Clinical characteristics, treatment and follow-up of Cockayne syndrome with renal involvement / 临床儿科杂志

Objective To explore the clinical features, treatment and follow-up of Cockayne syndrome with renal involvement. Method The clinical data of one child with Cockayne syndrome confirmed by gene detection with renal injury were reviewed, and the clinical features of renal involvement in Cockayne syndrome were summarized. Results A male child aged 3 years and 8 months had clinical manifestations of mental retardation, growth retardation, special face and photosensitive dermatitis, and renal involvement was manifested by nephrotic syndrome. Cranial CT showed symmetrically calcification in bilateral basal ganglia. The targeted next generation sequencing results showed homozygous mutations of c.394_398del and p.Leu132Asnfs in ERCC8 gene (NM_000082) of the child, and the same heterozygous mutation was found in both his parents (non-consanguineous marriage). After the diagnosis of nephrotic syndrome, full dose prednisone was given for experimental treatment. The urine protein decreased but did not disappear, which was considered hormone resistance. After 4 months of combined treatment with cyclosporin, the urine protein turned negative. During 20 months of follow-up, urine protein remained negative and renal function remained stable. The renal involvement in Cockayne syndrome was seldomly reported, and its clinical manifestations are heterogeneous. Condusion Renal involvement in Cockayne syndrome may be manifested with nephrotic syndrome which should be noticed.

Dent disease combined with renal failure:two case report and literature review / 临床儿科杂志

Objective To explore the etiology and prognosis of Dent disease combined with renal failure in children. Methods The clinical data of 2 children with Dent disease combined with renal failure from January 2014 to December 2016 were analyzed and the related literature was reviewed. Results Both of them were male, with the age of 8 and 10 years old respectively. Their renal functions were normal, and no renal calcification. Both of them had the history of upper respiratory tract virus infections within 1 week before the onset of renal failure. In case 1, acute phase (10 days) renal biopsy showed combined with acute tubulointerstitial nephritis, and his renal function recovered completely after glucocorticoids treatment. In case 2, renal biopsy at 6 months in course of disease showed the combined with subacute tubulointerstitial nephritis, and his renal function was improved partly after glucocorticoids treatment. Conclusions For children with Dent disease combined with acute renal failure, especially with upper respiratory tract virus infections and other inducement, renal biopsy should be early performed to exclude the possibility of acute tubulointerstitial nephritis, so that the treatment can be timely conducted and the prognosis can be improved.

Some reflections on pediatric renal diseases / 临床儿科杂志

Great successes have been achieved on the pediatric renal diseases under the guidance of The Group of Nephrology, Chinese Pediatric Society, Chinese Medical Association for the past thirty years. Especially that evidence-based guidelines and related interpretation for the diagnosis and treatment of common renal diseases in children were published from 2009 to 2016 unifies and standardizes the diagnosis and treatment of common pediatric renal diseases. However there are some divergences and doubts in clinical practice, and the author makes some reflections on some aspects of the clinical application.

Clinical features of autoimmune hepatitis patients with poor response to treatment / 中华肝脏病杂志

Objective@#To investigate the clinical features of autoimmune hepatitis (AIH) patients with poor response to treatment.@*Methods@#A total of 61 AIH patients were enrolled, among whom 49 (80.33%) achieved complete response (good response group) and 12 (19.67%) had incomplete response (poor response group). The two groups were compared in terms of clinical manifestations, laboratory markers, abdominal ultrasound findings, pathological features by liver biopsy, and response to treatment. Continuous data were expressed as mean ± standard deviation (x±s), and the t-test was used for comparison between groups; categorical data were expressed as rates or percentages, and the chi-square test was used for comparison between groups; a binary logistic regression analysis was used to determine influencing factors.@*Results@#Most patients were female in both groups, and there were no significant differences in sex ratio, mean age of onset, and general status including extrahepatic autoimmune disease between the two groups. Compared with the good response group, the poor response group had significantly higher levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), total bilirubin, immunoglobulin G, and immunoglobulin M (P < 0.05). Compared with the good response group, the poor response group had a significantly higher positive rate of autoimmune antibodies except anti-nuclear antibody (ANA), anti-smooth muscle antibody (SMA), antimitochondrial antibody (AMA), and AMA/M2 (75% vs 16.3%, P < 0.001), and there was a significant difference in the positive rate of gp210 antibody between the two groups (25% vs 0%, P < 0.01). There were significant differences between the poor response group and the good response group in the proportion of patients with liver cirrhosis (50.0 % vs 16.3%, P < 0.05) and splenomegaly (58.3% vs 22.4%, P < 0.05). The binary logistic regression analysis showed that a high serum level of ALP (odds ratio [OR] = 1.017, 95% confidence interval [CI] 1.001-1.033, P = 0.034), positive autoimmune antibodies except ANA, SMA, and AMA/M2 (OR = 70.842, 95% CI 2.132-2 354.371, P = 0.017), and liver cirrhosis (OR = 28.777, 95% CI 1.015-815.854, P = 0.049) were independent risk factors for initial treatment outcome.@*Conclusion@#A high serum level of ALP, positive autoimmune antibodies except ANA, SMA, and AMA/M2, and liver cirrhosis are closely associated with poor response in AIH patients.

Clinical phenotypes of hepatocyte nuclear factor 1 homeobox b-associated disease / 中华儿科杂志

Objective@#Hepatocyte nuclear factor 1 homeobox b (HNF1B) -associated disease is an autosomal dominant inherited disorder with a variable, multi-systemic phenotype. In China, five adult probands and one child proband with HNF1B-associated disease had been reported, whereas few fetuses are described. The aims of this retrospective study were to understand about the clinical manifestations of HNF1B-associated disease and to further improve the recognition of this disorder.@*Method@#Four patients (3 males, 1 female) and three fetuses with HNF1B mutations were included in this study. They were admitted to our hospital from January 2013 to March 2017. HNF1B mutations were detected using targeted next generation sequencing and quantitative real-time PCR or Sanger sequencing. HNF1B heterozygous deletion of exons 1-9 was found in 4 patients and 2 fetuses, and HNF1B heterozygous missense mutation in 1 fetus. These two mutations had been reported. Two patients and 1 fetus had de novo mutations. Results of renal ultrasonography with or without magnetic resonance imaging, biochemical investigations, urine routine examination and other necessary investigations in 7 cases were analyzed.@*Result@#Three patients were Han Chinese ethnicity, and one patient was Mongolian. In patients 1 and 4, abnormal fetal kidneys were discovered by routine ultrasonography, and the age at first feature identified in Patients 2 and 3 were 13 years and 28 years. Patient 3 had normal renal function and the remainder had reduced glomerular filtration rate. In addition, patient 4 presented with nephrotic syndrome and glycosuria, patient 2 with early onset hyperparathyroidism and renal osteodystrophy, and patient 3 with diabetes mellitus. All the 4 patients had renal structural abnormalities including bilateral multiple renal cysts, dysplasia and hyperechogenic kidneys. Only patient 3 had a positive family history of renal diseases, the remainder had a negative family history of renal diseases. In 3 fetuses, prenatal ultrasound anomalies were detected during the second trimester. These 3 fetuses had hyperechogenic kidneys with or without renal cysts. Polyhydramnios was detected in only one of the 3 fetuses. Two of the 3 fetuses had a positive family history of renal diseases.@*Conclusion@#Clinical phenotypes of HNF1B-related disease are heterogeneous, renal malformations clearly appear to be the most common manifestation, multiple renal cysts are characteristic, and patients can progress to impaired kidney function during childhood; HNF1B mutation is a differential diagnosis of fetal hyperechogenic kidneys or multiple renal cysts.

Red blood cell casts induced acute renal failure in IgA nephropathy: a childhood case report with literature review / 临床儿科杂志

Objective To explore the rare cause of renal failure in childhood IgA nephropathy.MethodsA six year-old boy presented with recurrent gross hematuria for 3 months and increased serum creatinine for 5 days, blood and urine routine test, renal function, urinary protein concentration and renal biopsy were performed for diagnosis.Results The boy had three episodes of recurrent gross hematuria with a predisposed respiratory tract infection, he recovered within a week after antibiotic therapy from previous two episodes, but oliguria and renal failure were occurred in the third episode. Renal biopsy showed IgA nephropathy with presence of red blood cell casts in as much as 50% of the tubular lumen and acute tubular lesion. His renal function recovered gradually to normal within 4 weeks after treatment with anti-infection, diuresis and alkalization of urine. Conclusions This article reported the renal failure case induced by tubular damage and obstruction by red blood cell casts in childhood IgA nephropathy.

Childhood hepatolenticular degeneration combined with thin basement membrane nephropathy: a case report with literature review / 临床儿科杂志

Objective To analyze the diagnostic approach on hepatolenticular degeneration combined with thin basement membrane nephropathy.Methods A girl presented with microscopic hematuria, liver dysfunction and hypocomplementemia was diagnosed with hepatolenticular degeneration combined with thin basement membrane nephropathy, her clinical data were summarized and analyzed retrospectively.Results A ten years old girl presented with microscopic hematuria and liver dysfunction for a year, dysarthria for a month, and combined with hypocomplementemia but without proteinuria. Renal biopsy showed thin basement membrane nephropathy. Ceruloplasmin was 23.10 mg/L and urinary copper concentration was 120μg, respectively, ocular slit lamp examination showed Kayser-Fleischer ring, cranial MRI showed preternatural signal in both basal and putamen nucleus, mutation analysis showed homozygous mutations in ATP7B and heterozygous mutation in COL4A3 gene,respectively.Conclussion Hepatolenticular degeneration should be suspected in those cases with persistence microscopic hematuria, liver dysfunction and hypocomplementemia.

Childhood IgA nephropathy combined with Alport syndrome: a report of 2 cases and literature review / 临床儿科杂志

Objective To explore the diagnosis and differential diagnosis of IgA nephropathy.Methods The clinical data of 2 children with IgA nephropathy were retrospectively analyzed.The pertinent literatures were reviewed.Results In 2 males aged 6 and 7 years,the clinical features were a large amount of proteinuria (mainly albumin),low serum albumin,high cholesterol,and persistent microscopic hematuria,which were in line with the diagnosis of nephrotic syndrome.The effects of hormone and immunosuppressive therapy were poor.Renal pathology immunofluorescence and light microscopy findings were in accord with mild to moderate mesangial proliferative IgA nephropathy (M1E0S0T0).Electron microscope showed glomerular basement membrane lesions (layering,breakage,and uneven thickness),which could not exclude Alport syndrome.Further gene detection confirmed a pathogenic mutation of COL4A5.Conclusions It is rare that IgA nephropathy is combined IgA nephropathy at the same time.Attention should by paid to those who had a poor effect of treatment or had a related family history in IgA patients because it is possible that IgA nephropathy and IgA nephropathy may occurred at the same time.

Childhood primary bladder telangiectasia:a case report and literature review / 临床儿科杂志

Objective To explore the diagnosis of primary bladder telangiectasia. Methods The clinical data of a child with primary bladder telangiectasia were reviewed. Results A 9-year-old girl had gross hematuria without obvious cause at 3 years old. After that she presented intermittent gross hematuria and persistent microscopic hematuria with blood clots in the urine following repeatedly respiratory tract infections, and had hemorrhagic shock once. Urine routine examination showed albumin 1+~2+ and RBC full in entire field of view. 24 hours urine protein quantitation was 0.96 g. Ultrasound of abdomen and urinary tract and enhanced CT of urinary system had no abnormal findings. Renal artery angiography showed no arteriovenous malformation or fistula. Cystoscopy showed telangiectasia. There was neither family history nor telangiectasia in other parts. Both genetic telangiectasia and ataxia telangiectasia gene mutation analysis were normal. Conclusion It is rarely seen primary bladder telangiectasia in children. However, children with early onset, long-term, and intermittent gross hematuria with blood clots, especially suffered with hemorrhagic shock, vascular disease should firstly be considered. And routine urinary imaging should be performed, including angiography and ,if necessary, cystoscopy.

Childhood fibrillary glomerulonephritis:one case report and literature review / 临床儿科杂志

Objective To explore the clinical features, diagnosis, and treatment of childhood fibrillary glomerulonephritis (FGN). Methods The clinical data of a child with FGN in April 2016 were analyzed retrospectively. Results A 12-year-old boy, who presented significant proteinuria (mainly albumin), hypoalbuminemia, hypercholesterolemia, and persistent microscopic hematuria in May 2010, met the criteria of nephrotic syndrome. Renal biopsy in May 2010 showed mesangial proliferative glomerulonephritis combined with glomerulosclerosis. It was not effective by treatment with intravenous infusion of methylprednisolone and prednisolone, and there were no responses by the combination with mycophenolate mofetil and traditional Chinese medicine. After admission, the second renal biopsy was performed. Under the light microscope, the moderate mesangial proliferative glomerulonephritis combined with membranoproliferative changes was observed. Under the electron microscope, the FGN was confirmed. Conclusion The first case of childhood FNG was diagnosed in China.

Effects of gross hematuria on the results in laboratory urine examination / 临床儿科杂志

Objectives To explore the effects of gross hematuria on the results of several parmeters in laboratory urine examination. Methods Eighty (80) children with IgA nephropathy and 40 cases with acute post-streptococcal glomerulonephritis hospitalized in our hospital from January 2014 to December 2015 were recruited. The ratio of urinary calcium and protein to creatinine, quantitative test of 24 h urinary calcium and protein, quantitative test of 24 h urinary albumin,α1-microglobulinuria, microalbuminuria and urine protein electrophoresis were tested during and after the gross hematuria, respectively. Results The ratio of urinary calcium and protein to creatinine, quantitative test of 24 h urinary calcium and protein were much higher in the duration of gross hematuria as compared to those after the duration of gross hematuria, while α1-microglobulinuria, microalbuminuria and quantitative test of 24 h urinary albumin showed no difference between the two periods. Conclusions Gross hematuria could increase the level of urinary calcium and protein, while quantitative test of 24 h urinary albremin is not affected.

Tacrolimus causes acute renal failure in the treatment of nephrotic syndrome in children:a report of 3 cases / 临床儿科杂志

Objective To explore the causes of acute renal failure resulted from tacrolimus in the treatment of nephrotic syndrome. Method The clinical data of acute renal failure caused by tacrolimus in treatment of nephrotic syndrome in 3 children during January 2012 and December 2015 were retrospectively analyzed. Results There were 2 male and 1 female aged 3, 11,and 13 years respectively. Clinical manifestations were consistent with simple type of primary nephrotic syndrome. One child was frequently recurrent and another two were secondary steroid resistant. The renal pathology showed minimal changes. Acute renal failure occurred within 4 weeks after treatment with tacrolimus on the basis of hormone therapy in all patients who had infection within one week. Renal function recovered to normal within 2 weeks after discontinuation or reduction of tacrolimus combined with anti-infection and diuresis treatment. Two children continued with tacrolimus, but the other one was replaced with cyclosporin A. The renal function of all patients remained normal during the follow-up for 10-42 months. Conclusion In the first 4 weeks of tacrolimus therapy in children with nephrotic syndrome, infection may lead to reversible acute renal failure.

Clinical and genetic features of X-linked Alport syndrome in men positive for the collagen Ⅳ α5 chain in epidermal basement membrane / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical and genetic features of X-linked Alport syndrome (XLAS) in men positive for the collagen α5(Ⅳ) chain in epidermal basement membrane.</p><p><b>METHOD</b>This was a retrospective study. Totally 725 families were diagnosed as Alport syndrome in Department of Pediatrics of Peking University First Hospital during January 1998 to December 2014, among them 450 patients were males with XLAS. Patients who met both of the following two criteria were included in this study. (1)Patients underwent α5(Ⅳ) chain staining in the epidermal basement membrane. (2)Mutations in COL4A5 gene were detected.Mann-Whitney test and χ(2) test were used.</p><p><b>RESULT</b>Totally 140 males with XLAS were included in this study, 18 cases were α5 (Ⅳ)-positive and 122 cases were α5 (Ⅳ)-negative. The two groups of patients were compared, the median age at analysis was 11.0 vs. 7.2 years (Z = -1.839, P = 0.066), the 24-hour urine protein was 1.50 vs. 0.57 g/d (Z = -1.212, P = 0.226), the rate of hearing loss was 28% vs. 53% (χ(2) = 3.619, P = 0.067), the number of patients progressed to end stage renal disease (ESRD) was 4 vs. 12 (χ(2) =2.377, P = 0.128), the median age of ESRD was 31.0 vs. 16.6 years (Z = -2.554, P = 0.011), the rate of missense mutations in COL4A5 gene was 67% vs. 52% (χ(2) = 1.424, P = 0.313).</p><p><b>CONCLUSION</b>Compared the two groups of patients with positive and negative staining for the collagen Ⅳ α5 chain in epidermal basement membrane, there was no significant difference in the proteinuria level, the rate of hearing loss and genotype of COL4A5 gene. But the patients with positive staining progressed to ESRD significantly later than the patients with negative staining.</p>

IgA nephropathy combined with hemangioma of bladder in children:a case report / 临床儿科杂志

Objective To explore the diagnosis of pediatric clinical hematuria disease. Methods The clinical data of one pediatric patient with IgA nephropathy combined with multiple bladder hemangioma were summarized and analyzed. Results For more than 6 years, 9-year-old female presented with repeated intermittent gross hematuria and persistent microscopic hematuria with the blood clot in urine after several respiratory tract infections. Routine urine test showed protein+++, RBC in full ifeld of vision/HP, and 0 . 54-1 . 02 g of 24 h urine protein quantitation. Early damage index of kidney is mainly based on microalbumin. The ultrasound showed no abnormal abdomen and urinary tract. Also there was no abnormality in enhanced urinary tract CT scan. Renal arteriography showed no ifstula or arteriovenous malformation. Pathological diagnosis of renal biopsy was focal proliferative IgA nephropathy. Cystoscopy examination suggested multiple hemangioma of bladder. Conclusion Bladder hemangioma is a rare condition in childhood. For children presented gross hematuria with blood clots, when the imaging ifnds no abnormalities or other diseases and the treatment of IgA nephropathy is unsatisfatry after diagnosis, the cystoscopy should be performed to exclude the possibility of bladder hemangioma.

Diagnosis and treatment of 6 cases of Dent’s disease / 临床儿科杂志

Objective To explore the diagnosis and treatment of Dent’s disease.MethodsThe clinical characteristics, treatment process and disease-causing gene mutation were retrospectively analyzed in 6 pediatric patients with Dent’s disease misdiagnosed of nephritic syndrome from January 2014 to August 2015.ResultsIn these 6 male patients aged 4.5-9.8 years old, the main clinical manifestations were nephropathy-level of proteinuria and transient low serum albumin (26-30 g/L) without obvious edema or high serum cholesterol. In 4 patients who had renal biopsy, 2 cases showed mesangial proliferative glomerulonephritis and other 2 cases showed focal segmental glomerulosclerosis. All of 6 patients were treated with at least one immunosuppressive agent after resistance to full dose of hormone and no changes in proteinuria were observed. After admission, the indexes of early renal damage and urinary protein electrophoresis pointed to low-molecular proteinuria. The ratio of alpha 1 micro albumin (α1-MG) / micro albumin (MA) (the early renal damage index) was?>?1, there was hypercalciuria, and renal function was normal. The B ultrasonography showed renal calciifcation in 2 patients. The ifndings in all the patients were in accord with the clinical diagnosis of Dent’s disease. Further genetic analysis conifrmed the presence ofCLCN5 gene mutation in these 6 patients.ConclusionAs a type of rare inherited renal tubular disorder, Dent’s disease is easily misdiagnosed, to which pediatricians need to pay attention. The early renal damage index, α1-MG/MA?>?1, can be regarded as one of the diagnostic criteria of renal tubular proteinuria.

The clinical features of hereditary nephrotic syndrome caused by NPHS 2 mutation in two pediatric patients / 临床儿科杂志

Objective To explore the clinical features of steroid resistant nephrotic syndrome caused by NPHS2 gene mutation. Methods The clinical data of two pediatric patients with steroid resistant nephrotic syndrome were retrospectively analyzed. The pertinent literatures were reviewed. Results Both patients were male with onset age at 2 and 3 years old. The clinical features were heavy proteinuria, hypoalbuminemia, and hypercholesterolemia, which met the diagnostic criteria of nephrotic syndrome. Renal pathology found one patient with focal segmental glomerulosclerosis, and other with minimal-change. Both of them suffered from recurrent inguinal hernioplasty and one was accompanied with hypoplasia of left testis. Gene detection verified a NPHS2 gene mutation. Both of them were hormone resistant at the beginning of onset and later hormone combined with different kinds of immunosuppressive therapy was still ineffective. Both of them entered the end-stage of renal disease 3 years after onset. Conclusions For male pediatric patients with steroid resistant nephrotic syndrome, combined with non-renal manifestations such as multiple hernia or testicular abnormalities, the possibility of the hereditary nephrotic syndrome caused by NPHS2 mutations should be considered.

Combined Pharmacokinetics-pharmacodynamics Study of Rabeprazole in Inhibition of Gastric Acid Secretion / 医药导报

Objective To investigate the pharmacokinetics ( PK ) and pharmacodynamics ( PD ) processes of rabeprazole in inhibiting gastric acid secretion with the combined PK-PD model. Methods A total of 10 healthy volunteers were given a intravenous infusion of 20 mg rabeprazole over a 30-min period. The concentration of rabeprazole in the plasma at different time points was detected by HPLC,and the PK parameters were calculated by DAS 2. 0 software. At the same time the intragastric pH was monitored over 24 hours to fit the PD parameters with indirect inhibition model. Results The main PK parameters,t1/2,Cmax,and AUC were(60. 5±17. 3)min,(1 299. 1±201. 0)ng·mL-1,and(106. 4±26. 0)mg·min·L-1, respectively.The corresponding PD parameters,Kin,Ke,IC50 and Imax were(8.200±3.362)h-1,(1.080±0.378)h-1,(0.286± 0. 129)mg·L-1 and(6. 93± 2. 15)pH,respectively. Conclusion The PK of rabeprazole in healthy volunteers conforms to one compartment model,and the PD fits the indirect response inhibition model. The equation can effectively establish the relationship between the blood drug concentration and the effect.

CT, MRI and PET-CT in the diagnosis of cervical cancer / 国际肿瘤学杂志

With the increase of the incidence and the refinement of clinical treatment,the clear preoperative staging and the assessment of tumor recurrence and metastasis of cervical cancer is particular important.Different results may be explained in the same tumor applied different methods of imaging examination,which influences the clinical diagnosis and treatment.So imaging examination plays a more and more important role in the assessment of preoperative staging and tumor recurrence.

Comparison of pathogenicity between Ureaplasma urealyticum serotype 1 and 3 in genital tract of female BALB/c mice / 中华皮肤科杂志

Objective To investigate the pathogenicity of the same concentration of Ureaplasma urealyticum serotype1 (Uu1) and 3 (Uu3),alone or in combination,in genital tract of female BALB/c mice.Methods A total of 144 estradiol-pretreated adult female BALB/c mice were randomly and equally divided into 3 groups to be inoculated intravaginally with the same concentration (106 copies/g) of Uu1 and Uu3 alone or in combination.Twelve estradiol-pretreated female BALB/c mice were inoculated with sterile culture solution and served as the control group.At 1,3,7,14,21,35 days after the inoculation,8 mice in each Uu-inoculated group and 2 mice in the control group were sacrificed.Tissue specimens were obtained from the cervix,endometria and fallopian tube and subjected to hematoxylin-eosin staining followed by light microscopy.Scanning electron microscopy was used to observe the tissue specimens collected at 14 days from cervical mucosa of mice infected by Uu.Chi-square test was performed for statistical evaluation.Results The total infection rate of Uu within 3-35 days after the inoculation was 35.0％ (14/40),47.5％ (19/40) and 62.5％ (25/40) in the Uu1 group,Uu3 group,and combination group respectively (x2 =6.07,P ＜ 0.05).None of these mice was infected by Uu in the control group.Conclusions At the same inoculation concentration,the combination of Uu1 and Uu3 shows the strongest pathogenicity in genital tract of BALB/c mice,followed sequentially by Uu3 and Uu1 alone.