Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

The feasibility and safety of disposable endoscope vs. conventional endoscope for upper gastrointestinal tract examination: a multicenter, randomized, parallel, non-inferiority trial.

BACKGROUND: A disposable upper gastrointestinal endoscope can effectively decrease infectious outbreaks associated with endoscope reuse. In the present study, we aimed to evaluate the feasibility and safety of a disposable endoscope for upper gastrointestinal examination. METHODS: In a prospective, randomized trial, 144 upper endoscopic procedures were allocated to either the disposable endoscope group or the conventional endoscope group. The primary outcomes were rates of excellent and good image qualities and maneuverability satisfaction. The second outcome included procedure duration, endoscopic diagnosis, and adverse events. RESULTS: A total of 144 subjects were enrolled in the present analysis and prospectively randomized to 2 study groups. Finally, 70 and 69 subjects were enrolled in the novel disposable endoscope group and the conventional endoscope group, respectively, due to the schedule cancellation of 5 subjects. The baseline characteristics of the patients were similar in both groups. The excellent and good image quality rates and maneuverability satisfaction of the novel disposable endoscope were not inferior to the conventional endoscope (p = 0.99 and p = 0.99, respectively). Moreover, no significant between-group difference was observed in the endoscopic results and adverse events (p = 0.30 and p = 1, respectively). However, the procedure duration in the novel disposable endoscope was longer compared with the conventional endoscope (8.40 ± 4.28 min vs. 5.12 ± 2.65 min, p < 0.001). CONCLUSIONS: The novel disposable endoscope was as safe, effective, and maneuverable as a conventional endoscope. However, the novel disposable endoscope was associated with a longer procedure duration.

Waist-to-height ratio, an optimal anthropometric indicator for metabolic dysfunction associated fatty liver disease in the Western Chinese male population.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been entitled as metabolic-dysfunction associated fatty liver disease (MAFLD). Therefore anthropometric indicators of adiposity may provide a non-invasive predictive and diagnostic tool for this disease. This study intended to validate and compare the MAFLD predictive and diagnostic capability of eight anthropometric indicators. METHODS: The study involved a population-based retrospective cross-sectional design. The Fangchenggang area male health and examination survey (FAMHES) was used to collect data of eight anthropometric indicators, involving body mass index (BMI), waist-to-height ratio (WHtR), waist-hip ratio (WHR), body adiposity index (BAI), cardiometabolic index (CMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and abdominal volume index (AVI). Receiver operating characteristics (ROC) curves and the respective areas under the curves (AUCs) were utilized to compare the diagnostic capacity of each indicator for MAFLD and to determine the optimal cutoff points. Binary logistic regression analysis was applied to identify the odds ratios (OR) with 95% confidence intervals (95% CI) for all anthropometric indicators and MAFLD. The Spearman rank correlation coefficients of anthropometric indicators, sex hormones, and MAFLD were also calculated. RESULTS: All selected anthropometric indicators were significantly associated with MAFLD (P < 0.001), with an AUC above 0.79. LAP had the highest AUC [0.868 (95% CI, 0.853-0.883)], followed by WHtR [0.863 (95% CI, 0.848-0.879)] and AVI [0.859 (95% CI, 0.843-0.874)]. The cutoff values for WHtR, LAP and AVI were 0.49, 24.29, and 13.61, respectively. WHtR [OR 22.181 (95% CI, 16.216-30.340)] had the strongest association with MAFLD, regardless of potential confounders. Among all the anthropometric indicators, the strongest association was seen between LAP and sex hormones. CONCLUSION: All anthropometric indicators were associated with MAFLD. WHtR was identified as the strongest predictor of MAFLD in young Chinese males, followed by LAP and AVI. The strongest association was found between LAP and sex hormones.

Pan-Cancer Analysis of the Roles and Driving Forces of RAB42.

RAB42 is a member of the RAS family. However, the roles and driving forces for RAB42 in tumors remain elusive. In this study, we performed a comprehensive pan-cancer analysis of the roles and regulatory mechanisms of RAB42 using bioinformatics and experiments. Online databases such as Sanger Box, ACLBI and TIDE were used to search for the expression levels, prognostic value and immune features of RAB42. We observed that RAB42 expression was upregulated in most tumors and was closely associated with poor prognosis. Enrichment analysis indicated that RAB42 was related to multiple biological functions, especially the immune process. RAB42 expression had a positive correlation with immune cell infiltration and immune checkpoint gene expression. RAB42 had a high predictive value for immunotherapy efficiency. Our study screened out susceptible drugs for the RAB42 protein by sensitivity analysis and virtual screening. Many key driver genes such as TP53 contributed to RAB42 expression. DNA methylation, super-enhancer and non-coding RNAs were the epigenetic factors responsible for RAB42 expression. In brief, RAB42 could serve as a diagnostic and prognostic biomarker in many tumor types. RAB42 might be a predictive biomarker and a new target for immunotherapy. Genetic and epigenetic factors were essential for RAB42 overexpression in tumors.

Effects of Irbesartan Pretreatment on Pancreatic ß-Cell Apoptosis in STZ-Induced Acute Prediabetic Mice.

The current study was performed to investigate the effects and potential effects of irbesartan pretreatment on pancreatic ß-cell apoptosis in a streptozotocin- (STZ-) induced acute mouse model of prediabetes. Twenty-four male BALB/C mice (18-22 g) were randomly divided into three groups: normal control group (NC, n = 6), STZ group (STZ, n = 8), and irbesartan + STZ group (IRB + STZ, n = 10). In the IRB + STZ group, mice were administered irbesartan (300 mg/kg per day) by gavage for one week. The STZ group and IRB + STZ group received STZ (80 mg/kg by intraperitoneal (IP) injection once). The NC group received normal saline (80 mg/kg by IP injection once). Fasting blood glucose prior to STZ injection and presacrifice was analysed using samples withdrawn from the caudal vein to confirm the induction of prediabetes. Haematoxylin and eosin staining, immunohistochemical detection of insulin, and apoptosis analysis were performed. Reverse transcription-quantitative polymerase chain reaction was used to detect angiotensin II type 1 receptor (AT1R), caspase-3, and p38 mitogen-activated protein kinase (MAPK) mRNA expression. Blood glucose was significantly higher in the STZ group (9.01 ± 1.1089 vs 4.78 ± 0.7026) and IRB + STZ group (7.86 ± 1.1811 vs 4.78 ± 0.7026) compared with the NC group (P < 0.05). In comparison to the STZ group, the islet cell damage was marginally improved in the IRB + STZ group, and the IRB + STZ group had a significantly lower apoptotic rate than the STZ group (22.42 ± 8.3675 vs 50.86 ± 5.3395, P < 0.001). AT1R expression in the IRB + STZ group was lower than that in the STZ group (1.56 ± 1.2207 vs 3.92 ± 2.4392, P < 0.05). The mRNA expression of caspase-3 in pancreatic tissue was significantly lower in the IRB + STZ group than in the STZ group (0.90 ± 0.7272 vs 1.88 ± 1.0572, P < 0.05). Similarly, the IRB + STZ group also had lower p38MAPK levels than the STZ group (1.16 ± 1.0642 vs 2.55 ± 1.7925, P > 0.05). In conclusion, irbesartan pretreatment improved glucose levels and insulin secretion and decreased islet ß-cell apoptosis to protect islet ß cells in an STZ-induced acute prediabetic mouse model.

S4646 polymorphism in CYP19A1 gene is associated with the efficacy of hormone therapy in early breast cancer.

PURPOSE: The aim was to verify the potential association between CYP19A1 genetic polymorphisms and clinical outcome of hormone therapy in hormone receptor (HR)-positive early breast cancer. METHODS: Genotyping for CYP19A1 rs4646 (C/A) polymorphism was performed on 287 women with HR-positive early breast cancer. Associations were evaluated between CYP19A1 rs4646 genotypes and disease-free survival (DFS). RESULTS: Totally, women with the minor allele (AA or AC) had an improved DFS when compared with those carrying the homozygous common allele (CC) (AA or AC vs. CC: 62.7 months versus 55.6 months; Hazard ratio (HR), 0.745; 95% CI, 0.562-0.988; P=0.04). The difference was further demonstrated by multivariate analyses (HR, 0.681; 95% CI, 0.506-0.917; P=0.011). In premenopausal women, AA genotype was associated with a prolonged DFS (AA versus CC or AC: 98.2 months versus 56.2 months; HR, 0.425; 95% CI, 0.198-0.914; P=0.024). In addition, women with the A allele had an improved DFS when compared with those carrying the homozygous C allele (AA or AC vs. CC: 62.7 months versus 55.6 months; HR, 0.709; 95% CI, 0.516-0.975; P=0.033). These findings were further confirmed by the Cox regression model (HR, 0.336, 0.670; 95% CI, 0.160-0.836, 0.479-0.938; P=0.017, 0.019). In postmenopausal women, rs4646 genotypes were significantly associated with DFS (AA versus AC versus CC: 32.7 months versus not reached versus 56.3 months; P=0.011). Women carrying AA variant had a poorer DFS than those with CC or AC genotypes (32.7 months versus 70.6 months; HR, 3.613; 95% CI, 1.380-9.457; P=0.005). Furthermore, being adjusted by the patients features in multivariate analyses, AA genotype remained an independent prognostic factor for DFS (HR, 3.614; 95% CI, 1.308-9.991; P=0.013). CONCLUSIONS: The homozygous minor allele (AA) of CYP19A1 rs4646 is significantly associated with improved clinical outcome of hormone therapy in premenopausal HR-positive early breast cancer patients, but with a worse impact on postmenopausal women. The findings are novel, if confirmed, genotyping for CYP19A1 rs4646 polymorphism may provide predictive information for better selection of endocrine treatment.