Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial.

BACKGROUND: Uncertainty exists about whether lowering systolic blood pressure to less than 120 mm Hg is superior to that of less than 140 mm Hg, particularly in patients with diabetes and patients with previous stroke. METHODS: In this open-label, blinded-outcome, randomised controlled trial, participants with high cardiovascular risk were enrolled from 116 hospitals or communities in China. We used minimised randomisation to assign participants to intensive treatment targeting standard office systolic blood pressure of less than 120 mm Hg or standard treatment targeting less than 140 mm Hg. The primary outcome was a composite of myocardial infarction, revascularisation, hospitalisation for heart failure, stroke, or death from cardiovascular causes, assessed by the intention-to-treat principle. This trial was registered with ClinicalTrials.gov, NCT04030234. FINDINGS: Between Sept 17, 2019, and July 13, 2020, 11 255 participants (4359 with diabetes and 3022 with previous stroke) were assigned to intensive treatment (n=5624) or standard treatment (n=5631). Their mean age was 64·6 years (SD 7·1). The mean systolic blood pressure throughout the follow-up (except the first 3 months of titration) was 119·1 mm Hg (SD 11·1) in the intensive treatment group and 134·8 mm Hg (10·5) in the standard treatment group. During a median of 3·4 years of follow-up, the primary outcome event occurred in 547 (9·7%) participants in the intensive treatment group and 623 (11·1%) in the standard treatment group (hazard ratio [HR] 0·88, 95% CI 0·78-0·99; p=0·028). There was no heterogeneity of effects by diabetes status, duration of diabetes, or history of stroke. Serious adverse events of syncope occurred more frequently in the intensive treatment group (24 [0·4%] of 5624) than in standard treatment group (eight [0·1%] of 5631; HR 3·00, 95% CI 1·35-6·68). There was no significant between-group difference in the serious adverse events of hypotension, electrolyte abnormality, injurious fall, or acute kidney injury. INTERPRETATION: For hypertensive patients at high cardiovascular risk, regardless of the status of diabetes or history of stroke, the treatment strategy of targeting systolic blood pressure of less than 120 mm Hg, as compared with that of less than 140 mm Hg, prevents major vascular events, with minor excess risk. FUNDING: The Ministry of Science and Technology of China and Fuwai Hospital. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Rationale and design of the Effects of intensive Systolic blood Pressure lowering treatment in reducing RIsk of vascular evenTs (ESPRIT): A multicenter open-label randomized controlled trial.

BACKGROUND: Lowering blood pressure (BP) effectively reduces the risk of cardiovascular (CV) events in high CV risk individuals. The optimal target of BP lowering among high CV risk individuals remains unclear. METHODS: The Effects of intensive Systolic blood Pressure lowering treatment in reducing RIsk of vascular evenTs (ESPRIT) trial is a multi-center, open-label, randomized controlled trial to compare the efficacy and safety of intensive BP lowering strategy (Systolic BP target <120 mm Hg) and standard BP lowering strategy (Systolic BP target <140 mm Hg). Participants aged at least 50 years old with baseline systolic BP within 130 to 180 mm Hg at high CV risk, defined by established CV diseases or 2 major CV risk factors, were enrolled. The primary outcome is a composite CV outcome of myocardial infarction, coronary or non-coronary revascularization, hospitalization or emergency department visit from new-onset heart failure or acute decompensated heart failure, stroke, or death from CV diseases. Secondary outcomes include components of the primary composite outcome, all-cause death, a composite of the primary outcome or all-cause death, kidney outcomes, as well as cognitive outcomes. RESULTS: Despite of the interruption of COVID-19 outbreak, the ESPRIT trial successfully enrolled and randomized 11,255 participants from 116 hospitals or primary health care institutions. The mean age of the participants was 64.6 (standard deviation [SD], 7.1) years, 4,650 (41.3%) were women. Among them 28.9%, 26.9% and 38.7% had coronary heart disease, prior stroke and diabetes mellitus, respectively. COVID-19 outbreak affected the BP lowering titration process of the trial, and delayed the reach of BP target. CONCLUSIONS: The ESPRIT trial will address the important question on the optimal BP lowering target for individuals with high CV risk, and generate high quality evidence for treating millions of patients from East Asian countries.

Distinct Associations Between Postdischarge Cognitive Change Patterns and 1-year Outcomes in Patients Hospitalized for Heart Failure.

BACKGROUND: The patterns of patients' cognitive function after hospital discharge for heart failure (HF), their prognostic implication and the predictors for new-onset cognitive impairment remain unknown. METHODS AND RESULTS: We included 2307 patients (64 ± 14 years, 36.4% female sex) hospitalized for HF from a cohort who completed cognitive testing before discharge and after 1 month. Among 1658 patients with normal cognition before discharge, 229 (13.8%) and 1429 (86.2%) had new-onset cognitive impairment and normal cognition at 1 month, respectively. Of the 649 with cognitive impairment, 315 (48.5%) and 334 (51.5%) had transient and persistent cognitive impairment, respectively. Multivariable analyses showed that, compared with normal cognition, patients with new-onset cognitive impairment had an increased risk of cardiovascular death or HF rehospitalization (hazard ratio 1.35, 95% confidence interval 1.07-1.70); patients with persistent cognitive impairment showed an increased risk, but it was not statistically significant (hazard ratio 1.17, 95% confidence interval 0.95-1.44); patients with transient cognitive impairment had a similar risk (hazard ratio 0.91, 95% confidence interval 0.73-1.13). Older age, females, lower education level, prior atherosclerotic cardiovascular diseases, lower health status, and lower Mini-Cog score before discharge predicted new-onset cognitive impairment. CONCLUSIONS: Acute HF substantially affects short-term cognition. Patients who have developed new-onset cognitive impairment have an increased risk of adverse outcomes. Monitoring cognition is necessary, particularly in high-risk patients.

Enhancement of Ammonium Oxidation at Microoxic Bioanodes.

Bioelectrochemical systems (BESs) are considered to be energy-efficient to convert ammonium, which is present in wastewater. The application of BESs as a technology to treat wastewater on an industrial scale is hindered by the slow removal rate and lack of understanding of the underlying ammonium conversion pathways. This study shows ammonium oxidation rates up to 228 ± 0.4 g-N m-3 d-1 under microoxic conditions (dissolved oxygen at 0.02-0.2 mg-O2/L), which is a significant improvement compared to anoxic conditions (120 ± 21 g-N m-3 d-1). We found that this enhancement was related to the formation of hydroxylamine (NH2OH), which is rate limiting in ammonium oxidation by ammonia-oxidizing microorganisms. NH2OH was intermediate in both the absence and presence of oxygen. The dominant end-product of ammonium oxidation was dinitrogen gas, with about 75% conversion efficiency in the presence of a microoxic level of dissolved oxygen and 100% conversion efficiency in the absence of oxygen. This work elucidates the dominant pathways under microoxic and anoxic conditions which is a step toward the application of BESs for ammonium removal in wastewater treatment.

Research, development, and evaluation of the practical effect of a storage inflow and outflow management system for consumables in the endocrinology department of a hospital.

BACKGROUND: This study was designed for the research and development (R&D) and application of a storage inflow and outflow management system enabling departments to perform efficient, scientific, and information-based consumable management. METHODS: In the endocrinology department of a hospital, expert and R&D teams in consumable management were set up, and an information-based storage inflow and outflow management system for consumables was designed and developed. The system was operated on a personal computer and was divided into three modules: public consumables, bed consumables, and quality control management. The functions of the system included storage inflow and outflow, early warnings, response to user queries, and statistics on consumables. Data were derived from the hospital information system (HIS,ZHIY SOFTWARE HIS VERSION4.0) and a questionnaire survey. Economic indicators, work efficiency of consumable management, nurse burnout, consumable stockroom management, and staff satisfaction were compared under manual management, Excel-based management, and the consumable storage inflow and outflow management system. The results of the questionnaire were analysed using the R software, version 4.1.0. RESULTS: Dates were obtained from manual management, Excel-based management and the consumable storage inflow and outflow management system. Under these three methods, the daily prices of department consumables per bed were 53.43 ± 10.27 yuan, 38.65 ± 8.56 yuan, and 31.98 ± 7.36 yuan, respectively, indicating that the new management system reduced costs for the department. The time spent daily on consumable management was shortened from 119.5 (106.75, 123.5) min to 56.5 (48.5, 60.75) to 20 (17.25, 24.25) min. Nurses' emotional fatigue and job indifference scores, respectively, decreased from 22.90 ± 1.65 and 8.75 ± 1.25 under manual management to 19.70 ± 1.72 and 6.90 ± 1.37 under Excel-based management and to 17.20 ± 2.04 and 6.00 ± 1.30 under the novel system; the satisfaction of the warehouse keeper and collection staff, respectively, increased from 76.62% and 80.78% to 91.6% and 90.5% to 98.8% and 98.5% under the three successive systems. CONCLUSIONS: The storage inflow and outflow management system achieved produced good results in the storage and classification of consumables.

Construction and validation of a revised satisfaction index model for the Chinese urban and rural resident-based basic medical insurance scheme.

BACKGROUND: Quality is the most important factor in satisfaction. However, the existing satisfaction index model of urban and rural resident-based basic medical insurance scheme (SIM_URRBMI) lacks the segmentation of perceived quality elements, it couldn't provide a reference for quality improvement and satisfaction promotion. This study aims to construct a revised SIM_URRBMI that can accurately and detailly measure perceived quality and provide feasible and scientific suggestions for improving the satisfaction of urban and rural residents' basic medical insurance scheme (URRBMI) in China. METHODS: Based on the theoretical framework of the American Customer Satisfaction Index, the elements of perceived quality were refined through literature review and expert consultation, and a pool of alternative measurement variables was formed. A three-stage randomized stratified cluster sampling was adopted. The main decision makers of URRBMI in the families of primary school students in 8 primary schools in Changsha were selected. Both the classic test theory and the item response theory were used for measurement variables selection. The reliability and validity of the model were tested by partial least squares (PLS)-related methods. RESULTS: A total of 1909 respondents who had URRBMI for their children were investigated. The SIM_URRBMI1.0 consists of 11 latent variables and 28 measurement variables with good reliability and validity. Among the three explanatory variables of public satisfaction, perceived quality had the largest total effect (path coefficient) (0.737). The variable with the greatest effect among the five first-order latent variables on perceived quality was the quality of the medical insurance policy (0.472). CONCLUSIONS: The SIM_URRBMI1.0 consists of 28 measurement variables and 11 latent variables. It is a reliable, valid, and standard satisfaction measurement tool for URRBMI with good prediction ability for public satisfaction. In addition, the model provides an accurate evaluation of the perceived quality, which will greatly help with performance improvement diagnosis. The most critical aspects of satisfaction improvement are optimizing the scope and proportion of reimbursement as well as setting appropriate level of deductible and capitation of URRBMI.

Engineering of the Small Noncoding RNA (sRNA) DsrA Together with the sRNA Chaperone Hfq Enhances the Acid Tolerance of Escherichia coli.

Acid tolerance of microorganisms is a desirable phenotype for many industrial fermentation applications. In Escherichia coli, the stress response sigma factor RpoS is a promising target for engineering acid-tolerant phenotypes. However, the simple overexpression of RpoS alone is insufficient to confer these phenotypes. In this study, we show that the simultaneous overexpression of the noncoding small RNA (sRNA) DsrA and the sRNA chaperone Hfq, which act as RpoS activators, significantly increased acid tolerance in terms of cell growth under modest acidic pH, as well as cell survival upon extreme acid shock. Directed evolution of the DsrA-Hfq module further improved the acid tolerance, with the best mutants showing a 51 to 72% increase in growth performance at pH 4.5 compared with the starting strain, MG1655. Further analyses found that the improved acid tolerance of these DsrA-Hfq strains coincided with activation of genes associated with proton-consuming acid resistance system 2 (AR2), protein chaperone HdeB, and reactive oxygen species (ROS) removal in the exponential phase. This study illustrated that the fine-tuning of sRNAs and their chaperones can be a novel strategy for improving the acid tolerance of E. coliIMPORTANCE Many of the traditional studies on bacterial acid tolerance generally focused on improving cell survival under extreme-pH conditions, but cell growth under less harsh acidic conditions is more relevant to industrial applications. Under normal conditions, the general stress response sigma factor RpoS is maintained at low levels in the growth phase through a number of mechanisms. This study showed that RpoS can be activated prior to the stationary phase via engineering its activators, the sRNA DsrA and the sRNA chaperone Hfq, resulting in significantly improved cell growth at modest acidic pH. This work suggests that the sigma factors and likely other transcription factors can be retuned or retimed by manipulating the respective regulatory sRNAs along with the sufficient supply of the respective sRNA chaperones (i.e., Hfq). This provides a novel avenue for strain engineering of microbes.

The effect and mechanism of miR-607/CANT1 axis in lung squamous carcinoma.

Lung squamous carcinoma (LUSC) is the second most frequent subtype of non-small cell lung cancer. Rarely gene alterations are identified in LUSC. Therefore, identifying LUSC-related genes to explain the relevant molecular mechanism is urgently needed. A potential biomarker, calcium-activated nucleotidase 1 (CANT1), was elevated in tissues of LUSC patients relative to normal cases based on the TCGA and/or GTEx database. CCK-8 and transwell tests were then implemented to measure the proliferative, invasive and migratory capacities, and showed that knockdown of CANT1 blocked LUSC cells proliferation. miR-607, predicted as an upstream factor for CANT1, was declined in LUSC using TargetScan analysis and luciferase activity test. Low miR-607 expression was related with unfavorable outcomes of LUSC patients. Moreover, miR-607 downregulation elevated cell viability, invasion and migration in LUSC cells, which was antagonized by si-CANT1. GEPIA website was accessed to estimate the relevance between CANT1 and epithelial-mesenchymal transition (EMT)-related positive factors. The protein levels of Fibronectin, Vimentin, Snail and ß-catenin were altered due to the abnormal CANT1 and miR-607 expression. Together, these data unveiled that miR-607/CANT1 pair may exert a vital role in the progression of LUSC through mediating EMT process, which would furnish an available therapeutic therapy for LUSC.

Mixed methods research on satisfaction with basic medical insurance for urban and rural residents in China.

BACKGROUND: There have been few studies on satisfaction with integrated basic medical insurance for urban and rural residents (URRBMI), and satisfaction with URRBMI is not very high because of the complexity of its policies and differences among the insured. The aim of the present study was to explore the factors that influence satisfaction with URRBMI in China and to provide scientific suggestions to the government for how to effectively manage and improve the policy. METHODS: An explanatory sequential design of mixed methods research was used. A quantitative research using a three-stage stratified cluster sampling method was used to randomly select the guardians of pupils who participated in URRBMI (n = 1335). The quantitative research was conducted to calculate the latent variables' scores and path coefficients between latent variables using SmartPLS3.0. With public trust, public satisfaction, and perceived quality as the target variables, important-performance analysis (IPA) was used to explore the important but underperforming factors, which were the key elements to improving satisfaction with URRBMI. A purposeful sampling strategy according to satisfaction level was used to obtain qualitative research subjects from among the quantitative research subjects. A qualitative research was conducted using semi-structured interviews, and the thematic analysis method was used to summarize the interview data. RESULTS: The three strongest paths were perceived quality to public satisfaction, with a total effect of 0.737 (t = 41.270, P < 0.001); perceived quality to perceived value, with a total effect of 0.676 (t = 31.964, P < 0.001); and public satisfaction to public trust, with a total effect of 0.634 (t = 31.305, P < 0.001). IPA revealed that public satisfaction and perceived quality were key factors for public trust and that perceived quality was of high importance for public satisfaction but had low performance. The policy quality was a determining factor for perceived quality. The qualitative research results showed that the most unsatisfactory aspect for the insured was the policy quality. CONCLUSIONS: This study found that improving quality is key to improving public satisfaction with and public trust in URRBMI. The government should improve the compensation level by broadening the channel of financing for the URRBMI fund, rationally formulating reimbursement standards, and broadening the scope of the drug catalog and the medical treatment projects. The government should establish a stable financing growth mechanism and effective methods of providing health education to improve public satisfaction and public trust.

Application of satisfaction index of basic medical insurance for rural and urban residents to pupils' familial decision making in Kunming and Changsha City. / åŸŽä¹¡å± æ°‘åŸºæœ¬åŒ»ç–—ä¿é™©æ»¡æ„åº¦æŒ‡æ•°æ¨¡åž‹åœ¨æ˜†æ˜Žå¸‚å’Œé•¿æ²™å¸‚å°å­¦ç”Ÿå®¶åº­å†³ç­–è€ ä¸­çš„åº”ç”¨.

OBJECTIVES: To verify the applicability and extensibility of the satisfaction index of basic medical insurance for rural and urban residents, and to explore the mechanism responsible for the satisfaction index in Kunming and Changsha City, and provide references for effective management and policy making. METHODS: A stratified cluster sampling method was conducted. A total of 560 familial decision makers were randomly selected in 24 classes of 14 schools of Kunming and Changsha City. Model reliability was tested by SPSS18.0. In addition, Smart PLS 3.0 was applied to conduct model validity test, calculate the satisfaction index, and to compare the model path coefficients of Kunming and Changsha by multi-group analysis. RESULTS: In the application of the satisfaction index of basic medical insurance for rural and urban residents in Kunming, Cronbach's α of the model was 0.93, split-half reliability coefficient was 0.90, and the latent variable composite reliability coefficient values were more than 0.86; the latent variable average variance extraction (AVE) values were greater than 0.66, and the square root of the AVE of each latent variable (all greater than 0.66) was larger than the correlation coefficient with other latent variables. The factor loading values were greater than 0.70, with statistical significance. The basic health insurance satisfaction index of Kunming and Changsha was 60.40 and 52.05, respectively. The difference between the path coefficient of Kunming and Changsha was not statistically significant except the path from public satisfaction to public loyalty. Perceived value had the largest direct and total effect on public satisfaction latent variable in Kunming City. While the perceived value had the largest direct effect on public satisfaction, and the perceived quality had the largest total effect on public satisfaction in Changsha City. CONCLUSIONS: The satisfaction index model reflects the satisfaction of pupils' basic medical insurance for urban and rural residents, and it also shows good reliability and validity in Changsha and Kunming. What's more the model can be extended to the national level to evaluate the satisfaction of basic medical insurance for urban and rural residents for primary school students. The basic health insurance satisfaction index of familial decision makers in Kunming is higher than that of Changsha. There are differences between Kunming and Changsha in the influential mechanism of the satisfaction index of for Chinese pupils with basic medical insurance for rural and urban residents, and the measures taken by the government and relevant departments to improve the satisfaction of basic medical insurance should be based on local conditions.

Longitudinal Trends in the Diagnosis of Attention-Deficit/Hyperactivity Disorder and Stimulant Use in Preschool Children on Medicaid.

OBJECTIVES: To describe trends in the diagnosis of attention-deficit/hyperactivity disorder (ADHD) and prescribing of stimulants in preschool-age children receiving Medicaid and to identify factors associated with the receipt of psychosocial care. STUDY DESIGN: Data were extracted from 2012-2016 Kentucky Medicaid claims for children aged <6 years. ADHD was identified using International Classification of Diseases, Tenth Revision codes F90.0, F90.1, F90.2, F90.8, and F90.9. Psychosocial therapy was defined as having at least 1 relevant Current Procedural Terminology code in a claim within the year. A generalized linear model with a logit link and binomial distribution was used to assess factors associated with receipt of psychosocial treatment in 2016. RESULTS: More than 2500 (1.24%) preschool-aged children receiving Medicaid had a diagnosis of ADHD in 2016, with 988 (38.2%) of those receiving a stimulant medication. Children in foster care were diagnosed with and/or treated for ADHD 4 times more often than other Medicaid recipients. Of the 1091 preschoolers receiving stimulants, 99 (9%) did not have a diagnosis of ADHD. There were no significant differences in diagnoses by race/ethnicity, but children reported to be black, Hispanic, or other race/ethnicity received stimulants at a lower rate than white children. Positive predictors for receiving psychosocial therapy in 2016 included having the diagnosis but not receiving a stimulant, having at least 1 prescription written by a psychiatrist, having comorbidities, and age. The use of stimulants in children aged <6 years declined from 0.9% in 2012 to 0.5% in 2016. CONCLUSIONS: Promising trends demonstrate a decreasing use of stimulants in preschoolers; however, continued vigilance is needed to promote the optimal use of psychosocial interventions.

Estimation of average treatment effects among multiple treatment groups by using an ensemble approach.

In observational studies, generalized propensity score (GPS)-based statistical methods, such as inverse probability weighting (IPW) and doubly robust (DR) method, have been proposed to estimate the average treatment effect (ATE) among multiple treatment groups. In this article, we investigate the GPS-based statistical methods to estimate treatment effects from two aspects. The first aspect of our investigation is to obtain an optimal GPS estimation method among four competing GPS estimation methods by using a rank aggregation approach. We further examine whether the optimal GPS-based IPW and DR methods would improve the performance for estimating ATE. It is well known that the DR method is consistent if either the GPS or the outcome models are correctly specified. The second aspect of our investigation is to examine whether the DR method could be improved if we ensemble outcome models. To that end, bootstrap method and rank aggregation method are used to obtain the ensemble optimal outcome model from several competing outcome models, and the resulting outcome model is incorporated into the DR method, resulting in an ensemble DR (enDR) method. Extensive simulation results indicate that the enDR method provides the best performance in estimating the ATE regardless of the method used for estimating GPS. We illustrate our methods using the MarketScan healthcare insurance claims database to examine the treatment effects among three different bones and substitutes used for spinal fusion surgeries. We draw conclusions based on the estimates from the enDR method coupled with the optimal GPS estimation method.

Dicer1 dysfunction promotes stemness and aggression in endometrial carcinoma.

Endometrial carcinoma is one of the most common gynecological malignancies, but the molecular events involved in the development and progression of endometrial carcinoma remain unclear. Dicer1 and cancer stem cells play important roles in cell motility and survival. This study investigated the role of the let-7 family and Dicer1 in the stemness of endometrial carcinoma cells. We profiled Dicer1 expression in clinical samples and explored its relationship with stem cell-associated markers and clinical parameters. We showed that Dicer1 dysfunction leads to the enrichment of tumor stemness features and tumor aggression both in vitro and in vivo. We also identified the mechanism related to this potential tumor-predisposing phenotype: loss of Dicer1 induced abnormal expression of the let-7 family, which comprises well-known tumor suppressors, thus regulating stemness in endometrial carcinoma cells.

Low-grade albuminuria is associated with poor memory performance in the nondemented Chinese elderly with type 2 diabetes.

Recent studies have correlated cognitive function with albuminuria. We investigated the association between low-grade albuminuria and cognitive performance in nondemented elderly with type 2 diabetes in Fuzhou, China. Between January, 2013 and December, 2014, a retrospective study was performed in 815 patients with type 2 diabetes (398 female and 417 male patients), ages ≥60 years, with normal urinary albumin to creatinine ratios (UACR <30 mg/g). Patients were stratified into tertiles based on UACR levels (lowest tertile, UACR <5.8 mg/g; highest tertile, UACR ≥18.1 mg/g). Cognitive function was measured using the Mini Mental State Examination. UACR tertiles correlated directly (p < 0.05) with age, duration of diabetes, systolic blood pressure (SBP), and pulse wave velocity (PWV). Patients in the second and highest tertiles performed significantly worse on memory and language than those in the lowest UACR tertile (p < 0.05). The association between UACR and memory loss was stronger in patients younger than 70 years of age and in those with a history of diabetes for less than 10 years. Low-grade albuminuria is associated with poor memory performance, especially in the youngest old (60-69 years) and in those with shorter duration of diabetes (< 10 years). Type 2 diabetics with urinary albumin excretion in the upper normal range were also at risk for declining memory performance.

[Association rule regarding chronic disease-relevant risk factors for the adults in Haidian District].

OBJECTIVE: To investigate the association patterns of chronic disease-relevant risk factors for the adults in Haidian District.
 Methods: Data for chronic disease-relevant risk factors for 3 219 adults in Haidian District in 2014 were collected and analyzed. SPSS 18.0 was used for statistical description and logistic regression. SPSS Modeler 14.1 was used to explore the association among the chronic disease-relevant risk factors.
 Results: Among men, 5 patterns of chronic disease-relevant risk factors were identified, which suggested that heavy drinking, inadequate intake of fruit and vegetables, and physical inactivity were associated with smoking while inadequate intake of fruit and vegetables and smoking were associated with physical inactivity. Among women, one pattern of chronic disease-relevant risk factor was identified, which suggested that inadequate intake of fruit and vegetables was associated with physical inactivity.
 Conclusion: Chronic disease-relevant risk factors are intercorrelated among the adults in Haidian District. Information on patterns of chronic disease-relevant risk factors could assist interventions targeting multiple behaviors simultaneously.

Prostaglandin E2 (PGE2) promotes proliferation and invasion by enhancing SUMO-1 activity via EP4 receptor in endometrial cancer.

Prostaglandin E2 (PGE2), a derivative of arachidonic acid, has been identified as a tumorigenic factor in many cancers in recent studies. Prostaglandin E synthase 2 (PTGES2) is an enzyme that in humans is encoded by the PTGES2 gene located on chromosome 9, and it synthesizes PGE2 in human cells. In our study, we selected 119 samples from endometrial cancer patients, with 50 normal endometrium tissue samples as controls, in which we examined the expression of PTGES2. Both immunohistochemistry (IHC) and Western blot analyses demonstrated that synthase PTGES2, which is required for PGE2 synthesis, was highly expressed in endometrium cancer tissues compared with normal endometrium. Stable PTGES2-shRNA transfectants were generated in Ishikawa and Hec-1B endometrial cancer cell lines, and transfection efficiencies were confirmed by RT-PCR and Western blot analyses. We found that PGE2 promoted proliferation and invasion of cells in Ishikawa and Hec-1B cells by cell counting kit-8 tests (CCK8) and transwell assays, respectively. PGE2 stimulation enhanced the expression of SUMO-1, via PGE2 receptor subtype 4 (EP4). Further analysis implicated the Wnt/ß-catenin signaling pathway function as the major mediator of EP4 and SUMO-1. The increase in SUMO-1 activity prompted the SUMOlyation of target proteins which may be involved in proliferation and invasion. These findings suggest SUMO-1 and EP4 as two potential targets for new therapeutic or prevention strategies for endometrial cancers.

Low-grade albuminuria associated with brachial-ankle pulse wave velocity in young adults with type 2 diabetes mellitus in China.

BACKGROUND: Cardiovascular disease is prevalent in type 2 diabetics, and microalbuminuria is associated with cardiovascular disease morbidity. We aimed to investigate the potential association between low-grade albuminuria and arterial stiffness in patients with type 2 diabetes. METHODS: Between 2009 and 2013, a retrospective study was performed in 578 patients with type 2 diabetes (339 male patients and 239 female patients) with normal urinary albumin-to-creatinine ratios (ACRs; <30 mg/g) from Fuzhou, China. Patients were stratified into tertiles based on urinary ACR levels (lowest tertile, urinary ACR < 4.8 mg/g; highest tertile, urinary ACR ≥ 20.1 mg/g). Arterial stiffness was measured via brachial-ankle pulse wave velocity. RESULTS: Brachial-ankle pulse wave velocity, age, duration of diabetes, systolic blood pressure and pulse wave velocity progressively increased across all urinary albumin-to-creatinine ratio tertiles (p < 0.05). Patients in the second and the highest tertiles had significantly elevated pulse wave velocity [114.6 mm/s (95% CI = 36.8-192.4) and 209.4 mm/s (95% CI = 131.8-286.9)], p = 0.004 and 0.000] compared with those in the lowest ACR tertile. The association between ACR and elevated pulse wave velocity still persisted in patients younger than 65 years of age and those with diabetes <10 years, conferring 45 or 51% greater risk of elevated pulse wave velocity (OR = 1.451; 95% CI = 1.119-1.881; p = 0.005 or OR = 1.515; 95% CI = 1.167-1.966; p = 0.0018) with each ACR tertile increment. Each ACR tertile increment conferred 31.7% higher risk of increased pulse wave velocity (OR = 1.317; 95% CI = 1.004-1.729; p = 0.0468). CONCLUSIONS: Patients with type 2 diabetes with urinary albumin excretion in the upper normal range were still at risk for target organ damage. Low-grade albuminuria might be an early marker for the detection of arterial stiffness in patients with type 2 diabetes, especially in younger patients with type 2 diabetes with shorter durations of disease.

Achieving robust synthetic tolerance in industrial E. coli through negative auto-regulation of a DsrA-Hfq module.

In industrial fermentation processes, microorganisms often encounter acid stress, which significantly impact their productivity. This study focused on the acid-resistant module composed of small RNA (sRNA) DsrA and the sRNA chaperone Hfq. Our previous study had shown that this module improved the cell growth of Escherichia coli MG1655 at low pH, but failed to obtain this desired phenotype in industrial strains. Here, we performed a quantitative analysis of DsrA-Hfq module to determine the optimal expression mode. We then assessed the potential of the CymR-based negative auto-regulation (NAR) circuit for industrial application, under different media, strains and pH levels. Growth assay at pH 4.5 revealed that NAR-05D04H circuit was the best acid-resistant circuit to improve the cell growth of E. coli MG1655. This circuit was robust and worked well in the industrial lysine-producing strain E. coli SCEcL3 at a starting pH of 6.8 and without pH control, resulting in a 250 % increase in lysine titer and comparable biomass in shaking flask fermentation compared to the parent strain. This study showed the practical application of NAR circuit in regulating DsrA-Hfq module, effectively and robustly improving the acid tolerance of industrial strains, which provides a new approach for breeding industrial strains with tolerance phenotype.

Effect of human epididymis protein 4 on hyperoxia-induced bronchial dysplasia in newborn rats.

OBJECTIVE: The study aimed to elucidate the role and the underlying mechanism of human epididymis protein 4 (HE4) in the pathogenesis of hyperoxia-induced bronchial dysplasia in newborn rats. METHODS: Forty neonatal Sprague-Dawley (SD) rats were separated into two groups: a normal control group (20.8% oxygen concentration) and a hyperoxia-induced group (85% oxygen concentration). Three time intervals of 24 h, 3 days and 7 days were chosen for each group. Haematoxylin-eosin staining was used to identify the pathological alterations in the lung tissue of the SD rats. Enzyme-linked immunosorbent assay was used to evaluate plasma protein levels. Real-time reverse transcription polymerase chain reaction was used to determine messenger RNA (mRNA) expression. RESULTS: In newborn SD rats, hyperoxia intervention within 7 days may result in acute lung damage. In the plasma and tissue of newborn SD rats, hyperoxia induction may raise levels of HE4, matrix metalloproteinases (MMP) 9 and tissue inhibitors of metalloproteinases (TIMP) 1. We discovered that the HE4 protein activates the phosphorylation of extracellular regulated protein kinases (ERK) and p65, activates the downstream MMP9 signalling pathway, inhibits MMP9 mRNA expression, inhibits protein activity, reduces type I collagen degradation, increases collagen secretion and promotes matrix remodelling and fibrosis in neonatal rat primary alveolar type II epithelial cells by overexpressing and silencing the HE4 gene. CONCLUSION: Through the ERK, MMP9 and TIMP1 signalling pathways, HE4 mediates the pathophysiological process of hyperoxia-induced lung damage in rats. Lung damage and lung basal remodelling are mediated by HE4 overexpression.

Association between plasma polyunsaturated fatty acids and depressive among US adults.

Background: Depression is associated with greater functional impairment and high societal costs than many other mental disorders. Research on the association between plasma polyunsaturated fatty acids (PUFAs) levels and depression have yielded inconsistent results. Objective: To evaluate whether plasma n-3 and n-6 PUFAs levels are associated with depression in American adults. Methods: A cross-sectional study included 2053 adults (aged ≥20 y) in the National Health and Nutrition Examination Survey (NHANES), 2011-2012. The level of plasma n-3 and n-6 PUFAs were obtained for analysis. Self-reported Patient Health Questionnaire-9 (PHQ-9) was used to identify the depression status. Binary logistic regression analysis was performed to evaluate the association between quartiles of plasma n-3 and n-6 PUFAs and depression after adjustments for confounders. Results: The study of 2053 respondents over 20 years of age with a weighted depression prevalence of 7.29% comprised 1,043 men (weighted proportion, 49.13%) and 1,010 women (weighted, 50.87%), with a weighted mean (SE) age of 47.58 (0.67) years. Significantly increased risks of depression over non-depression were observed in the third quartiles (OR = 1.65, 95% CI = 1.05-2.62) for arachidonic acid (AA; 20:4n-6); the third quartiles (OR = 2.20, 95% CI = 1.20-4.05) for docosatetraenoic acid (DTA; 22:4n-6); the third (OR = 2.33, 95% CI = 1.34-4.07), and highest quartiles (OR = 1.83, 95% CI = 1.03-3.26) for docosapentaenoic acid (DPAn-6; 22:5n-6); and the third (OR = 2.18, 95% CI = 1.18-4.03) and highest quartiles (OR = 2.47, 95% CI = 1.31-4.68) for docosapentaenoic acid (DPAn-3; 22:5n-3); the second (OR = 2.13, 95% CI = 1.24-3.66), third (OR = 2.40, 95% CI = 1.28-4.50), and highest quartiles (OR = 2.24, 95% CI = 1.08-4.69) for AA/docosahexaenoic acid (DHA; 22:6n-3) ratio compared with the lowest quartile after adjusting for confounding factors. Conclusion: Higher plasma levels of AA, DTA, DPAn-6, DPAn-3 PUFAs, and AA/DHA ratio may be potential risk factors for depression in US adults.