Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

OBJECTIVES: To investigate the correlation of PRELID1 with gastric cancer (GC) progression, prognosis, and epithelial-mesenchymal transition (EMT) and the underlying mechanisms. METHODS: We analyzed the data of 115 patients undergoing radical gastrectomy for GC in our hospital between February, 2018 and March, 2023 to explore the correlation of PRELID1 expression level in GC tissues with tumor progression and patient prognosis. In cultured GC cells, the effects of lentivirus-mediated overexpression or interference of PRELID1 were observed on cell migration, invasion and EMT. RESULTS: Immunohistochemical staining revealed significantly higher PRELID1 expression in GC tissues (P<0.001), whose expression level was positively correlated with CEA ≥5 ng/mL (P=0.007), CA199 ≥37 U/mL (P=0.007), G_3-4 stages (P=0.001), T_3-4 stages (P=0.001), and N_2-3 stages (P=0.020). Univariate and Cox multifactorial analysis showed that high PRELID1 level was an independent risk factor affecting 5-year survival of GC patients (P=0.001). In cultured GC cells, PRELID1 overexpression obviously promoted cell proliferation, migration, invasion, and the expressions of MMP2 and MMP9, and interference of PRELID1 produced the opposite changes. PRELID1 overexpression also increased the expressions of N-cadherin and vimentin and reduced the expression of E-cadherin. Mechanistic analyses showed that up-regulation of PRELID1 increased the expression of p-PI3K, p-AKT, and p-mTOR in GC cells, whereas its interference caused the opposite changes; the application of 740 Y-P, a PI3K/AKT pathway activator, significantly enhanced the migration, invasion, and EMT of GC cells with PRELID1 knockdown. CONCLUSIONS PRELID1 is highly expressed in GC and affects prognosis of the patients, and its high expression promotes migration, invasion and epithelial mesenchymal transition of GC cells possibly by activating the PI3K/AKT/mTOR pathway.
Humans ; Stomach Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Prognosis ; Cell Movement ; Cell Line, Tumor ; Male ; Female ; Middle Aged ; Signal Transduction ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism*

Objective To explore the effect of urine mixing degree on 24-hour urinary total protein(24 h UTP)in patients with chronic kidney disease(CKD).Methods From October 1,2023 to December 31,2023,30 hospitalized patients who needed to complete 24 h UTP testing in Zhongshan Hospital,Fudan University were selected.A 5 L unified container was used to collect urine for 24 hours.After collection and one hour's standing,the urine sample was divided into upper,middle,and lower equal parts according to volume,which was defined as direct-sampling group.Then,the urine samples were fully mixed with a magnetic stirrer and sampled again according to the above-mentioned three-equal sampling method,which was defined as mixed-sampling group.The generalized estimating equation was used to compare the urinary protein concentration before and after mixing and at different sampling location.Results The results of generalized estimating equation showed that after controlling the variable"sampling position",there was no significant difference in urinary protein concentration between the direct-sampling group and the mixed-sampling group.After controlling the variable"mixing method",there was still no significant difference in urinary protein concentration at different sampling positions.After adjusting the covariates such as age,gender,and estimated glomerular filtration rate(eGFR),the results were consistent.Conclusions With standard protocol,the entire 24-hour urine sample is a relatively even-distributed solution.After the total urine collection is completed,the temporary sample can be directly extracted from any level of the original urine within 1 hour,and the urine protein concentration of the sample multiplied by the urine volume can reflect the 24 h UTR.

Colorectal cancer is the most common malignant tumor of digestive tract, and BRAF V600E mutations occur in approximately 10% of patients with metastatic colorectal cancer (mCRC). Cancer patients harboring this mutation have a unique molecular profile and clinical phenotype; they show poor response to systemic chemotherapy, insensitivity to single BRAF inhibitor, and short survival rate. It is important to develop new therapeutic agents and clinical strategies to improve the prognosis of these patients. This review mainly introduces treatment methods for BRAF V600E-mutated mCRC and rationally derived combinations of targeted agents and immunotherapy.

Objective To analyze the clinical manifestations of delayed serological transfusion reactions(DSTR)after platelet transfusion in tumor patients,and to explore the transfusion strategy.Methods Clinical data and laboratory test re-sults of patients with positive antibody screening were analyzed after platelet transfusion in our hospital from January 1,2015 to June 30,2023,and the incidence rate,clinical characteristics and transfusion strategy of patients with DSTR were ana-lyzed.Results A total of 2 553 patients with 6 057 platelet transfusions were reviewed.Eight patients developed DSTR and received a total of 21 therapeutic amounts of platelets,and 5 patients were subsequently transfused with red blood cells.Rh system antibodies were detected in 7 cases(4 anti-E,1 anti-c/E,1 anti-C and 1 anti-c)and Kell system antibodies in 1 case.Conclusion Tumor patients may also develop DSTR after platelet transfusion.It is necessary to pay close attention to the antibody situation and perform matched transfusion when transfusing blood again.

Objective:To examine the satisfaction and teaching effectiveness of Health Statistics among students majoring in Public Utility Administration,and to provide valuable insights for optimizing current teaching practices and enhancing teaching effectiveness.Methods:A survey questionnaire,specifically designed for this study,was administered to 56 students of grade 2021 majoring in Public Utility Administration in our school.The questionnaire covered topics such as the difficulty of teaching content,learning satisfaction,and the Student Evaluation of Educational Quality(SEEQ)scale.Results:Non-parametric testing was considered the most difficult knowledge point,and male students found statistical inference of quantitative data was the most challenging,while female students found non-parametric testing was the most difficult.In terms of satisfaction,the highest score was obtained for pre-class review,while the lowest score was given to improving learning interest in Rain Classroom.The overall score for teaching effectiveness,as measured by SEEQ,was good across seven dimensions.Teaching enthusiasm received the highest score(4.40±0.43),while homework volume received the lowest score(3.23±0.37).With the exception of homework grading,satisfaction was positively correlated with most dimensions of teaching effectiveness evaluation.Conclusions:Despite perceiving the course as generally difficult,students expressed high satisfaction and overall positive evaluation of teaching effectiveness.Therefore,it is recommended to actively explore new teaching reforms to cultivate well-rounded applied talents for public utilities.

Objective:To explore the spatial autocorrelation and macro influencing factors of stroke mortality in Zhejiang Province in 2015-2020 and provide a scientific basis for stroke prevention and control strategy.Methods:The data on stroke death were obtained from Zhejiang Chronic Disease Surveillance System. The spatial distribution of stroke mortality was explored by mapping and spatial autocorrelation analysis. The spatial panel model analyzed the correlation between stroke mortality and socioeconomic and healthcare factors.Results:From 2015 to 2020, the average stroke mortality was 68.38/100 thousand. The standard mortality of stroke was high in the areas of east and low in the west, high in the south and low in the north. Moreover, positive spatial autocorrelation was observed (Moran's I=0.274-0.390, P<0.001). Standard mortality of stroke was negatively associated with per capita gross domestic product (GDP) ( β=-0.370, P<0.001), per capita health expenditure ( β=-0.116, P=0.021), number of beds per thousand population ( β=-0.161, P=0.030). Standard mortality of ischemic stroke was negatively associated with per capita GDP ( β=-0.310, P=0.002) and standard management rate of hypertension ( β=-0.462, P=0.011). Standard mortality of hemorrhagic stroke was negatively associated with per capita GDP ( β=-0.481, P<0.001), per capita health expenditure ( β=-0.184, P=0.001), number of beds per thousand population ( β=-0.288, P=0.001) and standard management rate of hypertension ( β=-0.336, P=0.029). Conclusions:A positive spatial correlation existed between stroke mortality in Zhejiang Province in 2015-2020. We must focus more on preventing and controlling strokes in relatively backward economic areas. Moreover, to reduce the mortality of stroke, increasing the investment of government medical and health funds, optimizing the allocation of medical resources, and improving the standard management rate of hypertension are important measures.

【Objective】 To evaluate the detection and distribution characteristics of anti-P1 in tumor patients, so as to aid in blood screening and transfusion safety. 【Methods】 The clinical data of 112 658 tumor patients who underwent blood preparation and transfusion in our hospital from January 2014 to December 2021 were retrospectively analyzed, and column agglutination technique was used to perform transfusion compatibility test. 【Results】 A total of 1 079 (0.96%, 1 079/112 658) cases were detected with unexpected antibodies, of which 71 (6.58%, 71/1 079) were identified as anti-P1. In anti-P1 cases, 59.15% (42/71) were males; 60.56% had no pregnancy history (P<0.01); 29.58% (21/71), 52.11%(37/71), 12.68%(9/71) and 5.63%(4/71) of anti-P1 patients were with type A, B, O and AB, respectively. 57 cases of anti-P1 patients (80.28%) had difficulty in ABO blood group identification. The incidence of interfering in patients with type B was higher than that of other blood types (P<0.05), as the frequency of w+ in reverse blood typing was higher than other reactive patterns (P<0.05). The incidence of gastric tumor and brain space-occupying lesion in patients with anti-P1 was higher than that in patients with other alloantibodies, while the incidence of gynecological tumors was lower (P<0.05). 【Conclusion】 Anti-P1 affects the ABO blood group identification of tumor patients, and most of them had difficulty in ABO blood group identification. Compared with patients with other alloantibodies, patients with anti-P1 are more likely to be male and suffer from gastric and brain tumors, but less likely from gynecological tumors.

Objective:To evaluate the accuracy of bedside lung ultrasound in predicting postoperative pulmonary complications (PPCs) in the patients undergoing radical resection of gastrointestinal cancer.Methods:One hundred and eight patients of both sexes, aged >18 yr, undergoing elective radical resection of gastrointestinal cancer with general anesthesia, were enrolled in the study. Lung ultrasound was performed before surgery (T 1) and at 2, 4 and 7 days after surgery (T 2-4). Lung ultrasound score (LUS) and B-line score were recorded. Serum procalcitonin (PCT) concentrations and blood routine were recorded, and systemic immune-inflammatory index (SII) was calculated. All the patients underwent chest CT examination before surgery and 7 days after surgery. The results of chest CT and clinical diagnosis were used as the gold standard for PPCs. The occurrence of PPCs within 7 days after surgery was recorded. The patients were divided into PPCs group and non-PPCs group according to the development of PPCs. Spearman′s correlation analysis was used to analyze the correlation of B-line score and LUS with PPCs, PCT and SII. The receiver operating curve was used to evaluate the accuracy of B-line score and LUB in predicting PPCs. Results:One hundred and three patients were finally enrolled in the study, including 45 patients in PPCs group and 58 patients in non-PPCs group, and the incidence of PPCs was 43.7%. Both B-line score and LUS were positively correlated with PPCs at T 1 ( P<0.001), and B-line score and LUS were positively correlated with PCT and SII at T 2-4 ( P<0.001). The AUC (95% confidence interval) of B-line score and LUB in predicting PPCs were 0.926 (0.879-0.972) and 0.909 (0.852-0.965), respectively ( P<0.001), the best cut-off values of B-line score and LUB in predicting PPCs were set at 25.5 and 11.5 respectively, and the sensitivity and specificity of B-line score were 0.80 and 0.88 respectively, and the sensitivity and specificity of LUB were 0.78 and 0.93 respectively. Conclusions:Bedside pulmonary ultrasonography (B-line score and LUS) can accurately predict the occurrence of PPCs in the patients undergoing radical resection of gastrointestinal cancer and dynamically evaluate the condition of PPCs, and B-line score >25.5 and LUS score >11.5 indicate a high risk of PPCs.

Objective:To determine the level of epilepsy knowledge of caregivers for children with epilepsy and analyze its influencing factors, and investigate caregivers' educational needs and their acceptance for remote education, in order to provide reference for clinical telenursing education.Methods:From March to September 2022, 221 caregivers of epileptic children in the outpatient department and ward of neurology department of Xuzhou Children's Hospital were recruited by convenient sampling method for cross-sectional investigation. The status of caregivers' knowledge and educational needs were investigated by the general information questionnaire, epilepsy knowledge questionnaire, epilepsy knowledge needs questionnaire and telenursing acceptance questionnaire, and the influencing factors of knowledge level were analyzed by multiple linear regression.Results:The average score of epilepsy knowledge of caregivers was (15.68 ± 6.43) points. The course of disease, taking medicine on time, education background and monthly income of caregivers were the influencing factors of caregivers' knowledge level, and the difference was statistically significant ( P <0.05). 94.12% (208/221)- 96.38% (213/221) of the caregivers had high educational needs, and they had the highest demand for safety guidance during seizures. Caregivers' acceptance of remote education was moderate, ranging from 34.39% (76/221) to 71.95% (159/221). Conclusions:Caregivers' epilepsy knowledge needs to be improved. Medical institutions should formulate education plans according to the different characteristics of caregivers. Caregivers have a high demand for nursing knowledge, and medical staff should increase health education. Before giving health education based on remote nursing platform, we should fully understand the attitude of caregivers to the platform, so that they can master disease knowledge, strengthen their disease management ability, and improve the quality of life of children.