h after plating,and their integrity was observed by immunofluorescence staining for α-actinin.The isolated AMCMs were infected with adenoviruses carrying an RFP-expressing vector and fluorescence images were obtained at 36 and 48 h post-infection and used to calculate transfection efficiency.The cells were cultured under hypoxic conditions for 45 min,reoxygenated for 24 h,and then stained with propidium iodide(PI)to verify establishment of the hypoxia/reoxygenation injury model.Results The survival rates of AMCMs at 2,24 and 48 h after plating were comparable,but survival was significantly reduced at 72 h.The integrity of the AMCMs was good and＞80%of the cells were transfected with adenovirus at 48 h.After hypoxia/reoxygenation treatment,42%of cells were stained by PI,suggesting successful establishment of the AMCM injury model.Conclusions In this study,we developed a non-Langendorff method for the fast and easy isolation of AMCMs with high cell viability.The isolated cells can be efficiently infected with adenovirus and respond to hypoxia/reoxygenation injury.These findings provide a systematic method for isolating AMCMs and for applying gene modification and hypoxia/reoxygenation injury in these cells.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

Health system performance and its influencing factors are measured from a subjective perspective in the context of high-quality development.Using data from the Chinese Social Survey from 2015 to 2021,this study constructed a health system performance index from the perspective of the sense of acquisition of the population and analyzed the change trends and influencing factors of China's health system performance through a multilayer regression model.The results showed that the comprehensive index of health system performance in China increased by 12.47%(β=6.143,P<0.01)from 41.732 in 2015 to 46.935 in 2021,of which the process index increased by 4.57%(β=2.391,P<0.01)from 43.961 to 45.968,and the outcome index increased from 48.501 to 58.009,an increase of 19.60%(β=11.504,P<0.01).Meanwhile,the sense of access to health system performance showed obvious heterogeneity,with factors such as gender,age,education,marital status,employment status,economic status,type of health insurance and type of area of residence significantly affecting the sense of access to health system performance of residents.The health system performance in China in the context of high-quality development has significantly improved,and the sense of access of residents has significantly increased.However,the improvement in the process dimension of the health system is relatively limited,and"difficult and expensive to see a doctor"remains serious.It's necessary to strength the health system performance of vulnerable groups,as well as rural areas.

Objective:To explore the effect and mechanism of family doctor contract services on the health of rural residents with chronic diseases.Methods:From June to August 2023,1 191 valid samples from 12 counties in 6 provinces were collected through face-to-face questionnaire survey.Tobit model and KHB method were used to analyze the effect of family doctor contract services on EQ-5D-5L utility index scores and its path.Results:The family doctor contract rate was 59.19％and the utility index score was 0.831.Family doctor contract services significantly improved the health utility index scores of chronic disease patients(β=0.047,P＜0.05);The utility index score was affected completely through public health services(β=0.028,P＜0.01,95％CI=0.009～0.047),and the indirect effect accounted for 66.77％of the total effect.Conclusion:The family doctor contract rate of rural residents with chronic diseases is low in China,and the health-related quality of life is not good.The family doctor contract services can improve the health-related quality of life of patients with chronic diseases mainly by improving public health services.It is urgent to strengthen the effects of family doctor contract services on medical service utilization and individual health behavior,so as to give full play to the health effects of family doctor contract services.

Objective:The main purpose of this study is to analyse the current situation and inequity status of children's medical security in China from the vision of children first.Methods:Using data from the China Family Panel Studies 2020 and based on the framework of universal health coverage cube,multivariate regression is used to analyse the differences in medical security between children and adults and among groups of children.Results:The participation rate of children in China is 80.96%,out-of-pocket ratios are 64.71%and 90.09%for inpatient and outpatient groups respectively.In terms of participation rate,insured children are less than that of adults(OR=0.434,P＜0.01);within children's groups,attending school(OR=2.075,P＜0.01)significantly increases children's participation rate,while left-behind by parent(s)(OR=0.791,P＜0.05)significantly decrease children's participation rate.With respect to service and cost coverage,children have higher out-of-pocket ratios compared to adults(β=0.066,P＜0.01);within children's groups,children eged 6 years and older have lower out-of-pocket medical expenses(β＜-0.316,P＜0.01),children with higher family income(β＜-0.022,P＜0.05),participated(β=-0.033,P＜0.01),and hospitalized(β=-0.270,P＜0.01)have lower out-of-pocket ratios.Conclusion:Double in equality exists in children's medical security in China.The level of children's health security in China is significantly lower than that of adults;within children's groups,children aged 0～5 years,not in school,left-behind by parent(s),and from lower-income families are more vulnerable.It is proposed to focus on increasing the participation rate of children through measures such as optimizing the contribution for children and launching family joint insurance.Policy design should also consider the needs of children and raise the level of children's benefits.Meanwhile,the focus should be on helping vulnerable groups in children,so as to ultimately achieve"children first"in health security.

Transcatheter aortic valve replacement(TAVR)is one of the most important guideline-recommended procedures for severe symptomatic aortic stenosis.Acute cerebral infarction is a serious complication after TAVR,with a high incidence rate and may significantly affect patient prognosis and quality of life.Thrombolysis and mechanical thrombectomy are standard treatments for acute cerebral infarction recommended by guidelines,but evidence of their efficacy and safety in patients undergoing TAVR is limited.We report a patient with acute cerebral infarction after TAVR,who were treated with emergency cerebral angiography and successful transcatheter thrombectomy.