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.

Objective:To investigate the effect of on-demand glucocorticoid strategy on the occurrence and outcome of porcine anti-lymphocyte globulin (p-ALG) -associated serum sickness in aplastic anemia (AA) .Methods:The data of AA patients who received in the Anemia Diagnosis and Treatment Center of Haematology Hospital, CAMS & PUMC from January 2019 to January 2022 were collected. Among them, 35 patients were enrolled in the on-demand group, with the glucocorticoid strategy adjusted based on the occurrence and severity of serum sickness; 105 patients were recruited in the usual group by matching the age and disease diagnosis according to 1∶3 ratio in patients who received a conventional glucocorticoid strategy in the same period. The incidences, clinical manifestations, treatment outcomes of serum sickness, and glucocorticoid dosage between the two groups were analyzed.Results:The incidences of serum sickness in the on-demand group and the usual group were 65.7% and 54.3% ( P=0.237) , respectively. The median onset of serum sickness was the same [12 (9, 13) d vs the 12 (10, 13) d, P=0.552], and clinical symptoms and signs, primarily joint, and/or muscle pain, fever, and rash were similar. Severity grades were both dominated by Grades 1-2 (62.8% vs 51.4%) , with only a few Grade 3 (2.9% vs 2.9%) , and no Grades 4-5. No significant difference in the serum sickness distribution ( P=0.530) . The median duration of serum sickness was the same [5 (3, 7) d vs 5 (3, 6) d, P=0.529], and all patients were completely cured after glucocorticoid therapy. In patients without serum sickness, the average dosage of prophylactic glucocorticoid per patient in the usual group was (469.48 ±193.57) mg (0 in the on-demand group) . When compared to the usual group, the average therapeutic glucocorticoid dosage per patient in the on-demand group was significantly lower [ (125.91±77.70) mg vs (653.90±285.56) mg, P<0.001]. Conclusions:In comparison to the usual glucocorticoid strategy, the on-demand treatment strategy could significantly reduce glucocorticoid dosage without increasing the incidence of serum sickness; in addition, the duration of serum sickness and the incidence of above Grade 2-serum sickness were similar.

Objective:To analyze the diagnostic value of cell-free plasma metagenomic next-generation sequencing (mNGS) pathogen identification for severe aplastic anemia (SAA) bloodstream infection.Methods:From February 2021 to February 2022, mNGS and conventional detection methods (blood culture, etc.) were used to detect 33 samples from 29 consecutive AA patients admitted to the Anemia Diagnosis and Treatment Center of the Hematology Hospital of the Chinese Academy of Medical Sciences to assess the diagnostic consistency of mNGS and conventional detection, as well as the impact on clinical treatment benefits and clinical accuracy.Results:①Among the 33 samples evaluated by mNGS and conventional detection methods, 25 cases (75.76%) carried potential pathogenic microorganisms. A total of 72 pathogenic microorganisms were identified from all cases, of which 65 (90.28%) were detected only by mNGS. ②All 33 cases were evaluated for diagnostic consistency, of which 2 cases (6.06%) were Composite, 18 cases (54.55%) were mNGS only, 2 cases (6.06%) were Conventional method only, 1 case (3.03%) was both common compliances (mNGS/Conventional testing) , and 10 cases (30.3%) were completely non-conforming (None) . ③All 33 cases were evaluated for clinical treatment benefit. Among them, 8 cases (24.24%) received Initiation of targeted treatment, 1 case (3.03%) received Treatment de-escalation, 13 cases (39.39%) received Confirmation, and the remaining 11 cases (33.33%) received No clinical benefit. ④ The sensitivity of 80.77%, specificity of 70.00%, positive predictive value of 63.64%, negative predictive value of 84.85%, positive likelihood ratio of 2.692, and negative likelihood ratio of 0.275 distinguished mNGS from conventional detection methods (21/12 vs 5/28, P<0.001) . Conclusion:mNGS can not only contribute to accurately diagnosing bloodstream infection in patients with aplastic anemia, but can also help to guide accurate anti-infection treatment, and the clinical accuracy is high.

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 evaluate right atrial (RA) volume and function in patients with hepatitis B cirrhosis by four-dimensional automatic quantitation analysis technique, and to explore its correlation with liver function grading.Methods:Ninety patients with hepatitis B cirrhosis who were clinically confirmed in Henan Provincial People′s Hospital from December 2020 to July 2021 were randomly enrolled as the research subjects. According to Child-Pugh liver function score criteria, the patients were divided into three groups: Child-Pugh A group ( n=31), Child-Pugh B group ( n=31), Child-Pugh C group ( n=28). Another 30 healthy volunteers with gender and age matched at the same period were selected as the control group. The RA maximum volume (RAVmax), RA minimum volume (RAVmin), RA presystolic volume (RAVpreA), RA maximum volume index (RAVImax), RA emptying volume (RAEV), RA ejection fraction (RAEF), RA reservoir longitudinal and circumferential strains (RASr, RASr-c), RA conduit longitudinal and circumferential strains (RAScd, RAScd-c), RA contraction longitudinal and circumferential strains (RASct, RASct-c) were obtained by four-dimensional automatic quantitation analysis technique. Spearman correlation analysis was used to explore the correlation between the volume and strain parameters of right atrium and liver function grading, and the independent correlation factors of RASr-c were analyzed by univariate and multivariate linear regression analyses. Results:Compared with the control group, Child-Pugh A and Child-Pugh B groups, RAVmax, RAVmin, RAVpreA, RAVImax, and RAEV were all increased in Child-Pugh C group (all P<0.05). Compared with control group, the absolute values of RASr, RASct, RASr-c and RASct-c were increased, and the absolute values of RAScd and RAScd-c were decreased in Child-Pugh A group (all P<0.05). Compared with control group, Child-Pugh A and Child-Pugh B groups, the absolute values of RASr, RAScd, RASct, RASr-c, RAScd-c and RASct-c were decreased in the Child-Pugh C group (all P<0.05). Correlation analysis showed that the volume and strain parameters of the right atrium were correlated with liver function grading. RASr-c was independently correlated with E/e, ALB and BNP(β=-0.543, 0.521, and -0.562 respectively, all P<0.05). Conclusions:During the compensatory stage in patients with hepatitis B cirrhosis, the RA functions of reservoir and contractile were increased, but the function of conduit was decreased. With the aggravation of liver cirrhosis, the RA functions of reservoir, conduit and contractile were all decreased. The four-dimensional volume and strain parameters of the right atrium were correlated with Child-Pugh liver function grading, and RASr-c was independently correlated with E/e, ALB and BNP.