This study aimed to develop and internally validate a clinical risk prediction model for precancerous lesions of gastric cancer (PLGC) in Helicobacter pylori (H. pylori)-positive individuals by integrating H. pylori strain typing, serological gastric function markers, lifestyle factors, and host susceptibility polymorphisms. A total of 82 H. pylori-positive outpatients who underwent gastroscopy with histopathology between July 2020 and December 2021 were enrolled and categorized into a PLGC group (n = 38; chronic atrophic gastritis, intestinal metaplasia, and/or dysplasia) and a non-PLGC control group (n = 44). Demographic, clinical, dietary, and lifestyle information was collected using standardized questionnaires. Fasting blood samples were obtained for pepsinogen I (PG I), pepsinogen II (PG II), pepsinogen I/II ratio (PGR), gastrin-17 (G-17), and serologic H. pylori typing (Type I vs Type II), and 4 gastric cancer susceptibility loci (PSCA rs2976392, PLCE1 rs2274223, PRKAA1 rs59133000, and MUC1 rs4072037) were genotyped using TaqMan assays. Multivariable logistic regression identified older age and Type I H. pylori infection as independent risk factors, whereas higher PG I, higher PGR, and frequent whole-grain intake were protective. Susceptibility loci were not retained in the final model. The derived model showed adequate calibration (Hosmer-Lemeshow P = .426) and strong discrimination (AUC = 0.969), with an optimal cutoff of 0.403 yielding 94.7% sensitivity and 93.2% specificity; bootstrap validation indicated stable performance. This model may support risk stratification and targeted surveillance among H. pylori-positive patients.
Gastric intestinal metaplasia (IM) is a critical precancerous lesion for gastric cancer (GC), strongly associated with bile reflux. While bile acids (BAs) are known drivers of IM, the underlying molecular mechanisms remain elusive. Here, we integrated multi-omics analysis, clinical validation, and preclinical models to elucidate the role of endoplasmic reticulum (ER)-mitochondria crosstalk in IM pathogenesis. We identified that the ER stress (ERS) sensor BiP was significantly upregulated in patients with bile reflux-associated IM. In a deoxycholic acid (DCA)-induced IM model using INS-GAS mice, pharmacological inhibition of IRE1α attenuated gastric mucosal injury and metaplastic progression. Mechanistically, we demonstrated that the mitochondrial chaperone HSPA9 acted as a critical effector at mitochondria-associated membranes (MAMs). Activation of the BiP-IRE1α-XBP1 axis upregulated HSPA9, facilitating excessive ER-to-mitochondria Ca2+ transfer. This calcium overload triggered mitochondrial dysfunction and oxidative stress, driving gastric epithelial transdifferentiation. Furthermore, network pharmacology identified quercetin as a novel BiP inhibitor. We validated that quercetin stabilized BiP conformation, suppressed the IRE1α-XBP1-HSPA9 signaling axis, and restored ER-mitochondrial Ca2+ homeostasis, thereby mitigating oxidative stress and alleviating DCA-induced IM. These findings unveil a pathogenic ER-mitochondria signaling axis and highlight HSPA9 as a potential therapeutic target, suggesting quercetin as a promising chemopreventive strategy for intercepting GC progression.
Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) is a prevalent liver disease worldwide, with its prevalence rising alongside the increase in metabolic syndrome (MetS), obesity and ageing. Machine learning (ML), as a powerful analysis tool to handle and analyse massive data/information, has been employed to enhance and refine the diagnosis, risk assessment, non-invasive screening, and treatment options against MASLD. This review thoroughly explores the application of ML in identifying MASLD-related genes and lipidomic biomarkers, non-invasive screening technologies such as ultrasound and imaging, and predicting the risk of disease progression to metabolic dysfunction-associated steatohepatitis (MASH) or more advanced stages, such as cirrhosis. Additionally, ML models have shown potential and definitive performance in accurately predicting and effectively managing the risk of comorbidities in relation to MASLD. By integrating clinical data, biochemical markers, imaging techniques, and an individual's biochemical metrics, ML offers a personalised medical approach that improves therapeutic strategies and holds promise for significant contributions to public health in the future.
BACKGROUND & AIMS:Cachexia is prevalent and prognostically adverse in decompensated cirrhosis. Diagnosis is challenging, especially in Asian populations, due to limitations of current criteria and scoring systems. This study aimed to develop and validate a biomarker-based model for predicting cachexia defined by the Asian Working Group for Cachexia (AWGC) in cirrhotic patients. METHODS:In this retrospective cohort study, 420 patients with decompensated cirrhosis were enrolled (295 in the training cohort, 125 in the external validation cohort). Cachexia was diagnosed according to AWGC criteria. LASSO regression selected predictive serum biomarkers. A nomogram-derived GDF-15-Albumin-CRP score was constructed, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA). RESULTS:In the training cohort, 158 patients (53.56%) had cachexia. LASSO regression identified serum growth differentiation factor-15 (GDF-15), albumin, and C-reactive protein (CRP) as the strongest predictors. The resulting GDF-15-Albumin-CRP score achieved an AUC of 0.736 (95% CI: 0.680-0.792) for cachexia prediction, significantly outperforming Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), and MELD-Na scores (all P < 0.05). DCA demonstrated clinical net benefit across a wide range of threshold probabilities. The score exhibited a strong risk gradient for cachexia (adjusted OR for the high- vs. low-risk group: 7.58; 95% CI: 2.68-21.46). External validation confirmed its performance (AUC = 0.723, 95% CI: 0.630-0.810). CONCLUSIONS:The GDF-15-Albumin-CRP score is a validated and clinically feasible tool predicting AWGC-defined cachexia in Asian cirrhotic patients, superior to traditional severity scores and potentially enabling earlier targeted intervention.
Objective: The prevalence of colonic diverticula is rising in eastern countries, possibly related to aging and the adoption of a western lifestyle. However, limited data exist regarding the distribution and endoscopic features of colonic diverticula in this population. This study aimed to assess the number, size, depth, and location of colonic diverticula in our study cohort. Patients and Methods: We collected data from patients who underwent colonoscopy at the Endoscopy Center of Tianjin Medical University General Hospital and Bao Di Clinical College of Tianjin Medical University. We thoroughly evaluated and documented any colonic diverticula encountered during the procedures. Logistic regression analysis was employed to explore associations between participant characteristics and the presence of colonic diverticula. Results: Our study included a total of 27,021 eligible patients from our colonoscopy database, among whom 1529 individuals (5.67%) exhibited one or more diverticulosis. Patients with colonic diverticula (mean age: 58.6) were significantly older and exhibited a male predominance compared with those without diverticula. Cases of right-sided, left-sided, and bilateral diverticulosis were recorded in 1161 (76.0%), 170 (11.1%), and 198 patients (12.9%), respectively. Patients with right-sided diverticula (mean age: 55.2), more common in males, were younger than those with left-sided diverticula (mean age: 67.1, P < 0.05), which were more frequent in females ( P < 0.001). Individuals aged 60 years or older (odds ratio: 4.32, P < 0.001) and those with bilateral diverticulosis (odds ratio: 21.2, P < 0.001) had a higher likelihood of having a greater burden of diverticula. Conclusion: Colonic diverticula in Northern China predominantly manifests as right-sided, more common in males, and associated with older age. Notably, patients with right-sided diverticulosis tend to be younger than those with left-sided diverticula. In addition, a higher burden of diverticula is more prevalent in individuals aged 60 years or older and those with a bilateral distribution pattern.
Functional constipation (FC) is a prevalent gastrointestinal disorder marked by impaired intestinal motility, affecting millions worldwide and significantly diminishing quality of life. Current therapeutic strategies provide only transient symptom relief and fail to restore colonic motor function. This study aims to explore the causal role of gut microbiota in FC, focusing on the mechanisms by which Roseburia intestinalis (RI) and its metabolite inosine improve intestinal motility. To identify protective gut taxa, we first performed bidirectional Mendelian randomization (MR) integrated with 16S rRNA sequencing on fecal samples from 30 FC patients and 30 healthy controls. Loperamide-induced constipation mouse models evaluated RI gavage effects on motility indicators, including fecal output (frequency and water content), gastrointestinal transit time, intestinal propulsion rate, colonic bead expulsion time, and ex vivo organ bath contractions. To elucidate the underlying mechanism, we conducted RNA sequencing on colonic tissues. Furthermore, comparative metabolomics was employed to identify the key bacterial metabolites responsible for RI’s effects. Finally, the proposed mechanism of action for both RI and its key metabolite was validated through a combination of histology, immunohistochemistry, immunofluorescence, quantitative PCR, and Western blot analyses. MR and sequencing identified RI as a protective factor (OR = 0.8675, P < 0.05), with reduced abundance in FC patients negatively correlating with symptom severity and quality-of-life scores. In constipation mouse models, RI gavage promoted intestinal motility, enhanced fecal water content and gastrointestinal transit, and ameliorated mucosal injury while improving mucus secretion. RNA sequencing revealed upregulation of Tagln (transgelin) and enrichment of the TGF-β pathway after RI intervention. Metabolomics analysis pinpointed inosine as a key RI-derived small-molecule metabolite, enriched in RI supernatant and depleted in FC patient feces. Inosine gavage improved motility and histology, increased TGF-β1, p-Smad3, and transgelin, and these effects were abolished by the TGF-β receptor inhibitor SB431542. These findings established that RI and its metabolite inosine promote intestinal motility via TGF-β1/p-Smad3 signaling and identified transgelin as the terminal effector of this cascade, offering mechanistic insight into microbiota–host interactions and pointing to therapeutic targets for gastrointestinal motility disorders.
Mucosa-associated lymphoid tissue (MALT) lymphoma of the small intestine is relatively rare, and the treatment guideline has not been established yet. Here we present a case of MALT lymphoma in the terminal ileum, which regressed after Helicobacter pylori (H. pylori) eradication. A 53-year-old man had complained of abdominal discomfort and underwent a gastrointestinal endoscopic examination. H. pylori-associated erosive gastritis was diagnosed, and superficial ulcerated lesions were also found in the terminal ileum. Histopathologic examination and immunohistochemical analyses of ileal biopsy specimens confirmed the diagnosis of MALT lymphoma. No distant lymph node metastasis or other organ involvement was detected in positron emission tomography/computed tomography. Surprisingly, the ileum reached mucosal healing after quadruple therapy regimens for H. pylori eradication without additional treatments. There were no signs of recurrence during the follow-up for 18 months. The unique case which located only in the ileum revealed that eradication of H. pylori might be an effective treatment and deserves further studies. Moreover, we also provide a detailed overview of recently published literature regarding the eradication treatment for intestinal MALT lymphoma.
Improving the diagnosis and treatment of gastric cancer is a significant challenge worldwide. Circular RNAs (circRNAs), a recently identified class of endogenous non-coding RNAs with covalently closed-loop structures, have emerged as key regulators in tumorigenesis. CircFoxo3 has been studied in various cancer types, while its functional role in GC remains poorly understood. In this study, we found that circFoxo3 is significantly upregulated in GC tissues and cell lines compared to paired normal controls. Functional analyses demonstrated that knockdown of circFoxo3 markedly inhibited GC cell proliferation and migration, whereas overexpression of circFoxo3 produced the opposite effects. Mechanistically, circFoxo3 knockdown reduced forkhead box (Fox) transcription factors FOXO3 mRNA and protein levels. FOXO3a is involved in regulating cancer cell proliferation. Bioinformatic analysis revealed high expression of FOXO3 in GC tumor samples, a finding confirmed in both GC tissues and cell lines. A tumor xenograft model was used to examine the effect of circFoxo3 on tumor growth in vivo. The low circFoxo3 expression reduced the volume of the tumor and decreased its proliferation. Collectively, our findings identify circFoxo3 as an oncogenic factor in GC progression.
Saccharomyces boulardii (Sb) is a probiotic yeast for the treatment of gastrointestinal disorders, including inflammatory bowel disease (IBD). Little is known about the modulatory capacity of the Sb in IBD. Here, we found that oral gavage of Sb supernatant (SbS) alleviated gut inflammation, protected the intestinal barrier, and reversed DSS-induced down-regulated activation of epidermal growth factor receptor (EGFR) in colitis. Mass spectrum analysis showed that thioredoxin (Trx) is one of the critical secreted soluble proteins participating in EGFR activation detected in SbS. Trx exerted an array of significant effects on anti-inflammatory activity, including alleviating inflammation, protecting gut barrier, suppressing apoptosis, as well as reducing oxidative stress. Mechanistically, Trx promoted EGFR ligand gene expression and transactivated EGFR in a concentration-dependent manner. EGFR kinase inhibitor could block Trx-mediated preventive effects of intestinal epithelial injury. Our data suggested that Sb-derived soluble protein Trx could serve as a potential prophylactic, as a novel postbiotic against colitis, which provides a new strategy for the precision prevention and treatment of IBD.
The gut microbiota during early life plays a crucial role in infant development. This microbial-host interaction is also essential for metabolism, immunity, and overall human health in later life. Early-life pharmaceutical exposure, mainly referring to exposure during pregnancy, childbirth, and infancy, may change the structure and function of gut microbiota and affect later human health. In this Review, we describe how healthy gut microbiota is established in early life. We summarise the commonly prescribed medications during early life, including antibiotics, acid suppressant medications and other medications such as antidepressants, analgesics and steroid hormones, and discuss how these medication-induced changes in gut microbiota are involved in the pathological process of diseases, including infections, inflammatory bowel disease, metabolic diseases, allergic diseases and neurodevelopmental disorders. Finally, we review some critical methods such as dietary therapy, probiotics, prebiotics, faecal microbiota transplantation, genetically engineered phages, and vagus nerve stimulation in early life, aiming to provide a new strategy for the prevention of adverse health outcomes caused by prescribed medications exposure in early life.
BACKGROUND:Vonoprazan and amoxicillin (VA) dual therapy as a mainstream Helicobacter pylori regimen has gained momentum worldwide, but the optimum dosages remain unclear. We aimed to compare the efficacy and safety of VA dual therapy with 2 g amoxicillin or 3 g amoxicillin, and to assess the short-term effects of therapy on the gut microbiota and antibiotic resistome. METHODS:We conducted an open-label, non-inferiority randomised controlled trial at 12 centres in China. Individuals infected with H pylori, aged 18-70 years, and without previous eradication therapy were recruited. Participants were randomly assigned at a 1:1 ratio (block size of six) to receive vonoprazan (20 mg twice a day) with either low-dose amoxicillin (1 g twice a day; LVA therapy) or high-dose amoxicillin (1 g three times a day; HVA therapy) for 14 days. Gastric biopsies were collected before treatment for detection of antibiotic resistance. Stool samples were collected at baseline, week 2, and week 8-10 for shotgun metagenomic sequencing. The primary outcome was the eradication rate of H pylori, assessed by 13C urea breath test, in both intention-to-treat and per-protocol analyses. Secondary outcomes were adverse events, adherence, antibiotic resistance, and alterations to the gut microbiota and antibiotic resistome. The margin used to establish non-inferiority was -0·10. The trial was registered with ClinicalTrials.gov, NCT05649709. FINDINGS:Between Feb 13, 2023, and Jan 25, 2024, 504 patients (204 [40%] male and 300 [60%] female; mean age 43 years [SD 13]) were randomly assigned to LVA therapy or HVA therapy (n=252 in each group). No infections were resistant to amoxicillin. The H pylori eradication rate was 85·3% (215 of 252; 95% CI 80·4 to 89·2) in the LVA group and 86·5% (218 of 252; 81·7 to 90·2) in the HVA group in the intention-to-treat analysis (p=0·70) and 88·8% (213 of 240; 84·1 to 92·2) and 92·4% (218 of 236; 88·3 to 95·1), respectively, in the per-protocol analysis (p=0·18). The efficacy of LVA was non-inferior to HVA in the intention-to-treat analysis (risk difference -1·2%, 95% CI -7·3 to 4·9, p=0·0022) and the per-protocol analysis (-3·6%, -9·0 to 1·7, p=0·0085). 31 (12%) patients in the LVA group and 43 (17%) patients in the HVA group reported adverse events. Adherence to therapy was 97% in the LVA group and 96% in the HVA group. The diversity of gut microbiota decreased after treatment but was restored to baseline at week 8-10 in both groups. The abundance of beta-lactam-related resistance genes was increased at week 2 after treatment, and was restored to pretreatment level at week 8-10 for the LVA group but not the HVA group. INTERPRETATION:LVA dual therapy was effective and non-inferior to HVA dual therapy as first-line treatment of H pylori infection and showed a non-lasting effect on the abundance of beta-lactam-related resistance genes. High amoxicillin dosage (eg, 3 g per day) is not required to achieve high cure rates with vonoprazan dual therapy. FUNDING:National Natural Science Foundation of China, Project for Academic and Technical Leaders of Major Disciplines in Jiangxi Province, and Key Research and Development Program of Jiangxi Province.
We sought to develop and validate a machine learning (ML) model for predicting multidimensional frailty based on clinical and laboratory data. Moreover, an explainable ML model utilizing SHapley Additive exPlanations (SHAP) was constructed. This study enrolled 622 patients hospitalized due to decompensating episodes at a tertiary hospital. The cohort data were randomly divided into training and test sets. External validation was carried out using 131 patients from other tertiary hospitals. The frail phenotype was defined according to a self-reported questionnaire (Frailty Index). The area under the receiver operating characteristics curve was adopted to compare the performance of five ML models. The importance of the features and interpretation of the ML models were determined using the SHAP method. The proportions of cirrhotic patients with nonfrail and frail phenotypes in combined training and test sets were 87.8% and 12.2%, respectively, while they were 88.5% and 11.5% in the external validation dataset. Five ML algorithms were used, and the random forest (RF) model exhibited substantially predictive performance. Regarding the external validation, the RF algorithm outperformed other ML models. Moreover, the SHAP method demonstrated that neutrophil-to-lymphocyte ratio, age, lymphocyte-to-monocyte ratio, ascites, and albumin served as the most important predictors for frailty. At the patient level, the SHAP force plot and decision plot exhibited a clinically meaningful explanation of the RF algorithm. We constructed an ML model (RF) providing accurate prediction of frail phenotype in decompensated cirrhosis. The explainability and generalizability may foster clinicians to understand contributors to this physiologically vulnerable situation and tailor interventions.
Background To investigate the amoxicillin dosage required to achieve high cure rates, we compared 2 and 3 grams of amoxicillin on the efficacy and safety of vonoprazan dual therapy. We also assessed the short-term effects of therapy on the gut microbiota and antibiotic resistome. Methods This was an open-label, randomised trial conducted in 12 centres in China. H. pylori-infected subjects without prior eradication therapy were randomly assigned to receive either vonoprazan (20 mg b.i.d.) with low (1 g b.i.d. or LVA) or high-dose amoxicillin (1 g t.i.d. or HVA) for 14 days. Gastric biopsies were collected during pretreatment to detect antibiotic resistance. Stool samples were collected for shotgun metagenomic sequencing. The primary outcome of this study was the eradication rate of H. pylori using both intention-to-treat and per-protocol analyses. The secondary outcomes included adverse events, adherence, antibiotic resistance rate and alterations of gut microbiota and antibiotic resistome. Results 504 patients were randomly assigned to LVA or HVA therapy (IDDF2024-ABS-0375 Figure 1). No infections were resistant to amoxicillin. The eradication rates were LVA = 85.3% and HVA = 86.5% (p=0.70) by intention to treat analysis and 88.8% and 92.4% (p=0.18) by per protocol analysis. The efficacy of LVA was non-inferior to HVA in intention to treat analysis (p=0.002) and per protocol analysis (p=0.009) (IDDF2024-ABS-0375 Figure 2). 31 patients (12%) in the LVA group and 43 patients (17%) in the HVA group reported adverse events (p=0.13). Adherence to therapy was 97% in the LVA group and 96% in the HVA group. The diversity of gut microbiota decreased after treatment but was restored to baseline at weeks 8-10 for both groups (IDDF2024-ABS-0375 Figure 3). The alpha diversity of total resistome was increased after treatment but was restored to pretreatment level at weeks 8-10 for both groups (IDDF2024-ABS-0375 Figure 4). Conclusions LVA therapy was effective and non-inferior to HVA dual therapy as the first-line treatment of H. pylori infection in China. Vonoprazan-amoxicillin dual therapy for 14 days had minimal effects on the gut microbiota and antibiotic resistome.
Aim:Sarcopenia,multidimensional frailty,and malnutrition represent common debilitating conditions in the context of cirrhosis,linked to a variety of dismal outcomes.We aimed to clarify their overlap and cumulative impact on long-term mortality in hospitalized patients with cirrhosis.Methods:Consecutive patients with cirrhosis were prospectively recruited from January 2018 to December 2020.The diagnosis of sarcopenia,multidimensional frailty,and malnutrition was standardized according to the consensus definition and our well-documented criteria.The preva-lence of the respective debilitating condition and the concurrence of this comorbidity were calculated.Results:In total,253 patients with cirrhosis aged 64 years with a female predominance(52.4%)were recruited.Sarcopenia was present in 20.9%(53/253),multidimensional frailty in 12.6%(32/253),and malnutrition in 44.7%(113/253)of the entire cohort.Approximately half of the patients had at least one debilitating condition(127/253).Sarcopenia and malnutrition co-existed in 33 nonfrail patients(13.0%)and multi-dimensional frailty and malnutrition in eight nonsarcopenic patients(3.2%).Fifteen(5.9%)subjects had all three debilitating conditions,namely malnutrition,sarcopenia,and frailty(MSF)group.The propor-tions of males,infections,and ascites were significantly higher in the MSF group.Patients in the MSF group had the highest levels of neutrophil-to-lymphocyte ratio and creatinine.The 2-year mortality rates in patients with three debilitating conditions,two conditions,one condition,and no conditions were 60.0%,23.8%,21.4%,and 13.5%,respectively.Multivariate Cox regression indicated the long-term mortality risk was approximately four-fold higher among patients in the MSF group compared to those with no conditions.Conclusions:A fraction of patients with cirrhosis exhibited comorbidities of sarcopenia,multidimensional frailty,and malnutrition,linked to a higher risk of long-term mortality.
Abstract Background The increasing prevalence of colonic diverticula likely correlated with aging and shift to western lifestyle in Oriental countries over past decades. However, limited data about the distribution and endoscopic characteristics of colonic diverticula are available until now. We aimed to evaluate the number, size, depth and location of colonic diverticula in our study population. Methods We collected data from patients who underwent colonoscopy at the endoscopy center of Tianjin Medical University General Hospital and Bao Di Clinical College of Tianjin Medical University. Any colon diverticula was carefully assessed and recorded. Associations between participant characteristics and colonic diverticula were determined by using logistic regression model. Results A total of 27021applicable patients were retrieved from our colonoscopy database, with 1529 participants (5.67%) present with one or more diverticulosis. Patients with colonic diverticula (mean age: 58.6) were significantly older and showed male preponderance than those without diverticula. Right-sided, left-sided and bilateral diverticulosis were found in 1161 (76.0%), 170 (11.1%) and 198cases (12.9%), respectively. The patients with right-sided diverticula (mean age: 55.2) which were frequently in male were younger than those with left-sided diverticula (mean age: 67.1, P < 0.05) which were frequently in female ( P <0.001). Participants represented aged ≥ 60years old (OR:4.32, P<0.001) and bilateral diverticulosis (OR:21.2,P<0.001) had an increased odds of having a greater burden . Conclusion t he colonic diverticula were predominantly right-sided, male, and older age in northern China. Of these, patients with right-sided diverticulosis were younger than those with left-sided ones. The emergence of crowed was more likely observed in the individuals with aged over than 60 years old and bilateral distributed pattern.
BACKGROUND:The Global Leadership Initiative on Malnutrition (GLIM) has been built to diagnose malnutrition; however, its validity among patients with cirrhosis remains enigmatic. We aimed to investigate the prevalence of malnutrition according to GLIM criteria and compare the differences by using a specific screening tool.METHODS:We conducted a descriptive cross-sectional study analyzing hospitalized patients. The Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) was chosen as the screening tool. Estimated prevalence was shown with and without the initial screening process. Diverse combinations of phenotypic and etiologic criteria and distinct body mass index (BMI) cutoffs were applied to detect frequency of malnourished patients with cirrhosis.RESULTS:Overall, 363 patients were recruited (median age, 64 years; 51.2% female). The prevalence of malnutrition according to GLIM criteria with and without RFH-NPT screening was 33.3% and 36.4%, respectively. Low BMI and inflammation represented the most prevalent combination resulting in a malnutrition diagnosis (42.4%), followed by low BMI and reduced food intake (39.4%). By contrast, the least prevalence was found when combining reduced muscle mass with inflammation to diagnose malnutrition. Furthermore, the frequency of malnourished and well-nourished participants was not statistically different when using divergent BMI reference values across the study population.CONCLUSIONS:GLIM criteria may serve a specific proxy to diagnose malnutrition, along with RFH-NPT screening. Relevant investigation is required to report on the applied combination of phenotypic/etiologic criteria, taking into consideration the marked impact of different models. More attempts are warranted to delineate the prognostic role of GLIM criteria in the context of cirrhosis.
目的 通过观察难治性胃食管反流病(rGERD)患者治疗前后精神心理及睡眠情况的变化,探讨阿戈美拉汀联合富马酸伏诺拉生治疗rGERD的效果.方法 选择2021年3月至2021年10月于天津医科大学总医院就诊的54例rGERD患者,分为常规组(26例)和试验组(28例).常规组给予富马酸伏诺拉生治疗,试验组在给予与常规组相同治疗的基础上,联合阿戈美拉汀治疗,疗程均为8周.采用胃食管反流病问卷(GERDQ)、抑郁症筛查量表(PHQ-9)、广泛性焦虑量表(GAD-7)及睡眠障碍评定量表(SDRS)对2组治疗前后的消化道症状、精神心理状态及睡眠情况进行比较,并采用治疗前后各项评分的差值比较2组的疗效.结果 2组患者的性别构成、平均年龄、平均病程,以及治疗前GERDQ、PHQ-9、GAD-7、SDRS评分的差异均无统计学意义(P均>0.05).治疗8周后,常规组治疗后GERDQ评分较治疗前下降[(6.58±0.26)分比(10.00±0.32)分],差异有统计学意义(P<0.05).试验组的治疗后GERDQ、PHQ-9、GAD-7及SDRS评分均较治疗前显著下降[(6.64±0.19)分、(2.86±0.64)分、(1.64±0.54)分、(6.50±0.81)分比(10.93±0.41)分、(8.07±1.05)分、(5.57±0.93)分、(12.50±1.35)分],差异均有统计学意义(P均<0.05).试验组治疗前后的GERDQ、PHQ-9、GAD-7及SDRS评分差值均显著大于常规组[(4.27±0.33)分、(5.21±0.57)分 、(3.93±0.53)分、(6.70±3.72)分比(3.42±0.31)分、(1.62±0.30)分、(0.88±0.37)分、(1.46±0.47)分],差异均有统计学意义(P均<0.05).2组患者治疗后均未发生不良反应.结论 rGERD患者存在精神心理异常和睡眠障碍,阿戈美拉汀联合富马酸伏诺拉生治疗能显著改善rGERD患者的消化道症状,并能缓解睡眠障碍及抑郁、焦虑状态,联合用药的疗效优于单用富马酸伏诺拉生.
Objective: To investigate the diagnostic value of a single hydrogen-methane breath test (SHMBT) for small intestinal bacterial overgrowth (SIBO). Method: The current investigation was a cross-sectional study. Questionnaires and SHMBTs were administered to 162 patients with gastrointestinal symptoms (case group) and 69 healthy volunteers (control group). Differences in SHMBT results between the two groups were assessed,and cut-off values of CH4 (methane) and H2 (hydrogen) were analyzed via receiver operating characteristic (ROC) curves. Lastly,archived SHMBT data from 2 655 patients with gastrointestinal symptoms (validation set) were used to evaluate the diagnostic value of the SHMBT with respect to SIBO. The Chi-square test,the Mann-Whitney U test,Spearman's Rank correlation analysis,and the Z test were used for statistical analysis. Results: Based on the international recommended diagnostic criteria for SIBO,which are fasting CH4 ≥10 ppm (parts per million) or H2 ≥20 ppm,the SHMBT-positive rate in the case group was significantly higher than that of control group (35.2% vs. 21.7%, χ2=4.08, P=0.043). Levels of CH4 and H2 were higher in the case group than in the control group [CH4: 3(2,7) vs. 3(1,3) ppm, H2: 11(4,22) vs. 10(5,15) ppm],and the difference in CH4 levels was statistically significant (Z=6.22,P=0.001). ROC curves were generated based on whether the subjects had gastrointestinal symptoms. The areas under the ROC curves were 0.633 for CH4 alone,0.531 for H2 alone, and 0.620 for CH4 combined with H2. The cut-off values were fasting CH4≥4 ppm,fasting H2≥13 ppm,and fasting CH4 ≥5 ppm (or CH4≥4 ppm and H2≥24 ppm),respectively. Measuring CH4 alone and CH4 combined with H2 was effective for determining the presence of gastrointestinal symptoms (P<0.05). When CH4 alone or CH4 combined with H2 were used as diagnostic indicators of SIBO, the respective SHMBT-positive rates in the validation set were 34.2% and 30.4%. These rates did not significantly differ from the SIBO-positive rate of 32.0% obtained via the international recommended diagnostic criteria (P>0.05). The specificity of CH4 alone was 79.9%,and the accuracy of CH4 alone was 68.8%. The specificity of CH4 combined with H2 was 85.0%,and the accuracy of CH4 combined with H2 was 71.7%. Conclusion: Rapid one-time determination of CH4 and H2 in exhaled breath may a viable diagnostic method for SIBO, and using CH4 combined with H2 (i.e.,fasting CH4≥5 ppm, or CH4 ≥4 ppm and H2 ≥24 ppm) as cutoff values may be feasible.
Objective: The prognosis for gastric cancer (GC), a prevalent tumor of the digestive system, is unfavorable. The involvement of glutathione peroxidase 3 (GPX3) in tumorigenesis is significant, yet its specific role in GC remains insufficiently investigated. Thus, the aim of this study was to determine the potential impact of GPX3 on GC and elucidate the underlying mechanism. Methods: The expression and survival of GPX3 in GC were analyzed using TCGA data. Additionally, the GPX3 mRNA and protein levels in GC were also assessed using datasets from GTEx, GEPIA, and HPA. A total of 38 pairs of GC tissues, along with their adjacent normal tissues, were collected from the Tianjin Medical University General Hospital, accompanied by detailed clinical information. The expression levels of GPX3 were subsequently determined for the purpose of validation. Following expression, correlation, and survival analyses, we proceeded to investigate the upstream non-coding RNA (ncRNA) of GPX3 using starBase and miRNet. Additionally, the co-expression networks of GPX3 were examined based on LinkedOmics. Lastly, we explored the correlation between GPX3 and immune cell infiltration, as well as the biomarkers of immune cells and immune checkpoints in GC. Furthermore, the GDSC database offered valuable drug sensitivity information. Results: A lower expression of GPX3 was observed in individuals with GC, while a higher expression of GPX3 was associated with a poorer prognosis. The DUBR/hsa-miR-502-3p/GPX3 pathway was identified as the most promising upstream ncRNA pathway related to GPX3 in GC. GO and KEGG enrichment analysis revealed that GPX3 expression was linked to coagulation cascades and cell locomotion. Furthermore, GPX3 levels in GC were positively correlated with immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. The group with low GPX3 expression also exhibited increased sensitivity to 5-fluorouracil, doxorubicin, and other drugs. Conclusions: Collectively, we hypothesized that the potential involvement of non-coding RNAs in the downregulation of GPX3 could contribute to the inhibition of tumor formation during the malignant transition from gastritis to GC. Nevertheless, it was plausible that GPX3 may also facilitate tumor progression to advanced stages by promoting immune cell infiltration and activating immune checkpoints.