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Abstract Background We aimed to clarify the controversial relationship between levels of high-sensitivity C-reactive protein (hs-CRP) and severity of depression in men and women. Methods Medical records were retrospectively analyzed for 1,236 inpatients at our medical center who were diagnosed with depression at discharge between January 2018 and August 2022. Depression severity was assessed during hospitalization using the 24-item Hamilton Depression Rating Scale. Potential associations between severity scores and hs-CRP levels were explored using multivariate linear regression as well as smooth curve fitting to detect non-linear patterns. Results In male patients, hs-CRP levels between 2.00 mg/L and 10.00 mg/L showed a non-linear association with depression severity overall (fully adjusted β = 1.69, 95% CI 0.65 to 2.72), as well as with severity of specific symptoms such as hopelessness, sluggishness, and cognitive disturbance. In female patients, hs-CRP levels showed a linear association with severity of cognitive disturbance (fully adjusted β = 0.07, 95% CI 0.01 to 0.12). These results remained significant after adjusting for age, body mass index, diabetes, hypertension, history of drinking, history of smoking, and estradiol levels. Discussion Levels of hs-CRP show sex-specific associations with depression severity, particularly levels between 2.00 and 10.00 mg/L in men. These findings may help develop personalized anti-inflammatory treatments for depression, particularly for men with hs-CRP levels of 2.00–10.00 mg/L.

ABSTRACTMagnetic coupling is an approach employed to prevent gas leakage by transforming the dynamic seal into a non-contact static seal for the recovery of natural gas pressure energy. The impact of thermal demagnetization necessitates the consideration of the heat dissipation characteristics resulting from eddy current losses in the rotating magnetic field. We performed a numerical study of thermal-magnetic coupling in a magnetic transmission validated by experimental results. The Maxwell software was utilized to simulate the distribution characteristics of induced current, while the Fluent software was employed to analyze the dissipation of heat caused by eddy currents. The obtained simulation results reveal a proportional increase in induced current and eddy current losses with the rotation speed. Also, the eddy current losses increase together with the thickness of the isolation cover, since more volume of the conducting media is affected by the eddy currents. Furthermore, reducing the electrical conductivities of the isolation cover and enhancing the internal flow rates can effectively decrease the temperature of the magnetic coupling and mitigate thermal demagnetization. These research findings offer valuable insights for the design and optimization of non-contact transmission methods, ultimately enhancing the safety of natural gas top-pressure energy recovery equipment.

Summary: Background: The need for new therapeutics for attention deficit hyperactivity disorder (ADHD) is evident. Brain, cerebrospinal fluid (CSF), and plasma protein biomarkers with causal genetic evidence could represent potential drug targets. However, a comprehensive screen of the proteome has not yet been conducted. Methods: We employed a three-pronged approach using Mendelian Randomization (MR) and Bayesian colocalization analysis. Firstly, we studied 608 brains, 214 CSF, and 612 plasma proteins as potential causal mediators of ADHD using MR analysis. Secondly, we analysed the consistency of the discovered biomarkers across three distinct subtypes of ADHD: childhood, persistent, and late-diagnosed ADHD. Finally, we extended our analysis to examine the correlation between identified biomarkers and Tourette syndrome and pervasive autism spectrum disorder (ASD), conditions often linked with ADHD. To validate the MR findings, we conducted sensitivity analysis. Additionally, we performed cell type analysis on the human brain to identify risk genes that are notably enriched in various brain cell types. Findings: After applying Bonferroni correction, we found that the risk of ADHD was increased by brain proteins GMPPB, NAA80, HYI, CISD2, and HYI, TIE1 in CSF and plasma. Proteins GMPPB, NAA80, ICA1L, CISD2, TIE1, and RMDN1 showed overlapped loci with ADHD risk through Bayesian colocalization. Overexpression of GMPPB protein was linked to an increase in the risk for all three ADHD subtypes. While ICA1L provided protection against both ASD and ADHD, CISD2 increased the probability of both disorders. Cell-specific studies revealed that GMPPB, NAA80, ICA1L, and CISD2 were predominantly present on the surface of excitatory-inhibitory neurons. Interpretation: Our comprehensive MR investigation of the brain, CSF, and plasma proteomes revealed seven proteins with causal connections to ADHD. Particularly, GMPPB and TIE1 emerged as intriguing targets for potential ADHD therapy. Funding: This work was partly funded by the Key R & D Program of Zhejiang (T.L. 2022C03096); the National Natural Science Foundation of China Project (C.Z. 82001413); Postdoctoral Foundation of West China Hospital (C.Z. 2020HXBH163).

Background: Palmoplantar warts (PWs) are a usual skin disease associated with human papillomavirus (HPV) that can affect patients’ quality of life. The traditional Chinese medicine (TCM) Weiren Xiaoyou formula (WRXYF) is a relatively gentle and effective therapy that has achieved good therapeutic effects in clinical practice, but its mechanism has not yet been studied. Methods: A meta-analysis was carried out to identify the potential advantages of topical TCM for PW treatment. Clinical cases suggested that WRXYF was an effective therapeutic agent against PWs. Network pharmacology was utilized to predict potential targets for the main bioactive compound, tanshinone IIA (Tan IIA), in WRXYF. High-performance liquid chromatography with electrospray mass spectrometry (HPLC/ESI-MS) was applied to detect major components. The bioactivity of Tan IIA against PWs was then validated with quantitative polymerase chain reaction (q-PCR), fluorescence in situ hybridization (FISH), electron microscopy and Western blotting. Results: A meta-analysis was conducted on 10 randomized clinical trials (RCTs) involving 2260 participants suggested that topical TCM could more effectively treat PWs than conventional medications. Network pharmacology identified Tan IIA as a candidate agent from 17 major compounds assessed by HPLC/ESI-MS because of its stable binding with 10 PW targets. HPV2, HPV27, and HPV57 were the main infectious strains in tissues obtained from PW patients and in HPV-infected HaCaT cells. Tan IIA treatment effectively destroyed viral particles and reduced the viral copy numbers of the three HPV subtypes. The results shown that Tan IIA has the ability to halt the cell cycle of HPV-infected HaCaT cells specifically in the G0/G1 phase. A total of 6 cell cycle-related proteins were regulated after Tan IIA treatment, demonstrating the role of Tan IIA in inhibiting the cell cycle. Conclusion: Tan IIA, the primary bioactive constituent in WRXYF, enhances PWs by halting the cell cycle in the G0/G1 phase via modulation of the p53 signaling pathway.

Abstract Background Network modeling has been proposed as an effective approach to examine complex associations among antecedents, mediators and symptoms. This study aimed to investigate whether the severity of depressive symptoms affects the multivariate relationships among symptoms and mediating factors over a 2-year longitudinal follow-up. Methods We recruited a school-based cohort of 1480 primary and secondary school students over four semesters from January 2020 to December 2021. The participants (n = 1145) were assessed at four time points (ages 10–13 years old at baseline). Based on a cut-off score of 5 on the 9-item Patient Health Questionnaire at each time point, the participants were categorized into the non-depressive symptom (NDS) and depressive symptom (DS) groups. We conducted network analysis to investigate the symptom-to-symptom influences in these two groups over time. Results The global network metrics did not differ statistically between the NDS and DS groups at four time points. However, network connection strength varied with symptom severity. The edge weights between learning anxiety and social anxiety were prominently in the NDS group over time. The central factors for NDS and DS were oversensitivity and impulsivity (3 out of 4 time points), respectively. Moreover, both node strength and closeness were stable over time in both groups. Conclusions Our study suggests that interrelationships among symptoms and contributing factors are generally stable in adolescents, but a higher severity of depressive symptoms may lead to increased stability in these relationships.

Abstract Schizophrenia has been linked to polymorphism in genes encoding components of the complement system, and hyperactive complement activity has been linked to immune dysfunction in schizophrenia patients. Whether and how specific complement components influence brain structure and cognition in the disease is unclear. Here we compared 52 drug-naïve patients with first-episode schizophrenia and 52 healthy controls in terms of levels of peripheral complement factors, cortical thickness (CT), logical memory and psychotic symptoms. We also explored the relationship between complement factors with CT, cognition and psychotic symptoms. Patients showed significantly higher levels of C1q, C4, factor B, factor H, and properdin in plasma. Among patients, higher levels of C3 in plasma were associated with worse memory recall, while higher levels of C4, factor B and factor H were associated with thinner sensory cortex. These findings link dysregulation of specific complement components to abnormal brain structure and cognition in schizophrenia.

Background Elevated platelet count (PLTc) is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis. However, the impact of antipsychotic medications on PLTc and its association with symptom improvement remain unclear.Aims We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related variables.Methods A total of 2985 patients with schizophrenia were randomised into seven groups. Each group received one of seven antipsychotic treatments and was assessed at 2, 4 and 6 weeks. Clinical symptoms were evaluated using the positive and negative syndrome scale (PANSS). Additionally, we measured blood cell counts and metabolic parameters, such as blood lipids. Repeated measures analysis of variance was used to examine the effect of antipsychotics on PLTc changes, while structural equation modelling was used to assess the predictive value of PLTc on PANSS changes.Results PLTc significantly increased in patients treated with aripiprazole (F=6.00, p=0.003), ziprasidone (F=7.10, p

With the aging of the population, the prevalence of osteoporosis and multimorbidity is increasing. Patients with osteoporosis often experience varying levels of emotional distress, including anxiety and depression. However, few studies have explored the patterns of multiple conditions and their impact on patients’ emotional distress. Here, we conducted a network analysis to explore the patterns of multimorbidities and their impact on emotional distress in 13,359 Chinese Han patients with osteoporosis. The results showed that multimorbidity was prevalent in Chinese patients with osteoporosis and increased with age, and was more frequent in males than in females, with the most common pattern of multimorbidity being osteoporosis and essential (primary) hypertension. Finally, we found that patients’ emotional distress increased with the number of multimorbidities, especially in female patients, and identified eight multimorbidities with high correlation to patients’ emotional distress.

Objective: Glucagon-like peptide (GLP)-1 is an incretin hormone that acts after food intake to stimulate insulin production, enhance satiety, and promote weight loss. Here we describe the discovery and characterization of ecnoglutide (XW003), a novel GLP-1 analog. Methods: We engineered a series of GLP-1 peptide analogs with an alanine to valine substitution (Ala8Val) and a γGlu-2xAEEA linked C18 diacid fatty acid at various positions. Ecnoglutide was selected and characterized in GLP-1 receptor signaling assays in vitro, as well as in db/db mice and a diet induced obese (DIO) rat model. A Phase 1, double-blind, randomized, placebo-controlled, single (SAD) and multiple ascending dose (MAD) study was conducted to evaluate the safety, tolerability, and pharmacokinetics of subcutaneous ecnoglutide injection in healthy participants. SAD doses ranged from 0.03 to 1.0 mg; MAD doses ranged from 0.2 to 0.6 mg once weekly for 6 weeks (ClinicalTrials.gov Identifier: NCT04389775). Results: In vitro, ecnoglutide potently induced cAMP (EC50 = 0.018 nM) but not GLP-1 receptor internalization (EC50 > 10 μM), suggesting a desirable signaling bias. In rodent models, ecnoglutide significantly reduced blood glucose, promoted insulin induction, and led to more pronounced body weight reduction compared to semaglutide. In a Phase 1 trial, ecnoglutide was generally safe and well tolerated as a once-weekly injection for up to 6 weeks. Adverse events included decreased appetite, nausea, and headache. The half-life at steady state ranged from 124 to 138 h, supporting once-weekly dosing. Conclusions: Ecnoglutide showed a favorable potency, pharmacokinetic, and tolerability profile, as well as a simplified manufacturing process. These results support the continued development of ecnoglutide for the treatment of type 2 diabetes and obesity.

Abstract Background Visual memory impairment is one of the most commonly complained symptoms in patients with major depressive disorder (MDD). Pattern glare is also a distorted visual phenomenon that puzzles patients with MDD. Nevertheless, how these two phenomena interact in MDD remains unknown. This study investigated the association between pattern glare and visual memory in MDD patients. Methods Sixty-two patients with MDD and forty-nine age-, sex- and education level-matched healthy controls (HCs) were included in this study. The Pattern Recognition Memory (PRM) test and the Brief Visual Memory Test-Revised (BVMT-R) were applied to measure visual memory. The pattern glare test including three patterns with different spatial frequencies (SFs) was used to explore pattern glare levels. Results Patients with MDD scored lower on the PRM-PCi, BVMT-R1, BVMT-R2, BVMT-R3, and BVMT-Rt and higher on the PRM-MCLd than HCs (all p

Abstract Background The Sheng-ji Hua-yu (SJHY) formula is a quite effective Traditional Chinese Medicines (TCM) in the treatment of delayed diabetic wounds. Previous research has shown that the SJHY formula has significant anti-inflammatory and wound-healing effects, but the precise mechanism remains unknown. The purpose of this study was to evaluate the effects of rhein, a compound extracted from SJHY formula, in keratinocytes and to investigate the underlying mechanisms. Methods Microscale thermophoresis (MST) technology was used to confirm that rhein binds directly to oestrogen receptors (ERs). Rhein was then used to treat keratinocytes in vitro. Cell cycle and proliferation analysis, Real-time polymerase chain reaction (RT-PCR) and Western-blot were conducted. Results Rhein increased the proportion of cells in the S phase of the cell cycle and promoted keratinocyte proliferation. ICI 182,780, an ER inhibitor, was also used to treat keratinocytes. The expression of c-myc mRNA and protein induced by rhein was antagonized by ICI 182,780, indicating that this induction is ER dependent. Intervention with ICI 182,780 had no effect on the upregulation of FosB and JunD, indicating that activator protein 1 (AP-1) members (FosB and JunD) are involved in rhein-induced c-myc mRNA and protein expression but does not require the ER. Conclusion The present study found that rhein stimulates keratinocyte proliferation by activating the oestrogen signalling pathway via the oestrogen receptor, which induces the expression of c-myc in collaboration with FosB and JunD, thereby accelerating the process of re-epithelialization.

BackgroundThere is an urgent need to identify differentiating and disease-monitoring biomarkers of schizophrenia, bipolar disorders (BD), and major depressive disorders (MDD) to improve treatment and management.MethodsWe recruited 54 first-episode schizophrenia (FES) patients, 52 BD patients, 35 MDD patients, and 54 healthy controls from inpatient and outpatient clinics. α-Melanocyte Stimulating Hormone (α-MSH), β-endorphin, neurotensin, orexin-A, oxytocin, and substance P were investigated using quantitative multiplex assay method. Psychotic symptoms were measured using the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS), manic symptoms using the Young Mania Rating Scale (YMRS), and depressive symptoms using 17 item-Hamilton Depression Rating Scale (HAMD). We additionally measured cognitive function by using a battery of tests given to all participants.Resultsα-MSH, neurotensin, orexin-A, oxytocin, and substance P were decreased in the three patient groups compared with controls. Neurotensin outperformed all biomarkers in differentiating patient groups from controls. There were no significant differences for 6 neuropeptides in their ability to differentiate between the three patient groups. Higher neurotensin was associated with better executive function across the entire sample. Lower oxytocin and higher substance p were associated with more psychotic symptoms in FES and BD groups. β-endorphin was associated with early morning wakening symptom in all three patient groups.ConclusionOur research shows decreased circulating neuropeptides have the potential to differentiate severe mental illnesses from controls. These neuropeptides are promising treatment targets for improving clinical symptoms and cognitive function in FES, BD, and MDD.

Abstract Background Identifying the causal genes at the risk loci and elucidating their roles in schizophrenia (SCZ) pathogenesis remain significant challenges. To explore risk variants associated with gene expression in the human brain and to identify genes whose expression change may contribute to the susceptibility of SCZ, here we report a comprehensive integrative study on SCZ. Methods We systematically integrated the genetic associations from a large-scale SCZ GWAS (N = 56,418) and brain expression quantitative trait loci (eQTL) data (N = 175) using a Bayesian statistical framework (Sherlock) and Summary data-based Mendelian Randomization (SMR). We also measured brain structure of 86 first-episode antipsychotic-naive schizophrenia patients and 152 healthy controls with the structural MRI. Results Both Sherlock (P = 3. 38 × 10−6) and SMR (P = 1. 90 × 10−8) analyses showed that TYW5 mRNA expression was significantly associated with risk of SCZ. Brain-based studies also identified a significant association between TYW5 protein abundance and SCZ. The single-nucleotide polymorphism rs203772 showed significant association with SCZ and the risk allele is associated with higher transcriptional level of TYW5 in the prefrontal cortex. We further found that TYW5 was significantly upregulated in the brain tissues of SCZ cases compared with controls. In addition, TYW5 expression was also significantly higher in neurons induced from pluripotent stem cells of schizophrenia cases compared with controls. Finally, combining analysis of genotyping and MRI data showed that rs203772 was significantly associated with gray matter volume of the right middle frontal gyrus and left precuneus. Conclusions We confirmed that TYW5 is a risk gene for SCZ. Our results provide useful information toward a better understanding of the genetic mechanism of TYW5 in risk of SCZ.

Abstract Background It is unclear whether psychotic experiences (PEs) gradually merge into states of clinical psychosis along a continuum which correspond to a dimensional classification or whether latent classes appear above a certain severity threshold which correspond better to diagnostic categories of psychosis. Methods Annual cross-sectional surveys, 2014–19, among Chinese undergraduates (N = 47,004) measured PEs, depression and etiological risk factors using standardized self-report instruments. We created a psychosis continuum with five levels and tested linear and extra-linear contrasts in associated etiological risk factors, before and after adjustment for depression. We carried out latent class analysis. Results Categorical expression of psychosis, including hallucinations and delusions, nuclear symptoms, and nuclear symptoms and depression were found at severe level 5. Etiological risk factors which impacted linearly across the continuum were more common for depression. Child maltreatment impacted extra-linearly on both psychosis and depression. Family history of psychosis impacted linearly on psychosis; male sex and urban birth impacted extra-linearly and were specific for psychosis. Four latent classes were found, but only at level 5. These corresponded to nuclear schizophrenia symptoms, nuclear schizophrenia and depressive symptoms, severe depression, and an unclassified category with moderate prevalence of PEs. Conclusion Quantitative and qualitative changes in the underlying structure of psychosis were observed at the most severe level along a psychosis continuum, where four latent classes emerged. These corresponded to existing categorical classifications but require confirmation with clinical interview. PEs are non-specific and our findings suggest some are on a continuum with depression, whilst others are on a continuum with non-affective psychosis. Differing patterns of impact from etiological risk factors across the spectrum of psychopathology determine outcome at the most severe level of these continua.

BackgroundSuicide is one of the leading causes of death for college students. The predictors of suicidal ideation among college students are inconsistent and few studies have systematically investigated psychological symptoms of college students to predict suicide. Therefore, this study aims to develop a suicidal ideation prediction model and explore important predictors of suicidal ideation among college students in China.MethodsWe recruited 1,500 college students of Sichuan University and followed up for 4 years. Demographic information, behavioral and psychological information of the participants were collected using computer-based questionnaires. The Radial Basis Function Neural Network (RBFNN) method was used to develop three suicidal ideation risk prediction models and to identify important predictive factors for suicidal ideation among college students.ResultsThe incidence of suicidal ideation among college students in the last 12 months ranged from 3.00 to 4.07%. The prediction accuracies of all the three models were over 91.7%. The area under curve scores were up to 0.96. Previous suicidal ideation and poor subjective sleep quality were the most robust predictors. Poor self-rated mental health has also been identified to be an important predictor. Paranoid symptom, internet addiction, poor self-rated physical health, poor self-rated overall health, emotional abuse, low average annual household income per person and heavy study pressure were potential predictors for suicidal ideation.ConclusionsThe study suggested that the RBFNN method was accurate in predicting suicidal ideation. And students who have ever had previous suicidal ideation and poor sleep quality should be paid consistent attention to.

Abstract Background Urban birth and upbringing show consistent associations with psychotic illness but the key urban exposures remain unknown. Associations with psychotic-like experiences (PEs) are inconsistent. These could be confounded by common mental disorders associated with PEs. Furthermore, associations between PEs and urban exposures may not extrapolate to psychotic disorders such as schizophrenia. Methods Annual cross-sectional surveys among first year Chinese undergraduates 2014–2019 (n = 47,004). Self-reported, hierarchical categorisation of psychosis: from psychoticism, paranoid ideation, schizotypal symptoms, nuclear syndrome using SCL-90-R, to clinical diagnosis of schizophrenia. Depressive symptoms using PHQ 9. Dissociative symptoms and posttraumatic stress disorder (PTSD) measured using PCL-C. Etiological factors of family history and childhood disadvantage. We studied effects of urban birth, urban living and critical times of exposure in childhood on psychosis phenotypes. Results Associations with urbanicity were found only after adjustments for depression. Urban birth was associated with paranoia (AOR 1.34, 1.18–1.53), schizotypal symptoms (AOR 1.59, 1.29–1.96), and schizophrenia (AOR 2.07, 1.10–3.87). The same phenotypes showed associations with urban residence > 10 years. Only schizophrenia showed an association with urban exposure birth-3 years (AOR 7.01, 1.90–25.86). Child maltreatment was associated with both psychosis and depression. Urbanicity measured across the total sample did not show any associations with demography, family history of psychosis, or child maltreatment. Sensitivity analysis additionally adjusting for dissociative symptoms and PTSD showed the same pattern of findings. Conclusions Urban birth and urban living showed a hierarchical pattern of increasing associations from paranoid ideation to schizotypal disorder to schizophrenia, confirming that associations for psychotic experiences could be extrapolated to schizophrenia, but only after adjusting for confounding from depression, dissociative symptoms and PTSD. Several etiological factors were the same for psychosis and depression. Future studies of PEs should adjust for confounding from common mental disorders and dissociative symptoms. Effects of urbanicity on psychosis were not explained by demography, family history of mental disorder, or child maltreatment.

Emerging evidence has demonstrated overlapping biological abnormalities underlying schizophrenia (SCZ), bipolar disorder (BP), and major depressive disorder (MDD); these overlapping abnormalities help explain the high heterogeneity and the similarity of patients within and among diagnostic categories. This study aimed to identify transdiagnostic subtypes of these psychiatric disorders based on lipidomics abnormalities. We performed discriminant analysis to identify lipids that classified patients (N = 349, 112 with SCZ, 132 with BP, and 105 with MDD) and healthy controls (N = 198). Ten lipids that mainly regulate energy metabolism, inflammation, oxidative stress, and fatty acylation of proteins were identified. We found two subtypes (named Cluster 1 and Cluster 2 subtypes) across patients with SCZ, BP, and MDD by consensus clustering analysis based on the above 10 lipids. The distribution of clinical diagnosis, functional impairment measured by Global Assessment of Functioning (GAF) scales, and brain white matter abnormalities measured by fractional anisotropy (FA) and radial diffusivity (RD) differed in the two subtypes. Patients within the Cluster 2 subtype were mainly SCZ and BP patients and featured significantly elevated RD along the genu of corpus callosum (GCC) region and lower GAF scores than patients within the Cluster 1 subtype. The SCZ and BP patients within the Cluster 2 subtype shared similar biological patterns; that is, these patients had comparable brain white matter abnormalities and functional impairment, which is consistent with previous studies. Our findings indicate that peripheral lipid abnormalities might help identify homogeneous transdiagnostic subtypes across psychiatric disorders.

Schizophrenia (SCZ) and bipolar disorder (BD) are debilitating neurodevelopmental disorders with high heritability. In this study, peripheral blood mononuclear cells (PBMCs) were donated by three females. An adolescent female was clinically diagnosed as first-episode SCZ. One of her cousins was clinically diagnosed as BD and another one was unaffected control. Induced pluripotent stem cells (iPSCs) were established with reprograming factors Oct4, Sox2, Nanog, Lin28, c-myc, Klf4, and SV40LT. All lines presented normal karyotype and highly expressed pluripotency markers in vitro. All iPSCs were capable to differentiate into derivatives of three germ layers in vivo.

Abstract Background Previous research using whole-brain neuroimaging techniques has revealed structural differences of grey matter (GM) in alcohol use disorder (AUD) patients. However, some of the findings diverge from other neuroimaging studies and require further replication. The quantity of relevant research has, thus far, been limited and the association between GM and abstinence duration of AUD patients has not yet been systematically reviewed. Methods The present research conducted a meta-analysis of voxel-based GM studies in AUD patients published before Jan 2021. The study utilised a whole brain-based d-mapping approach to explore GM changes in AUD patients, and further analysed the relationship between GM deficits, abstinence duration and individual differences. Results The current research included 23 studies with a sample size of 846 AUD patients and 878 controls. The d-mapping approach identified lower GM in brain regions including the right cingulate gyrus, right insula and left middle frontal gyrus in AUD patients compared to controls. Meta-regression analyses found increasing GM atrophy in the right insula associated with the longer mean abstinence duration of the samples in the studies in our analysis. GM atrophy was also found positively correlated with the mean age of the samples in the right insula, and positively correlated with male ratio in the left middle frontal gyrus. Conclusions GM atrophy was found in the cingulate gyrus and insula in AUD patients. These findings align with published meta-analyses, suggesting they are potential deficits for AUD patients. Abstinence duration, age and gender also affect GM atrophy in AUD patients. This research provides some evidence of the underlying neuroanatomical nature of AUD.

Bullous pemphigoid (BP) is a life-threatening autoimmune disease of the skin that is mainly characterized by a large range of tension blisters and intense itching of the skin. The 1-year mortality rate of BP was 23.5%. Superinfection caused by skin lesion ulceration is one of the important causes of disease death. Therefore, it is challenging to control infection and improve skin wound healing. Here, we report the case of an elderly woman who presented with BP and involved the oral mucosa. The patient was successfully treated with hormones combined with topical berberine, and 95% of the patients’ lesions healed completely after 1 month. In addition, we inductively analyzed the current treatments for BP to provide a reference for BP clinical treatment.

The aim of this study was to develop a brief version of cognitive assessment test for evaluating the efficacy of treatments targeting cognitive impairments in Chinese schizophrenia patients, to examine its reliability, and establish normative data. Stratified according to age, gender, and educational level, healthy adult subjects were recruited from fifteen institutions in seven administrative regions of China and 723 valid samples were obtained, of which 50 were retested. Generalized Linear Models were conducted to analyze the effects of age, sex, and education. There was no significant difference between genders, while significant effects were demonstrated respectively among age and education on the normative data of C-BCT. The Cronbach α of C-BCT is 0.75, and the test-retest reliability (ICC) ranged from 0.62 to 0.76. Normative data of C-BCT were generated by gender, age and education, and the effects of these demographic factors were analyzed. It revealed good internal consistency and test-retest reliability of C-BCT.

Abstract Background Residential mobility during childhood increases risk of psychopathology in adulthood and is a common experience among Chinese children. This study investigated associations between number and age of first move, etiological risk factors for psychopathology, and common mental disorders in adolescence and early adulthood. Methods The sample included 39,531 undergraduates (84.5% completion rate) age 15–34 years in their first year at a Chinese comprehensive university in annual cross-sectional surveys during 2014–2018. Common mental disorders measured using standardised self-report instruments. Data analysed using logistic regression models and interaction analysis. Results Half of all students experienced one or more moves of residence before age 15 years. Outcomes of Depression, Somatisation, Obsessive-compulsive disorder, Hallucinations and Delusions, and Suicide attempts showed dose-response relationships with increasing number of moves. Other etiological risk factors, including childhood disadvantage and maltreatment, showed similar dose response relationships but did not confound associations with mobility. We found interactions between reporting any move and being a left-behind child on depression and somatisation; number of moves and younger age at first move on depression, somatisation, suicide attempts and hallucinations and delusions. Conclusions Residential mobility in childhood is associated with psychopathology in adulthood and this association increases with increasing number of moves. Mobility is also associated with childhood disadvantage and maltreatment but associations with psychopathology are independent of these factors. Multiplicative effects were shown for multiple moves starting at a younger age and if the participant had been a left-behind child.

Schizophrenia (SCZ) is a debilitating neurodevelopmental disorder with a high heritability. In this study, peripheral blood mononuclear cells (PBMCs) were donated by a pair of dizygotic twins. The female was clinically diagnosed as SCZ by Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria, and her unaffected male sibling was healthy control. Induced pluripotent stem cells (iPSCs) were established using Episomal vectors carrying reprograming factors OCT4, SOX2, NANOG, LIN28, c-MYC, KLF4, and SV40LT. These lines with normal karyotype highly expressed pluripotency markers and are capable to differentiate into derivatives of three germ layers. Both lines are negative of mycoplasma.

PurposeUniversity students experience high levels of stress, and the prevalence of depression is higher than in the general population. The reason is not clear. More effective interventions and better prevention are needed.MethodsWe did annual cross-sectional surveys of Chinese undergraduates 2014–2018 (mean age 18.7 [SD 2.1], N = 39,573). We measured adaptation to university life using the Adolescent Self-rating Life Events Checklist (ASLEC) and common mental disorders using standardized self-report instruments. Regression analyses identified associations between childhood maltreatment, current family problems, stress in adaptation to undergraduate life, and psychiatric morbidity. Mediation analyses further tested relationships between these factors.ResultsChildhood maltreatment, current family problems, stress in adaptation, and psychiatric morbidity were all significantly associated with each other. The strongest association between childhood experiences and psychiatric morbidity was for sexual abuse and depression (OR = 3.39, 95%CI: 2.38–4.83, p < 0.001) and between stress from adaptation and somatic disorder (OR = 4.54, 95%CI: 3.62–5.68, p < 0.001). Associations between childhood maltreatment and stress from university life were partly mediated by psychiatric morbidity. Associations between family problems and psychiatric morbidity were mediated by stress from university life.ConclusionsStress from adaptation to university life and pressures from academic study exert stronger effects on psychiatric morbidity among students than childhood traumatic experiences and current family problems, although these factors are closely interrelated. Mental health services for students should focus on adaptation to university life and pressures from academic study as well as external factors of childhood trauma and family problems.

Abstract Background Visual deficits have been reported in abundance by recent studies on major depressive disorder. Pattern glare manifests as visual distortions, such as the symptoms of headache, glare, eyestrain, illusions of shapes, colors, and motion when viewing repetitive striped patterns, of which some can be observed in major depressive disorder. Inspired by what mentioned, the present study aims to explore whether there exists association between pattern glare and major depressive disorder and further attempts to explore possible clinical diagnostic value of pattern glare in major depressive disorder. Methods Twenty-four patients diagnosed with major depressive disorder (MDDs group) were compared with 30 age-, gender- and education level-matched healthy control subjects (HCs group) on their visual stress with black-and-white gratings of different spatial frequencies-0.3 (low-SF), 2.3 (mid-SF), and 9.4 (high-SF) cycles per degree (c/deg)-which was named pattern glare test. The MDDs group divided into first episode medication-free group (fMDD) and recurrent medicated group (rMDD), comparisons of pattern glare scores (PGS) were performed within the MDDs group. We used Pearson and Spearman analysis to explore the relationship between some clinical indexes and pattern glare scores. ROC (receiver operating characteristic) curve was used to evaluate whether pattern glare test was able to discriminate patients and healthy controls. Results The mid-SF pattern glare score significantly elevated in patients with major depressive disorder compared to control subjects. No differences of pattern glare scores were found between fMDD and rMDD. A significant negative correlation between mid-high difference and age in HCs group was found. There were no correlations between other variables and pattern glare scores. The mid-SF score has limited value in the diagnosis of major depressive disorder. Conclusions We observed an increased level of pattern glare in patients with major depressive disorder, reflecting the existence of cortical hyper-excitability in major depressive disorder. The mid-SF score may have a value in understanding cortical excitability in major depressive disorder.

Objective: To identify the potential biomarkers for predicting depression in diabetes mellitus using support vector machine to analyze routine biochemical tests and vital signs between two groups: subjects with both diabetes mellitus and depression, and subjects with diabetes mellitus alone.Methods: Electronic medical records upon admission and biochemical tests and vital signs of 135 patients with both diabetes mellitus and depression and 187 patients with diabetes mellitus alone were identified for this retrospective study. After matching on factors of age and sex, the two groups (n = 72 for each group) were classified by the recursive feature elimination-based support vector machine, of which, the training data, validation data, and testing data were split for ranking the parameters, determine the optimal parameters, and assess classification performance. The biomarkers were identified by 10-fold cross validation.Results: The experimental results identified 8 predictive biomarkers with classification accuracy of 78%. The 8 biomarkers are magnesium, cholesterol, AST/ALT, percentage of monocytes, bilirubin indirect, triglyceride, lactic dehydrogenase, and diastolic blood pressure. Receiver operating characteristic curve analysis was also adopted with area under the curve being 0.72.Conclusions: Some biochemical parameters may be potential biomarkers to predict depression among the subjects with diabetes mellitus.

Background: Neurobiological mechanisms underlying the development of major depressive disorder (MDD) may differ depending on onset ages. Our aim was to determine whether regional homogeneity (ReHo) changes in early-onset depression (EOD) and late-onset depression (LOD) are different, which could also delineate EOD and LOD.Methods: Ninety-one MDD patients and 115 healthy controls (HCs) were recruited, and resting-state functional magnetic resonance imaging data were collected. The ReHo comparison was conducted using analysis of variance.Results: Compared with HCs, MDD patients showed decreased ReHo in the left precentral gyrus and the left middle cingulum area, and increased ReHo in the left middle orbital frontal gyrus and superior temporal gyrus. Compared with LOD patients, young HC separately, EOD patients had significantly increased ReHo in the right inferior frontal triangular gyrus and the left postcentral gyrus. However, compared with young HC, EOD patients showed decreased ReHo in the right superior frontal gyrus/supplementary motor area and the right medial frontal gyrus. ReHo in the right inferior frontal triangular gyrus was negatively correlated with the severity of cognitive disturbance in LOD patients (r = −0.47, p = 0.002), but not in EOD patients (r = 0.21, p = 0.178).Conclusion: MDD patients with different onset ages may have different pathophysiological mechanisms; the EOD patients had more abnormal ReHo than LOD patients in the prefrontal lobe, especially the right inferior frontal triangular gyrus.

Background: Major depressive disorder (MDD) is a common disease which is complicated by metabolic disorder. Although MDD has been studied relatively intensively, its metabolism is yet to be elucidated.Methods: To profile the global pathophysiological processes of MDD patients, we used metabolomics to identify differential metabolites and applied a new database Metabolite set enrichment analysis (MSEA) to discover dysfunctions of metabolic pathways of this disease. Hydrophilic metabolomics were applied to identify metabolites by profiling the plasma from 55 MDD patients and 100 sex-, gender-, BMI-matched healthy controls. The metabolites were then analyzed in MSEA in an attempt to discover different metabolic pathways. To investigate dysregulated pathways, we further divided MDD patients into two cohorts: (1) MDD patients with anxiety symptoms and (2) MDD patients without anxiety symptoms.Results: Metabolites which were hit in those pathways correlated with depressive and anxiety symptoms. Altogether, 17 metabolic pathways were enriched in MDD patients, and 23 metabolites were hit in those pathways. Three metabolic pathways were enriched in MDD patients without anxiety, including glycine and serine metabolism, arginine and proline metabolism, and phenylalanine and tyrosine metabolism. In addition, L-glutamic acid was positively correlated with the severity of depression and retardation if hit in MDD patients without anxiety symptoms.Conclusions: Different kinds of metabolic pathophysiological processes were found in MDD patients. Disorder of glycine and serine metabolism was observed in both MDD patients with anxiety and those without.

Abstract Background A body of studies has focused on the olfactory impairment among people with schizophrenia. The effect of sex on this relationship has attracted the attention of researchers. These issues have not been studied much in Chinese schizophrenia patients. Methods We conducted a case-control study of 110 first-episode antipsychotic medicine naïve schizophrenia patients aged 18–35 years and 110 controls, matched by age and sex. Odour threshold, discrimination and identification were assessed by the “Sniffin’ Sticks” test. Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Results The odour threshold, discrimination and identification scores of patients with schizophrenia were significantly lower than those of the healthy control group. The difference in identification score had statistical significance between male and female patients with schizophrenia (t = − 2.45, P

Abstract This study aims to investigate the role of personality traits and subjective exposure experiences in posttraumatic stress disorder and depression symptoms. In Qingchuan, 21,652 children aged 7 to 15 years were assessed using face-to-face interviews one year after the Wenchuan earthquake in China. The Junior Eysenck Personality Questionnaire, a modified earthquake exposure scale, the UCLA Posttraumatic Stress Disorder Reaction Index (adolescent), and the Adolescent Depression Inventory were used to assess personality characteristics, trauma experiences, posttraumatic stress disorder and depression symptoms, respectively. The measurement was completed with 20,749 children. After adjusting for other factors by multinomial logistic regression analysis, neuroticism, having felt unable to escape from the disaster and having been trapped for a longer time were risk factors of posttraumatic stress disorder and depression symptoms. Socialization was a protective factor of them. Having felt extreme panic or fear was a risk factor of posttraumatic stress disorder symptoms. For depression symptoms, introversion and psychoticism were risk factors, and extraversion was a protective factor. This study was conducted with the largest representative sample of child survivors of a natural, devastating disaster in a developing country. These results could be useful for planning psychological intervention strategies for children and for influencing further research.

Background: Treatment of psoriasis is always difficult, which requires intensive scientific research. Objective: Tripterygium wilfordii Hook F (TwHF) with acitretin(TwHF + acitretin) is normally used in treating psoriasis. This study aimed to investigate the correlation of plasma miR-126 expression with risk and severity of psoriasis, and its predictive value of response to TwHF + acitretin treatment in psoriasis. Methods: MiRNA-126(MiR-126) expression in plasma was analyzed in psoriasis patients at month 0 (M0), M1, M3 and M6 and in health controls (HCs) at enrollment by qPCR. Psoriasis-affected body surface area (BSA) and Psoriasis Area and Severity Index (PASI) score were used to assess severity and treatment response. Results: Plasma miR-126 levels were decreased in psoriasis patients compared with HCs (P 0.05). Conclusion: Plasma miR-126 expression is negatively correlated with psoriasis risk and severity, and its high baseline level can be used as a biomarker to predict worse clinical response to TwHF + acitretin treatment in psoriasis.

Male and female patients with schizophrenia show significant differences in a number of important clinical features, yet the neural substrates of these differences are still poorly understood. Here we explored the sex differences in the brain functional aberrations in 124 treatment-naïve patients with first-episode schizophrenia (61 males), compared with 102 age-matched healthy controls (50 males). Maps of degree centrality (DC) and amplitude of low-frequency fluctuations (ALFF) were constructed using resting-state functional magnetic resonance imaging data and compared between groups. We found that: (1) Selective DC reduction was observed in the right putamen (Put_R) in male patients and the left middle frontal gyrus (MFG) in female patients; (2) Functional connectivity analysis (using Put_R and MFG as seeds) found that male and female patients have disturbed functional integration in two separate networks, i.e., the sensorimotor network and the default mode network; (3) Significant ALFF alterations were also observed in these two networks in both genders; (4) Sex specific brain functional alterations were associated with various symptoms in patients. These results suggested that sex-specific patterns of functional aberration existed in schizophrenia, and these patterns were associated with the clinical features both in male and female patients.

There is no highly effective chemotherapy for malignant gliomas to date. We found that dimethylaminomicheliolide (DMAMCL), a selective inhibitor of acute myeloid leukemia (AML) stem/progenitor cells, inhibited the growth of glioma cells.The distribution of DMAMCL in brain was analyzed by an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS) system. The anti-tumor evaluations of DMAMCL in vitro were performed by MTT, FACS and RT-PCR. In vivo, the mixture of C6 cells and matrigel was injected into caudatum, and the anti-tumor activity of DMAMCL was evaluated by tumor growth and rat survival. The toxicity of DMAMCL was evaluated by body weight, daily food intake, hematological or serum biochemical analyses, and histological appearance of tissues.The IC50 values of DMAMCL against the C6 and U-87MG cell lines in vitro were 27.18 ± 1.89 μM and 20.58 ± 1.61 μM, respectively. DAMMCL down-regulated the anti-apoptosis gene Bcl-2 and increased apoptosis in C6 and U-87MG cells in a dose-dependent manner. In a C6 rat tumor model, daily administration of DMAMCL for 21 days reduced the burden of C6 tumors by 60% to 88% compared to controls, and more than doubled the mean lifespan of tumor-bearing rats. Distribution analysis showed that the DMAMCL concentration was higher in the brain than in plasma. Evaluations for toxicity revealed that oral administration of DMAMCL at 200 or 300 mg/kg once a day for 21 days did not result in toxicity.These results suggest that DMAMCL is highly promising for the treatment of glioma.