Objective To investigate the chemical constituents in sponge Tedania sp..Methods Solvent extraction,gel and silica column chromatography were used to separate the chemical constituents,the structures of whichwere identified by physicochemical properties and spectral analyses.Results Six compounds were isolated and their structures were identified as cholesterol(1),stearic acid(2),?-sitosterol(3),daucosterol(4),4-hydroxybenzoic acid(5)and thymidine(6).Conclusion Compounds 1,2,3,5 were first found from this marine invertebrate.

Objective To analyze the impact factors for early renal damage in type 2 diabetic patients by the classification tree model.Methods A total of 601 patients with type 2 diabetes were enrolled.According to glomerular filtration rates and urine albumin quantification,the patients were divided into type 2 diabetes group (418 cases) and early diabetic renal damage group (183 cases).The clinical data of the patients were recorded to analyze the main influential factors for the microalbuminuria of type 2 diabetic patients using the Exhaustive CHAID classification tree algorithm.Results Six important explanatory variables were screened out by the classification tree model from the 34 candidate variables related to early renal damage,including fibrinogen,history of hypertension,retinopathy,Cys C levels,SBP and peripheral neuropathy.Elevated fibrinogen was the main factor.Conclusion The classification tree model can analyze the major influential factors of early renal damage in type 2 diabetic patients effectively,and it can help develop the prevention and treatment methods.

Objective To analyze the prevalence,risk factors of kidney disease in type 2 diabetic patients with KDIGO classification of chronic kidney disease,also to study cardiovascular and cerebrovascular diseases and death in these patients,so as to investigate the significance of the KDIGO classification system.Methods One thousand six hundred and forty-five type 2 diabetic patients who were in hospitalization from June 2008 to December 2012 were grouped according to the KDIGO classification of chronic kidney disease and the incidence of vascular disease was analyzed based on the classification.Clinical features were compared between patients with or without kidney disease.The risk factors of kidney disease and the death of diabetic patients were also investigated.Results There were 915 male and 730 female,aged a median (57.86±12.54) years with (6.35±6.30) years duration of diabetes mellitus among the 1645 cases,and 37.2％ of patients had concomitant kidney disease.According to the classi fi cation of CKD,patients in CKD group 3a,group 3b and CKD group 4-5 accounted for 5.7％,3.5％ and 7.6％,while 33.4％ of patients had proteinuria,among which 19.5％ with microalbuminuria,13.5％ with macroalbuminuria.On complications,patients with hypertension accounted for 49.5％,hyperlipidemia 67.7％,diabetic retinopathy 27.4％,cardiovascular and cerebrovascular diseases 18.5％ (coronary artery disease 16.5％,cerebrovascular diseases 8.8％).Statistical difference was detected in the incidence of diabetic retinopathy,coronary artery disease and cerebrovascular diseases between CKD group 3a and 3b (P ＜ 0.05).The duration of diabetes,concomitant hypertention especially with elevated systolic blood pressure,diabetic retinopathy and hyperuricemia were the independent risk factors for type 2 diabetic patients with kidney disease.Age,Scr,complicating cardiovascular and cerebrovascular diseases and advanced CKD stage were the independent risk factors for the death of type 2 diabetic patients with kidney disease.Conclusion KDIGO classification of chronic kidney disease enables better staging of kidney diseases in diabetic patients for management and prognosis.Diabetic patients have a higher prevalence of renal diseases and cardiovascular and cerebrovascular events than the general population.Early control of factors such as blood pressure and serum uric acid can delay the progression of kidney disease,and the predictive role of diabetic retinopathy should be emphasized.

OBJECTIVES: To investigate the genotypes and biochemical phenotypes of neonates with abnormal metabolism of butyrylcarnitine (C4). METHODS: One hundred and twenty neonates with increased C4 levels detected by tandem mass spectrometry in the neonatal screening at Children's Hospital, Zhejiang University School of Medicine from January 2018 to June 2023 were included. The initial screening data and recalled data of C4 and C4/C3 were collected and converted into multiples of C4 reference range. Next generation sequencing was performed and the exons with adjacent 50 bp regions of ACAD8 and ACADS genes were captured by liquid phase capture technique. Variant information was obtained by bioinformatic analysis and the pathogenicity were classified according to the American College of Medical Genetics and Genomics criteria. The Wilcoxon rank sum test was used to analyze the differences in C4 levels among neonates with different variation types. RESULTS: In total, 32 variants in ACAD8 gene were detected, of which 7 variants were reported for the first time; while 41 variants of ACADS gene were detected, of which 17 variants have not been previously reported. There were 39 cases with ACAD8 biallelic variations and 3 cases with ACAD8 monoallelic variations; 34 cases with ACADS biallelic variations and 36 cases with ACADS monoallelic variations. Furthermore, 5 cases were detected with both ACAD8 and ACADS gene variations. Inter group comparison showed that the multiples of C4 reference range in initial screening and re-examination of the ACAD8 biallelic variations and ACADS biallelic variations groups were significantly higher than those of the ACADS monoallelic variations group (all P<0.01), while the multiples in the ACAD8 biallelic variations group were significantly higher than those in the ACADS biallelic variations group (all P<0.01). The multiples of C4 reference range in the initial screening greater than 1.5 times were observed in all neonates carrying ACAD8 or ACADS biallelic variations, while only 25% (9/36) in neonates carrying ACADS monoallelic variations. CONCLUSIONS ACAD8 and/or ACADS gene variants are the main genetic causes for elevated C4 in newborns in Zhejiang region with high genotypic heterogeneity. The C4 levels of neonates with biallelic variations are significantly higher than those of neonates with monoallelic variations. The cut-off value for C4 level could be modestly elevated, which could reduce the false positive rate in tandem mass spectrometry neonatal screening.
Child ; Humans ; Infant, Newborn ; Acyl-CoA Dehydrogenase/genetics* ; Genotype ; Phenotype ; Carnitine/metabolism* ; Mutation

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*