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.

Objective:To explore the effects of Baduanjin and brisk walking on the sleep quality among fe-male college students.Methods:Ninety female college students with poor sleep quality[Pittsburgh Sleep Quality Index(PSQI)≥ 8]were recruited randomly assigned to Baduanjin,brisk walking,and control groups,with 30 par-ticipants in each.The Baduanjin and brisk walking groups participated in 10-week intervention(five 45-minute ses-sions per week),while the control group did not receive any intervention.Baseline and post-intervention assessments were conducted using the PSQI,a lung capacity test,echocardiography,and the Fatigue Scale(FS-14).Results:Af-ter 10 weeks,participants in both the Baduanjin and brisk walking groups got significantly lower PSQI and FS-14 total scores compared to baseline(Ps＜0.001).Cardiopulmonary function indicators,including stroke volume(SV),forced expiratory volume in one second(FEV1.0),the vital capacity-to-body mass index(VC/W),and maximum voluntary ventilation per minute(MVV),also significantly improved(Ps＜0.001).Furthermore,the Baduanjin group had significantly lower PSQI and FS-14 scores than both the brisk walking and control groups(P＜0.001),along with superior improvements in cardiopulmonary function(P＜0.001).Conclusion:This study in-dicates that Baduanjin is particularly effective in improving sleep quality,cardiopulmonary function,and reducing fatigue among female college students,showing advantages over brisk walking.

Objective:To investigate the long-term efficacy, safety and prognostic factors of intraoperative radiotherapy (IORT) for narrow-margin (resection margin < 1 cm) hepatectomy in patients with hepatocellular carcinoma (HCC) during radical surgery.Methods:A retrospective cohort study was conducted. The data of primary HCC patients undergoing radical surgery and narrow-margin hepatectomy IORT in the Cancer Hospital of the Chinese Academy of Medical Sciences from November 2009 to February 2019 were collected. IORT applied 6 MeV or 9 MeV electron beams and a single irradiation was given to the margin. Kaplan-Meier method was used for the overall survival (OS) and disease-free survival (DFS) analysis; log-rank test was used for survival comparison among subgroups. The recurrence patterns and adverse reactions were recorded. Univariate and multivariate Cox proportional hazards models were used to analyze the factors influencing the OS and DFS.Results:A total of 64 patients were enrolled, with the median age [ M ( Q1, Q3)] of 57 years (49, 63) years. All patients included 55 males (85.9%) and 9 females (14.1%). The median dose of IORT was 15 Gy (range: 12-17 Gy). The median follow-up time was 83.3 (64.4, 91.9) months. The 1-year, 3-year, 5-year, 7-year, 10-year OS rates were 90.4%, 80.6%, 75.5%, 71.4% and 47.6%, respectively; the 1-year, 3-year, 5-year, 7-year,10-year DFS rates were 77.8%, 68.1%, 59.6%, 57.6% and 38.4%, respectively. Univariate Cox regression analysis indicated that preoperative serum alpha-fetoprotein (AFP) > 400 ng/ml was an independent risk factor for poor OS (> 400 ng/ml vs. ≤ 400 ng/ml: HR = 6.57, 95% CI: 2.16-19.96, P < 0.001), while not the independent influencing factor of poor DFS ( HR = 1.71, 95% CI: 0.65-4.52, P = 0.277). The age ≤ 60 years or not, gender, viral hepatitis or not, American Joint Committee on Cancer stage, tumor diameter (> 5 cm or not), tumor number, degree of tumor differentiation, microvascular invasion or not, microsatellite nodules or not, anatomical liver resection or not, and the dose of IORT ≤15 Gy or not were not the independent influencing factors of poor OS and DFS (all P > 0.05). Kaplan-Meier method analysis showed that patients with preoperative serum AFP ≤ 400 ng/ml (48 cases) had better OS compared with those with preoperative serum AFP>400 ng/ml (16 cases) (5-year OS rate: 84.8% vs. 44.9%; 7-year OS rate: 79.9% vs.37.4%), and the difference was statistically significant ( P = 0.002). There was no statistically significant difference in the DFS between the 2 groups ( P = 0.134). During the follow-up, 28 patients (43.8%) relapsed, including 17 cases (26.6%) of early recurrence and 11 cases (17.2%) of late recurrence. No marginal recurrence was observed. There were 22 cases (34.4%) of intrahepatic recurrence alone, 2 cases (3.1%) of extrahepatic recurrence and 4 cases (6.3%) of stimutaneous recurrence inside and outside the liver. The 1-, 3-, 5- and 7-year cumulative recurrence rates inside the liver were 19.0%, 27.2%, 37.4% and 39.3% respectively, and the cumulative recurrence rates outside the liver were 6.4%, 8.0%, 9.6% and 9.6% respectively. There were no adverse reactions above grade 3 in the entire group. There were no surgery-related deaths within 30 d after the operation, and no radiation-induced liver disease occurred. Conclusions:Narrow-margin IORT helps HCC patients receiving hepatectomy to achieve favorable long-term survival and adverse reactions are tolerable. It can be used as a safe and effective adjuvant therapy alternative.

Objective To analyze the differences in cerebral blood flow(CBF)characteristics among children with different subtypes of attention deficit and hyperactivity disorder(ADHD)and their relationship with executive function using arterial spin labeling(ASL)technology.Methods A case-control study was conducted,including children diagnosed with ADHD at the outpatient clinic of Peking University Sixth Hospital from July 2015 to December 2019 as the ADHD group,and typically developing schoolchildren from January to December 2021 as the healthy control group.Both groups underwent pseudo-continuous ASL(pCASL)scanning to measure CBF,and executive function was assessed using the parent version of the Behavior Rating Inventory of Executive Function(BRIEF).Differences in CBF between ADHD children and healthy controls were com-pared.For brain regions showing significant group differences,CBF values were extracted and linear regression models were constructed with BRIEF scores to further explore the relationship between regional CBF and execu-tive function.Results A total of 134 boys with ADHD were included[83 with ADHD predominantly inat-tentive subtype(ADHD-Ⅰ)and 51 with ADHD combined subtype(ADHD-C)],along with 25 healthy control boys.Intergroup comparisons revealed that the CBF in the left middle temporal gyrus was significantly lower in ADHD-C children compared to both ADHD-Ⅰ children(P=0.010)and healthy controls(P＜0.001),while no significant difference was observed between ADHD-Ⅰ children and healthy controls(P=0.280).After adjusting for age and total IQ scores,the linear regression model showed that the CBF in the left middle temporal gyrus of ADHD-C children was negatively correlated with the planning/organization score on the BRIEF(β=-0.062,P=0.030).Conclusions The CBF in the left middle temporal gyrus of boys with ADHD-C is significantly lower than that of boys with ADHD-Ⅰ and healthy controls.This reduced regional CBF may be associated with executive function deficits in organization and planning abilities in ADHD-C,providing new insights into the neurobiological mechanisms underlying ADHD subtypes.

Objective:To explore the effects of Baduanjin and brisk walking on the sleep quality among fe-male college students.Methods:Ninety female college students with poor sleep quality[Pittsburgh Sleep Quality Index(PSQI)≥ 8]were recruited randomly assigned to Baduanjin,brisk walking,and control groups,with 30 par-ticipants in each.The Baduanjin and brisk walking groups participated in 10-week intervention(five 45-minute ses-sions per week),while the control group did not receive any intervention.Baseline and post-intervention assessments were conducted using the PSQI,a lung capacity test,echocardiography,and the Fatigue Scale(FS-14).Results:Af-ter 10 weeks,participants in both the Baduanjin and brisk walking groups got significantly lower PSQI and FS-14 total scores compared to baseline(Ps＜0.001).Cardiopulmonary function indicators,including stroke volume(SV),forced expiratory volume in one second(FEV1.0),the vital capacity-to-body mass index(VC/W),and maximum voluntary ventilation per minute(MVV),also significantly improved(Ps＜0.001).Furthermore,the Baduanjin group had significantly lower PSQI and FS-14 scores than both the brisk walking and control groups(P＜0.001),along with superior improvements in cardiopulmonary function(P＜0.001).Conclusion:This study in-dicates that Baduanjin is particularly effective in improving sleep quality,cardiopulmonary function,and reducing fatigue among female college students,showing advantages over brisk walking.

Objective:To evaluate and summarize the best evidence on nutritional management of children with inflammatory bowel disease (IBD) both domestically and internationally, so as to provide reference for clinical nursing practice.Methods:According to the "6S" evidence model, the literature on nutritional management of children with IBD was systematically searched in national and international computerized decision support systems, guideline websites, relevant professional association websites, and databases. The search period was from January 2014 to July 2024. The quality of the included literature was evaluated and the evidence was extracted, evaluated and integrated to form the best evidence.Results:A total of 15 papers were included, including three clinical decisions, five guidelines, two expert consensus, two position papers, and three systematic reviews. Thirty-four pieces of best evidence were extracted, focusing on six aspects of multidisciplinary team formation, nutritional assessment and monitoring, diet and nutrient management, nutritional support methods, exercise and obesity management, and follow-up and health education.Conclusions:This study summarizes the best evidence for nutritional management of children with IBD, which may provide a basis for clinical implementation of nutritional interventions. It is recommended that healthcare professionals screen for the best evidence, translate the evidence, and develop individualized nutritional management programs, taking into account the clinical context, professional opinion, and patient wishes.

Objective:To evaluate and summarize the best evidence on nutritional management of children with inflammatory bowel disease (IBD) both domestically and internationally, so as to provide reference for clinical nursing practice.Methods:According to the "6S" evidence model, the literature on nutritional management of children with IBD was systematically searched in national and international computerized decision support systems, guideline websites, relevant professional association websites, and databases. The search period was from January 2014 to July 2024. The quality of the included literature was evaluated and the evidence was extracted, evaluated and integrated to form the best evidence.Results:A total of 15 papers were included, including three clinical decisions, five guidelines, two expert consensus, two position papers, and three systematic reviews. Thirty-four pieces of best evidence were extracted, focusing on six aspects of multidisciplinary team formation, nutritional assessment and monitoring, diet and nutrient management, nutritional support methods, exercise and obesity management, and follow-up and health education.Conclusions:This study summarizes the best evidence for nutritional management of children with IBD, which may provide a basis for clinical implementation of nutritional interventions. It is recommended that healthcare professionals screen for the best evidence, translate the evidence, and develop individualized nutritional management programs, taking into account the clinical context, professional opinion, and patient wishes.

Objective:To investigate the long-term efficacy, safety and prognostic factors of intraoperative radiotherapy (IORT) for narrow-margin (resection margin < 1 cm) hepatectomy in patients with hepatocellular carcinoma (HCC) during radical surgery.Methods:A retrospective cohort study was conducted. The data of primary HCC patients undergoing radical surgery and narrow-margin hepatectomy IORT in the Cancer Hospital of the Chinese Academy of Medical Sciences from November 2009 to February 2019 were collected. IORT applied 6 MeV or 9 MeV electron beams and a single irradiation was given to the margin. Kaplan-Meier method was used for the overall survival (OS) and disease-free survival (DFS) analysis; log-rank test was used for survival comparison among subgroups. The recurrence patterns and adverse reactions were recorded. Univariate and multivariate Cox proportional hazards models were used to analyze the factors influencing the OS and DFS.Results:A total of 64 patients were enrolled, with the median age [ M ( Q1, Q3)] of 57 years (49, 63) years. All patients included 55 males (85.9%) and 9 females (14.1%). The median dose of IORT was 15 Gy (range: 12-17 Gy). The median follow-up time was 83.3 (64.4, 91.9) months. The 1-year, 3-year, 5-year, 7-year, 10-year OS rates were 90.4%, 80.6%, 75.5%, 71.4% and 47.6%, respectively; the 1-year, 3-year, 5-year, 7-year,10-year DFS rates were 77.8%, 68.1%, 59.6%, 57.6% and 38.4%, respectively. Univariate Cox regression analysis indicated that preoperative serum alpha-fetoprotein (AFP) > 400 ng/ml was an independent risk factor for poor OS (> 400 ng/ml vs. ≤ 400 ng/ml: HR = 6.57, 95% CI: 2.16-19.96, P < 0.001), while not the independent influencing factor of poor DFS ( HR = 1.71, 95% CI: 0.65-4.52, P = 0.277). The age ≤ 60 years or not, gender, viral hepatitis or not, American Joint Committee on Cancer stage, tumor diameter (> 5 cm or not), tumor number, degree of tumor differentiation, microvascular invasion or not, microsatellite nodules or not, anatomical liver resection or not, and the dose of IORT ≤15 Gy or not were not the independent influencing factors of poor OS and DFS (all P > 0.05). Kaplan-Meier method analysis showed that patients with preoperative serum AFP ≤ 400 ng/ml (48 cases) had better OS compared with those with preoperative serum AFP>400 ng/ml (16 cases) (5-year OS rate: 84.8% vs. 44.9%; 7-year OS rate: 79.9% vs.37.4%), and the difference was statistically significant ( P = 0.002). There was no statistically significant difference in the DFS between the 2 groups ( P = 0.134). During the follow-up, 28 patients (43.8%) relapsed, including 17 cases (26.6%) of early recurrence and 11 cases (17.2%) of late recurrence. No marginal recurrence was observed. There were 22 cases (34.4%) of intrahepatic recurrence alone, 2 cases (3.1%) of extrahepatic recurrence and 4 cases (6.3%) of stimutaneous recurrence inside and outside the liver. The 1-, 3-, 5- and 7-year cumulative recurrence rates inside the liver were 19.0%, 27.2%, 37.4% and 39.3% respectively, and the cumulative recurrence rates outside the liver were 6.4%, 8.0%, 9.6% and 9.6% respectively. There were no adverse reactions above grade 3 in the entire group. There were no surgery-related deaths within 30 d after the operation, and no radiation-induced liver disease occurred. Conclusions:Narrow-margin IORT helps HCC patients receiving hepatectomy to achieve favorable long-term survival and adverse reactions are tolerable. It can be used as a safe and effective adjuvant therapy alternative.

To analyze the differences in cerebral blood flow (CBF) characteristics among children with different subtypes of attention deficit and hyperactivity disorder (ADHD) and their relationship with executive function using arterial spin labeling (ASL) technology.

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.