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Abstract Objective This study aimed to examine prospective associations of different intensity levels and types of physical activity (PA) in early pregnancy with premature rupture of membranes (PROM) among Chinese pregnant women. Methods A total of 6284 pregnant women were included from the Tongji-Shuangliu Birth Cohort. Household/caregiving, occupational, sports/exercise and transportation activities during early pregnancy were investigated by the pregnancy physical activity questionnaire (PPAQ), and the diagnosis of PROM was ascertained during the whole pregnancy. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the associations between PA and PROM. Results Among the 6284 pregnant women, 1246 were identified to have PROM (19.8%). Women undertaking the highest level (3 third tertile) of PA during pregnancy appeared to have a lower risk of PROM [OR = 0.68, 95%CI 0.58–0.80) when compared to those at the lowest tertile of PA. Similarly, women with increased levels of light intensity activity, moderate-vigorous intensive, household/caregiving activity and meeting exercise guidelines during pregnancy were associated with reduced risks of PROM (OR = 0.69, 95% CI 0.59–0.81, OR = 0.70, 95% CI 0.60–0.82, OR = 0.62, 95% CI 0.53–0.73 and OR = 0.82, 95% CI 0.70–0.97, respectively). Conclusions High levels of PA of different intensities and PA of household/caregiving activities and meeting exercise guidelines during the first trimester were associated with a lower incidence of PROM. Trial registration The data of human participants in this study were conducted in accordance with the Helsinki Declaration. This study has been approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ([2017] No. S225). All participants provided written informed consent prior to enrollment. A statement to confirm that all methods were carried out in accordance with relevant guidelines and regulations.

Background Obesity is a major public health issue in China and around the world. While acupuncture is often used in clinical practice, there is a lack of conclusive evidence for its weight-loss effect. Thus we will conduct a parallel, randomised, sham-controlled trial to evaluate the efficacy and safety of acupuncture for treating obesity.Methods and analysis A total of 160 eligible participants with obesity will be randomly assigned to the verum acupuncture group or sham acupuncture group at a ratio of 1:1. All participants will be treated three times a week for a duration of 12 weeks, and followed up for another 16 weeks. The primary outcome is the percentage change in body weight from baseline to Week 12. The secondary outcomes include body mass index (BMI), waist circumference (WC), body fat percentage (BF%), blood pressure, fasting blood glucose, insulin, glycosylated haemoglobin A1c, blood lipids, and physical functioning score on the Short Form 36 Health Survey. Other secondary outcomes including psychological and social functions will also be evaluated using the body image scale, psychological function scale, and social function scale of the BODY-Q, Rosenberg Self-Esteem Scale, Patient Health Questionnaire-9, and Dutch Eating Behaviour Questionnaire. BMI, WC, BF% and blood pressure will be evaluated at Week 0, 4, 8, 12 and 28. Other secondary outcomes will be measured at Week 0, 12 and 28, respectively. Adverse events will be recorded in detail during the trial.Ethics and dissemination Ethical approval of this trial was granted by the Ethics Committee of Chengdu Sport University (2023–102). Written informed consent will be obtained from study participants before enrolment. The findings will be disseminated through peer-reviewed journals.Trial registration number Chinese Clinical Trial Registry (ChiCTR2200062092).

Lucaogou Formation in the Santanghu Basin is a special lacustrine fine-grained sedimentary deposits rich in volcanic debris and carbonate, with abundant shale oil resources. However, understanding of shale oil characteristics and genesis remains unclear. Lithofacies, sedimentary environment, and formation mechanisms of tuffaceous shale oil are investigated based on core and thin section observations, X-ray diffraction, field emission SEM and geochemical analysis. Results show that three mixed lithofacies types are developed in Lucaogou Formation: blocky tuff, laminated tuffaceous dolomite, and laminated dolomitic tuff. These lithofacies types are characterized by high content of felsic and dolostone, widespread organic matter, and low clay content. Formation of tuffaceous shale oil sweet spots is primarily influenced by four factors: inputting of volcanic ash as a high-quality source rocks and reservoirs provides good material basis; devitrification of volcanic glass, calcitization, and dissolution are crucial for formation of reservoirs; expulsion of source rocks with high-abundance organic matter expulsion facilitates migration and accumulation of hydrocarbon in adjacent reservoirs; fracture development improves reservoir permeability to form highly productive sweet spots. By analyzing characteristics and genesis of tuffaceous shale oil, the main controlling factors of reservoir physical property and oil saturation are clarified, which is of great significance for selection of shale oil exploration zones.

Parkinson’s disease (PD) is a ubiquitous brain cell degeneration disease and presents a significant therapeutic challenge. By injecting 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle, rats were made to exhibit PD-like symptoms and treated by intranasal administration of a low-dose (2 × 105) or high-dose (1 × 106) human neural stem cells (hNSCs). Apomorphine-induced rotation test, stepping test, and open field test were implemented to evaluate the motor behavior and high-performance liquid chromatography was carried out to detect dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindole-3-acetic acid in the striatum of rats. Animals injected with 6-OHDA showed significant motor function deficits and damaged dopaminergic system compared to the control group, which can be restored by hNSCs treatment. Treatment with hNSCs significantly increased the tyrosine hydroxylase-immunoreactive cell count in the substantia nigra of PD animals. Moreover, the levels of neurotransmitters exhibited a significant decline in the striatum tissue of animals injected with 6-OHDA when compared to that of the control group. However, transplantation of hNSCs significantly elevated the concentration of DA and DOPAC in the injured side of the striatum. Our study offered experimental evidence to support prospects of hNSCs for clinical application as a cell-based therapy for PD.

In order to further investigate the dosing scheme for circulating water in the steel industry，the spatial and temporal distribution of different water quality types was analyzed using principal component analysis. Moreover， the scaling index method was used to analyse the tendency of scaling in five regions under different water quality types and different concentration multiples to determine the dosing scheme. The principal component analysis showed that：groundwater was mainly affected by calcium hardness，conductivity，total alkali and chloride ions，while river water or municipal water was mainly affected by total iron and turbidity；the scaling index method shows that：groundwater was scaling for supplementary water，while river water or municipal water was corrosive for supplementary water；it was recommended that the concentration factor was 4-5 when groundwater was supplementary water，and 3-4 when river water or municipal water was supplementary water. Based on the type of water quality and the concentration factor in each area，the recommended dosing plan for each area is optimized.

In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine.

Background Comprehensive blood lipoprotein profiles and their association with incident coronary heart disease (CHD) among racially and geographically diverse populations remain understudied. Methods and Results We conducted nested case–control studies of CHD among 3438 individuals (1719 pairs), including 1084 White Americans (542 pairs), 1244 Black Americans (622 pairs), and 1110 Chinese adults (555 pairs). We examined 36 plasma lipids, lipoproteins, and apolipoproteins, measured by nuclear magnetic resonance spectroscopy, with incident CHD among all participants and subgroups by demographics, lifestyle, and metabolic health status using conditional or unconditional logistic regression adjusted for potential confounders. Conventionally measured blood lipids, that is, total cholesterol, triglycerides, low‐density lipoprotein‐cholesterol, and high‐density lipoprotein‐cholesterol, were each associated with incident CHD, with odds ratios (ORs) being 1.33, 1.32, 1.24, and 0.79 per 1‐SD increase among all participants. Seventeen lipoprotein biomarkers showed numerically stronger associations than conventional lipids, with ORs per 1‐SD among all participants ranging from 1.35 to 1.57 and a negative OR of 0.78 (all false discovery rate

Background In 2009, a workplace‐based hypertension management program was launched among men with hypertension in the Kailuan study. This program involved monitoring blood pressure semimonthly, providing free antihypertensive medications, and offering personalized health consultations. However, the cost‐effectiveness of this program remains unclear. Methods and Results This analysis included 12 240 participants, with 6120 in each of the management and control groups. Using a microsimulation model derived from 10‐year follow‐up data, we estimated costs, quality‐adjusted life years (QALYs), life‐years, and incremental cost‐effectiveness ratios (ICERs) for workplace‐based management compared with routine care in both the study period and over a lifetime. Analyses are conducted from the societal perspective. Over the 10‐year follow‐up, patients in the management group experienced an average gain of 0.06 QALYs with associated incremental costs of $633.17 (4366.85 RMB). Projecting over a lifetime, the management group was estimated to increase by 0.88 QALYs or 0.92 life‐years compared with the control group, with an incremental cost of $1638.64 (11 301.37 RMB). This results in an incremental cost‐effectiveness ratio of $1855.47 per QALY gained and $1780.27 per life‐year gained, respectively, when comparing workplace‐based management with routine care. In probabilistic sensitivity analyses, with a threshold willingness‐to‐pay of $30 765 per QALY (3 times 2019 gross domestic product per capita), the management group showed a 100% likelihood of being cost‐effective in 10 000 samples. Conclusions Workplace‐based management, compared with routine care for Chinese men with hypertension, could be cost‐effective both during the study period and over a lifetime, and might be considered in working populations in China and elsewhere.

Kidney disease is one of the most common diseases and end-stage renal failure has seriously endangered human health. Therefore it is quite imperative to explore its pathogenesis and devise effective measures to delay the progress of kidney diseases. Proviral integration site 1 of murine leukemia virus (PIM1) is a serine/threonine kinase with diverse biological functions of regulating cell cycle, apoptosis, immune responses, inflammation and mitochondrial integrity. This review focused upon PIM1 and its mechanistic role in the development of kidney disease, providing rationales for a proper management of kidney diseases in clinical practices.

Background: Birth asphyxia causes hypoxia or inadequate perfusion to the organs of newborns, leading to metabolism dysfunctions including blood glucose disorders. Methods: Neonates with and without birth asphyxia were retrospectively recruited from 53 hospitals in Hubei Province from January 1 to December 31, 2018. In summary, 875, 1139, and 180 cases in the control group, the mild asphyxia group, and the severe asphyxia group were recruited, respectively. Neonatal blood glucose values at postnatal 1, 2, 6, and 12 h (time error within 0.5 h was allowed) were gathered from the medical records. Results: The incidence rates of hyperglycemia in the control group, the mild asphyxia group and the severe asphyxia group were 2.97%, 7.90%, and 23.33%, respectively (p

The nickel content of nickel-based high-temperature alloy is between 50% and 70%, and the alloy contents of chromium, iron, cobalt, molybdenum, aluminum, titanium and tungsten are within 20%. A method of high resolution plasma mass spectrometry was established to determine the trace elements in nickel-based high-temperature alloy. According to the principle of large isotope abundance, small interference and high sensitivity, the isotopes and resolution of the elements to be measured were optimized, the interferences of most of the multi-atom and double-charged ions were effectively eliminated. The mass spectral interferences of matrix, compositions of alloy and dissolving acid on the trace elements were investigated. The appropriate internal standard of caesium was selected to overcome the matrix effect and reduce the signal drift. Chromium was extracted by methylisobutylone, the extraction efficiency reached up to 99.7%, which eliminated the mass spectral interference of principal component molybdenum in the nickel-based high-temperature alloy. The linear correlation coefficient of the calibration curve was greater than 0.999, and the method detection limit was between 0.002 1 and 0.074 μg/g. The trace elements in the reference material was analyzed, the relative standard deviation (RSD, n=6) was between 2.9% and 7.8%, and the measured value was very consistent with the standard value. This method is simple, fast, accurate and reliable, which can meet the requirement of trace elements determination in nickel-based high-temperature alloy.

Abstract The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant‐induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.

Abstract Background Liver plays an important role in maintaining glucose homeostasis. We aimed to examine the associations of liver enzymes and hepatic steatosis index (HSI, a reliable biomarker for non-alcoholic fatty liver disease) in early pregnancy with subsequent GDM risk, as well as the potential mediation effects of lipid metabolites on the association between HSI and GDM. Methods In a birth cohort, liver enzymes were measured in early pregnancy (6-15 gestational weeks, mean 10) among 6,860 Chinese women. Multivariable logistic regression was performed to examine the association between liver biomarkers and risk of GDM. Pearson partial correlation and least absolute shrinkage and selection operator (LASSO) regression were conducted to identify lipid metabolites that were significantly associated with HSI in a subset of 948 women. Mediation analyses were performed to estimate the mediating roles of lipid metabolites on the association of HSI with GDM. Results Liver enzymes and HSI were associated with higher risks of GDM after adjustment for potential confounders, with ORs ranging from 1.42 to 2.24 for extreme-quartile comparisons (false discovery rate-adjusted P-trend ≤0.005). On the natural log scale, each SD increment of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and HSI was associated with a 1.15-fold (95% CI: 1.05, 1.26), 1.10-fold (1.01, 1.20), 1.21-fold (1.10, 1.32), 1.15-fold (1.04, 1.27), and 1.33-fold (1.18, 1.51) increased risk of GDM, respectively. Pearson partial correlation and LASSO regression identified 15 specific lipid metabolites in relation to HSI. Up to 52.6% of the association between HSI and GDM risk was attributed to the indirect effect of the HSI-related lipid score composed of lipid metabolites predominantly from phospholipids (e.g., lysophosphatidylcholine and ceramides) and triacylglycerol. Conclusions Elevated liver enzymes and HSI in early pregnancy, even within a normal range, were associated with higher risks of GDM among Chinese pregnant women. The association of HSI with GDM was largely mediated by altered lipid metabolism.

Objective To investigate the neural network mechanism of fear induced by cortical functional electrical stimulation with stereotactic electrodes. Methods and Results A total of 20 patients with intractable epilepsy who were diagnosed and underwent stereotactic electrode implantation in Sanbo Brain Hospital of Capital Medical University from January 2021 to June 2022 were selected. Among them, 7 patients (35%) received 75 reconstructed electrode contacts [9.66% (75/776)] to induce fear emotional response. They were mainly distributed in temporal lobe [45.33% (34/75)], insula lobe [32% (24/75)] and cingulate gyrus [13.33% (10/75)]. According to the "seed and discovery" calculation method, the occurrence probability of evoked fear response electrode contacts in 9 general brain networks (auditory, left executive control, right executive control, sensorimotor, visuospatial, dorsal default mode, advanced vision, posterior salience and primary vision) was the highest in the dorsal default mode network, accounting for 84% (63/75). The whole brain functional connection values of the fear⁃inducing electrode contacts were retrieved from the neurosynth database, and the differences between the in⁃brain and out⁃brain functional connection values were calculated. It was found that the matching degree between the fear⁃inducing electrode contacts and the dorsal default mode network was the highest, followed by the posterior prominence network. Conclusions Based on stereo⁃electroencephalography (EEG), the fear response induced by cortical functional electrical stimulation was mainly related to the dorsal default mode network. The hippocampus, insula and cingulate gyrus are important network nodes of fear response. It is suggested that there is a shared neural circuit between the fear response induced by electrical stimulation and the fear experience acquired through conditioning.

ObjectiveTo provide the basis for dealing with similar incidents in the future， an outbreak of foodborne illness caused by the consumption of bread contaminated with Salmonella enteritidis was investigated.MethodsDescriptive epidemiological methods were used to analyze the clinical characteristics， epidemiological distribution and related risk factors of the cases. The etiological food was determined by retrospective cohort study. The biological samples， food remains and environmental samples of the cases and canteen employees were detected by laboratory testing. The causes of the outbreak were comprehensively analyzed based on the results of epidemiological investigation， laboratory tests and sanitary investigation.ResultsRetrospective cohort study showed that a batch of pre-packaged bread produced by a food factory in Chongqing on May 20， 2021 was the suspicious food. A total of 73 people ate the suspicious bread in this incident， and 55 of them got ill with a morbidity rate of 75.34% and a median incubation period of 15 h. At the same time， Salmonella enteritidis was detected in food remains， related environmental samples and anal swabs of patients.ConclusionThe incident was an outbreak of foodborne disease caused by bread contaminated with Salmonella enteritidis.

Abstract Background Recent studies found associations between non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS), but the causal nature of this association is still uncertain. Methods We performed a bidirectional two-sample Mendelian randomization (MR) analysis to test for the causal association between NAFLD and PCOS using data from a large-scale biopsy-confirmed NAFLD genome-wide association study (GWAS) (1483 cases and 17,781 controls) and PCOS GWAS (10,074 cases and 103,164 controls) in European ancestries. Data from glycemic-related traits GWAS (in up to 200,622 individuals) and sex hormones GWAS (in 189,473 women) in the UK Biobank (UKB) were used in the MR mediation analysis to assess potential mediating roles of these molecules in the causal pathway between NAFLD and PCOS. Replication analysis was conducted using two independent datasets from NAFLD and PCOS GWASs in the UKB and a meta-analysis of data from FinnGen and the Estonian Biobank, respectively. A linkage disequilibrium score regression was conducted to assess genetic correlations between NAFLD, PCOS, glycemic-related traits, and sex hormones using full summary statistics. Results Individuals with higher genetic liability to NAFLD were more likely to develop PCOS (OR per one-unit log odds increase in NAFLD: 1.10, 95% CI: 1.02–1.18; P = 0.013). Indirect causal effects of NAFLD on PCOS via fasting insulin only (OR: 1.02, 95% CI: 1.01–1.03; P = 0.004) and further a suggestive indirect causal effect via fasting insulin in concert with androgen levels were revealed in MR mediation analyses. However, the conditional F statistics of NAFLD and fasting insulin were less than 10, suggesting likely weak instrument bias in the MVMR and MR mediation analyses. Conclusions Our study suggests that genetically predicted NAFLD was associated with a higher risk of developing PCOS but less evidence for vice versa. Fasting insulin and sex hormones might mediate the link between NAFLD and PCOS.

Macrobrachium nipponense is a major farmed species freshwater shrimp in China and its genetic diversity is of high value in aquaculture. The construction of the Three Gorges Project has slowed down the water velocity in the Three Gorges Reservoir (TGR) and made the water more clear, which is more favourable for the survival and reproduction of M. nipponense. However, there are lack of studies on the genetic diversity of M. nipponense populations in the TGR. In this study, mitochondrial COI gene sequences were used as molecular marker to analyze the genetic diversity, genetic differentiation and historical demography of eight M. nipponense populations in the TGR. The results showed that the M. nipponense populations in TGR have high genetic diversity. There was some genetic differentiation between the four populations in lower reaches of the TGR and four populations in the upper reaches of the TGR. We also found that there was a significant correlation between genetic distance and geographical distance among the M. nipponense populations in the TGR. The M. nipponense population in the TGR has experienced population reduction in the recent year, which might be related to the ice age movement in the Little Ice Age and human activities. This study provides a theoretical basis for the rational development and protection of M. nipponense resources in the TGR.

Abstract Objective This study aimed to evaluate the surgical outcomes and relevant prognostic factors in patients with low‐grade epilepsy‐associated neuroepithelial tumors (LEAT) and, especially, to develop a scoring system to predict postoperative seizure outcomes. Methods The clinical data of patients who underwent epilepsy surgery for LEAT were retrospectively studied. The surgical outcomes of seizure and neurological statuses in patients were evaluated using Engel classification and modified Rankin Scale (mRS) scoring, respectively. A scoring system of seizure outcomes was constructed based on the weight of the β‐coefficient estimate of each predictor in the final multivariate predicting model of seizure outcomes. Results Of the 287 patients (106 female) enrolled, the median age was 19 years at surgery and 10 years at seizure onset, with a median duration of epilepsy of 60 months. Among 258 patients who were followed up for at least 12 months, 215 (83.3%) patients had a favorable seizure outcome (Engel class I) after surgery, and 43 (16.7%) patients had an unfavorable seizure outcome; longer duration of epilepsy, discordant magnetoencephalography (MEG) findings, and acute postoperative seizures were significantly included in the scoring system to predict unfavorable seizure outcomes, and in the scoring system, accumulated scoring of 0–19 scores was recorded, which were finally grouped into three risk levels: low risk (risk

Abstract Objective To examine the association of early-pregnancy serum C-peptide with incident gestational diabetes mellitus (GDM) and the predictive ability of maternal C-peptide for GDM. Methods A nested case–control study of 332 GDM cases and 664 controls was established based on the Tongji-Shuangliu Birth Cohort. The GDM cases and controls were matched at 1:2 on maternal age (± 3 years) and gestational age (± 4 weeks). Multivariable conditional logistic regression was applied to assess the association of C-peptide with risk of GDM. Partial Spearman’s correlation coefficients were estimated for the correlations between C-peptide and multiple metabolic biomarkers. C-statistics were calculated to assess the predictive ability of early-pregnancy C-peptide for GDM. Results Of 996 pregnant women, median maternal age was 28.0 years old and median gestational age was 11.0 weeks. After adjustment for potential confounders, the odds ratio of GDM comparing the extreme quartiles of C-peptide was 2.28 (95% confidence interval, 1.43, 3.62; P for trend

Abstract Though gut microbiome disturbance may be involved in the etiology of gestational diabetes mellitus (GDM), data on the gut microbiome's dynamic change during pregnancy and associations with gestational glucose metabolism are still inadequate. In this prospective study comprising 120 pairs of GDM patients and matched pregnant controls, a decrease in the diversity of gut microbial species and changes in the microbial community composition with advancing gestation are found in controls, while no such trends are observed in GDM patients. Multivariable analysis identifies 10 GDM‐related species (e.g., Alistipes putredinis), and the integrated associations of these species with glycemic traits are modified by habitual intake of fiber‐rich plant foods. In addition, the microbial metabolic potentials related to fiber fermentation (e.g., mannan degradation pathways) and their key enzymes consistently emerge as associated with both GDM status and glycemic traits. Microbial features especially those involved in fiber fermentation, provide an incremental predictive value in a prediction model with established risk factors of GDM. These data suggest that the gut microbiome remodeling with advancing gestation is different in GDM patients compared with controls, and dietary fiber fermentation contributes to the influence of gut microbiome on gestational glycemic regulation.

The ant colony algorithm faces dimensional catastrophe problems when solving the large-scale traveling salesman problem, which leads to unsatisfactory solution quality and convergence speed. To solve this problem, an adaptive ant colony optimization for large-scale traveling salesman problem (AACO-LST) is proposed. First, AACO-LST improves the state transfer rule to make it adaptively adjust with the population evolution, thus accelerating its convergence speed; then, the 2-opt operator is used to locally optimize the part of better ant paths to further optimize the solution quality of the proposed algorithm. Finally, the constructed adaptive pheromone update rules can significantly improve the search efficiency and prevent the algorithm from falling into local optimal solutions or premature stagnation. The simulation based on 45 traveling salesman problem instances shows that AACO-LST improves the solution quality by 79% compared to the ant colony system (ACS), and in comparison with other algorithms, the PE of AACO-LST is not more than 1% and the Err is not more than 2%, which indicates that AACO-LST can find high-quality solutions with high stability. Finally, the convergence speed of the proposed algorithm was tested. The data shows that the average convergence speed of AACO-LST is more than twice that of the comparison algorithm. The relevant code can be found on our project homepage.

ObjectiveThe aim of the study was to evaluate the clinicopathological features, as well as the surgical prognosis, of epilepsy-associated gangliogliomas (GG) with CD34 expression and BRAFV600E mutation.MethodsClinical data of patients who underwent epilepsy surgery for GG were retrospectively studied. Univariate and multivariate analyses were performed to evaluate the correlations of clinical and pathological factors with molecular markers of CD34 expression and BRAFV600E mutation in GG.ResultsA total of 208 patients with GG had immunohistochemical detection of CD34 expression (positive/negative: 184/24), and among them, 89 patients had immunohistochemical detection of BRAFV600E mutation (positive/negative: 54/35). By univariate and multivariate analyses, seizure aura (p = 0.025), concordance of ictal electroencephalogram (EEG) findings (p = 0.045) and medial temporal tumor (p = 0.030) were found to be related to CD34 expression, but only hospitalization time (p = 0.042) was different for BRAF-mutated status. In addition, drug-resistant epilepsy (p = 0.040) and concordance of interictal EEG findings (p = 0.009) were found to be associated with tumor progression-free survival (PFS) in univariate analysis, but only concordance of interictal EEG findings was with significance in multivariate analysis. However, CD34 expression or BRAFV600E mutation in GG was not found to be associated with surgical outcomes of seizure control and tumor PFS.ConclusionThe CD34 expression or BRAFV600E mutation in GG may partly influence the distribution of clinicopathological features of patients with epilepsy, but they may be not able to predict the surgical prognosis of seizure outcome and tumor recurrence.

The data set of this article is related to the paper “Dynamical structure of social map in ancient China” (2022)[1]. This article demonstrates the data of social relations between cities in ancient China, ranging from 618 AD to 1644 AD. The raw data of social associations between elites used to build social maps are extracted from the China Biographical Database. The raw data contain 14,610 elites and 29,673 social associations, which cover 366 cities. The dataset of this article is relevant both for social and natural scientists interested in the social and economic history of ancient China. The data can be used for further insights/analyses on the evolutionary pattern of geo-social architecture, and the geo-history from the viewpoint of social network.

The HDR ultra - low carbon duplex stainless steel forked joint could crack and fail during wire cutting and machining. In this paper, the causes of the above - mentioned cracking were comprehensively analyzed by means of crack macroscopic morphology analysis, analysis on the fracture of impact test sample, chemical composition analysis of substrate, mechanical property testing of cracked area, metallographic structure analysis, fracture microscopic morphology analysis, micro - area energy spectrum analysis and other items. Results showed that the reason for the cracking of HDR forked joint was that the cooling speed of HDR material was too low in the process of solution heat treatment, so a large number of σ phases precipitated at the grain boundaries in the microstructure. The σ phases were brittle, which made the HDR material suffer a sharp decrease in plasticity and toughness, and then cracked in the process of wire cutting and machining.

Abstract Background We aimed to prospectively evaluate the associations between the baseline and changes in high-density C-reactive protein (hs-CRP) and incident metabolic syndrome (MetS) in China and update the evidence based on a meta-analysis of cohort studies in different populations. Methods Data from the China Health and Retirement Longitudinal Study among adults aged 45 years or older were analyzed. Participants who were recruited in the study in 2011–2012 without MetS and successfully followed up to 2015–2016 were included in our final analysis. Logistic regressions were applied to examine the prospective associations of baseline and changes in hs-CRP with incident MetS and estimate corresponding odds ratios (ORs) and 95% confidence intervals (95% CIs). A meta-analysis was conducted to synthesize effect estimates from our findings and other cohort studies on this topic. Results Among 4,116 participants, 535 developed MetS after a 4-year follow-up. Compared with the participants with hs-CRP in the lowest quartile, those with hs-CRP in the second, third, and highest quartiles had higher odds of MetS, with multivariable-adjusted ORs (95% CIs) of 1.51 (1.12, 2.06), 1.50 (1.11, 2.04), and 1.83 (1.37, 2.47). For the hs-CRP changes, ORs (95% CIs) were 3.24 (2.51, 4.02), 3.34 (2.56, 4.38), and 3.34 (2.54, 4.40) respectively. One unit (log of 1 mg/L) increase in hs-CRP was associated with 23% higher risk of MetS (OR 1.23; 95% CI 1.10, 1.38). In a meta-analysis of 6 cohort studies, the pooled relative risk for MetS was 1.63 (1.38, 1.93) for the highest versus lowest level of hs-CRP. In addition, the pooled relative risk for MetS was 1.29 (1.05, 1.59) for each unit increase of hs-CRP after log-transformation. Conclusions Both higher baseline hs-CRP and longitudinal hs-CRP increases were associated with higher risks of incident MetS. Individuals with high hs-CRP levels may need to be closely monitored for future risk of MetS.

Abstract Background We prospectively examined the association between serum uric acid (SUA) levels and chronic kidney disease (CKD) in China and updated the evidence through a comprehensive meta-analysis of prospective studies worldwide. Methods Our original analyses were based on data from the China Health and Retirement Longitudinal Study. The primary exposure of interest was SUA at baseline, and the main outcome was incident CKD. Logistic regression models were used to examine the association between SUA levels and incident CKD. A meta-analysis was performed to pool our effect estimate and those from other cohort studies. Results During a 4-year follow-up, 180 participants developed incident CKD. Participants in the highest SUA quartile were 2.73 times as likely to develop incident CKD compared to those in the lowest quartile (multivariable-adjusted OR, 2.73; 95% CI, 1.65–4.50). Each 1 mg/dL increment in the SUA levels was associated with a 49% increased risk of incident CKD (multivariable-adjusted OR, 1.49; 95% CI, 1.28–1.74). In the meta-analysis of 30 cohort studies (including the current study), pooled relative risks (95% CIs) of incident CKD were 1.15 (1.10–1.21) for SUA each 1 mg/dL increment, 1.22 (1.14–1.30) for the highest versus lowest SUA group, and 1.17 (1.12–1.23) for hyperuricemia versus no hyperuricemia. Conclusions Baseline SUA levels were associated with higher risk of incident CKD in middle-aged and elderly Chinese adults, and this positive association was confirmed in the meta-analysis of multiple cohort studies. Our findings may imply that SUA levels need to be routinely monitored for future CKD risk.

Microbiome epidemiology is an emerging field for the discovery of novel disease biomarkers or intervention targets in human epidemiological studies. The determinants and consequences of human microbiome variations, especially for the gut microbiome, are both important and unsolved research questions, while the majority of findings of prior research are based on small-scale human studies with limited statistical power and a lack of replication/generalizability across different populations. Here, we initiated the Westlake Gut (WeGut) project, a consortium of gut microbiome-based human cohort studies in China. The WeGut project aims to provide a platform for the integration of gut microbiome data across different cohort studies, including two major components: 1) cohorts for healthy ageing and 2) cohorts for healthy pregnancy. The WeGut consortium includes seven core/foundation cohorts involving over 32,000 participants with gut microbiome and rich phenotype data across 17 provinces/megacities in China. Within the WeGut framework, we hope to disentangle the interplay among diet, lifestyle factors, host genetics and the gut microbiome in human health and explore the role of the gut microbiome for the precision prevention of chronic diseases in Chinese populations.

Depression is a common psychiatric comorbidity in patients with epilepsy, especially those with temporal lobe epilepsy (TLE). The aim of this study was to assess changes in high mobility group box protein 1 (HMGB1) expression in epileptic patients with and without comorbid depression. Sixty patients with drug-resistant TLE who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence ( n = 7/group). We also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in nondepressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy.

Background: Atrial fibrillation (AF) has affected millions of adults in the world. It is important to monitor and manage blood pressure (BP) in AF patients. The accuracy of BP monitoring in AF patients with noninvasive methods remains questionable, however. Objectives: To compare the accuracy of different noninvasive BP devices (oscillographic sphygmomanometer and pulse wave device) for BP measurement in elderly patients with AF, with a mercury sphygmomanometer as a reference. Design: This study was an observational study. Methods: Patients with AF from the inpatient department of cardiology were included from 1 January to 31 December 2020. BP measurements were performed by two trained nurses using a tee junction connection on the cuff to connect three sphygmomanometers. The Bland–Altman plot analysis was conducted to compare the agreement of BP measurements. We also compared the agreement of BP measurements through metrics such as accuracy, bias, and precision. Results: A total of 202 patients (54.5% female) were included. The Bland–Altman plot analysis showed that the lower and upper limits of agreement (LoAs) of pulse wave/reference were similar to the predefined acceptable clinical limits (10/5 mmHg). The bias and precision in both systolic and diastolic BP were significantly less in pulse wave/reference (a bias of 1.8 and 0.77 mmHg and a precision of 5.20 and 4.66 mmHg, respectively), with corresponding higher accuracy readings (98.51% for P10 in systolic BP and 85.64% for P5 in diastolic BP). Conclusion: A novel noninvasive sphygmomanometer – pulse wave device has a good concordance with a mercury sphygmomanometer in BP monitoring, and may be applicable to perform BP measurements in the elderly with AF.

Whilst certain environmental organochlorine pesticide exposure may still pose significant burden, the associations between dichloro-diphenyl-trichloroethane (DDT) and chronic kidney disease (CKD) remain disputable notwithstanding the potentially inaccurate disease definition between age groups. National DDT exposure burden atlas was depicted from 92,061 participants by measuring their serum concentrations of DDT congeners and major metabolite in the US from 1999 to 2016. Temporal analyses of these toxicant exposure suggested that although serum DDT concentrations exhibited recent decline, the detection rates remain up to 99.8% every year, posing great concern for exposure risk. A total of 3,039 US adults were further included from these participants demonstrating the weighted CKD prevalence of 40.2% using the new age-adapted CKD-EPI40 model compared to 28.0% using the current CKD-EPI method. After adjustment for covariates, logistic regression model results showed individual metabolites and total DDT burden were positively, yet monotonically, associated with risk of CKD incidence (P-trend for all

Abstract Pancreatic cancer is a highly aggressive and lethal digestive system malignancy. Our previous studies revealed the correlation of high levels of lncRNA SOX2OT expression with patients’ poor survival outcomes, the promoting role of SOX2OT in proliferation and cycle progression of pancreatic cancer cells, and the in vivo binding of SOX2OT to RNA binding protein FUS, which destabilized the protein expression of FUS. However, the mechanism of SOX2OT binding and inhibiting FUS protein stability remains unclear. In this study, we performed RNA pull-down, cycloheximide-chase, and ubiquitination assays to determine the effect of SOX2OT on FUS ubiquitination, and explored the specific regulatory mechanism of SOX2OT–FUS axis in pancreatic cancer cell migration, invasion, in vivo tumor growth, and metastasis through RNA sequencing. We found that SOX2OT binds to FUS through its 5′ and 3′ regions, resulting in FUS ubiquitination and degradation. The SOX2OT–FUS regulatory axis promotes migration, invasion, tumor growth, and metastasis ability of pancreatic cancer cells. The in-depth elaboration of the SOX2OT–FUS regulatory axis in pancreatic cancer may clarify the mechanism of action of SOX2OT and provide new ideas for pancreatic cancer treatment.

Abstract Background To prospectively examine the associations of baseline serum uric acid (SUA) and SUA changes with incident metabolic syndrome (MetS) and update the evidence through a meta-analysis. Methods Our analyses were based on the China Health and Retirement Longitudinal Study from 2011–2012 to 2015–2016. The exposures were baseline SUA and SUA changes, and the outcome was incident MetS assessed in 2015–2016. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A meta-analysis was conducted to synthesize evidence from all cohort studies on the same topic. Results Of 3779 participants (47.2% men; mean age: 59.5 years) without MetS, 452 participants developed MetS after a follow-up of 4 years. Compared to the lowest quartiles, the adjusted ORs (95% CIs) for MetS were 1.08 (0.77–1.50), 1.32 (0.95–1.82), and 1.55 (1.12–2.16) for three higher quartiles of baseline SUA, and 1.23 (0.89–1.71), 1.39 (1.00–1.93), and 1.89 (1.38–2.58) for three higher quartiles of SUA changes. Each increment of 1 mg/dL of baseline SUA level was associated with 19% higher odds of MetS (adjusted OR 1.19; 95% CI 1.07–1.33). In the meta-analysis of 24 cohort studies among 140,913 participants, the pooled relative risk (95% CI) was 1.32 (1.25–1.40) for the highest versus lowest SUA category, and 1.15 (1.09–1.21) for each 1 mg/dL increase in the SUA level. Conclusions Both baseline SUA and longitudinal SUA changes were positively associated with risk of MetS among middle-aged and elderly Chinese, which was supported by findings from a comprehensive meta-analysis across multiple populations. SUA levels might need to be monitored closely for subsequent risk of MetS in clinical practice.

This study aimed to investigate the effects of advanced glycation end products (AGEs) on the calcification of human arterial smooth muscle cells (HASMCs) and to explore whether AGEs can promote the calcification of HASMCs by activating the phosphoinositide 3-kinase (PI3K)/AKT-glycogen synthase kinase 3 beta (GSK3-β) axis. Cultured HASMCs were divided into five groups: blank control group, dimethyl sulfoxide (vehicle) group, AGEs group, LY294002 (AKT inhibitor) group, and TWS119 (GSK3-β inhibitor) group. Cells were pretreated with either vehicle, LY294002, or TWS119 for 2 hours followed by incubation with AGEs (25 μg/mL) for 5 days, and the expression levels of proteins in each group were analyzed by western blotting. AGE treatment promoted HASMC calcification, which coincided with increased expression of p-AKT and p-GSK3-β (serine 9). Also, AGEs upregulated the expression of osteoprotegerin and bone morphogenetic protein, and these effects were suppressed by LY294002 but enhanced by TWS119. In conclusion, AGEs promote calcification of HASMCs, and this effect is ameliorated by inhibition of AKT activity but potentiated by inhibition of GSK3-β activity. Hence, AGEs trigger HASMC calcification by regulating PI3K/AKT-GSK3-β signaling.

BackgroundHigh low-density lipoprotein-cholesterol (LDL-C) is a public health issue contributing to ischemic heart disease (IHD) and stroke.MethodIn this ecological study, we collected summary exposure values (SEVs), deaths, disability-adjusted life of years (DALYs), and Social Demographic Index (SDI) of high LDL-C from 1990 to 2019 using the query tool from the Global Burden of Disease (GBD) Collaborative Network. Outcomes include SEVs, deaths, and DALYs attributable to high LDL-C stratified by sex, age, region, SDI, countries, and territories. Estimated annual percentage changes (EAPCs) were applied to estimate annual trends of changes in these outcomes. We applied the weighted segmented regression with break-point estimation to detect the linear piecewise relationship between SDI and high LDL-C disease burden.ResultsGlobally, 3.00 million (95% uncertainty interval [UI], 2.35–3.76 million) people in 1990 and 4.40 million (95% UI, 3.30–5.65 million) people died from high LDL-C in 2019. The absolute annual burden from deaths and DALYs attributed to high LDL-C increased by 46% (95% UI, 35–56%) and 41% (95% UI, 31–50%) from 1990 to 2019. The age-standardized SEV, death, and DALY was decreased by 9% (95% UI, −11 to −8%), 37% (95% UI, −41−33%), and 32% (95% UI, −37 to −28%), respectively, during the study period. There was a negative association between SDI and high LDL-C-related age-standardized death and DALY rates when SDI surpassed 0.71 and 0.71, respectively.ConclusionAlthough the overall age-standardized burden of high LDL-C is controlled in the past 30 years, it remains increasing in moderate SDI countries, and decreasing trends are disappearing in high SDI countries. New challenges require new actions stratified by countries with different SDI levels.

Abstract Background Consumption of nuts improves cardio-metabolic risk factors in clinical trials and relates to lower risk of cardiovascular disease (CVD) in prospective observational studies. However, there has not been an adequately powered randomized controlled trial to test if nuts supplementation actually reduces incident CVD. In order to establish the feasibility of such a trial, the current study aimed to assess the acceptability and adherence to long-term nut supplementation amongst individuals at high CVD risk in China. Methods This protocol described a 6-month trial performed in Ningxia Province in China among participants with a history of CVD or older age (female ≥65 years, male ≥60 years) with multiple CVD risk factors. Participants were randomized to control (received non-edible gift), low dose walnut (30 g/d), or high dose walnut (60 g/d) groups in a 1:1:1 ratio. Walnuts were provided at no cost to participants and could be consumed according to personal preferences. Follow-up visits were scheduled at 2 weeks, 3 months and 6 months. The primary outcome was fasting plasma alpha linolenic acid (ALA) levels used as an indicator of walnut consumption. Secondary outcomes included self-reported walnut intake from the 24 h dietary recalls. The target sample size of 210 provided 90% statistical power with two-sided alpha of 0.05 to detect a mean difference of 0.12% (as percent of total fatty acid) in plasma ALA between randomized groups. Results Two hundred and ten participants were recruited and randomized during October 2019. Mean age of participants was 65 years (SD = 7.3), 47% were females, and 94% had a history of CVD at baseline. Across the three study groups, participants had similar baseline demographic and clinical characteristics. Discussion This trial will quantify acceptability and adherence to long-term walnut supplementation in a Chinese population at high risk of CVD. The findings will support the design of a future large trial to test the effect of walnut supplementation for CVD prevention. Trial registration NCT04037943 Protocol version: v3.0 August 14 2019

Objective To compare the efficacy of local anesthesia and general anesthesia of subthalamic nucleus deep brain stimulation (STN⁃DBS) for Parkinson's disease (PD). Methods Forty PD patients who underwent bilateral STN ⁃ DBS from January 2015 to January 2018 were retrospectively analyzed. Twenty⁃two patients underwent local anesthesia and 18 patients underwent general anesthesia. Pre⁃ and post⁃operative Unified Parkinson's Disease Rating Scale⁃Ⅲ (UPDRS⁃Ⅲ), Hoehn⁃Yahr, Activities of Daily Living (ADL), Wechsler Adult Intelligence Scale (WAIS), Wechsler Memory Scale (WMS), Hamilton Depression Rating Scale (HAMD)⁃17 and Hamilton Anxiety Rating Scale (HAMA)⁃14 were used to assess the motor symptoms, daily living function, cognitive function, memory, anxiety and depression. Results The target deviation of the second electrode in general anesthesia group was lower than that in local anesthesia group [(0.98 ± 0.39) mm vs. (1.21 ± 0.35) mm; t = ⁃ 2.041, P = 0.048], the target deviation of the first electrode was not statistically significant [(0.96 ± 0.29) mm vs. (1.01 ± 0.35) mm; t = ⁃ 0.496, P = 0.623]. At 6, 12, and 24 months after surgery, the "on" and "off" UPDRS⁃Ⅲ scores (P = 0.001, for all) and Hoehn⁃Yahr (P = 0.001, for all) in the general anesthesia group and the local anesthesia group were all significantly decreased compared with baseline, ADL score significanly increased (P = 0.001, for all). There were no significant differences in "on" and "off" UPDRS⁃Ⅲ, Hoehn⁃Yahr, ADL, WAIS and WMS scores between 2 groups (P > 0.05, for all). One day after surgery, the HAMA⁃14 in the local anesthesia group was higher than baseline (P = 0.027), in the general anesthesia group, HAMD⁃17 (P = 0.008) and HAMA⁃14 (P = 0.001) scores were lower than 1 d before surgery. The HAMD⁃17 (P = 0.001, for all) and HAMA ⁃ 14 (P = 0.001, for all) of 2 groups at 6, 12 and 24 months after surgery were all lower than baseline, 1 d before and 1 d after surgery. HAMD⁃17 score in the general anesthesia group was lower than the local anesthesia group (P = 0.048). Conclusions Both general anesthesia and local anesthesia STN⁃DBS can significantly improve PD motor symptoms and quality of life, as well as relieve the depression and anxiety symptoms, without affecting cognitive function and memory. Attention should be paid to mood fluctuations in using different anesthesia during the perioperative period. Choice of anesthesia method should be based on the patient's condition and indications. DOI：10.3969/j.issn.1672⁃6731.2020.12.006

Aims: Adequate intake of long-chain (LC) omega-3 polyunsaturated fatty acids ( n -3 PUFAs) is considered important for cardiovascular health. However, the effects of LC n -3 PUFAs on the risk of heart failure (HF) remain unclear. This systematic review and meta-analysis aimed to determine the role of LC n -3 PUFAs in the incidence of HF. Materials and Methods: Electronic databases were searched for studies up to 31 July 2021. Studies were included for the meta-analysis if they reported the adjusted associations between different dietary intakes or circulating concentrations of LC n -3 PUFAs and the risk of HF. A random-effect model was used to calculate the pooled estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for higher LC n -3 PUFA concentrations. Results: Thirteen studies were included in the meta-analysis. Eight studies comprising 316,698 individuals (11,244 incident HF cases), with a median follow-up of 10.7 years, showed that a higher dietary intake of LC n -3 PUFAs was associated with a lower risk of HF (highest versus lowest quintile: HR = 0.84, 95% CI = 0.75–0.94). Six studies, comprising 17,163 participants (2520 HF cases) with a median follow-up of 9.7 years, showed that higher circulating LC n -3 PUFA concentrations were associated with a lower risk of HF (highest versus lowest quintile: HR = 0.59, 95% CI = 0.39–0.91). Higher circulating docosahexaenoic acid concentrations were associated with a decreased risk of HF (top versus bottom quintile: HR = 0.44, 95% CI = 0.26–0.77). The associations between eicosapentaenoic acid (HR = 0.58, 95% CI = 0.26–1.25), docosahexaenoic acid (HR = 0.66, 95% CI = 0.24–1.82), and the risk of HF were not significant. Conclusion: High LC n -3 PUFA concentrations measured by dietary intake or circulating biomarkers are associated with a lower risk of developing HF.

BackgroundTo examine the prospective association between higher blood pressure (BP) and risk of type 2 diabetes mellitus (T2DM) in middle-aged and elderly Chinese adults.MethodsA total of 9,642 middle-aged and elderly Chinese adults (≥45 years old; 47.30% men) without diabetes from the China Health and Retirement Longitudinal Study were included for analyses. Participants were categorized into three groups: normal BP, prehypertension, and hypertension, according to the 2010 Chinese Guidelines for the Management of Hypertension. The incidence of T2DM was determined by self-reported physician diagnosis during two follow-up surveys conducted in 2013 to 2014 and 2015 to 2016.ResultsDuring the 4-year follow-up, 429 participants (4.45%) developed T2DM, including 3.51% of the men and 5.29% of the women. The incidence rates of T2DM were 2.57%, 3.75%, and 6.71% in the normal BP, prehypertension, and hypertension groups, respectively. After adjustment for age, sex, education level, residence, smoking status, alcohol consumption, body mass index, waist circumference, and dyslipidemia, both prehypertension (odds ratio [OR], 1.32; 95% confidence interval [CI], 0.98 to 1.77) and hypertension (OR, 2.02; 95% CI, 1.54 to 2.64) were associated with increased risk of T2DM, compared to those with a normal BP. The ORs associated with T2DM were 1.08 (95% CI, 1.03 to 1.13) for an increase of 10 mm Hg in systolic BP and 1.06 (95% CI, 1.01 to 1.10) for an increase of 5 mm Hg in diastolic BP.ConclusionHigher BP is a risk factor for T2DM in middle-aged and elderly Chines. It may be a potential target for diabetes prevention.

Abstract Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). It has been reported that the ribosome assembly factor Urb1 acts downstream of mTORC1/raptor signaling and contributes to digestive organ development in zebrafish. Previously, we highlighted that URB1 was overexpressed in CRC. Here, we assessed the mTORC1/regulatory associated protein with mTOR (RAPTOR)‐URB1 axis in CRC tumorigenesis. We found that RAPTOR was overexpressed in CRC tissues and cell lines, was a favorable predictor in patients with CRC, and positively correlated with URB1. Silencing of RAPTOR suppressed CRC cell proliferation and migration and induced cell cycle arrest and apoptosis in vitro and inhibited xenograft growth in vivo. Moreover, ectopic overexpression of RAPTOR exerted an inverse biological phenotype. Knockdown of RAPTOR quenched mTORC1 activity and reduced the expression of URB1 and cyclinA2 (CCNA2). In contrast, overexpression of RAPTOR activated mTORC1 and upregulated URB1 and CCNA2. Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Thus, RAPTOR promoted CRC proliferation, migration, and cell cycle progression by inducing mTORC1 signaling and transcriptional activation of both URB1 and CCNA2. Taken together, we concluded that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for CRC.

Objective To investigate the effect of miR-29a on the activity and apoptosis of fibroblast-like synoviocyte(FLS) in rheumatoid arthritis(RA). Methods The normal human FLS (n-FLS) and RA patients FLS (RA-FLS) were isolated and cultured,and the expression level of CHI3L1 protein was detected by Western blot. miR-29a mimics, si-NFAT5 and miR- 29a+NFAT5 were transfected into RA-FLS for 48 h. Then,the expression levels of miR-29a and NFAT5 mRNA were detected by RT-qPCR, the cell viability and apoptosis were detected by MTT assay and flow cytometry,respectively and the expression of p38, p-p38, cleaved-caspase3 proteins were detected by Western blot. Targeting relationship between miR-29a and NFAT5 was validated by dual fluorescent reporter gene detection system. Results Compared with n-FLS, the expression level of CHI3L1 protein in RA-FLS was increased significantly (P＜0.05). After over-expression of miR-29a or inhibition of NFAT5, the cell viability decreased, the apoptosis rate increased, the expression of p-p38 decreased, and the expression of cleaved-caspase3 increased significantly(P＜0.05). Luciferase activity of RA-FLS was significantly decreased in miR-29a and wild-type NFAT5 3′UTR co-transfection group, but increased in anti-miR-29a and wild-type NFAT5 3′UTR co-transfection group (P＜0.05). Over-expression of miR-29a significantly decreased the expression of NFAT5, and inhibition of miR-29a significantly increased the expression of NFAT5 (P＜0.05).Over-expression of NFAT5 can weaken the effect of over-expression of miR-29a on RA-FLS activity and apoptosis (P＜0.05). Conclusions miR-29a can inhibit the activity of RA-FLS and induce its apoptosis by targeting NFAT5 to down-regulate p38 MAPK signaling pathway.

Based on random vibration theory and fatigue analysis method in frequency domain,with finite element software to construct the battery pack failure model of random vibration fatigue analysis and to calculate the fatigue life of the structure,the analysis results are in good agreement with the test results. Analyze the failure mechanism of the structure and carry out structural design improvement,the simulation and test results show that the fatigue life of the improvement scheme is significantly improved,and it has better anti vibration durability.

Background: Assessing the relation between arthritis and cognitive impairment could expand the understanding of health consequences of arthritis. The aim was to prospectively examine the association between arthritis and cognitive functions among middle-aged and elderly Chinese.Methods: Our analyses were based on data from the nationwide China Health and Retirement Longitudinal Study (2011–2016). Arthritis was ascertained by self-reported doctor diagnosis during the baseline survey. Cognitive functions were evaluated in three domains including episodic memory, mental status, and global cognition. Linear mixed models were employed to assess the association between baseline arthritis and cognition functions.Results: Of 7,529 Chinese adults, 49.79% were men, and mean age was 57.53 years. During a follow-up of 4 years, participants with baseline arthritis showed lower scores of episodic memory [β = −0.08; 95% confidence interval (CI): −0.14, −0.03], mental status (β = −0.14; 95% CI: −0.22, −0.05), and global cognition (β = −0.22; 95% CI: −0.34, −0.11), compared to those without arthritis. In addition, participants with arthritis showed increased rates of decline in mental status and global cognition by 0.04 (95% CI: 0.01, 0.08) and 0.05 (95% CI: 0.01, 0.09) units per year, respectively.Conclusion: Arthritis was associated with subsequent risk of poorer cognitive functions and slightly faster declines in cognitive functions among Chinese middle-aged and elderly adults. Our findings should be confirmed in future large prospective studies in Chinese and other populations.

BackgroundWe aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality.Methods and findingsWe measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose-response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case-cohort, or nested case-control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≤3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels.ConclusionsIn a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms.

Objective: Pyrethroids-containing products are widely used as commercial and household insecticides. While animal studies and clinical case reports have shown acute cardiovascular outcomes of pyrethroids exposure, little has been known on the effect of chronic pyrethroid exposure on cardiovascular disease (CVD). We aimed to examine the associations between chronic pyrethroid exposure and CVD in the US adults. Methods: Cross-sectional data from the National Health and Nutrition Examination Survey 1999–2002 and 2007–2012 were analyzed. The exposure to pyrethroids was determined as the urinary level of 3-phenoxybenzoic acid (3-PBA), and CVD was ascertained based on self-reported physician diagnoses. Multivariable logistic regression models were fitted to evaluate associations of pyrethroid exposure with CVD, coronary heart disease (CHD), and stroke. Results: Included were 6,471 participants with a mean age of 44.77 years (standard error, 0.39) for final analyses. The weighted prevalence of CVD, CHD, and stroke was 6.85%, 4.57% and 2.27%, respectively. With adjustments for major confounders, participants in the highest tertile of urinary 3-PBA had higher odds of CVD (odds ratio, 1.58; 95% confidence interval: 1.12, 2.23) and CHD (OR, 1.75; 95% CI: 1.17, 2.61) compared to those in the lowest tertile. There were linear associations for CVD (P for trend = 0.04) and CHD (P for trend = 0.02). However, no significant association was noted for stroke (1.29; 0.78, 2.16) in the main analyses. Conclusions: 3-PBA was adversely associated with CVD and CHD in the US adults. Our findings highlight potential cardiovascular risk of chronic exposure to pyrethroids, and should be validated in large prospective studies in different populations in future.

Objectives: The original intracerebral hemorrhage (oICH) score is the severity score most commonly used in clinical intracerebral hemorrhage (ICH) research but may be influenced by hematoma expansion or intraventricular hemorrhage (IVH) growth in acute ICH. Here, we aimed to develop new clinical scores to improve the prediction of functional outcomes in patients with ICH.Methods: Patients admitted to the First Affiliated Hospital of Chongqing Medical University with primary ICH were prospectively enrolled in this study. Hematoma volume was measured using a semiautomated, computer-assisted technique. The dynamic ICH (dICH) score was developed by incorporating hematoma expansion and IVH growth into the oICH score. The ultra-early ICH (uICH) score was developed by adding the independent non-contrast CT markers to the oICH score. Receiver operating characteristic curve analysis was used to compare performance among the oICH score, dICH score, and uICH score.Results: There were 310 patients in this study which included 72 patients (23.2%) with hematoma expansion and 58 patients (18.7%) with IVH growth. Of 31 patients with two or more non-contrast computed tomography markers, 61.3% died, and 96.8% had poor outcomes at 90 days. After adjustment for potential confounding variables, we found that age, baseline Glasgow Coma Scale score, presence of IVH on initial CT, baseline ICH volume, infratentorial hemorrhage, hematoma expansion, IVH growth, blend sign, black hole sign, and island sign could independently predict poor outcomes in multivariate analysis. In comparison with the oICH score, the dICH score and uICH score exhibited better performance in the prediction of poor functional outcomes.Conclusions: The dICH score and uICH score were useful clinical assessment tools that could be used for risk stratification concerning functional outcomes and provide guidance in clinical decision-making in acute ICH.