Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Nuclear emergency medical rescue is one of the important courses of military medical professional education, and improving the training level of nuclear emergency medical rescue plays a very important role in improving post competency of trainees. Based on the problem of disconnection between "teaching" and "need" in the occupational education of nuclear emergency medical rescue in the past, this study proposes the curriculum goal of "the combination of three abilities" and performs the optimization and practice of the occupational education curriculum system of nuclear emergency medical rescue from the aspects of curriculum setting, curriculum content, teaching methods, and assessment and evaluation. The results show that the new curriculum system can significantly improve the comprehensive ability of nuclear emergency medical rescue among trainees and better meet the requirements for their posts, thereby playing an important role in cultivating high-quality military medical talents in nuclear emergency medical rescue.

Objective To compare clinical efficacy of robot-assisted(RA)and remote sensing navigation alignment(RSNA)system-assisted total knee arthroplasty(TKA).Methods From March 2023 to June 2023,60 patients who underwent the first unilateral TKA due to severe knee osteoarthritis(KOA)were admitted and divided into RSNA group and RA group according to different treatment methods,with 30 patients in each group.There were 5 males and 25 females in RSNA group,aged from 56 to 81 years old with an average of(66.33±7.16)years old;body mass index(BM1)ranged from 19.87 to 38.54 kg·m-2 with an average of(28.40±6.18)kg·m-2;the courses of disease ranged from 5 to 36 months with an average of(18.20±8.98)months;RSNA system was used to assist the positioning of osteotomy.There were 7 males and 23 females in RA group,aged from 55 to 82 years old with an average of(67.83±8.61)years old;BMI ranged from 19.67 to 37.25 kg·m-2 with an aver-age of(28.01±4.89)kg·m-2;the courses of disease ranged from 3 to 33 months with an average of(17.93±9.20)months;RA was performed.Operation time,incision length,latent blood loss at 2 weeks after operation and incidence of lower extremity thrombosis were compared between two groups.Hip-knee ankle angle(HKAA),HKAA deviation,lateral distal femoral angle(LDFA),medial proximal tibial angle(MPTA)and posterior tibial slope(PTS)were compared between two groups;Western Ontario McMaster Universities Osteoarthritis Index(WOMAC)and Knee Society score(KSS)were used to evaluate functional recovery before operation,3 and 6 months after operation.Results The operation was performed successfully in both groups,and there were no serious complications such as vascular and nerve injury during operation.The wound healed well at stage Ⅰafter operation,and the follow-up time was 6 months.The operation time,latent blood loss at 2 weeks after operation and inci-sion length in RSNA group were(94.35±5.75)min,(130.54±17.53)mland(14.73±2.14)cm,respectively;while(102.57±6.88)min,(146.33±19.47)ml and(16.78±2.32)cm in RA group,respectively.RSNA group was better than RA group(P＜0.05).No deep vein thrombosis occurred in both groups at 2 weeks after operation,5 patients occurred intermuscular vein throm-bosisin in RSNA group and 8 patients in RA group,the difference was not statistically significant(P＞0.05).In RSNA group,HKAA,LDFA and MPTA were(173.00±5.54)°,(86.96±3.45)°,(82.79±3.35)° before operation,and(178.34±1.85)°,(89.92±0.42)°,(89.84±0.73)° at 1 week after operation,respectively.In RA group,HKAA,LDFA and MPTA were(173.31±6.48)°,(87.15±3.40)° and(82.99±3.05)° before operation,and(178.52±1.79)°,(90.03±0.39)° and(90.15±0.47)° at 1 week after operation,respectively.HKAA,LDFA and MPTA were significantly improved in both groups at 1 week after oper-ation(P＜0.05).There were no significant difference in HKAA,LDFA,MPTA and PTS between two groups before operation and 1 week after operation(P＞0.05).There was no significant difference in deviation distribution of HKAA at 1 week after op-eration(x2=2.61 1,P=0.456).There were no significant difference in WOMAC and KSS between two groups before operation,3 and 6 months after operation(P＞0.05),and postoperative WOMAC and KSS at 3 and 6 months between two groups were im-proved compared with those before operation(P＜0.05).Conclusion Both RA and RSNA system assisted TKA could obtain ac-curate osteotomy,RA has higher surgical accuracy,RSNA system assisted operation has less trauma,and operation is simpler.

Objective To explore clinical accuracy of remote sensing navigation alignment(RSNA)system in total knee arthroplasty(TKA)and its influence on postoperative clinical efficacy.Methods From May 2021 to May 2022,60 knee os-teoarthritis(KOA)patients with Kellgren-Lawrence(K-L)grade Ⅲ to Ⅳ treated by unilateral primary TKA were selected and divided into RSNA group and traditional operation group according to treatment methods,and 30 patients in each group.There were 6 males and 24 females in RSNA group,aged from 55 to 86 years old with an average of(68.06±8.23)years old;body mass index(BMI)ranged from 22.15 to 34.58 kg·m-2 with an average of(28.20±3.01)kg·m-2;the courses of disease ranged from 2 to 60 months with an average of(18.80±14.80)months;13 patients with grade Ⅲ and 17 patients with grade Ⅳaccording to K-L grading.In traditional operation group,there were 8 males and 22 females,aged from 57 to 85 years old with an average of(67.26±6.32)years old;BMI ranged from 23.94 to 34.55 kg·m-2 with an average of(27.49±2.32)kg·m-2;the courses of disease ranged from 3 to 60 months with an average of(21.30±16.44)months;14 patients with grade Ⅲ and 16 pa-tients with grade Ⅳ according to K-L grading.Western Ontario and McMaster Universities(WOMAC)osteoarthritis index and Knee Society score(KSS)were used to evaluate functional recovery of patients.Hip-knee-ankle angle(HKAA),distal femoral valgus angle(FVA)and distal fermoral flexion angle(DFFA)were measured before operation.HKAA and HKAA deviation angle were measured at 1 week after operation,and defective rate of lower limb force line,femur prosthesis valgus angle(FP-VA)and femoral prosthesis flexion angle(FPFA),respectively,were calculated.Results There were no serious complications such as vascular and nerve injury during operation,and wound healed at stage Ⅰ.Both groups were followed up for 6 months.There were no significant difference in WOMAC index,KSS,HKAA,FVA and DFFA between two groups before operation(P＞0.05).The force line defect rate,HKAA,HKAA deviation angle,FPVA deviation angle and FPFA of RSNA group were 6.7％,(178.74±1.56)°,(1.25±1.56)°,(1.84±0.16)° and(4.85±2.46)°,respectively;while in traditional operation group were 20％,(176.73±3.46)°,(3.27±3.46)°,(2.44±0.26)°,(6.60±1.86)°;the difference between two groups were statistically sig-nificant(P＜0.05).There were no significant difference in WOMAC index and KSS between two groups at 3 and 6 months after operation(P＞0.05).Conclusion RSNA system could reduce defective rate of lower limb force line,FPVA deviation angle and FPFA after TKA,which is more accurate and easy to operate than traditional intramedullary localization surgery while ensuring postoperative efficacy.

Objective To analyze the concentration and exposure of vancomycin in children with gram-positive coccal infection,and the corresponding clinical efficacy and safety to support rational use of vancomycin in children.Methods We prospectively collected the clinical and laboratory data of 87 children with gram-positive coccal infection in the Children's Hospital of Fudan University from January 2012 to March 2021.Therapeutic drug monitoring(TDM)was conducted for vancomycin simultaneously,to acquire the data of serum through concentration(Cmin),peak concentration(Cmax),the area under the drug concentration-time curve in a 24-h interval(AUC0-24h)and the ratio ofAUC0-24h to the minimum inhibitory concentration(AUC0-24h/MIC).Results The median(P25,P75)age of the children enrolled in this study was 3.60(1.20,20.00)months.The median dose of vancomycin was 39.23(30.00,46.51)mg/kg.The median serum Cmin was 3.30(1.50,7.10)mg/L.Cmin achieved the target(5-15 mg/L)in 23 cases(26.4％).The median AUC0-24h was 213(174,293)mg·h/L and the median AUC0-24h/MIC was 221(128,349).Adaily dose of above 60 mg/kg in children could achieve the median value of AUC0-24h and AUC0-24h/MIC greater than 400,and the corresponding median age was 28.50(6.85,36.00)months.Multivariate logistic analysis showed a good correlation between Cmin and AUC0-24h(P=0.002).At the end of treatment,the clinical efficacy rate was 85.1％(74/87)and the bacterial eradication rate was 95.4％(83/87).No renal injury occurred during the treatment.Conclusions In this study,the median daily dosage,Cmin and A UC0-24h/MIC of vancomycin were below the recommended range at home and abroad.However,good clinical and microbiological efficacy were achieved in children at low vancomycin exposure.The probability of target attainment(PTA)for A UC0-24h and AUC0-24h/MIC ≥400 increased when the daily dose of vancomycin was＞60 mg/kg(corresponding to the median age of 28.50 months)or Cmin ≥ 5 mg/L.

Objective:To evaluate the safety of patients with hepatic adenoma undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:A retrospective analysis of the clinical characteristics and prognosis of eight patients with hepatic adenoma who underwent allo-HSCT in the Hematology Department of Peking University People’s Hospital from January 2010 to March 2024 was conducted.Results:Of the eight patients who underwent allo-HSCT with hepatic adenoma, one patient was considered MDS-h transfusion-dependent and seven had aplastic anemia. The median age of the patients was 23 years (13-48 years). The median time from the diagnosis of AA or MDS to transplantation was 14 years (6-24 years), whereas the median time from taking androgens to diagnosing hepatic adenoma was 9 years (5-13 years). Six cases underwent haplo-HSCT, one case underwent matched unrelated donor HSCT, and one case underwent matched related donor HSCT. All patients achieved neutrophil engraftment at a median time of 11.5 days (11-20 days) and PLT engraftment within 60 days at a median of 19 days (10-37 days) after haplo-HSCT. Moreover, seven patients developed CMV anemia after transplantation, three patients had hemorrhagic cystitis, and two patients developed acute GVHD. During and after transplantation, eight patients did not show severe liver function damage or rupture of hepatic adenoma. In relation to imaging size, four patients showed varying degrees of reduction in hepatic adenoma size after transplantation, whereas four patients did not show significant changes in hepatic adenoma size after transplantation. The median follow-up time was 540.5 (30-2 989) days. Of the eight patients, six survived and two died. Furthermore, no direct correlation was observed between death and hepatic adenoma.Conclusion:Patients with hepatic adenomas undergoing allo-HSCT are not contraindications for transplantation, which will not increase transplant-related mortality.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood. Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival. Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group.Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity. Conclusions The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.