Real-world experience of Fuzheng Yiqing granule as chemoprophylaxis against COVID-19 infection among close contacts: A prospective cohort study.

BACKGROUND: The objective of the current study was to evaluate whether the use of traditional Chinese medicine, Fuzheng Yiqing granule (FZYQG), was associated with a reduced infection risk of COVID-19 in close contacts. RESEARCH DESIGN AND METHODS: This was a prospective cohort study across 203 quarantine centres for close contacts and secondary contacts of COVID-19 patients in Yangzhou city. FZYQG group was defined as quarantined individuals who voluntarily took FZYQG; control group did not take FZYQG. The primary outcome was the coronavirus test positive rate during quarantine period. Logistic regression with propensity score inverse probability weighting was used for adjusted analysis to evaluate independent association between FZYQG and test positive rate. RESULTS: From July 13, 2021 to September 30, 2021, 3438 quarantined individuals took FZYQG and 2248 refused to take the granule. Test positive rate was significantly lower among quarantined individuals who took FZYQG (0.29% vs. 1.73%, risk ratio 0.17, 95% confidence interval (CI): 0.08-0.34, p < 0.001). On logistic regression, odds for test positive were decreased in FZYQG group (odds ratio: 0.16, 95% CI: 0.08-0.32, p < 0.001). CONCLUSIONS: Close and secondary contacts of COVID-19 patients who received FZYQG had a lower test positive rate than control individuals in real-world experience. TRIAL REGISTRATION: This study has been registered on Chinese Clinical Trial Registry (ChiCTR2100049590) on August 5, 2021.

Dazhu Hongjingtian Injection for Ischemic Stroke: Protocol for a Prospective, Multicenter Observational Study.

BACKGROUND: Although results from in vitro studies and small randomized controlled trials have shown positive effects of Dazhu hongjingtian injection (DZHJTI) on acute ischemic stroke (AIS), their generalizability to routine clinical practice remains to be established. OBJECTIVE: The primary aim of this study is to evaluate the effectiveness of DZHJTI treatment for AIS with regard to changes in the stroke-related neurological deficit from baseline to outpatient follow-up, mortality, subsequent vascular events, disability, and traditional Chinese medicine syndrome in real-world clinical settings. By monitoring for adverse events or significant changes in vital signs and laboratory parameters, we also aim to assess the safety of DZHJTI. METHODS: This prospective, multicenter cohort study plans to enroll 2000 patients with AIS within 14 days of symptom onset from 30 hospitals across China. Eligible patients will be followed up for 6 months after initiating medication treatments. The primary outcome will be the change in the National Institute of Health Stroke Scale score from baseline to outpatient follow-up. The secondary outcomes include overall mortality, stroke recurrence, new-onset major vascular events, global disability, and improvement of traditional Chinese medicine syndrome in 6 months. Adverse events or clinically significant changes in vital signs and laboratory parameters, regardless of the severity, will be recorded during the trial to assess the safety of DZHJTI. An augmented inverse propensity weighted estimator will be used to reduce variability and improve accuracy in average treatment effects estimation. RESULTS: The clinical trial registration was approved in October 2022, and the recruitment and enrollment of participants started in November 2022. The study's outcomes are expected to be published in 2025 in reputable, peer-reviewed health-related research journals. CONCLUSIONS: This real-world cohort study is the first to assess the effectiveness and safety of DZHJTI in treating AIS. It may provide additional clinical evidence, including the duration of response, long-term drug effectiveness, and subgroup efficacy data. The study results will be valuable for clinicians and patients seeking optimal treatment for AIS and could lead to better use of DZHJTI and improved patient outcomes. TRIAL REGISTRATION: ITMCTR ITMCTR2022000005; http://tinyurl.com/554ns8m5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52447.

The effectiveness and safety of Chinese Patent Medicines based on syndrome differentiation in patients following percutaneous coronary intervention due to acute coronary syndrome (CPM trial): A nationwide Cohort Study.

BACKGROUND: The incidence of cardiovascular events remains not unusual in patients following percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS). Chinese patent medicine (CPM) therapy based on syndrome differentiation in addition to conventional medicine (CM) had been expected to further reduce the risk of cardiovascular events. PURPOSE: To assess the effectiveness and safety of CPM based on syndrome differentiation in patients following PCI due to ACS. STUDY DESIGN: Nationwide prospective cohort study. METHODS: CPM study was conducted in 40 centers in mainland China. Patients following PCI due to ACS entered to syndrome differentiation-based CPM (SDCPM) or CM group according to whether they received CPM or not. The CPM comprised Guanxin Danshen dripping pills, Qishen Yiqi dripping pills, or Danlou tablets, and was used correspondingly with the syndrome differentiation of traditional Chinese medicine. The follow-up time was 36 months. The primary endpoint was composed of cardiac death, non-fatal myocardial infarction and urgent revascularization. The secondary endpoint included rehospitalization due to ACS, heart failure, stroke, other thrombotic events. Seattle Angina Questionnaire (SAQ) was used to evaluate quality of life. RESULTS: Between February 2012 and December 2018, ascertainment of the primary endpoint was completed in 2,724 patients of follow-up. 1,380 patients were in SDCPM group. At a median follow-up of 541 (interquartile range 513 - 564) days, the primary endpoint occurred in 126 (8.61%) patients in SDCPM group and 167 (11.62%) patients in CM group (adjusted hazard ratio [HR] = 0.70; [95% confidence interval [CI] 0.55 - 0.89]; p = 0.003). The secondary endpoint occurred in 144 (9.84%) patients in SDCPM group and 197 (13.71%) patients in CM group (adjusted HR = 0.66; [95% CI 0.53 - 0.82]; p < 0.001). The SAQ score in SDCPM group was higher than CM group (366.78 ± 70.19 vs 356.43 ± 73.80, p < 0.001). There were no significant differences of adverse events between two groups. CONCLUSION: In patients following PCI due to ACS, SDCPM in addition to CM treatment reduced the primary and secondary endpoints, as well as improved the quality of life without adverse events.

Mechanisms of immune response and cell death in ischemic stroke and their regulation by natural compounds.

Ischemic stroke (IS), which is the third foremost cause of disability and death worldwide, has inflammation and cell death as its main pathological features. IS can lead to neuronal cell death and release factors such as damage-related molecular patterns, stimulating the immune system to release inflammatory mediators, thereby resulting in inflammation and exacerbating brain damage. Currently, there are a limited number of treatment methods for IS, which is a fact necessitating the discovery of new treatment targets. For this review, current research on inflammation and cell death in ischemic stroke was summarized. The complex roles and pathways of the principal immune cells (microglia, astrocyte, neutrophils, T lymphocytes, and monocytes/macrophage) in the immune system after IS in inflammation are discussed. The mechanisms of immune cell interactions and the cytokines involved in these interactions are summarized. Moreover, the cell death mechanisms (pyroptosis, apoptosis, necroptosis, PANoptosis, and ferroptosis) and pathways after IS are explored. Finally, a summary is provided of the mechanism of action of natural pharmacological active ingredients in the treatment of IS. Despite significant recent progress in research on IS, there remain many challenges that need to be overcome.

Chinese Medicine Formula Huashibaidu Granule Early Treatment for Mild COVID-19 Patients: An Unblinded, Cluster-Randomized Clinical Trial.

Background: Previous research suggested that Chinese Medicine (CM) Formula Huashibaidu granule might shorten the disease course in coronavirus disease 2019 (COVID-19) patients. This research aimed to investigate the early treatment effect of Huashibaidu granule in well-managed patients with mild COVID-19. Methods: An unblinded cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. Two cabins were randomly allocated to a CM or control group, with 204 mild COVID-19 participants in each cabin. All participants received conventional treatment over a 7 day period, while the ones in CM group were additionally given Huashibaidu granule 10 g twice daily. Participants were followed up to their clinical endpoint. The primary outcome was worsening symptoms before the clinical endpoint. The secondary outcomes were cure and discharge before the clinical endpoint and alleviation of composite symptoms after the 7 days of treatment. Results: All 408 participants were followed up to their clinical endpoint and included in statistical analysis. Baseline characteristics were comparable between the two groups (P > 0.05). The number of worsening patients in the CM group was 5 (2.5%), and that in the control group was 16 (7.8%) with a significant difference between groups (P = 0.014). Eight foreseeable mild adverse events occurred without statistical difference between groups (P = 0.151). Conclusion: Seven days of early treatment with Huashibaidu granule reduced the likelihood of worsening symptoms in patients with mild COVID-19. Our study supports Huashibaidu granule as an active option for early treatment of mild COVID-19 in similar well-managed medical environments. Clinical Trial Registration:www.chictr.org.cn/showproj.aspx?proj=49408, identifier: ChiCTR2000029763.

Relationship Between Different Risk Factor Patterns and Follow-Up Outcomes in Patients With ST-Segment Elevation Myocardial Infarction.

Objective: Few studies have been concerned with the combined influences of the presence of multiple risk factors on follow-up outcomes in AMI patients. Our study aimed to identify risk factor patterns that may be associated with 1-year survival in male patients with ST-segment elevation myocardial infarction (STEMI). Methods: Data were from the China STEMI Care Project Phase 2 (CSCAP-2) collected between 2015 and 2018. A total of 15,675 male STEMI patients were enrolled in this study. Risk factor patterns were characterized using latent class analysis (LCA) according to seven risk factors. Associations between risk factor patterns and follow-up outcomes, including the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause death, were investigated by Cox proportional hazard regression analysis. Results: We obtained four risk factor patterns as "young and middle-aged with low levels of multimorbidity," "middle-aged with overweight," "middle-aged and elderly with normal weight," and "elderly with high multimorbidity." Four patterns had significant differences in event-free survival (P < 0.001). As compared with the patients of "young and middle-aged with low levels of multimorbidity" pattern, the risk of incidence of MACCE and all-cause death were increased in patients of "middle-aged with overweight" pattern (All-cause death: HR = 1.70, 95% CI:1.29~2.23; MACCE: HR = 1.49, 95% CI:1.29~1.72), "middle-aged and elderly with normal weight" pattern (All-cause death: HR = 3.04, 95% CI: 2.33~3.98; MACCE: HR = 1.82, 95% CI: 1.56~2.12), and "elderly with high multimorbidity" pattern (All-cause death: HR = 5.78, 95% CI: 4.49~7.42; MACCE: HR = 2.67, 95% CI: 2.31~3.10). Conclusions: By adopting a Latent Class Analysis Approach, STEMI patients can be characterized into four risk factor patterns with significantly different prognosis. The data is useful for the improvement of community health management in each specific subgroup of patients, which indicates a particular risk factor pattern.

Identification of genetic loci jointly influencing coronary artery disease risk and sleep traits of insomnia, sleep duration, and chronotype.

BACKGROUND: Accumulating evidence suggests a relationship between coronary artery disease (CAD) and sleep problems. Our study is aimed to investigate the shared genetic loci underlying this phenotypic association. METHODS: Combining summary statistics from different genome-wide association studies, we investigated overlap in single-nucleotide polymorphisms (SNPs) associated with CAD and sleep traits (insomnia symptoms, sleep duration, and chronotype) using conditional/conjunctional false discovery rate (condFDR/conjFDR) approach. Relevant variants are further evaluated for differential expression analysis, expression quantitative trait locus (eQTL) functionality, and gene ontology (GO) enrichment analysis. RESULTS: We observed substantial genetic enrichment in CAD condition on associations with sleep traits, which indicating polygenic overlap. Using conjFDR analysis, 26 loci jointly influencing CAD and sleep traits were identified. One locus was shared between CAD and sleep duration and represented the strongest shared signal detected (closest gene, MSL2; chromosome 3q22.3; conjFDR = 1.77 × 10-4). A consistent direction of allelic effect was observed between CAD and insomnia symptoms, while bi-directional effects were recognized between CAD, sleep duration, and chronotype. Replicable eQTL functionality was further identified for two loci: rs28398825 for FCHO1 in the frontal cortex and blood tissue, and rs8072451 for LRRC37A and its duplicate LRRC37A2 in several brain regions and blood tissue. GO analysis of the loci shared between CAD and sleep traits implicated cellular component related to synapse. CONCLUSIONS: Our findings provide new insight into the relationship between CAD and sleep traits. The mechanisms underlying these associations warrant further investigation.

General glycosylated hemoglobin goals potentially increase myocardial infarction severity in diabetes patients with comorbidities: Insights from a nationwide multicenter study.

AIMS/INTRODUCTION: We aimed to investigate the relationship between glycemic status and coronary artery disease (CAD) extent and severity in ST-elevation myocardial infarction (STEMI) patients, and further examine whether diabetes patients could benefit from glycosylated hemoglobin (HbA1c) below the recommended level. MATERIALS AND METHODS: Consecutive STEMI patients admitted in 2015-2017 across 244 hospitals were included in the China STEMI Care Project-2. We carried out a cross-sectional study comprising 8,370 participants with a record of HbA1c testing after admission. CAD extent and severity were assessed by admission heart rate, Killip classification and the number of stenosed vessels based on the coronary angiogram. RESULTS: Diabetes patients showed a greater risk for higher Killip class, admission tachycardia (admission heart rate ≥100 b.p.m.) and multivessel CAD (presence of left main and/or triple vessel disease). Likewise, HbA1c level was significantly associated with CAD extent and severity. While dividing diabetes patients according to general HbA1c targets (HbA1c ≤6.5, 6.5-7.0 and ≥7.0%), diabetes patients with HbA1c ≤6.5% showed a 1.30-fold higher risk for multivessel CAD (adjusted odds ratio 1.30, 95% confidence interval 1.05-1.62). In stratified analysis, the association was even stronger in patients with hypertension (adjusted odds ratio 1.41, 95% confidence interval 1.08-1.86) or hyperlipidemia (adjusted odds ratio 1.57, 95% confidence interval 1.17-2.12). CONCLUSIONS: HbA1c level is independently correlated with CAD extent and severity in STEMI patients. HbA1c below generally recommended levels might still increase the risk of CAD progression, especially for diabetes patients with hypertension or hyperlipidemia.

The Integrated Landscape of Biological Candidate Causal Genes in Coronary Artery Disease.

BACKGROUND: Genome-wide association studies (GWASs) have identified more than 150 genetic loci that demonstrate robust association with coronary artery disease (CAD). In contrast to the success of GWAS, the translation from statistical signals to biological mechanism and exploration of causal genes for drug development remain difficult, owing to the complexity of gene regulatory and linkage disequilibrium patterns. We aim to prioritize the plausible causal genes for CAD at a genome-wide level. METHODS: We integrated the latest GWAS summary statistics with other omics data from different layers and utilized eight different computational methods to predict CAD potential causal genes. The prioritized candidate genes were further characterized by pathway enrichment analysis, tissue-specific expression analysis, and pathway crosstalk analysis. RESULTS: Our analysis identified 55 high-confidence causal genes for CAD, among which 15 genes (LPL, COL4A2, PLG, CDKN2B, COL4A1, FES, FLT1, FN1, IL6R, LPA, PCSK9, PSRC1, SMAD3, SWAP70, and VAMP8) ranked the highest priority because of consistent evidence from different data-driven approaches. GO analysis showed that these plausible causal genes were enriched in lipid metabolic and extracellular regions. Tissue-specific enrichment analysis revealed that these genes were significantly overexpressed in adipose and liver tissues. Further, KEGG and crosstalk analysis also revealed several key pathways involved in the pathogenesis of CAD. CONCLUSION: Our study delineated the landscape of CAD potential causal genes and highlighted several biological processes involved in CAD pathogenesis. Further studies and experimental validations of these genes may shed light on mechanistic insights into CAD development and provide potential drug targets for future therapeutics.

Reference ranges and trajectories for blood pressure in pregnancy: findings from a follow-up study based on China Maternal and Newborn's Health Monitoring System.

Objectives: This study aimed to establish normal blood pressure reference ranges across gestation and maternal characteristics.Methods: We conducted a follow-up study including 29,200 Chinese normal pregnant women. Multilevel restrictive cubic spline models were used to calculate normal blood pressure reference ranges among all population and stratified groups.Results: In all normal pregnancies, the normal reference range of systolic blood pressure were 93.94-118.74 mmHg(2.5th-97.5th) and 97.35-124.63 mmHg at 12 and 37 weeks gestation, respectively while 58.79-74.21 mmHg and 59.19-78.25 mmHg were for diastolic blood pressure at 12 and 37 weeks gestation, which differed in subgroups stratified by prepregnancy body mass index and maternal age.Conclusion: This study provides evidence for blood pressure management in Chinese pregnant women.

Decreased GFR and its joint association with type 2 diabetes and hypertension with prevalence and severity of carotid plaque in a community population in China.

BACKGROUND: Type 2 diabetes (T2DM), hypertension and kidney dysfunction are known risk factors for cardiovascular disease, but their combined effect on carotid plaque remains uncertain. This study aims to assess the associations between T2DM, hypertension, kidney dysfunction and carotid plaque, and further explore the combined effect of three diseases. PATIENTS AND METHODS: We conducted a cross-sectional analysis among 3,815 community-dwelling adults in a Chinese atherosclerosis cohort. Estimated glomerular filtration rate (eGFR), hypertension and T2DM were evaluated as risk factors for carotid plaque. The presence, number and total area of carotid plaques were also assessed. Using logistic model, mutinomial logistic model and generalized linear regression model, the relationship between risk factors and carotid plaque was examined. RESULTS: T2DM, hypertension, decreased GFR, and, inversely, eGFR, were independently associated with the presence, number and total area of carotid plaque. Stratified analysis by T2DM and hypertension showed T2DM attenuated the association between eGFR change and carotid plaque. There was a cumulative relationship between three risk factors and carotid plaque burden. The OR for the number of plaques was 1.0 (reference), 1.55 to 2.03, 1.94 to 3.14, and 3.69 (all P<0.05), respectively, for individuals with none, one, two, and three risk factors. Likewise, combining three risk factors was associated with greater increase in total plaque area (ß, 20.63; 95% CI, 14.04-27.22). CONCLUSION: The coexistence of decreased GFR, diabetes and hypertension is associated with increased risk of carotid plaque, and these comorbidities may contribute additively to the development of plaque.

Grading effect of abnormal glucose status on arterial stiffness and a new threshold of 2-h post-load glucose based on a Chinese community study.

AIMS/INTRODUCTION: To investigate the relationship between various glucose metabolic status and arterial stiffness, and further explore the threshold of blood glucose indices for the risk of arterial stiffness. MATERIALS AND METHODS: The present cross-sectional study included 4,851 individuals from a Chinese community. Overnight fasting blood glucose and 2-h post-load glucose were sampled. Arterial stiffness was measured as brachial-ankle pulse wave velocity. The association was examined using generalized linear regression models. The threshold effect was explored using two piecewise linear regression models by the smoothing plot. RESULTS: After adjustment for covariates, isolated impaired fasting glucose, isolated impaired glucose tolerance, combined glucose intolerance and newly diagnosed diabetes mellitus were associated with a greater risk of arterial stiffness compared with normal glucose tolerance (B = 18.09, 95% confidence interval [CI] 0.42-35.76, P = 0.045; B = 28.51, 95% CI: 3.40-53.62, P = 0.026; B = 60.70, 95% CI: 38.37-83.04, P < 0.001; B = 95.06, 95% CI: 71.88-118.25, P < 0.001, respectively). Furthermore, there was a non-linear relationship between 2-h post-load glucose and arterial stiffness. A threshold for 2-h post-load glucose of 6.14 mmol/L was observed for the risk of arterial stiffness. CONCLUSIONS: Impaired fasting glucose, impaired glucose tolerance, combined glucose intolerance and newly diagnosed diabetes mellitus were related to a greater risk of arterial stiffness compared with normal glucose levels. A threshold for 2-h post-load glucose of 6.14 mmol/L probably exists for the risk of arterial stiffness.

A cross sectional study between the prevalence of chronic pain and academic pressure in adolescents in China (Shanghai).

BACKGROUND: The purpose of this study was to investigate the prevalence of four types of chronic pain (headache, abdominal pain, neck and shoulder pain (NSP), and low back pain (LBP)) and to explore the relationship between the prevalence of chronic pain and self-reported academic pressure in high school students in Shanghai, China. METHOD: Three thousand students were randomly surveyed on related issues using a questionnaire, and the results were analyzed using a multivariate logistic regression model. RESULTS: Among the 2849 high school students who completed the questionnaire, the overall prevalence rates of headache, abdominal pain, NSP, and LBP were 30.3, 20.9, 32.8, and 41.1%, respectively. The students in general experienced a heavy burden of learning, a high level of stress, and sleep deprivation, which were closely related to the four types of chronic pain. CONCLUSION: Chronic pain is a common condition in Chinese adolescents and is closely related to self-reported academic pressure.

[Relationship between the incidence of chronic pain and academic pressure in high school students].

OBJECTIVE: To explore the incidence of four types of chronic pain, i.e. headache, abdominal pain, neck & shoulder pain (NSP) and low back pain (LBP) and examine the relationship between the incidence of chronic pain and academic pressure in high school students. METHODS: A total of 3 000 high school students were randomly surveyed with a questionnaire on related issues. And the results were analyzed with a multivariate Logistic regression model. RESULTS: Among them, 2 849 completed the questionnaire. And the overall incident rates of headache, abdominal pain, NSP, and LBP were 30.3%, 20.9%, 32.8% and 41.1% respectively. The students generally experienced a heavy burden of learning, a high level of stress and sleep deprivation closely related to four types of chronic pain. CONCLUSION: As a common condition in Chinese adolescents, chronic pain is closely correlated with academic pressure.