Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective To establish a classification tree model for non-alcoholic fatty liver disease(NAFLD)among aircrews,screen for influencing factors of NAFLD,so as to provide scientific basis for prevention and intervention decisions for NAFLD.Methods Aircrews who underwent recuperation at a sanatorium from January 2019 to December 2023 were selected as the research objects.Their annual physical examination data were collected and the NAFLD detection rate was calculated.Age,body mass index(BMI),blood pressure,waist circumference,blood routine,biochemistry indexes,and thyroid function were incorporated,and a NAFLD risk model was constructed using classification regression tree method.The predictive performance of the NAFLD classification tree model was evaluated through model misclassification matrix,risk statistics,and receiver operating characteristic curve.Results A total of 4088 aircrews were included in the study,and NAFLD was detected in 380 persons(380/4088,9.30%).The NAFLD model consisted of three layers,and five explanatory variables affecting the onset of NAFLD were extracted,including BMI,triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),and total bilirubin(TBIL).BMI was located at the top of the classification tree and was the most important risk factor for NAFLD in aircrews.The area under the curve(AUC)of the model was 0.853.The predictive accuracy of NAFLD was 90.9%,indicating that the model has good accuracy and fitting effect.Conclusion In this study,the detection rate of NAFLD in aircrews was 9.30%.BMI,TG,HDL-C,ALT,and TBIL are risk factors for the onset of NAFLD.NAFLD is mainly related to weight gain and lipid metabolism disorders caused by unhealthy lifestyles.

Strengthening the cultivation of innovation ability is the new requirement put forward by the state for higher educa-tion.High-quality curriculum design is the primary means of achieving high-quality talent cultivation.By constructing the"disease case library"and"problem graph"of immune system and related diseases,and adopting the teaching method of"combining large and small cases and integrating online and offline",this study not only consolidates students'basic knowledge,but also builds a bridge for students from theory to practice,from knowledge accumulation to creation and application.It further exercises students'ability to dis-cover,analyze and solve problems,and enhances students'innovation awareness and ability.

Objective:To systematically evaluate studies validating the performance of the Global Leadership Initiative on Malnutrition (GLIM) in diagnosing malnutrition.Methods:Seven Chinese and English databases including Embase, Web of Science (WOS), PubMed, CINAHL, Cochrane Library, SinoMed, CNKI, Wanfang Data, and VIP Database were searched for articles on the validation of GLIM criteria published between September 2018 and September 2024. Two researchers independently performed literature screening and data extraction. The concurrent and predictive validity of the criteria was analyzed.Results:A total of 136 papers were included for analysis. The GLIM criteria for diagnosing malnutrition had a sensitivity of 77%, a specificity of 87%, and an area under the curve (AUC) of 0.90. Malnutrition diagnosed by the GLIM criteria predicted prolonged hospital and intensive care unit (ICU) stays, increased readmission and complication rates (both overall and infectious), reduced survivals (median, overall, and disease-free), and increased in-hospital and follow-up mortalities. Both moderate and severe malnutrition predicted decreased overall survival. However, only three studies analyzed the impact of nutritional therapy on the clinical outcomes of malnourished patients.Conclusions:The GLIM criteria accurately differentiate malnutrition and are a valid predictive tool of clinical outcomes. However, the validity criteria in these validation studies were questionable, along with high methodological heterogeneity. Furthermore, there is a lack of studies validating the role of nutritional therapy in improving the clinical outcomes of malnourished patients.

Objective:To systematically evaluate studies validating the performance of the Global Leadership Initiative on Malnutrition (GLIM) in diagnosing malnutrition.Methods:Seven Chinese and English databases including Embase, Web of Science (WOS), PubMed, CINAHL, Cochrane Library, SinoMed, CNKI, Wanfang Data, and VIP Database were searched for articles on the validation of GLIM criteria published between September 2018 and September 2024. Two researchers independently performed literature screening and data extraction. The concurrent and predictive validity of the criteria was analyzed.Results:A total of 136 papers were included for analysis. The GLIM criteria for diagnosing malnutrition had a sensitivity of 77%, a specificity of 87%, and an area under the curve (AUC) of 0.90. Malnutrition diagnosed by the GLIM criteria predicted prolonged hospital and intensive care unit (ICU) stays, increased readmission and complication rates (both overall and infectious), reduced survivals (median, overall, and disease-free), and increased in-hospital and follow-up mortalities. Both moderate and severe malnutrition predicted decreased overall survival. However, only three studies analyzed the impact of nutritional therapy on the clinical outcomes of malnourished patients.Conclusions:The GLIM criteria accurately differentiate malnutrition and are a valid predictive tool of clinical outcomes. However, the validity criteria in these validation studies were questionable, along with high methodological heterogeneity. Furthermore, there is a lack of studies validating the role of nutritional therapy in improving the clinical outcomes of malnourished patients.

Strengthening the cultivation of innovation ability is the new requirement put forward by the state for higher educa-tion.High-quality curriculum design is the primary means of achieving high-quality talent cultivation.By constructing the"disease case library"and"problem graph"of immune system and related diseases,and adopting the teaching method of"combining large and small cases and integrating online and offline",this study not only consolidates students'basic knowledge,but also builds a bridge for students from theory to practice,from knowledge accumulation to creation and application.It further exercises students'ability to dis-cover,analyze and solve problems,and enhances students'innovation awareness and ability.

Objective:To develop a candidate reference method for cortisol in human serum by isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC/MS/MS).Methods:An isotope-labeled internal standard was added to samples, followed by alkalizing with sodium carbonate solution and liquid-liquid extraction with n-hexane/ethyl acetate. Isoelution with a methanol aqueous solution was employed for liquid chromatographic separation, while ESI in the positive ion and multiple reaction monitoring mode were used for mass spectrometry. The volume of sample, standard, and internal standard solutions were all controlled by weighing, and the results were calculated by bracketing method. The accuracy, precision, specificity, linearity, LOD and LOQ of this method were evaluated referring to the CLSI C62-A and C50-A guidelines and the domestic expert consensus documents.Results:The method demonstrated excellent accuracy and precision with the bias of ERM-DA192, ERM-DA193 and RELA 2021-2023 all being less than 2%. The recovery of added cortisol ranged from 98.2% to 101.1%. Both intra- and inter-assay imprecisions was <2%. The method was free from interference by structural analogue and showed a good linearity in the range of 25-1 600 nmol/L. The LOD and LOQ were 0.5 nmol/L and 1.0 nmol/L, respectively. A cortisol assay kit (chemiluminescence immunoassay) traced to this candidate reference method was used to determine 46 clinical serum samples concurrently, and the two methods exhibited good correlation.Conclusions:A candidate reference method for the determination of cortisol in serum was established, demonstrating high sensitivity, good repeatability and accuracy. This method can serve as a reference for the measurement traceability and accuracy evaluation of routine methods.

Objective To explore potential genes associated with the pathogenesis of hypospadias using weighted Gene co-expression network analysis(WGCNA).Methods The WGCNA algorithm was used to process the hypospadias-related dataset GSE35034,and then a gene co-expression weight network was constructed to screen the modules with the highest correlation with hypospadias,and the genes in the modules were enriched and detected by gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG).Differential analysis was also performed to screen out differential genes.The differential genes were imported into the String database.Using Cytoscape software,the hub genes in the network were identified.The results screened by the above three methods were combined and analyzed,and the core genes in the intersection set were screened.Using the external dataset GSE121712,the core genes were verified by mRNA expression changes and subject work characterization receiver operating characteristic(ROC)curve diagnosis.Results Fifteen co-expression modules were obtained based on the WGCNA method.Ninety-three common differential genes meeting the conditions were obtained by differential analysis.Ten core genes were finally obtained by Cytoscape software analysis.Finally MEbrown module,differential genes and the 10 core genes yielded a total of 2 intersecting genes:FBXL16 and SYNDIG1.ROC curves verified that the intersecting genes were differentially expressed in patients with hypospadias versus normal subjects.Conclusion In this study,two key genes with significant correlation with hypospadias were obtained by WGCNA,which may be used for the early diagnosis and treatment of hypospadias after further study.

Objective To establish and optimize a method for simultaneous determination for the contents of sodium,potassium,calci-um and magnesium ions in serum using microwave digestion combined with ion chromatography,and evaluate its performance.Methods Serum samples were pretreated by microwave digestion,and four cations were quantitatively determined using ion chromatography.The linearity,precision,recovery and accuracy of the established method were verified with reference to the EP6-A and EP15-A3 docu-ments issued by the Clinical and Laboratory Standards Institute(CLSI).Results The imprecisions of determinations for sodium,po-tassium,calcium and magnesium ions expressed as coefficient of variation(CV)were 0.10％to 0.36％,0.15％to 0.48％,0.22％to 0.87％and 0.21％to 0.73％,respectively.The recoveries with adding standard of the four cations were between 97.3％and 103.0％.Referred to RELA2020 and RELA2021,the deviations of the analysis results were-0.57％to-0.14％,-0.84％to-0.16％,-1.82％to-0.37％,and-0.60％to 0.34％for sodium,potassium,calcium,and magnesium,respectively,and all the comparisons were pas-sed.The limits of detection/quantification were 0.017 5/0.058 3 mmol/L,0.000 5/0.001 7 mmol/L,0.009 9/0.032 9 mmol/L and 0.001 1/0.003 5 mmol/L for the four cations,indicating that after pretreatment,no significantly interfere from other impurities for the results of determination was found.Conclusion A method for simultaneous determination of sodium,potassium,calcium and magnesi-um ions in serum was successfully established and optimized using microwave digestion combined with ion chromatography.The method showed good precision and accuracy,simple operation,short time consumption and low cost,thus it could be used for quality improve-ment of clinical electrolyte testing in serum.

Refractory angina is characterized by recurrent and persistent angina with a duration of not less than three months， which is related to reversible ischemia and hypoxia caused by coronary stenosis and obstruction. It mainly involves obstructive coronary artery disease and non-obstructive coronary artery disease with coronary artery spasm and coronary microvascular dysfunction. “Stasis and toxin” play an important role in the pathogenesis of cardiovascular diseases. The pathogenesis of stasis and toxin is stubborn filthy turbidity featured by slow accumulation and sudden onset，and rapid changes，which coincides with the characteristics of refractory angina which is complex and changeable，prolonged and difficult to cure. The pathogenesis of refractory angina involves a combination of underlying deficiency and excessive manifestation， with "stasis and toxin" playing a crucial role as an important pathological factor in the whole process of refractory angina. Traditional Chinese medicine （TCM） employs a holistic approach known as "activating blood circulation and removing toxins"， which is supplemented by various methods to tonify Qi and warm Yang， nourish the kidneys and invigorate the spleen， clear heat and transform phlegm. This approach applies anti-inflammatory measures， regulates lipid metabolism， inhibits oxidative stress and thrombus formation， protects endothelial function in blood vessels， as well as establishes collateral circulation for the prevention and treatment of refractory angina. Therefore，based on the theory of "stasis and toxin"，combined with TCM theory and modern medical research，this paper discusses the pathogenesis of refractory angina and the prevention and treatment strategy of TCM，and elucidates the reasons for the difficulty in curing refractory angina and the relationship between refractory angina and common angina pectoris，coronary microvascular dysfunction，coronary artery spasm and obstructive coronary artery disease，hoping to provide certain theoretical basis and clinical ideas for the prevention and treatment of refractory angina with TCM.