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.

As a member of class I histone deacetylase (HDACs), HDAC8 is an important anticancer drug target. Based on our previously developed pharmacophore model for the HDAC8 inhibitor, we designed and synthesized 13 quinoline acid derivatives as new HDAC8 inhibitors. Among them, the compound SDFZ-E2 and SDFZ-E3 exhibited good HDAC8 inhibitory activities and isoform selectivity. In cell experiments, the target compounds SDFZ-E2 and SDFZ-E3 showed better antiproliferation activities than the known HDAC8 selective inhibitor PCI-34051. In addition, the proposed binding mode of SDFZ-E2 was investigated using molecular docking and molecular dynamics simulation. This work is a new attempt to develop HDAC8 selective inhibitor using quinoline as the scaffold, and the active compounds could serve as lead compounds for further structural optimization.

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.

Objective To investigate the primary symptoms of the common syndrome types in chronic gastritis through complex system modeling method,thus to provide evidence for the objectivity of the differentiation of traditional Chinese medicine(TCM)syndrome in chronic gastritis.Methods The complex system modeling methods of random forest,mutual information,rough sets,affinity propagation clustering and discriminant analysis were comprehensively used to screen the primary symptoms for the diagnosis of common syndrome types in chronic gastritis,such as syndrome of damp turbidity obstruction in the middle energizer,syndrome of spleen and stomach qi deficiency,syndrome of deficiency-cold in spleen and stomach,syndrome of liver depression and qi stagnation,and syndrome of stagnated heat in liver and stomach.And then the relationship between symptoms and syndromes types,and the relationship between symptoms and symptoms were mined.The diagnostic efficiency of the primary symptoms of chronic gastritis was evaluated by the discriminant analysis interactive validation method and the area under the receiver operating characteristic curve(AUC).Results The specific symptoms positively correlated with the syndrome of damp turbidity obstruction in the middle energizer were greasy coating,tooth-marked tongue,thick coating and enlarged tongue,while red tongue,thin coating and yellow coating were the identification symptoms negatively correlated with the syndrome,and their prediction accuracy was 79.2%with the AUC value being 0.868.The specific symptoms positively correlated with the syndrome of spleen and stomach qi deficiency were weakness,white coating,tooth-marked tongue,pale lip,and loose stools,while the identification symptoms negatively correlated with the syndrome were greasy moss and red tongue,and their prediction accuracy was 75.5%with the AUC value being 0.830.The specific symptoms positively correlated with the syndrome of deficiency-cold in spleen and stomach were cold limbs,preference of warmth in the epigastrium,and thin coating,while no identification symptoms negatively correlated with the syndrome,and their predictive accuracy was 79.2%with the AUC value being 0.836.The specific symptoms positively correlated with the syndrome of liver depression and qi stagnation were symptom aggravation due to emotional factors,distention or pain over hypochondriac region and belching,while the identification symptoms negatively correlated with the syndrome were weakness and greasy coating,and their predictive accuracy was 74.1%with the AUC value being 0.818.The specific symptoms positively correlated with the syndrome of stagnated heat in liver and stomach were red tongue,distention or pain over hypochondriac region and red lips,while the identification symptoms negatively correlated with the syndrome were greasy coating,white coating and thick coating,and their predictive accuracy was 79.9%with the AUC value being 0.845.The specific symptoms positively correlated with the common syndrome types in chronic gastritis mainly involved spleen,stomach and liver,and the disease-nature syndrome elements covered damp turbidity,qi deficiency,blood deficiency,cold dampness,yang deficiency,qi stagnation and heat.Conclusion The primary symptoms for the common syndrome types in chronic gastritis screened out through comprehensive application of complex system modeling methods are basically consistent with TCM theories,clinical practices and previous diagnostic criteria.Tongue and lip manifestations account for the largest proportion of the primary symptoms,indicating that tongue diagnosis and lip diagnosis are of great significance for the diagnosis of TCM syndrome types in chronic gastritis.

Purpose: We aimed to investigate factors that correlate with fecal calprotectin (FC) levels in children and adolescents with colorectal polyps. Methods: Pediatric patients aged <19 years who underwent colonoscopic polypectomy for a juvenile polyps (JPs) and FC tests were simultaneously conducted in a multicenter, retrospective study. Baseline demographics, colonoscopic and histological findings, and laboratory tests, including FC levels, were investigated. Correlations between the factors were investigated, and linear regression analysis revealed factors that correlated with FC levels. FC levels measured after polypectomies were investigated and the FC levels pre- and post-polypectomies were compared. Results: A total of 33 patients were included in the study. According to Pearson correlation analysis, the polyp size was the only factor that showed a statistically significant correlation with FC levels (r=0.75, p<0.001). Furthermore, according to the multivariate linear regression analysis, polyp size was the only factor that showed a statistically significant correlation with FC levels (adjusted R2=0.5718, β=73.62, p<0.001). The median FC level was 400 mg/ kg (interquartile range [IQR], 141.6–1,000 mg/kg), and the median polyp size was 14 mm (IQR, 9–20 mm). Nineteen patients underwent post-polypectomy FC tests. FC levels showed a significant decrease after polypectomy from a median of 445.2 mg/kg (IQR, 225–1,000) to 26.5 mg/kg (11.5–51) ( p<0.001). Conclusion FC levels significantly correlated with polyp size in children and adolescents with JPs.

Purpose: Gastrointestinal (GI) endoscopy is an important tool for diagnosing and treating GI diseases in children. This study aimed to analyze the current GI endoscopy practice patterns among South Korean pediatric endoscopists. Methods: Twelve members of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition developed a questionnaire. The questionnaire was emailed to pediatric gastroenterologists attending general and tertiary hospitals in South Korea. Results: The response rate was 86.7% (52/60), and 49 of the respondents (94.2%) were currently performing endoscopy. All respondents were performing esophagogastroduodenoscopy, and 43 (87.8%) were performing colonoscopy. Relatively rare procedures for children, such as double-balloon enteroscopy (DBE) (4.1%), endoscopic retrograde cholangiopancreatography (ERCP) (2.0%), and endoscopic ultrasound (EUS) (2.0%), were only performed by pediatric gastroenterologists at very few centers, but were performed by adult endoscopists in most of the centers; of all the respondents, 83.7% (41/49) performed emergency endoscopy. In most centers, the majority of the endoscopies were performed under sedation, with midazolam (100.0%) and ketamine (67.3%) as the most frequently used sedatives. Conclusion While most pediatric GI endoscopists perform common GI endoscopic procedures, rare procedures, such as DBE, ERCP, and EUS, are only performed by pediatric gastroenterologists at very few centers, and by adult GI endoscopists at most of the centers. For such rare procedures, close communication and cooperation with adult GI endoscopists are required.

Objective To compare the macular structure and microcirculation in both eyes of the patients with myopic anisometropia.Methods Optical coherence tomography angiography(OCTA)was employed to scan the macular areas in both eyes of 44 patients with myopic anisometropia.The patients were assigned into high and low groups based on the refractive diopter,and the parameters such as retinal thickness,choroidal thickness,vascular density,and perfusion density in the macular areas of both eyes were compared between the two groups.Results Other macular areas except the central and external nasal areas and the choroid of the fovea in the high group were thinner than those in the low group(all P<0.05).There was no statistically significant difference in retinal vascular density or perfusion density in different areas between the two groups(all P>0.05).Conclusion In the patients with myopic anisometropia,most areas of the retina in the case of high myopia is thinner than that in the case of low myopia,while there is no difference in retinal vascular density or perfusion density in both eyes.
Humans ; Anisometropia ; Choroid/blood supply* ; Microcirculation ; Myopia ; Retina ; Tomography, Optical Coherence/methods*

Myelodysplastic syndromes (MDS) are a subset of myeloid malignancies defined by clonality of immature hematopoietic stem cells that leads to faulty blood cell development. These syndromes can lead to an increased risk of infection and may transform into acute myeloid leukemia, making it critical to determine effective treatments for the condition. While hypomethylating agents such as azacitidine and decitabine, as well as stem cell transplants, have been delineated as favored treatments for MDS, not all patients are physiologically receptive to these treatments. However, black raspberries (BRBs) have been shown to exert hypomethylating effects in various malignancies, with minimal adverse effects and thus a broader range of potential candidacies. This study aimed to investigate the potential of BRBs to exert such effects on MDS using Addition of Sex Combs Like/Tet Methylcytosine Dioxygenase 2 (Asxl1/Tet2) double knockout mice (Vav-cre Asxl1fl/fl Tet2fl/fl ), which typically manifest symptoms around 25 weeks of age, mirroring genetic mutations found in humans with MDS. Following a 12-week dietary supplementation of Vav-cre Asxl1fl/fl Tet2fl/fl mice with 5% BRBs, we observed both hyper- and hypomethylation at multiple transcription start sites and intragenic locations linked to critical pathways, including hematopoiesis. This methylation profile may have implications for delaying the onset of MDS, prompting a need for in-depth investigation. Our results emphasize the importance of exploring whether an extended BRB intervention can effectively alter MDS risk and elucidate the relationship between BRB-induced methylation changes, thus further unlocking the potential benefits of BRBs for MDS patients.

Objective:To analyze the effects of microvascular invasion (MVI) and anatomical hepatectomy on early recurrence and survival of patients with hepatocellular carcinoma (HCC).Methods:The data of 246 patients with HCC admitted to 215 Hospital of Shaanxi Nuclear Industry, Chinese PLA General Hospital and Beijing Tsinghua Chang Gung Hospital from July 2008 to June 2019 were retrospectively analyzed, including 208 males and 38 females, aged (53.8±9.6) years. According to the occurrence of MVI, 246 patients were divided into the MVI group ( n=83) and control group ( n=163, without MVI). Hepatitis B virus (HBV) infection, preoperative alpha-fetoprotein (AFP), maximum tumor diameter, intraoperative blood loss were compared between the two groups. The recurrence-free survival and cumulative survival were compared between the two groups before and after the inverse probability weighted correction for propensity score. Results:The propensity score was calculated by logistic regression model. After inverse probability weighted correction, the virtual sample size was 247 cases (82 cases in MVI group and 165 cases in control group). The proportion of HBV infection, with a serum level of AFP > 200 μg/L, the maximum diameter of tumor and the intraoperative blood loss were higher in MVI group (all P<0.05). The risk of early recurrence in patients undergoing anatomical hepatectomy ( n=107) was lower than that in patients undergoing non-anatomical hepatectomy ( n=139) (univariate Cox regression analysis of HR=1.60, 95% CI: 1.06 to 2.42, P=0.020), but the overall survival was comparable (univariate Cox regression analysis of HR=1.66, 95% CI: 0.80 to 3.42, P=0.200). The recurrence-free survival (RFS) of MVI group was lower than that of the control group, and the postoperative cumulative survival rate was also lower before the inverse probability weighted correction of the tendency score. The RFS in MVI group was lower than that in control group after the tendency score was adjusted by inverse probability weighting ( HR=2.62, 95% CI: 1.61 to 4.27, P<0.001). There was no significant difference in the cumulative survival between the MVI and control group ( HR=2.09, 95% CI: 0.89 to 4.93, P=0.050). Conclusion:MVI is associated with early postoperative recurrence in patients with HCC, and the early recurrence rate after anatomical hepatectomy is lower than that after non-anatomical hepatectomy.