The impact of long-term antihypertensive treatment on wound healing after major non-cardiac surgery in patients with cardiovascular diseases: A meta-analysis.

Hypertension is a prevalent condition that poses significant challenges in the perioperative management of patients undergoing major non-cardiac surgery, particularly concerning wound healing and scar formation. This meta-analysis assesses the impact of long-term antihypertensive treatment on postoperative wound healing, examining data from seven studies involving patients who received such treatments compared to untreated controls. Our findings reveal that long-term antihypertensive therapy is associated with significantly improved wound healing outcomes, as indicated by lower REEDA scores (I2 = 96%, SMD = -25.71, 95% CI: [-33.71, -17.70], p < 0.01) 1 week post-surgery and reduced scar formation, demonstrated by lower Manchester Scar Scale scores (I2 = 93%, SMD = -37.29, 95% CI: [-44.93, -29.64], p < 0.01) 2 months post-surgery. These results underscore the potential benefits of antihypertensive treatment in enhancing surgical recovery and offer insights into optimising perioperative care for hypertensive patients.

EIF5A2 specifically regulates the transcription of aging-related genes in human neuroblastoma cells.

BACKGROUND: Post-transcriptional regulation plays a critical role in controlling biological processes such as aging. Previous studies have shown that eukaryotic initiation factor 5A (EIF5A) might play a crucial role in aging. It is unknown whether EIF5A2, a second isoform of EIF5A, could impact aging through post-transcriptional regulation. METHODS: In the present study, EIF5A2 overexpression (EIF5A2-OE) was induced in SH-SY5Y cells. RNA-seq, bioinformatics analysis and RT-qPCR validation experiments were then performed to explore the molecular mechanism of EIF5A2-mediated transcriptional regulation. Cell viability, proportion of senescent cells and the cell cycle were respectively determined by Cell Counting Kit-8, SA-ß­galactosidase and flow cytometry to evaluate the cell senescence. RESULTS: A total of 190 downregulated and 126 upregulated genes related to EIF5A2-OE were identified. Genes closely related to cellular aging processes such as unfolded protein response (UPR), cell adhesion and calcium signaling pathway were under global transcriptional regulation. Moreover, EIF5A2-OE promoted the viability of SH-SY5Y cells and reduced cell senescence in vitro. Among 30 genes with the most significant expression differences in EIF5A2-OE cells, we identified eight genes, including ASNS, ATF3, ATF4, CEBPB, DDIT3, HERPUD1, HSPA5 and XBP1, enriched in the UPR. Through EIF5A2-tanscription factors (TFs)-targets regulation network in EIF5A2-OE cells, we found three TFs, BHLHE40, RHOXF1 and TBX20, that targeted at these eight UPR-related genes. Verification test via the published database of human glial cell tissue showed only BHLHE40 and RHOXF1 were significantly associated with EIF5A2. CONCLUSIONS: Our findings suggest that EIF5A2 may alleviate cell senescence in vitro and mediate UPR-related genes via specific TFs. Thus, EIF5A2 could function as a regulator of aging via the regulation of transcription, which greatly expands the current understanding of the mechanisms of EIF5A2-mediated gene regulation.

Exogenous BMP-7 Facilitates the Recovery of Cardiac Function after Acute Myocardial Infarction through Counteracting TGF-ß1 Signaling Pathway.

Myocardial fibrosis after acute myocardial infarction (AMI) is one of the main causes of myocardial remodeling and heart function abnormalities. Bone morphogenetic protein-7 (BMP-7) has been reported to play essential roles in anti-fibrosis. In this study, we demonstrated the role of exogenous BMP-7 on myocardial fibrosis and heart function recovery after AMI. A rat model of AMI was established via ligation of the left anterior descending coronary artery (LAD). Twenty rats were grouped into sham group which underwent chest open operation, but did not receive LAD ligation. Another 40 rats underwent LAD ligation were randomly grouped into saline-treated group (n = 20) and BMP-7-treated group (n = 20) which received saline treatment or exogenous BMP-7 treatment for 14 days, respectively. Two weeks after LAD ligation, the survival rate of BMP-7-treated AMI group was significantly improved compared to the saline group. Moreover, the cardiac function was preserved as shown by echocardiography examination, and the infarcted size was limited upon BMP-7 treatment. In addition, we investigated the role of TGF-ß1 signaling pathway in BMP-7-mediated cardioprotective effects by analyzing the expression levels of TGF-ß1, Smad 2 and Smad 3 in the infarct zone, border zone, and non-infarct zone. Western blot and quantitative PCR results suggested that BMP-7 attenuated myocardial fibrosis through counteracting TGF-ß1 signaling pathway, thereby exerting cardioprotective effects. In conclusion, our data provide a potential therapeutic direction for preserving cardiac function and improving prognosis of AMI patients.

Endoplasmic reticulum stress-mediated aldosterone-induced apoptosis in vascular endothelial cells.

The aim of this study was to examine the effects of endoplasmic reticulum (ER) stress on aldosterone (Aldo)-induced apoptosis of endothelial cells. Glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP, a hallmark of ER-associated apoptosis) were used to evaluate ER stress. Western blotting and real-time PCR were used to analyze indicators of ER molecule. Apoptosis was detected by annexin V/propidium iodide staining and flow cytometry. Human umbilical vein endothelial cells (HUVECs) were stimulated with different concentrations of Aldo for different durations. Aldo promoted apoptosis of HUVECs and induced ER stress, as evidenced by increased expression of GRP78 and CHOP. siRNA knockdown of CHOP attenuated Aldo-mediated apoptosis. These results indicate that ER stress may be involved in Aldo-induced apoptosis of HUVECs.

The impact of Chinese volume-based procurement on pharmaceutical market concentration.

Objectives: Optimizing the pharmaceutical industrial structure is the key mission of China's healthcare reform. From the industrial structure perspective, this study empirically evaluated the impact of China's national volume-based procurement (NVBP) policy on market concentration in the hospital-end drug market. Methods: This study used drug procurement data of China's public medical institutions which obtained from the national database. A quasi-natural experiment was designed involving eleven pairs of matched treatment-control region combinations, with NVBP policy as the intervention measure. The market was defined by drug name (molecular boundary) and city/province (geographical boundary). Market changes were measured from three dimensions: the number of enterprises and products, market share, and Herfindahl-Hirschman index (HHI). Dual comparison approach and difference-in-difference (DID) method with fixed effect model were applied to quantify policy impacts. Results: The number of enterprises and products decreased by 18 and 83 in pilot regions after NVBP policy, far more than the decreases in control regions (6 and 21). The accumulative market share of 15 bid-winning enterprises increased by 53.67% in volume and 18.79% in value, among which the increment of enterprises with low baseline market share was more prominent (66.64% and 36.40%). Among three enterprise types, the market share of generic consistency evaluation (GCE) certificated generics significantly increased, GCE uncertificated generics significantly decreased, and originators slightly decreased. DID models indicated significantly positive impact of NVBP policy on market concentration, with HHI-volume and HHI-value increasing by 49.33% (ß = 0.401, p < 0.01) and 21.05% (ß = 0.191, p < 0.01). Conclusion: The implementation of NVBP promoted the intensive drug circulation and supply of Chinese public hospitals, intensifying the exit of GCE uncertificated generics from the hospital-end market. NVBP combined with GCE standards significantly improved market concentration, which brought a positive signal of pharmaceutical industrial structure optimization in China. In the future context of normalized and institutionalized NVBP, the balance should be further sought between low drug prices and reliable hospital drug supply, sustainable industry development.

A J-shaped relationship between body mass index and the risk of elevated liver stiffness: a cross-sectional study.

BACKGROUND: Liver stiffness (LS) is regarded as an indicator of the stages of liver fibrosis and liver cirrhosis. Numerous studies have investigated the relationship between body mass index (BMI) and LS; however, the conclusions remain controversial. In the current study, we utilized transient elastography (TE) technique, which could measure LS in a non-painful and noninvasive way, to explore the relationship between BMI and the risk of elevated LS in common community residents. METHODS: 5791 participants were included in the present study. To calculate BMI value, height and weight of the participants were carefully measured. Liver stiffness measurement (LSM) > 9.1 kPa was considered as a cutoff suggesting elevated LS. The relationship of BMI and risk of elevated LS was derived using generalized linear regression models, and the threshold effect was then analyzed by smooth curve fitting and segmented regression model. RESULTS: Elevated LS was detected in 230 participants (3.97%) using the TE technique. After potential confounders were adjusted according to the individual's demographic variables, underlying comorbidities and blood biochemical test results, we observed a J-shaped relationship between BMI and the risk of elevated LS, with the inflection point at 23.05 kg/m2. The effect size (and confidence interval) was 0.84 (0.71, 0.98) on the left side of the inflection point, and 1.32 (1.24, 1.41) on the right side of it. CONCLUSIONS: Our study found a novel J-shaped relationship between BMI and the risk of elevated LS assessed by TE technique. Abnormal BMI, either higher or lower, was associated with an increased risk of elevated LS.

Intima-medial thickness homogeneity in the common carotid artery: measurement method and preliminary clinical study.

BACKGROUND: To propose and test in a preliminary clinical study a novel method for calculating intima-medial thickness (IMT) homogeneity (IMTH). METHODS: IMT was measured off-line on every horizontal pixel line along the far wall of the common carotid artery, with previously validated software. IMTH was assessed by the SD, coefficient of variation, and interval distribution of obtained IMT values. This method was applied to 129 individuals (age, 40-60 years), including 49 healthy control subjects, 44 subjects at high risk of atherosclerosis, and 36 subjects with known atherosclerosis. Differences with a p value <0.05 were considered statistically significant. RESULTS: SD and coefficient of variation were higher in the high-risk than in the control group, as well as in high-risk and control subgroups with maximal IMT = 0.8 mm or mean IMT = 0.55-0.65 mm. There were 85.7, 62.8, and 36% of IMT values in the 0.4- to 0.6-mm range and 0.89, 13.8, and 21.2% of IMT values in the 0.8- to 1.2-mm range in the control, high-risk, and atherosclerosis groups, respectively. CONCLUSIONS: IMTH is a promising approach for the assessment of atherosclerosis, in addition to conventional IMT measurement. Further clinical studies are needed to assess its clinical usefulness.

Inhibition of miR-182-5p attenuates ROS and protects against myocardial ischemia-reperfusion injury by targeting STK17A.

Reperfusion therapy for acute myocardial infarction inevitably leads to ischemia-reperfusion (I/R) injury. A number of miRNAs are reported to be involved in I/R injury. This study aims to investigate the role and underlying mechanism of miR-182-5p in I/R injury. An in vivo model of I/R-induced rat myocardial injury and an in vitro model of H/R H9c2 cells were established to investigate the role and mechanism of miR-182-5p in I/R injury. The myocardial infarct size was determined by TTC staining. The serum CK-MB level was determined by ELISA kit. The miR-182-5p inhibitors or mimics were used to down-regulate or up-regulate its expression. The apoptosis and ROS were detected by flow cytometry. The expression of the proteins was detected by western blot. The binding of STK17A and miR-182-5p was validated by dual-luciferase reporter assay. The miR-182-5p was confirmed to be highly expressed in I/R injury rats and H/R H9c2 cells. Inhibition of miR-182-5p significantly reduced the infarct size and decreased the serum CK-MB level of I/R rats, and significantly reduced the ROS level but increased the level of MnSOD and catalase. While, an opposite effect was observed in the miR-182-5p mimics group. Furthermore, our results suggested that miR-182-5p targeted STK17A, and TK17A knockdown significantly increased the apoptotic rate and ROS level. The inhibitory effect of miR-182-5p inhibitors on apoptotic rate, ROS, MnSOD, and catalase levels were abrogated by siSTK17A. These results indicate that miR-182-5p regulates the apoptosis and ROS and protects against myocardial I/R injury by targeting STK17A.

Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19.

BACKGROUND: Several studies have described the clinical characteristics of patients with novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19), indicating severe patients tended to have higher neutrophil to lymphocyte ratio (NLR). Whether baseline NLR could be an independent predictor of in-hospital death in Chinese COVID-19 patients remains to be investigated. METHODS: A cohort of patients with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from January 1 to February 29 was retrospectively analyzed. The baseline data of laboratory examinations, including NLR, were collected. Univariate and multivariate logistic regression models were developed to assess the independent relationship between the baseline NLR and in-hospital all-cause death. A sensitivity analysis was performed by converting NLR from a continuous variable to a categorical variable according to tertile. Interaction and stratified analyses were conducted as well. RESULTS: 245 COVID-19 patients were included in the final analyses, and the in-hospital mortality was 13.47%. Multivariate analysis demonstrated that there was 8% higher risk of in-hospital mortality for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; P = 0.0147). Compared with patients in the lowest tertile, the NLR of patients in the highest tertile had a 15.04-fold higher risk of death (OR = 16.04; 95% CI, 1.14 to 224.95; P = 0.0395) after adjustment for potential confounders. Notably, the fully adjusted OR for mortality was 1.10 in males for each unit increase of NLR (OR = 1.10; 95% CI, 1.02 to 1.19; P = 0.016). CONCLUSIONS: NLR is an independent risk factor of the in-hospital mortality for COVID-19 patients especially for male. Assessment of NLR may help identify high risk individuals with COVID-19.

Nut consumption and risk of metabolic syndrome and overweight/obesity: a meta-analysis of prospective cohort studies and randomized trials.

BACKGROUND: Nut consumption has been shown to reduce the risk of cardiovascular disease. However, its role in the prevention of metabolic disorders, such as metabolic syndrome (Mets) and overweight/obesity, remains controversial. We therefore conducted a meta-analysis to determine the association of nut consumption with Mets and overweight/obesity. METHODS: Eligible studies were identified by searching the PubMed and Embase databases and by reviewing the references of relevant literatures. We used random effect models to pool the studies-specific risk ratio (RR) and weighted mean difference (WMD). RESULTS: This meta-analysis included six prospective cohort studies with 420,890 subjects and 62 randomized feeding trials with 7184 participants. Among the cohort studies, the summary RR for every 1-serving/week increase in nut intake was 0.96 (95% confidence interval [CI]: 0.92 to 0.99; n = 3) for Mets, 0.97 (95% CI: 0.95 to 0.98; n = 2) for overweight/obesity, and 0.95 (95% CI: 0.89 to 1.02; n = 2) for obesity. Pooling of randomized trials indicated that nut consumption was related to a significant reduction in body weight (WMD: - 0.22 Kg, 95% CI: -0.40 to - 0.04), body mass index (WMD: - 0.16 Kg/m2, 95% CI: -0.31 to - 0.01), and waist circumference (WMD: - 0.51 cm, 95% CI: -0.95 to - 0.07). These findings remained stable in the sensitivity analysis, and no publication bias was detected. CONCLUSION: Nut consumption may be beneficial in the prevention of Mets and overweight/obesity. Additional prospective studies are needed to enhance these findings and to explore the metabolic benefits for specific subclasses of nut.

Novel compound heterozygous mutations in low density lipoprotein receptor gene causes a severe phenotype in a Chinese hypercholesterolemia family.

Mutations in the low density lipoprotein receptor (LDLR) gene serve a causative role in the pathophysiology of familial hypercholesterolemia (FH), a common autosomal inherited disorder characterized by abnormal lipid metabolism. The aim of the present study was to investigate genetic defects in a Chinese family with FH. Clinical features and family histories were collected, as were the results of various laboratory tests, including determinations of serum lipid concentrations, ultrasonography and angiography results. Potential mutations in LDLR were screened using direct polymerase chain reaction (PCR) sequencing. Multiple sequence alignments, structure and hydrophobicity predictions were performed in silico. Novel compound heterozygote mutations in LDLR of the proband were identified, with a Trp577Term-bearing maternal allele and a Pro685Leu-bearing paternal allele. The proband, a 27-year-old male, had severe and diffuse coronary stenosis and non-ST segment elevation myocardial infarction, as well as multiple skin xanthomas and high serum lipid levels. The allele-dosage-dependent clinical features, including hypercholesterolemia and peripheral arterial atherosclerosis, were observed in the proband and the other heterozygous patients. Therefore, the coexistence of Pro685Leu and Trp577Term mutations in LDLR is a novel compound heterozygosis in Chinese patients and may lead to a severe FH phenotype. The explanation for the existence of compound heterozygous mutations instead of homozygous mutations in this particular family requires further study.

Chocolate Consumption and Risk of Coronary Heart Disease, Stroke, and Diabetes: A Meta-Analysis of Prospective Studies.

Although epidemiological studies have examined the role of chocolate in preventing cardiometabolic disease, the results remain inconsistent. Herein, we conducted a meta-analysis of prospective studies to determine the association between chocolate intake and risk of coronary heart disease (CHD), stroke, and diabetes. A systematical search in PubMed and Embase through March 2017, together with reference scrutiny of relevant literatures, was performed to identify eligible studies. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled using random effect models. Fourteen prospective studies of primary prevention with 508,705 participants were finally included, with follow-up durations ranging from 5 to 16 years. The summary RRs for the highest versus lowest chocolate consumption were 0.90 (95% CI: 0.82-0.97; n = 6) for CHD, 0.84 (95% CI: 0.78-0.90; n = 7) for stroke, and 0.82 (95% CI: 0.70-0.96; n = 5) for diabetes. Dose-response meta-analysis suggested a nonlinear association of chocolate consumption with all outcomes. For both CHD and stroke, there was little additional risk reduction when consuming chocolate ≥3 servings/week (one serving was defined as 30 g of chocolate). For diabetes, the peak protective effect of chocolate emerged at 2 servings/week (RR: 0.75, 95% CI: 0.63-0.89), with no benefit observed when increasing consumption above 6 servings/week. In conclusion, chocolate intake is associated with decreased risks of CHD, stroke, and diabetes. Consuming chocolate in moderation (≤6 servings/week) may be optimal for preventing these disorders.