The Molecular Characteristics and Therapeutic Implications of O-Glycan Synthesis in Pancreatic Cancer by Integrating Transcriptome and Single-Cell Data.

BACKGROUND: Glycans constitute the primary components of proteins that regulate key carcinogenic processes in cancer progression. This study investigated the significance of O-glycan synthesis in the pathogenesis, outcome, and therapy of pancreatic cancer (PC). METHODS: Transcriptomic data and clinical prognostic information of PC were acquired via TCGA and GEO databases. CSA database was used to obtain single-cell data of PC. The O-glycan biosynthesis signaling pathway and its related genes were acquired via the MSigDB platform. The nonnegative matrix factorization (NMF) clustering was utilized to construct the O-glycan biosynthesis-associated molecular subtypes in PC. The LASSO and Cox regression were utilized to build the prognostic prediction model. We utilized real-time quantitative PCR (qRT-PCR) to verify the expressed levels of model genes. Single-cell analysis was utilized to investigate the levels of target genes and O-glycan biosynthesis signaling pathway in the PC tumour microenvironment. RESULTS: We obtained 30 genes related to O-glycan biosynthesis, among which 15 were associated with the prognosis of PC. All PC samples were grouped into two distinct molecular subtypes associated with O-glycan biosynthesis: OGRGcluster C1 and OGRGcluster C2, and compared to OGRGcluster C1. PCs in OGRGcluster C2 had a more advanced clinical stage and pathological grade, worse prognosis, and more active O-glycan biosynthesis function. Immune analysis indicated that naïve B cell, CD8+ T cell, memory-activated CD4+ T cell, and monocytes displayed remarkably higher infiltration levels in OGRGcluster C1 while resting NK cell, macrophages M0, resting dendritic cell, activated dendritic cell, and neutrophils exhibited markedly higher infiltration levels in OGRGcluster C2. OGRGcluster C1 exhibited higher sensitivities to drugs, such as cisplatin, irinotecan, KRAS(G12C) inhibitor-12, oxaliplatin, paclitaxel, and sorafenib. Besides, we built the O-glycan biosynthesis-related prognostic model (including SPRR1B, COL17A1, and ECT2) with a good prediction performance. SPRR1B, COL17A1, and ECT2 were remarkably highly expressed in PC tissues and linked to a poor outcome. Single-cell analysis revealed that Oglycan biosynthesis was observed only in PC, and consistent with this, the target genes were significantly enriched in PC. CONCLUSION: We first constructed molecular subtypes and prognostic models related to O-glycan biosynthesis in PC. It is clear that O-glycan biosynthesis is related to the development, prognosis, immune microenvironment, and treatment of PC. This provides new strategies for stratification, diagnosis, and treatment of PC patients.

Integrated pharmacokinetic properties and tissue distribution of multiple active constituents in Qing-Yi Recipe: A comparison between granules and decoction.

BACKGROUND: Qing-Yi Recipe, a classic traditional Chinese medicine (TCM), is widely used for treating acute diseases of the abdomen, especially pancreatitis, the efficacy of which has been demonstrated in more than thirty clinical trials. However, the in-vivo pharmacodynamic material basis for this formula remains unclear. METHODS: A sensitive and accurate method for quantifying twenty-two potential bioactive constituents of Qing-Yi Recipe in biological samples was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and this method was fully validated. Then, the integrated pharmacokinetic properties of Qing-Yi Recipe and its major metabolites in rats were investigated using the post-listed granules at both dosages. Subsequently, tissue distributions of those constituents in nine organs (especially the pancreas) were determined, and the overall parameters between the two formulations were compared. RESULTS: Though the chemical profiles of the formulas varied across formulations, the overall exposure level was very similar, and baicalin, wogonoside, geniposide, rhein, costunolide, and paeoniflorin were the top six bioactive compounds in the circulation. All twenty-two natural products reached their first peak within 2 h, and several of them exhibited bimodal or multimodal patterns under the complicated transformation of metabolic enzymes, and the parameters of these products markedly changed compared with those of monomers. Diverse metabolites of emodin and baicalin/baicalein were detected in circulation and tissues, augmenting the in vivo forms of these compounds. Finally, the enrichment of tetrahydropalmatine and corydaline in the pancreas were observed and most compounds remained in the gastrointestinal system, providing a foundation basis for their potential regulatory effects on the gut microbiota as well as the intestinal functions. CONCLUSION: Herein, the pharmacokinetic properties and tissue distribution of multiple potential active constituents in Qing-Yi Recipe were investigated at two dosages, providing a pharmacodynamic material basis of Qing-Yi Recipe for the first time. This investigation is expected to provide a new perspective and reference for future studies on the physiological disposition and potential pharmacodynamic basis of traditional Chinese medicine to treat acute abdomen diseases.

Attention-Dominated Cognitive Dysfunction May Be a Biological Marker for Distinguishing SA from SI in Adolescents: A Network Analysis Study Based on Adolescent Depression.

Objective: Suicidal behavior is strongly correlated with depressive symptoms and the degree of suicidal ideation. Cognitive impairment may have varying degrees of influence on suicidal ideation (SI) and suicidal attempts (SA). The aim of this study was to identify the cognitive biomarkers that distinguish suicidal ideation from suicidal attempts in adolescents. Methods: The cross-sectional sample comprised 54 adolescents with major depressive disorder (MDD) and 32 healthy controls (HC). The THINC-it was utilized to assess cognitive function of all the samples. Suicidal ideation was examined by the Positive and Negative Suicide Ideation Scale (PANSI). Based on the type of data, one-way ANOVA or Kruskal-Wallis was performed to investigate group differences. Bonferroni post-hoc analysis was employed for regulating type I error for pairwise comparisons. Network analysis was used to compare the networks associated with suicidal ideation, depression symptoms, and cognitive function between SA and SI. Results: The depression symptoms (HAMD-17) (F=72.515, P<0.001) and suicidal ideation (PANSI) (F=267.952, P<0.001) in the SA were higher than those in the SI. Analysis of between-group differences showed SA performed worse in THINC-it, especially in "Spotter (SP)" (P=0.033), "Objective cognition score (OS)" (P=0.027) and "Composite score (CS)" (P=0.017). Compared with SI, network analysis revealed that SA had a unique network of cognitive function, depressive symptoms, and suicidal ideation. Nevertheless, both networks exhibit comparable performance concerning the node strength of cognitive function. Within their separate networks, the aspects of CS, OS, and SP have emerged as the three most crucial elements. Conclusion: Adolescents with SI or SA exhibit a broad spectrum of cognitive impairments. Attention impairment can be beneficial in discerning between SI and SA. Future interventions for adolescent suicide can center on attention and the comprehensive cognitive ability that it represents.

Identification of novel biomarkers based on lipid metabolism-related molecular subtypes for moderately severe and severe acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an unpredictable and potentially fatal disorder. A derailed or unbalanced immune response may be the root of the disease's severe course. Disorders of lipid metabolism are highly correlated with the occurrence and severity of AP. We aimed to characterize the contribution and immunological characteristics of lipid metabolism-related genes (LMRGs) in non-mild acute pancreatitis (NMAP) and identify a robust subtype and biomarker for NMAP. METHODS: The expression mode of LMRGs and immune characteristics in NMAP were examined. Then LMRG-derived subtypes were identified using consensus clustering. The weighted gene co-expression network analysis (WGCNA) was utilized to determine hub genes and perform functional enrichment analyses. Multiple machine learning methods were used to build the diagnostic model for NMAP patients. To validate the predictive effectiveness, nomograms, receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) were used. Using gene set variation analysis (GSVA) and single-cell analysis to study the biological roles of model genes. RESULTS: Dysregulated LMRGs and immunological responses were identified between NMAP and normal individuals. NMAP individuals were divided into two LMRG-related subtypes with significant differences in biological function. The cluster-specific genes are primarily engaged in the regulation of defense response, T cell activation, and positive regulation of cytokine production. Moreover, we constructed a two-gene prediction model with good performance. The expression of CARD16 and MSGT1 was significantly increased in NMAP samples and positively correlated with neutrophil and mast cell infiltration. GSVA results showed that they are mainly upregulated in the T cell receptor complex, immunoglobulin complex circulating, and some immune-related routes. Single-cell analysis indicated that CARD16 was mainly distributed in mixed immune cells and macrophages, and MGST1 was mainly distributed in exocrine glandular cells. CONCLUSIONS: This study presents a novel approach to categorizing NMAP into different clusters based on LMRGs and developing a reliable two-gene biomarker for NMAP.

Oxidative stress and autophagy-mediated immune patterns and tumor microenvironment infiltration characterization in gastric cancer.

Recent years have seen a sharp rise in the amount of research on the connection between oxidative stress, autophagy, and cancer cells. However, the significant functions of oxidative stress and autophagy-related genes (OARGs) in gastric cancer (GC) are yet to be investigated integrally. Therefore, it will be a new and promising concept to search for novel OARG-related biomarkers to predict the prognosis and treatment response of GC. First, we assessed changes in prognosis and tumor microenvironment (TME) characteristics across the various oxidative stress and autophagy-related modification patterns based on a detailed analysis of 17 OARGs with prognostic significance of 808 GC samples. We identified three distinct OARG alteration patterns which displayed unique biological characteristics and immune cell infiltration features. Using principal component analysis methods, the OARGscore was developed to evaluate the OARG modification patterns of certain tumors. The negative connection between OARGscore and immune cells was statistically significant. Increased survival, a higher incidence of mutations, and a better response to immunotherapy were all predicted to be related to patients' high-OARGscore. In addition, the candidate chemotherapeutic drugs were predicted using the oncoPredict program. The low-OARGscore group was predicted to benefit more from Ribociclib, Alisertib, Niraparib, Epirubicin, Olaparib, and Axitinib, while patients in the high-OARGscore group were predicted to benefit more from Afatinib, Oxaliplatin, Paclitaxel, 5-Fluorouracil, Dabrafenib and Lapatinib. Our findings offer a specific method for predicting a patient's prognosis and susceptibility to immunotherapy, as well as a promising insight of oxidative stress and autophagy in GC.

Associations between genetically predicted sex and growth hormones and facial aging in the UK Biobank: a two-sample Mendelian randomization study.

Background: Aging is an inescapable process, but it can be slowed down, particularly facial aging. Sex and growth hormones have been shown to play an important role in the process of facial aging. We investigated this association further, using a two-sample Mendelian randomization study. Methods: We analyzed genome-wide association study (GWAS) data from the UK Biobank database comprising facial aging data from 432,999 samples, using two-sample Mendelian randomization. In addition, single-nucleotide polymorphism (SNP) data on sex hormone-binding globulin (SHBG) and sex steroid hormones were obtained from a GWAS in the UK Biobank [SHBG, N = 189,473; total testosterone (TT), N = 230,454; bioavailable testosterone (BT), N = 188,507; and estradiol (E2), N = 2,607)]. The inverse-variance weighted (IVW) method was the major algorithm used in this study, and random-effects models were used in cases of heterogeneity. To avoid errors caused by a single algorithm, we selected MR-Egger, weighted median, and weighted mode as supplementary algorithms. Horizontal pleiotropy was detected based on the intercept in the MR-Egger regression. The leave-one-out method was used for sensitivity analysis. Results: SHBG plays a promoting role, whereas sex steroid hormones (TT, BT, and E2) play an inhibitory role in facial aging. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels had no significant effect on facial aging, which is inconsistent with previous findings in vitro. Conclusion: Regulating the levels of SHBG, BT, TT, and E2 may be an important means to delay facial aging.

Identification and immunological characterization of lipid metabolism-related molecular clusters in nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is now the major contributor to chronic liver disease. Disorders of lipid metabolism are a major element in the emergence of NAFLD. This research intended to explore lipid metabolism-related clusters in NAFLD and establish a prediction biomarker. METHODS: The expression mode of lipid metabolism-related genes (LMRGs) and immune characteristics in NAFLD were examined. The "ConsensusClusterPlus" package was utilized to investigate the lipid metabolism-related subgroup. The WGCNA was utilized to determine hub genes and perform functional enrichment analysis. After that, a model was constructed by machine learning techniques. To validate the predictive effectiveness, receiver operating characteristic curves, nomograms, decision curve analysis (DCA), and test sets were used. Lastly, gene set variation analysis (GSVA) was utilized to investigate the biological role of biomarkers in NAFLD. RESULTS: Dysregulated LMRGs and immunological responses were identified between NAFLD and normal samples. Two LMRG-related clusters were identified in NAFLD. Immune infiltration analysis revealed that C2 had much more immune infiltration. GSVA also showed that these two subtypes have distinctly different biological features. Thirty cluster-specific genes were identified by two WGCNAs. Functional enrichment analysis indicated that cluster-specific genes are primarily engaged in adipogenesis, signalling by interleukins, and the JAK-STAT signalling pathway. Comparing several models, the random forest model exhibited good discrimination performance. Importantly, the final five-gene random forest model showed excellent predictive power in two test sets. In addition, the nomogram and DCA confirmed the precision of the model for NAFLD prediction. GSVA revealed that model genes were down-regulated in several immune and inflammatory-related routes. This suggests that these genes may inhibit the progression of NAFLD by inhibiting these pathways. CONCLUSIONS: This research thoroughly emphasized the complex relationship between LMRGs and NAFLD and established a five-gene biomarker to evaluate the risk of the lipid metabolism phenotype and the pathologic results of NAFLD.

Identification of lipid metabolism-related biomarkers for diagnosis and molecular classification of atherosclerosis.

BACKGROUND: Atherosclerosis is now the main cause of cardiac-cerebral vascular diseases around the world. Disturbances in lipid metabolism have an essential role in the development and progression of atherosclerosis. Thus, we aimed to investigate lipid metabolism-related molecular clusters and develop a diagnostic model for atherosclerosis. METHODS: First, we used the GSE100927 and GSE43292 datasets to screen differentially expressed lipid metabolism-related genes (LMRGs). Subsequent enrichment analysis of these key genes was performed using the Metascape database. Using 101 atherosclerosis samples, we investigated the LMRG-based molecular clusters and the corresponding immune cell infiltration. After that, a diagnostic model for atherosclerosis was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. Finally, a series of bioinformatics techniques, including CIBERSORT, gene set variation analysis, and single-cell data analysis, were used to analyze the potential mechanisms of the model genes in atherosclerosis. RESULTS: A total of 29 LMRGs were found to be differentially expressed between atherosclerosis and normal samples. Functional and DisGeNET enrichment analyses indicated that 29 LMRGs are primarily engaged in cholesterol and lipid metabolism, the PPAR signaling pathway, and regulation of the inflammatory response and are also closely associated with atherosclerotic lesions. Two LMRG-related molecular clusters with significant biological functional differences are defined in atherosclerosis. A three-gene diagnostic model containing ADCY7, SCD, and CD36 was subsequently constructed. Receiver operating characteristic curves, decision curves, and an external validation dataset showed that our model exhibits good predictive performance. In addition, three model genes were found to be closely associated with immune cell infiltration, especially macrophage infiltration. CONCLUSIONS: Our study comprehensively highlighted the intricate association between lipid metabolism and atherosclerosis and created a three-gene model for future clinical diagnosis.

Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy.

This study aimed to explore the oxidative stress-protective effect of crocetin on H2O2-mediated H9c2 myocardial cells through in vitro experiments, and further explore whether its mechanism is related to the impact of mitophagy. This study also aimed to demonstrate the therapeutic effect of safflower acid on oxidative stress in cardiomyocytes and explore whether its mechanism is related to the effect of mitophagy. Here, an H2O2-based oxidative stress model was constructed and assessed the degree of oxidative stress injury of cardiomyocytes by detecting the levels of lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH Px). Reactive oxygen species (ROS)-detecting fluorescent dye DCFH-DA, JC-1 dye, and TUNEL dye were employed to assess mitochondrial damage and apoptosis. Autophagic flux was measured by transfecting Ad-mCherry-GFP-LC3B adenovirus. Mitophagy-related proteins were then detected via western blotting and immunofluorescence. However, crocetin (0.1-10 µM) could significantly improve cell viability and reduce apoptosis and oxidative stress damage caused by H2O2. In cells with excessive autophagic activation, crocetin could also reduce autophagy flow and the expression of mitophagy-related proteins PINK1 and Parkin, and reverse the transfer of Parkin to mitochondria. Crocetin could reduce H2O2-mediated oxidative stress damage and the apoptosis of H9c2 cells, and its mechanism was closely related to mitophagy.

Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of action of Wang Bu Liu Xing (Semen vaccariae) for colorectal cancer.

Background: Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Wang Bu Liu Xing [Semen vaccariae (SV)] is a traditional Chinese medicine (TCM) ingredient with anti-angiogenic and anti-tumor effects. However, little research has been done on the ingredients found in SV or the putative process by which SV fights CRC, and this paper aims to reveal the components of SV that are effective in treating CRC. Methods: The open database and online platform were used in this study, Symptom Mapping (SymMap) and Traditional Chinese Medicine Systems Pharmacology (TCMSP) for SV ingredient and targets, Gene Expression Omnibus (GEO) for differentially expressed genes (DEGs) of CRC, Database for Annotation Visualization and Integrated Discovery (DAVID) for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, STRING-Cytoscape for protein-protein interaction (PPI), AutoDockTools for Molecular docking and others. were conducted to determine how SV affects CRC and what are the most important components, potential targets, and signaling pathways. Results: The findings of the network pharmacology study indicated that swerchirin and CDK2 potential target gene for SV was connected to anti-CRC actions. SV may inhibit CRC by interacting with crucial targets like BCL2L1, CDK2, and SERPINE1. Additionally, KEGG analysis revealed that the p53 signaling pathway may be a driver of the anti-CRC impact of SV. Molecular docking showed that swerchirin can bind with its target protein in a good bond by intermolecular force. Conclusions: In this study, the pharmacological effects of SV were examined, along with its potential therapeutic impact on CRC. These effects of SV appear to be mediated via a variety of substances, targets, and pathways. SV exerts pharmacological effects in CRC, p53 signaling pathway is great value. The main molecular docking is CDK2 and swerchirin. Moreover, our research offers a promising method for characterizing therapeutic pathways and identifying molecules in TCM.

Controversial role of ILC3s in intestinal diseases: A novelty perspective on immunotherapy.

ILC3s have been identified as crucial immune regulators that play a role in maintaining host homeostasis and modulating the antitumor response. Emerging evidence supports the idea that LTi cells play an important role in initiating lymphoid tissue development, while other ILC3s can promote host defense and orchestrate adaptive immunity, mainly through the secretion of specific cytokines and crosstalk with other immune cells or tissues. Additionally, dysregulation of ILC3-mediated overexpression of cytokines, changes in subset abundance, and conversion toward other ILC subsets are closely linked with the occurrence of tumors and inflammatory diseases. Regulation of ILC3 cytokines, ILC conversion and LTi-induced TLSs may be a novel strategy for treating tumors and intestinal or extraintestinal inflammatory diseases. Herein, we discuss the development of ILCs, the biology of ILC3s, ILC plasticity, the correlation of ILC3s and adaptive immunity, crosstalk with the intestinal microenvironment, controversial roles of ILC3s in intestinal diseases and potential applications for treatment.

Genome-wide DNA methylation analysis in families with multiple individuals diagnosed with schizophrenia and intellectual disability.

OBJECTIVES: Schizophrenia (SZ) and intellectual disability (ID) are both included in the continuum of neurodevelopmental disorders (NDDs). DNA methylation is known to be important in the occurrence of NDDs. The family study is conducive to eliminate the effects of relative epigenetic backgrounds, and to screen for differentially methylated positions (DMPs) and regions (DMRs) that are truly associated with NDDs. METHODS: Four monozygotic twin families were recruited, and both twin individuals suffered from NDDs (either SZ, ID, or SZ plus ID). Genome-wide methylation analysis was performed in all samples and each family. DMPs and DMRs between NDD patients and unaffected individuals were identified. Functional and pathway enrichment analyses were performed on the annotated genes. RESULTS: Two significant DMPs annotated to CYP2E1 were found in all samples. In Family One, 1476 DMPs mapped to 880 genes, and 162 DMRs overlapping with 153 unique genes were recognised. Our results suggested that the altered methylation levels of FYN, STAT3, RAC1, and NR4A2 were associated with the development of SZ and ID. Neurodevelopment and the immune system may participate in the occurrence of SZ and ID. CONCLUSIONS: Our findings suggested that DNA methylation participated in the development of NDDs by affecting neurodevelopment and the immune system.

The combined signatures of the tumour microenvironment and nucleotide metabolism-related genes provide a prognostic and therapeutic biomarker for gastric cancer.

The tumour microenvironment (TME) is vital to tumour development and influences the immunotherapy response. Abnormal nucleotide metabolism (NM) not only promotes tumour cell proliferation but also inhibits immune responses in the TME. Therefore, this study aimed to determine whether the combined signatures of NM and the TME could better predict the prognosis and treatment response in gastric cancer (GC). 97 NM-related genes and 22 TME cells were evaluated in TCGA-STAD samples, and predictive NM and TME characteristics were determined. Subsequent correlation analysis and single-cell data analysis illustrated a link between NM scores and TME cells. Thereafter, NM and TME characteristics were combined to construct an NM-TME classifier. Patients in the NMlow/TMEhigh group exhibited better clinical outcomes and treatment responses, which could be attributed to the differences in immune cell infiltration, immune checkpoint genes, tumour somatic mutations, immunophenoscore, immunotherapy response rate and proteomap. Additionally, the NMhigh/TMElow group benefited more from Imatinib, Midostaurin and Linsitinib, while patients in the NMlow/TMEhigh group benefited more from Paclitaxel, Methotrexate and Camptothecin. Finally, a highly reliable nomogram was developed. In conclusion, the NM-TME classifier demonstrated a pretreatment predictive value for prognosis and therapeutic responses, which may offer novel strategies for strategizing patients with optimal therapies.

The safety and efficacy of sequential intramuscular/oral ziprasidone treatment of acute episode in patients with schizophrenia: a multicenter, open-labeled study.

BACKGROUND: Ziprasidone mesylate injection is an atypical antipsychotic drug which is recently approved in China. In combination with its oral formulation, sequential therapy with ziprasidone brings new interventions to patients with agitation in the acute phase of schizophrenia. The purpose of this 7-day multicenter study conducted in China was to evaluate the efficacy and safety of ziprasidone sequential treatment through intramuscular/oral routes in agitated patients with schizophrenia. METHODS: A total of 95 patients were enrolled from three centers in this study. The study duration was 7 days. In the first 3 days, subjects were administered an intramuscular injection of ziprasidone 10-40 mg daily and started sequentially with oral ziprasidone 40-80 mg at dinner (or lunch) from the day of the last intramuscular injection. In the following 4 days, according to the severity of the symptoms and the drug response, 120-160 mg of ziprasidone was orally administered daily. In total, six visits were scheduled to assess the Positive and Negative Syndrome Scale (PANSS), the Behavioral Activity Rating Scale (BARS), the Clinical Global Impression of Severity (CGI-S), and Improvement (CGI-I) scores throughout the procedure. Lastly, adverse events were recorded during treatment. RESULTS: Out of the 95 patients that were enrolled, 83 cases were effectively completed. Visits 3, 4, 6, PANSS, and PANSS-excited component (PANSS-EC) subscale points, and Visit 2-Visit 6 viewpoints, BARS scale points, and baseline scores denote a progressive downward trend (P < 0.001). In this study, 62 adverse events were reported. The most common adverse events were extrapyramidal symptoms (EPS) (23 cases) and excessive sedation(10 cases), and 13 cases of prolonged QTc interval were reported. CONCLUSIONS: Ziprasidone IM demonstrated significant and rapid reduction in agitation, and sequential oral formulation keep stability and continuation of the treatment can further ensure efficacy. Ziprasidone sequential therapy may provide a new approach to acute agitation in schizophrenic patients. TRIAL REGISTRATION: The Chinese Clinical Trials Registry; URL: https://www.chictr.org.cn : ChiCTR-OIC-16007970.

Multiply robust matching estimators of average and quantile treatment effects.

Propensity score matching has been a long-standing tradition for handling confounding in causal inference, however requiring stringent model assumptions. In this article, we propose novel double score matching (DSM) utilizing both the propensity score and prognostic score. To gain the protection of possible model misspecification, we posit multiple candidate models for each score. We show that the de-biasing DSM estimator achieves the multiple robustness property in that it is consistent if any one of the score models is correctly specified. We characterize the asymptotic distribution for the DSM estimator requiring only one correct model specification based on the martingale representations of the matching estimators and theory for local Normal experiments. We also provide a two-stage replication method for variance estimation and extend DSM for quantile estimation. Simulation demonstrates DSM outperforms single score matching and prevailing multiply robust weighting estimators in the presence of extreme propensity scores.

Effectiveness of one-week internet-delivered cognitive behavioral therapy for insomnia to prevent progression from acute to chronic insomnia: A two-arm, multi-center, randomized controlled trial.

Acute insomnia is common and a substantial proportion of people with acute insomnia (i.e. 3 days to 3 months) transit into chronic insomnia (i.e. 3 months or longer). Therefore, early intervention for acute insomnia is vital to prevent chronicity. Previous trials with small sample sizes have shown that brief versions of both individual and group-based face-to-face cognitive behavioral therapy for insomnia (CBT-I) can improve insomnia symptoms among those with acute insomnia. However, it is unknown whether one-week internet-delivered cognitive behavioral therapy for insomnia (CBT-I) is effective in treating acute insomnia. This was a randomized controlled trial and 192 participants were randomly assigned to the CBT-I group (n = 95) or control group (n = 97). The primary outcome was the incidence of chronic insomnia, determined via a structured diagnostic questionnaire for insomnia disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Secondary outcomes were Insomnia Severity Index (ISI), Dysfunctional Beliefs and Attitudes about Sleep (DBAS), Epworth Sleepiness Scale (ESS), Pre-sleep Arousal Scale (PSAS), Ford Insomnia Response to Stress Test (FIRST), Sleep Hygiene and Practices Scale (SHPS), Hospital Anxiety and Depression Scale (HADS), and Short-Form 12-Item Health Survey version 2 (SF-12v2). At week 12, the incidence of chronic insomnia was significantly lower in the CBT-I group compared with control group (33.3% [27/81] vs. 65.8% [52/79]). Participants in the CBT-I group achieved significantly more improvements in ISI, ESS, PSAS, FIRST, SHPS, HADS-Depression, and the mental component summary and physical component summary of SF-12v2 than control group, but not DBAS and HADS-Anxiety. This one-week internet-delivered CBT-I program is an effective tool to prevent the chronicity of acute insomnia.

Effect of sarcopenia on survival in patients after pancreatic surgery: a systematic review and meta-analysis.

Background: Numerous studies have reported sarcopenia to be associated with unfavorable outcomes in patients who have undergone pancreatectomy. Therefore, in this meta-analysis, we examined the relationship between sarcopenia and survival after pancreatic surgery. Methods: PubMed, Embase, and Cochrane Library were searched for studies that examined the association between sarcopenia and survival after pancreatic surgery from the inception of the database until June 1, 2023. Hazard ratio (HR) for overall survival (OS) and/or progression-free survival (PFS) of sarcopenia and pancreatic surgery were extracted from the selected studies and random or fixed-effect models were used to summarize the data according to the heterogeneity. Publication bias was assessed using Egger's linear regression test and a funnel plot. Results: Sixteen studies met the inclusion criteria. For 13 aggregated univariate and 16 multivariate estimates, sarcopenia was associated with decreased OS (univariate analysis: HR 1.69, 95% CI 1.48-1.93; multivariate analysis: HR 1.69; 95% CI 1.39-2.05, I2 = 77.4%). Furthermore, sarcopenia was significantly associated with poor PFS of pancreatic resection (Change to univariate analysis: HR 1.74, 95% CI 1.47-2.05; multivariate analysis: HR 1.54; 95% CI 1.23-1.93, I2 = 63%). Conclusion: Sarcopenia may be a significant prognostic factor for a shortened survival following pancreatectomy since it is linked to an elevated risk of mortality. Further studies are required to understand how sarcopenia affects long-term results after pancreatic resection.Systematic review registrationRegistration ID: CRD42023438208 https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

Six complex microbial inoculants for removing ammonia nitrogen from waters.

To determine the effect of microbial inoculants on the removal of ammonia nitrogen (NH4 + -N), six different complex microbial inoculants were studied. In this study, their effectiveness on NH4 + -N removal was compared, and their microbial community composition was determined. High-throughput sequencing results showed that Proteobacteria and Firmicutes were the dominant phyla in six samples. Before the reaction, Bacillus, Cyanobacteria, and Mitochondria genera were the dominant genera. The dominant genera were significantly different after the reaction with the addition of bacterial agents. The six water samples were Massilia, Escherichia-Shigella, Brevibacillus, Mitsuaria, Bacillus, and Ralstonia. Among the six complex microbial inoculants, "Gandu nitrifying bacteria (NR4 )" have the best removal effect on NH4 + -N. In addition, the removal effect of six different bacterial agents on chemical oxygen demand (COD) was compared. The results showed that "Bilaiqing ammonia nitrogen removal bacteria agent (NR5 )" has the best removal effect on COD. Single-factor experiments suggested that the optimal conditions for NR4 bacteria were pH 7, 30°C, 1.0 g/L of bacterial agent dosage and a wide range of NH4 + -N from 30 to 300 mg/L. PRACTITIONER POINTS: The nitrogen removal effects of six different microbial agents were compared. High-throughput sequencing provides important insights into the study of ammonia nitrogen removal by microbial communities. Analysis of six different complex bacterial agents by high-throughput sequencing. The relative abundance of microorganisms is not proportional to the ability to remove NH4 + -N Good application effect in urban landscape water body.