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 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.

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.

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

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 investigate the clinical characteristics of patients with acquired aplastic anemia (AA) accompanied by abnormal antinuclear antibody (ANA) and autoantibodies and their effects on the efficacy of immunosuppressive therapy (IST).Method:A retrospective case-control study was conducted, analyzing the clinical data of 291 patients with AA who underwent IST and were screened for autoantibodies at initial diagnosis between January 2018 and December 2019 at Blood Diseases Hospital, Chinese Academy of Medical Sciences. According to the titer of ANA at the initial diagnosis, extracted nuclear antigen antibodies (ENAs) abnormality and the change of ANA titer after treatment, the treatment responses of 3 months and 6 months after IST were compared. The correlation between clinical features and ANA abnormality was analyzed by univariate and multivariate logistic regression analysis. The parameters of univariate analysis P<0.1 were included in multivariate analysis, stepwise regression analysis and subgroup analysis. Results:A total of 291 patients were included in the study, of which 145 (49.83%) were male. Among all patients, 147 (50.52%) tested positive for ANA at initial diagnosis, with titers of 1∶100, 1∶320, and 1∶1 000 observed in 94, 47, and 6 cases, respectively. Female gender, older age, presence of paroxysmal nocturnal hemoglobinuria (PNH) clone, and higher levels of IgG, IgA, and thyroid hormone were significantly associated with ANA positivity at initial diagnosis, while white cell counts, reticulocytes, and free triiodothyronine were significantly lower than that of ANA-negatively patients (all P<0.05). Furthermore, logistic regression analyses revealed that female gender ( OR=1.980, 95% CI 1.206-3.277), older age ( OR=1.017, 95% CI 1.003-1.032), and presence of PNH clone ( OR=1.875, 95% CI 1.049-3.408) were independent risk factors for ANA positivity at initial diagnosis. Subgroup analysis indicated that the risk of ANA positivity at initial diagnosis was even higher in PNH clone-positive patients in the subgroups of females ( OR=1.24, 95% CI 1.02-1.51), severe AA ( OR=1.26, 95% CI 1.07-1.47), and age≥40 years ( OR=1.26, 95% CI 1.05-1.52) (all P<0.05). However, ANA titers at initial diagnosis, presence of other abnormal ENAs, and changes in ANA titers after treatment with IST were not correlated with treatment response (all P>0.05). Conclusions:Approximately 50% of patients with AA had abnormal ANA, and their presence was significantly associated with female gender, older age, and presence of PNH clone at initial diagnosis. However, the presence of abnormal ANA and changes in ANA titers after treatment did not affect the efficacy of IST in patients with AA.

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.