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 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 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 study whether Bayesian penalized likelihood (BPL) and its optimized reconstruction algorithm can improve the reconstructed image quality of low count total-body PET.Methods:Eight patients (5 males, 3 females, age (67.2±6.3) years) who underwent hybrid 18F-FDG PET/MR total-body scans at Department of Nuclear Medicine in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected retrospectively from January to June in 2023. Total-body PET/MR images of them were included and list-mode data were reconstructed with four methods, namely 25% counts conventional reconstruction (group 1), 100% counts conventional reconstruction (group 2), 25% counts BPL reconstruction (group 3), and 25% counts optimized BPL reconstruction (group 4). At last, 32 total-body PET images were obtained. SUV max and SUV mean in different ROIs and tumor metabolic volume (MTV) were measured. Total lesion glycolysis (TLG) and parameters of image quality including the ratio of lesion to background (L/B) and image signal-to-noise ratio (SNR) were calculated. Then the differences in all the parameters among the four groups were analyzed by repeated measures analysis of variance and Friedman test. Quantitative differences between BPL reconstruction and optimized BPL with the 100% counts conventional reconstruction were compared respectively by using the Bland-Altman (BA) plot. Results:For the inter-group comparison, except for SUV mean in the muscle ( F=0.38, P=0.767), SUV max and SUV mean in other ROIs were statistically different ( F values: 8.15-36.08, χ2=18.15, all P<0.01), as well as MTV and L/B ( χ2 values: 10.65, 13.35, P values: 0.014, 0.004), but not for TLG ( χ2=4.95, P=0.175) or SNR ( F=2.64, P=0.076). For the pairwise comparison, the differences between group 2 and group 3 were the most significant (all P<0.05). Compared with group 2, there were no significant differences for SUV max and SUV mean of the cerebellar cortex and lesions in group 4 (all P>0.05), as well as MTV and L/B (both P>0.05). In addition, compared with group 1, SUV max of liver and muscle in group 2 were decreased (both P<0.05), while there were no significant differences in group 4 (all P>0.05). BA plots showed that the differences of SUV, MTV, and TLG between group 4 and group 2 were smaller obviously than those between group 3 and group 2. Conclusion:BPL reconstruction can improve low focus detection sensitivity induced by low counts, but it will cause significant changes for PET quantification, which can be solved by optimized BPL reconstruction.

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 investigate epidemiological and clinical characteristics of botulism, and the adverse events among those received botulinum antitoxin treatment.Methods:Patients with discharge diagnosis as botulism in the Second Affiliated Hospital of Xinjiang Medical University were enrolled between 2017 and 2021. The epidemiological and clinical characteristics were evaluated. Infection and mechanical ventilation as in-hospital outcomes according to baseline characteristics were analyzed. Patients with and without the interested outcomes were compared. The adverse outcomes among those received botulinum antitoxin treatment were investigated. Those with and without the adverse outcomes were also compared.Results:Sixty-seven cases of botulism were enrolled, and most cases got sick between January and March (32/67, 47.8%); among them 62 cases were Han ethnicity (92.5%); prevalence was highest in Aksu region (15/67, 22.4%); commonly seen symptoms and signs included fatigue (58/67, 86.6%), dysphagia (48/67, 71.6%), dizziness (42/67, 62.7%), ptosis (42/67, 62.7%), blurred vision (41/67, 61.2%), and limb weakness (35/67, 52.2%). Compared with patients without in-hospital infection ( n=52), patients with in-hospital infection ( n=15) were more likely to have severe botulism (0/52 vs 5/15, χ 2=19.79, P<0.001), diplopia (16/52, 30.8% vs 11/15, χ 2=8.77, P=0.003), dysarthria (17/52, 32.7% vs 11/15, χ 2=7.91, P=0.005), consciousness disorder (1/52, 1.9% vs 4/15, χ 2=10.32, P=0.008). Compared with patients without mechanical ventilation (62/67, 92.5%), patients with mechanical ventilation (5/67, 7.5%) were more likely to have severe botulism (5/5 vs 0/62, χ 2=41.17, P<0.001), and consciousness disorder (4/5 vs 1/62, 1.6%, χ 2=29.58, P<0.001). Among 67 cases of botulism, 19 cases (28.4%) had adverse events after receiving antitoxin treatment, with an average of 6.5 days from the antitoxin treatment beginning to the adverse event onset; among the 19 cases, 18 cases (94.7%) had rash. Age, sex, and severity did not differ between the groups with ( n=19) and without adverse events ( n=48) after receiving antitoxin treatment. Conclusions:Fatigue, dysphagia, dizziness, ptosis were the most frequent symptoms and signs in the botulism in Xinjiang Uygur Autonomous Region, China. Infection was a commonly seen complication of botulism, and proactive prevention and close monitoring were needed. Adverse events after receiving antitoxin were prevalent, and might not be associated with age, sex, and severity of botulism.

OBJECTIVE To investigate the effects of polyphyllin Ⅵ（PPⅥ） on the proliferation and apoptosis of glioma cells and potential mechanism. METHODS Using human glioma LN229 cells as objects， MTT assay was used to detect the survival rate after treated with different concentrations of PPⅥ [0 （control group）， 1， 2， 4， 8， 16， 32， 64 μmol/L] for different time （24， 48， 72 h）. The clone formation experiments were adopted to detect the number of cell clones and clone formation rate after being treated with different concentrations of PPⅥ [0 （control group）， 2， 4， 8 μmol/L] for 14 days. The flow cytometry and Western blot assay were used to detect the apoptotic rate of cells， the expressions of apoptosis-related protein [B cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， cleaved caspase-3]， and the expressions of related proteins of Fas/Fas ligand （FasL） death receptor pathway and protein kinase B （Akt）/glycogen synthesis kinase-3β （GSK-3β） pathway after being treated with different concentrations of PPⅥ [0（control group）， 4， 8 μmol/L] for 24 h. RESULTS Compared with the control group， the survival rate of cells， the number of clones and clone formation rate， the protein expression of Bcl-2， and the phosphorylation levels of Akt and GSK-3β protein were decreased significantly in different concentration groups of PPⅥ （P＜0.05 or P＜0.01）. The apoptotic rate， the protein expressions of Bax， cleaved caspase-3， Fas， FasL and cleaved caspase-8 were increased significantly （P＜0.05 or P＜ 0.01）. CONCLUSIONS PPⅥ can inhibit the proliferation and induce the apoptosis of human glioma LN229 cells， which may be related to the activation of the Fas/FasL death receptor pathway and the inhibition of the Akt/GSK-3β pathway.