Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

Objective To investigate the role and mechanism of ferroptosis in cochlear hair cell injury induced by exposure to ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate(GenX).Methods Mouse cochlear hair cell line HEI-OC1 was assigned to control,GenX,ferrostatin-1(Fer-1),and GenX+Fer-1 groups.CCK-8 assay was used to assess the cytotoxicity of GenX and the rescue effect of Fer-1 co-treatment.Western blotting and qRT-PCR were employed to measure the protein and transcriptional expression of ferroptosis markers,cochlear function indicators,blood labyrinth barrier markers,and ferroptosis-related pathway.FerroOrange,Bodipy(C11),mitochondrial membrane potential assay kit(JC-1),and adenosine triphosphate(ATP)assay were applied to detect Fe2? accumulation,lipid peroxidation,mitochondrial membrane dysfunction,and cellular ATP levels,respectively.Results Exposure to 200 μmol/L GenX for 12 h significantly reduced the viability of HEI-OC1 cells(P<0.01),down-regulated the protein levels of glutathione peroxidase 4(Gpx4),solute carrier family 7 member 11(Slc7a11),and ferroptosis suppressor protein 1(Fsp1)(P<0.05),whereas up-regulated acyl-coa synthetase long-chain family member 4(Acsl4)(P<0.01),and decreased the expression of cochlear hair-cell function genes and blood labyrinth barrier genes(P<0.05).These changes were accompanied with Fe2+accumulation,elevated lipid peroxidation,mitochondrial membrane damage,and reduced ATP production(P<0.001).Addition of Fer-1 restored cell viability(P<0.05),restored the expression of ferroptosis related proteins(P<0.05),and improved the expression of several hair-cell function and blood labyrinth barrier genes(P<0.05).In parallel,the GenX+Fer-1 group exhibited reduced Fe2? accumulation,lower lipid peroxidation,attenuated mitochondrial membrane damage,and increased ATP level(P<0.001).Conclusion GenX induces iron-metabolism dysregulation and lipid peroxidation,and then leads to differentiation impairment of cochlear hair cells and barrier functions via the ferroptotic System Xc?-Gpx4-Fsp1 axis.

Objective:s To investigate the risk factors for delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) in patients with acute carbon monoxide poisoning (ACOP) and to develop predictive models based on machine learning algorithms.Methods:Patients with ACOP hospitalized at the First Affiliated Hospital of Zhengzhou University from August 2019 to October 2024 were included, with the occurrence of DEACMP as the outcome measure. The dataset was randomly divided into training and validation sets at a ratio of 7:3. Lasso regression was used to select features influencing the outcome in training sets. Nine machine learning models—including Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Support Vector Machine (SVM)—were constructed. Receiver operating characteristic (ROC) curves were plotted and the area under the curve (AUC) calculated for each model. Calibration curves were used to assess accuracy, and decision curve analysis (DCA) was applied to evaluate clinical utility. The SHapley Additive exPlanations (SHAP) method was employed to visualize and interpret the best-performing model.Results:A total of 264 ACOP patients were included, of whom 54 (20.5%) developed DEACMP. Lasso regression identified eight key feature variables. Based on these factors, predictive models were constructed, showing good AUC stability across the nine machine learning models in both training (0.92–0.99) and validation sets (0.85–0.91). The RF model performed best, with an AUC of 0.99 in the training set and 0.90 in the validation set; its calibration curve and DCA curve also demonstrated excellent performance. SHAP analysis of the RF model revealed the importance ranking of factors from highest to lowest as follows: Glasgow Coma Scale (GCS) score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, diastolic blood pressure (DBP), and drinking history.Conclusions:The RF model exhibited the highest predictive performance for DEACMP occurrence in ACOP patients. The influencing factors, ranked in order of importance from highest to lowest, are as follows: GCS score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, DBP, and drinking history.

Objective:To investigate the discomfort of chest wall approach area in patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach (GUA), and to analyze its influencing factors. To provide a basis for the development of targeted improvement measures.Methods:A total of 153 patients with GUA from May. 2023 to Aug. 2023 in the Department of Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University were selected as the study subjects. The general information questionnaire was collected one day before operation, the pain scales were assessed one day and three days after operation, and the pain and numbness scales were assessed one month after operation. The t test or χ2 test was used for comparison of baseline data between groups according to different types of variables. The patients were divided into two groups: less than moderate pain group (two postoperative average VAS scores<4) and more than moderate pain group (two postoperative average VAS scores ≥4). Mild numbness group (postoperative VAS score<4) ; Moderate and severe numbness group (postoperative VAS score ≥4). Multivariate binary Logistic regression was performed with pain discomfort and numbness discomfort as dependent variables to find possible influencing factors. Results:A total of 153 valid questionnaires were collected. There were 125 patients in the moderate pain group; There were 28 patients in the moderate and above pain group. There were 94 patients in the mild numbness group. There were 59 patients in the moderate to severe numbness group. Multivariate binary Logistic regression results showed that, exercise habits ( OR=0.07 95% CI=0.006, 0.409), operation duration ( OR=1.026 95% CI=1.001, 1.054), total drainage volume ( OR=1.122 95% CI=1.07, P<0.05), 1.198), and drainage tube indwelling time ( OR=0.012 95% CI=0.0, 0.187) had an impact on the discomfort of the chest wall approach area, and the difference was statistically significant ( P<0.05). Gender, BMI, marital status, education, occupation, handed-side surgery, handed-side axillary surgery, smokess and alcohol history, intraoperative blood loss, and length of hospital stay had no effect on the discomfort of chest wall approach area, and the difference was not statistically significant ( P>0.05) . Conclusion:Exercise habits, operation duration, total drainage volume, and drainage duration are independent predictors of discomfort in GUA patients.

Objective:To observe any effect of family rehabilitation interventions based on digital health management on elderly type 2 diabetes mellitus (T2DM) patients with sarcopenia.Methods:One hundred elderly T2DM patients with sarcopenia who had been discharged from hospital after treatment were divided into an observation group and a control group, each of 50. Both groups continued the diet control and training begun during their hospitalization, but the observation group was additionally provided with family rehabilitation based on digital health management. Before and after 3 months, the glucose and lipid metabolism and sarcopenia of both groups were evaluated with related symptom indexes, and their levels of diabetes self-management were compared.Results:Significant improvement was observed in both groups, but the average glucose and lipid metabolism indexes and sarcopenia-related symptom indexes of the observation group were significantly better than the control group′s averages. Their diabetes self-management was also significantly superior.Conclusion:Family rehabilitation based on digital health management can significantly improve glucose and lipid metabolism and muscle mass in elderly T2DM patients with sarcopenia. Such intervention is worthy of promotion and application in clinical practice.

Systemic lupus erythematosus (SLE) is an acute or chronic autoimmune disease characterized by the presence of pathogenic autoantibodies and immune complexes, and multiorgan damage. It is a highly heterogeneous disease and commonly developed in women of childbearing age. The cause of systemic immunopathological injury in SLE is due to the production of autoantibodies by overactivated autoreactive B cells. The treatment of SLE by targeting B cells is very effective, suggesting the critical role of B cells in the development and progression of SLE. However, the current B cell depletion therapies all target the total B cell population, which are not capable of clearing specifically autoreactive B cells since the specific marker molecules and the mechanisms associated with the development of SLE remain unclear. With the development of science and technology, high-throughput sequencing technology provides new ideas for the study of B cell abnormalities in SLE. This review focuses on the progress in high-throughput sequencing to reveal new abnormalities in B cell receptors, new B cell subsets and B cell-related novel therapeutic targets, hoping to provide reference for better understanding the pathogenesis and exploring therapeutic strategies.

Objective To study the relationship between blood microRNA-133b(miR-133b)and solu-ble fms-like tyrosine kinase 1(sFLT1)levels with the prognosis in the patients with endometrial cancer.Methods A total of 122 patients with endometrial cancer visited in the gynecology department of this hospital from January 2015 to January 2016 were prospectively selected as the study subjects,and divided into the sur-vival group(n=58)and death group(n=64)according to the 5-year prognosis of the patients with endome-trial cancer.The miR-133b and sFLT1 levels were compared between the two groups.The COX regression was used to analyze the relationship between miR-133b and sFLT1 with the prognosis of the patients with en-dometrial cancer.Results The levels of miR-133b and sFLT1 in the survival group were higher than those in the death group,and the differences were statistically significant(P＜0.05).The median survival time in the miR-133b low-level group was shorter than that in the miR-133b high level group,and the difference was sta-tistically significant(P＜0.05).The median survival time of the sFLT1 low level group was shoeter than that in the sFLT1 high level group,and the difference was statistically significant(P＜0.05).The FIGO stageⅢ-Ⅳ and lymph node metastasis were the independent risk factors for the prognosis of endometrial cancer(P＜0.05),and the pathological G1-G2,high level of miR-133b and sFLT1 were the independent protective factors for the prognosis of endometrial cancer(P＜0.05).Conclusion The miR-133b and sFLTl low levels in the patients with endometrial cancer are associated with the disease progression,and both are the independ-ent risk factors of prognosis.

Injection fear is widespread in the population, which can cause patients to tolerate or avoid injection, reduce treatment compliance, and increase the burden of healthcare. Choosing appropriate injection fear assessment tools in clinical practice is helpful to understand the degree, psychological characteristics and influencing factors of individual injection fear. In this paper, the contents, characteristics and application methods of fear of injection assessment tools at home and abroad are reviewed, in order to provide reference for the application and development of fear of injection assessment tools for medical staff.

Objective:To observe the characteristics and outcomes of hospital-acquired venous thromboembolism (HA-VTE), and to guide the clinic to take preventive measures for high-risk patients to reduce the incidence of HA-VTE.Methods:The clinical data of 1 570 hospitalized patients with HA-VTE from December 2013 to December 2019 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed, including the basic information, department, risk factor evaluation of venous thromboembolism (VTE), prevention and outcomes, etc.Results:During the period, the total incidence of HA-VTE was 0.50% (1 570/317 047). The annual incidence of HA-VTE increased year by year, from 0.19% (85/44 737) in 2014 to 0.82% (564/68 780) in 2019. The incidence of HA-VTE in elderly patients (age ≥65 years old) was significantly higher than that in young and middle-aged patients (age form 18 to 64 years old): 0.96% (970/100 768) vs. 0.28% (600/216 279), and there was statistical difference ( χ2 = 654.96, P<0.01). There was no statistical difference in the incidence of HA-VTE between male and female: 0.51% (780/151 617) vs. 0.48% (790/165 430), χ2 = 2.19, P>0.05. HA-VTE patients were mainly distributed in the neurology department, emergency department, neurosurgery department, orthopedics department, vascular surgery department, general surgery department, etc, with the highest proportion of 27.83% (437/1 570) in neurology department. The departments with high incidence of HA-VTE were intensive care unit, emergency department, stroke center, orthopedics department, rehabilitation department and neurology department, with the highest incidence of 7.69% (7/91) in intensive care unit. The hospital stay in patients with HA-VTE was significantly longer than that in patients without HA-VTE: 14 (9, 20) d vs. 7 (3, 11) d, and there was statistical difference ( Z = - 39.75, P<0.01). During hospitalization, 94 patients died, and 7 cases (0.45%, 7/1 570) were directly caused by HA-VTE. Only 0.13% (2/1 570) of the patients underwent the risk factor evaluation of VTE. Conclusions:The annual incidence of HA-VTE has a clear upward trend, and the incidence of critical illness and elderly patients is the highest. HA-VTE significantly prolonged the average hospital stay of patients and increased the risk of death. Screening and evaluation should be strengthened, high-risk groups should be identified, and active preventive measures should be taken to reduce the risk of HA-VTE.