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Growing evidence shows that long non-coding RNAs (lncRNAs) are widely involved in the progression of multiple diseases, including ischemic stroke. The aim of this study was to explore the function and underlying mechanism of lncRNAs small nucleolar RNA host gene 1 (SNHG1) in ischemic stroke. SNHG1 and salt-induced kinase 1 (SIK1) were upregulated in oxygen–glucose deprivation/reperfusion (OGD/R)-induced bEnd3 cells. SNHG1 downregulation promoted OGD/R-induced injury through decreasing cell proliferation and increasing apoptosis, which was reversed by upregulating SIK1 or downregulating miR-298. Moreover, SIK1 interference had similar functions with SNHG1 knockdown in OGD/R-treated bEnd3 cells. In addition, miR-298 was a direct target of SNHG1 and could specifically bind to SIK1. Furthermore, SNHG1 functioned as a molecular sponge of miR-298 to regulate SIK1 expression. SNHG1 knockdown enhanced OGD/R-induced injury in bEnd3 cells by regulating miR-298/SIK1 axis, which might provide promising therapeutic target for treatment of ischemic stroke.

Introduction Lung injury has several inciting etiologies ranging from trauma (contusion and hemorrhage) to ischemia reperfusion injury. Reflective of the injury, tissue and cellular injury increases proportionally with the injury stress and is an area of potential intervention to mitigate the injury. This study aims to evaluate the therapeutic benefits of recombinant human MG53 (rhMG53) protein in porcine models of acute lung injury (ALI). Materials and Methods We utilized live cell imaging to monitor the movement of MG53 in cultured human bronchial epithelial cells following mechanical injury. The in vivo efficacy of rhMG53 was evaluated in a porcine model of hemorrhagic shock/contusive lung injury. Varying doses of rhMG53 (0, 0.2, or 1 mg/kg) were administered intravenously to pigs after induction of hemorrhagic shock/contusive induced ALI. Ex vivo lung perfusion system enabled assessment of the isolated porcine lung after a warm ischemic induced injury with rhMG53 supplementation in the perfusate (1 mg/mL). Results MG53-mediated cell membrane repair is preserved in human bronchial epithelial cells. rhMG53 mitigates lung injury in the porcine model of combined hemorrhagic shock/contusive lung injury. Ex vivo lung perfusion administration of rhMG53 reduces warm ischemia-induced injury to the isolated porcine lung. Conclusions MG53 is an endogenous protein that circulates in the bloodstream. Therapeutic treatment with exogenous rhMG53 may be part of a strategy to restore (partially or completely) structural morphology and/or functional lung integrity. Systemic administration of rhMG53 constitutes a potential effective therapeutic means to combat ALI.

Herein, we proposed a novel biosensor based on a high-density "hot spot" Au@SiO2 array substrate and rolling circle amplification (RCA) strategy for the ultrasensitive detection of CpG methyltransferase (M.SssI) activity. In the presence of M.SssI, the RCA process can be triggered, causing the augmentation of the single-stranded DNA (ssDNA) at the tail of the double-stranded DNA (dsDNA), and the ssDNA can be hybridized with numerous DNA probes labeled with Raman reporters in the next steps. Afterwards, the resultant ssDNA can be modified to the Au@SiO2 array substrate with the SERS enhancement factor of 7.49 × 106. The substrate was synthesized by using a monolayer SiO2 array to pick up the Au nanoparticle (AuNP) array and finite-difference time-domain (FDTD) simulation showed its excellent SERS effect. Particularly, the developed biosensor displayed a significant sensitivity with a broad detection range covering from 0.005 to 50 U mL-1, and the limits of detection (LODs) in PBS buffer and human serum were 2.37 × 10-4 U mL-1 and 2.51 × 10-4 U mL-1, respectively. Finally, in order to verify the feasibility of its clinical application, the serum samples of healthy subjects and breast cancer, prostate cancer, gastric cancer and cervical cancer patients were analyzed, and the reliability of the results was also confirmed by western blot (WB) experiments. Taking advantage of these merits, the proposed biosensor can be a very promising alternative tool for the detection of M.SssI activity, which is of vital importance in the early detection and prevention of tumors.

In this study, we aimed to investigate the relationship between body mass index (BMI), waist circumference (WC) or waist-to-hip ratio (WHR) and oligomenorrhea or irregular menstruation in Chinese women of childbearing age. A total of 1,423 Han women aged 19–39 years who were routinely examined at the Physical Examination Center of Peking University People's Hospital were enrolled by convenience sampling method. All participants were asked to fill up menstrual questionnaires. Binary logistic regression models were used to assess the odds ratio (OR) of different BMI, WC and WHR groups for the prevalence of oligomenorrhea and irregular menstruation. Moreover, we used the ROC curves to compare the predictive effects of BMI, WC and WHR on oligomenorrhea and irregular menstruation. Among the 1,423 participants, 93 women (6.5%) had BMI ≥ 30 kg/m2, 6.5% of the participants had oligomenorrhea, and 22.6% had irregular menstrual menstruation. Overall, those with BMI ≥30 kg/m2 (OR = 2.543; 95%CI 1.332–4.856; p = .005) or WC ≥ 90 cm (OR = 2.023; 95%CI 1.198–3.416; p = .008) were more likely to have long menstrual cycle. The prevalence of irregular menstruation was higher in the BMI ≥30 kg/m2 (OR = 2.509; 95%CI 1.591–3.958; p < .001), WC ≥ 90 cm (OR = 2.299; 95%CI 1.619–3.265; p < .001) and WHR ≥ 0.86 (OR = 1.739; 95%CI 1.293–2.339; p < .001) groups. The ROC curve showed that all three anthropometric indices had predictive effect, while there was no significant difference in predicting oligomenorrhea. WC was a better predictor for irregular menstruation compared with BMI. Obesity, oligomenorrhea and irregular menstruation were common in Chinese women of childbearing age, and obesity was associated with oligomenorrhea and irregular menstruation. Abdominal obesity might have a stronger predictive effect on irregular menstruation.

TRIM family proteins play integral roles in the innate immune response to virus infection. MG53 (TRIM72) is essential for cell membrane repair and is believed to be a muscle-specific TRIM protein. Here we show human macrophages express MG53, and MG53 protein expression is reduced following virus infection. Knockdown of MG53 in macrophages leads to increases in type I interferon (IFN) upon infection. MG53 knockout mice infected with influenza virus show comparable influenza virus titres to wild type mice, but display increased morbidity accompanied by more accumulation of CD45+ cells and elevation of IFNβ in the lung. We find that MG53 knockdown results in activation of NFκB signalling, which is linked to an increase in intracellular calcium oscillation mediated by ryanodine receptor (RyR). MG53 inhibits IFNβ induction in an RyR-dependent manner. This study establishes MG53 as a new target for control of virus-induced morbidity and tissue injury., TRIM proteins are known to play critical roles in the context of viral infection. Here the authors establish MG53 (TRIM72) suppresses IFN and inflammation by modulation of ryanodine receptor related intracellular calcium induction.

MG53 is a member of the TRIM protein family that is predominantly expressed in striated muscles and participates in cell membrane repair. Controversy exists regarding MG53’s role in insulin signaling and manifestation of diabetes. We generated db/db mice with either whole-body ablation or sustained elevation of MG53 in the bloodstream in order to evaluate the physiological function of MG53 in diabetes. To quantify the amount of MG53 protein in circulation, we developed a monoclonal antibody against MG53 with high specificity. Western blot using this antibody revealed lower or no change of serum MG53 levels in db/db mice or patients with diabetes compared with control subjects. Neither whole-body ablation of MG53 nor sustained elevation of MG53 in circulation altered insulin signaling and glucose handling in db/db mice. Instead, mice with ablation of MG53 were more susceptible to streptozotocin-induced dysfunctional handling of glucose compared with the wild-type littermates. Alkaline-induced corneal injury demonstrated delayed healing in db/db mice, which was restored by topical administration of recombinant human (rh)MG53. Daily intravenous administration of rhMG53 in rats at concentrations up to 10 mg/kg did not produce adverse effects on glucose handling. These findings challenge the hypothetical function of MG53 as a causative factor for the development of diabetes. Our data suggest that rhMG53 is a potentially safe and effective biologic to treat diabetic oculopathy in rodents.

Introduction To improve the accuracy of ultrasound techniques for the assessment of carotid stenosis, we designed a novel carotid artery stenosis ultrasound scale (CASUS), and evaluated its accuracy, reliability, and its value in predicting the occurrence of cardiovascular and cerebrovascular diseases in a prospective study. Methods A total of 750 patients with first-time ischemic stroke and hospitalized within 24 h were enrolled in the study. Using color Doppler ultrasound (CDUS), the degree of stenosis and blood flow (BF) in bilateral internal carotid arteries (ICA) and the V1-V3 segment of vertebral arteries (VA) was assessed. Cubic simulation curves for BF and global blood flow (GBF) over the stenosis score (SS), total stenosis score (TSS), and radiological imaging- total stenosis score (RI-TSS) were fitted and compared. The receiver operating characteristic (ROC) curves using TSS, RI-TSS, or GBF to predict various ischemic stroke endpoints were also analyzed and compared. Results There was a linear relationship between SS and BF both ICA and VA (R2 were 0.734 and 0.783, respectively, both P P P P > 0.05). Conclusions The novel CASUS can better reflect the level of cerebral reperfusion in patients with ischemic stroke and can better predict the occurrence of cardiovascular and cerebrovascular diseases.

Purpose: The aim of this study is to evaluate the influence of arm movements from adduction to abduction on intracavitary electrocardiogram and the position of a catheter tip. Methods: Overall, 192 peripherally inserted central catheter lines were placed under intracavitary electrocardiogram guidance and 188 of them were enrolled in the study. The catheter was first placed at a time point corresponding to the peak P wave with the arm in adduction. The arm was then abducted to 90° without changing catheter insertion length. During the procedure, basal electrocardiogram, intracavitary electrocardiogram, and radiographs with the arm in adduction and abduction were recorded. Amplitude wave changes and catheter movements were measured on electrocardiogram records and radiographs, respectively. Results: In 188 cases, the P wave displayed typical changes, and 97.8% (184/188) catheters were successfully placed correctly. At the peak P wave, the amplitude of the peak P wave was 8.64 times greater than that of the basal P wave, and the P/R ratio was 0.61. When the arm was abducted to 90°, the amplitude of the P wave dropped to 57% of its peak, P/R decreased from 0.61 to 0.34, and the catheter tip moved cephalad 1.00 and 0.77 vertebral body units in male and female patients, respectively. Conclusion: Peripherally inserted central catheter moves toward the heart when the arm position changes from abduction to adduction. Peripherally inserted central catheter tip placement at the peak P wave with patient’s arm in adduction is accurate and can prevent the catheter from advancing too low. R wave can function as a reference for observing P wave changes during peripherally inserted central catheter placement.

BackgroundAvailable evidence on the comparative efficacy and acceptability of psychotherapies for post-traumatic stress disorder (PTSD) in children and adolescents remains uncertain.ObjectiveWe aimed to compare and rank the different types and formats of psychotherapies for PTSD in children and adolescents.MethodsWe searched eight databases and other international registers up to 31 December 2020. The pairwise meta-analyses and frequentist network meta-analyses estimated pooled standardised mean differences (SMDs) and ORs with random-effects model. Efficacy at post-treatment and follow-up, acceptability, depressive and anxiety symptoms were measured.FindingsWe included 56 randomised controlled trials with 5327 patients comparing 14 different types of psychotherapies and 3 control conditions. For efficacy, cognitive processing therapy (CPT), behavioural therapy (BT), individual trauma-focused cognitive–behavioural therapy (TF-CBT), eye movement desensitisation and reprocessing, and group TF-CBT were significantly superior to all control conditions at post-treatment and follow-up (SMDs between −2.42 and −0.25). Moreover, CPT, BT and individual TF-CBT were more effective than supportive therapy (SMDs between −1.92 and −0.49). Results for depressive and anxiety symptoms were similar to the findings for the primary outcome. Most of the results were rated as ‘moderate’ to ‘very low’ in terms of confidence of evidence.ConclusionsCPT, BT and individual TF-CBT appear to be the best choices of psychotherapy for PTSD in young patients. Other types and different ways of delivering psychological treatment can be alternative options. Clinicians should consider the importance of each outcome and the patients’ preferences in real clinical practice.

Banana is a major fruit crop throughout the world with abundant lignocellulose in the pseudostem and rachis residues for biofuel production. In this study, we collected a total of 11 pseudostems and rachis samples that were originally derived from different genetic types and ecological locations of banana crops and then examined largely varied edible carbohydrates (soluble sugars, starch) and lignocellulose compositions. By performing chemical (H2SO4, NaOH) and liquid hot water (LHW) pretreatments, we also found a remarkable variation in biomass enzymatic saccharification and bioethanol production among all banana samples examined. Consequently, this study identified a desirable banana (Refen1, subgroup Pisang Awak) crop containing large amounts of edible carbohydrates and completely digestible lignocellulose, which could be combined to achieve the highest bioethanol yields of 31–38% (% dry matter), compared with previously reported ones in other bioenergy crops. Chemical analysis further indicated that the cellulose CrI and lignin G-monomer should be two major recalcitrant factors affecting biomass enzymatic saccharification in banana pseudostems and rachis. Therefore, this study not only examined rich edible carbohydrates for food in the banana pseudostems but also detected digestible lignocellulose for bioethanol production in rachis tissue, providing a strategy applicable for genetic breeding and biomass processing in banana crops.

Background The prognosis of pancreatic cancer (PC) is extremely poor, and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC. Methods We searched PubMed, Web of Science, EBSCO, and Cochrane library databases for articles that described efficacy and safety of FOLFIRINOX in patients with metastatic PC, from January 1996 to July 2020. The primary outcomes targeted included overall survival (OS) and progression-free survival (PFS). Results We found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR 0.76, 95% Cl 0.67–0.86, pppp>0.05). The main adverse events (AEs) targeted hematological toxicity and the gastrointestinal system, and included febrile neutropenia, a reduction in white blood cells and appetite, as well as diarrhea. Conclusion These findings indicated that FOLFIRINOX has potential benefits for the prognosis of patients with metastatic PC. Furthermore, there is no difference between the regimen of FOLFIRINOX and nab-paclitaxel + gemcitabine in this study. The application of FOLFIRINOX should be according to the actual situation of the patients and the experience of the doctors. Graphical abstract

The community-associated Methicillin-resistant Staphylococcus aureus strain (CA-MRSA) is highly virulent and has become a major focus of public health professionals. Phenol-soluble modulins (PSM) are key factors in its increased virulence. δ-Toxin belongs to PSM family and has copious secretion in many S. aureus strains. In addition, δ-toxin exists in the S. aureus culture supernatant as both N-terminus formylated δ-toxin (fδ-toxin) and deformylated δ-toxin (dfδ-toxin) groups. Although δ-toxin has been studied for more than 70 years, its functions remain unclear. We isolated and purified PSMs from the supernatant of S. aureus MW2, and found fibrils and oligomers aggregates by Size Exclusion Chromatography. After analyzing PSM aggregates and using peptide simulations, we found that the difference in the monomer structure of fδ-toxin and dfδ-toxin might ultimately lead to differences in the aggregation ability: fδ-toxin and dfδ-toxin tend to form fibrils and oligomers respectively. Of note, we found that fδ-toxin fibrils enhanced the stability of biofilms, while dfδ-toxin oligomers promoted their dispersal. Additionally, oligomeric dfδ-toxin combined with PSMα to form a complex with enhanced functionality. Due to the different aggregation capabilities and functions of fδ-toxin and dfδ-toxin, we speculate that they may be involved in the regulation of physiological activities of S. aureus. Moreover, the dfδ-toxin oligomer not only provides a new form of complex in the study of PSMα, but also has significance as a reference in oligomer research pertaining to some human amyloid diseases.

Scope The beneficial effects of probiotics in reducing gastrointestinal inflammation and in preventing colorectal cancer have been reported, but the mechanism underlying the immunomodulatory effect of probiotics in inhibiting extra-intestinal tumor progression remains unclear. Methods and results This study shows that probiotic supplementation attenuate lung metastasis of melanoma cells in mice. Feeding mice with VSL#3 probiotics change the composition and proportion of gut microbiota. The changes in gut bacteria composition, such as in the abundance of Lachnospiraceae, Streptococcus, and Lachnoclostridium, are associated with the production of short-chain fatty acids in the gut. The concentrations of propionate and butyrate are upregulated in gut and blood after feeding VSL#3, and the increase in propionate and butyrate levels promotes the expression of chemokine (C-C motif) ligand 20 (CCL20) in lung endothelial cells and the recruitment of T helper 17 (Th17) cells to the lungs via the CCL20/chemokine receptor 6 axis. The recruitment of Th17 cells decreases the number of tumor foci in lungs and attenuates the lung metastasis of melanoma cells in mice. Conclusions The results provide new information on the role and mechanisms of action of probiotics in attenuating extra-intestinal tumor metastasis.

Background COVID-19 cases resurged worldwide in the second half of 2020. Not much is known about the changes in public responses to containment measures from the initial outbreak to resurgence. Monitoring public responses is crucial to inform policy measures to prepare for COVID-19 resurgence. Objective This study aimed to assess and compare public responses to containment measures during the initial outbreak and resurgence of COVID-19 in China. Methods We curated all COVID-19–related posts from Sina Weibo (China’s version of Twitter) during the initial outbreak and resurgence of COVID-19 in Beijing, China. With a Python script, we constructed subsets of Weibo posts focusing on 3 containment measures: lockdown, the test-trace-isolate strategy, and suspension of gatherings. The Baidu open-source sentiment analysis model and latent Dirichlet allocation topic modeling, a widely used machine learning algorithm, were used to assess public engagement, sentiments, and frequently discussed topics on each containment measure. Results A total of 8,985,221 Weibo posts were curated. In China, the containment measures evolved from a complete lockdown for the general population during the initial outbreak to a more targeted response strategy for high-risk populations during COVID-19 resurgence. Between the initial outbreak and resurgence, the average daily proportion of Weibo posts with negative sentiments decreased from 57% to 47% for the lockdown, 56% to 51% for the test-trace-isolate strategy, and 55% to 48% for the suspension of gatherings. Among the top 3 frequently discussed topics on lockdown measures, discussions on containment measures accounted for approximately 32% in both periods, but those on the second-most frequently discussed topic shifted from the expression of negative emotions (11%) to its impacts on daily life or work (26%). The public expressed a high level of panic (21%) during the initial outbreak but almost no panic (1%) during resurgence. The more targeted test-trace-isolate measure received the most support (60%) among all 3 containment measures in the initial outbreak, and its support rate approached 90% during resurgence. Conclusions Compared to the initial outbreak, the public expressed less engagement and less negative sentiments on containment measures and were more supportive toward containment measures during resurgence. Targeted test-trace-isolate strategies were more acceptable to the public. Our results indicate that when COVID-19 resurges, more targeted test-trace-isolate strategies for high-risk populations should be promoted to balance pandemic control and its impact on daily life and the economy.

Background To investigate the efficacy and safety of omega-3 fatty acids (O3FA) in treating depressive disorders in children and adolescents. Method We conducted a comprehensive search in electronic databases and hand-searched articles included for relevant studies. We included randomized controlled trials which studied on O3FA for treatment of children and adolescents with depression. The standard mean differences (SMDs) and the odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by a random-effects model. The primary outcomes were end-point depressive symptoms scores (efficacy) and all-cause discontinuation (safety). The secondary outcome of response rate was also assessed. Subgroup analyses were performed by age, severity of depression and dosage. Risk of bias assessment was performed based on the Jadad score and the Cochrane Collaboration’s risk-of-bias method. Results A total of four studies with 153 participants were included. In terms of efficacy, there was no significant difference of end-point depressive symptoms scores between O3FA and placebo (SMD = − 0.12, 95% CI − 0.53 to 0.30, P = 0.58; I2= 30%). In terms of safety, the all-cause discontinuation showed no statistical significance between O3FA and placebo (OR = 1.3, 95% CI 0.58 to 2.93, P = 0.53; I2= 0%). The response rate of O3FA was also not significant better than that of placebo (OR = 1.57, 95% CI 0.26 to 9.39, P = 0.62; I2= 71%). Besides, there were also no significant differences in those subgroup analyses outcomes. The risk of bias of included trials were not high. Conclusions Only considering the limited evidence of O3FA in the acute treatment of major depressive disorder, it did not seem to offer a clear advantage for children and adolescents.

High workloads and heavy academic pressure can have significant implications for the risk for depression and poor quality of life (QoL). This study aimed to investigate QoL and depressive symptoms in medical students undergoing postgraduate neurology specialty training in China. The survey covered demographic characteristics, the 8-itemMedical Outcomes Study Short-Formquestionnaire (SF-8), and the 2-itemPrimary Care Evaluation of Mental Disorders depression screening tool. Logistic regression analysis was used to investigate the determinants of QoL and depressive symptoms. Participants were 1,814 postgraduates from 249 hospitals in 27 Chinese provinces. The mean SF-8 physical and mental component summary scores were 78.17 (standard deviation [SD] 15.20) and 68.33 (SD 17.15), respectively. One-third of respondents had depressive symptoms, and those without depressive symptoms had significantly higher QoL scores. The multivariate regression analysis showed that factors independently associated with depressive symptoms were being in the second year of study, a lower household income, and less sleep time. Although QoL among our sample of Chinese medical students undergoing postgraduate neurology specialty training was favorable relative to other comparable populations, one-third of respondents had depressive symptoms. Accurate measures should be taken to change this situation.

Irisin, a muscle-origin protein derived from the extracellular domain of the fibronectin domain-containing 5 protein (FNDC5), has been shown to modulate mitochondria welfare through paracrine action. Here, we test the hypothesis that irisin contributes to cardioprotection after myocardial infarction by preserving mitochondrial function in cardiomyocytes. Animal model studies show that intravenous administration of exogenous irisin produces dose-dependent protection against ischemia/reperfusion (I/R)-induced injury to the heart as reflected by the improvement of left ventricular ejection fraction and the reduction in serum level of cTnI (n = 15, P0.05). I/R-induced apoptosis of cardiomyocytes is reduced after irisin treatment. The irisin-mediated protection has, at least in part, an effect on mitochondrial function because administration of irisin increases irisin staining in the mitochondria of the infarct area. Irisin also reduces I/R-induced oxidative stress as determined by mitochondrial membrane potential evaluation and superoxide FLASH event recording (n = 4, P0.05). The interaction between irisin and superoxide dismutase2 (SOD2) plays a key role in the protective process because irisin treatment increases SOD activity (n = 10, P0.05) and restores the mitochondria localization of SOD2 in cardiomyocytes (n = 5, P0.05). These results demonstrate that irisin plays a protective role against I/R injury to the heart. Targeting the action of irisin in mitochondria presents a novel therapeutic intervention for myocardial infarction.

The tumour susceptibility gene 101 (TSG101) is reported to play important roles in the development and progression of several human cancers. However, its potential roles and underlined mechanisms in human hepatocellular carcinoma (HCC) are still needed to be further clarified. In the present study, we reported that knock down of TSG101 suppressed the proliferation, migration and invasion of HCC cells, while overexpression of TSG101 facilitated them. Molecularly, the results revealed that knock down of TSG101 significantly decreased the cell cycle related regulatory factor p53 and p21. In another point, knock down of TSG101 also obviously decreased the level of metallopeptidase inhibitor TIMP1 (Tissue inhibitors of metalloproteinases 1), which results in inhibition of MMP2, MMP7 and MMP9. In contrast, overexpression of TSG101 had opposite effects. The iTRAQ proteomics analysis identified that oncogenic protein PEG10 (Paternally expressed gene 10) might be a potential downstream target of TSG101. Further investigation showed that TSG101 interacted with PEG10 and protected it from proteasomal degradation thereby regulating the expression of p53, p21 and MMPs. Finally, we found that both TSG101 and PEG10 proteins are up‐regulated and presented a direct correlation in HCC patients. In conclusion, these results suggest that TSG101 is up‐regulated in human HCC patients, which may accelerate the proliferation, migration and invasion of HCC cells through regulating PEG10.

Background Depression is a leading cause of disability worldwide. There is increasing evidence showing that depression is associated with the pathophysiology in amygdala; however, the underlying mechanism remains poorly understood. Method We established a rat model of chronic social defeat stress (CSDS) and conducted a series of behavior tests to observe behavioral changes. Then liquid chromatography mass spectrometry (LC–MS)-based metabolomics and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics were employed to detect metabolomes and proteomes in the amygdala, respectively. Ingenuity pathway analysis (IPA) and other bioinformatic analyses were used to analyze differentially expressed metabolites and proteins. Results The significantly lower sucrose preference index in the sucrose preference test and longer immobile time in the forced swim test were observed in the CSDS rats compared with control rats. In the multi-omics analysis, thirty-seven significantly differentially expressed metabolites and 123 significant proteins were identified. Integrated analysis of differentially expressed metabolites and proteins by IPA revealed molecular changes mainly associated with synaptic plasticity, phospholipase c signaling, and glutamine degradation I. We compared the metabolites in the amygdala with those in the hippocampus and prefrontal cortex from our previous studies and found two common metabolites: arachidonic acid and N-acetyl- l -aspartic acid among these three brain regions. Conclusion Our study revealed the presence of depressive-like behaviors and molecular changes of amygdala in the CSDS rat model, which may provide further insights into the pathogenesis of depression, and help to identify potential targets for antidepressants.

Pandemics have become more frequent and more complex during the twenty-first century. Posttraumatic stress disorder (PTSD) following pandemics is a significant public health concern. We sought to provide a reliable estimate of the worldwide prevalence of PTSD after large-scale pandemics as well as associated risk factors, by a systematic review and meta-analysis. We systematically searched the MedLine, Embase, PsycINFO, Web of Science, CNKI, WanFang, medRxiv, and bioRxiv databases to identify studies that were published from the inception up to August 23, 2020, and reported the prevalence of PTSD after pandemics including sudden acute respiratory syndrome (SARS), H1N1, Poliomyelitis, Ebola, Zika, Nipah, Middle Eastern respiratory syndrome coronavirus (MERS-CoV), H5N1, and coronavirus disease 2019 (COVID-19). A total of 88 studies were included in the analysis, with 77 having prevalence information and 70 having risk factors information. The overall pooled prevalence of post-pandemic PTSD across all populations was 22.6% (95% confidence interval (CI): 19.9-25.4%, I2: 99.7%). Healthcare workers had the highest prevalence of PTSD (26.9%; 95% CI: 20.3-33.6%), followed by infected cases (23.8%: 16.6-31.0%), and the general public (19.3%: 15.3-23.2%). However, the heterogeneity of study findings indicates that results should be interpreted cautiously. Risk factors including individual, family, and societal factors, pandemic-related factors, and specific factors in healthcare workers and patients for post-pandemic PTSD were summarized and discussed in this systematic review. Long-term monitoring and early interventions should be implemented to improve post-pandemic mental health and long-term recovery.

Background Porcine reproductive and respiratory syndrome virus (PRRSV) infection can cause severe reproductive failure in sows and respiratory distress in pigs of all ages, leading to major economic losses. To date, there are still no effective strategies to prevent and control PRRSV. Antibody-dependent enhancement (ADE), a phenomenon in which preexisting non-neutralizing antibodies or sub-neutralizing antibodies facilitate virus entry and replication, may be a significant obstacle in the development of effective vaccines for many viruses, including PRRSV. However, the contribution of ADE to PRRSV infection remains controversial, especially in vivo. Whether attenuated PRRSV vaccines prevent or worsen subsequent disease in pigs infected by novel PRRSV strains requires more research. In the present study, in vivo experiments were conducted to evaluate ADE under different immune statuses, which were produced by waiting different lengths of time after vaccination with a commercially available attenuated highly pathogenic PRRSV (HP-PRRSV) vaccine (JXA1-R) before challenging the pigs with a novel heterologous NADC30-like strain. Results Piglets that were vaccinated before being challenged with PRRSV exhibited lower mortality rates, lower body temperatures, higher bodyweight gain, and lower viremia. These results demonstrate that vaccination with JXA1-R alleviated the clinical signs of PRRSV infection in all vaccinated groups. Conclusions The obtained data indicate that the attenuated vaccine test here provided partial protection against the NADC30-like strain HNhx. No signs of enhanced PRRSV infection were observed under the applied experimental conditions. Our results provide some insight into the molecular mechanisms underlying vaccine-induced protection or enhancement in PRRSV.

Major depressive disorder is a serious and complex mental illness, and multiple brain regions are involved in its pathogenesis. There is increasing evidence that the amygdala is involved in depression; however, the underlying molecular mechanisms remain unclear. In this study, we applied a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomic and isobaric tags for relative and absolute quantitation (iTRAQ) proteomic to study changes in the amygdala in a chronic unpredictable mild stress (CUMS) rat model of depression. Differential analysis identified 42 metabolites and 171 proteins that were differentially expressed in the CUMS and control groups. Integrated analyses revealed two major changes in the amygdala of CUMS rats: (1) perturbations in amino acids and carbohydrate metabolism, transport-/catabolism-related proteins activity, and metabolic enzyme activity; (2) abnormal expression of synaptogenesis and oxidative phosphorylation-associated proteins.

Cutaneous lupus erythematosus (CLE) is an autoimmune disease with a broad range of cutaneous manifestations. In skin lesions of CLE, keratinocytes primarily undergo apoptosis. Interferon-κ(IFN-κ) is belonged to type I interferons (type I IFNs) and is selectively produced by keratinocytes. Recently, keratinocytes selectively produced IFN-κ is identified to be a key to trigger type I interferon responses in CLE. Other immune cells such as plasmacytoid dendritic cells (pDCs) are identified to be relevant origin of type I interferons (type I IFNs) which are central to the development of CLE lesions and responsible for mediating Th1 cell activity. Other types of cells such as neutrophils, B cells and Th17 cells also are involved in the development of this disease. The close interaction of those cells composes a comprehensive and complicated network in CLE. In this review, we discussed the aberrant distribution and function of different cells types involved in this disease and will offer a new direction for research and therapy in the near future.

Simple Summary The risk of developing colorectal cancer at a younger age has increased, but current therapies are either risky or limited. We aim to demonstrate that the combination treatment of artemisinin derivatives and TRAIL could be a potential therapy to kill colon cancer cells. We found that artemisinin derivatives increase death receptor production and further sensitize colon cancer cells to TRAIL-induced apoptosis. Furthermore, we explored the role of P53 in response to artemisinin derivatives, which transactivates Death Receptor 5 (DR5) and the cyclin-dependent kinase inhibitor P21. Finally, a 3D tumor spheroid model also confirmed the efficacy of the combination treatment. Abstract Artemisinin derivatives, widely known as commercial anti-malaria drugs, may also have huge potential in treating cancer cells. It has been reported that artemisinin derivatives can overcome resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in liver and cervical cancer cells. In our study, we demonstrated that artesunate (ATS) and dihydroartemisinin (DHA) are more efficient in killing colon cancer cells compared to artemisinin (ART). ATS/DHA induces the expression of DR5 in a P53 dependent manner in HCT116 and DLD-1 cells. Both ATS and DHA overcome the resistance to DHER-induced apoptosis in HCT116, mainly through upregulating death receptor 5 (DR5). We also demonstrate that DHA sensitizes HCT116 cells to DHER-induced apoptosis via P53 regulated DR5 expression in P53 knockdown assays. Nevertheless, a lower effect was observed in DLD-1 cells, which has a single Ser241Phe mutation in the P53 DNA binding domain. Thus, the status of P53 could be one of the determinants of TRAIL resistance in some cancer cells. Finally, the combination treatment of DHA and the TRAIL variant DHER increases cell death in 3D colon cancer spheroid models, which shows its potential as a novel therapy.

Highlights • This was the first study on suicidal and self-harm ideation (SSI) in hospital staff during a public health crisis. • 744 (6.47%) hospital staff reported a suicidal and self-harm ideation. • The epidemic-related factors, the psychological status and need, and the perceived stress and support were associated with SSI in hospital staff. • The current SSI in the initial phase of a pandemic might lower than that in non-pandemic days., The COVID-19 pandemic put global medical systems under massive pressure for its uncertainty, severity, and persistence. For detecting the prevalence of suicidal and self-harm ideation (SSI) and its related risk factors among hospital staff during the COVID-19 pandemic, this cross-sectional study collected the sociodemographic data, epidemic-related information, the psychological status and need, and perceived stress and support from 11507 staff in 46 hospitals by an online survey from February 14 to March 2, 2020. The prevalence of SSI was 6.47%. Hospital staff with SSI had high family members or relatives infected number and the self-rated probability of infection. Additionally, they had more perceived stress, psychological need, and psychological impact. On the contrary, hospital staff without SSI reported high self-rated health, willingness to work in a COVID-19 ward, confidence in defeating COVID-19, and perceived support. Furthermore, they reported better marital or family relationship, longer sleep hours, and shorter work hours. The infection of family members or relatives, poor marital status, poor self-rated health, the current need for psychological intervention, perceived high stress, perceived low support, depression, and anxiety were independent factors to SSI. A systematic psychological intervention strategy during a public health crisis was needed for the hospital staff's mental well-being.

The pandemic of COVID-19 has caused millions of infections, which has led to a great loss all over the world, socially and economically. Due to the false-negative rate and the time-consuming of the conventional Reverse Transcription Polymerase Chain Reaction (RT-PCR) tests, diagnosing based on X-ray images and Computed Tomography (CT) images has been widely adopted. Therefore, researchers of the computer vision area have developed many automatic diagnosing models based on machine learning or deep learning to assist the radiologists and improve the diagnosing accuracy. In this paper, we present a review of these recently emerging automatic diagnosing models. 70 models proposed from February 14, 2020, to July 21, 2020, are involved. We analyzed the models from the perspective of preprocessing, feature extraction, classification, and evaluation. Based on the limitation of existing models, we pointed out that domain adaption in transfer learning and interpretability promotion would be the possible future directions., In ICRAI 2020: 2020 6th International Conference on Robotics and Artificial Intelligence

Background Understanding public behavioral responses to the coronavirus disease (COVID-19) epidemic and the accompanying infodemic is crucial to controlling the epidemic. Objective The aim of this study was to assess real-time public awareness and behavioral responses to the COVID-19 epidemic across 12 selected countries. Methods Internet surveillance was used to collect real-time data from the general public to assess public awareness and rumors (China: Baidu; worldwide: Google Trends) and behavior responses (China: Ali Index; worldwide: Google Shopping). These indices measured the daily number of searches or purchases and were compared with the numbers of daily COVID-19 cases. The trend comparisons across selected countries were observed from December 1, 2019 (prepandemic baseline) to April 11, 2020 (at least one month after the governments of selected countries took actions for the pandemic). Results We identified missed windows of opportunity for early epidemic control in 12 countries, when public awareness was very low despite the emerging epidemic. China's epidemic and the declaration of a public health emergency of international concern did not prompt a worldwide public reaction to adopt health-protective measures; instead, most countries and regions only responded to the epidemic after their own case counts increased. Rumors and misinformation led to a surge of sales in herbal remedies in China and antimalarial drugs worldwide, and timely clarification of rumors mitigated the rush to purchase unproven remedies. Conclusions Our comparative study highlights the urgent need for international coordination to promote mutual learning about epidemic characteristics and effective control measures as well as to trigger early and timely responses in individual countries. Early release of official guidelines and timely clarification of rumors led by governments are necessary to guide the public to take rational action.

Activation of AMPK emerges as a potential therapeutic approach to metabolic diseases. AdipoRon is claimed to be an adiponectin receptor agonist that activates AMPK through adiponectin receptor 1 (AdipoR1). However, AdipoRon also exhibits moderate inhibition of mitochondrial complex I, leading to increased risk of lactic acidosis. In order to find novel AdipoRon analogues that activate AMPK without inhibition of complex I, 27 analogues of AdipoRon were designed, synthesized and biologically evaluated. As results, benzyloxy arylamide B10 was identified as a potent AMPK activator without inhibition of complex I. B10 dose-dependently improved glucose tolerance in normal mice, and significantly lowered fasting blood glucose level and ameliorated insulin resistance in db/db diabetic mice. More importantly, unlike the pan-AMPK activator MK-8722, B10 did not cause cardiac hypertrophy, probably owing to its selective activation of AMPK in the muscle tissue but not in the heart tissue. Together, B10 represents a novel class of AMPK activators with promising therapeutic potential against metabolic disease.

Summary Background Depressive disorders are common in children and adolescents. Antidepressants, psychotherapies, and their combination are often used in routine clinical practice; however, available evidence on the comparative efficacy and safety of these interventions is inconclusive. Therefore, we sought to compare and rank all available treatment interventions for the acute treatment of depressive disorders in children and adolescents. Methods We did a systematic review and network meta-analysis. We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, PsycINFO, ProQuest, CINAHL, LiLACS, international trial registries, and the websites of regulatory agencies for published and unpublished randomised controlled trials from database inception until Jan 1, 2019. We included placebo-controlled and head-to-head trials of 16 antidepressants, seven psychotherapies, and five combinations of antidepressant and psychotherapy that are used for the acute treatment of children and adolescents (≤18 years old and of both sexes) with depressive disorder diagnosed according to standard operationalised criteria. Trials recruiting participants with treatment-resistant depression, bipolar disorder, psychotic depression, treatment duration of less than 4 weeks, or an overall sample size of fewer than ten patients were excluded. We extracted data following a predefined hierarchy of outcome measures, and assessed risk of bias and certainty of evidence using validated methods. Primary outcomes were efficacy (change in depressive symptoms) and acceptability (treatment discontinuation due to any cause). We estimated summary standardised mean differences (SMDs) or odds ratios (ORs) with credible intervals (CrIs) using network meta-analysis with random effects. This study was registered with PROSPERO, number CRD42015020841. Findings From 20 366 publications, we included 71 trials (9510 participants). Depressive disorders in most studies were moderate to severe. In terms of efficacy, fluoxetine plus cognitive behavioural therapy (CBT) was more effective than CBT alone (–0·78, 95% CrI −1·55 to −0·01) and psychodynamic therapy (–1·14, −2·20 to −0·08), but not more effective than fluoxetine alone (–0·22, −0·86 to 0·42). No pharmacotherapy alone was more effective than psychotherapy alone. Only fluoxetine plus CBT and fluoxetine were significantly more effective than pill placebo or psychological controls (SMDs ranged from −1·73 to −0·51); and only interpersonal therapy was more effective than all psychological controls (–1·37 to −0·66). Nortriptyline (SMDs ranged from 1·04 to 2·22) and waiting list (SMDs ranged from 0·67 to 2·08) were less effective than most active interventions. In terms of acceptability, nefazodone and fluoxetine were associated with fewer dropouts than sertraline, imipramine, and desipramine (ORs ranged from 0·17 to 0·50); imipramine was associated with more dropouts than pill placebo, desvenlafaxine, fluoxetine plus CBT, and vilazodone (2·51 to 5·06). Most of the results were rated as “low” to “very low” in terms of confidence of evidence according to Confidence In Network Meta-Analysis. Interpretation Despite the scarcity of high-quality evidence, fluoxetine (alone or in combination with CBT) seems to be the best choice for the acute treatment of moderate-to-severe depressive disorder in children and adolescents. However, the effects of these interventions might vary between individuals, so patients, carers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis. Funding National Key Research and Development Program of China.

Temporal relation classification, an important branch of relation extraction, aims to identify the time sequence among events. Currently, Shortest Dependency Path (SDP) is widely used in various kinds of neural network models to capture the crucial information from sentences. However, while eliminating irrelevant words in event sentences, SDP will miss some useful information, e.g., time expressions. To address the above issue, we propose a neural network method incorporating the temporal cues to AC-GCN (Augmented Contextualized Graph Convolutional Network) to classify temporal relations. Firstly, we introduce the semantic role labeling and heuristic rules to extract the time expressions corresponding to event triggers and other words in SDPs, respectively. Then, the SDP with time expression (i.e., T-SDP) is encoded by a Bi-LSTM with the parameter sharing mechanism and fed into GCN to classify temporal relations. The experimental results on TimeBank-Dense show that our proposed model outperforms all baselines significantly.

Background and Purpose— Blood pressure (BP) control in the early phase of stroke is controversial to reduce the risk of poststroke cognitive impairment (PSCI). This study was to investigate the impact of BP levels in the early phase of ischemic stroke and stroke subtype on PSCI. Methods— Seven hundred and ninety-six patients with acute ischemic stroke were included. Cognitive function was assessed after stroke onset using the Montreal Cognitive Assessment. Patients were divided into quintiles according to systolic BP and diastolic BP levels in the early phase. Subtype analyses were according to Trial of ORG 10172 in Acute Stroke Treatment classification (infarct cause) and Oxfordshire Community Stroke Project classification (infarct location). Results— After adjusting for multiple variables, the quintiles with the lowest systolic BP (Q1, 102–127 mm Hg) and with the highest systolic BP (Q5, 171–215 mm Hg) were associated with increased PSCI risk (odds ratio, 1.83; 95% confidence interval, 1.64–2.28; P =0.007 in Q1; odds ratio, 2.32; 95% confidence interval, 1.74–2.90; P P =0.031; total anterior circulation infarct: odds ratio, 1.68; 95% confidence interval, 1.32–2.15; P =0.001). Conclusions— Lower or higher BP in the early phase of ischemic stroke was correlated with increased PSCI risk at 3 months. Maintaining systolic/diastolic BP in the levels of 143 to 158/93 to 102 mm Hg might be beneficial to reduce the occurrence of PSCI. Moreover, large artery atherosclerosis subtype and total anterior circulation infarct subtype were correlated with increased PSCI risk at 3 months. Clinical Trial Registration— URL: https://www.chictr.org . Unique identifier: ChiCTR-TRC-14004804.

MG53 is a muscle-specific TRIM-family protein that presides over the cell membrane repair response. Here, we show that MG53 present in blood circulation acts as a myokine to facilitate tissue injury-repair and regeneration. Transgenic mice with sustained elevation of MG53 in the bloodstream (tPA-MG53) have a healthier and longer life-span when compared with littermate wild type mice. The tPA-MG53 mice show normal glucose handling and insulin signaling in skeletal muscle, and sustained elevation of MG53 in the bloodstream does not have a deleterious impact on db/db mice. More importantly, the tPA-MG53 mice display remarkable dermal wound healing capacity, enhanced muscle performance, and improved injury-repair and regeneration. Recombinant human MG53 protein protects against eccentric contraction-induced acute and chronic muscle injury in mice. Our findings highlight the myokine function of MG53 in tissue protection and present MG53 as an attractive biological reagent for regenerative medicine without interference with glucose handling in the body., MG53 is a protein that regulates the cell membrane repair process, and it’s been suggested that it might play a role in diabetes. Here, the authors demonstrate that circulating MG53 functions as a myokine to facilitate tissue injury-repair and regeneration without impacting glucose handling.

Major depressive disorder (MDD) in children and adolescents is a recurrent and disabling condition globally but its pathophysiology remains poorly elucidated and there are limited effective treatments available. We performed metabolic profiling of plasma samples based on ultra-high-performance liquid chromatography equipped with quadrupole time-offlight mass spectrometry to explore the potential biomarkers of depression in children and adolescents with MDD. We identified several perturbed pathways, including fatty acid metabolism—particularly the polyunsaturated fatty acids metabolism, and purine metabolism—that were associated with MDD in these young patients. In addition, inosine was shown as a potential independent diagnostic biomarker for MDD, achieving an area under the ROC curve of 0.999 in discriminating drug-naive MDD patients and 0.866 in discriminating drug-treated MDD from healthy controls. Moreover, we found evidence for differences in the pathophysiology of MDD in children and adolescents to that of adult MDD, specifically with tryptophan metabolism. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and the pathophysiology and diagnostic biomarker of child and adolescent MDD.

Deep brain stimulation (DBS) has been applied in treatment-resistant depression (TRD) as a putative intervention targeting different brain regions. However, the antidepressant effects of DBS for TRD in recent clinical trials remain controversial.We searched Scopus, EMBASE, the Cochrane Library, PubMed, and PsycINFO for all published studies investigating the efficacy of DBS in TRD up to Feb 2017. Hamilton depression rating scale (HDRS) scores and Montgomery-Asberg depression rating scale (MARDS) scores were compared between baseline levels and those after DBS using the standardized mean difference (SMD) with 95% confidence intervals (CIs). The pooled response and remission rates were described using Risk Difference with 95% CIs.We identified 14 studies of DBS in TRD targeting the subcallosal cingulate gyrus (SCG), ventral capsule/ventral striatum (VC/VS), medial forebrain bundle (MFB), and nucleus accumbens (NAcc). The overall effect sizes showed a significant reduction in HDRS after DBS stimulation in these four regions, with a standardized mean difference of -3.02 (95% CI=-4.28 to -1.77, p0.00001) for SCG, -1.64 (95% CI=-2.80 to -0.49, p=0.005) for VC/VS, -2.43 (95% CI=-3.66 to -1.19, p=0.0001) for MFB, and -1.30 (95% CI=-2.16 to -0.44, p=0.003) for NAcc. DBS was effective, with high response rates at 1, 3, 6, and 12months. Some adverse events (AEs), especially some specific AEs related to targeting regions, occurred during the DBS treatment.DBS significantly alleviates depressive symptoms in TRD patients by targeting the SCG, VC/VS, MFB, and NAcc. Several adverse events might occur during DBS therapy, although it is uncertain whether some AEs can be linked to DBS treatment. Further confirmatory trials are required involving larger sample sizes.

Major depressive disorder (MDD) is a heterogeneous and multi-factorial disorder, and the underlying molecular mechanisms remain largely unknown. However, many studies have indicated that the molecular mechanisms underlying depression in response to different stress may differ. After screening, 28–30 rats were included in each model of depression (chronic unpredictable mild stress (CUMS); learned helplessness (LH); chronic restraint stress (CRS); or social defeat (SD)). Non-targeted gas chromatography-mass spectrometry was used to profile the metabolic changes in the hippocampus. As a result, all four models exhibited significant depression-like behavior. A total of 30, 24, 19, and 25 differential metabolites were identified in the CUMS, LH, CRS, and SD models, respectively. Interestingly, the hierarchical clustering results revealed two patterns of metabolic changes that are characteristic of the response to cluster 1 (CUMS, LH) and cluster 2 (CRS, SD) stress, which represent physical and psychological stress, respectively. Bioinformatic analysis suggested that physical stress was mainly associated with lipid metabolism and glutamate metabolism, whereas psychological stress was related to cell signaling, cellular proliferation, and neurodevelopment, suggesting the molecular changes induced by physical and psychological stress were different. Nine shared metabolites were opposite in the directions of change between physical and psychological models, and these metabolites were associated with cellular proliferation and neurodevelopment functions, indicating the response to physical and psychological stress was different in the activation and deactivation of the final common pathway to depression. Our results provide a further understanding of the heterogeneity in the molecular mechanisms of MDD that could facilitate the development of personalized medicine for this disorder.

INTRODUCTION Although previous conventional meta-analyses and network meta-analyses have provided some important findings about pharmacological treatments for children and adolescents with depressive disorders in the past decades, several questions still remain unsolved by the aggregate data from those meta-analyses. Individual participant data meta-analysis (IPD-MA) enables exploration of the impacts of individual characteristics on treatment effects, allowing matching of treatments to specific subgroups of patients. We will perform an IPD-MA to assess the efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents. METHODS AND ANALYSIS We will systematically search for all double-blind randomised controlled trials (RCTs) that have compared any new-generation antidepressant with placebo for the acute treatment of major depressive disorder in children and adolescents, in the following databases: PubMed, EMBASE, the Cochrane Library, PsycINFO, Web of Science, CINAHL, LILACS and ProQuest Dissertations. We will contact all corresponding authors of included RCTs and ask for their cooperation in this project by providing individual participant data from the original trials. The primary outcomes will include efficacy, measured as the mean change of depression symptoms by Children's Depression Rating Scale Revised (CDRS-R), and tolerability, measured as the proportion of patients who withdrew from the trials early due to adverse effects. The secondary outcomes will include response rates, remission rates, deterioration rate, all-cause discontinuation, suicidal-related outcomes and global functioning outcome. Using the raw de-identified study data, we will use mixed-effects logistic and linear regression models to perform the IPD-MAs. The risk of bias of included studies will be assessed using the Cochrane risk of bias tool. We will also detect the publication bias and effects of non-participation of eligible studies. DISSEMINATION Ethical approval is not required given that informed consent has already been obtained from the patients by the trial investigators before the included trials were conducted. This study may have considerable implications for practice and help improve patient care. PROSPERO REGISTRATION NUMBER CRD42016051657.

We aimed to provide an overview of psychotherapy in young anxious children (mean age

In this study, we evaluate the efficacy and safety of interpersonal psychotherapy (IPT) for adolescents with depression. We searched our existing database and electronic databases, including PubMed, Cochrane, EMBASE, PsycINFO, Web of Science, and CINAHL databases (from inception to May 2016). We included randomized controlled trials comparing IPT with various control conditions, including waitlist, psychological placebo, treatment as usual, and no treatment, in adolescents with depression. Finally, we selected seven studies comprising 538 participants comparing IPT with three different control conditions. Pooled analyses suggested that IPT was significantly more effective than control conditions in reducing depressive symptoms at post-treatment and follow-up, and increasing the response/remission rate at post-treatment. IPT was also superior to control conditions for all-cause discontinuation and quality of life/functioning improvement outcomes. However, there was no evidence that IPT reduces the risk of suicide from these data. Meta-analysis demonstrated publication bias for primary efficacy, while the adjusted standardized mean difference using the trim-and-fill method indicated IPT was still significantly superior to the control conditions. Current evidence indicates IPT has a superior efficacy and acceptability compared with control conditions in treating adolescents with depression.

BACKGROUND The aim of this study was to investigate the relation between mid-term blood pressure (BP) variability (BPV) within 7 days of onset and the prognosis in acute stroke patients. METHODS Total 873 acute ischemic stroke patients were included in this study. Mid-term BPV was evaluated through the calculations of coefficient of variation (CV) of the systolic BP (SBP) and diastolic BP (DBP) within 7 days of onset. Clinical outcomes were assessed using the recovery situations of neurological function at 3 months, the primary outcome (symptomatic recurrent stroke) and the secondary outcomes (recurrent stroke, all-cause mortality, and the composite of cardiovascular events) within 12 months. RESULTS Among 873 patients with ischemic stroke, 83 died, 125 developed recurrent stroke, and 212 developed cardiovascular events during 12 months' follow-up. At 3 months, systolic or diastolic BPV (within 7 days of onset) was associated with the recovery situations of neurological function in three models (all P < 0.05). Both higher CV of SBP and CV of DBP were significantly correlated with the increased risk of recurrent stroke (hazard ratio [HR] = 2.32, 95% confidence interval [CI]: 1.29-4.18, P = 0.005 for CV of SBP; HR = 2.33, 95% CI: 1.29-4.19, P = 0.005 for CV of DBP) and composite cardiovascular events (HR = 2.22, 95% CI: 1.41-3.48, P = 0.001 for CV of SBP; HR = 2.21, 95% CI: 1.41-3.47, P = 0.001 for CV of DBP) during 12 months' follow-up. CONCLUSIONS After acute ischemic stroke, high systolic or diastolic BPV within 7 days of onset was associated with the recovery situations of neurological function at 3 months, and recurrent stroke and composite cardiovascular events within 12 months. CLINICAL TRIAL REGISTRATION URL: http://www.chictr.org.cn. Unique identifier: ChiCTR-TRC-14004804.

Background: Cancer cells have to take metabolic transformation in tumor progression when facing need of increased energy and adequate vascularization. However, molecular mechanism is not fully known. In this study, we showed that expression of carnitine palmitoyltransferase 1C (Cpt1c), as a member of the gate-keeper enzymes , which transferring long-chain fatty acids into mitochondria to further oxidation, which is regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions. Methods: Firstly, we used qRT-PCR to detect expression of Cpt1c in papillary thyroid carcinomas tissues compared with paired normal tissues. Secondly, to evaluate whether Cpt1c is induced under metabolic stress, models of hypoxia (0.2% oxygen) and glucose deprivation for cultured papillary thyroid carcinomas cells were established. Lastly, KTC-1 cells were treated with AICAR (as an agonist of AMPK) and Compound C (as an inhibitor of AMPK) to investigate the correlation of AMPK activity with Cpt1c expression under metabolic stress. Results: Cpt1c is higher in papillary thyroid carcinomas tissues compared with paired normal tissues. Furthermore, Cpt1c up-regulation promotes cancer cell growth and metastasis. In addition, the results showed that Cpt1c expression is induced by metabolic stress, including hypoxia and low glucose treatment. Consistently, Cpt1c can protect cells from cancer cells death caused by hypoxia and low glucose. Lastly, Cpt1c expression is regulated by AMPK activity. Conclusion: Here we describe that induction of Cpt1c expression facing metabolic stress in papillary thyroid carcinomas is at least partly regulated by AMPK activity and ultimately contribute to development and progression of papillary thyroid carcinomas.

Background Few meta-analyses have focused on the effect of cognitive behavioral therapy (CBT) for depression in children. Study Selection Randomized controlled trials comparing CBT with control conditions for depression in children (≤13 years old) were included. Data Sources Seven electronic databases (PubMed, Embase, CENTRAL, Web of Science, PsycINFO, CINAHL, and LiLACS) were searched from inception to September 2015. Data Extraction and Synthesis The primary efficacy was defined as mean change scores in depressive symptoms, and the second efficacy (remission) was a score below the threshold for a diagnosis of depression, both after treatment and at the end of follow-up. We also measured acceptability by the proportion of participants who discontinued treatment up to posttreatment. Results Nine studies with 306 participants were selected for this analysis. At posttreatment, CBT was significantly more effective than control conditions in terms of primary efficacy (standardized mean difference, −0.41; 95% confidence interval [CI], −0.64 to −0.18) and secondary efficacy (odds ratio [OR], 2.16; 95% CI, 1.24 to 3.78). At follow-up, the results were consistent with those of efficacy outcomes at posttreatment, with a standardized mean difference of −0.34 and an OR of 2.04. CBT had no statistical more all-cause discontinuations than the control group (OR, 0.69; 95% CI, 0.26 to 1.82). However, subgroup analyses found that CBT was only significantly more effective than nontreatment, while it was not better than wait list or psychological placebo. Conclusions CBT seems to be more beneficial in the treatment of depression in children than nontreatment; however, this finding is limited by the small size of the trials and low literature quality.

Porcine reproductive and respiratory syndrome virus (PRRSV) has caused tremendous economic losses in the swine industry since its emergence in the late 1980s. PRRSV exploits various strategies to evade immune responses and establish chronic persistent infections. Suppressor of cytokine signaling (SOCS) 1, a member of the SOCS family, is a crucial intracellular negative regulator of innate immunity. In this study, it was shown that SOCS1 can be co-opted by PRRSV to evade host immune responses, facilitating viral replication. It was observed that PRRSV induced SOCS1 production in porcine alveolar macrophages, monkey-derived Marc-145 cells, and porcine-derived CRL2843-CD163 cells. SOCS1 inhibited the expression of IFN-β and IFN-stimulated genes, thereby markedly enhancing PRRSV replication. It was observed that the PRRSV N protein has the ability to upregulate SOCS1 production and that nuclear localization signal–2 (NLS-2) is essential for SOCS1 induction. Moreover, SOCS1 upregulation was dependent on p38/AP-1 and JNK/AP-1 signaling pathways rather than classical type I IFN signaling pathways. In summary, to our knowledge, the findings of this study uncovered the molecular mechanism that underlay SOCS1 induction during PRRSV infection, providing new insights into viral immune evasion and persistent infection.

Background In China, the shortage of doctors leads to stressful clinical work and increasing turnover. Medical students undergoing postgraduate specialty training will be the country’s medical workforce in the coming decades, but are also subject to high workloads and academic pressure. This may have significant implications for burnout and career choice regret. Despite the importance of burnout and career choice regret, the status and relationship of these aspects in Chinese neurology postgraduates are largely unexplored, and associated factors remain unknown. Methods This study investigated the prevalence of and factors influencing burnout and career choice regret among neurology postgraduates in China. We conducted a national cross-sectional study of Chinese neurology postgraduates. Data were collected using a self-administered questionnaire that covered demographic information, the Maslach Burnout Inventory, and additional item to assess career choice regret. Results Of 4902 neurology postgraduates, 2008 returned completed questionnaires (response rate 41%). After excluding incomplete questionnaires, data for 1814 participants were analyzed. In total, 83.6% of participants had experienced symptoms of burnout, and 46.6% reported career choice regret. Binary logistic regression analysis showed postgraduate entrance examination scores, marital status, and having children were associated with burnout (all P

Background The aortic valve of the heart experiences constant mechanical stress under physiological conditions. Maladaptive valve injury responses contribute to the development of valvular heart disease. Here, we test the hypothesis that MG 53 (mitsugumin 53), an essential cell membrane repair protein, can protect valvular cells from injury and fibrocalcific remodeling processes associated with valvular heart disease. Methods and Results We found that MG 53 is expressed in pig and human patient aortic valves and observed aortic valve disease in aged Mg53−/− mice. Aortic valves of Mg53−/− mice showed compromised cell membrane integrity. In vitro studies demonstrated that recombinant human MG 53 protein protects primary valve interstitial cells from mechanical injury and that, in addition to mediating membrane repair, recombinant human MG 53 can enter valve interstitial cells and suppress transforming growth factor‐β‐dependent activation of fibrocalcific signaling. Conclusions Together, our data characterize valve interstitial cell membrane repair as a novel mechanism of protection against valvular remodeling and assess potential in vivo roles of MG 53 in preventing valvular heart disease.

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The cornea plays an important role in transmitting light and providing protection to the eye, but is susceptible to injury and infection. Standard treatments for corneal wounds include topical lubricants, antibiotics, bandage contact lens, and surgery. However, these measures are often ineffective. Here we show that MG53, a protein with an essential role in cell membrane repair, contributes to the corneal injury-repair process. Native MG53 is present in the corneal epithelia, tear film, and aqueous humor, suggesting its potential function in corneal homeostasis. Knockout of MG53 in mice causes impaired healing and regenerative capacity following injury. Exogenous recombinant human MG53 (rhMG53) protein protects the corneal epithelia against mechanical injury and enhances healing by promoting migration of corneal fibroblasts. Using in vivo alkaline-induced injury to the rat cornea, we show that rhMG53 promotes re-epithelialization and reduces post-injury fibrosis and vascularization. Finally, we show that rhMG53 modulates TGF-β-mediated fibrotic remodeling associated with corneal injury. Overall, our data support the bi-functional role of MG53 in facilitating corneal healing and maintaining corneal transparency by reducing fibrosis and vascularization associated with corneal injuries., Heather Chandler, Tao Tan, Chunlin Yang et al. find that the cell membrane repair protein MG53 plays a key role in repairing cornea injury. Using mouse and rat models, they show that recombinant human MG53 protects the cornea against injury and enhances healing.

New findings suggest that schizophrenia may be linked to gut bacteria., Schizophrenia (SCZ) is a devastating mental disorder with poorly defined underlying molecular mechanisms. The gut microbiome can modulate brain function and behaviors through the microbiota-gut-brain axis. Here, we found that unmedicated and medicated patients with SCZ had a decreased microbiome α-diversity index and marked disturbances of gut microbial composition versus healthy controls (HCs). Several unique bacterial taxa (e.g., Veillonellaceae and Lachnospiraceae) were associated with SCZ severity. A specific microbial panel (Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae) enabled discriminating patients with SCZ from HCs with 0.769 area under the curve. Compared to HCs, germ-free mice receiving SCZ microbiome fecal transplants had lower glutamate and higher glutamine and GABA in the hippocampus and displayed SCZ-relevant behaviors similar to other mouse models of SCZ involving glutamatergic hypofunction. Together, our findings suggest that the SCZ microbiome itself can alter neurochemistry and neurologic function in ways that may be relevant to SCZ pathology.

Background Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people. Methods We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023. Findings We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo (standardised mean difference −0·51, 95% credible interval [CrI] −0·99 to −0·03). In terms of tolerability, fluoxetine was also better than duloxetine (odds ratio [OR] 0·31, 95% CrI 0·13 to 0·95) and imipramine (0·23, 0·04 to 0·78). Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo (5·49, 1·96 to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively). In terms of heterogeneity, the global I2 values were 33·21% for efficacy and 0% for tolerability. Interpretation When considering the risk–benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated.

Women are an important part of the medical workforce, yet little is known about gender differences in psychological morbidity, burnout, job stress and job satisfaction among neurologists. This study assessed gender differences in a large national sample of Chinese neurologists. Multivariate analyses were performed to examine associations. A total of 5558 neurologists were included in the analysis. Compared with their male counterparts, female neurologists were generally younger; were less likely to be married or to have children; had higher levels of education; were in practice for a shorter period of time; were less likely to hold senior roles; and had lower incomes. Male and female neurologists worked similar hours and spent a similar number of nights on call. No gender differences were found in psychological morbidity, burnout, and high levels of job stress for female and male, respectively. Women had higher emotional exhaustion scores, while men were more likely to have low levels of job satisfaction. The multivariate analysis showed that factors independently associated with psychological morbidity, burnout, high levels of job stress and low levels of job satisfaction were generally similar for women and men. These findings increase our understanding of gender differences in psychological morbidity, burnout, job stress, and job satisfaction among neurologists. As more women join the medical profession, these differences may be useful in designing medical training and practice.

// Mohamad Elbaz 1, 2, 5 , Dinesh Ahirwar 1, 2 , Zhang Xiaoli 3 , Xinyu Zhou 6 , Maryam Lustberg 4 , Mohd W. Nasser 1, 2 , Konstantin Shilo 1, 2 , Ramesh K. Ganju 1, 2 1 Department of Pathology, Wexner Medical Center, Ohio State University (OSU), OH, USA 2 The Comprehensive Cancer Center, Ohio State University (OSU), Wexner Medical Center, OH, USA 3 Center for Biostatistics, Ohio State University (OSU), OH, USA 4 Department of Internal Medicine, Ohio State University (OSU), OH, USA 5 Department of Pharmacology, Pharmacy School, Helwan University, Helwan, Egypt 6 Department of surgery, Davis Heart and Lung Research Institute, Ohio State University, OH, USA Correspondence to: Ramesh K. Ganju, email: Ramesh.ganju@osumc.edu Keywords: TRPV2, chemotherapy, TNBC, uptake, doxorubicin Abbreviations: Transient Receptor Potential Vanilloid type 2 (TRPV2), Triple negative Breast cancer (TNBC), Doxorubicin (Dox), CBD (cannabidiol). Received: March 24, 2016 Accepted: April 27, 2016 Published: May 27, 2016 ABSTRACT Transient receptor potential vanilloid type-2 (TRPV2) is an ion channel that is triggered by agonists like cannabidiol (CBD). Triple negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Chemotherapy is still the first line for the treatment of TNBC patients; however, TNBC usually gains rapid resistance and unresponsiveness to chemotherapeutic drugs. In this study, we found that TRPV2 protein is highly up-regulated in TNBC tissues compared to normal breast tissues. We also observed that TNBC and estrogen receptor alpha negative (ERα - ) patients with higher TRPV2 expression have significantly higher recurrence free survival compared to patients with lower TRPV2 expression especially those who were treated with chemotherapy. In addition, we showed that TRPV2 overexpression or activation by CBD significantly increased doxorubicin (DOX) uptake and apoptosis in TNBC cells. The induction of DOX uptake was abrogated by TRPV2 blocking or downregulation. In vivo mouse model studies showed that the TNBC tumors derived from CBD+DOX treated mice have significantly reduced weight and increased apoptosis compared to those treated with CBD or DOX alone. Overall, our studies for the first time revealed that TRPV2 might be a good prognostic marker for TNBC and ERα - breast cancer patient especially for those who are treated with chemotherapy. In addition, TRPV2 activation could be a novel therapeutic strategy to enhance the uptake and efficacy of chemotherapy in TNBC patients.