Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney, and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways.

BACKGROUND: Jianpi Gushen Huayu Decoction (JPGS) has been used to clinically treat diabetic nephropathy (DN) for many years. However, the protective mechanism of JPGS in treating DN remains unclear. AIM: To evaluate the therapeutic effects and the possible mechanism of JPGS on DN. METHODS: We first evaluated the therapeutic potential of JPGS on a DN mouse model. We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics. Furthermore, we examined the effects of JPGS on c-Jun N-terminal kinase (JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3). RESULTS: The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress. Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice. A total of 51 differential metabolites were screened. Pathway analysis results indicated that nine pathways significantly changed between the control and model groups, while six pathways significantly altered between the model and JPGS groups. Pathways related to cysteine and methionine metabolism; alanine, tryptophan metabolism; aspartate and glutamate metabolism; and riboflavin metabolism were identified as the key pathways through which JPGS affects DN. Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors. CONCLUSION: JPGS could markedly treat mice with streptozotocin (STZ)-induced DN, which is possibly related to the regulation of several metabolic pathways found in kidneys. Furthermore, JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathway-mediated apoptosis in DN mice.

Associations between depressive symptoms and quality of life among residents of Wuhan, China during the later stage of the COVID-19 pandemic: A network analysis.

BACKGROUND: Various populations have experienced significant increases in depression and decreased quality of life (QOL) during the coronavirus disease 2019 (COVID-19) pandemic. This network analysis study was designed to elucidate interconnections between particular depressive symptoms and different aspects of QOL and identify the most clinically important symptoms in this network among adults in Wuhan China, the initial epicenter of the COVID-19 pandemic. METHODS: This cross-sectional, convenience-sampling study (N = 2459) was conducted between May 25 to June 18, 2020, after the lockdown policy had been lifted in Wuhan. Depressive symptoms and QOL were measured with the Patient Health Questionnaire-9 (PHQ-9) and first two items of the World Health Organization Quality of Life Questionnaire - brief version (WHOQOL-BREF), respectively. A network structure was constructed from the extended Bayesian Information Criterion (EBIC) model. Network centrality strength and bridge strength were evaluated along with the stability of the derived network model. RESULTS: Loss of energy (DEP-4) and Guilt feelings (DEP-6) were the two central symptoms with the highest strength as well as the two most prominent bridge symptoms connecting the clusters of depression and quality of life (QOL) in tandem with the two nodes from the QOL cluster. Network structure and bridge strengths remained stable after randomly dropping 75 % of the sample. CONCLUSION: Interventions targeting "Loss of energy" and "Guilt feelings" should be evaluated as strategies for reducing depressive symptoms and promoting improved QOL in COVID-19-affected populations.

Prevalence and correlates of suicide attempts in Chinese individuals with borderline personality disorder.

Background: To date, few empirical studies have examined the clinical characteristics of suicide attempts (SA) in individuals with borderline personality disorder (BPD) in China. Aims: To examine the prevalence and factors associated with SA in Chinese individuals with BPD. Methods: In this cross-sectional study, 84 patients with BPD were recruited from a large public psychiatric hospital in Wuhan, China, between 2013 and 2015. Trained experienced psychiatrists interviewed participants to collect clinical data, including demographics, axis I and axis II diagnoses of mental disorders according to the DSM-IV-TR, number of hospitalizations, and history of SA. An interview outline was used to identify the existence of lifetime SA. In addition, the Beck Depression Inventory-II, Buss & Perry Aggression Questionnaire, Child Trauma Questionnaire-Short Form, and Beck Hopelessness Scale were administered to assess respondents' depressive symptoms, aggression, childhood traumatic experiences, and hopelessness. Results: Fifty-two (61.9%) patients reported attempting suicide during their lifetime. Univariate logistic regression analysis screened 7 factors associated with SA in individuals with BPD into Multiple logistic regression analysis: female sex, unemployment, major depressive disorder (MDD), hostility, self-aggression, depressive symptoms, and emotional neglect. Multiple logistic regression analysis identified 3 significant and independent correlates of SA: MDD [odds ratio (OR) = 26.773, 95% confidence interval (CI) = 3.914-183.132, P = 0.001], hostility (OR = 1.073, CI = 1.019-1.130, P = 0.007), and self-aggression (OR = 1.056, CI = 0.998-1.119, P = 0.060). Conclusion: Chinese individuals with BPD have a high risk of suicide. Correlates of SA in this population differ to some extent from those in Western populations as reported in the literature. Paying attention to MDD and some types of aggression in Chinese individuals with BPD may help identify their risk of suicide. Future large-sample cohort study may improve the limitations of this study and further confirm the point of view above.

Mapping post-traumatic stress disorder symptoms and quality of life among residents of Wuhan, China after the COVID-19 outbreak: A network perspective.

OBJECTIVES: The Coronavirus Disease 2019 (COVID-19) outbreak may have a long-term impact on mental health in the general population. This study examined inter-relationships between post-traumatic stress disorder symptoms (PTSS) and quality of life (QOL) in Wuhan residents after the COVID-19 outbreak using network approach. METHODS: A cross-sectional survey was conducted between May 25 and June 18, 2020. PTSS and QOL were measured using Chinese versions of the Post -Traumatic Stress Disorder Checklist - Civilian Version and the World Health Organization Quality of Life Questionnaire - brief version, respectively. RESULTS: A total of 2598 participants were included. A network analysis revealed "Avoiding reminders", "Feeling emotionally numb", "Avoiding thoughts", "Hypervigilance", and "Reliving experiences" as the most central (influential) nodes in PTSS network models both before and after controlling for covariates. The connection between "Avoiding thoughts" and "Avoiding reminders" had the strongest edge. Three symptom communities were detected and can be summarized as "re-experiencing and avoidance", "negative changes in thinking and mood", and "hyperarousal". The bridge symptoms connecting PTSS and QOL were "Sleep disturbances", "Irritability", and "Loss of interest". LIMITATIONS: Limitations included the cross-sectional study design, self-report measures in data collection, and lack of follow-ups beyond the initial phase of the pandemic. CONCLUSIONS: PTSS were common among Wuhan residents even after the initial COVID-19 outbreak had passed. Attention should be paid to lingering symptoms of avoiding reminders, emotional numbness, avoiding thoughts, hypervigilance, and reliving experiences in treating PTSS related to the COVID-19 outbreak.

Effect of drug combination on tacrolimus target dose in renal transplant patients with different CYP3A5 genotypes.

Various factors, including genetic polymorphisms, drug-drug interactions, and patient characteristics influence the blood concentrations of tacrolimus in renal transplant patients. In the present study, we established a population pharmacokinetic model to explore the effect of combined use of Wuzhi capsules/echinocandins and the patients' biochemical parameters such as haematocrit on blood concentrations and target doses of tacrolimus in renal transplant patients with different CYP3A5 genotypes. The aim of the study was to propose an individualised tacrolimus administration regimen for early renal transplant recipients.In this retrospective cohort study, we included 240 renal transplant recipients within 21 days of surgery (174 males and 66 females, mean age 39.4 years), who received tacrolimus alone (n = 54), in combination with Wuzhi capsules (99) or caspofungin (57) or micafungin (30). We collected demographic characteristics, clinical indicators, CYP3A5 genotypes, and 1950 steady-state concentrations of tacrolimus and included them in population pharmacokinetic model. An additional 110 renal transplant recipients and 625 steady-state concentrations of tacrolimus were included for external validation of the model. The population pharmacokinetic model was established and Monte Carlo was used to simulate probabilities for achieving the target concentration for individual tacrolimus administration.A two-compartment model of first-order absorption and elimination was developed to describe the population pharmacokinetics of tacrolimus. CYP3A5 genotypes and co-administration of Wuzhi capsules, as well as time after renal transplantation and haematocrit, were important factors affecting the clearance of tacrolimus. We found no obvious change in trend in the scatter plot of tacrolimus clearance rate vs. haematocrit. The Monte Carlo simulation indicated the following recommended doses of tacrolimus alone: 0.14 mg⋅kg-1⋅d-1 for genotype CYP3A5*1*1, 0.12 mg⋅kg-1⋅d-1 for CYP3A5*1*3, and 0.10 mg⋅kg-1⋅d-1 for CYP3A5*3*3. For patients receiving the combination with Wuzhi capsules, the recommended doses of tacrolimus were 0.10 mg⋅kg-1⋅d-1 for CYP3A5*1*1, 0.08 mg⋅kg-1⋅d-1 for CYP3A5*1*3, and 0.06 mg⋅kg-1⋅d-1 for CYP3A5*3*3 genotypes. Caspofungin or micafungin had no effect on the clearance of tacrolimus in renal transplant recipients.The population pharmacokinetics of tacrolimus in renal transplant patients was evaluated and the individual administration regimen of tacrolimus was simulated. For early kidney transplant recipients receiving tacrolimus treatment, not only body weight, but also CYP3A5 genotypes and drugs used in combination should be considered when determining the target dose of tacrolimus.

Comparison of cognitive impairments with lipid profiles and inflammatory biomarkers in unipolar and bipolar depression.

Cognitive impairments is one of important accompanied symptom in Unipolar depressive disorder (UD) and bipolar disorder (BD) that was hard to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. In this study, we could highlight the difference of cognitive ability in UD and BD by testing lipid profiles and inflammatory biomarkers in major depressive episodes (MDE). 207 subjects (96 unipolar and 111 bipolar depressed patients) were included in this study. We applied Montreal Cognitive Assessment (MoCA) to test cognitive ability. The 24-item Hamilton Depression Rating Scale was used for assessment at the beginning of treatment. A series of clinical variables and lipid profiles were collected from clinic record. We detected pro-inflammatory biomarkers Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), C-reaction protein (CRP) levels and brain-derived neurotrophic factor (BDNF) by enzyme linked immunosorbent assay. From the results, cognitive impairments were more popular in BD than UD, most obviously in severe cognitive impairments (MoCA score<23). And UD showed better cognitive ability than BD in MoCA, particularly in language domain. Compared lipid profiles like total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB) and lipoprotein α (Lpα), we found that ApoB was higher in BD than UD that maybe a risk factor in cognition. There was no obviously difference in TC, TG, HDL-C, LDL-C, ApoA1, or Lpα. Also, we found CRP level in BD was higher than UD, and showed no significant difference in IL-1ß and IL-6 levels. Furthermore, BDNF level which was neurotrophic biomarker for cognition and mood was significantly declined in BD compared with UD. Correlation analysis showed that ApoB and CRP was negative closed associated with MoCA scores. And BDNF level was positive related with cognitive ability in MDE patients. From our results mentioned that quantitative lipid profiles and inflammatory biomarkers analysis might help to objectively identify between these disorders and up our understanding of their pathophysiology. And ApoB, CRP and BDNF could be as potential peripheral candidates in cognitive evaluation to distinguish UD and BD.

Mapping Network Connectivity Among Symptoms of Depression and Pain in Wuhan Residents During the Late-Stage of the COVID-19 Pandemic.

Background: Symptoms of depression and pain often overlap, and they negatively influence the prognosis and treatment outcome of both conditions. However, the comorbidity of depression and pain has not been examined using network analysis, especially in the context of a pandemic. Thus, we mapped out the network connectivity among the symptoms of depression and pain in Wuhan residents in China during the late stage of the COVID-19 pandemic. Methods: This cross-sectional study was conducted from May 25, 2020 to June 18, 2020 in Wuhan, China. Participants' depressive and pain symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ9) and a pain numeric rating scale (NRS), respectively. Network analyses were performed. Results: In total, 2,598 participants completed all assessments. PHQ4 (fatigue) in the depression community showed the highest strength value, followed by PHQ6 (worthlessness) and PHQ2 (depressed or sad mood). PHQ4 (fatigue) was also the most key bridge symptom liking depression and pain, followed by PHQ3 (sleep difficulties). There were no significant differences in network global strength (females: 4.36 vs. males: 4.29; S = 0.075, P = 0.427), network structure-distribution of edge weights (M = 0.12, P = 0.541), and individual edge weights between male and female participants. Conclusion: Depressive and pain symptoms showed strong cross-association with each other. "Fatigue" was the strongest central and bridge symptom in the network model, while "sleep difficulties" was the second strongest bridge symptom. Targeting treatment of both fatigue and sleep problems may help improve depressive and pain symptoms in those affected.

Network Analysis of Depressive Symptoms Among Residents of Wuhan in the Later Stage of the COVID-19 Pandemic.

Background: Depression has been a common mental health problem during the COVID-19 epidemic. From a network perspective, depression can be conceptualized as the result of mutual interactions among individual symptoms, an approach that may elucidate the structure and mechanisms underlying this disorder. This study aimed to examine the structure of depression among residents in Wuhan, the epicenter of the COVID-19 outbreak in China, in the later stage of the COVID-19 pandemic. Methods: A total of 2,515 participants were recruited from the community via snowball sampling. The Patient Health Questionnaire was used to assess self-reported depressive symptoms with the QuestionnaireStar program. The network structure and relevant centrality indices of depression were examined in this sample. Results: Network analysis revealed Fatigue, Sad mood, Guilt and Motor disturbances as the most central symptoms, while Suicide and Sleep problems had the lowest centrality. No significant differences were found between women and men regarding network structure (maximum difference = 0.11, p = 0.44) and global strength (global strength difference = 0.04; female vs. male: 3.78 vs. 3.83, p = 0.51), a finding that suggests there are no gender differences in the structure or centrality of depressive symptoms. Limitations: Due to the cross-sectional study design, causal relationships between these depressive symptoms or dynamic changes in networks over time could not be established. Conclusions: Fatigue, Sad mood, Guilt, and Motor disturbances should be prioritized as targets in interventions and prevention efforts to reduce depression among residents in Wuhan, in the later stage of the COVID-19 pandemic.

Mental health status and quality of life in close contacts of COVID-19 patients in the post-COVID-19 era: a comparative study.

Close contacts of those with COVID-19 (CC) may experience distress and long-lasting mental health effects. However, the mental health status and quality of life (QOL) in CC have not been adequately examined. This study examined the mental health status and QOL in CC during the post-COVID-19 period. This cross-sectional study comprised 1169 CC and 1290 who were non-close contacts (non-CC). Demographic data were collected; depression, fatigue, post-traumatic stress symptoms (PTSS) and QOL were assessed using the Patient Health Questionnaire - 9 items (PHQ-9), fatigue numeric rating scale, Post-Traumatic Stress Disorder Checklist - 17 items (PCL-17), and the World Health Organization Quality of Life Questionnaire - brief version (WHOQOL-BREF), respectively. Analysis of covariance was used to compare depressive symptoms, QOL, fatigue, and PTSS between the CC and non-CC groups. Multiple logistic regression analyses were performed to determine the independent correlates for depression, fatigue, PTSS, and QOL in the CC group. Compared to the non-CC group, the CC group reported significantly more severe depression (F(1, 2458) = 5.58, p = 0.018) and fatigue (F(1, 2458) = 9.22, p = 0.002) in the post-COVID-19 period. No significant differences in PTSS and QOL between the CC and non-CC groups were found (F(1, 2458) = 2.93, p = 0.087 for PTSS; F(1, 2458) = 3.45, p = 0.064 for QOL). In the CC group, younger age, financial loss due to COVID-19, and perception of poor or fair health status were significantly associated with depression and fatigue, while frequent use of mass media was significantly associated with fatigue. In conclusion, close contacts of COVID-19 patients experienced high levels of depression and fatigue in the post-COVID-19 period. Due to the negative effects of depression and fatigue on daily functioning, early detection and timely interventions should be provided to this neglected population.

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients.

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms might influence the occurrence of coronary heart disease (CHD) in T2DM patients. The purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD in T2DM patients. Methods A total of 197 subjects with T2DM were studied, of which 95 patients with CHD. The genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method, and compared between patients with CHD and those without CHD. Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD (P=0.011). However, there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD. Furthermore, the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine (Hcy) levels (≤15 µmol/L) (P=0.006), while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hcy levels (>15 µmol/L) (P=0.491). Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hcy levels.

Independent replications and integrative analyses confirm TRANK1 as a susceptibility gene for bipolar disorder.

Genetic analyses for bipolar disorder (BD) have achieved prominent success in Europeans in recent years, whereas its genetic basis in other populations remains relatively less understood. We herein report that the leading risk locus for BD in European genome-wide association studies (GWAS), the single-nucleotide polymorphism (SNP) rs9834970 near TRANK1 at 3p22 region, is also genome-wide significantly associated with BD in a meta-analysis of four independent East Asian samples including 5748 cases and 65,361 controls (p = 2.27 × 10-8, odds ratio = 1.136). Expression quantitative trait loci (eQTL) analyses and summary data-based Mendelian randomization (SMR) analyses in multiple human brain samples suggest that lower TRANK1 mRNA expression is a principal BD risk factor explaining its genetic risk signals at 3p22. We also identified another SNP rs4789 in the 3' untranslated region (3'UTR) of TRANK1 showing stronger eQTL associations as well as genome-wide significant association with BD. Despite the relatively unclear neuronal function of TRANK1, our mRNA expression analyses in the human brains and in rat primary cortical neurons reveal that genes highly correlated with TRANK1 are significantly enriched in the biological processes related to dendritic spine, synaptic plasticity, axon guidance and circadian entrainment, and are also more likely to exhibit strong associations in psychiatric GWAS (e.g., the CACNA1C gene). Overall, our results support that TRANK1 is a potential BD risk gene. Further studies elucidating its roles in this illness are needed.

Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals: A Genome-Wide Association Study and Meta-analysis.

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood. Objective: To explore the genetic basis of BD in the Han Chinese population. Design, Setting, and Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020. Main Outcomes and Measures: Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association. Results: The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956). Conclusions and Relevance: This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

Identification of a novel germ cell marker MnTdrd from the oriental river prawn Macrobrachium nipponense.

Germ cell-specific genes play an important role in establishing the reproductive system in sexual organisms and have been used as valuable markers for studying gametogenesis and sex differentiation. Previously, we isolated a vasa transcript as a germ cell marker to trace the origin and migration of germ cells in the oriental river prawn Macrobrachium nipponense. Here, we identified a new germ cell-specific marker MnTdrd RNA and assessed its temporal and spatial expression during oogenesis and embryogenesis. MnTdrd transcripts were expressed in high abundance in unfertilized eggs and embryos at cleavage stage and then dropped significantly during late embryogenesis, suggesting that MnTdrd mRNA is maternally inherited. In situ hybridization of ovarian tissue showed that MnTdrd mRNA was initially present in the cytoplasm of previtellogenic oocyte and localized to the perinuclear region as the accumulation of yolk in vitellogenic oocyte. Whole-mount in situ hybridization of embryos showed that MnTdrd-positive signals were only localized in one blastomere until 16-cell stage. In the blastula, there were approximately 16 MnTdrd-positive blastomeres. During embryonized-zoea stage, the MnTdrd-positive cells aggregated as a cluster and migrated to the genital rudiment which would develop into primordial germ cells (PGCs). The localized expression pattern of MnTdrd transcripts resembled that of the previously identified germ cell marker vasa, supporting the preformation mode of germ cell specification. Therefore, we concluded that MnTdrd, together with vasa, is a component of the germ plasm and might have critical roles in germ cell formation and differentiation in the prawn. Thus, MnTdrd can be used as a novel germ cell marker to trace the origin and migration of germ cells.

Cognitive Behavioural Therapy for Insomnia Monotherapy in Patients with Medical or Psychiatric Comorbidities: a Meta-Analysis of Randomized Controlled Trials.

This is a meta-analysis of randomized controlled trials (RCTs) comparing cognitive behaviour therapy for insomnia (CBT-I) monotherapy with active control treatment for insomnia in patients with medical or psychiatric comorbidities. Both international (PubMed, EMBASE, PsycINFO, Cochrane Library) and Chinese (WanFang, and CNKI) databases were systematically searched. The random effects model was used. Thirteen RCTs comparing CBT-I (n = 441) and active controls (n = 412) groups were included. CBT-I group showed significant advantage over active controls at post-treatment assessment in terms of Insomnia Severity Index (ISI; SMD = -0.74), sleep onset latency (SMD = -0.36), wake after sleep onset (SMD = -0.21), sleep quality (SMD = 0.56), Pittsburgh sleep quality index total scores (PSQI; SMD = -0.76) and the total score of dysfunctional beliefs and attitudes about sleep scale (DBAS; SMD = -1.09). Subgroup analyses revealed significant improvement in sleep onset latency in patients with psychiatric disorders (SMD = -0.45), while significant reduction of number of wakeup after sleep onset was found in patients with medical conditions (SMD = -0.31). This meta-analysis found that CBT-I monotherapy had greater efficacy than other active control treatment for insomnia in patients with medical or psychiatric comorbidities.

Estrogen Receptor α Agonist is Beneficial for Young Female Rats Against Chronic Unpredicted Mild Stress-Induced Depressive Behavior and Cognitive Deficits.

BACKGROUND: Women are reported more likely to develop depression and dementia. However, the involved mechanism is poorly understood. OBJECTIVE: Here, we clarified the role of estrogen receptor α (ERα) in depression and cognitive deficit in young female rats. METHODS: After being exposed to 7-weeks' chronic unpredicted mild stress (CUMS), the depression resilient rats (Res rats) and depressed rats (Dep rats) were selected according to their records in sucrose preference test, forced swimming test, and open field test. Their cognition abilities were tested by Morris water maze. Proteomic assay, immunoprecipitation, western blotting, immunohistochemical, and Nissl staining were also used to understand the involved mechanism. RESULTS: Compared with control rats and Res rats, Dep rats showed cognitive deficits and hippocampal impairments revealed by proteomic data, neuron losses, increased cleaved caspase-3, ß-catenin phosphorylation, and glycogen synthase kinase3ß (GSK3ß) activation. As ERα, but not ERß, was found declined in hippocampi of Dep rats, 4,4k,4a-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT, an ERα agonist, 1 mg/kg/day), was used to treat Dep rats (Dep + PPT). Twenty days later, the depressive behaviors, cognition deficits, and hippocampal neuron loss were rescued in Dep + PPT rats. Furthermore, Res and Dep + PPT rats had higher levels of ß-catenin combined with ERα and lower levels of ß-catenin combined with GSK3ß than Dep rats in hippocampi. CONCLUSION: These results demonstrated hippocampal ERα is an important pro-resilient factor in CUMS-induced depressive behaviors and cognitive deficits. It was also given that the neuroprotection afforded by hippocampal ERα/Wnt interactions have significant implications for cognition and emotion in young females.

Cognitive behavioural therapy monotherapy for insomnia: A meta-analysis of randomized controlled trials.

This was a meta-analysis of randomized controlled trials (RCTs) comparing the effects of cognitive behavioural therapy for insomnia (CBTI) as a monotherapy and active control treatments in persons with insomnia who have no major medical conditions or psychiatric comorbidities. PubMed, PsycINFO, EMBASE, Cochrane Library databases, WanFang and CNKI were systematically and independently searched. Standardized mean differences (SMDs) and risk ratio (RR) with their 95% confidence intervals (CIs) were calculated. Nine RCTs with 12 treatment arms comparing CBTI (n = 479) and active control (n = 510) groups were analyzed. Compared to the active control group, the CBTI group showed significantly less improvement in insomnia at post-CBTI assessment in terms of sleep efficiency (SMD: 0.32, 95% CI: 0.00 to 0.63), sleep latency (SMD: -0.33, 95% CI: -0.56 to -0.09), wake after sleep onset (SMD: -0.27, 95% CI: -0.52 to -0.01), the total scores of Pittsburgh Sleep Quality Index (SMD: -0.52, 95% CI: -0.86 to -0.19), the Insomnia Symptom Index (SMD: -0.68, 95% CI: -1.01 to -0.36), the Dysfunctional Attitudes and Beliefs About Sleep Scale (SMD: -0.76, 95% CI: -1.25 to -0.27), and the Athens Insomnia Scale (SMD: -0.66, 95% CI: -1.07 to -0.24). In this meta-analysis, CBTI monotherapy showed no advantage in improving insomnia compared with other standard treatments.

Further confirmation of netrin 1 receptor (DCC) as a depression risk gene via integrations of multi-omics data.

Genome-wide association studies (GWAS) of major depression and its relevant biological phenotypes have been extensively conducted in large samples, and transcriptome-wide analyses in the tissues of brain regions relevant to pathogenesis of depression, e.g., dorsolateral prefrontal cortex (DLPFC), have also been widely performed recently. Integrating these multi-omics data will enable unveiling of depression risk genes and even underlying pathological mechanisms. Here, we employ summary data-based Mendelian randomization (SMR) and integrative risk gene selector (iRIGS) approaches to integrate multi-omics data from GWAS, DLPFC expression quantitative trait loci (eQTL) analyses and enhancer-promoter physical link studies to prioritize high-confidence risk genes for depression, followed by independent replications across distinct populations. These integrative analyses identify multiple high-confidence depression risk genes, and numerous lines of evidence supporting pivotal roles of the netrin 1 receptor (DCC) gene in this illness across different populations. Our subsequent explorative analyses further suggest that DCC significantly predicts neuroticism, well-being spectrum, cognitive function and putamen structure in general populations. Gene expression correlation and pathway analyses in DLPFC further show that DCC potentially participates in the biological processes and pathways underlying synaptic plasticity, axon guidance, circadian entrainment, as well as learning and long-term potentiation. These results are in agreement with the recent findings of this gene in neurodevelopment and psychiatric disorders, and we thus further confirm that DCC is an important susceptibility gene for depression, and might be a potential target for new antidepressants.

Two new NiII and ZnII metal-organic frameworks of glutarate and 1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene ligands: syntheses, structures and luminescence sensing properties.

Two new metal-organic frameworks (MOFs), namely, three-dimensional poly[diaquabis{µ2-1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene}bis(µ2-glutarato)dinickel(II)] monohydrate], {[Ni2(C5H6O4)2(C16H18N4)2(H2O)2]·H2O}n or {[Ni2(Glu)2(1,4-mbix)2(H2O)2]·H2O}n, (I), and two-dimensional poly[[{µ2-1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene}(µ2-glutarato)zinc(II)] tetrahydrate], {[Zn(C5H6O4)(C16H18N4)]·4H2O}n or {[Zn(Glu)(1,4-mbix)]·4H2O}n (II), have been synthesized hydrothermally using glutarate (Glu2-) mixed with 1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene (1,4-mbix), and characterized by single-crystal X-ray diffraction, IR and UV-Vis spectroscopy, powder X-ray diffraction, and thermogravimetric and photoluminescence analyses. NiII MOF (I) shows a 4-connected 3D framework with point symbol 66, but is not a typical dia network. ZnII MOF (II) displays a two-dimensional 44-sql network with one-dimensional water chains penetrating the grids along the c direction. The solid-state photoluminescence analysis of (II) was performed at room temperature and the MOF exhibits highly selective sensing toward Fe3+ and Cr2O72- ions in aqueous solution.

Identification of a functional 339 bp Alu insertion polymorphism in the schizophrenia-associated locus at 10q24.32.

Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) or small indels robustly associated with schizophrenia; however, the functional risk variations remain largely unknown. We investigated the 10q24.32 locus and discovered a 339 bp Alu insertion polymorphism (rs71389983) in complete linkage disequilibrium (LD) with the schizophrenia GWAS risk variant rs7914558. The presence of the Alu insertion at rs71389983 strongly repressed transcriptional activities in in vitro luciferase assays. This polymorphism may be a target for future mechanistic research. Our study also underlines the importance and necessity of considering previously underestimated Alu polymorphisms in future genetic studies of schizophrenia.