A novel model based on ubiquitination-related gene to predict prognosis and immunotherapy response in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a common cancer that is increasingly becoming a global health problem and a major public health concern. In order to improve patient outcomes, additional biomarkers and targets must be explored. Ubiquitination-related genes (URGs), as tumor regulators, exhibit multiple functions in tumor development. Our objective was to examine the influence of URGs on the prognosis of patients with HCC. Methods: By utilizing unsupervised cluster analysis, we were able to identify URGs in the database and create a risk score profile for predicting the prognosis of patients with HCC. The model's clinical application was explored using subject operating characteristic curves, survival analysis, and correlation analysis. We additionally examined the variances in clinical traits, immune infiltration, somatic genetic alterations, and responsiveness to treatment among high- and low-risk populations identified by the prognostic model. Scores for immune cell infiltration and immune-related pathway activity were determined by performing ssGSEA enrichment analysis. Additionally, to investigate potential mechanisms, we utilized GO, KEGG and GSVA analyses. Results: We developed a risk scoring model that relies on genes associated with ubiquitination. As the risk score increased, the malignancy and prognosis of the tumor worsened. The high-risk and low-risk groups exhibited notable disparities in relation to the immune microenvironment, genes associated with immune checkpoints, sensitivity to drugs, and response to immunotherapy. Conclusion: The utilization of a risk model that relies on genes associated with ubiquitination can serve as a biomarker to assess the prognosis of patients with HCC, and aid in the selection of suitable therapeutic agents.

Effect of Helicobacter pylori infection on body fat percentage in middle-aged and elderly populations.

Obesity, which is associated with excessive accumulation of body fat, is emerging as a new public health problem. Bioelectrical impedance analysis (BIA) is a non-invasive and straightforward method to analyze body composition, providing a more accurate estimate of obesity than the commonly used body mass index. The primary objective of this study was to examine the potential impact of Helicobacter pylori (H. pylori) infection on body fat percentage in a population using cross-sectional and cohort studies. METHODS: A population of people who underwent physical examinations at Taizhou Hospital between 2017 and 2022 was included. The participants underwent various tests, including urea breath test, hematological examination, and anthropometric measurement, in addition, their body fat percentage was determined through the use of BIA. Univariate and multifactorial regression analyses were conducted to identify factors associated with excess body fat. RESULTS: There was a difference in body fat percentage between H. pylori positive and negative populations. The population was divided into young and middle-aged and elderly according to age, and H. pylori infection was found to differ only in the middle-aged and elderly population. Multifactorial logistic regression showed that H. pylori infection remained associated with excess body fat in the middle-aged and elderly population. A subsequent cohort study confirmed the association of persistent H. pylori infection with excess body fat in the population. CONCLUSION: H. pylori was negatively associated with excess body fat in middle-aged and elderly populations, and long-term H. pylori infection has a negative effect on body fat in people.

Haptoglobin 2-2 Genotype is Related to the Severity of Liver Damage in Hepatitis B Patients with Liver Steatosis.

BACKGROUND: The Haptoglobin (Hp) genotypes have been linked to immune diseases and play a significant role in metabolic diseases. This study aimed to analyze the correlation between Hp gene polymorphism and the severity of hepatitis B accompanied by liver steatosis. METHODS: A total of 182 with Hepatitis B and concurrent hepatic steatosis were included in the study. Clinical biochemical indices for each participant were recorded. DNA was extracted from peripheral blood leukocytes for globin genotyping. Of these participants, 128 underwent biopsy from which histological data were collected. RESULTS: Subjects with hepatitis B and hepatic steatosis carrying the Hp 2-2 genotype exhibited elevated alanine transaminase (ALT), c-glutamyl transferase (GGT), and aspartate amino transferase (AST) levels. In contrast, high-density lipoprotein (HDL) levels and the copy number of Hepatitis B Virus (HBV)-DNA were significantly reduced in those with the Hp 2-2 genotype (p < 0.05). Furthermore, individuals processing the Hp 2-2 genotype demonstrated a heightened hepatitis score and advanced fibrosis stage (p < 0.05). Notably, the Hp 2-2 genotype was independently associated with increased inflammation (odds ratio (OR) = 7.059, p < 0.001) and progressive fibrosis (OR = 3.05, p < 0.022). CONCLUSIONS: The Hp 2-2 genotype is significantly associated with increased severity in cases of hepatitis B with coexisting hepatic steatosis.

Helicobacter pylori infection increases the risk of carotid plaque formation: Clinical samples combined with bioinformatics analysis.

Objective: Infection with Helicobacter pylori (H. pylori) may increase atherosclerosis, which can lead to carotid plaque formation. Our study examined the relationship between H. pylori infection and carotid plaque formation, and its underlying mechanisms. Methods: A total of 36,470 people who underwent physical examination in Taizhou Hospital Health Examination Center from June 2017 to June 2022 were included in this study. All people participated in the urease test, neck ultrasound, blood pressure detection, anthropometric measurement and biochemical laboratory examination. In addition, the GSE27411 and GSE28829 datasets in the Gene Expression Omnibus (GEO) database were used to analyze the mechanism of H. pylori infection and atherosclerosis progression. Results: H. pylori infection, sex, age, blood lipids, blood pressure, fasting blood glucose, glycated hemoglobin and body mass index were risk factors for carotid plaque formation. An independent risk factor was still evident in the multivariate logistic regression analysis, indicating H. pylori infection. Furthermore, after weighted gene coexpression network analysis (WGCNA), we discovered 555 genes linked to both H. pylori infection and the advancement of atherosclerosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed a strong correlation between these genes and immunity, infection, and immune disorders. SsGSEA analysis showed that H. pylori infection and atherosclerosis included changes in the immune microenvironment. Finally, three genes MS4A6A, ADAMDEC1 and AQP9 were identified to be involved in the formation of atherosclerosis after H. pylori infection. Conclusion: Our research affirms that H. pylori is a unique contributor to the formation of carotid plaque, examines the immune microenvironment associated with H. pylori infection and advanced carotid atherosclerosis, and offers fresh perspectives on how H. pylori infection leads to atherosclerosis.

Persistent Helicobacter pylori infection leads to elevated fasting plasma glucose level: A retrospective cohort study based on a nondiabetes Chinese population.

BACKGROUND AND AIM: The relationship between Helicobacter pylori (H. pylori) and fast plasma glucose (FPG) on nondiabetes populations is still inconclusive. Nowadays, not only the high infection rate of H. pylori but also the high FPG level is threatening the Chinese people. METHODS: A retrospective cohort study has been established to analyze the relationship between H. pylori infection and FPG level, 18 164 individuals performed healthy examination in Taizhou Hospital Health Examination Center from 2017 to 2022 were included, and hematological indicators, body parameters, and H. pylori detection by 13 C-urea breath test were collected from patients. The follow-up intervals were greater than 12 months. RESULTS: H. pylori infection was regarded as an independent risk factor for elevated FPG after multivariate logistic regression. Additionally, the average interval time were 33.6 ± 13.3 months. Mean changed FPG values in the persistent infection group were higher than in the subgroup of persistent negative (P = 0.029) as well as eradication infection (P = 0.007). The aforementioned changes began to appear after 2 years of follow-up. Similarly, when compared with the subgroup of persistent infection, mean changed triglyceride/high density lipoprotein (TG/HDL) values were much lower in the subgroup of persistent negative (P = 0.008) and eradication infection (P = 0.018), but the differences appeared after 3 years of follow-up. CONCLUSIONS: H. pylori infection is an independent risk factor for elevated FPG in non-diabetes mellitus (DM) individuals. Persistent H. pylori infection causes an increase in FPG level and TG/HDL, which may be a risk factor for diabetes mellitus.

Relationship between Helicobacter pylori and glycated hemoglobin: a cohort study.

Background: Helicobacter pylori (H. pylori) has increasingly been shown to be related to extragastric diseases. Glycated hemoglobin A1c (HbA1c), an indicator of glycemic control, is closely linked to the event of diabetes. The purpose of this research was to analyze the association between H. pylori and HbA1c through a cohort study. Methods: The population who underwent multiple physical checkups in the physical examination center of Taizhou Hospital was included. All of them underwent urea breath test, serological examination and physical parameter measurement. Multiple regression was used for analyzing the influencing factors of HbA1c. In addition, the result of HbA1c on H. pylori infection was studied by restricted cubic spline (RCS) analysis. The triglyceride glucose (TyG) index represents the level of insulin resistance (IR) in the population. The population was classified on the basis of primary and last H. pylori infection, therefore, the variations of HbA1c and TyG index among totally different teams were investigated. Results: Multiple regression demonstrated that H. pylori was an influential factor in HbA1c. RCS analysis showed a nonlinear relationship between HbA1c and H. pylori infection. When HbA1c>5.7%, the chance of H. pylori infection was considerably enlarged. Additionally, long-term H. pylori infection increased HbA1c levels, while HbA1c levels decreased after H. pylori eradication. Similarly, long-term H. pylori infection also increased the TyG index. Conclusion: Prediabetes increases the danger of H. pylori infection, long-term H. pylori infection increases HbA1c and IR levels, and wipeout of H. pylori could have a positive impact for glycemic control in the population.

Helicobacter pylori infection increases the risk of nonalcoholic fatty liver disease in diabetic population.

Background: The effect of Helicobacter pylori (H. pylori) on nonalcoholic fatty liver disease (NAFLD) in the population is still controversial. Diabetes and NAFLD are both metabolically related diseases, and no studies have classified the population to study the effect of H. pylori infection on NAFLD in diabetics. Methods: A population of people who were examined in the Taizhou Hospital Health Examination Center from 2017 to 2022 was included, and hematological indicators, body parameters, ultrasound data, and H. pylori detection by urea nitrogen test were collected from patients. All physical examination populations were divided into diabetic and non-diabetic populations. Results: After multivariate logistic regression, H. pylori infection remained an independent risk factor for NAFLD in diabetics, but it had no significant effect on NAFLD in non-diabetic population. Additionally, there was a nonlinear relationship between glycosylated hemoglobin and H. pylori infection in diabetic population. Moreover, the incidence of NAFLD in diabetics increased with persistent H. pylori infection. Conclusion: In the diabetic population, H. pylori infection does increase the risk of developing NAFLD. Glycemic control and eradication of H. pylori infection may have positive implications for reducing the incidence of NAFLD in diabetic population.

Aberrant Spontaneous Brain Activity and its Association with Cognitive Function in Non-Obese Nonalcoholic Fatty Liver Disease: A Resting-State fMRI Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been proven to be associated with an increased risk of cognitive impairment and dementia, and this association is more significant in non-obese NAFLD populations, but its pathogenesis remains unclear. Our study aimed to explore the abnormalities of spontaneous brain activity in non-obese NAFLD patients by resting-state fMRI (RS-fMRI) and their relationship with cognitive function. METHODS: 19 non-obese NAFLD, 25 obese NAFLD patients, and 20 healthy controls (HC) were enrolled. All subjects underwent RS-fMRI scan, psychological scale assessment, and biochemical examination. After RS-fMRI data were preprocessed, differences in low-frequency fluctuation amplitude (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were compared among the three groups. Furthermore, the relationship between RS-fMRI indicators and cognitive and clinical indicators were performed using correlation analysis. RESULTS: The cognitive function was declined in both NAFLD groups. Compared with obese NAFLD patients, non-obese NAFLD patients showed increased ALFF and ReHo in the left middle temporal gyrus (MTG), increased ReHo in the sensorimotor cortex and reduced FC between left MTG and right inferior frontal gyrus (IFG). Compared with HC, non-obese NAFLD patients showed increased ALFF and ReHo in the left calcarine cortex and fusiform gyrus (FG), decreased ALFF in the bilateral cerebellum, and reduced FC between left FG and right IFG and left angular gyrus. In addition to the same results, obese patients showed increased activity in different regions of the bilateral cerebellum, while decreased ALFF in the right superior frontal gyrus and ReHo in the right orbitofrontal cortex (OFC). Correlation analysis showed that in non-obese patients, the ALFF values in the FG and the FC values between the left MTG and the right IFG were associated with cognitive decline, insulin resistance, and fasting glucose disorder. CONCLUSIONS: Non-obese NAFLD patients showed abnormal local spontaneous activity and FC in regions involved in the sensorimotor, temporo-occipital cortex, cerebellum, and reward system (such as OFC), some of which may be the potential neural mechanism difference from obese NAFLD patients. In addition, the temporo-occipital cortex may be a vulnerable target for cognitive decline in non-obese NAFLD patients.

The Feasibility of Applying Artificial Intelligence to Gastrointestinal Endoscopy to Improve the Detection Rate of Early Gastric Cancer Screening.

Convolutional neural networks in the field of artificial intelligence show great potential in image recognition. It assisted endoscopy to improve the detection rate of early gastric cancer. The 5-year survival rate for advanced gastric cancer is less than 30%, while the 5-year survival rate for early gastric cancer is more than 90%. Therefore, earlier screening for gastric cancer can lead to a better prognosis. However, the detection rate of early gastric cancer in China has been extremely low due to many factors, such as the presence of gastric cancer without obvious symptoms, difficulty identifying lesions by the naked eye, and a lack of experience among endoscopists. The introduction of artificial intelligence can help mitigate these shortcomings and greatly improve the accuracy of screening. According to relevant reports, the sensitivity and accuracy of artificial intelligence trained on deep cirrocumulus neural networks are better than those of endoscopists, and evaluations also take less time, which can greatly reduce the burden on endoscopists. In addition, artificial intelligence can also perform real-time detection and feedback on the inspection process of the endoscopist to standardize the operation of the endoscopist. AI has also shown great potential in training novice endoscopists. With the maturity of AI technology, AI has the ability to improve the detection rate of early gastric cancer in China and reduce the death rate of gastric cancer related diseases in China.

Feasibility of transgastric endoscopic gallbladder-preserving surgery for benign gallbladder diseases (with video).

BACKGROUND: With the increasing realization of the importance of gallbladder function, choledochoscopic gallbladder-preserving surgery has been advocated for benign gallbladder diseases. However, limited information is available regarding the use of endoscopic gallbladder-preserving surgery (EGPS) for patients with benign gallbladder diseases. The aim of this study was to evaluate the feasibility of EGPS for benign gallbladder diseases. METHODS: Between June 2020 and January 2021, 22 patients with gallbladder stones and/or gallbladder polyps were treated with EGPS. The main outcome measures included the rate of complications, residual gallbladder stones, and gallbladder stone recurrence. RESULTS: In this study, transgastric EGPS was successfully performed in 22 patients (13 female, 9 male) with benign gallbladder diseases, and included 8 cases of multiple gallstones, 4 cases of gallbladder polyps with gallstones, 6 cases of multiple gallbladder polyps, 2 cases of single gallstone, and 2 case of singe gallbladder polyp. The median time of transgastric EGPS was 118 min. During hospitalization, 4 patients suffered localized peritonitis (4/22, 18.2%), and these patients successfully recovered after conservative medical treatment. None of the patients experienced massive bleeding, delayed bleeding, diffuse peritonitis, or any other serious complications. During the median follow-up of 4 months, 1 patient suffered residual gallstone, while no gallstone recurrence or deaths related to transgastric EGPS occurred in any patients. CONCLUSIONS: Transgastric EGPS appears to be a feasible treatment method in selected patients with benign gallbladder diseases. However, as it is a new technique, further studies are needed to explore the long-term effectiveness of transgastric EGPS.

Fecal Fungi Dysbiosis in Nonalcoholic Fatty Liver Disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) can systematically harm more aspects of human health than just the liver. In addition to the potential roles of the gut microbiota in NAFLD, commensal fungi can functionally replace intestinal bacteria in maintaining the host immune response in the gut by reversing disease susceptibility. Therefore, gut commensal fungi should be studied to help understand NAFLD. METHODS: The fungal compositions of 79 patients with NAFLD and 34 matched healthy subjects were studied via internal transcribed spacer sequencing. In the NAFLD group, 32 patients underwent liver biopsies to evaluate the associations between gut fungi and NAFLD development. RESULTS: The fungal microbiota distribution was skewed in the patients with NAFLD. The relative abundances of Talaromyces, Paraphaeosphaeria, Lycoperdon, Curvularia, Phialemoniopsis, Paraboeremia, Sarcinomyces, Cladophialophora, and Sordaria were higher in patients with NAFLD, whereas the abundances of Leptosphaeria, Pseudopithomyces, and Fusicolla were decreased. Patients with NAFLD exhibited more co-occurring fungal intrakingdom correlations. Several fungi were found to be associated with liver injury, lipid metabolism, and the development of NAFLD. CONCLUSIONS: This study found that gut fungi may play some roles in NAFLD development. Research on gut fungi may be of great value in diagnosing and monitoring NAFLD.

Study on the new strategy and key techniques for accurate prevention and treatment of nonalcoholic steatohepatitis based on intestinal target bacteria.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has emerged as a major health problem worldwide; according to statistics, 10% to 25% of patients with NAFLD can progress to nonalcoholic steatohepatitis (NASH). A link between the composition and metabolites of intestinal microbiota and the development of NAFLD is becoming clearer. It is believed that microbiota factors are driving forces of hepatic steatosis and inflammation. The formulated food that contains prebiotics and dietary fiber may improve NAFLD by altering the intestinal flora and its metabolites. METHODS: The study plan to recruit adult patients (18-75 years, n = 120) with NAFLD, range of alanine aminotransferase is 1.5 to 5 times upper limit of normal (ULN) or liver biopsy is confirmed as NASH. Participants will be randomly allocated into 2 groups: formulated food (n = 80) and a placebo group (n = 40) for 24 weeks. Both groups will receive lifestyle and nutritional advice. The primary endpoint is a decrease in MRS-PDFF by more than 30% from baseline at 24 weeks. The secondary endpoints include the change of anthropometric, liver function, glycolipid metabolism, and systemic inflammation at 4, 12, and 24 weeks. In addition, we consider the changes in intestinal microbiota as an exploration to assess the abundance and diversity at 24 weeks. Weeks 24 to 36 are the follow-up period of drug withdrawal. DISCUSSION: This clinical trial will provide evidence of efficacy and safety of formulated food as a potential new therapeutic agent for NAFLD patients. TRIAL REGISTRATION: The trial is registered in the China Clinical Trial Center (ChiCTR1800016178).

The Role of Intestinal Fungi and Its Metabolites in Chronic Liver Diseases.

Current studies have confirmed that liver diseases are closely related to intestinal microorganisms; however, those studies have mainly concentrated on bacteria. Although the proportion of intestinal microorganisms accounted for by colonizing fungi is very small, these fungi do have a significant effect on the homeostasis of the intestinal microecosystem. In this paper, the characteristics of intestinal fungi in patients with chronic liver diseases such as alcoholic liver disease, nonalcoholic fatty liver disease and cirrhosis are summarized, and the effects of intestinal fungi and their metabolites are analyzed and discussed. It is important to realize that not only bacteria but also intestinal fungi play important roles in liver diseases.

Berberine prevents non-alcoholic steatohepatitis-derived hepatocellular carcinoma by inhibiting inflammation and angiogenesis in mice.

Hepatocellular carcinoma (HCC) is one of the most malignant and poor prognosis tumors, which was increasingly caused by nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) in western countries. In this study, we aimed to investigate the mechanism and therapeutic prospect of berberine in the treatment of NASH-HCC mice. Combination of STZ injection and high fat and high-cholesterol diet (HFHC) was used to establish NASH-HCC model. The effect of berberine intervention is studied from histology, biochemistry and molecular level. Our results showed that administration of berberine to NASH-HCC mice reduced the incidence of tumors and mitigated NASH. Berberine significantly reduced the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol (TC). Transcriptome sequencing and bioinformatics analysis identified numberous genes and various pathways may participate in the favorite effect of berberine. Specifically, berberine suppressed the expressions of genes related to lipogenesis, inflammation, fibrosis and angiogenesis. Moreover, our results showed that berberine suppressed phosphorylation of p38MAPK and ERK as well as COX2 expression significantly. This suggested berberine achieved its biological functions mainly by regulating inflammation and angiogenesis genes involving p38MAPK/ERK-COX2 pathways. This study demonstrated the anti-tumor effects of berberine and its possible mechanism, providing a potential drug for treating NASH-HCC.

Haptoglobin 2-2 Genotype is Associated with More Advanced Disease in Subjects with Non-Alcoholic Steatohepatitis: A Retrospective Study.

INTRODUCTION: Haptoglobin (Hp) genotypes were reported as an independent risk factor for metabolic diseases. This study aimed to investigate the association between Hp gene polymorphism and the severity of nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 441 subjects (NAFLD group, n = 272; healthy control, n = 169) were recruited, and their clinical biochemical parameters were measured in all subjects. Haptoglobin genotyping was performed using genomic DNA extracted from peripheral blood leukocytes. Among the NAFLD group, 107 patients underwent liver biopsy, and histology was evaluated by a pathologist on the basis of the CRN scoring system. RESULTS: NAFLD patients had much lower frequency of Hp 1-1 genotype and higher frequency of Hp 2-2 than healthy controls (0.4% vs 9.5%, 55.8% vs 47.9%, P < 0.001). NAFLD patients with Hp 2-2 genotype had much higher levels of body mass index (BMI), total cholesterol (TC), liver enzymes, ferritin, and controlled attenuation parameter (CAP) values than non-Hp 2-2 genotype (P < 0.05). In histology, patients with nonalcoholic steatohepatitis (NASH) had higher frequency of Hp 2-2 genotype than non-NASH patients (71.3% vs 22.2%, P < 0.001); patients with significant fibrosis had higher frequency of Hp 2-2 genotype (78.3% vs 54.8%, P < 0.05) than no/mild fibrosis patients. NAFLD patients with Hp 2-2 genotype had higher proportion with higher steatosis scores, lobular inflammation scores, ballooning scores, NAFLD activity scores (NAS), and fibrosis stages (P < 0.05 for all) than Hp 2-2 groups. Furthermore, Hp 2-2 genotype was independently associated with NASH (OR = 5.985, P < 0.05) and significant fibrosis (OR = 6.584, P < 0.05). CONCLUSIONS: Hp 2-2 genotype is closely associated with the severity of NAFLD.