Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial.

BACKGROUND: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice. METHODS: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days. RESULTS: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83]). CONCLUSIONS: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180.

Impact of Sacubitril/Valsartan on Cardiac Structure and Blood Levels of miRNA-328 and NT-proBNP in Patients with CHD and Chronic Heart Failure.

Objective: This study specifically investigates the impact of sacubitril/valsartan on cardiac structural remodeling and modulation of blood levels of miRNA-328 and NT-proBNP in patients with coronary heart disease (CHD) complicated by chronic heart failure (CHF). We aim to determine whether sacubitril/valsartan offers advantages over traditional therapies regarding cardiac morphology and molecular biomarkers, thus providing insights into its potential role in managing CHD and CHF. Methods: From January 2020 to January 2023, CHD patients with chronic heart failure were randomized into two groups for this study. Both groups received standard treatments: the control group received valsartan, while the study group received sacubitril/valsartan. Therapeutic outcomes were analyzed, including changes in cardiac structure, function, miRNA-328, and NT-proBNP levels in the blood, along with noting any adverse reactions. Results: The total effective rate in the study group was 86.67%, significantly higher than that in the control group (71.67%) (P < .05). After treatment, both groups exhibited reductions in left atrial anterior and posterior diameter, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter compared to before treatment, with the study group showing lower values than the control group (P < .05). The left ventricular ejection fraction (LVEF) increased in both groups, with the study group showing a higher increase than the control group. Additionally, the end-diastolic volume and end-systolic volume decreased in both groups after treatment, with the study group showing greater decreases than the control group (P < .05). Moreover, both groups exhibited reductions in peripheral blood levels of miRNA-328 and NT-proBNP, with the study group showing greater reductions than the control group (P < .05). There was no significant difference in the incidence of adverse reactions between the study group and the control group during treatment (P > .05). Conclusion: Sacubitril/valsartan significantly improves cardiac function and structure in patients with CHD complicated by CHF, effectively reducing levels of miRNA-328 and NT-proBNP in the blood. It demonstrates safety and high value in clinical applications.

The rate of child restraint system use among children aged under six years in China.

AIMS: The child restraint system (CRS) for vehicles is designed to provide specialized protection for children in the event of a crash. The aim of the study was to investigate the rate of CRS use and analyze the factors associated with CRS use among children aged under six years in China, and to provide further insight into developing strategies for promoting public health education. METHODS: This is a cross-sectional study. The study sites were 36 primary healthcare institutions in 12 provinces across China, and the participants were 34,503 guardians of children aged 0-6 years. Guardians who owned private cars were included and completed surveys about their experience using CRS. Odds ratios and 95% confidence intervals were calculated using multivariate logistic regression models. RESULTS: The overall rate of CRS use among children aged under six years in China was 17.3%. Multivariate logistic regression analysis revealed that living in an urban area, low age of the child, guardians having higher education and being looked after by parents had a significant positive association with CRS use among children aged under six years. CONCLUSIONS: This study confirms that there is a low rate of CRS use among children aged under six years in China, highlighting the considerable need for CRS use education, advocacy and promotion of increasing use.

PDSS2 Inhibits the Ferroptosis of Vascular Endothelial Cells in Atherosclerosis by Activating Nrf2.

ABSTRACT: Cardiovascular disease ranks the leading cause of mortality worldwide. Prenyldiphosphate synthase subunits collectively participate in the formation and development of atherosclerosis (AS). This study aimed to investigate the role of PDSS2 in AS and its underlying mechanisms. Human coronary artery endothelial cells (HCAECs) were treated with oxidized low-density lipoprotein to establish the AS model. The gene expression levels were determined by qRT-PCR, Western blot, and ELISA. CCK-8, colony formation was applied to determine the proliferation of HCAECs. Chromatin immunoprecipitation assay and luciferase assay were applied to verify the interaction between PDSS2 and Nrf2. The results showed that the serum levels of PDSS2 and Nrf2 were decreased in patients with AS. Overexpression of PDSS2 suppressed the release of reactive oxygen species, iron content and ferroptosis of HCAECs, and promoted the proliferation of HCAECs. Moreover, PDSS2 activated antioxidant Nrf2. PDSS2 interacted with Nrf2 to alleviate the ferroptosis of HCAECs. However, knockdown of Nrf2 alleviated the effects of PDSS2 on the proliferation and ferroptosis of HCAECs. In vivo assays, overexpression of PDSS2 and Nrf2 suppressed the progression of AS. In conclusion, overexpression of PDSS2 suppressed the ferroptosis of HCAECs by promoting the activation of Nrf2 pathways. Thence PDSS2 may play a cardio-protective role in AS.

Model to assess workload of village doctors in the National Essential Public Health Services Program in six provinces of China.

BACKGROUND: No studies, particularly quantitative analyses, have been conducted regarding the workload of village doctors in the National Essential Public Health Services (NEPHS) program and differences in service delivery by village doctors, according to region and services. In this study, we developed a quantitative analysis approach to measure the workload of NEPHS provided by village doctors in six provinces of China in 2016. We aimed to identify areas and services of the NEPHS needing improvement, so as to implement targeted measures to ensure adequate delivery of NEPHSs in rural remote underserved areas. METHODS: Based on survey data from 300 town hospital centers (THCs) located in 60 counties in the six selected provinces, we calculated village doctors' share of workload under the NEPHS using the equivalent value (EV) model. To define the workload and corresponding EV of each NEPHS, a series of five meetings was held with THC managers, public health workers, family physicians, nurses and village doctors. Field observations were conducted to verify the workload and EV of each service. RESULTS: Village doctors' share of the workload under the NEPHS program was 43.71% across the 300 sampled THCs in six provinces. The village doctors' workload shares for different NEPHS ranged from 17.14 to 57.00%. The percentage workload undertaken by village doctors under the NEPHS program varied across different provinces, with the highest proportion 63.4% and the lowest 28.5%. CONCLUSIONS: The total NEPHS workload assigned to village doctors by THCs in the six sampled provinces exceeded the Chinese government's requirement of 40%, but the workload proportion in some provinces was less than 40%. In addition, the percentage workload for some NEPHS undertaken by village doctors was lower than others. We suggest conducting district-level analysis of the workload among village doctors under the NEPHS program using the EV method, to identify areas and services needing improvement, to implement targeted measures to expand and promote health service provision in China's rural underserved areas.

MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment.

OBJECTIVE: This post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial) assessed the individual variation in total homocysteine (tHcy)-lowering response after an average 4.5 years of 0.8 mg daily folic acid therapy in Chinese hypertensive adults and evaluated effect modification by methylenetetrahydrofolate reductase (MTHFR) C677T genotypes and serum folate levels. APPROACH AND RESULTS: This analysis included 16 413 participants from the CSPPT, who were randomly assigned to 2 double-blind treatment groups: either 10-mg enalapril+0.8-mg folic acid or 10-mg enalapril, daily and had individual measurements of serum folate and tHcy levels at baseline and exit visits and MTHFR C677T genotypes. Mean baseline tHcy levels were comparable between the 2 treatment groups (14.5±8.5 versus 14.4±8.1 µmol/L; P=0.561). After 4.5 years of treatment, mean tHcy levels were reduced to 12.7±6.1 µmol/L in the enalapril+folic acid group, but almost stayed the same in the enalapril group (14.4±7.9 µmol/L, group difference: 1.61 µmol/L; 11% reduction). More importantly, tHcy lowering varied by MTHFR genotypes and serum folate levels. Compared with CC and CT genotypes, participants with the TT genotype had a more prominent L-shaped curve between tHcy and serum folate levels and required higher folate levels (at least 15 ng/mL) to eliminate the differences in tHcy by genotypes. CONCLUSIONS: Compared with CC or CT, tHcy in the TT group manifested a heightened L-shaped curve from low to high folate levels, but this difference in tHcy by genotype was eliminated when plasma folate levels reach ≈15 ng/mL or higher. Our data raised the prospect to tailor folic acid therapy according to individual MTHFR C677T genotype and folate status. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Angiopoietin-Like 7 Contributes to Angiotensin II-Induced Proliferation, Inflammation and Apoptosis in Vascular Smooth Muscle Cells.

INTRODUCTION: Angiotensin II (AngII) induces hypertension and pathophysiological vascular thickening and atherosclerosis. This study aims to validate the effects of Angiopoietin-like 7 (ANGPTL7) in AngII-induced hypertension. METHODS: ANGPTL7 in blood samples were determined by quantitative real-time polymerase chain reaction. AngII-induced cell growth were detected by CCK-8. Cell cycle arrest and cell apoptosis by downregulation of ANGPTL7 were detected by flow cytometric assay. AngII-induced inflammation was evaluated by Western blotting and ELISA. RESULTS: ANGPTL7 was highly expressed in patients with hypertension. AngII promoted cell viability and the expression level of ANGPTL7 in vascular smooth muscle cells (VSMC). Downregulation of ANGPTL7 inhibited AngII-induced cell proliferation and cell inflammation. Moreover, ANGPTL7 expression decreases also promoted cell apoptosis. CONCLUSIONS: Downregulation of ANGPTL7 reversed AngII-induced cell proliferation and cell inflammation and promoted apoptosis in AngII-induced VSMC cells. Therefore, ANGPTL7 can be a potential target in AngII-induced hypertension.

Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men.

BACKGROUND AND PURPOSE: We aimed to examine whether the efficacy of folic acid therapy in the primary prevention of stroke is jointly affected by smoking status and baseline folate levels in a male population in a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). METHODS: Eligible participants of the CSPPT were randomly assigned to a double-blind daily treatment of a combined enalapril 10-mg and folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. In total, 8384 male participants of the CSPPT were included in the current analyses. The primary outcome was first stroke. RESULTS: The median treatment duration was 4.5 years. In the enalapril-alone group, the first stroke risk varied by baseline folate levels and smoking status (never versus ever). Specifically, there was an inverse association between folate levels and first stroke in never smokers (P for linear trend=0.043). However, no such association was found in ever smokers. A test for interaction between baseline folate levels and smoking status on first stroke was significant (P=0.045). In the total sample, folic acid therapy significantly reduced the risk of first stroke in never smokers with folate deficiency (hazard risk, 0.36; 95% confidence interval, 0.16-0.83) and in ever smokers with normal folate levels (hazard risk, 0.69; 95% confidence interval, 0.48-0.99). CONCLUSIONS: Baseline folate levels and smoking status can interactively affect the risk of first stroke. Our data suggest that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect on stroke. Our findings need to be confirmed by future randomized trials. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Impact of achieved blood pressure on renal function decline and first stroke in hypertensive patients with chronic kidney disease.

Background: The effect of achieved blood pressure (BP) on first stroke and renal function decline among hypertensive patients with mild to moderate chronic kidney disease (CKD) is still uncertain. Methods: In total, 3230 hypertensive patients with estimated glomerular filtration rate 30-60 mL/min/1.73 m2 and/or proteinuria were included in the present analyses. Eligible participants were randomly assigned to a daily treatment of a combined enalapril 10 mg and folic acid 0.8 mg tablet or an enalapril 10 mg tablet alone. Participants were followed up every 3 months. The study outcomes included first stroke and the progression of CKD. Results: The median antihypertensive treatment duration was 4.7 years. Compared with participants with a time-averaged on-treatment systolic blood pressure (SBP) of 135 to ≤140 mmHg, the incidence of total first stroke [1.7% versus 3.3%; hazard ratio (HR), 0.51; 95% confidence interval (CI): 0.26-0.99] and ischemic stroke (1.3% versus 2.8%; HR, 0.46; 95% CI: 0.22-0.98) decreased significantly in those with a time-averaged SBP of ≤135 mmHg. Furthermore, a time-averaged diastolic blood pressure (DBP) of ≤80 mmHg, compared with a time-averaged DBP level of 80 to ≤90 mmHg, was significantly related to a decreased risk of hemorrhagic stroke (0.2% versus 0.9%; HR, 0.18; 95% CI: 0.04-0.80). However, compared with participants with a time-averaged SBP of 135 to ≤140 mmHg, a lower but non-significant trend of CKD progression was found in those with a time-averaged SBP of ≤130 mmHg. Conclusions: A BP treatment level of ≤135/80 mmHg, compared with a BP treatment level of 135-140/80-90 mmHg, could lead to a decreased risk of first stroke in hypertensive patients with mild-to-moderate CKD.

Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers.

We sought to examine the potential modifiers in the association between long-term low-dose folic acid supplementation and the reduction of serum total homocysteine (tHcy) among hypertensive patients, using data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 16 867 participants who had complete data on tHcy measurements at both the baseline and exit visit. After a median treatment period of 4·5 years, folic acid treatment significantly reduced the tHcy levels by 1·6 µmol/l (95 % CI 1·4, 1·8). More importantly, after adjustment for baseline tHcy and other important covariates, a greater degree of tHcy reduction was observed in certain subgroups: males, the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, higher baseline tHcy levels (≥12·5 (median) v. <12·5 µmol/l), lower folate levels (<8·0 (median) v. ≥8·0 ng/ml), estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 (v. 60-<90 and ≥90 ml/min per 1·73 m2), ever smokers and concomitant use of diuretics (P for all interactions <0·05). The degree of tHcy reduction associated with long-term folic acid supplementation can be significantly affected by sex, MTHFR C677T genotypes, baseline folate, tHcy, eGFR levels and smoking status.

Prevalence of Anemia and its Risk Factors among Children under 36 Months Old in China.

This study aims to evaluate the prevalence and sociodemographic factors of anemia in children <36 months old in China. In this study, data of 24 235 children were investigated from 32 primary health care (PHC) facilities in 11 province-level regions. Pearson χ2-test and logistic regression model were used to estimate potential risk factors associated with anemia. The overall prevalence of anemia was 24.4%, and 32.8% children from rural areas were anemic, but no statistically significant difference was observed between male and female. Predictors of anemia are different regions of China, cesarean delivery, premature birth and neonatal asphyxia. We also found that education level and income of children's parents are important determinants of childhood anemia. In additional, feeding practice would affect anemia among children aged 6-12 months. Our results could provide some insights for prevention and control of childhood anemia in PHC facilities.

Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients.

BACKGROUND AND PURPOSE: We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial. METHODS: A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke. RESULTS: The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (<200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18-1.97; P=0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril-folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56-0.84; P<0.001; number needed to treat, 78; 95% confidence interval, 52-158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril-folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75-1.30; P=0.982). The effect was greater among participants with elevated total cholesterol (P for interaction=0.024). CONCLUSIONS: Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Cellulose-Based Biosensors for Esterase Detection.

Cellulose has emerged as an attractive substrate for the production of economical, disposable, point-of-care (POC) analytical devices. Development of novel methods of (bio)activation is central to broadening the application space of cellulosic materials. Ironically, such efforts are stymied by the inherent biocompatibility and recalcitrance of cellulose fibers. Here, we have elaborated a versatile, chemo-enzymatic approach to activate cellulosic materials for CuAAC "click chemistry", to develop new fluorogenic esterase sensors. Gentle, aqueous modification conditions facilitate broad applicability to cellulose papers, gauzes, and hydrogels. Tethering of the released fluorophore to the cellulose surface prevents signal degradation due to diffusion and enables straightforward, sensitive visualization with a simple light source in resource-limited situations.

An economic-research-based approach to calculate community health-staffing requirements in Xicheng District, Beijing.

BACKGROUND: A shortage of community health professionals has been a crucial issue hindering the development of CHS. Various methods have been established to calculate health workforce requirements. This study aimed to use an economic-research-based approach to calculate the number of community health professionals required to provide community health services in the Xicheng District of Beijing and then assess current staffing levels against this ideal. METHODS: Using questionnaires, we collected relevant data from 14 community health centers in the Xicheng District, including resident population, number of different health services provided, and service volumes. Through 36 interviews with family doctors, nurses, and public health workers, and six focus groups, we were able to calculate the person-time (equivalent value) required for each community health service. Field observations were conducted to verify the duration. RESULTS: In the 14 community health centers in Xicheng District, 1752 health workers were found in our four categories, serving a population of 1.278 million. Total demand for the community health service outstripped supply for doctors, nurses, and public health workers, but not other professionals. The method suggested that to properly serve the study population an additional 64 family doctors, 40 nurses, and 753 public health workers would be required. CONCLUSIONS: Our calculations indicate that significant numbers of new health professionals are required to deliver community health services. We established time standards in minutes (equivalent value) for each community health service activity, which could be applied elsewhere in China by government planners and civil society advocates.

A model to estimate the cost of the National Essential Public Health Services Package in Beijing, China.

BACKGROUND: In order to address several health challenges, the Chinese government issued the National Essential Public Health Services Package (NEPHSP) in 2009. In China's large cities, the lack of funding for community health centers and consequent lack of comprehensive services and high quality care has become a major challenge. However, no study has been carried out to estimate the cost of delivering the services in the package. This project was to develop a cost estimation approach appropriate to the context and use it to calculate the cost of the NEPHSP in Beijing in 2011. METHODS: By adjusting models of cost analysis of primary health care and workload indicators of staffing need developed by the World Health Organization, a model was developed to estimate the cost of the services in the package through an intensive interactive process. A total of 17 community health centers from eight administrative districts in Beijing were selected. Their service volume and expenditure data in 2010 were used to evaluate the costs of providing the NEPHSP in Beijing based on the applied model. RESULTS: The total workload of all types of primary health care in 17 sample centers was equivalent to the workload requirement for 14,056,402 standard clinic visits. The total expenditure of the 17 sample centers was 26,329,357.62 USD in 2010. The cost of the workload requirement of one standard clinic visit was 1.87 USD. The workload of the NEPHSP was equivalent to 5,514,777 standard clinic visits (39.23 % of the total workload). The model suggests that the cost of the package in Beijing was 7.95 USD per capita in 2010. The cost of the NEPHSP in urban areas was lower than suburban areas: 7.31 and 8.65 USD respectively. CONCLUSIONS: The average investment of 3.97 USD per capita in NEPHSP was lower than the amount needed to meet its running costs. NEPHSP in Beijing is therefore underfunded. Additional investment is needed, and a dynamic cost estimate mechanism should be introduced to ensure services remain adequately funded.

Efficacy and safety of omega-3-acid ethyl acetate 90 capsules in severe hypertriglyceridemia: A randomized, controlled, multicenter study.

Omega-3-acid ethyl acetate 90 capsules (containing 465 mg of eicosapentaenoic acid and 375 mg docosahexaenoic acid) is composed of highly purified omega-3 polyunsaturated fatty acid (PUFA) ethyl esters, whose lipid-lowering effect for severe hypertriglyceridemia (HTG) treatment is unclear. This study aimed to evaluate the efficacy and safety of omega-3-acid ethyl acetate 90 capsules in patients with severe HTG. In this randomized, double-blind, placebo-controlled, multicenter study, 239 patients with severe HTG were enrolled and randomized (1:1) into omega-3 group (N = 122) and placebo group (N = 117) to receive 12-week corresponding treatments. Lipid-related indexes were obtained at treatment initiation (W0), 4 weeks (W4), W8, and W12 after treatment. Adverse events and adverse drug reactions were recorded. Triacylglycerols (TAG), total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), and apolipoprotein C-III (Apo C-III) at W4, W8, and W12 were decreased in the omega-3 group versus the placebo group (all p < 0.05). Moreover, the percentage changes of TAG, TC, non-HDL-C, and VLDL-C from W0 to W4, W8, and W12, and the percentage change of Apo C-III from W0 to W4 and W8, were more obvious in the omega-3 group compared with the placebo group (all p < 0.05). However, no difference was observed in the percentage changes of HDL-C, low-density lipoprotein cholesterol (LDL-C), and LDL-C/HDL-C ratio during follow-up between groups (all p > 0.05). Additionally, there was no discrepancy in adverse events and adverse drug reactions between groups (all p > 0.05). Omega-3-acid ethyl acetate 90 capsules exhibit satisfied lipid-lowering effect with tolerable safety profile in patients with severe HTG.

Dynamic natural components and morphological changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome and mild chronic kidney disease at the 1-year follow-up and clinical significance at the 5-year follow-up.

INTRODUCTION: The natural outcome of coronary plaque in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD) is unique, which can be analyzed quantitatively by optical flow ratio (OFR) software. METHODS: A total of 184 ACS patients with at least one nonculprit subclinical atherosclerosis (NSA) detected by optical coherence tomography (OCT) at baseline and 1-year follow-up were divided into non-CKD group (n = 106, estimated glomerular filtration rate (eGFR)> 90 mL/(min×1.73 m2)) and mild CKD group (n = 78, 60≤eGFR<90 mL/(min×1.73 m2)). Changes of normalized total atheroma volume (TAVn) of NSA was the primary endpoint at the 1-year follow-up. RESULTS: Patients with mild CKD showed more TAVn progression of NSA than non-CKD (p = 0.019) from baseline to the 1-year follow-up, which was mainly due to an increase in calcium TAVn (p<0.001). The morphological change in the maximal calcification thickness (p = 0.026) was higher and the change in the distance from the calcified surface to the contralateral coronary media membrane (ΔC-to-M) at the maximal cross-sectional calcium area was lower (p<0.001) in mild CKD group than in non-CKD group. Mild CKD had more NSA related MACEs at the 5-year follow-up than non-CKD (30.8% vs. 5.8%, p = 0.045). CONCLUSIONS: Mild CKD patients had more plaque progression of NSA which showed the increase of calcium component with more protrusion into the lumen morphologically at the 1-year follow-up and a higher corresponding incidence of NSA-related MACEs at the 5-year follow-up. TRIAL REGISTRATION: Clinical Trial registration ClinicalTrials.gov. NCT02140801. https://classic.clinicaltrials.gov/ct2/show/NCT02140801.

New structural motif for carboxylic acid perhydrolases.

Some serine hydrolases also catalyze a promiscuous reaction--reversible perhydrolysis of carboxylic acids to make peroxycarboxylic acids. Five X-ray crystal structures of these carboxylic acid perhydrolases show a proline in the oxyanion loop. Here, we test whether this proline is essential for high perhydrolysis activity using Pseudomonas fluorescens esterase (PFE). The L29P variant of this esterase catalyzes perhydrolysis 43-fold faster (k(cat) comparison) than the wild type. Surprisingly, saturation mutagenesis at the 29 position of PFE identified six other amino acid substitutions that increase perhydrolysis of acetic acid at least fourfold over the wild type. The best variant, L29I PFE, catalyzed perhydrolysis 83-times faster (k(cat) comparison) than wild-type PFE and twice as fast as L29P PFE. Despite the different amino acid in the oxyanion loop, L29I PFE shows a similar selectivity for hydrogen peroxide over water as L29P PFE (ß(0)=170 vs. 160 M(-1)), and a similar fast formation of acetyl-enzyme (140 vs. 62 U mg(-1)). X-ray crystal structures of L29I PFE with and without bound acetate show an unusual mixture of two different oxyanion loop conformations. The type II ß-turn conformation resembles the wild-type structure and is unlikely to increase perhydrolysis, but the type I ß-turn conformation creates a binding site for a second acetate. Modeling suggests that a previously proposed mechanism for L29P PFE can be extended to include L29I PFE, so that an acetate accepts a hydrogen bond to promote faster formation of the acetyl-enzyme.

Occupational Risk Factors for Physical and Mental Health in Primary Healthcare Providers: A National Cross-Sectional Survey from 62 Urban Communities in China.

Purpose: To understand the physical and mental health status of primary healthcare providers (PHPs) including physicians, nurses and other staff and the workplace risk factors for depression, anxiety and intention-to-leave. Patients and Methods: In December 2021, a national cross-sectional survey was conducted from 62 urban communities in China, and all PHPs were invited to complete a standardized questionnaire. Information on demographic, health-related lifestyle, cardiovascular risk factors and physical health status, occupational stress and intention-to-leave was collected. Depression and anxiety were assessed using the Zung Self-Rating Anxiety/Depression Scale (SAS/SDS). Results: A total of 4901 PHPs were included. 67.0% males currently drank alcohol vs 25.3% in females; 36.0% males currently smoked cigarettes vs 1.4% in females. Notably, more than half males were overweight or obese, but this proportion was 24.2% in females. The prevalence of chronic diseases, including hypertension, diabetes, dyslipidemia, non-alcoholic fatty liver disease, gout, and disease clustering were higher in males than in females. The prevalence of depression and anxiety were high, 50% had depression, of whom 15.6% had moderate/severe depression. Over 15% participants had varied levels of anxiety, and approximately 4% had moderate/severe anxiety. PHPs who aged 18-29 (OR: 1.31, 95% CI: 1.05-1.64), were males (OR: 1.34, 95% CI: 1.14-1.57), with lower professional title (comparing with staff with senior title, the ORs of the intermedium, junior and none were 1.83, 2.18 and 2.49, respectively), took charge in nursing (OR: 1.41, 95% CI: 1.20-1.65), with higher perceived stress level (OR: 1.82, 95% CI: 1.41-2.34), and suffering from severe fatigue (OR: 2.55, 95% CI: 1.99-3.27) were more likely to have depression. Likewise, PHPs who were younger, with intermedium professional title, had higher perceived pressure level, and higher fatigue levels were more likely to have anxiety. Conclusion: The mental health of PHPs is worrisome, with a high burden of chronic diseases and occupational risk factors. Younger PHPs, nurses, and those with higher levels of work pressure and fatigue are more vulnerable to psychological problems. The high prevalence of intention-to-leave calls for strategies that relieve the workplace stress and enhance the human resource capability.

Comparative Study on Chronic Obstructive Pulmonary Disease Screening Tools in Primary Healthcare Institutions in Beijing, China.

Background: Chronic obstructive pulmonary disease (COPD) has a high incidence rate in China, but the diagnosis rate remains insufficient. This study aimed to explore and compare COPD screening tools for primary healthcare institutions in China. Purpose: Exploring COPD Screening Tools and Their Combined Use for Primary Healthcare Institutions in China. Patients and Methods: From September 2022 to March 2023, a screening for COPD was conducted among residents aged 35 years and above in primary healthcare institutions in Beijing, China. The screening involved the use of the CAPTURE scale, COPD-SQ scale, and peak expiratory flow rate test. Any positive results from these screening tests were followed by further pulmonary function testing to confirm the diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic (ROC) curves were calculated for each screening tool alone and in combination. Results: A total of 986 individuals completed the screening tests. The positive rates for the CAPTURE scale, COPD-SQ scale, and peak flow meter screening were 41.78%, 29.11%, and 52.03%, respectively. Of the participants, 166 (24.09%) underwent pulmonary function tests, with an average age of 61.69±13.68 years. The peak flow meter screening showed the highest sensitivity (83.78%) when used alone, while the COPD-SQ scale exhibited the best specificity (59.69%), positive predictive value (31.58%), and negative predictive value (58.56%). Significant differences (P<0.05) were observed between any two of the three screening tools. Among the combinations, the peak flow meter screening + COPD-SQ scale showed the highest accuracy, with a Youden index of 0.277 and an AUC of 0.638. Conclusion: There is variation in the accuracy of existing screening tools for COPD when used alone. For primary healthcare institutions, the optimal COPD screening tool is the combination of peak flow meter screening and the COPD-SQ questionnaire. If limited by screening equipment conditions, the COPD-SQ questionnaire can be used alone for screening.