Global, regional, and national time trends in mortality for stroke, 1990-2019: An age-period-cohort analysis for the global burden of disease 2019 study and implications for stroke prevention.

BACKGROUND: Despite the fact that stroke is the second leading cause of death globally, a comprehensive and comparable assessment of mortality, and epidemiologic trends has not been conducted for most regions.We estimated the global and regional burden of stroke from 1990 to 2019 using data from the 2019 Global Study of Diseases, Injuries, and Risk Factors. METHODS: For the period between 1990 and 2019, we used an age-period-cohort model to calculate the annual percentage changes in mortality (net drifts), local drifts, and period and cohort relative risks (period/cohort effects). Meanwhile, to quantify the temporal trends in stroke age-standardised mortality rate (ASMR), Average annual percentage changes (AAPCs) were determined by sex, area. With the potential to uncover disparities and treatment gaps in stroke care, this approach enables the examination and differentiation of age, period, and cohort effects in mortality trends. FINDINGS: Global stroke deaths in 2019 were 6,552,725 (95% UI 5,995,200 to 7,015,139). Between 1990 and 2019, the ASMR declined globally by 36.43% (95% UI -41.65 to -31.2), with decreases in all SDI quintiles. The net drift in stroke mortality from 1990 to 2019 varied from -2.83% per year (95% confidence interval [CI]:-3.39 to -2.77) in countries with a high Socio-demographic Index (SDI) to -1.21% per year (95% CI: -1.26 to -1.16) in countries with a low SDI. During the past 30 years, favorable mortality reductions were generally found in high-SDI countries (net drift = -3.1% [95% CI: -3.4 to -2.8] per year) and high-middle SDI countries (-2.8% [-3.0 to -2.6]). However, 31 of 204 countries had either increasing trends (net drifts≥0.0%) or stagnated reductions (≥ - 0.5%) in mortality. The relative risk of mortality generally showed improving trends over time and in successively younger birth cohorts among high and high-middle SDI countries, with the exceptions of Kuwait, Ukraine, Kazakhstan, Guam, RussianFederation, Lithuania, Turkey, Montenegro, Serbia, Bosnia and Herzegovin, and Bulgaria. INTERPRETATION: Notwithstanding mortality from stroke has increased globally over the past 30 years, adverse period and cohort effects have been found in many countries, calling into question the adequacy of healthcare for stroke patients of all ages. These lapses have a significant impact on the likelihood of achieving the Sustainable Development Goal (SDG) targets on mortality from age 60+ and NCDs.

Interpretable machine learning for 28-day all-cause in-hospital mortality prediction in critically ill patients with heart failure combined with hypertension: A retrospective cohort study based on medical information mart for intensive care database-IV and eICU databases.

Background: Heart failure (HF) combined with hypertension is an extremely important cause of in-hospital mortality, especially for the intensive care unit (ICU) patients. However, under intense working pressure, the medical staff are easily overwhelmed by the large number of clinical signals generated in the ICU, which may lead to treatment delay, sub-optimal care, or even wrong clinical decisions. Individual risk stratification is an essential strategy for managing ICU patients with HF combined with hypertension. Artificial intelligence, especially machine learning (ML), can develop superior models to predict the prognosis of these patients. This study aimed to develop a machine learning method to predict the 28-day mortality for ICU patients with HF combined with hypertension. Methods: We enrolled all critically ill patients with HF combined with hypertension in the Medical Information Mart for IntensiveCare Database-IV (MIMIC-IV, v.1.4) and the eICU Collaborative Research Database (eICU-CRD) from 2008 to 2019. Subsequently, MIMIC-IV was divided into training cohort and testing cohort in an 8:2 ratio, and eICU-CRD was designated as the external validation cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression with internal tenfold cross-validation was used for data dimension reduction and identifying the most valuable predictive features for 28-day mortality. Based on its accuracy and area under the curve (AUC), the best model in the validation cohort was selected. In addition, we utilized the Shapley Additive Explanations (SHAP) method to highlight the importance of model features, analyze the impact of individual features on model output, and visualize an individual's Shapley values. Results: A total of 3,458 and 6582 patients with HF combined with hypertension in MIMIC-IV and eICU-CRD were included. The patients, including 1,756 males, had a median (Q1, Q3) age of 75 (65, 84) years. After selection, 22 out of a total of 58 clinical parameters were extracted to develop the machine-learning models. Among four constructed models, the Neural Networks (NN) model performed the best predictive performance with an AUC of 0.764 and 0.674 in the test cohort and external validation cohort, respectively. In addition, a simplified model including seven variables was built based on NN, which also had good predictive performance (AUC: 0.741). Feature importance analysis showed that age, mechanical ventilation (MECHVENT), chloride, bun, anion gap, paraplegia, rdw (RDW), hyperlipidemia, peripheral capillary oxygen saturation (SpO2), respiratory rate, cerebrovascular disease, heart rate, white blood cell (WBC), international normalized ratio (INR), mean corpuscular hemoglobin concentration (MCHC), glucose, AIDS, mean corpuscular volume (MCV), N-terminal pro-brain natriuretic peptide (Npro. BNP), calcium, renal replacement therapy (RRT), and partial thromboplastin time (PTT) were the top 22 features of the NN model with the greatest impact. Finally, after hyperparameter optimization, SHAP plots were employed to make the NN-based model interpretable with an analytical description of how the constructed model visualizes the prediction of death. Conclusion: We developed a predictive model to predict the 28-day mortality for ICU patients with HF combined with hypertension, which proved superior to the traditional logistic regression analysis. The SHAP method enables machine learning models to be more interpretable, thereby helping clinicians to better understand the reasoning behind the outcome and assess in-hospital outcomes for critically ill patients.

The Ameliorative Effect of Berberine on Vascular Calcification by Inhibiting Endoplasmic Reticulum Stress.

ABSTRACT: Vascular calcification (VC), which currently cannot be prevented or treated, is an independent risk factor for cardiovascular events. We aimed to investigate the ameliorative effect of berberine on VC via the activation of Akt signaling and inhibition of endoplasmic reticulum stress (ERS). The VC model was induced by high-dose Vitamin D 3 in rats and beta-glycerophosphate in primary vascular smooth muscle cells of rat aortas, which were evaluated by Alizarin red staining to determine the calcium content and alkaline phosphatase activity. ERS was determined by the levels of GRP78 and CHOP, whereas that of the Akt signaling pathway was determined by the levels of phosphorylated Akt and GSK3ß. VC was significantly ameliorated by berberine treatment in vivo and in vitro, and the inhibition of ERS and the activation of the Akt/GSK3 signaling pathway. In the vascular smooth muscle cells of primary rats, tunicamycin, an ERS activator, blocked the ameliorative effect of berberine on VC and ERS, but not the activation of Akt/GSK3. The ameliorative effects of berberine on VC, ERS, and the Akt signaling pathway were all prevented by inhibitor IV. Four-phenylbutyric acid, an ERS inhibitor, can restore the ameliorative effect of berberine on VC and ERS that was blocked by inhibitor IV. Our results are the first to demonstrate the ameliorative effect of VC that was mediated by the activation of the Akt signaling pathway and inhibition of ERS. These results may provide a new pharmaceutical candidate for the prevention and treatment of VC.

Diagnostic performance of blood-based liquid biopsies in hepatocellular carcinoma: A protocol for systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer associated with poor prognosis. Early diagnosis is crucial to improve its prognosis. Blood-based liquid biopsies are promising methods in detecting HCC. However, their accuracies have not been systematically assessed, so it is essential to conduct a meta-analysis to evaluate the diagnostic performance of blood-based liquid biopsies in detecting HCC. METHODS: We will search PubMed, EMBASE, Cochrane Library, Web of Science, Medline, China National Knowledge Infrastructure(CNKI) for the relevant studies that assessed the diagnostic performance of blood-based liquid biopsies including circulating tumor cells(CTCs), circulating tumor DNA(ctDNA), and exosomes(EVs) in HCC patients from inception to September 2020. Two researchers will independently extract the data and use Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) to evaluate the quality of included literature. We will also conduct the pool diagnostic value, heterogeneity across studies and reporting bias. All the statistical analysis will be conducted by Stata V.15.0 and Meta-disc V.1.4. RESULTS: This review will evaluate the pooled diagnostic value of blood-based liquid biopsies in HCC. CONCLUSION: This review will summarize the current published evidence of blood-based liquid biopsies in diagnosing HCC, which may provide a great opportunity for promotion and application of them. OPEN SCIENCE FRAMEWORK(OSF) REGISTRATION NUMBER: September 3, 2020. https://osf.io/9n4yz.

Diagnostic performance of circulating MicroRNAs in acute ischemic stroke: A protocol for systematic review and meta-analysis.

INTRODUCTION: Increasing evidences showed differential expression of circulating microRNAs (miRNAs) in patients with acute ischemic stroke (AIS), indicating that miRNAs might serve as promising biomakers in the diagnosis of AIS. However, their accuracy has not been systematically evaluated, so it is necessary to conducted a meta-analysis to evaluate the diagnostic value of miRNAs in AIS patients. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, Medline, China National Knowledge Infrastructure (CNKI) will be searched for the relevant studies that explored the potential diagnostic values of miRNAs in AIS patients from inception to August 2020. Data will be extracted by two researchers independently; risk of bias of the meta-analysis will be evaluated by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Data will be synthesised and heterogeneity will be evaluated. All of the above statistical analysis will be performed using Stata V.15.0 and Meta-disc V.1.4. RESULTS: This study will assess the pooled diagnostic performance of circulating miRNAs in AIS. CONCLUSION: This study will clarify confusions about the specificity and sensitivity of circulating miRNAs in diagnosing AIS, which could further guide the promotion and application of them.Open Science Framework (OSF) registration number: 2020, August 19. https://osf.io/6tjf3.

The Trp64Arg polymorphism in ß3 adrenergic receptor (ADRB3) gene is associated with adipokines and plasma lipids: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: Recently, some studies claim that adipokines may modulate plasma lipids. More interestingly, the ADRB3 Trp64Arg polymorphism may regulate adipokines and play an essential role in lipids metabolism. This study aims to clarify the associations of ADRB3 Trp64Arg polymorphism with plasma adipokines and lipid levels. METHODS: Twenty-two studies (5527 subjects) and 121 studies (54,059 subjects) were respectively identified for the association analyses of adipokines and lipids. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to estimate the strength of the Trp64Arg variant in adipokines and plasma lipids. All results were recalculated after eliminating the studies with heterogeneity. RESULTS: The carriers of the C allele (Arg at 64th position was encoded by the C allele) had higher levels of leptin and lower levels of adiponectin than the non-carriers. The carriers of the C allele had higher levels of triglycerides (TG), total cholesterol (TC), and lower levels of high-density lipoprotein cholesterol (HDL-C) than the non-carriers. Subgroup analysis certified an ethnicity (Asians), disease status (obesity), and gender (females) specific association. Sensitivity analysis indicated that the analysis results were robust and stable. Meta-regression indicated that obesity was related to adiponectin. CONCLUSIONS: The C allele carriers of Trp64Arg polymorphism had a slight but significant influence on lipid levels, and the remarkable effects specific existed in obese Asian women. The associations of Trp64Arg polymorphism with dyslipidemia may partly be mediated by the effect of this polymorphism on adipokines. The association of Trp64Arg polymorphism with obesity may partly be mediated by the effect of this polymorphism on adipokines. The C allele carriers had abnormal levels of adipokines and lipids, and it indicated that the Trp64Arg polymorphism might represent a genetic risk factor for coronary artery disease (CAD).

Acute myocardial infarction as the first manifestation of Takayasu arteritis: A case report.

RATIONALE: Takayasu arteritis (TA) is a chronic inflammatory disease involving the aorta and its major branches. Initial diagnosis is usually difficult due to the highly variable symptoms. Acute myocardial infarction (AMI) is a very rare presentation in patients with TA. Moreover, the choice of early management for these patients is not well established. PATIENT CONCERNS: A 34-year-old woman was taken to the Emergency Department of our hospital, presenting with a sudden onset and persistent retrosternal chest pain radiating to both upper extremities for 2 hours. Blood pressures were different between 2 arms with 151/115 mm Hg on the right arm and 140/100 mm Hg on the left arm. DIAGNOSES: The patient was diagnosed with TA according to the medical history, physical examination, and vascular imaging. INTERVENTIONS: Primary percutaneous coronary intervention (PPCI) was performed to restore the coronary flow of left anterior descending. Meanwhile, combination of oral glucocorticoids and immunosuppressive agents was administered to halt disease progression of TA. OUTCOMES: Chest pain was relieved without rest and exertional angina. The patient achieved long-term remission without symptom relapse during our follow-up. LESSONS: Percutaneous coronary intervention was essential and effective in AMI of TA. Timely immunosuppressive therapy could improve the long-term outcome.

Efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus: a randomized controlled trial.

OBJECTIVE: To assess the efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with single oral metformin in a randomized controlled trial (RCT). METHODS: A total of 132 patients with T2DM were enrolled in the study, who only took metformin (500-1000 mg/day) for at least three months and with inadequate glycemic control (7.0% ≤ hemoglobin A1c ≤ 9.0% ) in the past three months. The patients stopped taking metformin with lifestyle interventions for three weeks, and 105 patients qualified for the program. They were randomly divided into the Sancai powder group and the metformin group (1500 mg/day). The follow-up period was for 12 weeks. Comparisons of several variables were analyzed. RESULTS: No significant differences were found between the two groups in hemoglobin A1c (HbA1c), fasting plasma glucose (FPG) and 2 h post-meal glucose (2hPG), although they had decreased significantly (P < 0.01). Homeostasis model assessment of beta cell function index was significantly improved in Sancai powder group (P < 0.01), and there were significant differences in the changes of homeostasis model assessment of insulin resistance and insulin sensitivity index in the two groups (P < 0.05). Sancai powder significantly reduced triglyceride level (P < 0.05), although there was no significant difference in the body weight and body mass index in the two groups. CONCLUSION: In this 12-week study, Sancai powder could significantly reduce hemoglobin A1c, FPG and 2hPG levels, improved beta-cell function and insulin resistance of the T2DM inadequately controlled with metformin.

Dengzhanhua preparations for acute cerebral infarction.

BACKGROUND: Dengzhanhua preparations are widely used in China. Many controlled trials have been undertaken to investigate the efficacy of dengzhanhua preparations in the treatment of acute cerebral infarction. OBJECTIVES: To assess whether dengzhanhua preparations are effective and safe at improving outcomes in patients with acute cerebral infarction. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched October 2007), the Chinese Stroke Trials Register (last searched June 2006), the trials register of the Cochrane Complementary Medicine Field (last searched June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2 2006), MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), AMED (the Allied and Complementary Medicine Database, 1985 to June 2006), the China Biological Medicine Database (CBM-disc, 1979 to June 2006), and Chinese Knowledge Infrastructure (CNKI,1994 to October 2007). We also searched the reference lists of relevant articles. SELECTION CRITERIA: Randomised and quasi-randomised controlled clinical trials of dengzhanhua preparations regardless of duration, dosage and route of administration in patients with confirmed acute cerebral infarction. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, assessed trial quality, and extracted the data. MAIN RESULTS: We included nine trials, all conducted in China, involving 723 participants. The method of randomisation and concealment was poorly described. The included trials compared dengzhanhua injection plus routine therapy with routine therapy alone. Patients were enrolled up to one week after the onset of stroke. No trials reported data on the pre-specified primary or secondary outcomes. In a post-hoc comparison of dengzhanhua injection plus routine therapy versus routine therapy alone, dengzhanhua injection showed a statistically significant benefit on the outcome 'marked neurologic improvement' (relative risk 1.53; 95% confidence interval 1.36 to 1.72). No serious adverse effects were reported. AUTHORS' CONCLUSIONS: Due to the generally low methodological quality and small sample size of the included trials in this systematic review, we could not draw a firm conclusion.