Possible PKHD1 Hot-spot Mutations Related to Early Kidney Function Failure or Hepatofibrosis in Chinese Children with ARPKD: A Retrospective Single Center Cohort Study and Literature Review.

PKHD1 mutations are generally considered to cause autosomal recessive polycystic kidney disease (ARPKD). ARPKD is a rare disorder and one of the most severe conditions leading to end-stage renal disease in childhood. With the biallelic deletion mutation, patients have difficulty in surviving the perinatal period, resulting in perinatal or neonatal death. This study retrospectively analyzed patient characteristics, imaging characteristics, laboratory examinations and family surveys from 7 Chinese children with different PKHD1 gene mutations diagnosed by high-throughput sequencing from January 2014 to February 2018. Of the 7 children, there were 3 males and 4 females. Eight missense mutations, two frameshift mutations, two deletion mutations, and two intronic slicing mutations were identified. Six of the mutations have not previously been identified. In the literature search, we identified a total of 29 Chinese children with PKHD1 mutations. The missense mutation c.2507T>C in exon 24 was found in one patient in our study, and five patients with liver fibrosis but normal renal function were reported in the literature. The missense mutation c.5935G>A in exon 37 was found in two patients in our study and three cases in the literature. Four patients had renal failure at an age as young as 1 year of those five patients with the missense mutation c.5935G>A in exon 37. It was concluded that: (1) Kidney length more than 2-3 SDs above the mean and early-onset hypertension might be associated with PKHD1-associated ARPKD; (2) The more enlarged the kidney size is, the lower the renal function is likely to be; (3) c.5935G>A may be a hot spot that leads to early renal failure in Chinese children with PKHD1 mutations; (4) c.2507T>C may be a hot-spot mutation associated with hepatic lesions in Chinese children with PKHD1.

Patient safety education among chinese medical undergraduates: An empirical study.

Patient safety education is conducive to medical students' cognition on patient safety and to improvement of medical quality and safety. Developing patient safety education for medical students is more and more widely recognized by World Health Organization and countries all over the world. However, in China, patient safety courses aiming at medical students are relatively few, and there are few reports about the effect of patient safety courses. This paper explored the influence of patient safety curriculum on medical students' attitude to and knowledge of patient safety. The patient safety curriculum was carried out for 2011-grade undergraduates of Tongji Medical College, Huazhong University of Science and Technology. The students participated in the class according to free choice. After the curriculum, the information of gender, major, attended course, attitude toward patient safety, and knowledge of laws and regulations of the 2011-grade undergraduates were collected. After rejecting invalid questionnaires, the number of undergraduates that participated in the survey was 112 (61 students did not take part in the curriculum; 51 took part in). Chi-square test was applied to analyze patient safety education's influence on medical students' attitude to patient safety and their knowledge mastery situation. The influence of patient safety education on the attitude of medical students to patient safety was not significant, but that on their knowledge of patient safety was remarkable. No matter male or female, as compared with medical students who had not accepted patient safety education, they both had a better acquisition of knowledge after having this education (for male students: 95% CI, 4.556-106.238, P<0.001; for female students: 95% CI, 3.183-33.238, P<0.001). Students majoring in Western Medicine had a relatively better mastery of knowledge of patient safety after receiving patient safety education (95% CI, 6.267-76.271, P<0.001). Short-term patient safety education cannot change medical students' stereotyped cognition on matters related to patient safety, but it can effectively enhance their knowledge of laws and regulations of patient safety.

Effects of tanshinone IIA on the transforming growth factor ß1/Smad signaling pathway in rat cardiac fibroblasts.

OBJECTIVES: This study explores the mechanism of tanshinone IIA (TSN)-mediated inhibition of myocardial fibrosis by investigating the effect of TSN on transforming growth factor ß1 (TGFß1) signal transduction in rat cardiac fibroblasts (CFs). MATERIALS AND METHODS: CFs were isolated from neonatal Sprague-Dawley rats by trypsin digestion and differential adhesion and stimulated with 5 ng/mL TGFß1 and TSN (10(-6), 10(-5), or 10(-4) mol/L). The expression of fibronectin (FN) mRNA in the CFs was determined using reverse transcriptase-polymerase chain reaction and the protein expression of FN and Smads in CFs was detected using Western blot. The intracellular expression and localization of Smads in the CFs were analyzed using immunocytochemistry. RESULTS: TGFß1 induced the expression of FN and Smads in a time-dependent manner. At the end of the culture treatment, the mRNA expression of FN and the expression of phosphorylated Smad2/3 (p-Smad2/3) increased significantly (P < 0.01). TSN pretreatment (10(-5) and 10(-4) mol/L) reduced the expression of FN and p-Smad2/3 (P < 0.01) following TGFß1 stimulation and led to a significant decrease in the nuclear staining intensity and a positive rate of p-Smad2/3 (P < 0.05 and P < 0.01, respectively). CONCLUSION: The inhibitory effect of TSN on myocardial fibrosis may be associated with its inhibition of TGFß1-induced Smad2/3 phosphorylation and p-Smad2/3 nuclear translocation, which blocks the TGFß1/Smad signaling pathway in CFs.

Twenty-three-year review of disease patterns from renal biopsies: an experience from a pediatric renal center.

BACKGROUND: The aim of this study was to investigate the clinical and pathological characteristics as well as their associations with trends for diseases in 1,579 pediatric renal biopsies from 1989 to 2012. METHODS: The clinical and pathological data were retrospectively analyzed for children undergoing renal biopsy from 1989 to 2012 in our hospital. RESULTS: Primary glomerulonephritis (PGN) accounted for 60.1% of total cases, followed by secondary glomerulonephritis (SGN) (31.2%) and hereditary nephropathy (8.3%). The major clinical patterns of PGN and SGN were nephritic syndrome (NS) and Henoch-Schönlein purpura nephritis (HSPN), respectively. Minimal change disease/mild disease (MCD/ML), IgAN and mesangial proliferative glomerulonephritis (MsPGN) were the most common pathological patterns of PGN. Male patients were most likely to suffer from NS, HBV-associated glomerulonephritis (HBVGN) or Alport syndrome, while females were most likely to suffer from isolated hematuria, rapidly progressive glomerulonephritis (RPGN), lupus nephritis (LN), ANCA-associated glomerulonephritis or thin basement membrane disease. The proportions of NS, isolated hematuria, acute nephritic syndrome, chronic nephritic syndrome, HBVGN, LN and hemolytic uremic syndrome changed significantly with aging. The clinical patterns of PGN were significantly correlated with the distribution of pathological types: MCD/ML and IgMN presented most often as NS; MCD/ML and IgAN presented most often as isolated hematuria; IgAN and MsPGN presented most often as hematuria with proteinuria. The spectrum of NS, HSPN, HBVGN and IgAN changed during the 23 years, and the percentage of repeated renal biopsies was low (1.2%) in pediatric cases with kidney disease. CONCLUSIONS: Glomerular diseases in children are closely related to age and sex of patient. The spectrum of kidney diseases from our center has changed significantly over the last 23 years.

Increased plasma acylation-stimulating protein in pediatric proteinuric renal disease.

Hyperlipidemia has been well recognized as a striking feature of nephrotic syndrome and other renal diseases. However, the underlying pathophysiological mechanisms still have not yet been elucidated. In this study, we evaluated acylation-stimulating protein (ASP) and complement component 3 (C3) in children (n=48) with various forms of proteinuric renal disease [nephrotic syndrome, acute poststreptococcal infection glomerulonephritis (APSGN), and lupus nephritis (LN)] in comparison with age- and gender-matched controls (n=279). In children with proteinuric renal disease, various aberrations in plasma lipids were noted, including increased triglyceride, cholesterol, and low-density lipoprotein cholesterol (LDL-C) (all p<0.0001). Whereas C3 was not altered in children with nephrotic syndrome (1.05+/-0.05 g/L vs. 1.29+/-0.04 controls), the decrease was pronounced in children with LN and APSGN (0.42+/-0.11, p<0.05 and 0.30+/-0.06, p<0.001, respectively). Plasma C3 correlated positively with lipid parameters [triglyceride, cholesterol, LDL-C, apolipoprotein B (apoB), high-density lipoprotein cholesterol (HDL-C) and apoA1] and inversely with total protein, blood urea nitrogen, and creatinine. By contrast, plasma ASP was significantly elevated in all proteinuric renal diseases (101.4+/-7.1 nmol/L nephrotic syndrome, 90.9+/-14.1 LN, and 81.8+/-7.2 APSGN vs. 44.3+/-1.5 controls, p<0.05 to p<0.001), and this increase was correlated with changes in lipid parameters (triglycerides and apoA1). In summary, these results demonstrate alterations in C3 and ASP that may contribute to or compensate for dyslipidemia.

[Clinical and pathological characterization of antineutrophil cytoplasmic antibody associated small vasculitis in children].

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA) associated small vasculitides (ASV) are rare in children and often complicated in clinical manifestations and have very poor prognosis. In order to deepen our understanding of ANCA-associated small vasculitis (ASV) in children, the present study aimed to characterize their clinical manifestations, serum ANCA and renal histopathological findings and outcomes in Chinese children. METHODS: Serum ANCA was qualitatively tested with indirect immunofluorescence microscopy and anti-proteinase 3 (PR(3)) and anti-myeloperoxidase (MPO) activity were quantitated by enzyme-linked immunosorbent assays (ELISA), and renal biopsies were done to investigate the pathological changes. The clinical manifestation, serum ANCA and renal histopathological findings and outcome were characterized in 5 children with ANCA associated small vasculitis. RESULTS: (1) Five children with ANCA associated small vasculitis only accounted for 1.20% of children in whom renal biopsy was performed and 0.25% of hospitalized children with renal diseases during the same period. The age of onset of the 5 children with ASV was between 8 to 12 years with mean age 10.5 years. All ASV children were female. (2) All ASV children were negative for C-ANCA and showed normal anti-proteinase 3 activities, but positive for P-ANCA with high anti-myeloperoxidase activities between 98 to 242 kEU/L. The mean value of MPO-ANCA was 154.5 kEU/L (normal range < 12.7 kEU/L). (3) All ASV in the children was microscopic polyarteritis with wide-spread glomerular crescents formation and capillary tuft fibrinoid necrosis. Variety of complement C3 deposits and weak immunoglobulin deposits were noted in all ASV but one child who showed relatively strong deposits of IgA and IgM. The electronic dense deposits were mainly located in subendothelial space but were also found in the glomerular basement membrane in one child. (4) Three children with ASV died within one year after diagnosis, and two got remission and restored renal function after combined pulse therapy with methylprednisolone and cyclophosphamide (CTX), but remained to have hematuria and small amount of proteinuria after 1 and 5 year follow-up, respectively. CONCLUSION: Childhood ASV was female and P-ANCA predominant, more vulnerable to progress to renal failure and poorer in prognosis than adult cases. Qualitative and quantitative ANCA measurement and renal biopsy were key to the diagnosis of ASV in children.