Mutations in CD2AP, mapped to 6pL2. 3 and encoding CD2 - associated protein ( CD2AP), are responsible for autosomal recessive or autosomal dominant steroid - resistant nephrotic syndrome (SRNS). CD2AP plays a key role in the slitdiaphragm network of the kidney, which is necessary for the structure and ultrafiltration functions of the slitdiaphragm. The CD2AP homozygous mutation results in early - onset SRNS while heterozygous expression of the CD2AP mutation has increased susceptibility to glomerular injury.No recurrence of proteinuria was observed in the patient with SRNS with CD2AP homozygousmutationafter the renal transplantation. Therefore, detection of the CD2AP gene in the patients suffering from SRNS will be beneficial to making therapeutic decisions and predicting prognoses.

Objective To elucidate the mutations of NPHS1 gene in children with sporadic steroid-resistant nephrotic syndrome (SRNS) in Southern Chinese Han ethnic group.Methods Peripheral blood samples were collected for genetic analysis from 40 patients with sporadic SRNS and 50 healthy volunteers as control.Genomic DNA was isolated from peripheral blood leucocytes.Twenty-nine exons and exon-intron boundaries of the NPHS1 gene were amplified by polymerase chain reaction.Mutational analysis was performed by DNA sequencing directly.Results Seven variants,928G＞A(D310N),2677A＞G (T893A),2869G＞C (V957L),IVS8+30C＞T,IVS21+14G＞A,IVS25-23C＞T and *142T＞C,of NPHS1 gene were found in 6 of 40 children with sporadic SRNS,whereas they were not found in 50 healthy controls.2677A ＞G,IVS8 +30C ＞T,IVS21 +14G＞A,IVS25-23C ＞T and *142T＞C were novel.Moreover,thirteen already reported NPHS1 polymorphisms,294C＞T,349G＞A,IVS3+15C＞T,IVS3+61A＞G,803G＞A,IVS8+68A＞G,1339G ＞A,1802G ＞C,2223C ＞T,2289C ＞T,IVS24 +36C ＞T,3315G＞A and IVS27 +45C ＞T,were detected in some patients and controls. Conclusions NPHS1 mutations in 6 of 40 children with sporadic SRNS in Southern Chinese Han ethnic group (15％) are detected.NPHS1 mutations are existed in Southern Chinese children,so it is necessary to perform the mutation analysis of NPHS1 gene in those children patients.

Objective To build a multi‐level hierarchical structure model of the influencing factors for hierarchical medical system ,to identify the role relationship between all the factors and transmission pathways ,and to recommend on developing China′s hierarchical medical system . Methods Thirty influencing factors were identified in a screening based on literature review for the hierarchical medical system .On such basis ,16 influencing factors were identified by three health policy experts ,which affect operations of the current system .Interpretative structural modeling was called into play in the end to analyze the hierarchy relationship between various influencing factors and the conduction loops .Results There exist among the 16 factors a 3‐level hierarchical structureand two conduction loops .The factor directly limiting the hierarchical medical system is two‐way referral,and most internal core drivers arehuman resources development and governance mechanism.By means of self‐growth and external constraints ,they exert their influence on the operation of hierarchical medical system .Conclusions There are interactive hierarchical effects among the factors ,merging into three node elements of functional role,inter‐entity relationshipand patient participation.

The main work and achievements of clinical pathway work in China since 2009 were systematically reviewed in the paper. It analyzed the problems existing in the implementation of clinical pathway management in China, and suggested on such management in the future. The suggestions include:deeper understanding, convergence with the payment system reform, strengthened quality control, further informatization,and better performance appraisal system.

PURPOSE: Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation. METHODS: C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. RESULTS: Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol. CONCLUSIONS Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.
Humans ; Animals ; Mannitol/pharmacology* ; Brain Edema ; Neural Stem Cells/metabolism* ; MAP Kinase Signaling System ; p38 Mitogen-Activated Protein Kinases/pharmacology* ; Cell Proliferation