ObjectiveTo investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase （FAH） in the progression of glioblastoma （GBM）. MethodsDifferential expression analysis was performed on the TCGA-GBM， GSE4290， and GSE116520 datasets. Weighted gene co-expression network analysis （WGCNA） was used to identify key modules， and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments， and pathway analysis was performed to explore the underlying mechanisms. ResultsA total of 152 overlapping genes were identified across the three GBM datasets （P<0.05）. WGCNA revealed that the turquoise module was most strongly associated with tumor purity， stromal score， immune score， and ESTIMATE score （P<0.001）. Compared with normal tissues， three prognostic genes （CTSD， FAH， and THBD） were upregulated in GBM and correlated with immune infiltration （P<0.05）. FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues， and its expression was significantly associated with age stratification and TP53 mutation （P<0.05）. CCK-8 assay results showed that， compared with the shNC group， the proliferative activity of GBM cells in the shFAH group was reduced （P<0.001）. Transwell migration and invasion assays demonstrated that， relative to the shNC group， the numbers of migrated and invaded cells in the shFAH group decreased （P<0.05）. Western blot analysis revealed that the protein expression levels of PI3K， p-AKT， and p-mTOR in the shFAH group decreased compared with those in the shNC group （P<0.05）. In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group （P<0.001）. ConclusionFAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.

Objective:To evaluate the effectiveness and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with stage 4/M neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter clinical trial conducted by Sun Yat-sen Memorial Hospital, Children′s Hospital of Nanjing Medical University, Children′s Hospital, Zhejiang University School of Medicine, the First Affiliated Hospital of Guangxi Medical University, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. From March, 2019 to August, 2023, 25 children with confirmed with stage 4/M NB and received allo-HSCT were enrolled. The patients received either unrelated cord blood transplantation (UCBT) or peripheral blood stem cell transplantation (PBSCT). Conditioning regimens for UCBT was fludarabine+busulfan+cyclophosphamide+topotecan, and for PBSCT was fludarabine+busulfan+melphalan+thiotepa+antithymocyte globulin, respectively. Until the last follow-up date of September, 2023, the overall survival (OS) rate and event free survival (EFS) rate were analyzed to evaluate efficacy. The engraftment rate and transplant-related complications were statistically assessed to evaluate safety. Survival analysis was performed using the Kaplan-Meier method.Results:Of the 25 patients, there were 15 males and 10 females. The age at transplantation was 5.7 (3.8, 7.3) years. The engraft rate was 100%, with recovery time of neutrophil as 15.7 (12.5, 17.0) d, and the recovery time of platelets as 33.5 (18.0, 48.0) d. Seventeen of the 25 children (68%) developed acute graft versus host disease (aGVHD), occurred at 18.0 (13.0, 22.5) d after transplantation, including 13 of grade Ⅲ-Ⅳ cases. The main sites of aGVHD were skin and intestinal tract. After treatment, 13 cases improved, 4 patients developed chronic graft-versus-host disease (cGVHD). After allo-HSCT, 14 children received maintenance therapy. Twenty of the 25 patients survived, the 2-year cumulative OS rate was (80±9)%, and 2-year EFS rate was (56±11)%. Nine cases (36%) relapsed, the time from allo-HSCT to disease relapse was 10.9 (5.5, 16.0) months. Five cases (20%) died. The hematopoietic stem cell transplantation associated mortality rate was 4% (1/25).The 2-year OS rate of patients who had partial remission prior to allo-HSCT was significant lower than those who had complete remission prior to allo-HSCT ((33±25)% vs. 100%, P=0.037). Conclusion:allo-HSCT is an effective treatment for patients with stage 4/M NB.

Objective To explore the effect of Echinetin(ECH)pretreatment on alleviating intestinal bar-rier dysfunction caused by severe acute pancreatitis(SAP).Methods Totally 36 rats were randomly divided into Sham group,SAP group and SAP+ECH group,with 12 rats in each group.Pancreatitis was induced by retrograde injection of 3％sodium taurocholate into pancreatic duct.Histological examination was performed on the pancreas of experimental rats to determine whether the pancreatitis model of rats was successfully con-structed.Intestinal barrier function was evaluated by intestinal pathological scores,serum diamine oxidase(DAO)activity and endotoxin levels,and bacterial translocation in mesenteric lymph nodes.The mRNA and protein expression levels of tight junction proteins ZO-1 and occludin were detected by quantitative fluorescent PCR(qPCR)and Western blot,and the protein expression levels of high mobility frame-1 protein(HMGB1),Toll-like receptor 4(TLR4)and protein kinase R(PKR)were detected by Western blot.Results ECH had no significant effect on the histological changes of pancreas,but could improve the intestinal mucosal barrier damage and membrane permeability associated with SAP.Although ECH does not affect the mRNA expres-sion levels of ZO-1 and occludin in ileum of SAP rats,it could significantly increase the expression levels of ZO-1 and occludin,and ECH treatment could significantly reduce the expression levels of HMGB1,TLR4 and PKR in ileum of SAP rats.Conclusion ECH can reduce the intestinal barrier dysfunction induced by SAP,and its effect on intestinal barrier function may be related to the inhibition of the HMGB1/TLR4/PKR pathway.

Objective To investigate the value of gut metabolites in predicting the development of severe acute pancreatitis(SAP),myocardial injury,and adverse outcomes in patients with acute pancreatitis(AP).Methods A total of 80 SAP patients admitted to Cangzhou Hospital of Integrated Chinese and Western Medicine from April 2023 to April 2024 were selected as the severe group,and 80 non-severe AP patients were selected as the non-severe group.The levels of serum amylase,lipase,acetic acid,propionic acid,butyric acid,and total short-chain fatty acids(SCFAs)in feces,serum bile acid(BA),trimethylamine n-oxide(TMAO),myocardial injury-related indicators[creatine kinase isoenzymes(CK-MB),cardiac troponin T(cTnT),N-terminal pro-b-type natriuretic peptide(NT-proBNP)],C-reactive protein(CRP),acute physiology and chronic health evaluation II(APACHE II)and bedside index for severity in acute pancreatitis(BISAP)were compared between the two groups at admission.Patients in the severe group were followed up for 30 days and divided into a survival subgroup(n=61)and a non-survival subgroup(n=19)based on their prognosis.The levels of total SCFAs,BA,and TMAO were compared between these two subgroups.Spearman correlation analysis was used to analyze the correlation of serum amylase,lipase,total SCFAs,BA,and TMAO levels with myocardial injury-related indicators and disease severity scores in all patients.Multivariate logistic regression analysis was used to identify the influencing factors for the occurrence of SAP.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of total SCFAs,BA,TMAO,and their combination for the occurrence of SAP.Results Compared with the non-severe group,the severe group had significantly lower levels of acetic acid,propionic acid,butyric acid,and total SCFAs(P<0.01),and significantly higher levels of BA,TMAO,CK-MB,cTnT,NT-proBNP,CRP,and APACHE II and BISAP scores.Within the severe group,the non-survival subgroup had significantly lower levels of total SCFAs(P<0.05)and significantly higher levels of BA and TMAO(P<0.05)compared to the survival subgroup.Spearman analysis showed that the levels of CK-MB,cTnT,NT-proBNP,CRP,and the APACHE II and BISAP scores were negatively correlated with total SCFAs levels and positively correlated with BA and TMAO levels(P<0.001).Multivariate logistic regression analysis revealed that total SCFAs,BA,and TMAO were independent influencing factors for the occurrence of SAP(P<0.05).ROC curve analysis showed that the area under the curve(AUC)for total SCFAs,BA,TMAO,and their combination in predicting the occurrence of SAP were 0.951,0.797,0.790,and 0.974,respectively(P<0.001).The AUC for the combination of the three markers was larger than that of any single marker,indicating good predictive efficacy.Conclusion The levels of gut metabolites SCFAs,BA,and TMAO in SAP patients are independent factors associated with myocardial injury and prognosis.

Objective:To evaluate the effectiveness and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with stage 4/M neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter clinical trial conducted by Sun Yat-sen Memorial Hospital, Children′s Hospital of Nanjing Medical University, Children′s Hospital, Zhejiang University School of Medicine, the First Affiliated Hospital of Guangxi Medical University, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. From March, 2019 to August, 2023, 25 children with confirmed with stage 4/M NB and received allo-HSCT were enrolled. The patients received either unrelated cord blood transplantation (UCBT) or peripheral blood stem cell transplantation (PBSCT). Conditioning regimens for UCBT was fludarabine+busulfan+cyclophosphamide+topotecan, and for PBSCT was fludarabine+busulfan+melphalan+thiotepa+antithymocyte globulin, respectively. Until the last follow-up date of September, 2023, the overall survival (OS) rate and event free survival (EFS) rate were analyzed to evaluate efficacy. The engraftment rate and transplant-related complications were statistically assessed to evaluate safety. Survival analysis was performed using the Kaplan-Meier method.Results:Of the 25 patients, there were 15 males and 10 females. The age at transplantation was 5.7 (3.8, 7.3) years. The engraft rate was 100%, with recovery time of neutrophil as 15.7 (12.5, 17.0) d, and the recovery time of platelets as 33.5 (18.0, 48.0) d. Seventeen of the 25 children (68%) developed acute graft versus host disease (aGVHD), occurred at 18.0 (13.0, 22.5) d after transplantation, including 13 of grade Ⅲ-Ⅳ cases. The main sites of aGVHD were skin and intestinal tract. After treatment, 13 cases improved, 4 patients developed chronic graft-versus-host disease (cGVHD). After allo-HSCT, 14 children received maintenance therapy. Twenty of the 25 patients survived, the 2-year cumulative OS rate was (80±9)%, and 2-year EFS rate was (56±11)%. Nine cases (36%) relapsed, the time from allo-HSCT to disease relapse was 10.9 (5.5, 16.0) months. Five cases (20%) died. The hematopoietic stem cell transplantation associated mortality rate was 4% (1/25).The 2-year OS rate of patients who had partial remission prior to allo-HSCT was significant lower than those who had complete remission prior to allo-HSCT ((33±25)% vs. 100%, P=0.037). Conclusion:allo-HSCT is an effective treatment for patients with stage 4/M NB.

Medical mutual aid is an important component of multi-level medical security system. West China Second University Hospital of Sichuan University led the establishment of the pediatric specialty alliance " West China Women and Children Alliance". Based on customized and inclusive mutual insurance product " Family Doctor Mutual Aid Plan", the alliance implemented key links such as mutual aid product forms, patient risk protection, institutional financing and hematopoiesis, and distribution of benefits to all parties, explored innovative mutual aid funding, payment, and incentive mechanisms, forming a closed-loop pediatric tiered diagnosis and treatment service system with the Mutual Aid Plan as the core. This system operated continuously under the " Four-in-One" framework, stimulating the integration of medical insurance and service supply systems while enhancing the synergistic effect between mutual insurance and social security. It has formed a distinctive health-centered multi-level medical security system within the alliance, and could provide reference for the construction and exploration of hierarchical diagnosis and treatment system.

Objective: To preliminarily develop Health Literacy Scale for pupils, providing a tool for dynamic monitoring and related health literacy research among pupils. Methods: Through policy and literature review, the health literacy evaluation index system of pupils was established. Through two rounds of expert consultation, the evaluation index system and scale item pool of three levels in primary school were formed, and "Evaluation Scale 1.0" was developed. Through two panel discussions, health education experts, teachers and students were invited to provide advices on the content, expression and structure of scale 1.0, turning it into "Evaluation Scale 2.0", and completing the preliminary development of the scale. Results: The health literacy assessment index system of primary school students includes three levels，including level-1 was Grade 1-2, level-2 was Grade 3-4,level-3 was Grade 5-6, covering two level indexes. The scale for primary school students contained five horizontal dimensions and four vertical dimensions. In the Delphi consultation, the response rate was 100%, and the authority coefficient was 0.85. After item selection and modification, the final version of level-1, level-2 and level-3 scales contained 36, 44 and 50 items respectively. Conclusion The development of Health Literacy Evaluation Scale for pupils has high applicability and practical value.

IgG4-related diseases have a low incidence and are easily misdiagnosed as tumors in clinical treatments. A 26-year-old male patient was admitted to the hospital because of a left adrenal tumor found in health examination for more than 5 months. The tumor in the left adrenal region could be seen from abdominal CT, and the retroperitoneal laparoscopic resection of the left adrenal tumor was performed. Postoperative pathology was consistent with IgG4-related diseases, and serum IgG4 was abnormally high. After 2 months’ follow-up, serum IgG4 returned to normal, and no special discomfort.

OBJECTIVE: To compare the clinical application and health economic values of non-invasive prenatal testing (NIPT) and second trimester serum screening (STSS). METHODS: A retrospective analysis was carried out on 54 026 singleton pregnant women undergoing NIPT and STSS from March 1, 2018 to December 31, 2019 in Changsha Maternal and Child Health Care Hospital. For pregnant women with high-risk results of NIPT, prenatal diagnosis and follow-up of pregnancy outcomes were conducted. The data was grouped to 4 screening models, and their cost-benefit was analyzed. RESULTS: The sensitivity, specificity and positive predictive value of NIPT were all higher than STSS. Screening models 1 to 4 have prevented the birth of 71, 29, 52 and 54 patients with Down syndrome, respectively. The safety index of screening models 1 to 4 were 0.0036, 0.3944, 02215 and 0.1281, respectively. When the price of NIPT was decreased to 600 RMB, the cost-benefit of the screening models 1 to 4 was 0.46, 0.65, 0.44 and 0.40 million RMB, respectively. CONCLUSION NIPT has a better detection performance than STSS. When the price of NIPT is 600 RMB, screening model 1 has the best screening effect and the highest accuracy, safety index and health economical value.
Child ; China ; Cost-Benefit Analysis ; Down Syndrome/diagnosis* ; Female ; Humans ; Pregnancy ; Prenatal Diagnosis/methods* ; Retrospective Studies

Objective:To evaluate the effectiveness and safety of transepithelial photorefractive keratectomy (TransPRK) assisted by smart pluse technology (SPT) for the correction of high myopia.Methods:An observational case series study was conducted.Sixty high myopic patients (107 eyes) with spherical equivalent (SE)≥-6.0 D who received TransPRK assisted by SPT from January to December 2016 in Eye Hospital of Wenzhou Medical University were enrolled.Uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) of the patients were examined and recorded in logarithm of the minimum angle of resolution (LogMAR) units, and refraction was examined with a subjective refractometer.The healing of corneal epithelium and corneal haze was observed with a slit lamp.Intraocular pressure (IOP) was measured with the non-contact tonometer.Safety index (SI) and efficacy index (EI) were analyzed.The follow-up time was 12 months.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Eye Hospital of Wenzhou Medical University (No.2019-197-k-177). Written informed consent was obtained from each patient prior to any medical examination.Results:The mean epithelial healing time was (3.77±1.02) days.There were statistically significant differences in UCVA and BCVA between before and after surgery ( Z=380.812, 267.313; both at P<0.001). And the 7-day, 6-month, and 12-month postoperative BCVA were better than preoperative BCVA, showing statistically significant differences (all at P<0.05). Mean SI was 1.10±0.12, and mean EI was 1.05±0.17 at 12 months after surgery.There was no significant difference between the attempted SE before surgery (-8.02±1.36)D and the achieved SE at 12 months after surgery (-8.04±1.51)D ( P=0.523). SE in the predictive range within ±0.50 D accounted for 79% (85/107) and that within ±1.0 D accounted for 92% (98/107). The IOP was slightly increased in 3 eyes at 7 days and 7 eyes at 1 month after surgery, respectively, which returned to normal after the use of ophthalmic solution for lowing IOP.The incidence of haze severer than grade 1 was less than 1% (1 eye), and haze gradually disappeared after application of drugs. Conclusions:TransPRK assisted by SPT for high myopia shows good safety, effectiveness and predictability.It is an ideal corneal surface surgery to correct high myopia.