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Background. Diabetes mellitus (DM) can induce cardiomyocyte injury and lead to diabetic cardiomyopathy (DCM) which presently has no specific treatments and consequently increase risk of mortality. Objective. To characterize the therapeutic effect of 6-gingerol (6-G) on DCM and identify its potential mechanism. Methods. In vivo streptozotocin- (STZ-) induced DM model was established by using a high-fat diet and STZ, followed by low-dose (25 mg/kg) and high-dose (75 mg/kg) 6-G intervention. For an in vitro DCM model, H9c2 rat cardiomyoblast cells were stimulated with high glucose ( glucose = 33 mM) and palmitic acid (100 μM) and then treated with 6-G (100 μM). Histological and echocardiographic analyses were used to assess the effect of 6-G on cardiac structure and function in DCM. Western blotting, ELISA, and real-time qPCR were used to assess the expression of ferroptosis, inflammation, and the Nrf2/HO-1 pathway-related proteins and RNAs. Protein expression of collagen I and collagen III was assessed by immunohistochemistry, and kits were used to assay SOD, MDA, and iron levels. Results. The results showed that 6-G decreased cardiac injury in both mouse and cell models of DCM. The cardiomyocyte hypertrophy and interstitial fibrosis were attenuated by 6-G treatment in vivo and resulted in an improved heart function. 6-G inhibited the expression of ferroptosis-related protein FACL4 and the content of iron and enhanced the expression of anti-ferroptosis-related protein GPX4. In addition, 6-G also diminished the secretion of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. 6-G treatment activated the Nrf2/HO-1 pathway, enhanced antioxidative stress capacity proved by increased activity of SOD, and decreased MDA production. Compared with in vivo, 6-G treatment of H9c2 cells treated with high glucose and palmitic acid could produce a similar effect. Conclusion. These findings suggest that 6-G could protect against DCM by the mechanism of ferroptosis inhibition and inflammation reduction via enhancing the Nrf2/HO-1 pathway.

Uterine fibroids (UFs) are the most common benign gynecological tumor and greatly affect reproductive health in women of reproductive age. Some studies have indicated an association between UFs and several cardiovascular disease (CVD) risk factors. To determine whether UFs are associated with increased blood pressure, we performed a cross-sectional study and meta-analysis. In the cross-sectional study, 8401 participants who underwent a physical examination at the First Affiliated Hospital of Shantou University Medical College from June 2011 to June 2013 were divided into a uterine fibroid group (1617 cases) and a control group (6784 cases) to assess the relationship between UFs and blood pressure. Then, we conducted a systematic review to confirm the results. The cross-sectional study showed that UFs were associated with an increased rate of elevated blood pressure [OR = 1.35, 95% confidence interval (CI): 1.016-1.792]. The meta-analysis revealed a significant association between UFs and the prevalence of hypertension [pooled OR = 1.44, 95% CI: 1.17-1.75, P = 0.0004; I

Endothelial progenitor cells (EPCs), which are precursors of endothelial cells (ECs), have the capacity to circulate, proliferate and differentiate into mature ECs. EPCs are primarily identified by the uptake of 1,1‐dioctadecyl‐3,3,3,3‐tetramethylindocarbocyanine‐labelled acetylated low‐density lipoprotein (Dil‐acLDL) and the binding of fluorescein‐isothiocyanate (FITC)‐conjugated Ulex europaeus agglutinin lectin (FITC‐UEA‐I). However, the cytoplasm and nucleus are usually stained by FITC‐UEA‐I via a typical method to double‐stain late EPCs. It is necessary to explore a new method to improve the quality of fluorescence photomicrographs of late EPCs stained with FITC‐UEA‐I. Here, we described an updated protocol for double‐staining late EPCs with Dil‐acLDL and FITC‐UEA‐I, with the cells more optimally stained with FITC‐UEA‐I.

Background The cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relationships with IHD. This study aimed to use Mendelian randomization to evaluate whether genetically-predicted n-3 PUFAs affect IHD and cardiometabolic risk factors (CRFs). Methods Genetic variants strongly (p –8) and independently (r2 > 0.1) associated with n-3 PUFAs were derived from the CHARGE Consortium (including 8,866 subjects of European ancestry) and were used as instrumental variables (IVs) for evaluating the effect of n-3 PUFAs, including α-linolenic acid (ALA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Data on the associations between the IVs and IHD, myocardial infarction, and CRFs (including diabetes, lipids, blood pressure, body mass index, and waist-to-hip ratio (WHR)) were obtained from the UK Biobank SOFT CAD GWAS with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (113,937 IHD cases and 339,115 controls), the Myocardial Infarction Genetics and CARDIoGRAM Exome consortia (42,335 MI cases and 78,240 controls), the DIAbetes Genetics Replication And Meta-analysis consortium (26,676 diabetes mellitus cases and 132,532 controls), the Global Lipids Genetics Consortium (n = 196,475), the International Consortium for Blood Pressure (n = 69,395), and the meta-analysis of GWAS for body fat distribution in the UK Biobank and Genetic Investigation of Anthropometric Traits (n = 694,649). Results Genetically-predicted higher ALA was associated with lower risk of IHD, type 2 diabetes (T2D), and lower serum lipids. The effect size per 0.05-unit increase (about 1 standard deviation) in plasma ALA level) was − 1.173 (95% confidence interval − 2.214 to − 0.133) for IHD. DPA and EPA had no association with IHD but were associated with a higher risk of T2D, higher levels of lipids or WHR. DHA had no association with IHD or CRFs. Conclusions Our study suggests a benefit of ALA for IHD and its main risk factors. DHA, DPA, and EPA had no association with IHD but were partly associated with increasing cardiometabolic risk factors.

Background: Recent studies have demonstrated a correlation between intestinal flora and the severity of myocardial infarction as well as post-myocardial infarction repair. However, few studies have investigated whether probiotics reduce mortality and improve cardiovascular outcomes in patients with acute myocardial infarction. In this study, we will conduct a randomized controlled trial (RCT) to evaluate the effect of probiotics on in-hospital mortality and incidence of major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI). Methods: This is an open-label, randomized, controlled, superiority clinical trial involving 2594 adult patients who diagnosed with acute myocardial infarction. Patients will be randomized to (1)receive bifidobacteria triple viable capsule (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) 840 mg, twice a day, plus standard treatment strategy during the hospital stay , for a maximum of 30 days, or (2)receive the standard treatment strategy and will not take the bifidobacterium triple live capsule. The primary outcome was in-hospital all-cause mortality. Discussion: The purpose of this clinical trial is to determine whether probiotics can reduce in-hospital mortality and improve prognosis in patients with AMI, and the results will provide evidence for probiotics as a complementary treatment for AMI. Trial registration: Chinese Clinical Trials Registry ChiCTR2000038797. Registered on 2 October 2020.

First two decades of the twenty-first century are characterised by epidemics of non-communicable diseases such as many hundreds of millions of patients diagnosed with cardiovascular diseases and the type 2 diabetes mellitus, breast, lung, liver and prostate malignancies, neurological, sleep, mood and eye disorders, amongst others. Consequent socio-economic burden is tremendous. Unprecedented decrease in age of maladaptive individuals has been reported. The absolute majority of expanding non-communicable disorders carry a chronic character, over a couple of years progressing from reversible suboptimal health conditions to irreversible severe pathologies and cascading collateral complications. The time-frame between onset of SHS and clinical manifestation of associated disorders is the operational area for an application of reliable risk assessment tools and predictive diagnostics followed by the cost-effective targeted prevention and treatments tailored to the person.This article demonstrates advanced strategies in bio/medical sciences and healthcare focused on suboptimal health conditions in the frame-work of Predictive, Preventive and Personalised Medicine (3PM/PPPM). Potential benefits in healthcare systems and for society at large include but are not restricted to an improved life-quality of major populations and socio-economical groups, advanced professionalism of healthcare-givers and sustainable healthcare economy. Amongst others, following medical areas are proposed to strongly benefit from PPPM strategies applied to the identification and treatment of suboptimal health conditions:Stress overload associated pathologiesMale and female healthPlanned pregnanciesPeriodontal healthEye disordersInflammatory disorders, wound healing and pain management with associated complicationsMetabolic disorders and suboptimal body weightCardiovascular pathologiesCancersStroke, particularly of unknown aetiology and in young individualsSleep medicineSports medicineImproved individual outcomes under pandemic conditions such as COVID-19.

Suboptimal health status (SHS) is a reversible stage between health and illness that is characterized by health complaints, low energy, general weakness, and chronic fatigue. The Suboptimal Health Status Questionnaire-25 (SHSQ-25) has been validated in three major populations (African, Asian, and Caucasian) and is internationally recognized as a reliable and robust tool for health estimation in general populations. This study focused on the development of K-SHSQ-25, a Korean version of the SHSQ-25, from its English version.The SHSQ-25 was translated from English to Korean according to international guidelines set forth by the World Health Organization (WHO) for health instrument translation between different languages. A subsequent cross-sectional survey involved 460 healthy South Korean participants (aged 18-83 years; 65.4% females) to answer the 25 questions focusing on the health perspectives of 5 domains, 1) fatigue, 2) cardiovascular health, 3) digestive tract, 4) immune system and 5) mental health. The K-SHSQ-25 was further validated using tests for reliability, internal consistency, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA).The version of K-SHSQ-25 achieved linguistic, cultural, and conceptual equivalence to the English version. The intraclass correlation coefficient (ICC) of test-retest reliability for individual items ranged from 0.88 to 0.99. Reliability estimates based on internal consistency reached a Cronbach's α of 0.953; the Cronbach's α for each domain ranged from 0.76 to 0.94. Regarding construct validity, the EFA of the K-SHSQ-25 generally replicated the multidimensional structure (fatigue, cardiovascular, digestive, immune system, and mental health) and 25 questions. The CFA revealed that the root mean square error of approximation (RMSEA), goodness-of-fit index (GFI) and adjusted goodness of fit index (AGFI) were excellent (RMSEA = 0.0690.08, GFI = 0.9290.90, AGFI = 0.9070.90). The five domains of the K-SHSQ-25 showed significant correlations with each other (r = 0.59-0.81, P0.001). The cut-off point of K-SHSQ-25 for SHS was determined as an SHS score of 25. The prevalence of SHS in this study was 60.0% (276/460), with 47.8% (76/159) for males and 58.5% for females (176/301).Our results indicate that the Korean version of SHSQ-25, K-SHSQ-25, is a transcultural equivalent, robust, valid, and reliable assessment tool for evaluating SHS in the Korean-speaking population.

Background To date, most countries worldwide have declared that the pandemic of COVID-19 is over, while the WHO has not officially ended the COVID-19 pandemic, and China still insists on the personalized dynamic COVID-free policy. Large-scale nucleic acid testing in Chinese communities and the manual interpretation for SARS-CoV-2 nucleic acid detection results pose a huge challenge for labour, quality and turnaround time (TAT) requirements. To solve this specific issue while increase the efficiency and accuracy of interpretation, we created an autoverification and guidance system (AGS) that can automatically interpret and report the COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) results relaying on computer-based autoverification procedure and then validated its performance in real-world environments. This would be conductive to transmission risk prediction, COVID-19 prevention and control and timely medical treatment for positive patients in the context of the predictive, preventive and personalized medicine (PPPM). Methods A diagnostic accuracy test was conducted with 380,693 participants from two COVID-19 test sites in China, the Hong Kong Hybribio Medical Laboratory (n = 266,035) and the mobile medical shelter at a Shanghai airport (n = 114,658). These participants underwent SARS-CoV-2 RT-PCR from March 28 to April 10, 2022. All RT-PCR results were interpreted by laboratorians and by using AGS simultaneously. Considering the manual interpretation as gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were applied to evaluate the diagnostic value of the AGS on the interpretation of RT-PCR results. Results Among the 266,035 samples in Hong Kong, there were 16,356 (6.15%) positive, 231,073 (86.86%) negative, 18,606 (6.99%) indefinite, 231,073 (86.86%, negative) no retest required and 34,962 (13.14%, positive and indefinite) retest required; the 114,658 samples in Shanghai consisted of 76 (0.07%) positive, 109,956 (95.90%) negative, 4626 (4.03%) indefinite, 109,956 (95.90%, negative) no retest required and 4702 (4.10%, positive and indefinite) retest required. Compared to the fashioned manual interpretation, the AGS is a procedure of high accuracy [99.96% (95%CI, 99.95–99.97%) in Hong Kong and 100% (95%CI, 100–100%) in Shanghai] with perfect sensitivity [99.98% (95%CI, 99.97–99.98%) in Hong Kong and 100% (95%CI, 100–100%) in Shanghai], specificity [99.87% (95%CI, 99.82–99.90%) in Hong Kong and 100% (95%CI, 99.92–100%) in Shanghai], PPV [99.98% (95%CI, 99.97–99.99%) in Hong Kong and 100% (95%CI, 99.99–100%) in Shanghai] and NPV [99.85% (95%CI, 99.80–99.88%) in Hong Kong and 100% (95%CI, 99.90–100%) in Shanghai]. The need for manual interpretation of total samples was dramatically reduced from 100% to 13.1% and the interpretation time fell from 53 h to 26 min in Hong Kong; while the manual interpretation of total samples was decreased from 100% to 4.1% and the interpretation time dropped from 20 h to 16 min at Shanghai. Conclusions The AGS is a procedure of high accuracy and significantly relieves both labour and time from the challenge of large-scale screening of SARS-CoV-2 using RT-PCR. It should be recommended as a powerful screening, diagnostic and predictive system for SARS-CoV-2 to contribute timely the ending of the COVID-19 pandemic following the concept of PPPM.

AimThe aim of this study is to evaluate the association between serum sodium concentrations at hospital admission and all-cause mortality within 365 days post-discharge in patients with atrial fibrillation (AF) without heart failure (HF).MethodsThe prospective cohort study enrolled 1,446 patients with AF without HF between November 2018 and October 2020. A follow-up was performed 30, 90, 180, and 365 days after enrollment through outpatient visits or telephone interviews. All-cause mortality was estimated in three groups according to serum sodium concentrations: hyponatremia (< 135 mmol/L), normonatremia (135–145 mmol/L), and hypernatremia (> 145 mmol/L). We estimated the risk of all-cause mortalities using univariable and multivariable Cox proportional hazards models with normonatremia as the reference.ResultsThe all-cause mortalities of hyponatremia, normonatremia, and hypernatremia were 20.6, 9.4, and 33.3% within 365 days post-discharge, respectively. In the univariable analysis, hyponatremia (HR: 2.19, CI 1.5–3.2) and hypernatremia (HR: 4.03, CI 2.32–7.02) increased the risk of all-cause mortality. The HRs for hyponatremia and hypernatremia were 1.55 (CI 1.05–2.28) and 2.55 (CI 1.45–4.46) after adjustment for age, diabetes mellitus, loop diuretics, antisterone, antiplatelet drugs, and anticoagulants in the patients with AF without HF. The association between serum sodium concentrations and the HRs of all-cause mortality was U-shaped.ConclusionDysnatremia at hospital admission was an independent factor for all-cause mortality in patients with AF without HF within 365 days post-discharge.

Background Suboptimal health status (SHS) is a reversible state between ideal health and illness and it can be effectively reversed by risk prediction, disease prevention, and personalized medicine under the global background of predictive, preventive, and personalized medicine (PPPM) concepts. More and more Chinese nurses have been troubled by psychological symptoms (PS). The correlation between PS and SHS is unclear in nurses. The purpose of current study is to investigate the prevalence of SHS and PS in Chinese nurses and the relationship between SHS and PS along with predisposing factors as well as to discuss the feasibility of improving health status and preventing diseases according to PPPM concepts in Chinese nurses. Methods A cross-sectional study was conducted with the cluster sampling method among 9793 registered nurses in Foshan city, China. SHS was evaluated with the Suboptimal Health Status Questionnaire-25 (SHSQ-25). Meanwhile, the PS of depression and anxiety were evaluated with Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) self-assessment questionnaires. The relationship between PS and SHS in Chinese nurses was subsequently analyzed. Results Among the 9793 participants, 6107 nurses were included in the final analysis. The prevalence of SHS in the participants was 74.21% (4532/6107) while the symptoms of depression and anxiety were 47.62% (2908/6107) and 24.59% (1502/6107) respectively. The prevalence of SHS in the participants with depression and anxiety was significantly higher than those without the symptoms of depression (83.3% vs 16.7%, P P P Conclusions There is a high prevalence of SHS and PS in Chinese nurses. PS in Chinese nurses are associated with SHS. Physical exercise is a protective factor for SHS and PS so that the exercise should be strongly recommended as a valuable preventive measure well in the agreement with PPPM philosophy. Along with SDS and SAS, SHSQ-25 should also be highly recommended and applied as a novel predictive/preventive tool for the health measures from the perspectives of PPPM in view of susceptible population and individual screening, the predisposition to chronic disease preventing, personalization of intervention, and the ideal health state restoring.

Background Recognising the early signs of ischemic stroke (IS) in emergency settings has been challenging. Machine learning (ML), a robust tool for predictive, preventive and personalised medicine (PPPM/3PM), presents a possible solution for this issue and produces accurate predictions for real-time data processing. Methods This investigation evaluated 4999 IS patients among a total of 10,476 adults included in the initial dataset, and 1076 IS subjects among 3935 participants in the external validation dataset. Six ML-based models for the prediction of IS were trained on the initial dataset of 10,476 participants (split participants into a training set [80%] and an internal validation set [20%]). Selected clinical laboratory features routinely assessed at admission were used to inform the models. Model performance was mainly evaluated by the area under the receiver operating characteristic (AUC) curve. Additional techniques—permutation feature importance (PFI), local interpretable model-agnostic explanations (LIME), and SHapley Additive exPlanations (SHAP)—were applied for explaining the black-box ML models. Results Fifteen routine haematological and biochemical features were selected to establish ML-based models for the prediction of IS. The XGBoost-based model achieved the highest predictive performance, reaching AUCs of 0.91 (0.90–0.92) and 0.92 (0.91–0.93) in the internal and external datasets respectively. PFI globally revealed that demographic feature age, routine haematological parameters, haemoglobin and neutrophil count, and biochemical analytes total protein and high-density lipoprotein cholesterol were more influential on the model’s prediction. LIME and SHAP showed similar local feature attribution explanations. Conclusion In the context of PPPM/3PM, we used the selected predictors obtained from the results of common blood tests to develop and validate ML-based models for the diagnosis of IS. The XGBoost-based model offers the most accurate prediction. By incorporating the individualised patient profile, this prediction tool is simple and quick to administer. This is promising to support subjective decision making in resource-limited settings or primary care, thereby shortening the time window for the treatment, and improving outcomes after IS.

BackgroundRecent studies of fibroblast growth factor 21 (FGF21), first recognized as a regulator of glucose and lipid metabolism, have found that the level of in serum FGF21 is associated with the prognosis of many cardiovascular diseases, but its relationship to acute heart failure (AHF) patients remains unknown. Our study aimed to investigate whether circulating FGF21 could predict the short-term prognosis of AHF patients.MethodsFour hundred and two AHF patients and 19 healthy controls were recruited into the prospective cohort study, and blood samples of participants were collected, in tubes without anticoagulant, within the first 24 h after hospital admission. Serum FGF21 levels were detected by enzyme-linked immunosorbent assay (ELISA). All patients were followed-up at least 6 months after discharge. The primary endpoint was all-cause death, and secondary endpoint was a composite endpoint of death and heart failure readmission. Mortality and composite end point events were analyzed using Kaplan-Meier curves. ROC curves compared the difference between the FGF21 and NT-proBNP in predicting 3- and 6-months mortality. Time-to-event data were evaluated using Kaplan-Meier estimation and Cox proportional hazards models.ResultsIn the present study, the serum FGF21 concentrations were significantly higher in the 402 AHF patients enrolled, compared with the 19 healthy controls (p < 0.001). The average age was 70 (±12) years, and 58% were males. Participants were divided into two groups according to the median FGF21 level (262 pg/ml): a high FGF21 group (n = 201, FGF21 ≥ 262 pg/ml) and low FGF21 group (n = 201, FGF21 p < 0.001). ROC analysis shows that FGF21 was better than NT-proBNP in predicting death at both 3 (AUC, 0.77 vs. 0.63, p < 0.001) and 6 months (AUC, 0.78 vs. 0.66).ConclusionHigh baseline FGF21 levels are associated with adverse clinical outcomes in AHF patients. Serum FGF21 might be a potential predictive biomarker of AHF patients.

Background: The association between impaired fasting glucose level (IFG) and coronary heart disease (CAD) remain controversial. In the present study, we sought to ascertain a relationship of IFG with the number of diseased coronary artery and occurrence of myocardial infarction, among CAD cases.Methods: We studied 1,451 consecutive no-diabetic patients who underwent coronary angiography at the First Affiliated Hospital of Shantou University Medical College in Southern China. Demographic, biochemical, clinical and angiographic data were collected.Results: The prevalence of IFG was higher in patients with angiographically confirmed CAD than in subjects without angiographic evidence of CAD (33.4 versus 28.2%, p = 0.034). Compared with CAD cases without IFG, CAD cases with IFG had a higher odds ratio (OR) of having triple-vessel disease as opposed to having single- or double-vessel disease [OR = 1.53, 95% confidence interval (CI) = 1.13–2.07]. Furthermore, the occurrence of MI was higher in CAD cases with IFG than in CAD cases without IFG (OR = 1.73, 95% CI = 1.27–2.36).Conclusions: There is an association between IFG and a predisposition to severe CAD indicated by triple vessel disease or myocardial infarction.

BackgroundAcute aortic syndrome, mainly involving aortic dissection (AD) and intramural hematoma (IMH), is a life-threatening emergency with high mortality. Shock index (SI) well predicts poor outcomes of severely ill patients, but the ability of SI to prognose acute AD and IMH patients is not well known. This study aimed to investigate the association of admission SI with the 30-day, all-cause in-hospital mortality in acute AD and IMH patients.MethodsThis is a retrospective and single-center cohort study. According to Stanford classification, firstly, we showed the baseline characteristics in acute AD and IMH patients. Univariate and multivariate methods were used to evaluate the association between SI and the in-hospital mortality of acute AD and IMH. Then, patients were divided into two groups by their SIs (SIResultsThis study involved 1250 consecutively recruited Chinese patients diagnosed with acute AD or IMH (Stanford A: 553 (44.2%); Stanford B: 697 (55.8%)). The 30-day, all-cause in-hospital mortality of Stanford A AD and IMH patients was 23.1% (128/553) but was 4.7% (33/697) for Stanford B AD and IMH patients. The SI significantly increased the risk of 30-day, all-cause in-hospital mortality in AD and IMH patients (Stanford A: HR 3.941, 95%CI 2.350-6.612, pConclusionIncreased admission SI can serve as a good predictor of the 30-day, all-cause in-hospital mortality in patients with acute AD and IMH, especially for the patients without surgery or TEVAR.

Coagulation tests are affected by many factors, such as age, race, and gestation. Although coagulation test results vary by ABO blood type, reference intervals of different ABO blood groups remain to be determined. This study aims to investigate the reference ranges of coagulation tests for different ABO blood groups in the Han population in South China.A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College. In all, 9600 individuals aged between 20 and 79 years were included. Coagulation tests, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time, and fibrinogen, were performed.There was a significant difference in PT, INR, and aPTT among ABO blood groups. PT and INR varied slightly between ABO blood groups. There was a higher aPTT value in individuals in the O blood group than in those in non-O blood groups, in both males and females across the included age range. No differences were found in thrombin time and fibrinogen between the ABO blood groups.The study provides reference data on coagulation tests from ABO blood groups in South China. The established reference intervals specific to ABO blood type, sex, and age may improve clinical decisions based on coagulation tests.

Genome-wide association studies (GWAS) have identified over 60 genetic loci associated with immunoglobulin G (IgG) N-glycosylation; however, the causal genes and their abundance in relevant tissues are uncertain. Leveraging data from GWAS summary statistics for 8,090 Europeans, and large-scale expression quantitative trait loci (eQTL) data from the genotype-tissue expression of 53 types of tissues (GTEx v7), we derived a linkage disequilibrium score for the specific expression of genes (LDSC-SEG) and conducted a transcriptome-wide association study (TWAS). We identified 55 gene associations whose predicted levels of expression were significantly associated with IgG N-glycosylation in 14 tissues. Three working scenarios, i.e., tissue-specific, pleiotropic, and coassociated, were observed for candidate genetic predisposition affecting IgG N-glycosylation traits. Furthermore, pathway enrichment showed several IgG N-glycosylation-related pathways, such as asparagine N-linked glycosylation, N-glycan biosynthesis and transport to the Golgi and subsequent modification. Through phenome-wide association studies (PheWAS), most genetic variants underlying TWAS hits were found to be correlated with health measures (height, waist-hip ratio, systolic blood pressure) and diseases, such as systemic lupus erythematosus, inflammatory bowel disease, and Parkinson’s disease, which are related to IgG N-glycosylation. Our study provides an atlas of genetic regulatory loci and their target genes within functionally relevant tissues, for further studies on the mechanisms of IgG N-glycosylation and its related diseases.

Background: Low-dose rivaroxaban and low-intensity warfarin are widely used in Asia for patients with atrial fibrillation (AF). However, in Asians, it is unclear whether low-dose rivaroxaban and low-intensity warfarin can improve the prognosis of AF. In this study, we investigate the survival benefits of low-dose rivaroxaban and low-intensity warfarin in Asian patients with AF in clinical practice.Methods: This cohort study used medical records in a single tertiary hospital in China, between 2019 and 2020, to identify patients with AF who used rivaroxaban or warfarin, or had no anticoagulant therapy. Follow-ups were performed through telephone contact or medical record review. Cox proportional hazards models were used to compare the risk of mortality of patients in the anticoagulant-untreated group vs. warfarin-treated groups and rivaroxaban-treated groups.Results: A total of 1727 AF patients, discharged between 2019 and 2020, were enrolled in this cohort, of which 873 patients did not use any anticoagulant, 457 patients received warfarin and 397 patients used rivaroxaban. Multivariable analysis showed that, of all the warfarin groups, patients with an international normalized ratio (INR) below 2, good INR control, or poor INR control had a significantly lower risk of mortality compared with that of patients without anticoagulants (HR 0.309, p = 0.0001; HR 0.387, p = 0.0238; HR 0.363, p < 0.0001). Multivariable Cox proportional hazard analyses also demonstrated that, compared with the no anticoagulant group, all rivaroxaban dosage groups (≤10 mg, HR 0.456, p = 0.0129; 15 mg, HR 0.246, p = 0.0003; 20 mg, HR 0.264, p = 0.0237) were significantly associated with a lower risk of mortality.Conclusion: Despite effects being smaller than observed with recommended optimal anticoagulation, the use of warfarin with an INR below 2, poor INR control and the use of low-dose rivaroxaban may still provide survival benefits, suggesting viable alternatives that enable physicians to better resolve decisional conflicts concerning the risks and benefits of anticoagulant therapies, as well as for patients in need of but unable to receive standard anticoagulant therapy due to bleeding risk or other factors, such as financial burden, concerns of adverse outcomes, as well as low treatment compliance and persistence.

Background Both DNA genotype and methylation of antisense non-coding RNA in the INK4 locus (ANRIL) have been robustly associated with coronary artery disease (CAD), but the interdependent mechanisms of genotype and methylation remain unclear. Methods Eighteen tag single nucleotide polymorphisms (SNPs) of ANRIL were genotyped in a matched case–control study (cases 503 and controls 503). DNA methylation of ANRIL and the INK4/ARF locus (p14ARF, p15INK4b and p16INK4a) was measured using pyrosequencing in the same set of samples (cases 100 and controls 100). Results Polymorphisms of ANRIL (rs1004638, rs1333048 and rs1333050) were significantly associated with CAD (p ANRIL gene dosage (p ANRIL polymorphisms and myocardial infarction/acute coronary syndrome (MI/ACS) (p > 0.05). Methylation levels of ANRIL were similar between the two studied groups (p > 0.05), but were different in the rs1004638 genotype, with AA and AT genotype having a higher level of ANRIL methylation (pos4, p = 0.006; pos8, p = 0.019). Further Spearman analyses indicated that methylation levels of ANRIL were positively associated with systolic blood pressure (pos6, r = 0.248, p = 0.013), diastolic blood pressure (pos3, r = 0.213, p = 0.034; pos6, r = 0.220, p = 0.028), and triglyceride (pos4, r = 0.253, p = 0.013), and negatively associated with high-density lipoprotein cholesterol (pos2, r = − 0.243, p = 0.017). Additionally, we identified 12 transcription factor binding sites (TFBS) within the methylated ANRIL region, and functional annotation indicated these TFBS were associated with basal transcription. Methylation at the INK4/ARF locus was not associated with ANRIL genotype. Conclusions These results indicate that ANRIL genotype (tag SNPs rs1004638, rs1333048 and rs1333050) mainly affects coronary atherosclerosis, but not MI/ACS. There may be allele-related DNA methylation and allele-related binding of transcription factors within the ANRIL promoter.

Background: Previous studies have reported that biomarkers of liver injury and renal dysfunction were associated with hypertensive disorders of pregnancy (HDP). However, the associations of these biomarkers in early pregnancy with the risk of HDP and longitudinal blood pressure pattern during pregnancy were rarely investigated in prospective cohort studies.Methods: A total of 1,041 pregnant women were enrolled in this prospective cohort study. BP was assessed in four stages throughout pregnancy. The following biomarkers were measured at early pregnancy before 18 weeks gestation: lactate dehydrogenase (LDH), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), uric acid (UA), and estimated glomerular filtration rate (eGFR). Linear mixed-effects and logistic regression models were used to examine the associations of these biomarkers with longitudinal BP pattern during pregnancy and HDP incidence, respectively.Results: In unadjusted models, higher serum UA, GGT, ALP, and LDH levels, as well as lower eGFR and AST/ALT, were associated with higher BP levels during pregnancy and an increased risk of HDP. After adjustment for maternal age, pre-pregnancy BMI and other potential confounders, UA, GGT, ALP, and LDH remained positively associated with both BP and HDP. However, eGFR and AST/ALT were not associated with HDP after adjusting for potential confounders. When including all 6 biomarkers simultaneously in multivariable analyses, increased UA, GGT, and ALP significantly associated with gestational hypertension and preeclampsia.Conclusion: This study suggests that increased UA, GGT, and ALP in early-pregnancy are independent risk factors of gestational hypertension and preeclampsia.

Background: The existing prediction models lack the generalized applicability for chronic heart failure (CHF) readmission. We aimed to develop and validate a widely applicable nomogram for the prediction of 180-day readmission to the patients.Methods: We prospectively enrolled 2,980 consecutive patients with CHF from two hospitals. A nomogram was created to predict 180-day readmission based on the selected variables. The patients were divided into three datasets for development, internal validation, and external validation (mean age: 74.2 ± 14.1, 73.8 ± 14.2, and 71.0 ± 11.7 years, respectively; sex: 50.2, 48.8, and 55.2% male, respectively). At baseline, 102 variables were submitted to the least absolute shrinkage and selection operator (Lasso) regression algorithm for variable selection. The selected variables were processed by the multivariable Cox proportional hazards regression modeling combined with univariate analysis and stepwise regression. The model was evaluated by the concordance index (C-index) and calibration plot. Finally, the nomogram was provided to visualize the results. The improvement in the regression model was calculated by the net reclassification index (NRI) (with tenfold cross-validation and 200 bootstraps).Results: Among the selected 2,980 patients, 1,696 (56.9%) were readmitted within 180 days, and 1,502 (50.4%) were men. A nomogram was established by the results of Lasso regression, univariate analysis, stepwise regression and multivariate Cox regression, as well as variables with clinical significance. The values of the C-index were 0.75 [95% confidence interval (CI): 0.72–0.79], 0.75 [95% CI: 0.69–0.81], and 0.73 [95% CI: 0.64–0.83] for the development, internal validation, and external validation datasets, respectively. Calibration plots were provided for both the internal and external validation sets. Five variables including history of acute heart failure, emergency department visit, age, blood urea nitrogen level, and beta blocker usage were considered in the final prediction model. When adding variables involving hospital discharge way, alcohol taken and left bundle branch block, the calculated values of NRI demonstrated no significant improvements.Conclusions: A nomogram for the prediction of 180-day readmission of patients with CHF was developed and validated based on five variables. The proposed methodology can improve the accurate prediction of patient readmission and have the wide applications for CHF.

Objective. Lesions of COVID-19 can be clearly visualized using chest CT images, and hence provide valuable evidence for clinicians when making a diagnosis. However, due to the variety of COVID-19 lesions and the complexity of the manual delineation procedure, automatic analysis of lesions with unknown and diverse types from a CT image remains a challenging task. In this paper we propose a weakly-supervised framework for this task requiring only a series of normal and abnormal CT images without the need for annotations of the specific locations and types of lesions. Approach. A deep learning-based diagnosis branch is employed for classification of the CT image and then a lesion identification branch is leveraged to capture multiple types of lesions. Main Results. Our framework is verified on publicly available datasets and CT data collected from 13 patients of the First Affiliated Hospital of Shantou University Medical College, China. The results show that the proposed framework can achieve state-of-the-art diagnosis prediction, and the extracted lesion features are capable of distinguishing between lesions showing ground glass opacity and consolidation. Significance. The proposed approach integrates COVID-19 positive diagnosis and lesion analysis into a unified framework without extra pixel-wise supervision. Further exploration also demonstrates that this framework has the potential to discover lesion types that have not been reported and can potentially be generalized to lesion detection of other chest-based diseases.

Background Hypertension is the most important risk factor for aortic dissection. We aimed to assess the association of systolic blood pressure (SBP) and diastolic blood pressure (DBP) at admission with aortic-related adverse events (ARAE) after thoracic endovascular aortic repair (TEVAR). Methods All patients (n = 269) admitted with type B aortic dissection (BAD) for TEVAR were included. ARAE at 3, 24, and 60 months were evaluated as outcomes. Cox proportional regression analysis was performed. Results No variables were found to be predictors of 3-month ARAE by multiple analysis. Independent predictors of 24-month ARAE were DBP at admission (hazard ratio [HR] per 10 mm Hg decrement, 1.318; 95% confidence interval [CI] 1.059–1.641; p = 0.013), cerebrovascular accident (HR 1.965; 95% CI 1.097–3.522; p = 0.023) and obesity (HR 2.922; 95% CI 1.096–7.795; p = 0.032). DBP at admission (HR per 10 mm Hg decrement, 1.276; 95% CI 1.038–1.569; p = 0.021) was also a predictor of 60-month ARAE. In the non-chronic group (n = 223), DBP at admission was evaluated as an independent predictor of 3-month (HR per 10 mm Hg decrement, 1.809; 95% CI 1.084–3.018; p = 0.023), 24-month (HR per 10 mm Hg decrement, 1.344; 95% CI 1.070–1.688; p = 0.011) and 60-month (HR per 10 mm Hg decrement, 1.338; 95% CI 1.065–1.682; p = 0.013) ARAE. In the chronic group (n = 46), no variables were found to be independent predictors of 3-month, 24-month, or 60-month ARAE. Conclusions DBP at admission can predict ARAE in patients with BAD after TEVAR, whereas SBP was not associated with ARAE. The relationship between DBP at admission and outcomes appears to be more prominent in non-chronic patients.

Cardiovascular disease is a common complex trait that calls for next-generation biomarkers for precision diagnostics and therapeutics. The most common type of post-translational protein modificatio...

Preeclampsia (PE) is one of the major causes of maternal and perinatal mortality worldwide. This study aimed to determine the immunological characteristics of PE patients and normal pregnancy at the T cell receptor beta-chain (TRB) level by using high-throughput sequencing. High-throughput sequencing was performed to analyze the expression of TRB-CDR3 in circulating T cells. T cells were isolated from 36 healthy pregnant women, 24 patients with severe PE, and 18 patients with moderate PE. Rearranged mRNA sequences were assigned to their germline V, D, and J counterparts, and translated into proper amino acids by the IMGT database. In general, PE samples had more TRB-CDR3 reads and types than those of normal pregnant woman in the circulation, but the mean number of TRB-CDR3 reads and unique TRB-CDR3 reads in severe group was lower than that in the moderate group. In PE patients, the V7_9 and V20_1 gene loci were more prevalent than in healthy pregnant women. In addition, 4 kinds of TRB-CDR3 peptides were found to be highly relevant to the pathogenesis of PE. Of them, peptides matched to herpes simplex virus antigen-specific T cells were much lower in PE samples.

Objective: Study the association of adropin and hypertensive disorders complicating pregnancy (HDCP). Methods: Patients with HDCP were matched with normotensive women (47 pairs). Adropin concentrations were detected by enzyme-linked immunosorbent assay. Results: Compared with the controls, the serum adropin levels were lower in the HDCP group (P < 0.001) and in HDCP subgroups (gestational hypertension, mild preeclampisa, and severe preeclampsia, term, preterm, early onset, and late onset) (all P < 0.05). After adjustment for confounders, adropin remained negatively associated with HDCP (P = 0.027). Conclusion: Lower adropin concentration is significantly associated with HDCP, suggesting that higher or normal adropin levels may be protective against HDCP.

Background Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are assumed to be prognostic factors in many diseases such as inflammatory diseases, cardiovascular diseases and cancer. However, NLR and PLR are race specific, it is important to determine the reference values of NLR and PLR in different races. The study aimed to investigate the reference range of NLR and PLR in Chinese Han population from Chaoshan region in South China. Methods A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College in South China. Five thousand healthy adults aged 20–69 years were included. NLR and PLR were determined. Results Of 5000 healthy adults, 2500 men and 2500 women were included. The mean NLR and PLR across all ages for men and women were 1.59 ± 0.59, 92.88 ± 28.70, 1.62 ± 0.64 and 108.02 ± 32.99, respectively. The 95% reference range of NLR in normal male and female are 0.43~2.75 and 0.37~2.87, PLR are 36.63~149.13 and 43.36~172.68, respectively. The female had a higher NLR at age 30~49 than the male while the NLR at age 60~69 was higher in male than in female. The PLR was higher in female than in male. Conclusion The study provides reference data on NLR and PLR from different age and sex groups in South China. NLR and PLR varied with age and sex.

Purpose The purpose of this paper is to investigate the superior relationship between blood lipid- and cardiovascular disease (CVD)-related hematological parameters using superior grey relational analysis (GRA). Design/methodology/approach A total of 294 individuals who underwent simultaneous routine blood examination and blood lipid examination in the Physical Examination Center of the First Affiliated Hospital of Shantou University Medical College were included in this study. Superior GRA was performed to find out the superior factor in CVD-related hematological parameters and blood lipids. CVD-related hematological parameters included red blood cell distribution width, white cell count, and platelet count, platelet distribution width, mean platelet volume, as well as platelet crit. The indicators of blood lipids analyzed here consist of low-density lipoprotein, high-density lipoprotein, triglyceride and total cholesterol. Findings The results showed that all the grey relational degree of hematological parameters and blood lipids were over 0.8; the superior factor in hematological parameters was PLT, whereas TC was the superior factor in blood lipids. Practical implications Findings of this study suggested that hematological parameters are closely related to blood lipids and a potential role for hematological parameters in the prediction of dyslipidemia, which need further study; TC has the greatest influence on hematological parameters, whereas TG displays a minimal impact. Originality/value To the authors’ best knowledge, it was the first study to analyze the relationship between various CVD-related hematological parameters and blood lipids via superior GRA.

PurposeBased on the prediction of the consumption of medical materials, the purpose of this paper is to study the applicability of the grey model method to the field and its predicted accuracy.Design/methodology/approachThe ABC classification method is used to classify medical consumables and select the analysis objects. The GM (1,1) model predicts the annual consumption of medical materials. The GM (1,1) modeling of the consumption of the selected medical materials in 2006~2017 was carried out by using the metabolite sequence and the sequence topology subsequence, respectively. The average rolling error and the average rolling accuracy are calculated to evaluate the prediction accuracy of the model.FindingsThe ABC classification results show that Class A projects, which account for only 9.79 percent of the total inventory items, occupy most of the inventory funds. Eight varieties with varying purchases and usages and complete historical data were selected for further analysis. The subsequence GM(1,1) model group constructed by two different methods predicts and scans the annual consumption of eight kinds of medical materials, and the rolling precision can reach more than 90 percent.Originality/valueThe metabolic GM (1,1) model is an ideal predictive model that can meet the requirements for a short-term prediction of medical material consumption (Zhang et al., 2014). The GM (1,1) model is more suitable for a short-term prediction of medical material consumption with less data modeling.

Background Several ECG criteria have been widely used for diagnosis of left ventricular hypertrophy (LVH) in clinical practice. However, their performance in a general Chinese population is limited. Methods and results A multi‐stage, stratified cluster sampling across China was performed and 7415 representative Chinese adults aged 18–85 years were analyzed. ECG was collected by using GE MAC 5500 machine. The association between five ECG‐LVH criteria (i.e., Peguero–Lo Presti, Cornell, Cornell product, Sokolow–Lyon and Sokolow–Lyon product) and echocardiographic LVH (Echo‐LVH) was assessed by Pearson's correlation, diagnostic statistics like predictive values, and receiver operating characteristics (ROC) curve. We found that the prevalence of the Echo‐LVH was 11% while ECG‐LVH ranged from 3% to 27%. All ECG‐LVH criteria had high negative predictive value (NPV) (89%) and specificity (73–96%) but low positive predictive value (PPV) (12–24%) and sensitivity (4–29%). The newly Peguero–Lo Presti criteria had higher sensitivity (29%) but lower specificity (73%) and accuracy (68%) compared with other criteria. Cornell product had the best diagnostic performance (AUC: 0.59), as well as the highest specificity (96%) and accuracy (86%) but lowest sensitivity (4%). Among single‐lead components of ECG criteria, RaVL voltage and QRS duration performed relatively better than others. Hypertensive and older individuals had higher sensitivity but lower specificity and accuracy than their counterparts. Conclusion ECG‐LVH criteria had high NPV to detect Echo‐LVH. Though with higher sensitivity, Peguero–Lo Presti criteria did not have better diagnostic performance to detect Echo‐LVH. RaVL and QRS duration had stronger association with Echo‐LVH among all single‐lead components.

Background The Suboptimal Health Status Questionnaire-25 (SHS-Q-25) developed to measure Suboptimal Health Status has been used worldwide, but its construct validity has only been tested in the Chinese population. Applying Structural Equation Modelling, we investigate aspects of the construct validity of the SHS-Q-25 to determine the interactions between SHS subscales in a Ghanaian population. Methods The study involved healthy Ghanaian participants (n = 263; aged 20–80 years; 63% female), who responded to the SHSQ-25. In an exploratory factor and parallel analysis, the study extracted a new domain structure and compared to the established five-domain structure of SHSQ-25. A confirmatory factor analysis (CFA) was conducted and the fit of the model further discussed. Invariance analysis was carried out to establish the consistency of the instrument across multi-groups. Results The extracted domains were reliable with Cronbach’s $$\alpha$$ α of 0.846, 0.820 and 0.864 respectively, for fatigue, immune-cardiovascular and cognitive. The CFA revealed that the model fit indices were excellent $$\left( {{\text{RMSEA}} = 0.049~ < ~0.08,\,{\text{CFI}} = 0.903 > 0.9,\,{\text{GFI}} = 0.880 < 0.9,\,{\text{TLI}} = 0.907 > 0.9} \right)$$ RMSEA = 0.049 < 0.08 , CFI = 0.903 > 0.9 , GFI = 0.880 < 0.9 , TLI = 0.907 > 0.9 . The fit indices for the three-domain model were statistically superior to the five-domain model. There were, however, issues of insufficient discriminant validity as some average variance extracts were smaller than the corresponding maximum shared variance. The three-domain model was invariant for all constrained aspects of the structural model across age, which is an important risk factor for most chronic diseases. Conclusion The validity tests suggest that the SHS-Q25 can measure SHS in a Ghanaian population. It can be recommended as a screening tool to early detect chronic diseases especially in developing countries where access to facilities is diminished.

Background: Although mortality remains high in patients with atrial fibrillation (AF), there have been limited studies exploring machine learning (ML) models on mortality risk prediction in patients with AF.Objectives: This study sought to develop an ML model that captures important variables in order to predict all-cause mortality in AF patients.Methods: In this single center prospective study, an ML-based mortality prediction model was developed and validated using a dataset of 2,012 patients who experienced AF from November 2018 to February 2020 at the First Affiliated Hospital of Shantou University Medical College. The dataset was randomly divided into a training set (70%, n = 1,223) and a validation set (30%, n = 552). A total of 122 features were collected for variable selection. Least absolute shrinkage and selection operator (LASSO) and random forest (RF) algorithms were used for variable selection. Ten ML models were developed using variables selected by LASSO or RF. The best model was selected and compared with conventional risk scores. A nomogram and user-friendly online tool were developed to facilitate the mortality predictions and management recommendations.Results: Thirteen features were selected by the LASSO regression algorithm. The LASSO-Cox model achieved an area under the curve (AUC) of 0.842 in the training dataset, and 0.854 in the validation dataset. A nomogram based on eight independent features was developed for the prediction of survival at 30, 180, and 365 days following discharge. Both the time dependent receiver operating characteristic (ROC) and decision curve analysis (DCA) showed better performances of the nomogram compared to the CHA2DS2-VASc and HAS-BLED models.Conclusions: The LASSO-Cox mortality predictive model shows potential benefits in death risk evaluation for AF patients over the 365-day period following discharge. This novel ML approach may also provide physicians with personalized management recommendations.

Background Dyslipidemia and local inflammation at sites of lipid deposition on blood vessel walls have been demonstrated to be risk factors for patients with acute aortic dissection (AAD). Statins have anti-inflammatory and lipid-lowering effects, which suggest that statins may play an important role in the prevention and treatment of AAD. Some retrospective studies show that statins can protect patients with aortic dissection. However, the effect of statins on the survival of AAD patients has been scarcely investigated, especially in randomized trials. In this study, we will perform a randomized clinical trial to understand whether statins can reduce in-hospital mortality of AAD patients. Methods A total of 384 subjects diagnosed with AAD in the First Affiliated Hospital of Shantou University Medical College will be recruited. Participants will be randomly divided into an atorvastatin-treated or control group. The primary outcome will be the in-hospital mortality at 30 days. Discussion This study is designed to verify the efficacy of atorvastatin on reducing in-hospital mortality of patients with AAD. The aim is to provide a new means of improving survival as a complement to conventional drug therapy. Trial registration Chinese Clinical Trials Registry ChiCTR1900023515. Registered on 1 June 2019.

Background: Genetic polymorphisms, age, gender and body weight are major determinants of warfarin dose requirements. Our previous study showed that patients with non-O blood groups required higher doses of warfarin than those with O blood groups. However, the underling mechanism was not well known.Objectives: The study aimed to investigate the influence of ABO blood group, age and gender on the values of coagulation tests in patients with acute deep vein thrombosis in Chinese Han population.Methods: A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College in Southern China. Two hundreds and 35 patients with confirmed diagnosis of acute deep vein thrombosis were included. Coagulation tests were determined.Results: Of 235 patients with acute deep vein thrombosis of lower extremities, 70 patients had blood group A (29.79%), 71 patients had blood group B (30.21%), 30 patients had blood group AB (12.77%), and 64 patients had blood group O (27.23%). The study showed no difference about coagulation tests among the patients with different blood groups. Coagulation tests were not affected by age and gender.Conclusion: Our study showed that ABO blood group, age and gender had no effects on coagulation tests in patients with acute deep vein thrombosis

OBJECTIVETo establish normal reference range for the fetal right myocardial performance index (RMPI), and compare the reference range between in vitro fertilization (IVF) fetuses and spontaneous pregnancy (SP) fetuses by automatic measurement of the RMPI.METHODSFrom September 2019 to January 2020, 410 participants, who were at 19-40 weeks' gestation, were enrolled into the current study. Among 410 participants, there were 371 spontaneous pregnancies which were matched as control group, and the experimental group involved 39 singleton pregnancies conceived by IVF. RMPI was calculated as (a-b)/b. The three readings were obtained and averaged per examination, with intra-observer repeatability assessed by intraclass correlation coefficient (ICC) and 95% confidence interval (CI). The ‘a’ and ‘b’ intervals were measured at 3 different caliper positions in each fetus: beginning of the original valve clicks (‘original’), beginning of the reflected tricuspid and pulmonary closure clicks (‘reflected’), and peak of valve clicks (‘peak’).RESULTSThe RMPI of SP fetuses was 0.43±0.05 (mean ± standard deviation (SD)), and the RMPI of IVF fetuses was 0.42 ±0.05 (mean ± SD). There was no significant difference in normal reference range of right MPI between IVF fetuses and SP fetuses. No strong correlation was also noted between RMPI with gestational age and heart rate.CONCLUSIONNormal reference ranges of RMPI of IVF fetuses and SP fetuses were established, and no significant difference between IVF fetuses and SP fetuses was found.

Objective It is unclear whether uterine fibroids are associated with the occurrence of hypertensive disorders of pregnancy (HDP). Thus, this study aimed to evaluate the association between uterine fibroids and HDP in a prospective cohort. Methods Overall, 2404 pregnant women who received antenatal care were enrolled in a prospective cohort in China between 2014 and 2016; 2277 women met the inclusion criteria of this study. The clinical characteristics of participants were assessed via questionnaires and physical examinations at baseline (before the 20th week of gestation), 21st-27th, 28th-34th, and 35th-39th gestational weeks. Ultrasound examination was performed before the 20th week of pregnancy to determine the presence of uterine fibroids. Linear mixed-effect and Cox proportional hazard regression models were used to analyze the association of uterine fibroids with blood pressure and HDP. Results Of 2277 pregnant women, 242 (10.6%) had uterine fibroids, and 45 (2.0%) subsequently developed HDP. The incidence of HDP in women with and without uterine fibroids was 5% (n = 12) and 1.6% (n = 33), respectively. The longitudinal SBPs and DBPs were significantly higher in women with uterine fibroids than in those without. The multivariable Cox model showed that the presence of uterine fibroids was associated with increased HDP risk (adjusted hazard radio: 2.95, 95% confidence interval: 1.35-6.44). Conclusion Uterine fibroids in early pregnancy were associated with an increased HDP risk. Blood pressure of women with uterine fibroids should be closely monitored, and HDP preventive measures are crucial.

Background The association between different ABO blood groups and mortality of aortic dissection (AD) remains controversial. This study aimed to examine whether different ABO blood groups affect the prognosis of AD. Methods Demographic and clinical data were collected from 877 patients diagnosed with AD from 2015 to 2019 in the First Affiliated Hospital of Shantou University Medical College. The association between in-hospital mortality of AD patients and ABO blood group was analyzed using Cox proportional hazards regression models. Results This retrograde cohort study demonstrated that for 877 patients, male gender, non-O blood group, Stanford type B AD (TBAD), higher presenting systolic and diastolic blood pressure, and being a recipient of aortic arch replacement surgery (surgery) or endovascular stent-graft implantation (stent-graft) were associated with decreased in-hospital mortality of AD. In Cox proportional hazards models, non-O blood group was associated with lower risk of early mortality regardless of adjustment (HR = 0.668, 95% confidence interval [CI] 0.473–0.944 before adjustment, HR = 0.662, 95% CI 0.468–0.935 after adjustment for age and sex, and HR = 0.641, 95% CI 0.453–0.906 after adjustment for AD types, SBP and surgery). Further analyses revealed that for patients diagnosed with type A AD (TAAD), non-O blood group renders a significant 34.3% decrease in the risk of in-hospital mortality compared with blood group O. Specifically, this difference in mortality risk was found among TAAD patients who did not undergo surgery (HR = 0.579, 95% CI 0.377–0.889), rather than those who did. There was no significant difference in early mortality for patients with TBAD, whether or not stent-grafts were implanted. Conclusions Non-O blood type decreases the risk of in-hospital mortality, especially for TAAD, in AD patients without surgical intervention. More attention must be paid to blood type O TAAD patients without surgical interventions, and early surgical intervention may be an effective means to decrease in-hospital mortality of TAAD.

Background COVID-19(Corona Virus Disease 2019) outbreaks around the world and is highly infectious, which may cause people prone to anxiety and depression. As a particular group, pregnant women need more attention. The aim of study is to investigate the mental health status of pregnant women during the outbreak of COVID-19, and analyze factors affecting the mental health status of pregnant women.Methods Using a self-designed questionnaire, self-rated anxiety scale(SAS), self-rated depression scale (SDS), we conducted a web-based survey on 1160 pregnant women during the outbreak of COVID-19.Results Compared with general adults in some regions of China, the scores of SAS and SDS were both significantly higher in pregnant women during the outbreak of COVID-19 (P Conclusions During the outbreak of COVID-19, pregnant women are prone to anxiety or depression, highlighting the necessity of further attention on those subjects. It is of great significance to provide on-time psychological intervention and psychological counseling for pregnant women with poor mental health.

Background: Dyslipidemia and local inflammation at sites of lipid deposition on blood vessel walls have been demonstrated to be risk factors for patients with acute aortic dissection (AAD). Statins have anti-inflammatory and lipid-lowering effects, which suggest that statins may play an important role in prevention and treatment of AAD. Some retrospective studies show that statins can protect patients with aortic dissection. However, the effect of statins on survival of AAD patients have been scarcely investigated, especially in randomized trials. In this study, we will perform a randomized controlled trial (RCT) to evaluate the effect of statins on in-hospital mortality of AAD patients. Methods: A total of 384 subjects diagnosed with AAD in the First Affiliated Hospital of Shantou University Medical College will be recruited. Participants will be randomly divided into atorvastatin-treated or placebo groups. The primary outcome will be the in-hospital mortality. Discussion: This study is designed to verify the safety and efficacy of atorvastatin in patients with AAD. The aim is to provide a new way to improve survival as a complement to conventional drug therapy.Trial registration: Registered by Chinese Clinical Trials Registry (Registration number:ChiCTR1900023515,http://www.chictr.org.cn/edit.aspx?pid=38275&htm=4).Registered 1 June 2019.

Background：Chronic Obstructive Pulmonary Disease（COPD) is an inflammatory airway disease characterized by the presence of expiratory flow limitation. Exacerbations of COPD are common acute events. During epidemic of COVID-19, concerns have been raised with regard to mask- using because of increasing respiratory resistance. In this study, we aimed to evaluate the relationship between the vital signs , inflammation index, hypercapnia, hypoxia and mask-using in AECOPD patients.Methods：This retrospective study was performed at a tertiary hospital, and enrolled 23 patients with AECOPD who were hospitalized three or more times in the respiratory department. Patients in Group C were hospitalized and used masks during the epidemic period of COVID-19. Patient’s data of the previous two hospitalizations from the medical record system divided into group A and group B according to the time sequence. Vital signs, inflammation index, artery blood gas from medical record system and questionnaires of three hospitalizations in the same patient were collected to perform paired test.Results: Surgical mask using increased the levels of PaCO2 (8.98mm Hg; p = 0.004), HCO3-act (4.1mmol/L; p =0.006), BE (3.01mmol/L; p =0.019) and systolic blood pressure (11.39mm Hg; p = 0.01) in patients with AECOPD compared to last hospitalization. Surgical mask using for 30 to 120 minutes is associated with hypercapnia. There were no significant differences observed between group B and group A without using mask in vital signs, inflammation index, and artery blood gas.Conclusions: In this study, we found that systolic blood pressures and PaCO2, HCO3-act, BE were significantly elevated in AECOPD patients using masks compared to the other groups without masks. In addition，the changes in PaCO2,HCO3-act,BE is closely related to serum chloride concentration. Therefore, it is need to increase awareness and understanding of the use of masks in patients with chronic cardiopulmonary diseases.

Background and aims Loss of the cholesteryl ester transfer protein (CETP) function affects HDLc levels, but its effects on major HDL protein component ApoA1 are not well understood in patients with acute myocardial infarction (AMI). Methods and results We investigated the effects of an East Asian loss-of-function variant (rs2303790; p.D442G) in CETP gene on HDLc and ApoA1 levels and its relationship with AMI. A total of 2327 AMI patients and 2615 age- and sex-matched controls from INTERHEART-China study were included. In controls, both levels of HDLc (1.24 vs. 1.04 mmol/L, P = 0.001) and ApoA1 (1.48 vs. 1.37 mmol/L, P = 0.042) were significantly higher in CETP variant G allele carriers compared to CETP wildtype D allele carriers. In AMI patients, levels of HDLc were significantly higher (1.14 vs. 1.01 mmol/L, P = 0.013) while levels of ApoA1 were not statistically difference (1.31 vs. 1.32 mmol/L, P = 0.468) in CETP variant group compared to CETP wildtype group. Moreover, CETP variant is associated with HDLc increase, but is not associated with AMI risk (P = 0.564), even after adjusting for age, sex, history of hypertension and diabetes, waist to hip ratio, smoking, total cholesterol, LDL cholesterol, triglycerides, physical activity, depression, alcohol, vegetables and fruit consumption. Conclusions Loss of CETP function is associated with increased HDLc and ApoA1 levels in healthy subjects, and in AMI patients, it is associated with HDLc levels but not ApoA1 levels. The lack of association of CETP variant with AMI may be related to the inability to increase ApoA1 levels and warranted further studies.

Background Whether the in vitro fertilization (IVF) has an effect on the cardiac function of the fetus is very important to evaluate the safety of the technique. The aim of this paper is to establish normal reference range for the fetal right myocardial performance index (RMPI), and compare the reference range between IVF fetuses and spontaneous pregnancy (SP) fetuses by automatic measurement of the RMPI. Methods Three hundred seventy-one spontaneous singleton pregnancies (the control group) and 39 singleton pregnancies conceived by IVF (the experimental group) were enrolled into the current study. An automatic measurement system was used to acquire the RMPI. The cardiac function of the two groups was compared by t-test. Results There was no significant difference in normal reference range of RMPI between IVF fetuses and SP fetuses (RMPI 0.42 ± 0.05 vs 0.43 ± 0.05). No strong correlation was also noted between RMPI with gestational age and heart rate. Conclusions Normal reference ranges of RMPI of IVF fetuses and SP fetuses were established, and no significant difference between IVF fetuses and SP fetuses in RMPI was found. Thus, these findings may suggest that IVF has little impact on cardiac function of the fetus.