IntroductionClinical studies have demonstrated a potential association between chronic hepatitis caused by hepatitis B virus (HBV) infection and osteoporosis. However, the causal relationship between HBV infection and osteoporosis remains to be determined.MethodsWe investigated whether HBV infection is causally associated with osteoporosis using Mendelian randomization (MR) in East Asian and European populations, respectively. The data we utilized were obtained from the genome-wide association studies (GWAS) database. Various MR methods, including inverse variance weighted (IVW), MR Egger, weighted median, simple median and simple mode were employed to estimate the association between HBV infection and osteoporosis. Heterogeneity analysis and sensitivity tests were performed to ensure the robustness of the results. Bayesian co-localization (coloc) analysis was also applied to calculate the posterior probability of causal variants and to identify common genetic variants between HBV infection and osteoporosis.ResultsMR analysis indicated that HBV infection increased the risk of osteoporosis onset in two East Asian cohort (IVW, OR = 1.058, 95% CI = 1.021 to 1.097, P = 0.002 and OR = 1.067, 95% CI = 1.029 to 1.106, P < 0.001). However, a clear effect of genetic susceptibility to HBV on the enhanced risk of osteoporosis was not observed in two European cohort (IVW, OR = 1.000, 95% CI = 0.999 to 1.001, P = 0.171 and OR = 1.003, 95% CI = 0.981 to 1.025, P = 0.780). Additional MR methods and sensitivity analyses further validated the reliability and robustness of our results. Bayesian co-localization analysis revealed co-localization of HBV infection and osteoporosis on STAT4 at rs11889341based on East Asian GWAS data.ConclusionsOur study identified a causal relationship between HBV infection and osteoporosis in East Asian and European populations. These results provided strong evidence that HBV infection augmented the risk of developing osteoporosis in East Asian populations and provided novel therapeutic targets.

IntroductionNon-small cell lung cancer (NSCLC) is a prevalent respiratory system tumor. Triggered transposable element derivative 1 (TIGD1) exhibits significant overexpression in various tumor cells and tissues, suggesting its involvement in cancer progression.MethodsClinical data and gene expression profiles of lung adenocarcinoma were collected from TCGA, UCSC XENA, and GEO databases. Computational techniques and empirical studies were employed to analyze the role of TIGD1 in NSCLC. Cellular experiments were conducted using the H1299 cell line, including RNA interference, cell viability assays, quantitative PCR, wound-healing assays, western blotting, and plate clone formation assays.ResultsBioinformatics analysis revealed TIGD1’s potential as a biomarker for diagnosing and predicting lung cancer. It also indicated promise as a target for immune-related therapy and targeted drug therapy. Cellular studies confirmed TIGD1’s involvement in cancer cell proliferation, invasion, and migration. Furthermore, an association between TIGD1 and the PI3K/AKT signaling pathway was suggested.DiscussionThe findings suggest that TIGD1 plays a vital role in NSCLC progression, making it a potential diagnostic biomarker and therapeutic target. The association with the PI3K/AKT signaling pathway provides insights into the underlying molecular mechanisms. Integrating computational analysis with empirical studies enhances our understanding of TIGD1’s significance in NSCLC and opens avenues for further research into targeted therapies.

Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related deaths worldwide. Different treatment approaches are typically employed based on the stage of NSCLC. Common clinical treatment methods include surgical resection, drug therapy, and radiation therapy. However, with the introduction and utilization of immune checkpoint inhibitors, cancer treatment has entered a new era, completely revolutionizing the treatment landscape for various cancers and significantly improving overall patient survival. Concurrently, treatment resistance often poses a critical challenge, with many patients experiencing disease progression following an initial response due to treatment resistance. Increasing evidence suggests that the tumor microenvironment (TME) plays a pivotal role in treatment resistance. Tumor-associated macrophages (TAMs) within the TME can promote treatment resistance in NSCLC by secreting various cytokines activating signaling pathways, and interacting with other immune cells. Therefore, this article will focus on elucidating the key mechanisms of TAMs in treatment resistance and analyze how targeting TAMs can reduce the levels of treatment resistance in NSCLC, providing a comprehensive understanding of the principles and approaches to overcome treatment resistance in NSCLC.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder with intricate pathogenic mechanisms. Despite the availability of various oral medications for controlling the condition, reports of poor glycemic control in type 2 diabetes persist, possibly involving unknown pathogenic mechanisms. In recent years, the gut microbiota have emerged as a highly promising target for T2DM treatment, with the metabolites produced by gut microbiota serving as crucial intermediaries connecting gut microbiota and strongly related to T2DM. Increasingly, traditional Chinese medicine is being considered to target the gut microbiota for T2DM treatment, and many of them are edible. In studies conducted on animal models, edible traditional Chinese medicine have been shown to primarily alter three significant gut microbiotal metabolites: short-chain fatty acids, bile acids, and branched-chain amino acids. These metabolites play crucial roles in alleviating T2DM by improving glucose metabolism and reducing inflammation. This review primarily summarizes twelve edible traditional Chinese medicines that improve T2DM by modulating the aforementioned three gut microbiotal metabolites, along with potential underlying molecular mechanisms, and also incorporation of edible traditional Chinese medicines into the diets of T2DM patients and combined use with probiotics for treating T2DM are discussed.

The high prevalence of constipation after fracture surgery brings intolerable discomfort to patients on the one hand, and affects post-surgery nutrient absorption on the other hand, resulting in poor prognosis. Given the acknowledged probiotic properties of Lactobacillus rhamnosus, 100 fracture patients with post-surgery constipation were centrally enrolled and administered orally with L. rhamnosus JYLR-127 to assess the efficacy of probiotic-adjuvant therapy in alleviating post-fracture constipation symptoms. The results showed that L. rhamnosus JYLR-127 improved fecal properties, promoted gastrointestinal recovery, and relieved constipation symptoms, which were mainly achieved by elevating Firmicutes (p < 0.01) and descending Bacteroidetes (p < 0.001), hence remodeling the disrupted intestinal microecology. In addition, blood routine presented a decrease in C-reactive protein levels (p < 0.05) and an increase in platelet counts (p < 0.05) after probiotic supplementation, prompting the feasibility of L. rhamnosus JYLR-127 in anti-inflammation, anti-infection and hemorrhagic tendency prevention after fracture surgery. Our study to apply probiotics in ameliorating constipation after fracture surgery is expected to bless the bothered patients, and provide broader application scenarios for L. rhamnosus preparations.

Abstract Parkinson's disease (PD) is a common neurodegenerative disease with limited treatment and no cure, hence, broadening PD drug spectrum is of great significance. At present, engineered microorganisms are attracting increasing attention. In this study, we constructed an engineered strain of Clostridium butyricum‐GLP‐1, a C. butyricum (a probiotic) that consistently expresses glucagon‐like peptide‐1 (GLP‐1, a peptide‐based hormone with neurological advantage) in anticipation of its use in PD treatment. We further investigated the neuroprotective mechanism of C. butyricum‐GLP‐1 on PD mice models induced by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine. The results indicated that C. butyricum‐GLP‐1 could improve motor dysfunction and ameliorate neuropathological changes by increasing TH expression and reducing the expression of α‐syn. Moreover, we confirmed that C. butyricum‐GLP‐1 improved microbiome imbalance of PD mice by decreasing the relative abundance of Bifidobacterium at the genus level, improved gut integrity, and upregulated the levels of GPR41/43. Surprisingly, we found it could exert its neuroprotective effects via promoting PINK1/Parkin mediated mitophagy and attenuating oxidative stress. Together, our work showed that C. butyricum‐GLP‐1 improves PD by promoting mitophagy, which provides an alternative therapeutic modality for PD.

Helicobacter pylori ( H. pylori ) is a major risk factor of gastric cancer (GC). The SUMO-activating enzyme SAE1(SUMO-activating enzyme subunit 1), which is indispensable for protein SUMOylation, involves in human tumorigenesis. In this study, we used the TIMER and TCGA database to explore the SAE1 expression in GC and normal tissues and Kaplan–Meier Plotter platform for survival analysis of GC patients. GC tissue microarray and gastric samples from patients who underwent endoscopic treatment were employed to detect the SAE1expression. Our results showed that SAE1 was overexpressed in GC tissues and higher SAE1 expression was associated with worse clinical characteristics of GC patients. Cell and animal models showed that H. pylori infection upregulated SAE1, SUMO1, and SUMO2/3 protein expression. Functional assays suggested that suppression of SAE1 attenuated epithelial-mesenchymal transition (EMT) biomarkers and cell proliferation abilities induced by H. pylori . Cell and animal models of ROS inhibition in H. pylori showed that ROS could mediate the H. pylori -induced upregulation of SAE1, SUMO1, and SUMO2/3 protein. RNA sequencing was performed and suggested that knockdown of SAE1 could exert an impact on IGF-1 expression. General, increased SUMOylation modification is involved in H. pylori -induced GC.

The current study aims to evaluate the potential roles of taking probiotics postoperatively in attenuating the gastrointestinal complications and disturbed gut microbiota in colorectal cancer (CRC) patients undergoing chemotherapy. One hundred eligible CRC patients who were treated with radical surgery and needed to receive chemotherapy were recruited. Half of them were randomly assigned to the Probio group to take a probiotic combination from post-operation to the end of the first chemotherapeutic course. The other half of patients taking placebo instead were classified as the Placebo group. Gastrointestinal complications such as nausea, acid reflux, abdominal pain, abdominal distention, constipation, and diarrhea were recorded during chemotherapy. Fecal samples were collected preoperatively and after the first cycle of postoperative chemotherapy for 16S rRNA high-throughput sequencing and short-chain fatty acids (SCFAs) analysis. Results showed that probiotics administration could effectively reduce chemotherapy-induced gastrointestinal complications, particularly in diarrhea (p < 0.01). Additionally, chemotherapy also reduced the bacterial diversity indexes of the gut microbiota in CRC patients, which could be significantly increased by taking probiotics. Moreover, this chemotherapy caused significant changes in the composition of the gut microbiota, as indicated by decreased phylum levels of Firmicutes and increased Bacteroidetes, Proteobacteria, and Verrucomicrobia. In particular, several bacterial genera such as Akkermansia and Clostridium were significantly increased, while Prevotella, Lactobacillus, and Roseburia were decreased (p < 0.05). However, probiotic administration could effectively restore these taxa changes both at the phylum and genus levels, and mildly increase the genus levels of Bifidobacterium, Streptococcus, and Blautia. Furthermore, probiotics could also promote the production of SCFAs, particularly increasing acetate, butyrate, and propionate (p < 0.0001). These results support the beneficial effects of the probiotic interventions as novel alternative or complementary strategies in chemoprevention.

Abstract Digestive system tumours are the most common malignancies worldwide, causing huge number of deaths each year. With the increases in morbidity and mortality, it is imperative to identify new therapeutic targets. Melanoma-associated antigen-A6 (MAGEA6) is a member of the cancer/testicular antigen (CTA) family. There are increasing amount of evidence supporting that MAGEA6 plays an important role in the development of solid tumours. However, there has been no comprehensive analysis of MAGEA6 in digestive system tumours. Therefore, our objective was to investigate the expression level, clinical significance and related biological functions of MAGEA6 in digestive system tumours. In this study, we integratively analysed the data from multiple databases of patients with digestive system tumours. Our results showed that MAGEA6 was highly expressed in most digestive system tumours as compared with normal tissues, whereas patients with higher expression of MAGEA6 had a worse prognosis. Based on co-expression analysis, there was a close interaction between MAGEA6 and MAGEA3. Furthermore, differential gene enrichment analysis indicated that MAGEA6 was mainly involved in the formation of extracellular structure, DNA replication, mitosis and the p53 signalling pathway. These results suggest that MAGEA6 is as a prognostic factor with functional importance in digestive system tumours.

Helicobacter pylori (H. pylori) infection is considered a class I carcinogen in the pathogenesis of gastric cancer. In recent years, the interaction relationship between H. pylori infection and autophagy has attracted increasing attention. Most investigators believe that the pathogenesis of gastric cancer is closely related to the formation of an autophagosome-mediated downstream signaling pathway by H. pylori infection-induced cells. Autophagy is involved in H. pylori infection and affects the occurrence and development of gastric cancer. In this paper, the possible mechanism by which H. pylori infection affects autophagy and the progression of related gastric cancer signaling pathways are reviewed.

BackgroundIn recent years, the rapid development of digestive endoscopy technology has brought revolutionary changes to endoscopic therapy. A growing number of articles have been published annually. We aimed to explore global scientific outputs and hotspots of endoscopic mucosal resection (EMR) published by different countries, organizations, and authors.MethodsWe extracted relevant publications from the Web of Science Core Collection (WOSCC) on June 23, 2022. We examined the retrieved data by bibliometric analysis (e.g., cocited and cluster analysis, keyword co-occurrence) using the software CiteSpace and VOSviewer to analyze and predict the trends and hot spots in this field.ResultsA total of 2,695 papers were finally identified. The results showed that the number of articles fluctuated with the year and reached its peak in 2021. NATIONAL CANCER CENTER JAPAN was the most influential institution. MICHAEL J BOURKE and YUTAKA SAITO are two of the most prolific scholars. ENDOSCOPY and GASTROINTESTINAL ENDOSCOPY were the most productive journals. “Early gastric cancer” and “Barrett's esophagus” were the focus of EMR research. “Adverse events”, “cold snare polypectomy” and “outcomes” have become increasingly popular in recent years and could become hot spots in the future.ConclusionIn this study, we summarized the characteristics of the publications; identified the most influential countries, institutions, and journals; and identified the leading topics in the EMR field.

Background: Marginal ulcer bleeding is a cause of upper gastrointestinal bleeding, but the effi-cacy of emergency endoscopic hemostasis and risk factors for rebleeding have not been fully explored. The purpose of the current study was to investigate the rebleeding rate and risk fac-tors after emergency endoscopic hemostasis for marginal ulcer bleeding.Methods: We conducted a retrospective study of 105 patients who underwent emergency endo-scopic hemostasis due to marginal ulcer bleeding from January 2015 to July 2021. Patients included in this study were divided into rebleeding and non-rebleeding groups.Results: Among the 105 patients, 15.2% (16/105) patients developed rebleeding within 30 days after endoscopic hemostasis, and 87.5% of the patients had rebleeding within 7 days. The mean age of these patients was 60.3 +/- 12.3 years, and 95 of them were male. In the univariate analy-sis, an ulcer size >10 mm, a PLT count <100 x 10"9/L and an AIMS65 score >2 were risk factors for rebleeding. According to the multivariable analysis, an ulcer size >10 mm (OR: 3.715; 95% CIs: 1.060-14.250; p = 0.043) and a PLT count <100 x 10"9/L (OR: 4.480; 95% CIs: 1.099-18.908; p = 0.035) were independent risk factors for rebleeding.Conclusion: Emergency endoscopic hemostasis is an effective treatment for marginal ulcer bleeding. An ulcer size >10 mm and a PLT count <100 x 10"9/L were independent risk factors for rebleeding within 30 days after endoscopic hemostasis for marginal ulcer bleeding. (c) 2022 Elsevier Masson SAS. All rights reserved.