BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis (MASH), liver fibrosis, cirrhosis, and relevant complications. The liver mainly comprises hepatocytes, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), immune cells (T cells, B cells), and hepatic stellate cells (HSCs). Crosstalk among these different liver cells, endogenous aberrant glycolipid metabolism, and altered gut dysbiosis are involved in the pathophysiology of MASLD. This review systematically examines advances in understanding the molecular pathogenesis of MASLD, with a focus on emerging therapeutic targets and translational clinical trials. We first delineate the crucial regulatory mechanisms involving diverse liver cells and the gut-liver axis in MASLD development. These cell-specific pathogenic insights offer valuable perspectives for advancing precision medicine approaches in MASLD treatment. Furthermore, we evaluate potential therapeutic targets and summarize clinical trials currently underway. By comprehensively updating the MASLD pathophysiology and identifying promising strategies, this review aims to facilitate the development of novel pharmacotherapies for this increasingly prevalent condition.
Humans ; Fatty Liver/therapy* ; Animals ; Liver/pathology* ; Kupffer Cells/metabolism* ; Hepatocytes/metabolism* ; Hepatic Stellate Cells/metabolism*

BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

This article combs and summarizes the entire process of rare disease selection and priority theme determination,including the application and preliminary review of rare diseases,standardization of disease theme information,the evaluation methods of evidence sorting and disease selection for priority se-lection of disease themes,and other aspects of the content were analyzed in depth.It is expected to provide reference for the subsequent selection of rare diseases,improve the fairness,rationality and scientificity of rare disease selection,and further promote research and decision-making in China's rare disease-related fields.

Objective To determine the time point when porcine pancreatic elastase(PPE)induced abdominal aortic aneurysm(AAA)reaches the regression phase in mice and observe the histological characteristics of AAA in regression phase.Methods AAAs were induced by transient intraluminal infusion of PPE in C57BL/6J mice.The diameters of the mouse abdominal aortas were measured before PPE infusion and sacrifice time,day 14 for AAA progression phase or day 56 for regression phase after PPE infusion,respectively.The histological characteristics of the aneurysm lesion site on day 14 and day 56 after surgery were compared and analyzed.Results The diameters of the abdominal aortas were significantly increased in both day 14 and day 56 after PPE infusion groups(diameter growth rate 147％and 155％,respectively)as compared to the baseline diameters.In the day 14 group,the infused aortas showed typical AAA characteristics,such as elastin break/degradation,medial smooth muscle cells depletion,and inflammatory cell diffused infiltration.In the day 56 group after PPE infusion,although the artery diameter did not change significantly as compared to the day 14 group,histology showed that elastin was partially repaired,new smooth muscle cells were added to the damaged aorta media,the infiltrated inflammatory cells were significantly subsided,and the adventitia neovascularization was reduced,showing a significant feature of the disease regression phase.Conclusion In the PPE-induced mouse AAA model,day 56 after surgery is an appropriate time point for observing aneurysm regression,and the histological characteristics of the regression are obvious.

Objective: To investigate the prevalence, awareness, treatment and control rates of diabetes among residents in Fangshan District, Bejing Municipality, so as to provide reference for strengthening the prevention and control of diabetes. Methods: The residents aged 18 to 79 years were selected in Fangshan District using multistage stratified cluster sampling method from March to June 2023. Demographic information, lifestyle, body mass index, fasting blood glucose, and blood lipid were collected through questionnaire surveys, physical examinations and laboratory tests. The prevalence, awareness, treatment and control rates of diabetes among residents were analyzed and their influencing factors were identified using a multivariable logistic regression model. Results: A total of 4 438 residents were enrolled, including 2 367 males (53.33%) and 2 071 females (46.67%), and had a mean age of (44.99±14.90) years. The prevalence, awareness, treatment and control rates of diabetes were 15.75%, 57.37%, 56.22% and 22.90%, respectively. Multivariable logistic regression analysis showed that age (aged 30 to 39 years, OR=1.624, 95%CI: 1.011-2.609; aged 40 to 49 years, OR=3.469, 95%CI: 2.163-5.561; aged 50 to 59 years, OR=4.202, 95%CI: 2.595-6.803; aged 60 to 69 years, OR=7.229, 95%CI: 4.406-11.862; aged 70 to 79 years, OR=7.929, 95%CI: 4.665-13.479), obesity (OR=1.368, 95%CI: 1.071-1.748), hypertension (OR=1.943, 95%CI: 1.601-2.359) and dyslipidemia (OR=2.754, 95%CI: 2.287-3.317) were the factors affecting the prevalence of diabetes. Sex (women, OR=1.529, 95%CI: 1.019-2.293), age (aged 40 to 49 years, OR=4.971, 95%CI: 1.681-14.698; aged 50 to 59 years, OR=6.070, 95%CI: 2.045-18.020; aged 60 to 69 years, OR=6.902, 95%CI: 2.287-20.832; aged 70 to 79 years, OR=6.954, 95%CI: 2.191-22.070) and hypertension (OR=1.906, 95%CI: 1.337-2.718) were the factors affecting the awareness of diabetes. Age (aged 40 to 49 years, OR=4.699, 95%CI: 1.594-13.855; aged 50 to 59 years, OR=5.990, 95%CI: 2.023-17.732; aged 60 to 69 years, OR=7.134, 95%CI: 2.370-21.470; aged 70 to 79 years, OR=6.639, 95%CI: 2.102-20.964) and hypertension (OR=1.857, 95%CI: 1.304-2.645) were the factors affecting the treatment of diabetes. Age (aged 40 to 49 years, OR=2.948, 95%CI: 1.349-6.438; aged 60 to 69 years, OR=2.344, 95%CI: 1.049-5.234) was the factor affecting the control of diabetes. Conclusions The prevalence rate of diabetes among residents in Fangshan District was high, and the improvements of awareness rate, treatment rate and control rate were not obvious. Health education and management of diabetes should be strengthened for elderly, hypertensive and dyslipidemic residents.

Bronchial asthma （asthma for short） is a common clinical respiratory disease mainly characterized by chronic airway inflammation， with complicated pathogenesis and a long treatment cycle. It is lingering and difficult to be cured， and lack specific drugs. Oxidative stress is a new focus in the research on the pathogenesis of asthma and a potential key target for the treatment. Under physiological conditions， the oxidative and antioxidative systems in the body are in a dynamic balance， and the two antagonize each other to maintain normal life activities. In the case of asthma attack， oxidation products such as reactive oxygen species （ROS）， malondialdehyde （MDA）， and nitric oxide （NO） are produced excessively， while the content of antioxidants such as superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） is reduced. As a result， the oxidation exceeds the removal of oxidation products， which aggravates oxidative stress. In addition， the overproduction of ROS activates oxidative stress-related signaling pathways to produce pro-inflammatory factors， exacerbating inflammation， which leads to lung and airway tissue damage. In recent years， traditional Chinese medicine has garnering increasing attention because of the unique advantages in the treatment of asthma， especially in regulating redox balance， alleviating oxidative stress in asthma patients， and reducing inflammation. On the one hand， by inhibiting the mitogen-activated protein kinase （MAPK） and transcription factor （NF）-κB signaling pathways， traditional Chinese medicine can reduce the content of oxidation products and pro-inflammatory factors from the source. On the other hand， by activating the nuclear factor-erythroid 2-related factor 2 （NrF2） signaling pathway， traditional Chinese medicine can elevate the levels of antioxidant enzymes and enhance the antioxidant system to neutralize the excessive accumulation of oxidation products. Therefore， the adjustment of redox balance state by traditional Chinese medicine may be a new means and a new direction for the prevention and treatment of asthma in the future. This paper summarizes the oxidative stress-related pathways in the pathogenesis of asthma and reviews the latest research progress in the regulation of oxidative stress-related pathways by Chinese medicine extracts and prescriptions in the treatment of asthma， with a view to providing a fuller， more solid， and more scientific theoretical basis for the clinical and basic research on the prevention and treatment of asthma by traditional Chinese medicine.

Objective: To evaluate the distribution characteristics and health risk of trichloromethane (TCM) in the drinking water supply of primary and middle schools in rural areas of Tianjin, so as to provide a scientific basis for improving drinking water safety in rural schools. Methods: A total of 60 water samples from 30 rural primary and middle schools in 10 agricultural districts of Tianjin were collected from April to June (dry season) and July to October (wet season) in 2023 with direct selection method. The content of TCM was detected according to the Standard Methods for the Examination of Drinking Water, and a risk assessment method recommended by the United States Environmental Protection Agency was used to evaluate the health risk of TCM through oral exposure. Results: The concentration of TCM in drinking water was no detection to 54.00 μg/L, with an average of (13.44±14.88) μg/L, and the value was higher during the wet season [12.90(1.40,32.28)μg/L] than the dry season [2.40(1.40,18.13)μg/L] (Z=-2.09, P<0.05). The concentration of TCM for primary and middle schools were [3.38(1.40,20.75) μg/L] and [5.30(1.40,28.23)μg/L] respectively, and there was no statistically significant difference between different types of schools (Z=0.50, P>0.05). The carcinogenic risk through oral exposure ranged from 3.84×10-7 to 2.05×10-5, while the noncarcinogenic risk ranged from (0.00-0.16), all within the acceptable range. Children aged 6 to 9 years old were at the highest risk. Conclusions TCM has been detected in the drinking water of rural primary and middle schools to a certain extent in Tianjin, and attention should be paid to the potential health risks of oral exposure. The monitoring and management of disinfection byproducts in drinking water should be strengthened to further reduce the risk of exposure to children.

Myasthenia gravis (MG) is an autoimmune disorder mediated by autoantibodies that target the neuromuscular junction. The detection of pathogenic autoantibodies is crucial for the diagnosis and assessment of the disease. Commercial testing institutions and hospitals commonly use techniques such as radioimmunoprecipitation, enzyme-linked immunosorbent assay, or cell-based assay to test the serum of MG patients. However, these methods have limitations in terms of sensitivity and specificity, and there is a lack of direct comparative studies using high-level evidence-based medicine. The recent release of the SCREAM study using data from Chinese individuals confirms the advantages of cell-based assay, providing level Ⅰ evidence for the preferred recommendation of MG laboratory diagnosis and filling the gap in both domestic and international fields. However, the results obtained from the aforementioned testing methods are difficult to use for longitudinal comparison of patients and may not serve as the best biomarkers for disease monitoring. This article attempts to discuss this question by combining recent advances in understanding the pathogenic autoantibodies of MG and provides an outlook on future developments.

Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.