BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome

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).

Background::Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD.Methods::This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. Results::During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). Conclusions::LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

Objective:To discuss the host proteins that interact with the Nelson Bay orthoreovirus(NBV)σNS protein in the fibroblasts L929 of the mice,and to clarify the effect of host proteins on the viral replication.Methods:The bait plasmid pGBKT7-S3 expressing σNS protein was constructed,and sequencing technology was used to verify the accurate expression of the bait plasmid in the Y2H yeast cells.The pGBKT7-S3 and pGADT7 plasmids were separately and jointly transformed into the Y2HGold yeast cells,plated on solid medium,and the colony growth was observed to confirm that the σNS protein was non-toxic to the yeast cells and could not self-activate the reporter gene.The bait plasmid pGBKT7-S3 was hybridized with the cDNA library in fibroblasts L929 of the mice,and the plasmids encoding the interacting proteins were extracted from the positive clones.The positive sequencing results were screened for the proteins interacting with NBV σNS through the Uniprot database.Gene Ontology(GO)functional enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis,and STRING bioinformatics analysis were performed on the interacting proteins.Results:A total of 61 positive clones were successfully screened.The DNA sequencing analysis and BLAST alignment removed 23 positive clones that did not match the database or were similar in sequence.The positive sequencing results identified 38 proteins interacting with NBV σNS through the Uniprot database.Thirty-one proteins were involved in cellular biological processes;thirty-six proteins were cellular anatomical components;thirty-one proteins had binding functions.Five proteins were part of the mitochondrial respiratory chain;seven proteins were ribosomal proteins and components of the ribosomal subunits;two proteins were involved in iron metabolism homeostasis.The GO functional enrichment analysis results showed that the interacting proteins were enriched in biological processes(BP)such as cellular processes,metabolic processes,biological regulation,localization,and response to stimuli;the cellular components were mainly cellular anatomical components and protein-containing complexes;the molecular functions were concentrated in binding,catalytic activity,structural molecule activity,and transporter activity.The KEGG signaling pathway enrichment analysis results showed that the proteins were highly enriched in translation,folding,sorting,and degradation pathways of genetic information processing and were mainly associated with the digestive system in the organism;they were linked to various viral infections and cancers.The STRING analysis results showed that the interacting proteins included ribosomal proteins,protein modification proteins,metabolic proteins,and immune proteins.Conclusion:The host proteins that interact with NBV σNS protein are successfully screened,and these host proteins play important roles in viral replication.

Humans ; Cohort Studies ; Body Mass Index ; Percutaneous Coronary Intervention ; Coronary Artery Disease ; Inflammation ; Treatment Outcome ; Risk Factors

Objective : To screen the RNA binding proteins interacting with NBV nonstructural protein σNS in host cells and to analyze their bioinformatics functions. Methods : In this study , the eukaryotic expression vector pEF⁃HA⁃MB⁃S3 of NBV σ NS was constructed and transfected into HEK293T cells after verification. After RNase A treatment , the obtained protein lysate was enriched by immunoprecipitation to enrich σNS binding proteins , identified and analyzed by LC⁃MS/MS mass spectrometry , and the properties and specific functions of proteins were discovered with the help of related Bioinformatics tools. Results : In this study , 32 candidate RNA binding proteins interacting with NBV σNS proteins were successfully screened , and the results of bioanalysis showed that these proteins were mainly located in cytoplasm and nucleus , and were mainly involved in biological processes such as cell metabolism , biological regulation , virus translation and transcription. Conclusion This study preliminarily analyzes the function of RNA binding proteins interacting with NBV σNS , which lays a foundation for further study on the mechanism of σNS protein in NBV life cycle.

The key technology of the device for the viviperception of the animal mesenteric microcirculation is to simulate the celiac environment in the device. The technical requirements of the device for microcirculation viviperception are that the observation box should be able to "keep warm, preserve moisture, continually perfuse, and fix the sample"; and the lighting should be "intense", "convergence", and "cool". After actual application, it was found that the newly designed and developed the device by research personnel of Wannan Medical College for the viviperception of the animal mesenteric microcirculation can meet the technical requirements, which is able to "keep warm, preserve moisture, continually perfuse, and fix the sample", and using LED lamp as the microscope light source is "intense", "convergence", and "cool". This device is ingenious and reasonable in design, stable in technology, convenient in operation, and competent in microcirculation viviperception. It solves the technical problem to simulate the celiac environment for mesenteric microcirculation viviperception. The device provides convenience to observe and study the microcirculation, which is worth to be applicated widely.

Objective: To observe the use of clopidogrel and related factors for patients with acute coronary syndrome (ACS) in terms of early use, loading dose, dual antiplatelet therapy (DAPT) and maintenance dose hospitalized in non-PCI country hospitals in China. Methods: Patients hospitalized for ACS from 101 non-PCI country hospitals across China were recruited prospectively from October 2011 to November 2014. In-hospital clopidogrel use rate, the proportions of early use (within 24 hours), loading dose use (≥300 mg), DAPT (early use combined with aspirin) and maintenance dose use (following dose≥75 mg/d) were analyzed. Generalized estimated equation (GEE) model was used to explore factors associated to in-hospital clopidogrel use and loading dose use in both univariate and multivariate analyses, adjusting for cluster effect. Results: A total of 14 809 ACS patients were included, with an average age of (64.1±11.6) years and 60% (8 888/14 809) were male. The in-hospital clopidogrel use rate was 66.4% (9 828/14 809), which varied across different regions, years and sub-types of ACS (all P<0.05). Among users, the proportions of patients with early use, DAPT and maintenance dose use were 91.3% (8 734/9 562), 89.2% (8 526/9 562) and 95.1% (9 094/9 562), respectively, but the proportion of patients received loading dose was only 41.8% (3 995/9 562). Multivariate analyses showed that patients who admitted to hospital in earlier years and with non-ST elevation ACS, ≥75 years old, female, non-smoking, illiterate, heart rate≥100 beats per minute, atrial fibrillation, not on ECG monitoring, and not using other anti-ACS drugs were less likely to receive clopidogrel (all P<0.05). And those clopidogrel users who with non-ST elevation ACS, ≥75 years old, non-smoking, illiterate, not using other anti-ACS drugs were less likely to receive loading dose (all P<0.05). Conclusion The use rate of clopidogrel and the loading dose among in-hospital ACS patients are both low and remain to be improved in non-PCI county hospitals in China. Special attention should be paid on non-ST elevation ACS, ≥75 years old, female, and illiterate patients to increase the rational use of clopidogrel and the loading dose.

Objective: To evaluate the predictive value of GRACE discharge score on the long-term out-of-hospital coronary thrombotic events (CTE) after percutaneous coronary intervention (PCI) with drug-eluting stents. Methods: Present study was a prospective, observational, single center study. 10 724 consecutive patients underwent PCI in Fuwai Hospital between January and December 2013 were included, stents were implanted with conventional method. After PCI, patients were prescribed aspirin 100 mg once daily indefinitely, and either clopidogrel 75 mg once daily or ticagrelor 90 mg twice daily for at least 1 year. A total of 9 782 patients were included in the final analysis after excluding patients who did not undergo successful stent implantation, who were not discharged on dual anti-platelet therapy (DAPT), who only underwent bare-metal stents, who experienced in-hospital major bleeding, stent thrombosis, myocardial infarction (MI) or death,and who lost follow up. Clinical data were collected from all patients. 9 543 patients with complete baseline data were further analyzed for risk stratification and predictive value of GRACE discharge score. CTE was defined as stent thrombosis or spontaneous myocardial infarction. All patients were followed through Fuwai Hospital Follow-up Center, and evaluated either by phone, letter, or clinic visits or at 1, 6, 12 and 24 months after PCI. Risk stratification was performed according to the GRACE discharge score, and the predictive value of the GRACE discharge score was assessed using the receiver operating characteristic (ROC) curve. Results: After 2 years follow-up, there were 95 CTE among the 9 782 patients. The patients were divided into 2 groups according to the presence or absence of CTE: CTE group (95 cases) and no CTE group (9 687 cases). GRACE discharge score was significantly higher in CTE group than no CTE group (82.98±27.58 vs. 75.51±22.46, t=-2.57, P=0.012). According to risk stratification of GRACE discharge score, the patients were divided into low-risk (≤88) group (n=6 902), moderate-risk (89-118) (n=2 988) and high-risk (>118) (n=343) groups. As compared to the low-risk group, CTE risk in moderate- and high-risk groups was 1.59 times (HR 1.59, 95%CI 1.01-2.52, P=0.046) and 3.89 times higher (HR 3.89, 95%CI 1.98-7.65, P<0.001), respectively. Further analysis showed that the GRACE score had predictive value in the total cohort for CTE (area under the receiver operating characteristic (AUROC) 0.576, 95%CI 0.512-0.640, P=0.012) and in the acute coronary syndromes(ACS) subgroup for CTE: (AUROC 0.594, 95%CI 0.509-0.680, P=0.019), but not in the non-ACS subgroup: (AUROC 0.561, 95%CI 0.466-0.657, P=0.187). Conclusion GRACE discharge score can predict the long-term out-of-hospital CTE in patients undergoing PCI with drug-eluting stents and treated with DAPT, and patients can be stratified into the low-, moderate- and high-risk groups of CTE by the GRACE discharge score.