OBJECTIVE To investigate the clinicopathologic characteristics of childhood renal diseases.METHODS A retrospective analysis of 1316 renal biopsies performed over the past 20 years was performed. RESULTS Of the 1316 patients, 383(29.09% ) were diagnosed as nephrotic syndrome, 291(22.00%) as acute nephritis syndrome, 224 (17.21%) as isolated hematuria, 209 (15.87%) as purpura nephritis, and 96(7.30% ) as hepatitis B virus-associated nephritis . Mesangial proliferation was the most common pathological change (756 cases; 57.45%), followed by IgA nephropathy (113 cases; 8.59%), endothelial capillary proliferation(112 cases; 8.51%), membranous nephropathy (66 cases; 5.02%), and various minor and minimal changes (59 cases; 4.48%). Alport syndrome, congenital nephrotic syndrome, thin basement membrane nephropathy, fibrillary glomerulopathy disease, and Fabry disease were confirmed by electronic microscopy. IgA, IgM and C1q nephropathy were definitely diagnosed using immune histochemistry or immunofluorescent. A diagnosis of primary glomerular disease was made in 69.53% of the cases (915 cases); secondary glomerular disease was noted in 26.14%(344 cases). Of the 915 cases of primary glomerular disease, 375 (941.0%) had nephrotic syndrome. Secondary glomerular disease due to purura nephritis was common (209/344; 60.8%). CONCLUSIONS Primiary glomerular disease predominates in children. Nephrotic syndrome is the most common clinical diagnosis. Mesangial proliferation is the most common pathological patterns in children with renal disease.［Chin J Contemp Pediatr, 2007, 9 (2) :117-121］

OBJECTIVE: To establish a urinary proteomic map on two-dimensional polyacrylamide gelelectrophoresis (2-DE) in children with idiopathic nephrotic syndrome (INS). METHODS: The proteins from INS children were purified by four various means, separated by 2-DE, and stained by silver. RESULTS The sequential preparation of urinary proteins by acetone precipitation and dislysis, when the sample was 300 μg, resulted in a clear background, well-resolved and reproducible 2-DE urinary protemic map in children with INS. CONCLUSIONS A steady 2-DE technique for urinary protemic map in children with INS was established, which can be effectively applied in urinary proteomics of the disease.［Chin J Contemp Pediatr, 2007, 9 (2):122-124］

OBJECTIVE: To investigate the role of mast cells in the development of renal interstitial fibrosis in children with Henoch-Schonlein purpura nephritis (HSPN) and possible mechanisms. METHODS: Paraffin-embedded renal biopsy tissue sections from 20 children with HSPN were examined for the levels of tryptase-β and transforming growth factor-β1 (TGF-β1) by immunohistochemical staining. Mast cells were counted by toluidine blue staining. Masson staining was used to assess the level of renal interstitial fibrosis and renal histopathological scores. Normal renal tissue sections from 5 nephrectomized children for nephroma were used as control group. RESULTS: The percentages of positive tryptase-β cells-and mast cells and the TGF-β1 expression in the HSPN group were significantly higher than those in the control group (P <0.05). The percentages of positive tryptase-β cells and mast cells and the TGF-β1 expression in renal tissue were positively correlated with the glomeruli histopathological score (r =0.940,0.920,0.937, respectively; P <0.05) and were also positively correlated with the histopathological score of renal interstitium (r=0.903,0.859,0.948, respectively; P <0.05). The level of renal interstitial fibrosis was positively correlated with the percentages of positive tryptase-β cells and mast cells and the expression of TGF-β1 (r =0.790, 0.766, 0.858, respectively; P <0.05). There was a positive correlation between the percentages of positive tryptase-β cells and mast cells (r =0.941, P <0.05), between the percentage of positive tryptase-β cells and the TGF-β1 expression (r =0.897, P <0.05) and between the percentage of positive mast cells and the TGF-β1 expression (r =0.942, P <0.05). CONCLUSIONS: Tubulointerstitial mast cell infiltration is associated with the development of renal interstitial fibrosis in children with HSPN. Mast cells together with TGF-β1 and mast cell-derived tryptase-β may be involved in the development of the renal interstitial fibrosis in HSPN.［Chin J Contemp Pediatr, 2007, 9 (2):125-128］

OBJECTIVE: This study investigated the clinical manifestations and renal pathological findings of 95 children with Henoch-Schonlein purpura nephritis (HSPN)in order to explore the relationship between clinical manifestations and renal pathology in HSPN. METHODS: According to clinical manifestations, 95 HSP patients were classified into six clinical groups: 1) normal urine analysis; 2) isolated hematuria or proteinuria; 3) proteinuria with hematuria; 4) acute nephritis; 5) nephrotic syndrome; 6) acute nephritis with over 50 mg/(kg.d) of proteinuria. The severity of the renal pathological findings was determined based on the classification of the International Study of Kidney Disease (ISKDC), including grades I-VI. The relationship between clinical manifestations and the severity of renal pathological findings was studied. RESULTS: Nephrotic syndrome was the most common clinical diagnosis (26 cases), followed by proteinuria with hematuria (23 cases), normal urine analysis (20 cases), isolated hematuria or proteinuria (15 cases), acute nephritis with over 50 mg/(kg.d) of proteinuria (7 cases) and acute nephritis (4 cases). Twenty-five out of 26 patients with nephrotic syndrome had an ISKDC classification of grade III-IV. All of the four patients with acute nephrits had a classification of grade IIIb. The 7 cases of acute nephritis with over 50 mg/(kg.d) of proteinuria had a classification of grade IIIa-V. The 20 patients with normal urine analysis had a classification of grade Iia-IIIb. There were no significant differences in ISKDC classification among the patients with normal urine analysis, isolated hematuria or proteinuria, and hematuria plus proteinuria. As the course progressed, the degree of renal pathological changes in patients with isolated hematuria or proteinuria and hematuria plus proteinuria became more serious. Of all the 95 patients, 58% had co-deposition of immunoglobulins A, G and M. The percentage of co-deposition of immunoglobulins A, G and M was related to the disease course and the severity of renal pathological findings. CONCLUSIONS: HSPN children with nephrotic syndrome or acute nephritis with or without proteinuria had relatively severe renal pathological changes. The clinical manifestations were not always in parallel with the severity of renal pathological findings in HSPN children. With the course progressing, the renal pathological changes tended to be serious. The severe renal pathological manifestations came with co-deposition of immunogolobulins A, G and M in the glomerulin .［Chin J Contemp Pediatr, 2007, 9 (2):129-132］

OBJECTIVE: To investigate the expression of fibroblast growth factor receptor-4 (FGFR4) in fetal kidneys and pathological kidneys of children in order to show the roles of fibroblast growth factor (FGF) and FGFR4 in the development of fetal kidneys and renal diseases.METHODS: The expression of FGFR4 was detected by immumohistochemistry in the normal fetal kidney at 8 to 34 weeks of gestation age (n=18) and 82 children with renal disease, including 28 cases of primary nephrotic syndrome (PNS), 12 acute glomerulonephritis (AGN), 20 Henoch-Schoenlein purpura nephritis (HSPN), and 22 isolated hematuria (IHU). A correlation analysis between renal pathological scores and FGFR4 expression was performed.RESULTS: 1) FGFR4 expression was weakly in renal vesicle and primitive tubules of S-shaped body, irrecognizable in urteric bud and podocytes of C-stage, and negative in mesenchyme and condensing mesenchyme. The immunostaining of FGFR4 was intense in distal tubules and collecting ducts, but was negative in mature glomeruli and proximal tubules. 2) FGFR4 was expressed in all pathological sections of various renal diseases. FGFR4 expression was intense in tubules but weak in glomeruli. It was principally expressed in distal tubules and partially in proximal tubules. The tubules with very strong expressions of FGFR4 presented abnormal structures including dilation and atrophy, especially in proximal tubules. 3) There were no significant differences in the FGFR4 expression in various parts of the kidney among various renal diseases. There were also no significant differences in the FGFR4 expression in renal tubules among the four different pathological types of renal diseases: focal segmental glomerularsclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN), mesangial proliferative glomerulonephritis (MsPGN), and minimal change disease (MCD). The FGFR4 expression in podocytes in the MPGN group was noticeably higher than that of the other pathological type group(P<0.05). 4) The FGFR4 expression in proximal tubules positively correlated with the pathological score of tubules (r=0.463682, P<0.05) but negatively correlated with the pathological score of glomeruli (r=- 0.0277, P<0.05). The FGFR4 expression in both distal tubules and podocytes negatively correlated with the pathological score of tubules or glomeruli (P<0.05). CONCLUSIONS: The development of fetal kidneys in the early period could not be regulated by FGF-FGFR4 signal which takes part in the development of renal tubules and collecting duct in the mature period. The FGFR4 expression is related with renal pathology in children with PNS, AGN, HSPN or IHU. A proper increase of FGFR4 expression is beneficial to the recovery of renal tissues but an over-expression relates to a severe renal damage.［Chin J Contemp Pediatr, 2007, 9 (2):133-138］

OBJECTIVE: To study the evidence-based therapy of edema in nephrotic syndrome by analyzing the literatures systematically. METHODS: The literatures related to the treatment of nephrotic edema were retrieved from the following: Chinese Biological Medicine Database (CBM-disk), Chinese Journals Full-text Database (CNKI, 1994-2006), Chinese Technological Periodicals Database (VIP, 1989-2006), Chinese Evidence Biological Medicine/Cochrane Central Database (CEBM/CCD), Cochrane Library Database, MEDLINE (1966-2006), EMBASE (1975-2006), MEDLARS, SCI (1985-2006) and OVID by electron and craft search with the following key words: nephrotic syndrome, edema, recalcitrant edema, refractory edema or resistant nephrotic edema, and treatment, diuretic therapy or human albumin treatment. The relevant literatures on randomized controlled trials (RCT) that met the criteria were statistically analyzed by the Coorporative network software RevMan 4.2.RESULTS: A total of 113 articles were searched (60 in Chinese and 53 in English), of which 12 were RCT. Three of the 12 articles were included for Meta analysis. Meta analysis showed that dextran-40 together with furosemide was effective for nephrotic edema. Human albumin solution could be used in nephrotic edema patients with coexistent severe hypoalbuminemia. A combination of diuretics by intravenous drip infusion was effective for diuretic-resistant nephrotic edema.CONCLUSIONS: The treatment for nephrotic edema should be individualized. The evidence of treatment of nephrotic edema has not been fully elucidated. Further multicentre, large sample, and randomized controlled trials are needed.［Chin J Contemp Pediatr, 2007, 9 (2):139-143］

OBJECTIVE: To study the mobilization effects of stem cell factor (SCF) along with granulocyte colony-stimulating factor（G-CSF）on bone marrow stem cells and endothelial progenitor cells in rats with unilateral ureteral obstruction (UUO). METHODS: Fifty-six healthy male Wistar rats were randomly divided into seven groups: control, SCF, G-CSF, SCF+G-SCF, Sham-operated, UUO and UUO+SCF+G-CSF groups (n=8 each). The rats from the control, SCF, G-CSF and SCF+G-CSF groups were hypodermically injected with normal saline (2 mL/kg), SCF (200 μg/kg), G-CSF (200 μg/kg) and SCF along with G-CSF respectively for 5 days. The rats from the UUO and UUO+SCF+G-CSF groups were subjected to the ligation of right ureter and then were hypodermically injected with normal saline (2 mL/kg) and SCF (200 μg/kg)+G-CSF (200 μg/kg) respectively for 5 days. The sham-operated group had the same operative approach as the UUO and the UUO+SCF+G-CSF groups but the right ureter was not ligated. After operation they received a hypodermical injection of 2 mL/kg normal saline for 5 days. Five days later blood samples were collected. The percentages of CD34+ and CD34+/CD133+ cells in intravenous blood mononuclear cells were detected by flow cytometry. Serum contents of glutamate-pyruvate transaminase (GPT), glutamic oxalacetic transaminase (GOT), urea nitrogen and creatinin were measured. RESULTS: Except for the sham-operated group, the other five groups (SCF, G-CSF, SCF+G-SCF, UUO and UUO+ SCF+G-CSF groups) had significantly higher percentage of CD34+ cells and CD34+/CD133+ cells in intravenous blood mononuclear cells than the control group (P<0.05). There were significant differences in the percentage of CD34+ cells and CD34+/CD133+ cells among the five groups (P<0.05). The UUO+SCF+G-CSF group showed the highest percentage of CD34+ cells and CD34+/CD133+ cells, followed by the SCF+G-CSF group. There were no significant differences in serum contents of GPT, urea nitrogen and creatinin among the seven groups. Except the UUO group showed higher GOT contents, there were no significant differences in the GOT contents among the other six groups.CONCLUSIONS: The mobilization effects of SCF and G-CSF on bone marrow stem cells and endothelial progenitor cells were not always in paraller. A combination of SCF and G-CSF can effectively mobilize stem cells and endothelial progenitor cells, and side effects were not found in the liver and the kidney.［Chin J Contemp Pediatr, 2007, 9 (2):144-148］

OBJECTIVE: Pulmonary surfactant protein-D (SP-D) is regarded as a valuable biomarker in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This study was to explore the changes of SP-D content in lung tissue following ALI and the effect of dexamethasone (Dex) on the SP-D content in young rats. METHODS: One hundred and forty-four 21-day-old Sprague-Dawley rats were randomly assigned into control, ALI and Dex-treated groups. ALI was induced by intraperitoneal injection of lipopolysaccharide (LPS) (4 mg/kg) in the rats from the ALI and Dex-treated groups. Normal saline was given for the control group. Dex (5 mg/kg) was administered 1 hr after LPS injection in the Dex-treated group. At each time interval of 6, 12, 24, 36, 48 and 72 hrs after LPS injection, eight rats of each group were randomly chosen and sacrificed. Western blot was employed to detect the content of SP-D in lung tissues. RESULTS: The pulmonary SP-D content decreased significantly at 36, 48 and 72 hrs after LPS administration in the ALI group, and reduced to a nadir (0.92±0.11 vs 3.27±0.52) at 48 hrs compared with that of the control group (P<0.01). The SP-D content in the Dex-treated group increased significantly at 36,48 and 72 hrs after LPS administration when compared with the ALI group (P<0.01). A significant difference in the SP-D content between the Dex-treated and the control group was noted only at 72 hrs after LPS administration (P<0.05). CONCLUSIONS: The SP-D content in lung tissue was reduced following ALI in young rats at the early stage. Early administration of Dex can significantly increase the pulmonary SP-D content.

OBJECTIVE: To study the effect of methotrexate (MTX), a folic acid antagonist which can lead to folic acid deficient, on the cardiac development and on the expressions of BMP2b and HAS2 in zebrafish. METHODS: The zebrafish embryos at 6-48 hrs post fertilization (hpf) were treated with various concentrations of MTX (0.5×10-3 , 1.0 ×10-3 and 2.0×10-3 M). At 48 hpf, the percentage of cardiac malformation and heart rate were recorded. The zebrafish embryos at 6-10 hpf treated with 1.5×10-3 M MTX were used as the MTX treatment group. At 24 and 48 hpf the cardiac morphology was observed under a microscope. The expressions of BMP2b and HAS2 in zebrafish were detected by in situ antisense RNA hybridization and real-time PCR. RESULTS: 6-12 hpf, the early embryonic developmental stage, was a sensitive period that MTX affected cardiac formation of zebrafish. The retardant cardiac development and the evidently abnormal cardiac morphology was found in the MTX treatment group. The results of in situ antisense RNA hybridization showed that the expressions of BMP2b and HAS2 in the zebrafish heart were reduced in the MTX treatment group at 36 and 48 hpf. The real-time PCR results demonstrated that the BMP2b expression decreased at 12, 24, 36 and 48 hpf, and that the HAS2 expression decreased at 24, 36 and 48 hpf in the treatment group compared with the control group without MTX treatment. CONCLUSIONS: The inhibition of folic acid function may affect cardiac development of early embryos, resulting in a retardant development and a morphological abnormality of the heart in zebrafish, possibly by down-regulating the expressions of BMP2b and HAS2. ［Chin J Contemp Pediatr, 2007, 9 (2):159-163］

OBJECTIVE: Some research has shown that the brain white matter damage is closely related to apoptosis of pre-oligodendrocytes. The relationship of bcl-2 protein, a protein of anti-apoptosis, with brain white matter damage in neonatal rats is rarely reported. This study examined the changes of bcl-2 protein expression following brain white matter damage in neonatal rats. METHODS: Ninety 2-day-old Sprague-Dawley (SD) rats were randomly divided into 2 groups: experimental group (n=45) and control group (n=45).Brain white matter damage was induced by ligation of the right common artery, followed by 6% hypoxia exposure in the rats from the experimental group. The rats of the control group were sham-operated, without hypoxia-ischemia treatment. The expression of bcl-2 protein in the periventricular white matter and the callositas was detected by immunohistochemical technique. Apoptosis of neurocytes in these tissues was detected by TUNEL. RESULTS: The apoptosis index of neurocytes in the experimental group was up-regulated at 4, 12 and 24 hrs and at 3 and 7 days, peaking at 3 days after white matter damage, compared with the control group (P < 0.05). The expression of bcl-2 protein in the experimental group began to increase at 1 hr, reached a peak at 12 hrs and remained a higher level until 3 days after white matter damage compared with that observed in the control group (P< 0.05). CONCLUSIONS: The expression of bcl-2 protein increased at the early stage of white matter damage in neonatal rats. The peak of apoptosis lagged behind that of the bcl-2 protein expression, which suggests that bcl-2 protein may have protective effects against neuronal apoptosis.

OBJECTIVE: This study examined the protein and mRNA contents of angiotesin converting enzyme (ACE), angiotensin II (Ang II) and type I collagen and the changes of lung histomorphology in neonatal rats with hyperoxia-induced chronic lung disease (CLD) and investigated the protection of captopril against CLD and the possible mechanism. METHODS: A total of 240 term neonatal Wistar rats were randomly assigned into air, model, normal saline and captopril-treated groups (n=60 each). The air group was exposed to room air (FiO2=0.21) immediately after birth. The other three groups were exposed to hyperoxia (FiO2=0.9）for 21 days to induce lung injury. The captopril-treated group received captopril daily ( 30 mg/kg ) by intragastric administration between the 7th and 21st days of hyperoxia exposure. The normal saline group was administrated with normal saline instead. At each time interval of 1, 3, 7, 14 and 21 days after experiment, six rats of each group were randomly chosen and sacrificed. The protein and mRNA levels of ACE, Ang II and type I collagen were measured by enzyme-linked immunosorbentassay, radio-immunity technique and RT-PCR. The changes of lung histomorphology were observed under a light microscope. RESULTS: The protein and mRNA expressions of ACE, Ang II and type I collagen increased significantly in the model and normal saline groups on the 14th and peaked on the 21st days of exposure compared with those of the air group (P<0.05 or 0.01). Captopril treatment reduced significantly the protein and mRNA expressions of ACE, Ang II and type I collagen compared the model and normal saline groups on the 14th and 21st days, although the values were significantly higher than the air group (P<0.05 ).The histopathologic examination demonstrated broadened lung interstitium and reduced alveolar quantity and lung fibrosis was developed in the model and normal saline groups on the 14th day of exposure. Captopril treatment obviously alleviated the changes of lung histomorphology. CONCLUSIONS: Captopril can inhibit the protein and mRNA expressions of ACE, Ang II and type I collagen and alleviate lung fibrosis in neonatal rats with hyperoxia-induced lung injury/CLD. This may contribute to one of the possible mechanisms underlying the protective effects of captopril against lung injury/CLD.

OBJECTIVE: To investigate the role of oxidative stress in the pathogenesis of retinal injury induced by hyperoxia. METHODS: Sixty immature Sprague-Dawley (SD) rats, born at a gestational age of 21days, were randomly exposed to room air (air group, n=30) or 95% oxygen (hyperoxia group, n=30) immediately after birth. Plasma 8-iso-prostaglandin F2ɑ (8-iso-PGF2α) levels were determined by ELISA. The ultrastructures of the retina were observed under a transmission electron microscope. RESULTS: The plasma 8-iso-PGF2α contents of the air group were 19.09±5.57, 18.24±5.91 and 17.00±5.58 pg/mL on the 3rd, 7th and 14th days after birth, respectively (F=1.024, P>0.05). The plasma 8-iso-PGF2 contents in the hyperoxia group on the 3rd (28.33±5.59 pg/mL), the 7th day (51.20±15.01 pg/mL) and 14th day (84.54±14.85 pg/mL) after birth were significantly higher than those of the air group (t=2.863, P<0.05; t=5.073, P<0.01; t=11.006, P<0.01). Moreover, the plasma 8-iso-PGF2 contents in the hyperoxia group increased with the prolonged hyperoxia exposure (F=150.7, P < 0.01). The ultrastructures of retina in the air group were normal. Hyperoxia exposure resulted in abnormalities of the ultrastructures of retina, manifesting as the membrane discs rarefied, twisted and disrupted and mitochondrial swelling. CONCLUSIONS: Oxidative stress can results in retinal injury in immature rats. An increased plasma level of 8-iso-PGF2α is related to the injury degree of retina.