B7-H3 suppresses CD8+ T cell immunologic function through reprogramming glycolytic metabolism.

Malignant neoplasms pose a formidable threat to human well-being. Prior studies have documented the extensive expression of B7 homolog 3 (B7-H3 or CD276) across various tumors, affecting glucose metabolism. Yet, the link between metabolic modulation and immune responses remains largely unexplored. Our study reveals a significant association between B7-H3 expression and advanced tumor stages, lymph node metastasis, and tumor location in oral squamous cell carcinoma (OSCC). We further elucidate B7-H3's role in mediating glucose competition between cancer cells and CD8+ T cells. Through co-culturing tumor cells with flow cytometry-sorted CD8+ T cells, we measured glucose uptake and lactate secretion in both cell types. Additionally, we assessed interferon-gamma (IFN-γ) release and the immune and exhaustion status of CD8+ T cells. Our findings indicate that B7-H3 enhances glycolysis in OSCC and malignant melanoma, while simultaneously inhibiting CD8+ T cell glycolysis. Silencing B7-H3 led to increased IFN-γ secretion in co-cultures, highlighting its significant role in modulating CD8+ T cell functions within the tumor microenvironment and its impact on tumorigenicity. We also demonstrate that glycolysis inhibition can be mitigated by exogenous glucose supplementation. Mechanistically, our study suggests B7-H3's influence on metabolism might be mediated through the phosphoinositide3-kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathway. This research unveils how B7-H3 affects immune functions via metabolic reprogramming.

Thiol-Triggered Tandem Dearomative Michael Addition/Intramolecular Henry Reaction of 2-Nitrobenzofurans: Access to Sulfur-Containing Polyheterocyclic Compounds.

An efficient dearomative cyclization of 2-nitrobenzofurans via a thiol-triggered tandem Michael addition/intramolecular Henry reaction has been developed. A range of thiochromeno[3,2-b]benzofuran-11-ols and tetrahydrothieno[3,2-b]benzofuran-3-ols could be obtained in up to 99% yield and up to >20:1 dr. The valuable thiochromone fused benzofurans could be prepared with the reaction of 2-nitrobenzofurans and 2-mercaptobenzaldehyde via the tandem dearomative Michael addition/intramolecular Henry reaction/rearomatization/oxidative dehydrogenation process in a one-pot two-step operation. A mechanism for the reaction was tentatively proposed.

Emerging functions and therapeutic targets of IL-38 in central nervous system diseases.

Interleukin (IL)-38 is a newly discovered cytokine of the IL-1 family, which binds various receptors (i.e., IL-36R, IL-1 receptor accessory protein-like 1, and IL-1R1) in the central nervous system (CNS). The hallmark physiological function of IL-38 is competitive binding to IL-36R, as does the IL-36R antagonist. Emerging research has shown that IL-38 is abnormally expressed in the serum and brain tissue of patients with ischemic stroke (IS) and autism spectrum disorder (ASD), suggesting that IL-38 may play an important role in neurological diseases. Important advances include that IL-38 alleviates neuromyelitis optica disorder (NMOD) by inhibiting Th17 expression, improves IS by protecting against atherosclerosis via regulating immune cells and inflammation, and reduces IL-1ß and CXCL8 release through inhibiting human microglial activity post-ASD. In contrast, IL-38 mRNA is markedly increased and is mainly expressed in phagocytes in spinal cord injury (SCI). IL-38 ablation attenuated SCI by reducing immune cell infiltration. However, the effect and underlying mechanism of IL-38 in CNS diseases remain inadequately characterized. In this review, we summarize the biological characteristics, pathophysiological role, and potential mechanisms of IL-38 in CNS diseases (e.g., NMOD, Alzheimer's disease, ASD, IS, TBI, and SCI), aiming to explore the therapeutic potential of IL-38 in the prevention and treatment of CNS diseases.

Validation of the DBP-1333b upper-arm blood pressure monitor according to the AAMI/ESH/ISO universal standard (ISO 81060-2:2018+Amd.1:2020).

To evaluate the accuracy of the DBP-1333b upper-arm blood pressure (BP) measuring device in the adult population according to the AAMI/ESH/ISO universal standard (ISO 81060-2:2018+Amd.1:2020). Subjects were recruited in the adult population. The test device was an arm-type electronic sphygmomanometer (DBP-1333b) and the reference device was a desktop sphygmomanometer (XJ11D). Using the BP data measured by the desktop sphygmomanometer as reference BP, the accuracy of the non-invasive BP module of the test device was evaluated to determine whether it met the requirements. Data from 90 individuals were analysed. According to Criterion 1, the mean difference of SBP between the test and reference device was 0.19 mmHg and the SD was 7.45 mmHg. The mean difference of DBP was -0.59 mmHg and the SD was 6.47 mmHg. The mean difference of both SBP and DBP was less than 5 mmHg, and the SD was less than 8 mmHg, which met the requirements. According to Criterion 2, SD of SBP was 5.79 mmHg, which was less than 6.95 mmHg and met the requirements. The SD of DBP was 5.58 mmHg, which was less than 6.93 mmHg and met the requirements. It was concluded that the DBP-1333b complies with the AAMI/ESH/ISO universal standard (ISO 81060-2:2018+Amd.1:2020) and can be recommended for use by the adults.

Enhanced Photoinduced Carrier Separation in Fe-MOF-525/CdS for Photocatalytic Hydrogen Evolution: Improved Catalytic Dynamics with Specific Active Sites.

Single-atom metal-anchored porphyrin-based metal-organic frameworks (MOFs) have shown excellent light absorption, catalytic sites, and high stability during photocatalytic reactions, while there are still challenges for facile assembly with quantum dots to enhance catalytic dynamics. Herein, a kind of Fe single atom-doped MOF material (Fe-MOF-525) was ball milled with CdS in a proper ratio through Fe-N4 and Fe-N-C bonding, which showed the enhanced photoinduced carrier separation ability. As a result, extended light absorption ranges of CdS/Fe-MOF-5252.3 induced the promotion of the photocatalytic hydrogen (H2) value (3638.6 µmol g-1 h-1), which was 7.2 and 2.3 times higher than those of Fe-MOF-525 and CdS. In this work, the facile synthetic technique, specific active sites, and enhanced catalytic dynamics in the composite highlight the future research on MOF-based heterojunctions and their potential photocatalysis applications..

Research progress of biomineralization for the diagnosis and treatment of malignant tumors.

Malignant tumors have long been a prominent subject of research in order to foster innovation and advancement in diagnostic and therapeutic modalities. However, the current clinical treatment of malignant tumors faces significant limitations. In light of recent advancements, the World Health Organization (WHO) officially designated malignant tumors as a chronic disease in 2006. Accordingly, maintaining the tumor in a stable state and minimizing its detrimental impact on the body emerges as a potentially advantageous approach to oncological treatment. One emerging strategy that has garnered substantial attention from the academic community is the construction of a biomineralized layer surrounding solid tumors for tumor blockade therapy. This innovative approach is regarded as safe, effective, and long-lasting. This review aims to provide a comprehensive summary of the advancements made in the utilization of biomineralization for the diagnosis and treatment of malignant tumors.

Fabrication of a micro/nanocomposite structure on the surface of high oxygen concentration titanium to promote bone formation.

This study investigated the properties of the micro/nano composite structure on the surface of high oxygen concentration titanium (HOC-Ti) after anodic oxidation modification (HOC-NT) and evaluated its biocompatibility as a dental implant material in vitro and in vivo. HOC-Ti was produced by titanium powders and rutile powders using the powder metallurgy method. Its surface was modified by anodic oxidation. After detecting the electrochemical characteristics, the surface properties of HOC-NT were investigated. MC3T3 and MLO-Y4 cells were employed to evaluate the biocompatibility of HOC-NT and cocultured to study the effects of the changes in osteocytes induced by HOC-NT on osteoblasts. While, its possible mechanism was investigated. In addition, osseointegration around the HOC-NT implant was investigated through in vivo experiments. The results showed that a unique micronano composite structure on the HOC-Ti surface with excellent hydrophilicity and suitable surface roughness was created after anodic oxidation promoted by its electrochemical characteristics. The YAP protein may play an important role in regulating bone remodeling by ß-catenin and Rankl/OPG Signaling Pathways. An in vivo study also revealed an accelerated formation rate of new bone and more stable osseointegration around the HOC-NT implant. In view of all experimental results, it could be concluded that the unique morphology of HOC-NT has enhanced physicochemical and biological properties. The promotion of bone formation around implants indicated the feasibility of HOC-NT for applications in oral implants.

The interactions between host genome and gut microbiome increase the risk of psychiatric disorders: Mendelian randomization and biological annotation.

BACKGROUND: The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association studies on human genome and gut microbiome (mbGWAS) have revealed important host-microbiome interactions. However, establishing causal relationships between specific gut microbiome features and psychological conditions remains challenging due to insufficient sample sizes of previous studies of mbGWAS. METHODS: Cross-cohort meta-analysis (via METAL) and multi-trait analysis (via MTAG) were used to enhance the statistical power of mbGWAS for identifying genetic variants and genes. Using two large mbGWAS studies (7,738 and 5,959 participants respectively) and12 disease-specific studies from the Psychiatric Genomics Consortium (PGC), we performed bidirectional two-sample mendelian randomization (MR) analyses between microbial features and psychiatric diseases (up to 500,199 individuals). Additionally, we conducted downstream gene- and gene-set-based analyses to investigate the shared biology linking gut microbiota and psychiatric diseases. RESULTS: METAL and MTAG conducted in mbGWAS could boost power for gene prioritization and MR analysis. Increases in the number of lead SNPs and mapped genes were witnessed in 13/15 species and 5/10 genera after using METAL, and MTAG analysis gained an increase in sample size equivalent to expanding the original samples from 7% to 63%. Following METAL use, we identified a positive association between Bacteroides faecis and ADHD (OR, 1.09; 95 %CI, 1.02-1.16; P = 0.008). Bacteroides eggerthii and Bacteroides thetaiotaomicron were observed to be positively associated with PTSD (OR, 1.11; 95 %CI, 1.03-1.20; P = 0.007; OR, 1.11; 95 %CI, 1.01-1.23; P = 0.03). These findings remained stable across statistical models and sensitivity analyses. No genetic liabilities to psychiatric diseases may alter the abundance of gut microorganisms.Using biological annotation, we identified that those genes contributing to microbiomes (e.g., GRIN2A and RBFOX1) are expressed and enriched in human brain tissues. CONCLUSIONS: Our statistical genetics strategy helps to enhance the power of mbGWAS, and our genetic findings offer new insights into biological pleiotropy and causal relationship between microbiota and psychiatric diseases.

A novel technique for implant-supported fixed complete rehabilitation based on a dynamic virtual patient.

BACKGROUND: A digital workflow for implant-supported fixed complete prostheses (ISFCP) using photogrammetry (PG), virtual articulator (VA), and virtual facebow (VF) data remains a challenge. METHODS: The novel ISFCP technique included four steps: (1) formation of a dynamic virtual patient, (2) integration of PG data, (3) fabrication of a diagnostic ISFCP, and (4) fabrication of a definitive ISFCP and test of the deviation. RESULTS: Dynamic virtual patients were formed by integrating PG, VA, and VF data. The cumulative root mean square deviation between the designed data and actual definitive prosthesis was 140.4 µm. CONCLUSIONS: The novel technique for ISFCP fabrication described in this paper can help optimise the clinical efficiency and quality of ISFCP but requires an initial learning curve. CLINICAL SIGNIFICANCE: This technique provides a direct workflow, using PG, VA, and VF data, to fabricate ISFCP based on the provisional restoration.

Extended characterization of IL-33/ST2 as a predictor for wound age determination in skin wound tissue samples of humans and mice.

Interleukin (IL)-33, an important inflammatory cytokine, is highly expressed in skin wound tissue and serum of humans and mice, and plays an essential role in the process of skin wound healing (SWH) dependent on the IL-33/suppression of tumorigenicity 2 (ST2) pathway. However, whether IL-33 and ST2 themselves, as well as their interaction, can be applied for skin wound age determination in forensic practice remains incompletely characterized. Human skin samples with injured intervals of a few minutes to 24 hours (hs) and mouse skin samples with injured intervals of 1 h to 14 days (ds) were collected. Herein, the results demonstrated that IL-33 and ST2 are increased in the human skin wounds, and that in mice skin wounds, there is an increase over time, with IL-33 expression peaking at 24 hs and 10 ds, and ST2 expression peaking at 12 hs and 7 ds. Notably, the relative quantity of IL-33 and ST2 proteins < 0.35 suggested a wound age of 3 hs; their relative quantity > 1.0 suggested a wound age of 24 hs post-mouse skin wounds. In addition, immunofluorescent staining results showed that IL-33 and ST2 were consistently expressed in the cytoplasm of F4/80-positive macrophages and CD31-positive vascular endothelial cells with or without skin wounds, whereas nuclear localization of IL-33 was absent in α-SMA-positive myofibroblasts with skin wounds. Interestingly, IL-33 administration facilitated the wound area closure by increasing the proliferation of cytokeratin (K) 14 -positive keratinocytes and vimentin-positive fibroblasts. In contrast, treating with its antagonist (i.e., anti-IL-33) or receptor antagonist (e.g., anti-ST2) exacerbated the aforementioned pathological changes. Moreover, treatment with IL-33 combined with anti-IL-33 or anti-ST2 reversed the effect of IL-33 on facilitating skin wound closure, suggesting that IL-33 administration facilitated skin wound closure through the IL-33/ST2 signaling pathway. Collectively, these findings indicate that the detection of IL-33/ST2 might be a reliable biomarker for the determination of skin wound age in forensic practice.

Association between childhood trauma and white matter deficits in first-episode schizophrenia.

OBJECTIVE: This study aimed to investigate the relationship between childhood trauma (ChT) and white matter (WM) deficits in first-episode schizophrenia (FES). METHODS: A total of 103 individuals with FES and 206 healthy control individuals (HCs) were enrolled and assessed based on ChT Questionnaire (CTQ) and Positive and Negative Symptoms Scale (PANSS). Diffusion tensor imaging was acquired on a Signa 3.0 T scanner. Map of fractional anisotropy (FA) was analyzed using Tract-Based Spatial Statistics. Hierarchical logistic regression analyses were used to examine associations of sociodemographic characteristics, total CTQ scores, and WM deficits. RESULTS: Compared with the HCs group, the FES group showed significantly lower FA in several WM bundles (left anterior thalamic radiation, left inferior frontal-occipital fasciculus, left cingulum, forceps major, and forceps minor), and the mean FA value in these WM bundles was inversely related to the total CTQ score. In addition, a higher CTQ score may increase the risk of schizophrenia, while higher FA values may decrease the risk of schizophrenia. CONCLUSION: This study demonstrates that individuals with FES evince widespread cerebral WM abnormalities and that these abnormalities were associated with ChT. These results provide clues about the neural basis and potential biomarkers of schizophrenia.

Early Efficacy of Antipsychotic Medications at Week 2 Predicts Subsequent Responses at Week 6 in a Large-scale Randomized Controlled Trial.

BACKGROUND: Since the early clinical efficacy of antipsychotics has not yet been well perceived, this study sought to decide whether the efficacy of antipsychotics at week 2 can predict subsequent responses at week 6 and identify how such predictive capacities vary among different antipsychotics and psychotic symptoms. METHODS: A total of 3010 patients with schizophrenia enrolled in a randomized controlled trial (RCT) and received a 6-week treatment with one antipsychotic drug randomly chosen from five atypical antipsychotics (risperidone 2-6 mg/d, olanzapine 5-20 mg/d, quetiapine 400-750 mg/d, aripiprazole 10-30 mg/d, and ziprasidone 80-160 mg/d) and two typical antipsychotics (perphenazine 20-60 mg/d and haloperidol 6-20 mg/d). Early efficacy was defined as the reduction rate using the Positive and Negative Syndrome Scale (PANSS) total score at week 2. With cut-offs at 50% reduction, logistic regression, receiver operating characteristic (ROC) and random forests were adopted. RESULTS: The reduction rate of PANSS total score and improvement of psychotic symptoms at week 2 enabled subsequent responses to 7 antipsychotics to be predicted, in which improvements in delusions, lack of judgment and insight, unusual thought content, and suspiciousness/ persecution were endowed with the greatest weight. CONCLUSION: It is robust enough to clinically predict treatment responses to antipsychotics at week 6 using the reduction rate of PANSS total score and symptom relief at week 2. Psychiatric clinicians had better determine whether to switch the treatment plan by the first 2 weeks.

Associations between urban birth or childhood trauma and first-episode schizophrenia mediated by low IQ.

Exposure to urban birth, childhood trauma, and lower Intelligence Quotient (IQ) were the most well-established risk factors for schizophrenia in developed countries. In developing countries, whether urban birth is a risk factor for schizophrenia and how these factors are related to one another remain unclear. This study aimed to investigate whether IQ mediates the relationship between urban birth or childhood trauma and first-episode schizophrenia (FES) in China. Birthplace, childhood trauma questionnaire (CTQ), and IQ were collected from 144 patients with FES and 256 healthy controls (HCs). Hierarchical logistic regression analysis was conducted to investigate the associations between birthplace, childhood trauma, IQ, and FES. Furthermore, mediation analysis was used to explore the mediation of IQ in the relationship between birthplace or childhood trauma and FES. After adjusting for age, sex and educational attainment, the final model identified urban birth (odds ratio (OR) = 3.15, 95% CI = 1.54, 6.44) and childhood trauma (OR = 2.79, 95% CI = 1.92, 4.06) were associated an elevated risk for FES. The 52.94% total effect of birthplace on the risk of FES could be offset by IQ (indirect effect/direct effect). The association between childhood trauma and FES could be partly explained by IQ (22.5%). In total, the mediation model explained 70.5% of the total variance in FES. Our study provides evidence that urban birth and childhood trauma are associated with an increased risk of FES. Furthermore, IQ mediates the relationship between urban birth or childhood trauma and FES.

Patterns of Convergence and Divergence Between Bipolar Disorder Type I and Type II: Evidence From Integrative Genomic Analyses.

Aim: Genome-wide association studies (GWAS) analyses have revealed genetic evidence of bipolar disorder (BD), but little is known about the genetic structure of BD subtypes. We aimed to investigate the genetic overlap and distinction of bipolar type I (BD I) & type II (BD II) by conducting integrative post-GWAS analyses. Methods: We utilized single nucleotide polymorphism (SNP)-level approaches to uncover correlated and distinct genetic loci. Transcriptome-wide association analyses (TWAS) were then approached to pinpoint functional genes expressed in specific brain tissues and blood. Next, we performed cross-phenotype analysis, including exploring the potential causal associations between two BD subtypes and lithium responses and comparing the difference in genetic structures among four different psychiatric traits. Results: SNP-level evidence revealed three genomic loci, SLC25A17, ZNF184, and RPL10AP3, shared by BD I and II, and one locus (MAD1L1) and significant gene sets involved in calcium channel activity, neural and synapsed signals that distinguished two subtypes. TWAS data implicated different genes affecting BD I and II through expression in specific brain regions (nucleus accumbens for BD I). Cross-phenotype analyses indicated that BD I and II share continuous genetic structures with schizophrenia and major depressive disorder, which help fill the gaps left by the dichotomy of mental disorders. Conclusion: These combined evidences illustrate genetic convergence and divergence between BD I and II and provide an underlying biological and trans-diagnostic insight into major psychiatric disorders.

Childhood Trauma and Mental Health Status in General Population: A Series Mediation Examination of Psychological Distress in COVID-19 Pandemic and Global Sleep Quality.

Background: Coronavirus-2019 (COVID-19) has been coexisting with humans for almost 2 years, consistently impacting people's daily life, medical environment, and mental health. This study aimed to test the series mediation model triggered by childhood trauma, in which perceived psychological impact of COVID-19 pandemic and sleep quality mediated the path sequentially and led to adverse mental health outcomes. Methods: A cross-sectional design involving 817 participants were enrolled via WeChat online survey. Participants completed questionnaires, including demographic features, the Childhood Trauma Questionnaire, Impact of Event Scale-Revised (IES-R) questionnaire, Pittsburgh Sleep Quality Index (PSQI) questionnaire, and Depression, Anxiety, and Stress Scale (DASS-21). Pearson correlations and hierarchical multiple linear regression were employed to examine the association of childhood trauma and psychological stress of COVID-19, sleep quality, and mental health status. In addition, a series mediate analysis was carried out to examine sequence mediating effects of psychological impact of COVID-19 and sleep quality between childhood trauma and mental health status. Results: The results showed that childhood trauma is positively and significantly related to psychological distress of COVID-19 pandemic, sleep quality, and mental health status (p < 0.05). Hierarchical multiple linear regression analysis shown that demographic features explained 4.4, 2.1, and 4.0% of the total variance in DASS-21, IES-R, and PSQI total scale scores, respectively. Adding childhood trauma significantly increased the model variance of DASS-21 (ΔR 2 = 0.129, F = 126.092, p = 0.000), IES-R (ΔR 2 = 0.062, F = 54.771, p = 0.000), and PSQI total scale scores (ΔR 2 = 0.055, F = 48.733, p = 0.000), respectively. Moreover, the series mediation model showed that the perceived impact of the COVID-19 pandemic and sleep quality were sequential mediators between childhood trauma and mental health status (proportion explained: 49.17%, p < 0.05). Conclusion: Amid the ravages of COVID-19, childhood trauma predicts poor mental health status, in part because of greater psychological impact related to COVID-19 and poorer global sleep quality. In order to improve mental health, future researchers should pay more attention to individuals with childhood trauma, for its association with greater stress related to life events and poorer sleep quality.

Optimal Dose of Serotonin Reuptake Inhibitors for Obsessive-Compulsive Disorder in Adults: A Systematic Review and Dose-Response Meta-Analysis.

Background: Obsessive-compulsive disorder (OCD) is a common chronic mental disorder with a high disability rate. Serotonin reuptake inhibitors (SRIs), including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, such as clomipramine, are the most common choices for the pharmacological treatment of OCD. Optimizing their use is pivotal in guiding clinical practice of OCD. However, there are few studies on the optimal dose of SRIs and there is controversy about their dose-response relationship and optimal target dose. Therefore, the objective of this study was to summarize the relationship between the dose and effect of SRIs, as well as the optimal dose of SRIs for OCD, as to propose future research directions. Methods: Medline, Embase, Biosis, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and CINAHL were searched for relevant publications, and the search was up to February 22, 2020. We used a one-stage, robust error meta-regression (REMR) model to deal with the correlated dose-response data for SRIs from different studies. Doses of SRIs were converted to fluoxetine equivalents when performing dose-response analysis. Review Manager Program Version 5.3 and STATA software package (version 15.1) were applied to analyze data. The study protocol was registered with PROSPERO (number CRD42020168344). Results: Eleven studies involving 2,322 participants were included in final analysis. For SRIs, the dose-efficacy curve showed a gradual increase trend in the 0-40-mg dose range and then had a decreased trend in doses up to 100 mg fluoxetine equivalent. Dropouts due to adverse effects gradually increased throughout the inspected dose slope. The curve of dose of all-cause dropouts suggested no relationship between them. Sensitivity analysis proved that these results were robust. Conclusion: The systematic review found that the optimal dose for efficacy was about 40mg fluoxetine equivalent. Tolerability decreased with increased doses, and there was no significant correlation between acceptability and doses of SRIs. Therefore, the optimal dose of SRIs needs to consider effectiveness and tolerability. Systematic Review Registration: [PROSPERO], identifier [CRD42020168344].

Prevalence and Risk Factors of Mental Health Problems Among Healthcare Workers During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

Objective: The purpose of this meta-analysis was to summarize the prevalence and risk factors of mental health problems among healthcare workers during the COVID-19 pandemic. Methods: We applied an optimized search strategy across the PubMed, EMBASE, Scopus, PsycINFO, and four Chinese databases, with hand searching supplemented to identify relevant surveys. Studies were eligible for inclusion if they were published in peer-reviewed literature and used a validated method to assess the prevalence and risk factors of mental health problems among healthcare workers during the COVID-19 pandemic. Heterogeneity was quantified using Q statistics and the I 2 statistics. The potential causes of heterogeneity were investigated using subgroup analysis and meta-regression analysis. Sensitivity analysis was performed to examine the robustness of the results. Results: We pooled and analyzed data from 20 studies comprising 10,886 healthcare workers. The prevalence of depression, anxiety, insomnia, post-traumatic stress symptoms, phobia, obsessive-compulsive symptoms, and somatization symptoms was 24.1, 28.6, 44.1, 25.6, 35.0, 16.2, and 10.7%, respectively. Female and nurses had a high prevalence of depression and anxiety. Frontline healthcare workers had a higher prevalence of anxiety and a lower prevalence of depression than the those in the second-line. Furthermore, the proportion of moderate-severe depression and anxiety is higher in the frontline. Additionally, four studies reported on risk factors of mental health problems. Conclusions: In this systematic review, healthcare workers have a relatively high prevalence of depression, anxiety, insomnia, post-traumatic stress symptoms, phobia, obsessive-compulsive symptoms, and somatization symptoms during the COVID-19 pandemic, and focus should be on the healthcare workers at high risk of mental problems. Mental health problems in healthcare workers should be taken seriously, and timely screening and appropriate intervention for the high-risk group are highly recommended. Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020179189.

Longitudinal trajectory analysis of antipsychotic response in patients with schizophrenia: 6-week, randomised, open-label, multicentre clinical trial.

BACKGROUND: Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design. AIMS: This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934). METHOD: Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups. RESULTS: The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine. CONCLUSIONS: The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.