Background: Type 2 diabetes mellitus (T2DM) is a complex, multifactorial disease with a significant global burden. Although genome-wide association studies (GWAS) have identified many T2DM-associated variants, most lie in non-coding regions, making it difficult to interpret their functional roles. Methods: We aimed to identify genetically regulated Cytosine–phosphate–Guanine (CpG) sites associated with T2DM by conducting a methylome-wide association study (MWAS), followed by Mendelian randomization (MR) and functional validation using human pancreatic cells and mouse models. MWAS was performed using summary statistics from large-scale GWAS and a DNA methylation (DNAm) prediction model to test associations between genetically predicted DNAm and T2DM. Results: We identified 111 CpG sites significantly associated with T2DM in Europeans, including 8 novel sites near genes not previously linked to T2DM. These findings were replicated in independent datasets. Many CpGs also showed associations with cardiometabolic traits, highlighting shared epigenetic mechanisms. Trans-ethnic MR analysis confirmed consistent effects for six CpGs in East Asians. Functional analysis revealed that several CpGs regulate gene expression in human pancreatic α- and β-cells. Among them, 2´-5´-oligoadenylate synthetase like (OASL) expression, regulated by a significant CpG, was differentially expressed in α-cells of T2DM cases compared to controls. Supporting evidence from mouse models suggests a role for OASL in glucose regulation. Conclusion Our study identifies novel genetically regulated CpG sites associated with T2DM risk and highlights OASL as a potential epigenetic regulator of glucose metabolism in α-cells. These findings provide mechanistic insights into the epigenetic architecture of T2DM and suggest potential targets for cross-ethnic biomarker development and therapeutic intervention.

BACKGROUND/OBJECTIVES: The microbiota present in human milk (HM) plays a crucial role in infant health and development. Maintaining it during storage and thawing is vital for preserving its beneficial properties; however, the effects of storage period, temperature, and thawing conditions on HM are not well understood. SUBJECTS/METHODS: HM samples from lactating mothers were collected and stored under different temperature conditions (room temperature [RT], refrigeration, and −20°C) for different durations (1 week and 4 weeks), and thawed using different methods (RT, bottle warmer, and microwave), followed by analysis of their microbiota. RESULTS: Storing HM samples at RT for a week and at −20°C for four weeks resulted in a significant reduction in microbiota diversity, whereas the other treatments did not lead to a significant change in beta diversity. In the microbiota distance analysis, HM samples stored at −20°C for a week showed the highest similarity to the initial microbiota compared to those after one week of storage at RT or in a refrigerator. Microwave thawing after 1 week of freezing resulted in the greatest alteration in the initial microbiota composition, whereas thawing at RT or with a bottle warmer showed comparable microbial profiles. CONCLUSION The most suitable method for storing and thawing HM while preserving the microbiota is to store it at −20°C for up to one week and thaw it using a bottle warmer.

Intra-abdominal Hernia with Bowel Obstruction Triggering Multi-organ Failure: The Role of Preoperative Enteritis This report details the clinical course of a 41-year-old male who developed fulminant multiple organ dysfunction syndrome following emergency surgery for a strangulated intra-abdominal hernia. Preoperative manifestations, including diarrhea and marked leukocytosis, pointed towards an underlying infectious enteritis. We posited that surgical release of the obstructed, ischemic bowel segment precipitated a massive systemic influx of endotoxins and inflammatory mediators, triggering septic shock and rapid sequential organ failure. This case underscored the critical need to suspect concomitant gastrointestinal infection in patients presenting with mechanical bowel obstruction accompanied by infectious signs. Aggressive perioperative sepsis management encompassing early empiric antimicrobial therapy, vigilant hemodynamic monitoring, and preparedness for advanced organ support is essential to mitigate this severe complication.

BACKGROUND: Physical inactivity is a significant yet underappreciated risk factor for cardiovascular disease (CVD), particularly among older adults. The aim of this study was to analyze the global burden of CVD attributable to physical inactivity in individuals aged 70 years and older from 1990 to 2021 using the Global Burden of Disease data. METHODS: We assessed trends in disability-adjusted life years (DALYs) and deaths, decomposed changes into population growth, aging, and epidemiological factors, and examined health inequalities across sociodemographic index (SDI) regions. RESULTS: From 1990 to 2021, a substantial rise in DALYs was observed, especially in low and middle SDI regions, with a 120.06% increase in the low SDI region, but a 23.10% decline in the high SDI region. Decomposition analysis identified population aging and growth as primary drivers for the burden, contributing 66.39% and 83.56% to the increase in middle and low SDI regions, respectively. By contrast, epidemiological improvements alleviated burden in the high SDI region (54.91%). Gender disparities persisted, with women experiencing a higher burden. Inequality analysis indicated a shift in CVD burden towards the low SDI region, with declining concentration indices for DALYs (-0.03 to -0.13) and deaths (-0.07 to -0.15). The Bayesian age-period-cohort projections suggest continued increases in DALYs and deaths through 2050, with women disproportionately affected. CONCLUSIONS These findings highlight the urgent need for targeted interventions promoting physical activity, improving healthcare access, and implementing region-specific prevention strategies.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

Objective:To investigate the uptake patterns of 18F-fluorodeoxy glucose ( 18F-FDG) in the endometrium using positron emission tomography (PET) imaging and to differentiate these from stage IA endometrial cancer. Methods:From September 2022 to April 2024, a prospective inclusion of 354 women without gynecological diseases and no hormone usage who underwent 18F-FDG PET-CT examinations at the affiliated hospital of Qingdao University were set as the physiological group, while a group containing 42 cases of Stage IA endometrial carcinoma was also set. The physiological group was divided into five groups based on the menstrual cycle: menstrual period, proliferative phase, ovulatory phase, secretory phase, and menopausal phase. The images were analyzed using visual and quantitative measurements; quantitative analysis indicators were standardized uptake value maximum (SUVmax) and the region of interest/liver ratio (R/L value). Receiver operating characteristic (ROCs) curve was used to determine the optimal cutoff values for SUVmax and R/L value. A clinical model was established using binary logistic regression, and ROC curves were drawn to evaluate the predictive performance of the model. Results:The uptake of 18F-FDG in the endometrium exhibited cyclical variations throughout different physiological phases, with higher uptakes observed during the menstrual and ovulation phases (SUVmax values of 6.66±3.26 and 3.89±1.21, respectively), which are significantly higher than those in the proliferative phase [median SUVmax of 2.54 (2.02, 3.47)], secretory phase (SUVmax of 2.55±0.86), and menopausal phase [SUVmax median of 2.04 (1.69, 2.29)]. During the menstrual and ovulation phases, the radiotracer accumulation patterns were triangular in 105 cases, oval in 32 cases, and round-like in 2 cases. All 42 cases of endometrial cancer showed 18F-FDG uptake, with radiotracer accumulation patterns being round-like in 17 cases, oval in 10 cases, triangular in 9 cases, and irregular in 6 cases. There were statistically significant differences in the shapes of radiotracer concentration between the menstrual, ovulatory periods, and endometrial carcinoma (both P＜0.001). The SUVmax and R/L values in menstrual period and ovulatory period were significantly lower than that in endometrial carcinoma group ( P＜0.001). During the menstrual phase, the optimal cutoff values for SUVmax and R/L in distinguishing between endometrial and endometrial cancer were 12.59 and 3.81, respectively, with corresponding AUCs of 0.885 and 0.842. After incorporating endometrial uptake morphology into the model, the AUCs was improved to 0.969 and 0.948, respectively. During the ovulatory phase, the optimal cutoff values for SUVmax and R/L were 5.96 and 2.85, respectively, with AUCs of 0.984 and 0.968. After integrating endometrial uptake morphology into the model, the AUCs were increased to 0.999 and 0.998, respectively. Conclusions:The 18F-FDG PET imaging of the endometrium shows higher uptake during the menstrual and ovulatory periods, primarily triangular in shape; endometrial carcinoma uptake is significantly higher than the physiological uptake during the menstrual and ovulatory periods, mainly in circular, oval, and irregular shapes. When SUVmax≥5.96, R/L≥2.85, combined with the physiological cycle of the subjects and the morphological characteristics of the radiotracer concentration, it is possible to effectively differentiate between physiological uptake and Stage IA endometrial carcinoma.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

Objective:To investigate the uptake patterns of 18F-fluorodeoxy glucose ( 18F-FDG) in the endometrium using positron emission tomography (PET) imaging and to differentiate these from stage IA endometrial cancer. Methods:From September 2022 to April 2024, a prospective inclusion of 354 women without gynecological diseases and no hormone usage who underwent 18F-FDG PET-CT examinations at the affiliated hospital of Qingdao University were set as the physiological group, while a group containing 42 cases of Stage IA endometrial carcinoma was also set. The physiological group was divided into five groups based on the menstrual cycle: menstrual period, proliferative phase, ovulatory phase, secretory phase, and menopausal phase. The images were analyzed using visual and quantitative measurements; quantitative analysis indicators were standardized uptake value maximum (SUVmax) and the region of interest/liver ratio (R/L value). Receiver operating characteristic (ROCs) curve was used to determine the optimal cutoff values for SUVmax and R/L value. A clinical model was established using binary logistic regression, and ROC curves were drawn to evaluate the predictive performance of the model. Results:The uptake of 18F-FDG in the endometrium exhibited cyclical variations throughout different physiological phases, with higher uptakes observed during the menstrual and ovulation phases (SUVmax values of 6.66±3.26 and 3.89±1.21, respectively), which are significantly higher than those in the proliferative phase [median SUVmax of 2.54 (2.02, 3.47)], secretory phase (SUVmax of 2.55±0.86), and menopausal phase [SUVmax median of 2.04 (1.69, 2.29)]. During the menstrual and ovulation phases, the radiotracer accumulation patterns were triangular in 105 cases, oval in 32 cases, and round-like in 2 cases. All 42 cases of endometrial cancer showed 18F-FDG uptake, with radiotracer accumulation patterns being round-like in 17 cases, oval in 10 cases, triangular in 9 cases, and irregular in 6 cases. There were statistically significant differences in the shapes of radiotracer concentration between the menstrual, ovulatory periods, and endometrial carcinoma (both P＜0.001). The SUVmax and R/L values in menstrual period and ovulatory period were significantly lower than that in endometrial carcinoma group ( P＜0.001). During the menstrual phase, the optimal cutoff values for SUVmax and R/L in distinguishing between endometrial and endometrial cancer were 12.59 and 3.81, respectively, with corresponding AUCs of 0.885 and 0.842. After incorporating endometrial uptake morphology into the model, the AUCs was improved to 0.969 and 0.948, respectively. During the ovulatory phase, the optimal cutoff values for SUVmax and R/L were 5.96 and 2.85, respectively, with AUCs of 0.984 and 0.968. After integrating endometrial uptake morphology into the model, the AUCs were increased to 0.999 and 0.998, respectively. Conclusions:The 18F-FDG PET imaging of the endometrium shows higher uptake during the menstrual and ovulatory periods, primarily triangular in shape; endometrial carcinoma uptake is significantly higher than the physiological uptake during the menstrual and ovulatory periods, mainly in circular, oval, and irregular shapes. When SUVmax≥5.96, R/L≥2.85, combined with the physiological cycle of the subjects and the morphological characteristics of the radiotracer concentration, it is possible to effectively differentiate between physiological uptake and Stage IA endometrial carcinoma.

Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83％.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P＜0.05);infection rate presented increased trend with the increase of age and BMI(both P＜0.001),and decreased trend with the increase of education(P＜0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95％CI:1.031-3.693),age 55-64 years old(OR=2.473,95％CI:1.279-4.781),other occupations(OR=0.530,95％CI:0.292-0.964),teachers(OR=0.439,95％CI:0.242-0.794),students(OR=0.445,95％CI:0.233-0.851),junior high school education or below(OR=1.412,95％CI:1.025-1.944),BMI＜18.5 kg/m2(OR=0.762,95％CI:0.586-0.991),co-living with indicator cases(OR=1.621,95％CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95％CI:1.083-1.540)were the influential fac-tors for LTBI(all P＜0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.

Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P＜0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P＞0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.