SUMOylation at the crossroads of gut health: insights into physiology and pathology.

SUMOylation, a post-translational modification involving the covalent attachment of small ubiquitin-like modifier (SUMO) proteins to target substrates, plays a pivotal role at the intersection of gut health and disease, influencing various aspects of intestinal physiology and pathology. This review provides a comprehensive examination of SUMOylation's diverse roles within the gut microenvironment. We examine its critical roles in maintaining epithelial barrier integrity, regulating immune responses, and mediating host-microbe interactions, thereby highlighting the complex molecular mechanisms that underpin gut homeostasis. Furthermore, we explore the impact of SUMOylation dysregulation in various intestinal disorders, including inflammatory bowel diseases and colorectal cancer, highlighting its implications as a potential diagnostic biomarker and therapeutic target. By integrating current research findings, this review offers valuable insights into the dynamic interplay between SUMOylation and gut health, paving the way for novel therapeutic strategies aimed at restoring intestinal equilibrium and combating associated pathologies.

Assessment of the quality, diagnosis, and therapeutic recommendations of clinical practice guidelines on patients with Helicobacter pylori infection: A systematic review.

We conducted this study to systematically review and assess the current clinical practice guidelines (CPGs) related to the diagnosis and treatment of Helicobacter pylori (H. pylori) infection. The aim was to evaluate the quality of these included CPGs and provide clinicians with a convenient and comprehensive reference for updating their own CPGs. We searched four databases to identify eligible CPGs focusing on H. pylori diagnosis and treatment recommendations. The results were presented using evidence mappings. Quality and clinical applicability were assessed comprehensively using AGREE-II and AGREE-REX. Statistical tests, specifically Bonferroni tests, were employed to compare the quality between evidence-based guidelines and consensus. A total of 30 eligible CPGs were included, comprising 17 consensuses and 13 guidelines. The quality showed no statistical significance between consensuses and guidelines, mainly within the moderate to low range. Notably, recommendations across CPGs exhibited inconsistency. Nevertheless, concerning diagnosis, the urea breath test emerged as the most frequently recommended method for testing H. pylori. Regarding treatment, bismuth quadruple therapy stood out as the predominantly recommended eradication strategy, with high-dose dual therapy being a newly recommended option. Our findings suggest the need for specific organizations to update their CPGs on H. pylori or refer to recently published CPGs. Specifically, CPGs for pediatric cases require improvement and updating, while a notable absence of CPGs for the elderly was observed. Furthermore, there is a pressing need to improve the overall quality of CPGs related to H. pylori. Regarding recommendations, additional evidence is essential to elucidate the relationship between H. pylori infection and other diseases and refine test indications. Clinicians are encouraged to consider bismuth quadruple or high-dose dual therapy, incorporating locally sensitive antibiotics, as empirical radical therapy. .

Constructed the ceRNA network and predicted a FEZF1-AS1/miR-92b-3p/ZIC5 axis in colon cancer.

The purpose of this study was to identify the role of FEZF1-AS1 in colon cancer and predicted the underlying mechanism. We extracted sequencing data of colon cancer patients from The Cancer Genome Atlas database, identified the differential expression of long noncoding RNA, microRNA, and messenger RNA, constructed a competitive endogenous RNA network, and then analyzed prognosis. Then, we used the enrichment analysis databases for functional analysis. Finally, we studied the FEZF1-AS1/miR-92b-3p/ZIC5 axis. We detected the expression of FEZF1-AS1, miR-92b-3p, and ZIC5 via quantitative reverse transcription-PCR, transfected colon cancer cell RKO with lentivirus and conducted FEZF1-AS1 knockdown, and performed cancer-related functional assays. It indicated that many RNA in the competitive endogenous RNA network, such as ZIC5, were predicted to be related to overall survival of colon cancer patients, and enrichment analysis showed cancer-related signaling pathways, such as PI3K/AKT signaling pathway. The expression of FEZF1-AS1 and ZIC5 was significantly higher and that of miR-92b-3p was lower in the colon cancer than in the normal colon tissues. FEZF1-AS1 promoted the migration, proliferation, as well as invasion of RKO. According to the prediction, FEZF1-AS1 and ZIC5 might competitively bind to miR-92b-3p, leading to the weakening of the inhibitory impact of miR-92b-3p on ZIC5 and increasing expression of ZIC5, thus further activating the PI3K/AKT signaling pathway, which led to the occurrence and development of colon cancer. The study suggested that FEZF1-AS1 might be an effective diagnosis biomarker for colon cancer.

Effect of dihydromyricetin on hepatic encephalopathy associated with acute hepatic failure in mice.

CONTEXT: Hepatic encephalopathy (HE) is a complex neuropsychiatric disease caused by liver failure. Dihydromyricetin (DMY) is a traditional medicine used to treat liver injury. OBJECTIVE: To investigate the effects of dihydromyricetin (DMY) on hepatic encephalopathy associated with acute hepatic failure mice models established by thioacetamide (TAA) exposure. MATERIALS AND METHODS: Female BALB/c mouse were randomly divided into control, DMY, TAA, and TAA + DMY groups (n = 8). The first two groups were intraperitoneally injected with saline or 5 mg/kg DMY, respectively. The last two groups were injected with 600 mg/kg TAA to establish HE models, and then the mice in the last group were treated with 5 mg/kg DMY. Neurological and cognition functions were evaluated 24 and 48 h after injection. Mice were sacrificed after which livers and brains were obtained for immunoblot and histopathological analysis, while blood was collected for the analysis of liver enzymes. RESULTS: In the TAA + DMY group, ALT and AST decreased to 145.31 ± 12.88 U/L and 309.51 ± 25.92 U/L, respectively, whereas ammonia and TBIL decreased to 415.67 ± 41.91 µmol/L and 3.31 ± 0.35 µmol/L, respectively. Moreover, MDA decreased to 10.74 ± 3.97 nmol/g, while SOD and GST increased to 398.69 ± 231.30 U/g and 41.37 ± 21.84 U/g, respectively. The neurological score decreased to 2.87 ± 0.63, and the number of GFAP-positive cells decreased to 41.10 ± 1.66. Furthermore, the protein levels of TNF-α, IL-6, and GABAA in the cortex decreased. CONCLUSIONS: We speculate that DMY can serve as a novel treatment for HE.

Seven Hormonal Biomarkers for Diagnosing Endometriosis: Meta-Analysis and Adjusted Indirect Comparison of Diagnostic Test Accuracy.

OBJECTIVE: To compare the diagnostic accuracy of different hormonal biomarkers and to find the most effective hormonal biomarker for the diagnosis of endometriosis. DATA SOURCES: We conducted a systematic search using PubMed, EMBASE, Cochrane Library, and China Biomedical Literature to identify relevant studies from the first day of databases to August 2018. METHODS OF STUDY SELECTION: Two independent reviewers screened for study eligibility and extracted data. Random controlled trials, cross-sectional studies, case-control studies, and cohort studies evaluating the diagnostic accuracy of hormonal markers for endometriosis were included. TABULATION, INTEGRATION, AND RESULTS: We included 17 studies that involved 1279 participants and evaluated 7 hormonal biomarkers. The pooled sensitivity and specificity in endometriosis were .79 (.71, .86) and .89 (.82, .94) for aromatase, .30 (.18, .46) and .80 (.65, .90) for human chorionic gonadotropin/luteinizing hormone receptor, .75 (.66, .83) and .47 (.34, .60) for estrogen receptor (ER)-α, .65 (.56, .74) and .68 (.55, .80) for ER-ß, .45 (.38-.52) and .92 (.85-.97) for serum prolactin, .69 (.51, .83) and .30 (.16, .49) for estrogen sulfotransferase, and .73 (.60-.84) and .48 (.33-.63) for 17ß-hydroxysteroid dehydrogenase type 2 (17ßHSD2). Compared with human chorionic gonadotropin/luteinizing hormone receptor, ER-α, ER-ß, estrogen sulfotransferase, and 17ßHSD2, aromatase had a higher sensitivity, specificity, positive likelihood ratio, and diagnostic odds ratio. The specificities of aromatase and serum prolactin were comparable, but the sensitivity, positive likelihood ratio, and positive likelihood ratio of serum prolactin were much lower than that of aromatase. CONCLUSION: Aromatase may be an excellent diagnostic test for endometriosis. However, because of the moderate quality of the included studies and the limited sample size, this result requires more research to validate. (PROSPERO registration number: PROSPERO 2018 CRD42018105126.).

[Studies on sexual organs and embryological development morphology of Pterocypsela formosana].

In this study, the embryological characters of Pterocypsela formosana (Asteraceae) were investigated with the traditional paraffin section methods. The anther has 4 sporangiates, the anther wall development follows the dicotyledonous type and comprises of an epidermis, endothelium, a middle layer and a single-layered tapetum, the tapetum belongs to glandular type. Meiosis of the microspore mother cells is of the simultaneous type, for the formation of mostly tetrahedral tetrad, the mature pollen grains are 2 celled. The ovary is bicarpellate, unilocular, one ovule and basal placenta, the ovule is unitegmic, tenuinucellate, inverted campylotropous and with developed endothelium, archesporial cell of megaspore differentiates immediately below the nucellar epidermis and functions as megasporocyte after development and belongs to tenuinucellate ovule type. The megasporocyte undergoes meitotic to form a liner tetrad, only one chalazal megaspore becomes the functional megaspore which forms female gametophyte including 7-celled and 8-nucleated after three successive mitosis, the female gametophyte is of the Polygonum type. Two polar nuclei melt into a secondary nuclei before fertilization, the chalazal antipodal cells are ephemeral and degenerate shortly after forming. Fertilization is porogamous and belongs to premitotic type of syngamy. The division of the primary endosperm nucleus is earlier than the zygote, the endosperm is of the nuclear type with the presence of haustoria, and the embryogeny belongs to asterad type chicory variant. The developed suspensor on early stage has important significance to the embryo development.

Nets in fibrosis: Bridging innate immunity and tissue remodeling.

Fibrosis, a complex pathological process characterized by excessive deposition of extracellular matrix components, leads to tissue scarring and dysfunction. Emerging evidence suggests that neutrophil extracellular traps (NETs), composed of DNA, histones, and antimicrobial proteins, significantly contribute to fibrotic diseases pathogenesis. This review summarizes the process of NETs production, molecular mechanisms, and related diseases, and outlines the cellular and molecular mechanisms associated with fibrosis. Subsequently, this review comprehensively summarizes the current understanding of the intricate interplay between NETs and fibrosis across various organs, including the lung, liver, kidney, skin, and heart. The mechanisms by which NETs contribute to fibrogenesis, including their ability to promote inflammation, induce epithelial-mesenchymal transition (EMT), activate fibroblasts, deposit extracellular matrix (ECM) components, and trigger TLR4 signaling were explored. This review aimed to provide insights into the complex relationship between NETs and fibrosis via a comprehensive analysis of existing reports, offering novel perspectives for future research and therapeutic interventions.

Sialylation in the gut: From mucosal protection to disease pathogenesis.

Sialylation, a crucial post-translational modification of glycoconjugates, entails the attachment of sialic acid (SA) to the terminal glycans of glycoproteins and glycolipids through a tightly regulated enzymatic process involving various enzymes. This review offers a comprehensive exploration of sialylation within the gut, encompassing its involvement in mucosal protection and its impact on disease progression. The sialylation of mucins and epithelial glycoproteins contributes to the integrity of the intestinal mucosal barrier. Furthermore, sialylation regulates immune responses in the gut, shaping interactions among immune cells, as well as their activation and tolerance. Additionally, the gut microbiota and gut-brain axis communication are involved in the role of sialylation in intestinal health. Altered sialylation patterns have been implicated in various intestinal diseases, including inflammatory bowel disease (IBD), colorectal cancer (CRC), and other intestinal disorders. Emerging research underscores sialylation as a promising avenue for diagnostic, prognostic, and therapeutic interventions in intestinal diseases. Potential strategies such as sialic acid supplementation, inhibition of sialidases, immunotherapy targeting sialylated antigens, and modulation of sialyltransferases have been utilized in the treatment of intestinal diseases. Future research directions will focus on elucidating the molecular mechanisms underlying sialylation alterations, identifying sialylation-based biomarkers, and developing targeted interventions for precision medicine approaches.

Focusing on non-responders to infliximab with ulcerative colitis, what can we do first and next?

BACKGROUND: Ulcerative colitis (UC) is a chronic immune-mediated inflammation of the colorectum, for which infliximab (IFX) is currently the mainstay of treatment. However, one-third of patients with UC still fail to benefit from the IFX therapy, and early exposure to IFX impairs the efficacy of other subsequent biologics. Therefore, personalized therapeutic system is urgently needed to assist in clinical decision-making and precision treatment. METHODS: Four microarray datasets of colonic biopsies from UC patients treated with IFX were obtained from the GEO database to form the Training Cohort and Validation Cohort. Differentially expressed genes (DEGs) in Training Cohort were identified and enriched for GO, KEGG and immune cell infiltration analysis. A prediction model for IFX efficacy was developed based on the LASSO and Logistic regression. The predictive accuracy of the model was verified by the Validation Cohort, and the model-genes/proteins were validated by immunohistochemistry. Gene-drug, gene-ncRNA interaction analysis were performed to identify drugs or non-coding RNAs (ncRNAs) that potentially interacted with the model-genes. Homology Modeling and Molecular Docking were conducted to filter the optimal candidate as the subsequent adjuvant or alternative for IFX in predicted non-responders. At last, the down-regulation of the key model-gene/protein CYP24A1 by the drug candidate Deferasirox was verified by Western Blot and qRT-PCR Assay based on cellular experiments. RESULTS: A total of 113 DEGs were identified in the Training Cohort, mainly enriched in inflammatory cell chemotaxis, migration, and response to molecules derived from intestinal microbiota. Activated pro-inflammatory innate immune cells, including neutrophils, M1 macrophages, activated dendritic cells and mast cells, were significantly enriched in colons of non-responders. The prediction model based on three model-genes (IFI44L, CYP24A1, and RGS1) exhibited strong predictive efficacy, with AUC values of 0.901 and 0.80 in the Training and Validation Cohorts, respectively. Higher expression of the three model-genes/proteins in colons of non-responders to IFX was confirmed by clinical colonic mucosal biopsies. 4 Drugs (Calcitriol, Lunacalcipol, Deferasirox, Telaprevir), 15 miRNAs and 66 corresponding lnRNAs interacting with model-genes were identified. The protein 3D structure of the key model-gene/protein (human-derived CYP24A1) was developed. Through the Molecular Docking and cellular experimental validation, Deferasirox, which significantly down-regulated both the RNA and protein expression of CYP24A1, was identified as the optimal adjuvant or alternative for IFX in predicted non-responders with UC. CONCLUSION: This study developed a novel prediction model for pre-assessing the efficacy of IFX in patients with UC, as the first step towards personalized therapy. Meanwhile, drugs and non-coding RNAs were provided as potential candidates to develop the next-step precise treatment for the predicted non-responders. In particular, Defeasirox appears to hold promise as an adjuvant or alternative to IFX for the optimization of UC therapy.

Dihydromyricetin ameliorates experimental ulcerative colitis by inhibiting neutrophil extracellular traps formation via the HIF-1α/VEGFA signaling pathway.

Dihydromyricetin (DHM), which has various biological functions, possesses therapeutic potential for ulcerative colitis (UC). Neutrophil extracellular traps (NETs) and their components play a crucial role in several pathological processes in UC. However, whether DHM alleviates UC by regulating NETs remains unclear. Mice with dextran sulfate sodium (DSS)-induced acute colitis were treated with DHM at different concentrations, and the severity of colitis was evaluated by assessing body weight, colon length, histological scores, cytokine production, and epithelial barrier integrity. To quantify and visualize NETs, the expression of cell free-DNA (cf-DNA) in serum and Cit-H3 in colonic tissue was analyzed via western blotting and immunofluorescence analysis. HL-60 cells and mouse bone marrow-derived neutrophils (BMDNs) were used to evaluate the effects of DHM on NETs in vitro. NETs were treated with DHM at varying concentrations or DNase I and used to repair the intestinal epithelial barrier in a Caco-2/HIEC-6 cell monolayer model. Furthermore, the genes targeted by DHM through neutrophils for alleviating UC were identified by screening online databases, and the results of network pharmacological analysis were verified via western blotting and quantitative real-time polymerase chain reaction. DHM alleviated DSS-induced colitis in mice by reversing weight loss, increased DAI score, colon length shortening, enhanced spleen index, colonic pathological damage, cytokine production, and epithelial barrier loss in a dose-dependent manner. In addition, it inhibited the formation of NETs both in vivo and in vitro. Based on the results of network pharmacological analysis, DHM may target HIF-1α and VEGFA through neutrophils to alleviate UC. Treatment with PMA increased the expression of HIF-1α and VEGFA in D-HL-60 cells and BMDNs, whereas treatment with DHM or DNase I reversed this effect. Treatment with DMOG, an inhibitor of HIF prolyl hydroxylase (HIF-PH), counteracted the suppressive effects of DHM on NETs formation in D-HL-60 cells and BMDNs. Accordingly, it partially counteracted the protective effects of DHM on the intestinal epithelial barrier in Caco-2 and HIEC-6 cells. These results indicated that DHM alleviated DSS-induced UC by regulating NETs formation via the HIF-1α/VEGFA signaling pathway, suggesting that DHM is a promising therapeutic candidate for UC.

Exploration of mRNA nanoparticles based on DOTAP through optimization of the helper lipids.

Lipid nanoparticles (LNPs) are one of the most efficient carriers for RNA packaging and delivery, and vaccines based on mRNA-LNPs have received substantial attention since the outbreak of the COVID-19 pandemic. LNPs based on 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) have been widely used in preclinical and clinical settings. A novel non-viral gene delivery system called LNP3 was previously developed, which was composed of DOTAP, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and cholesterol. One of the helper lipids in this carrier was DOPE, which belongs to phospholipids. Given that substituting DOPE with non-phospholipids as helper lipids can increase the delivery efficiency of some LNPs, this study aimed to examine whether non-phospholipids can be formulated with DOTAP as helper lipids. It was found that monoglycerides with C14:0, C16:0, C18:0, C18:1, and C18:2 mediated mRNA transfection, and the transfection efficiency varied between C18:0, C18:1, and C18:2. Furthermore, substituting of the glycerol with other moieties such as the cholesterol or the ethanolamine similarly mediated mRNA transfection. The introduction of cholesterol can further improve the transfection capacity of some DOTAP-based LNPs. One of the best-performing formulations, LNP3-MO, was used to mediate luciferase-mRNA expression in vivo, and the luminescence signal was found to be mainly enriched in the lung and spleen. In addition, the level of SARS-CoV-2 spike antibody in the serum increased after three doses of LNP3-MO mediated SARS-CoV-2 spike mRNA. Altogether, this study demonstrates that non-phospholipids are promising helper lipids that can be formulated with DOTAP to facilitate efficient delivery of mRNAs in vitro and in vivo with organ-specific targeting.

Dihydromyricetin alleviates inflammatory bowel disease associated intestinal fibrosis by inducing autophagy through the PI3K/AKT/mTOR signaling pathway.

Intestinal fibrosis is a common complication of inflammatory bowel disease and is characterized by tissue stiffening and luminal narrowing. Dihydromyricetin (DHM) can alleviate liver fibrosis and renal interstitial fibrosis by inducing autophagy. However, whether DHM can alleviate intestinal fibrosis remains unclear. This study is aimed at evaluating the role and mechanism of action of DHM in inflammatory bowel disease-associated intestinal fibrosis. Mice were administered dextran sulfate sodium (DSS) in drinking water to induce inflammatory bowel disease-associated intestinal fibrosis. HE staining, qPCR, and Western blotting were used to analyze colon inflammation. Masson's trichrome staining, qPCR, Western blotting, and immunofluorescence staining were used to evaluate the severity of fibrosis. Transmission electron microscopy and Western blotting were used to assess the activation of autophagosomes. The human colonic fibroblast line CCD-18Co was cultured in the presence of TGF-ß1 to develop a fibrotic phenotype. Immunofluorescence staining, Western blotting, and qPCR were used to assess the alteration of fibrosis markers and used to investigate whether DHM-induced autophagy was involved in the inactivation of CCD-18Co cells. Additionally, the role of the PI3K/AKT/mTOR pathway was investigated. DHM alleviated intestinal inflammation and inhibited the progression of intestinal fibrosis. Additionally, DHM induced the activation of autophagy, thereby alleviating intestinal fibrosis, and downregulated the PI3K/AKT/mTOR signaling pathway in vitro. Overall, this study demonstrated that DHM can inhibit the progression of intestinal fibrosis and activation of colonic fibroblasts by inducing autophagy through the PI3K/AKT/mTOR signaling pathway, thereby playing a preventive and therapeutic role in intestinal fibrosis.

Glycosyltransferase GLT8D1 and GLT8D2 serve as potential prognostic biomarkers correlated with Tumor Immunity in Gastric Cancer.

BACKGROUND: Glycosylation involved in various biological function, aberrant glycosylation plays an important role in cancer development and progression. Glycosyltransferase 8 domain containing 1 (GLT8D1) and GLT8D2, as members of the glycosyltransferase family proteins, are associated with transferase activity. However, the association between GLT8D1/2 and gastric cancer (GC) remains unclear. We aimed to investigate the potential prognostic value and oncogenic role of GLT8D1/2 in GC. METHODS: The relationship between GLT8D1/2 and GC was evaluated through comprehensive bioinformatics approaches. A series of factors like gene expression patterns, Kaplan-Meier survival analyses, Cox regression analyses, prognostic nomogram, calibration curves, ROC curves, function enrichment analyses, tumor immunity association, genetic alterations, and DNA methylation were included. Data and statistical analyses were performed using R software (v3.6.3). RESULTS: Both GLT8D1 and GLT8D2 expression were significantly upregulated in GC tissues(n = 414) compared with normal tissues(n = 210), and high expression of GLT8D1/2 was remarkably correlated with poor prognosis for GC patients. Cox regression analyses implied that GLT8D1/2 could act as independent prognostic factors in GC. Furthermore, gene function analyses indicated that multiple signaling pathways involving tumor oncogenesis and development enriched, such as mTOR, cell cycle, MAPK, Notch, Hedgehog, FGF, and PI3K-Akt signaling pathways. Moreover, GLT8D1/2 was significantly associated with immune cell infiltration, immune checkpoint genes, and immune regulators TMB/MSI. CONCLUSION: GLT8D1/2 may serve as potential prognostic markers of poor prognosis in GC correlated with tumor immunity. The study provided an insight into identifying potential biomarkers and targets for prognosis, immunotherapy response, and therapy in GC.

Antibiotics Resistance Prevalence of Helicobacter pylori Strains in Northwest China.

Purpose: This study aims to estimate the resistance rate of Helicobacter pylori (HP) to commonly used antibiotics and analyze the potential influencing factors in northwest regions of China. Patients and Methods: HP-positive patients visiting the outpatient department of multiple hospitals were enrolled in the study. Then, gastric mucosal biopsy specimens were collected for HP isolation, culture, and investigation of the resistance rate of HP to amoxicillin, metronidazole, tetracycline, levofloxacin, and clarithromycin by Epsilometer test (E-test) antibiotic susceptibility testing. In addition, multi-drug resistance, the influence of HP eradication history, age, and region of residence on drug resistance rate were analyzed. Results: In total, 198 HP clinical strains were successfully isolated and cultured. The resistance rates of amoxicillin, metronidazole, tetracycline, levofloxacin, and clarithromycin were 16.16%, 85.86%, 7.58%, 46.46%, and 55.05%, respectively. The multi-drug resistance rates demonstrated that dual and triple resistances were 30.30% and 22.73%, respectively. The quadruple resistance rate reached 9.60%. Our results revealed that the prior eradication history of HP significantly increased levofloxacin and clarithromycin resistance. Metronidazole and levofloxacin resistances significantly differed among different age groups, which presented an upward trend with increasing age. Drug resistance rates varied with geographic regions, especially amoxicillin and clarithromycin resistance, which were highest in Hexi Corridor and Longnan regions. Conclusion: The current situation of HP resistance to common antibiotics is severe. Tetracycline is the most sensitive antibiotic, followed by amoxicillin, the first choice for HP eradication. However, the eradication failure of HP may lead to an increase in the resistance rate. Therefore, it is necessary to strengthen the standardized diagnosis and treatment of HP to improve the primary eradication rate.

Impact of biological agents and tofacitinib for moderate-to-severe ulcerative colitis on health-related quality of life: a protocol for a network meta-analysis.

INTRODUCTION: In the past few years, several options have been proposed as alternative and more effective therapeutic drugs for moderate-to-severe ulcerative colitis (UC), such as biological agents and tofacitinib. Most of the clinical studies related to UC aimed to evaluate the efficacy of the drugs on clinical outcomes such as disease activity and side effects. This review aims to compare the impact of infliximab, adalimumab, golimumab, ustekinumab, vedolizumab and tofacitinib for moderate-to-severe UC on health-related quality of life (HRQoL), thereby guiding clinical treatment and scientific research of this disease. METHODS AND ANALYSIS: We will search PubMed, Embase and Cochrane Library from inception until July 2021 for all randomised controlled trials (RCTs) reported in English as double-blind comparing infliximab, adalimumab, golimumab, ustekinumab, vedolizumab or tofacitinib as induction or maintenance therapies with another or with placebo in moderate-to-severe UC on HRQoL. The primary outcome of this study is changes in the mean difference in HRQoL scores. Data of each pairwise comparison will be synthesised to obtain summary standardised mean differences for continuous outcomes and ORs for dichotomous outcomes. Then, a network meta-analysis (NMA) will be performed, and a common-effects Mantel-Haenszel NMA will be conducted for dichotomous outcomes, while a random-effects NMA will be used for all other outcomes. Finally, we will follow the Grading of Recommendations, Assessment, Development and Evaluations approach to assess the confidence in estimates derived from NMA of the main outcomes. ETHICS AND DISSEMINATION: Only published secondary data will be used in this study, and therefore ethics approval is not required. The findings will be published in a peer-reviewed medical journal. PROSPERO REGISTRATION NUMBER: CRD42021225048.

Comparative efficacy and safety of high-dose dual therapy, bismuth-based quadruple therapy and non-bismuth quadruple therapies for Helicobacter pylori infection: a network meta-analysis.

Helicobacter pylori (H. pylori) infection is associated with the development of multiple diseases. The eradication rate of H. pylori has gradually decreased, suggesting the need to discover more effective therapies. This study aimed to compare the effectiveness of first-line treatments including high-dose dual therapy (HDDT), bismuth-based quadruple therapy (BQT), sequential therapy (ST), concomitant therapy (CT) and hybrid therapy (HT) by network meta-analysis (NMA). A comprehensive search on PubMed, Embase, Cochrane Library and Web of Science, was performed from their inception to 1 September 2019. A network analysis of randomized controlled trials (RCTs) comparing first-line therapies were carried out using Stata 14.0 and Revman 5.2. Moreover, a sensitivity analysis was conducted by omitting non-Asian studies. Finally, 41 RCTs with 14 119 patients were included. The NMA showed that, in terms of eradication rate, ST for 10 days (ST-10) was significantly lower than CT for 10 or 14 days (CT ≥ 10). Sensitivity analysis among the Asian population showed that ST-10 denoted the lowest effectiveness among the interventions. The ranking results based on probability showed that HDDT ranked first for the eradication rate. As for adverse events, HDDT was significantly less than BQT and CT regardless of duration, while BQT for 14 days represented higher adverse events than ST, HT and CT ≥ 10. HDDT ranked first among the therapies. In conclusion, HDDT for 14 days appeared to be the most optimal first-line therapy for H. pylori among the Asian population with comparable efficacy and compliance but causing fewer adverse events.

Associating the risk of three urinary cancers with obesity and overweight: an overview with evidence mapping of systematic reviews.

BACKGROUND: The relationship between cancer with overweight and obesity has been extensively reported. However, the association between urinary cancers with these risk factors remains unclear, with existing reports showing conflicting findings. The current review, therefore, sought to clarify the latter association by assessing the methodological and reporting quality of existing systematic reviews on the subject. METHODS: We first screened PubMed, EMBASE, and Cochrane Library databases for relevant literature and subjected the resulting articles to meta-analysis. We adopted the AMSTAR-2 and PRISMA checklists for assessing methodological and reporting quality, respectively, then performed meta-analyses to determine the relationship between incidence and mortality of three types of urinary cancers with obesity and overweight. Indirect comparisons were also done across subgroups. RESULTS: All systematic reviews (SRs) were of critically low methodological quality. Seventeen SRs had minimal reporting flaws, and 11 SRs had minor reporting flaws. We found an association between obesity with an incidence of kidney (RR = 1.68, 95% CI 1.47-1.92), bladder (RR = 1.1, 95% CI 1.07-1.13), and prostate (RR = 1.02, 95% CI 0.91, 1.13) cancers. Similarly, overweight was associated with the incidence of the three types of cancer, recording RR values of 1.37 (95% CI 1.26-1.48), 1.07 (95% CI 1.03-1.1), and 1 (95% CI 0.93, 1.07) for kidney, bladder, and prostate cancers, respectively. With regard to the dose analysis, the RR of BMI (per 5 kg/m2 increase) was associated with kidney (RR = 1.24, 95% CI 1.2-1.28), bladder (RR = 1.03, 95% CI 1.02-1.05), and prostate (RR = 1.02, 95% CI 1.01, 1.03) cancers. CONCLUSIONS: This comprehensive quantitative analysis provides an affirmation that overweight and obesity are strong risk factors for kidney cancer, owing to a strong association between them. Conversely, a weak association between overweight and obesity with bladder and prostate cancers confirms their status as mild risk factors for the 2 types of cancer. But due to the low quality of included SRs, the results need to be interpreted with caution. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019119459.

The value of four imaging modalities in diagnosing lymph node involvement in rectal cancer: an overview and adjusted indirect comparison.

Several systematic reviews have investigated the accuracy of imaging modalities for lymph node involvement of rectal cancer, but there are considerable differences in conclusions. This overview aimed to assess the methodological and reporting quality of systematic reviews that evaluated the diagnostic value of imaging modalities for lymph node involvement in patients with rectal cancer and to compare the diagnostic value of different modalities for lymph node involvement. The PubMed, EMBASE, Cochrane Library and Chinese Biomedicine Literature were searched to identify relevant systematic reviews. The methodological quality was assessed using the AMSTAR checklist, and the reporting quality was assessed using PRISMA-DTA checklist. The indirect comparison was conducted to compare the accuracy of different imaging modalities. Seven systematic reviews involving 353 primary studies were included. The median (Range) AMSTAR scores were 6.0 (4.0-9.0); the median (Range) PRISMA-DTA scores were 18.0 (11.0-23.0). Sensitivity of MRI [0.69 (95% CI 0.63, 0.77)] was significantly higher than that of ERUS [0.57 (95% CI 0.53, 0.62)]. Specificity of ERUS [0.80 (95% CI 0.77, 0.83)] was significantly higher than that of CT [0.72 (95% CI 0.67, 0.78)]. Positive likelihood ratio of EUS [3.04 (95% CI 2.75, 3.36)] was significantly higher than that of CT [2.21 (95% CI 1.69, 2.90)]. EUS had better diagnostic value than CT and ERUS in the diagnosis of lymph node involvement. Compared with CT and ERUS, MRI was more sensitive. EUS and MRI had comparable diagnostic accuracy, but no modality was proved to be particularly accurate.

Improvement needed in the network geometry and inconsistency of Cochrane network meta-analyses: a cross-sectional survey.

OBJECTIVES: The aim of the study was to investigate the general characteristics and methodological and reporting quality of network meta-analyses (NMAs) published in the Cochrane library. STUDY DESIGN AND SETTING: We conducted a comprehensive search of the Cochrane library in April 2018 and included 42 NMAs. We used the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 to assess methodological quality and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-NMA for reporting quality. Stratified analysis and correlation analysis were conducted to explore the factors that might affect the quality. RESULTS: A total of 42 NMAs investigated 29 topics. The compliance of PRISMA-NMA was moderate. Only 26.2% NMAs described the geometry of network, 64.3% presented the network plot, and 33.3% fully assessed the inconsistency. The overall methodological quality was low. Only 11.9% NMAs explained the selection of study designs, and 40.5% investigated the publication bias. The compliance of PRISMA-NMA was higher with the increase of the AMSTAR 2 compliance rates (Spearman's ρ = 0.630, P = 0.000). NMAs with statistical or epidemiological authors often better reported the titles (P = 0.032). Compared with nonfunding NMAs, nonindustry funding NMAs often better reported data collection process (P = 0.028), planned methods of analysis (P = 0.034), and synthesis of results (P = 0.028). CONCLUSION: The quality still needs to be further improved, especially referring to the assessment of publication bias, the geometry of network, and assessment and exploration of inconsistency.

The association between body mass index and the risk of different gastrointestinal cancers: A protocol for an overview of systematic reviews.

BACKGROUND: Changes in our lifestyle over the past few decades have led to a significant increase in the worldwide prevalence of both overweight (defined as a body mass index [BMI]≥25 kg/m) and obesity (BMI≥30 kg/m), thus leading to numerous harmful consequences for an individual's health. Several meta-analyses support the link between obesity and different gastrointestinal cancers, but substantial heterogeneity exists between studies. We will synthesize published systematic reviews to evaluate the association between body mass index (BMI) and the incidence and mortality of different gastrointestinal cancers. METHODS: PubMed, EMBASE, and the Cochrane Library will be systematically searched for systematic reviews, meta-analyses, and pooled analyses in July, 2018. Two review authors will independently screen titles and abstracts for relevance, assess full texts for inclusion, carry out data extraction, and appraise methodological quality using AMSTAR checklist and reporting quality using PRISMA statement. The association between BMI and different gastrointestinal cancers will be estimated by computing the pooled relative risk (RR) and its 95% confidence interval (CI), which will be calculated from the adjusted RR, odds ratio, or hazard ratio, and 95% CI offered in the studies. Heterogeneity between studies will be assessed with the I statistic as a measure of the proportion of total variation in estimates that is due to heterogeneity, where I values of 25%, 50%, and 75% correspond to cut-off points for low, moderate, and high degrees of heterogeneity. The random effects model will be used as the pooling method when significant heterogeneity existed and the fixed effect model will be used when no heterogeneity was observed. Possible publication bias will be tested by Begg and Egger test. DISCUSSION: This overview of systematic reviews will provide an accessible, comprehensive synthesis with which to inform clinicians and the development of guidelines for the management of the individuals with high BMI. ETHICS AND DISSEMINATION: Only published secondary data will be used in this study, and therefore ethics approval is not required.PROSPERO registration number: CRD42018107334.