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Abstract Mental health is deteriorating far and fast globally post-COVID. Though there were already over one billion people living with mental disorders pre-pandemic, in the first year of COVID-19 alone, the prevalence of anxiety and depression soared by 25% worldwide. In light of the chronic shortages of mental health resources and talents, along with disruptions of available health services caused by pandemic-related restrictions, technology is widely believed to hold the key to addressing the rising mental health crises. However, hurdles such as fragmented and oftentimes suboptimal patient protection measures substantially undermine technology’s potential to address the global mental health crises reliably and at scale. To shed light on these issues, this paper aims to discuss the post-pandemic mental health challenges and opportunities, and the strategies and solutions the global mental health community could leverage to protect and elevate society’s mental health in the long run.

Abstract Background Unintentional injuries is the leading cause of death in children aged 6–18 in China. Previous studies on the association between the guardians’ educational levels and unintentional injuries in children have been inconclusive, and it remains unclear among the Chinese population. Therefore, this study aimed to identify the association between guardians’ educational levels and unintentional injuries in children aged 6–18 in Shenzhen, China. Methods This cross-sectional study enrolled 9,903 children aged 6–18 in Shenzhen in 2020 using a multistage cluster sampling method. Information on the children and guardians were collected, and unintentional injuries in the past year was examined by using two nested questions. Logistic regression analyses were used to test the association between the guardians’ educational levels and unintentional injuries in children aged 6–18, and the crude odds ratios (ORs) and adjusted ORs with 95% confidence intervals (95% CI) were calculated. Results 275 of the 9,903 children reported experiencing at least one unintentional injuries in the past year, and the weighted incidence of unintentional injuries was 6.3% (95% CI: 5.8–6.8%) in children aged 6–18 in Shenzhen, China. The incidence of unintentional injuries differed significantly in the guardians’ education levels (P

Objectives: This study aimed to investigate the factors associated with the spontaneous clearance of Chlamydia trachomatis, a phenomenon that, despite a growing body of literature, remains understudied in the context of women in China. Methods: Spontaneous clearance was defined as the transition from a positive to negative Chlamydia status over time without the use of antichlamydial therapy. Data from 5935 women aged 18 years and older who participated in the Clinical-Based Health Check program were analyzed. Eligible participants had no history of Neisseria gonorrhoeae infection, pelvic inflammatory disease, recent antibiotic use, or pregnancy and had an interval between the screening and follow-up visits of more than 3 days. Logistic regression was used to identify factors influencing spontaneous clearance. Results: Spontaneous clearance occurred in 23.9% (50/209) of the participants, typically with a median interval of 27 days. Significant factors included an interval >45 days, an age >35 years, the use of an intrauterine device (IUD), and the presence of clue cells. Conclusion: Spontaneous clearance of C. trachomatis is significantly affected by age, the interval between two tests, IUD use, and the presence of clue cells. Screening strategies should prioritize women under 35 years of age who do not use IUDs and test negative for clue cells for more effective chlamydia prevention and management.

Summary: Background: Globally, fall-related injuries are a substantial problem, and 80% of fatal falls occur in low-income and middle-income countries. We aimed to measure time from injury to hip-fracture surgery in people aged 50 years or older living in low-income and middle-income regions, as well as to measure the proportion of patients with surgical stabilisation of their hip fracture within 72 h of admission to hospital and to identify risk factors associated with surgical delay. Methods: For this secondary analysis, we analysed data collected from Africa, Latin America, China, India, and Asia (excluding China and India) for the International Orthopaedic Multicentre Study in Fracture Care (INORMUS) between March 29, 2014, and June 15, 2022. Patients from INORMUS were included in this analysis if they were aged 50 years or older and had an isolated, primary hip fracture sustained from a ground-level fall. Staff at participating hospitals identified patients with musculoskeletal injury and referred them for assessment of eligibility. We report time from injury to surgery as three distinct time periods: time from injury to hospital admission, time from admission to surgery, and a total time from injury to surgery. Date and time of injury were self-reported by patients at the time of study recruitment. If time to hospital admission after injury exceeded 24 h, patients reported the primary reason for delayed admission. Reasons for surgery, no surgery, and surgical delay were reported by the treating team. For patients undergoing surgery, multivariable regression analyses were used to identify risk factors for surgical delay. Findings: 4486 adults aged 50 years or older with an isolated, primary hip fracture were enrolled in INORMUS from 55 hospitals in 24 countries. Countries were grouped into five regions: Africa (418 [9·3%] of 4486), Latin America (558 [12·4%]), China (1680 [37·4%]), India (1059 [23·6%]) and Asia (excluding China and India; 771 [17·2%]). Of 4486 patients, 3805 (84·8%) received surgery. The rate of surgery was similar in all regions except in Africa, where only 193 (46·3%) of 418 patients had surgery. Overall, 2791 (62·2%) of 4486 patients were admitted to hospital within 24 h of injury. However, 1019 (22·7%) of 4486 patients had delayed hospital admission of 72 h or more from injury. The two most common reasons for delayed admission of more than 24 h were transfer from another hospital (522 [36·2%] of 1441) and delayed care-seeking because patients thought the injury would heal on its own (480 [33·3%]). Once admitted to hospital, 1451 (38·1%) of 3805 patients who received surgery did so within 72 h (median 4·0 days [IQR 1·7–6·0]). Regional variation was seen in the proportion of patients receiving surgery within 72 h of hospital admission (92 [17·9%] of 514 in Latin America, 53 [27·5%] of 193 in Africa, 454 [30·9%] of 1471 in China, 318 [44·4%] of 716 in Asia [excluding China and India], and 534 [58·6%] of 911 in India). Of all 3805 patients who received operative treatment, 2353 (61·8%) waited 72 h or more from hospital admission. From time of injury, the proportion of patients who were surgically stabilised within 72 h was 889 (23·4%) of 3805 (50 [9·7%] of 517 in Latin America, 31 [16·1%] of 193 in Africa, 277 [18·8%] of 1471 in China, 189 [26·4%] of 716 in Asia [excluding China and India], and 342 [37·5%] of 911 in India). Interpretation: Access to surgery within 72 h of hospital admission was poor, with factors that affected time to surgery varying by region. Data are necessary to understand existing pathways of hip-fracture care to inform the local development of quality-improvement initiatives. Funding: The National Health and Medical Research Council of Australia, the Canadian Institutes of Health Research, McMaster Surgical Associates, Hamilton Health Sciences, and the US National Institutes of Health.

Di-hexyl phthalate (2-ethylhexyl) (DEHP) has been confirmed to cause female reproductive toxicity in humans and model animals by affecting the survival of ovarian granulosa cells (GCs), but the interrelationships between DEHP's on autophagy, apoptosis, and inflammation in GCs are not clear. Our previous study demonstrated that DEHP exposure resulted in the disturbance of intestinal flora associated with serum LPS release, which in turn led to impaired ovarian function. LPS has also been shown to determine cell fate by modulating cellular autophagy, apoptosis, and inflammation. Therefore, this study investigated the role and link between LPS and autophagy, apoptosis, and inflammation of GCs in DEHP-induced ovarian injury. Here, we constructed an in vivo injury model by continuous gavage of 0–1500 mg/kg of DEHP in female mice for 30 days and an in vitro injury model by treatment of human ovarian granulosa cells (KGN) cells with mono-2- ethylhexyl ester (MEHP, an active metabolite of DEHP in vivo). In addition, the expression of relevant pathway molecules was detected by immunohistochemistry, immunofluorescence, qRT-PCR, and Western blotting after the addition of the autophagy inhibitor 3-methyladenine (3-MA), the apoptosis inhibitor Z-VAD- FMK and the NF-κB inhibitor BAY11-7082. The current study found that autophagy and apoptosis were significantly activated in GCs of DEHP-induced atretic follicles in vivo and found that MEHP-induced KGN cells autophagy and apoptosis were independent and potentially cytotoxic of each other in vitro. Further studies confirmed that DEHP exposure resulted in LPS release from the intestinal tract and entering the ovary, thereby participating in DEHP-induced inflammation of GCs. In addition, we found that exogenous LPS synergized with MEHP could activate the NF-κB signaling pathway to induce inflammation and apoptosis of GCs in a relatively prolonged exposure condition. Meanwhile, inhibition of inflammatory activation could rescue apoptosis and estrogen secretion function of GCs induced by MEHP combined with LPS. These results indicated that the increased LPS influenced by DEHP might cooperate with MEHP to induce inflammatory apoptosis of GCs, an important cause of ovarian injury in mice.

Abstract Background The endoplasmic reticulum (ER) regulates critical processes, including lipid synthesis, which are affected by transmembrane proteins localized in the ER membrane. One such protein, transmembrane protein 147 (TMEM147), has recently been implicated for its role in hepatocellular carcinoma (HCC) tumorigenesis; however, the mechanisms remain unclear. We investigated the role of TMEM147 in HCC and the underlying mechanisms. Methods TMEM147 expression was examined in human HCC cells and adjacent non-tumorous tissues using quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. In vitro and in vivo studies were conducted to investigate the impact of TMEM147 on the progression of HCC. Proteins interacting with TMEM147 were identified via RNA-seq, immunoprecipitation, and mass spectrometry analyses. Lipidomic analysis and enzyme-linked immunosorbent assay (ELISA) were employed to determine and analyze cholesterol and 27-hydroxycholesterol (27HC) contents. Extensive experimental techniques were used to study ferroptosis in HCC cells. The fatty acid content of macrophages affected by TMEM147 was quantified using ELISA. Macrophage phenotypes were determined using immunofluorescence assay and flow cytometric analysis. Results TMEM147 mRNA and protein levels were increased in HCC cells, and the increased TMEM147 expression was associated with a poor survival. TMEM147 promoted tumor cell proliferation and metastases in vitro and in vivo. The protein was found to interact with the key enzyme 7-dehydrocholesterol reductase (DHCR7), which affected cellular cholesterol homeostasis and increased the extracellular levels of 27HC in HCC cells. TMEM147 also promoted the expression of DHCR7 by enhancing the activity of signal transducer and activator of transcription 2. 27HC expression upregulated glutathione peroxidase 4 in HCC, leading to ferroptosis resistance and promotion of HCC proliferation. HCC cell-derived 27HC expression increased the lipid metabolism in macrophages and activated peroxisome proliferator-activated receptor-γ signaling, thereby activating M2 macrophage polarization and promoting HCC cell invasion and migration. Conclusions Our results indicate that TMEM147 confers ferroptosis resistance and M2 macrophage polarization, which are primarily dependent on the upregulation of cellular cholesterol homeostasis and 27HC secretion, leading to cancer growth and metastasis. These findings suggest that the TMEM147/STAT2/DHCR7/27HC axis in the tumor microenvironment may serve as a promising therapeutic target for HCC. Graphical Abstract

Abstract Background Premature ovarian failure (POF) is one of the leading causes of female infertility and is accompanied by abnormal endocrine, seriously affecting female quality of life. Previous studies have demonstrated that mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for POF. However, the mechanism remains obscure. This study aims to investigate the therapeutic effect of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on ovarian function in the POF rat model and explore the underlying mechanisms. Methods The ovarian function was evaluated by ovarian morphology, histology, estrous cycle, hormone levels (AMH, E2, FSH, and LH), and fertility ability to investigate the effect of hUC-MSCs on the POF rats model. The cytokines levels were assayed in serum using protein array to explore the mechanisms of hUC-MSCs therapy for POF. The excessive autophagy levels were evaluated using a co-culture system of 3D MSCs spheroids with human ovarian granulosa cell line (KGN) or primary ovarian granulosa cells (GCs) to understand the paracrine effect of hUC-MSCs on GCs. The related proteins expression of autophagy and PI3K/AKT/mTOR pathway was detected using Western Blotting and/or in various inhibitors supplement to further demonstrate that vascular endothelial growth factor A (VEGFA) secreted by hUC-MSCs can alleviate excessive autophagy of ovarian GCs via PI3K/AKT/mTOR signaling pathway. The ovarian culture model in vitro was applied to confirm the mechanism. Results The ovarian function of POF and the excessive autophagy of ovarian GCs were restored after hUC-MSCs transplantation. The protein array result demonstrated that VEGF and PI3K/AKT might improve ovarian function. in vitro experiments demonstrated that VEGFA secreted by hUC-MSCs could decrease oxidative stress and inhibit excessive autophagy of ovarian GCs via PI3K/AKT/mTOR pathway. The ovarian culture model results confirmed this mechanism in vitro. Conclusion The hUC-MSCs can alleviate excessive autophagy of ovarian GCs via paracrine VEGFA and regulate the PI3K/AKT/mTOR signaling pathway, thereby improving the ovarian function of POF.

Abstract Background As the population ages, mild cognitive impairment (MCI) and type 2 diabetes mellitus (T2DM) become common conditions that often coexist. Evidence has shown that MCI could lead to reduced treatment compliance, medication management, and self‐care ability in T2DM patients. Therefore, early identification of those with increased risk of MCI is crucial from a preventive perspective. Given the growing utilization of decision trees in prediction of health‐related outcomes, this study aimed to identify MCI in T2DM patients using the decision tree approach. Methods This hospital‐based case–control study was performed in the Endocrinology Department of Xiangya Hospital affiliated to Central South University between March 2021 and December 2022. MCI was defined based on the Petersen criteria. Demographic characteristics, lifestyle factors, and T2DM‐related information were collected. The study sample was randomly divided into the training and validation sets in a 7:3 ratio. Univariate and multivariate analyses were performed, and a decision tree model was established using the chi‐square automatic interaction detection (CHAID) algorithm to identify key predictor variables associated with MCI. The area under the curve (AUC) value was used to evaluate the performance of the established decision tree model, and the performance of multivariate regression model was also evaluated for comparison. Results A total of 1001 participants (705 in the training set and 296 in the validation set) were included in this study. The mean age of participants in the training and validation sets was 60.2 ± 10.3 and 60.4 ± 9.5 years, respectively. There were no significant differences in the characteristics between the training and validation sets (p > .05). The CHAID decision tree analysis identified six key predictor variables associated with MCI, including age, educational level, household income, regular physical activity, diabetic nephropathy, and diabetic retinopathy. The established decision tree model had 15 nodes composed of 4 layers, and age is the most significant predictor variable. It performed well (AUC = .75 [95% confidence interval (CI): .71–.78] and .67 [95% CI: .61–.74] in the training and validation sets, respectively), was internally validated, and had comparable predictive value compared to the multivariate logistic regression model (AUC = .76 [95% CI: .72–.80] and .69 [95% CI: .62–.75] in the training and validation sets, respectively). Conclusion The established decision tree model based on age, educational level, household income, regular physical activity, diabetic nephropathy, and diabetic retinopathy performed well with comparable predictive value compared to the multivariate logistic regression model and was internally validated. Due to its superior classification accuracy and simple presentation as well as interpretation of collected data, the decision tree model is more recommended for the prediction of MCI in T2DM patients in clinical practice.

Abstract Autism spectrum disorder (ASD) presents a significant risk to human well‐being and has emerged as a worldwide public health concern. Twenty‐eight children with ASD and 33 healthy children (HC) were selected for the quantitative determination of their plasma metabolites using an ultraperformance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) platform. A total of 1997 metabolites were detected in the study cohort, from which 116 metabolites were found to be differentially expressed between the ASD and HC groups. Through analytical algorithms such as least absolute shrinkage selection operator (LASSO), support vector machine (SVM), and random forest (RF), three potential metabolic markers were identified as FAHFA (18:1(9Z)/9‐O‐18:0), DL‐2‐hydroxystearic acid, and 7(S),17(S)‐dihydroxy‐8(E),10(Z),13(Z),15(E),19(Z)‐docosapentaenoic acid. These metabolites demonstrated superior performance in distinguishing the ASD group from the HC group, as indicated by the area under curves (AUCs) of 0.935, 0.897, and 0.963 for the three candidate biomarkers, respectively. The samples were divided into training and validation sets according to 7:3. Diagnostic models were constructed using logistic regression (LR), SVM, and RF. The constructed three‐biomarker diagnostic model also exhibited strong discriminatory efficacy. These findings contribute to advancing our understanding of the underlying mechanisms involved in the occurrence of ASD and provide a valuable reference for clinical diagnosis.

Objectives Type 2 diabetes mellitus (T2DM) is a serious public health issue. Compared with the general population, patients with T2DM have a higher risk of poor sleep quality, which could ultimately result in poor prognosis. Therefore, this study aimed to evaluate sleep quality and its associated factors among patients with T2DM in Hunan, China.Design This was a cross-sectional study.Setting A tertiary hospital in Hunan, China.Participants Patients with T2DM hospitalised at the Endocrinology Department were consecutively enrolled between March 2021 and December 2022. Sociodemographic characteristics, lifestyle factors and T2DM-related information were collected retrospectively.Primary and secondary outcome measures Sleep quality was evaluated using the Pittsburgh Sleep Quality Index, with a cut-off value of >7 suggesting poor sleep quality. Multivariate logistic regression analysis was used to determine factors associated with poor sleep quality.Results Of the 1039 participants included, 1001 provided complete data. The mean age of the study sample was 60.24±10.09 years, and 40.5% (95% CI 37.5% to 43.5%) of patients had poor sleep quality. Multivariate logistic regression analysis showed that female sex (adjusted OR (aOR) 1.70, 95% CI 1.25 to 2.29), unmarried status (aOR 1.72, 95% CI 1.05 to 2.83), diabetic retinopathy (aOR 1.38, 95% CI 1.04 to 1.83), diabetic foot (aOR 1.80, 95% CI 1.11 to 2.93) and a per capita monthly household income of >5000 RMB (aOR 0.66, 95% CI 0.47 to 0.93) were associated with poor sleep quality.Conclusions Nearly two-fifths of patients with T2DM reported poor sleep quality in Hunan, China. Sex, marital status, diabetic retinopathy, diabetic foot and household income were independently associated with sleep quality among patients with T2DM in Hunan, China.

Abstract Background Type 2 diabetes mellitus (T2DM) is highly prevalent worldwide and may lead to a higher rate of cognitive dysfunction. This study aimed to develop and validate a nomogram‐based model to detect mild cognitive impairment (MCI) in T2DM patients. Methods Inpatients with T2DM in the endocrinology department of Xiangya Hospital were consecutively enrolled between March and December 2021. Well‐qualified investigators conducted face‐to‐face interviews with participants to retrospectively collect sociodemographic characteristics, lifestyle factors, T2DM‐related information, and history of depression and anxiety. Cognitive function was assessed using the Mini‐Mental State Examination scale. A nomogram was developed to detect MCI based on the results of the multivariable logistic regression analysis. Calibration, discrimination, and clinical utility of the nomogram were subsequently evaluated by calibration plot, receiver operating characteristic curve, and decision curve analysis, respectively. Results A total of 496 patients were included in this study. The prevalence of MCI in T2DM patients was 34.1% (95% confidence interval [CI]: 29.9%–38.3%). Age, marital status, household income, diabetes duration, diabetic retinopathy, anxiety, and depression were independently associated with MCI. Nomogram based on these factors had an area under the curve of 0.849 (95% CI: 0.815–0.883), and the threshold probability ranged from 35.0% to 85.0%. Conclusions Almost one in three T2DM patients suffered from MCI. The nomogram, based on age, marital status, household income, duration of diabetes, diabetic retinopathy, anxiety, and depression, achieved an optimal diagnosis of MCI. Therefore, it could provide a clinical basis for detecting MCI in T2DM patients.

Di-(2-ethylhexyl) phthalate (DEHP) is widely used in various plastics but has been demonstrated to cause female reproductive toxicity. However, the exact mechanism underlying the ovarian damage induced by DEHP remains unclear. In this study, DEHP was administered orally to 5-week-old female mice for 30 days at doses of 0, 250, 500, and 1000 mg/kg/day. The findings demonstrated that DEHP exposure disrupted ovarian function and follicular development as well as induced oxidative stress and autophagy in ovarian granulosa cells (GCs). Further, 200 µM mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP in vivo, induced autophagy in both human ovarian granulosa cells line (KGN) and mouse primary GCs within 24 h in vitro. However, it did not affect the p62-dependent autophagy flux. Furthermore, MEHP-induced autophagy was inhibited by the autophagy inhibitor 3-MA and exacerbated by the autophagy activator rapamycin, indicating that MEHP induces excessive autophagy in GCs. Subsequently, we found that MEHP-induced autophagic cell death was primarily attributed to oxidative damage from elevated intracellular ROS levels. Meanwhile, MEHP exposure induced nuclear translocation of erythroid-derived factor 2-related factor (Nrf2), a key regulator of antioxidant activity resulting in activating antioxidant effects. Interestingly, we also found that MEHP-induced increase in p62 competitively binds Keap1, thereby facilitating nuclear translocation of Nrf2 and establishing a positive feedback loop in antioxidant regulation. Therefore, this study demonstrated that inhibition of Nrf2 could aggravate oxidative damage and enhance excessive autophagy caused by MEHP, while activation of Nrf2 could reverse the trend. These findings have also been reinforced in studies of cultured ovaries in vitro. Our study suggests that the p62-Keap1-Nrf2 pathway may serve as a potential protective mechanism against DEHP-induced oxidative stress and excessive autophagy in mouse GCs.

Abstract Background Depression and diabetes are major health challenges, with heavy economic social burden, and comorbid depression in diabetes could lead to a wide range of poor health outcomes. Although many descriptive studies have highlighted the prevalence of comorbid depression and its associated factors, the situation in Hunan, China, remains unclear. Therefore, this study aimed to identify the prevalence of comorbid depression and associated factors among hospitalized type 2 diabetes mellitus (T2DM) patients in Hunan, China. Methods This cross-sectional study involved 496 patients with T2DM who were referred to the endocrinology inpatient department of Xiangya Hospital affiliated to Central South University, Hunan. Participants’ data on socio-demographic status, lifestyle factors, T2DM-related characteristics, and social support were collected. Depression was evaluated using the Hospital Anxiety and Depression Scale-depression subscale. All statistical analyses were conducted using the R software version 4.2.1. Results The prevalence of comorbid depression among hospitalized T2DM patients in Hunan was 27.22% (95% Confidence Interval [CI]: 23.3–31.1%). Individuals with depression differed significantly from those without depression in age, educational level, per capita monthly household income, current work status, current smoking status, current drinking status, regular physical activity, duration of diabetes, hypertension, chronic kidney disease, stroke, fatty liver, diabetic nephropathy, diabetic retinopathy, insulin use, HbA1c, and social support. A multivariable logistic regression model showed that insulin users (adjusted OR = 1.86, 95% CI: 1.02–3.42) had a higher risk of depression, while those with regular physical activity (adjusted OR = 0.48, 95% CI: 0.30–0.77) or greater social support (adjusted OR = 0.20, 95% CI: 0.11–0.34) had a lower risk of depression. The area under the curve of the receiver operator characteristic based on this model was 0.741 with a sensitivity of 0.785 and specificity of 0.615. Conclusions Depression was moderately prevalent among hospitalized T2DM patients in Hunan, China. Insulin treatment strategies, regular physical activity, and social support were significantly independently associated with depression, and the multivariable model based on these three factors demonstrated good predictivity, which could be applied in clinical practice.

Abstract Background To summarize the up-to-date empirical evidence on trial-level characteristics of randomized controlled trials associated with treatment effect estimates. Methods A systematic review searched three databases up to August 2020. Meta-epidemiological (ME) studies of randomized controlled trials on intervention effect were eligible. We assessed the methodological quality of ME studies using a self-developed criterion. Associations between treatment effect estimates and trial-level characteristics were presented using forest plots. Results Eighty ME studies were included, with 25/80 (31%) being published after 2015. Less than one-third ME studies critically appraised the included studies (26/80, 33%), published a protocol (23/80, 29%), and provided a list of excluded studies with justifications (12/80, 15%). Trials with high or unclear (versus low) risk of bias on sequence generation (3/14 for binary outcome and 1/6 for continuous outcome), allocation concealment (11/18 and 1/6), double blinding (5/15 and 2/4) and smaller sample size (4/5 and 2/2) significantly associated with larger treatment effect estimates. Associations between high or unclear risk of bias on allocation concealment (5/6 for binary outcome and 1/3 for continuous outcome), double blinding (4/5 and 1/3) and larger treatment effect estimates were more frequently observed for subjective outcomes. The associations between treatment effect estimates and non-blinding of outcome assessors were removed in trials using multiple observers to reach consensus for both binary and continuous outcomes. Some trial characteristics in the Cochrane risk-of-bias (RoB2) tool have not been covered by the included ME studies, including using validated method for outcome measures and selection of the reported results from multiple outcome measures or multiple analysis based on results (e.g., significance of the results). Conclusions Consistently significant associations between larger treatment effect estimates and high or unclear risk of bias on sequence generation, allocation concealment, double blinding and smaller sample size were found. The impact of allocation concealment and double blinding were more consistent for subjective outcomes. The methodological and reporting quality of included ME studies were dissatisfactory. Future ME studies should follow the corresponding reporting guideline. Specific guidelines for conducting and critically appraising ME studies are needed.

With downward scaling of the micro-bumps in three-dimensional integrated circuits, surface inter-diffusion becomes dominant, changing the kinetic path of intermetallic compounds (IMC) formation and causing serious reliability issues. However, an in-depth understanding of the surface inter-diffusion process and the corresponding influence on the formation mechanism of IMC in a micro-bump remain unclear. We conducted annealing at 170 ℃, over 16 h for pillar type Sn/Cu micro-bumps and observed a unique 2-step sidewall Cu3Sn IMC formation phenomenon on the FIB-cut clean surface of the micro-bumps. It is found the two-step sidewall IMC formation is dominated by the surface inter-diffusion of Sn and Cu atoms. Density functional theory calculations reveal that the activation energy barrier of nucleation for sidewall Cu3Sn IMC is about 1/3 of that of sidewall Cu6Sn5 on corresponding interfacial IMC layers, making the formation of sidewall Cu3Sn dominant. Moreover, we proposed a kinetic model that can predict the mean lateral growth rate of the sidewall IMC which may cause fatal short-circuit failure.

Sepsis after trauma increases the risk of mortality rate for patients in intensive care unit (ICUs). Currently, it is difficult to predict outcomes in individual patients with sepsis due to the complexity of causative pathogens and the lack of specific treatment. This study aimed to identify metabolomic biomarkers in patients with multiple trauma and those with multiple trauma accompanied with sepsis. Therefore, the metabolic profiles of healthy persons designated as normal controls (NC), multiple trauma patients (MT), and multiple trauma complicated with sepsis (MTS) (30 cases in each group) were analyzed with ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS)-based untargeted plasma metabolomics using collected plasma samples. The differential metabolites were enriched in amino acid metabolism, lipid metabolism, glycometabolism and nucleotide metabolism. Then, nine potential biomarkers, namely, acrylic acid, 5-amino-3-oxohexanoate, 3b-hydroxy-5-cholenoic acid, cytidine, succinic acid semialdehyde, PE [P-18:1(9Z)/16:1(9Z)], sphinganine, uracil, and uridine, were found to be correlated with clinical variables and validated using receiver operating characteristic (ROC) curves. Finally, the three potential biomarkers succinic acid semialdehyde, uracil and uridine were validated and can be applied in the clinical diagnosis of multiple traumas complicated with sepsis.

BackgroundThyroid carcinoma (THCA) has a low mortality rate, but its incidence has been rising over the years. We need to pay attention to its progression and prognosis. In this study, a transcriptome sequencing analysis and bioinformatics methods were used to screen key genes associated with THCA development and analyse their clinical significance and diagnostic value.MethodsWe collected 10 pairs of THCA tissues and noncancerous tissues, these samples were used for transcriptome sequencing to identify disordered genes. The gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Comprehensive analysis of thyroid clinicopathological data using The Cancer Genome Atlas (TCGA). R software was used to carry out background correction, normalization and log2 conversion. We used quantitative real-time PCR (qRT–PCR) and Western blot to determine differentially expressed genes (DEGs) expression in samples. We integrated the DEGs expression, clinical features and progression-free interval (PFI). The related functions and immune infiltration degree were established by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and single-sample Gene Set Enrichment Analysis (ssGSEA). The UALCAN database was used to analyse the methylation level.ResultsWe evaluated DEGs between normal tissue and cancer. Three genes were identified: regulator of G protein signaling 8 (RGS8), diacylglycerol kinase iota (DGKI) and oculocutaneous albinism II (OCA2). The mRNA and protein expression levels of RGS8, DGKI and OCA2 in normal tissues were higher than those in THCA tissues. Better survival outcomes were associated with higher expression of RGS8 (HR=0.38, P=0.001), DGKI (HR=0.52, P=0.022), and OCA2 (HR=0.41, P=0.003). The GO analysis, KEGG analysis and GSEA proved that the coexpressed genes of RGS8, DGKI and OCA2 were related to thyroid hormone production and peripheral downstream signal transduction effects. The expression levels of RGS8, DGKI and OCA2 were linked to the infiltration of immune cells such as DC cells. The DNA methylation level of OCA2 in cancer tissues was higher than that in the normal samples.ConclusionsRGS8, DGKI and OCA2 might be promising prognostic molecular markers in patients with THCA and reveal the clinical significance of RGS8, DGKI and OCA2 in THCA.

Background: The safety of prescribing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) during acute kidney injury (AKI) remains unclear. We aimed to investigate the associations of ACEI/ARB therapy in AKI with the risk of mortality, acute kidney disease (AKD), and hyperkalemia.Methods: We conducted a retrospective monocentric study, which included patients in Massachusetts between 2008 and 2019 from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching was performed for the endpoint analysis. The association between ACEI/ARB therapy and mortality was assessed using Cox proportional hazards regression models. Logistic regression was used to assess the risk of AKD and hyperkalemia.Results: Among the 19,074 individuals with AKI admitted to the intensive care unit (ICU), 3,244 (17.0%) received ACEI/ARBs, while 15,830 (83.0%) did not. In the propensity score-matched sample of 6,358 individuals, we found a decreased risk of mortality in those who received ACEI/ARBs compared to those who did not (hazard ratio [HR] for ICU mortality: 0.34, 95% confidence interval [CI]: 0.27–0.42); HR for in-hospital mortality: 0.47, 95% CI: 0.39–0.56; HR for 30-day mortality: 0.47, 95% CI: 0.40–0.56; HR for 180-day mortality: 0.53, 95% CI: 0.45–0.62). However, the use of ACEI/ARBs was associated with a higher risk of AKD (risk ratio [RR]: 1.81; 95% CI: 1.55–2.12). There was no significant association between ACEI/ARBs and an increased risk of hyperkalemia (RR: 1.21; 95% CI: 0.96–1.51).Conclusions: ACEI/ARB treatment during an episode of AKI may decrease all-cause mortality, but increases the risk of AKD. Future randomized controlled trials are warranted to validate these findings.

Objective: Previous studies have suggested that blood pressure variability (BPV) is associated with an increased risk of mortality and cardiovascular events in patients on dialysis. However, the results are inconsistent. A comprehensive literature review was conducted to analyze the association between BPV and outcomes in patients on dialysis. Methods: Articles in Embase, Medline, and Web of Science from the date of inception through January 1, 2020, were identified. The outcomes were all-cause and cardiovascular mortality and cardiovascular events. The risk of bias was assessed using the Newcastle-Ottawa scale tool. Random effects models were used to pool the overall effect sizes. Two reviewers extracted the data independently. Meta-regression and subgroup analyses were performed to explore potential heterogeneity. Results: Fifteen eligible studies were included, and all enrolled hemodialysis recipients only. The overall risk of bias for the included studies was low. A 1-SD increase in systolic BPV was associated with higher risks of all-cause mortality (HR = 1.18; 95% CI 1.11–1.26, I2 = 53.8%), cardiovascular mortality (HR = 1.23; 95% CI 1.10–1.37, I2 = 57.2%), and cardiovascular events (HR = 1.27; 95% CI 1.07–1.51, I2 = 69.3%). Likewise, a 1-SD increase in diastolic BPV was associated with higher HR for all-cause and cardiovascular mortality (HR = 1.14; 95% CI 1.05–1.23, I2 = 0.0%, and HR = 1.14; 95% CI 0.94–1.38, I2 = 0.0%, respectively). Conclusions: A greater BPV is associated with higher risks of cardiovascular and mortality outcomes in patients on hemodialysis. Further research is required to determine whether BPV may be useful either as a marker enabling individualized treatment of cardiovascular risk or as a treatment target in its own right.

Objective The effect of the serum chloride (Cl) level on mortality in critically ill patients with acute kidney injury (AKI) remains unknown. We sought an association between mortality and serum Cl. Methods We identified AKI patients in the eICU Collaborative Research Database from 2014 to 2015 at 208 US hospitals. The outcomes included in-hospital and intensive care unit (ICU) mortality. Time-varying covariates Cox regression models and the Kaplan-Meier (K-M) curves were used to assess the association between serum Cl levels and mortality. Multivariable adjusted restricted cubic spline models were used to analyze the potential nonlinear relationship between mortality and serum Cl. Results In total, 4,234 AKI patients were included in the study. Compared with normochloremia (98≤chlorideConclusions Lower serum Cl levels after ICU admission was associated with increased in-hospital and ICU mortality in critically ill patients with AKI. The results should be verified in well-designed prospective studies.

ObjectiveThe effect of the serum chloride (Cl) level on mortality in critically ill patients with acute kidney injury (AKI) remains unknown. We sought an association between mortality and serum Cl.MethodsWe identified AKI patients in the eICU Collaborative Research Database from 2014 to 2015 at 208 US hospitals. The outcomes included in-hospital and intensive care unit (ICU) mortality. Time-varying covariates Cox regression models and the Kaplan-Meier (K-M) curves were used to assess the association between serum Cl levels and mortality. Multivariable adjusted restricted cubic spline models were used to analyze the potential nonlinear relationship between mortality and serum Cl.ResultsIn total, 4,234 AKI patients were included in the study. Compared with normochloremia (98≤chlorideConclusionsLower serum Cl levels after ICU admission was associated with increased in-hospital and ICU mortality in critically ill patients with AKI. The results should be verified in well-designed prospective studies.

Mounting evidence has linked air pollution with dementia and temperature modifies the association of air pollution with other disease. However, their interactions on dementia are unclear. We used a prospective cohort study (the UK Biobank) included 498 660 adults without cognitive impairment or dementia at baseline and followed up for 11.50 years (5734 907 person-years). We applied Cox proportional hazards regression with time-varying exposures to examine the effects of air pollutants [particulate matter (PM _2.5 , PM _10 ), nitrogen oxides (NO _2 , NO _X ) and sulphur dioxide (SO _2 )], the mean and variability of seasonal temperature, and their interactions on dementia. During the follow-up time, we ascertained 4119 cases of dementia. We observed a higher hazard of incident dementia for 1 μ g m ^−3 increase in SO _2 (hazard ratio [HR] = 1.11; 95% confidence interval [CI]: 1.08, 1.14), NO _2 (HR [95% CI] = 1.02 [1.01, 1.02]), NO _X (HR [95% CI] = 1.01 [1.00, 1.01]), PM _2.5 (HR [95% CI] = 1.03 [1.02, 1.05]), and PM _10 (HR HR [95% CI] = 1.02 [1.00, 1.03]). A lower risk of dementia in summertime temperature variability (HR for 1 °C increment above 1.27 °C = 0.61; 95% CI: 0.51, 0.72) was found. We observed a nonlinear relationship between higher risk of dementia and higher summer temperatures, and strong U-shaped relation of both wintertime temperature and wintertime temperature variability with dementia. We found the significantly synergistic effect between SO _2 and summertime temperature ( p < 0.001), the antagonistic effect between NO _2 ( p = 0.043), NO _X ( p = 0.026) and summertime temperature variability. Participants in a lower social economic position dominated susceptibility in temperature-air pollution interaction on dementia. In conclusion, some evidence of interactive effects between summer temperature and air pollutants was found, but no consistent interaction could be identified during the winter. Our study added weight to the evidence of air pollutants, temperature and their interaction on the onset of dementia.

In the present study, the complete mitogenome sequence of a Acanthorhodeus chankaensis Dybowsky from Cao’e River was sequenced and identified. The assembled mitogenome of A. chankaensis is 16,676 bp in length, it contains 22 transfer-RNA genes, 13 protein-coding genes, 2 ribosomal-RNA genes, and 2 non-coding regions. It shows conserved gene arrangement with other Cyprinidae fishes. The overall nucleotide composition of A. chankaensis mitogenome sequence is A: 28.96%, G: 17.11%, T: 27.46%, and C: 26.47%. The phylogenetic analysis showed that the complete mitogenome could contribute to the phylogenetic analyses and population genetics study of A. chankaensis and Acanthorhodeus fish.

T-cell function impairment is one of the major determinants of tumour immune evasion. Here, the authors show that the hostile conditions in the tumour microenvironment lead to C/EBP homologous-protein upregulation in T cells via ER stress, resulting in repression of T-bet and consequent inhibition of CD8+ T cell function.”

SLC41A3, as a member of the 41st family of solute carriers, participates in the transport of magnesium. The role of SLC41A3 in cancer prognosis and immune regulation has rarely been reported. This study was designed to analyze the expression status and prognostic significance of SLC41A3 in pan-cancers. The mRNA expression profiles of SLC41A3 were obtained from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), the Broad Institute Cancer Cell Line Encyclopedia (CCLE), and the International Cancer Genome Consortium (ICGC). The Cox regression and Kaplan-Meier analyses were used to evaluate the prognostic value of SLC41A3 in pan-cancer. Furthermore, the correlation between SLC41A3 expression and immune cells infiltration, immune checkpoint, mismatch repair (MMR), DNA methyltransferase (DNMT), tumor mutation burden (TMB), and microsatellite instability (MSI) were calculated using data form TCGA database. The results showed that the expression of SLC41A3 was down-regulated in kidney renal clear cell carcinoma (KIRC), and was associated with poor overall survival and tumor-specific mortality. Whereas, the expression of SLC41A3 was up-regulated in liver hepatocellular carcinoma (LIHC), and the results of Cox regression analysis revealed that SLC41A3 was an independent factor for LIHC prognosis. Meanwhile, a nomogram including SLC41A3 and stage was built and exhibited good predictive power for the overall survival of LIHC patients. Additionally, correlation analysis suggested a significant correlation between SLC41A3 and TMB, MSI, MMR, DNMT, and immune cells infiltration in various cancers. The overall survival and disease-specific survival analysis revealed that the combined SLC41A3 expression and immune cell score, TMB, and MSI were significantly associated with clinical outcomes in ACC, LIHC, and UVM patients. Therefore, we proposed that SLC41A3 may serve as a potential prognostic biomarker for cancer.

Summary: Background: The Lancet Commission on Global Surgery established the Three Delays framework, categorising delays in accessing timely surgical care into delays in seeking care (First Delay), reaching care (Second Delay), and receiving care (Third Delay). Globally, knowledge gaps regarding delays for fracture care, and the lack of large prospective studies informed the rationale for our international observational study. We investigated delays in hospital admission as a surrogate for accessing timely fracture care and explored factors associated with delayed hospital admission. Methods: In this prospective observational substudy of the ongoing International Orthopaedic Multicenter Study in Fracture Care (INORMUS), we enrolled patients with fracture across 49 hospitals in 18 low-income and middle-income countries, categorised into the regions of China, Africa, India, south and east Asia, and Latin America. Eligible patients were aged 18 years or older and had been admitted to a hospital within 3 months of sustaining an orthopaedic trauma. We collected demographic injury data and time to hospital admission. Our primary outcome was the number of patients with open and closed fractures who were delayed in their admission to a treating hospital. Delays for patients with open fractures were defined as being more than 2 h from the time of injury (in accordance with the Lancet Commission on Global Surgery) and for those with closed fractures as being a delay of more than 24 h. Secondary outcomes were reasons for delay for all patients with either open or closed fractures who were delayed for more than 24 h. We did logistic regression analyses to identify risk factors of delays of more than 2 h in patients with open fractures and delays of more than 24 h in patients with closed fractures. Logistic regressions were adjusted for region, age, employment, urban living, health insurance, interfacility referral, method of transportation, number of fractures, mechanism of injury, and fracture location. We further calculated adjusted relative risk (RR) from adjusted odds ratios, adjusted for the same variables. This study was registered with ClinicalTrials.gov, NCT02150980, and is ongoing. Findings: Between April 3, 2014, and May 10, 2019, we enrolled 31 255 patients with fractures, with a median age of 45 years (IQR 31–62), of whom 19 937 (63·8%) were men, and 14 524 (46·5%) had lower limb fractures, making them the most common fractures. Of 5256 patients with open fractures, 3778 (71·9%) were not admitted to hospital within 2 h. Of 25 999 patients with closed fractures, 7141 (27·5%) were delayed by more than 24 h. Of all regions, Latin America had the greatest proportions of patients with delays (173 [88·7%] of 195 patients with open fractures; 426 [44·7%] of 952 with closed fractures). Among patients delayed by more than 24 h, the most common reason for delays were interfacility referrals (3755 [47·7%] of 7875) and Third Delays (cumulatively interfacility referral and delay in emergency department: 3974 [50·5%]), while Second Delays (delays in reaching care) were the least common (423 [5·4%]). Compared with other methods of transportation (eg, walking, rickshaw), ambulances led to delay in transporting patients with open fractures to a treating hospital (adjusted RR 0·66, 99% CI 0·46–0·93). Compared with patients with closed lower limb fractures, patients with closed spine (adjusted RR 2·47, 99% CI 2·17–2·81) and pelvic (1·35, 1·10–1·66) fractures were most likely to have delays of more than 24 h before admission to hospital. Interpretation: In low-income and middle-income countries, timely hospital admission remains largely inaccessible, especially among patients with open fractures. Reducing hospital-based delays in receiving care, and, in particular, improving interfacility referral systems are the most substantial tools for reducing delays in admissions to hospital. Funding: National Health and Medical Research Council of Australia, Canadian Institutes of Health Research, McMaster Surgical Associates, and Hamilton Health Sciences.

OBJECTIVE:Previous studies have shown that visit-to-visit blood pressure variability (BPV) is associated with chronic kidney disease (CKD). However, the results have not been consistent among studies. This systematic review and meta-analysis was conducted to comprehensively assess the association between visit-to-visit BPV and the risk of CKD. METHODS:Medline, Embase, and the Cochrane Library were searched from the date of inception through 1 August 2019 using the terms "blood pressure variability," "chronic kidney disease," "nephropathy," and other comparable terms. The primary outcome was the development of CKD. Two reviewers extracted the data independently. Meta-analysis was performed using a random effects model. RESULTS:Fourteen studies were included in the systematic review and meta-analysis. The risk of CKD was significantly greater in patients with high baseline systolic blood pressure variability (SBPV) than in patients with low baseline SBPV: the standard deviation (SD) showed relative risk (RR) of 1.69 and 95% CI of 1.38-2.08, the coefficient of variation (CV) showed RR of 1.23 and 95% CI of 1.12-1.36, and variance independent of mean (VIM) showed RR of 1.40 and 95% CI of 1.15-1.71. RRs for each unit increase in visit-to-visit SBPV and risk of CKD were 1.05 (95% CI: 1.03-1.07) for SD, 1.06 (95% CI: 1.03-1.09) for CV, and 1.1 (95% CI: 0.96-1.25) for VIM. Diastolic BPV was similarly predictive of CKD based on SD and CV. CONCLUSIONS:Increased visit-to-visit BPV might be an independent risk factor for CKD. However, significant heterogeneity was present; thus, future prospective studies are needed to confirm our findings. Our results indicate that treatment of hypertension should control blood pressure levels and prevent abnormal fluctuations in blood pressure to reduce the risk of CKD.

Abstract Background Road traffic accident (RTA), an unexpected traumatic event, may not only lead to death and serious physical injuries, but also could put survivors at an increased risk for a wide range of psychiatric disorders, particularly acute stress disorder (ASD). Early assessment of trauma-related psychological responses is important because acute trauma responses in the early post-traumatic period are among the robust predictors of long-term mental health problems. However, estimates of the prevalence of ASD among RTA survivors varied considerably across studies. Therefore, this meta-analysis aimed to identify the pooled prevalence of ASD among RTA survivors. Methods A systematic literature search in the databases of PubMed, PsycINFO, PsycARTICLES, Embase and Web of Science was performed from their inception dates to December 2017. Subject headings were used to identify relevant articles, and the search strategy was adjusted across databases. Heterogeneity across studies was evaluated by Cochran’s χ 2 test and quantified by the I 2 statistic. Subgroup analyses were performed to identify the pooled prevalence in relation to the country of study, instrument used to identify ASD, age, gender and traumatic brain injury. When significant heterogeneity was observed, the influence of some potential moderators was explored using meta-regression analyses. Results Thirteen eligible studies conducted in 8 countries were included. A total of 2989 RTA survivors were assessed, of which 287 were identified with ASD. The overall heterogeneity was high across studies (I 2=96.8%, P

Abstract Background The p.R4810K and other rare variants of ring finger protein 213 gene (RNF213) were illustrated as susceptibility variants for moyamoya (MMD) and non-moyamoya intracranial artery stenosis/occlusion disease (ICASO) recently. However, the effect sizes of p.R4810K were in great discrepancy even in studies of the same ethnic population and firm conclusions of other rare variants have been elusive given the small sample sizes and lack of replication. Thus, we performed this study to quantitatively evaluate whether or to what extent the rare variants of RNF213 contribute to MMD and ICASO in different populations. Methods A systematic search of PubMed, EMBASE, ISI web of science, CNKI, and WANFANG DATA was conducted up to 5 September 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effect models based on the between-study heterogeneity. The subgroup analyses were performed by the ethnicity and family history. Sensitivity and publication bias analysis were performed to test the robustness of associations. All the statistical analyses were conduct using STATA 12.0. Results Twenty studies including 2353 MMD cases and 5488 controls and 11 studies including 1778 ICASO cases and 3140 controls were included in this study. Pooled ORs indicated that RNF213 p.R4810K significantly increased MMD and ICASO risk in East Asians with great effect sizes of discrepancy (dominant model: odds ratios 184.04, 109.77, and 31.53 and 10.07, 28.52, and 5.59 for MMD and ICASO, respectively, in Japan, Korea, and China). It significantly increased familial MMD risk in Japan, Korea, and China with 5 ~ 36 times larger effect sizes than that for sporadic ones in each country (dominant model ORs 1802.44, 512.42, 1109.02 and 134.35, 99.82, and 30.52, respectively, for familial and sporadic cases). The effect sizes of RNF213 p.R4810K to sporadic MMD were 3 ~ 4 times larger in Japan and Korea than those in China. RNF213 p.R4810K also increased the ICASO risk in Japan and Korea with 2 ~ 4 times larger effect sizes than that in China (dominant model ORs 10.71, 28.52, and 5.59, respectively). Another two rare variants- p.E4950D and p.A5021V significantly increased MMD risk in Chinese population (dominant model ORs 9.06 and 5.01, respectively). Various other rare variants in RNF213 were identified in Japanese, Chinese, European, and Hispanic American populations without association evidence available yet. Conclusions This meta-analysis shows the critical roles of RNF213 p.R4810K in MMD especially familial MMD and ICASO in Japan, Korea, and China. Except for RNF213 p.R4810K, MMD seems to have more complex determiners in China. Distinct genetic background exists and other environmental or genetic factor(s) may contribute to MMD. Studies focused on delineating the ethnicity-specific factors and pathological role of RNF213 variants in MMD and ICASO are needed.

Background/Aims: Shikonin, a compound extracted from Zicao, has been demonstrated to hold anti-bacterial, anti-inflammatory, and anti-tumor activities in various diseases and it has been shown to protect human organs from injuries. However, the effect of shikonin on the recovery of spinal cord injury (SCI) remains unknown. This study was designed to estimate the potential therapeutic effect and underlying mechanism of shikonin on SCI in vivo. Methods: In the study, we used HE staining, ELISA assay, transfection assay, TUNEL assay, real time PCR and Western blot to detect the effects of shikonin on spinal cord injury in rats. Results: we showed that shikonin could promote the recovery of motor function and tissue repair after SCI treatment in rats SCI model. Moreover, we demonstrated that shikonin inhibited the spinal cord edema in SCI model of rats. According to further investigation, shikonin induced the reduction of inflammatory response through decreasing the expression levels of HMGB1, TLR4 and NF-κB after SCI injury. In addition, we also found that shikonin could suppress the apoptosis and expression of caspase-3 protein in SCI model of rats. Conclusion: Our results demonstrated that shikonin induced the recovery of tissue repair and motor function via inactivation of HMGB1/TLR4/NF-κB signaling pathway in SCI model of rats. Meanwhile, shikonin regulated the inflammation response in SCI by suppressing the HMGB1/TLR4/NF-κB signaling pathway. The described mechanism sheds novel light on molecular signaling pathway in spinal cord injury and secondary injury including inflammatory response.

Abstract Background Post-traumatic stress disorder (PTSD) is one of the most prevalent long-term psychiatric disorders among survivors of traumatic events. It is well established that social support has been related to the onset of PTSD after natural disasters. However, very little is known whether or not social support has had an influence on the recovery from the PTSD that was diagnosed after floods. This study, therefore, made a follow-up assessment of PTSD in flood victims 13–14 years after they were diagnosed with PTSD in 2000 to measure the prevalence rate of PTSD among them and identify the association between social support and their recovery from PTSD. Methods Victims who had experienced Dongting Lake flood in 1998 and had been diagnosed as having PTSD in 2000 were enrolled in this study. A follow-up survey was done between the years 2013 and 2014 to diagnose the victims again of PTSD using the DSM-IV criteria. Social support and its three dimensions were measured using the Chinese version of Social Support Rating Scale (SSRS), including objective support, subjective support and support utilization. Data were collected through face-to-face interviews using a structured questionnaire. Bivariate and multivariate logistic regression analyses were used to examine the relationship between social support and the recovery from PTSD after flood. Results Out of 321 subjects with prior PTSD, 51 (15.89 %) were diagnosed as still having PTSD. Logistic regression analyses indicated that the recovery from prior PTSD was significantly associated with social support (odds ratio (OR) =0.202, 95 % confidence interval (95 % CI): 0.047–0.878), subjective support (OR = 0.236, 95 % CI: 0.080–0.694) and support utilization (OR = 0.245, 95 % CI: 0.071–0.844). Conclusions The prevalence rate of current PTSD indicates that natural disasters, such as floods, may affect the mental health of victims for a long time. Social support was significantly associated with the recovery from prior PTSD, especially subjective support and support utilization.

BACKGROUND:Although numerous studies have indicated that exposure to natural disasters may increase survivors' risk of post-traumatic stress disorder (PTSD) and anxiety, studies focusing on the long-term psychological outcomes of flood survivors are limited. Thus, this study aimed to estimate the prevalence of PTSD and anxiety among flood survivors 17 years after the 1998 Dongting Lake flood and to identify the risk factors for PTSD and anxiety. METHODS:This cross-sectional study was conducted in December 2015, 17 years after the 1998 Dongting Lake flood. Survivors in hard-hit areas of the flood disaster were enrolled in this study using a stratified, systematic random sampling method. Well qualified investigators conducted face-to-face interviews with participants using the PTSD Checklist-Civilian version, the Zung Self-Rating Anxiety Scale, the Chinese version of the Social Support Rating Scale and the Revised Eysenck Personality Questionnaire-Short Scale for Chinese to assess PTSD, anxiety, social support and personality traits, respectively. Logistic regression analyses were used to identify factors associated with PTSD and anxiety. RESULTS:A total of 325 participants were recruited in this study, and the prevalence of PTSD and anxiety was 9.5% and 9.2%, respectively. Multivariable logistic regression analyses indicated that female sex, experiencing at least three flood-related stressors, having a low level of social support, and having the trait of emotional instability were risk factors for long-term adverse psychological outcomes among flood survivors after the disaster. CONCLUSIONS:PTSD and anxiety were common long-term adverse psychological outcomes among flood survivors. Early and effective psychological interventions for flood survivors are needed to prevent the development of PTSD and anxiety in the long run after a flood, especially for individuals who are female, experience at least three flood-related stressors, have a low level of social support and have the trait of emotional instability.

The design, synthesis and structure-activity relationship studies of some novel trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are described. The activities of these compounds were evaluated by the CCR4-MDC chemotaxis inhibition assay. Compound 1, which we have previously reported as a potent antagonist of CCR4, was employed as the positive control. The results indicated that most of the synthesized compounds exhibited some chemotaxis inhibition activity against CCR4. Of these new compounds, compounds 6c, 12a and 12b, with IC50 values of 0.064, 0.077 and 0.069 μM, respectively, showed higher or similar activity compared with compound 1 (IC50 of 0.078 μM). These compounds provide a basis for further structural modifications. The systematic structure-activity relationship of these trisubstituted pyrimidine amide derivatives was discussed based on the obtained experimental data. The results from the SAR study may be useful for identifying more potent CCR4 antagonists.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The main difficulties in applying technologies based on hydrate formation are the slow hydrate formation rate, low storage capacity, severe formation conditions and environmentally devastating promoters. Nano-sized graphene oxide has special microstructure features such as its functional groups and a large specific surface area, which can lead to high heat and mass transfer efficiency, large gas dissolution, fast nucleation and formation rate. In this work, CO2 hydrate formation with and without graphene oxide nanoparticles was investigated. Herein, the promoting mechanism and effects of graphene oxide concentrations in different initial pressures ranging from 3 to 5 MPa at 279 K on CO2 hydrate formation process were studied experimentally. The experimental results showed that graphene oxide can shorten the induction time by 53–74.3% and increase the gas consumption up to 5.1–15.9% under different system pressures. Based on the results, the optimum concentration was ascertained as 50 ppm under which condition, the induction time and the reaction time were the shortest while the pressure drop and the gas consumption reached the maximum.

After the social learning models were proposed, finding solutions to the games becomes a well-defined mathematical question. However, almost all papers on the games and their applications are based on solutions built either upon an ad-hoc argument or a twisted Bayesian analysis of the games. Here, we present logical gaps in those solutions and offer an exact solution of our own. We also introduce a minor extension to the original game so that not only logical differences but also differences in action outcomes among those solutions become visible.