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*

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

【Objective】 To investigate the therapeutic effect of Huaier on acute pancreatitis (AP) and its potential mechanism. 【Methods】 A mouse model of cerulean-induced AP was used to verify the therapeutic effect of Huaier in vivo. HE staining and immunohistochemical staining were used to evaluate the histopathological changes of the pancreas, and transmission electron microscopy was used to observe the pyroptosis morphology of the pancreas. In vitro, 266-6 cell line was used as the experimental carrier to verify the protective effect of Huaier on acinar cells. Electron microscopy and Western blotting were used to evaluate the pyroptosis level of acinar cells, and ROS fluorescence probe was used to detect the oxidative stress state of acinar cells. 【Results】 Huaier significantly alleviated the severity of AP in mice. HE staining of pancreas showed that necrosis and inflammatory cell infiltration were reduced, and the level of serum amylase was decreased. Immunohistochemical staining and Western blotting showed that Huaier effectively inhibited the expressions of pyroptosis-related molecules such as NLRP3 and GSDMD in pancreatic tissue. Electron microscopy showed that Huaier could reduce the pyroptosis level of pancreatic acinar cells under inflammatory state. In addition, the level of ROS in acinar cells was significantly reduced after the intervention of Huaier, and ROS-mediated pyroptosis of acinar cells could be effectively inhibited by Huaier. 【Conclusion】 Huaier can effectively reduce the severity of AP by inhibiting ROS-mediated pyroptosis of acinar cells.

Objective:To investigate the role of immunoglobulin-like domain-containing receptor 2 (Ildr2) in renal fibrosis induced by ischemia-reperfusion.Methods:Ildr2 knockout mice (KO group) were constructed using CRISPR/Cas9 technology, and wild-type mice were as the control group (WT group). The unilateral renal ischemia-reperfusion (UIR) model (UIR group) was constructed by clamping the left renal pedicle, and was divided into KO-UIR group and WT-UIR group after modeling. Sham operation mice (sham group) were not treated with ischemia. Serum creatinine was measured by creatinine oxidase method. Blood urea nitrogen was detected by the diacetyloxime colorimetric method. The urinary albumin level was measured by enzyme-linked immunosorbent assay, and urinary albumin/creatinine ratio was calculated. HE, PAS and MASSON staining were used to detect the infiltration of inflammatory cells and the degree of fibrosis in renal tissues. The mRNA expression levels of Ildr2, kidney injury-associated molecules neutrophil gelatinase-associated lipocalin ( NGAL) and kidney injury molecule-1 ( KIM-1), fibrosis markers typeⅠcollagen α 1 ( Col1α1), fibronectin 1 ( Fn1), α-smooth muscle actin ( α-SMA) and connective tissue growth factor ( CTGF), as well as inflammation-related molecules macrophage marker F4/80 and monocyte chemoattractant protein-1 ( MCP-1) were detected by real time quantitative PCR (qRT-PCR). The protein levels of Ildr2, α-SMA and Col1α1 were detected by immunofluorescence and Western blotting. Results:(1) qRT-PCR and Western blotting showed that the expression levels of Ildr2 mRNA and protein in UIR group were significantly lower than those in sham group (both P<0.05). (2) There were no significant differences in body weight, serum creatinine, blood urea nitrogen, total cholesterol, low density lipoprotein, high density lipoprotein and triglyceride between KO group and WT group (all P>0.05). qRT-PCR results showed that there were no significant differences in the mRNA expression levels of NGAL, KIM-1, α-SMA, Col1α1, CTGF, Fn1, MCP-1 and F4/80 between KO group and WT group (all P>0.05). Histological staining showed no abnormal inflammatory cell infiltration and interstitial fibrosis between KO group and WT group. (3) Compared with the WT-UIR group, serum creatinine and blood urea nitrogen in the KO-UIR group were significantly higher (both P<0.05). qRT-PCR results showed that the mRNA expression levels of NGAL, F4/80, MCP-1, Col1α1, α-SMA, and CTGF in the KO-UIR group were significantly higher than those in the WT-UIR group (all P<0.05). Immunofluorescence and Western blotting results also showed that the protein expression levels of Col1α1 and α-SMA in the KO-UIR group were significantly higher than those in the WT-UIR group (all P<0.05). Histological staining showed that, compare with WT-UIR group, KO-UIR group had more severe inflammatory infiltration and more collagen fiber deposition. Conclusion:Ildr2 knockout does not cause phenotypic changes in mice under normal physiological conditions. Ildr2 plays a regulatory role in UIR injury, and Ildr2 deletion aggravates the degree of renal fibrosis induced by UIR.

【Objective】 Based on Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database, survival analysis was used to screen the key prognostic genes involved of pancreatic cancer patients. 【Methods】 Two pancreatic cancer gene chips (Microarray) from the GEO database and transcriptome sequencing (RNA-seq) from the TCGA database were used to filter the survival-related genes using Kaplan-Meier (KM) analysis and Cox risk model, and the target genes were intersected. Prognosis-associated genes were screened first and then pathway enrichment analysis or immune-enrichment analysis was performed based on these genes to find out their potential molecular mechanisms in regulating pancreatic cancer. 【Results】 In this study, five survival-related genes (i.e., CDO1, DCBLD2, FAM83A, ITGA3 and SLC16A3) were screened out. Multifactorial Cox regression analysis and clinical correlation analysis showed that high CDO1 expression was a protective factor for pancreatic cancer prognosis, and its antitumor effect was associated with its role in inhibiting the malignant biological behavior of pancreatic cancer cells and promoting the infiltration of immune killer cells in pancreatic cancer. 【Conclusion】 This study suggests that CDO1 is a potential tumor suppress gene of pancreatic cancer, and the tumor inhibition effect of CDO1 may be related to its role in remodeling the immune microenvironment of pancreatic cancer.

Objective:To analyze the clinical characteristics of acute pancreatitis.Methods:The retrospective case-control study was conducted. The clinical data of 558 patients with acute pancreatitis who were admitted to The First Affiliated Hospital of Xi′an Jiaotong University from June 2015 to June 2023 were collected. There were 352 males and 206 females, aged (46±15)years. Observation indicators: (1) general situations of acute pancreatitis patients; (2) etiology of acute pancreatitis patients; (3) severity of acute pancreatitis patients; (4) chronic diseases in acute pan-creatitis patients; (5) complications in acute pancreatitis patients; (6) subgroup analysis of patients with recurrent acute pancreatitis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Bonferroni correction was used for pairwise comparison. Results:(1) General situations of acute pancreatitis patients. There were significant differences in gender, age, total duration of hospital stay, smoking, and alcohol consumption between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (2) Etiology of acute pancreatitis patients. There were significant differences in gallstones and hyperlipidemia between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (3) Severity of acute pancreatitis patients. Of the 443 patients with first episode of acute pancreatitis and 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pan-creatitis were 320 and 83, 24 and 9, 99 and 23, showing no significant difference between them ( P>0.05). (4) Chronic diseases in acute pancreatitis patients. There were significant differences in com-plication as hyperlipidemia, fatty liver and diabetes between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (5) Complications in acute pancrea-titis patients. There was no significant difference in terms of acute necrotic collection, acute peripan-creatic fluid accumulation, walled-off necrosis, pancreatic pseudocyst, infectious pancreatic necrosis, systemic inflammatory response syndrome, respiratory system complications, circulatory system complications, renal complications, sepsis, abdominal compartment syndrome, or pancreatic ence-phalopathy between the first episode of acute pancreatitis patients and the recurrent acute pancrea-titis patients ( P>0.05). (6) Subgroup analysis of patients with recurrent acute pancreatitis. ① Combination with chronic diseases. Of the 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pancreatitis were 83, 9, 23, and there were 25, 8, 11 cases of them with hyperlipidemia, respectively, showing a significant difference among them ( P<0.05). ② Complications. Of the 115 patients with recurrent acute pancreatitis, there were 44 cases with hyperlipidemia and 71 cases without hyper-lipidemia, and there were significant differences in acute peripancreatic fluid accumulation and renal complications between them ( P<0.05). Conclusions:Recurrent acute pancreatitis is more common in males. Compared with first episode of acute pancreatitis, cases with recurrent acute pancreatitis usually have younger age, shorter total duration of hospital stay, higher proportion of smoking and drinking. The etiology of recurrent acute pancreatitis is composed of lower levels of biliary diseases and higher levels of hyperlipidemia. Patients with recurrent acute pancreatitis have higher proportion of comorbidities as hyperlipidemia, fatty liver and diabetes. There was no signifi-cant difference in the incidence of complications between first episode of acute pancreatitis and recurrent acute pancreatitis. Compared with recurrent acute pancreatitis patients without concomi-tant hyperlipidemia, recurrent acute pancreatitis patients with concomitant hyperlipidemia are more prone to acute peripancreatic fluid accumulation and renal complications.

Objective:To explore the efficiency of MR psychoradiology examination in screening and classification of psychiatric disorders as well as its potential clinical application.Methods:Retrospective study was conducted for 144 patients with MR psychoradiology examination, who were diagnosed mental disorders based on International Statistical Classification of Diseases and Related Health Problems Tenth Revision (ICD-10) from September 2018 to July 2020 in West China Hospital of Sichuan University. As our previous studies, imaging diagnostic models were constructed based on gray matter volume (GMV) analysis for four kinds of psychiatric disorders, including depression, anxiety disorder, bipolar disorder and schizophrenia. For 120 patients with psychiatric disorders, the GMV change pattern of brain regions was detected and subtyped by MR psychoradiology examination with 50% similarity threshold of the above imaging diagnostic models. The diagnostic efficiency of MR psychoradiology examination was evaluated with references of clinical diagnose. For 24 patients with dementia, brain atrophy was additionally measured by conventional MR examination and MR psychoradiology examination respectively.Results:The sensitivity, specificity, Youden index and accuracy of MR psychoradiology in identifying the four psychiatric disorders were 86.6% (84/97), 69.6% (16/23), 0.56 and 83.3% (100/120), including depression [77.8% (28/36), 69.0% (58/84), 0.47, 71.7% (86/120)], schizophrenia [58.8% (10/17), 91.3% (94/103), 0.50, 86.7% (104/120)], bipolar disorder [42.1% (8/19), 96.0% (97/101), 0.38, 87.5% (105/120)] and anxiety disorder [24.0% (6/25), 100% (95/95), 0.24, 84.2% (101/120)]. As for 24 patients with dementia, 58.3% (14/24) were detected with brain atrophy by conventional MR examination, while 91.7% (22/24) were detected by MR psychoradiology examination.Conclusions:MR psychoradiology can detect the subtle brain structural abnormalities of patients with mental disorders. Although it can′t be used as an independent biomarker for disease diagnosis till now, it is of great help in improving the accuracy and objectivity of diagnosis.

Objective To investigate the effect of gadolinium chloride (GdCl3) on the H22 experimental hepatocarcinogenesis in mice. Methods Totally 80 mice were inflicted to experimental hepatoma by implanting H22 cells to their liver lobes, and then equally and randomly divided into experimental hepatoma group (B) and GdCl3 pretreatment group (10 mg/kg, C). Another 40 mice served as normal control group (A). Ten mice from every group were killed respectively 7, 14, and 28 d after implantation. The left 10 mice were used for recording survival time and measuring the mass weight. Hepatic pathological histology was observed, and the expression of TNF-? was detected by ELISA and RT-PCR. Results ①Survival time was obviously higher in group B than in group C (P