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Background Positive antineutrophil cytoplasmic antibody (ANCA) serology in adult-onset lupus nephritis (LN) is associated with more active disease and distinct renal pathology, but data with respect to childhood-onset LN remain scarce. Here, we aimed to determine the impact of positive ANCA serology on clinical and histopathologic features and renal outcomes in children with LN from multiple centers. Methods Clinical and histopathologic data of 61 ANCA-positive and 330 ANCA-negative LN children (1Results Among 61 ANCA-positive LN children, 86.9% of them had antimyeloperoxidase antibodies. Both ANCA-positive and ANCA-negative children had high disease activities with median SLEDAI-2K of 16 (13, 20). Hematuria was more prominent (urinary RBC +++ ∼ ++++: 45.9% vs 26.7%, p = 0.011), while fever (42.6% vs. 58.2%, p = 0.035), alopecia (3.3% vs. 14.5%, p = 0.019), photosensitivity (0% vs. 8.2%, p = 0.013), and pleurisy (4.9% vs. 15.8%, p = 0.026) were less common in ANCA-positive children. Higher proportions of segmental sclerosis (23.7% vs. 9.8%, p = 0.025), crescentic formation (36.4% vs. 16.3%, p = 0.009), and capillary wall thickening (24.5% vs. 11.0%, p = 0.01) were observed in biopsies of ANCA-positive children. Long-term renal survival did not differ significantly between two groups ( p = 0.300). Conclusions Positive ANCA serology in LN children was associated with different clinical and histopathologic features compared to those with negative ANCA serology. Further studies are needed to clarify the pathogenic role of ANCAs in childhood-onset LN and confirm their association with prognosis.

A copper-catalyzed, three-component, one-pot, 1,3-dipole cycloaddition/oxidation has been developed to construct pyrrolo[2,1-a]isoquinolinoquinone derivatives, with environmentally friendly oxygen as the oxidant. The pyrrolo[2,1-a]isoquinolinoquinone products were obtained from naturally available tetrahydroisoquinolines, 1,4-naphthoquinones, and benzaldehydes in medium yields.

The effect of recombinant human GH (rhGH) in Chinese children with chronic kidney disease (CKD) is unclear.This was a 52-week, multicenter, randomized, open-label, negative-controlled phase 3 study. Prepubertal subjects were randomized 1:1 to either daily subcutaneous injections of rhGH 0.05 mg/kg/day or no treatment for 52 weeks.A total of 68 subjects with a mean age of 7.8 ± 3.27 years were enrolled. At week 52, the height standard deviation score (HT-SDS) in the treated group increased by 0.75 ± 0.58, which was significantly higher compared with 0.17 ± 0.47 in the untreated group (least squares mean 0.58, 95% confidence interval, 0.32-0.84; P 0.001). At week 52, significant improvements were observed in other growth parameters (height velocity [P 0.001]), insulin-like growth factor 1 (IGF-1) SDS [P 0.001], IFG-1/insulin-like growth factor binding protein-3 molar ratio [P 0.001], and height [P 0.001]) compared with the untreated control. Seven patients reported treatment-related adverse events (TRAEs) and most TRAEs were mild in severity. Most subjects recovered without further intervention.Daily rhGH for 52 weeks in children with CKD-induced growth retardation significantly improved HT-SDS and other growth parameters without compromising safety.The efficacy and safety of growth hormone (GH) therapy in Chinese children with chronic kidney disease (CKD) are unclear. This study found that giving short stature Chinese children with CKD daily recombinant human growth hormone (rhGH) for 52 weeks improved growth parameters without compromising safety. This study's information can give physicians the confidence to treat these patients in their clinical practice.

Homozygous deletion of NPHP1 can lead to isolated nephronophthisis (NPHP) and syndromic disorders. However, the phenotype of scalp tumor and hydroureteronephrosis in NPHP patients with homozygous deletion of NPHP1 has not been reported. Clinical data, laboratory results, and genetic testing of 4 NPHP patients were collected. Examination of their eyes, heart, and urinary tract and of their hepatobiliary, skeletal, and central nervous systems was evaluated. Isolated NPHP was observed in 1 case, and syndromic disorders were observed in the other 3 patients. Their syndromic disorders showed NPHP combined with central nervous system defects, eye involvement, scalp tumor, arachnoid cyst, or hydroureteronephrosis. Large homozygous deletions covering the whole NPHP1 gene locus were identified in all 4 patients. We report a novel phenotype of scalp tumor and hydroureteronephrosis in NPHP patients with homozygous deletion of NPHP1, paving an avenue for further research on NPHP1-associated deformity in the skin and the urinary system.

Low interfacial adhesion seriously limits the wide application of PBO fiber in composites. To solve this problem, a novel hierarchical reinforcement strategy was developed by introducing epoxy sizing, nanoreinforcement of amino-functionalized silicon dioxide (SiO

Background Mutations in the ADCK4 gene cause steroid-resistant nephrotic syndrome (NS), namely ADCK4-associated glomerulopathy. Reportedly, 38.5% of patients with ADCK4-associated glomerulopathy had end-stage renal disease (ESRD) at the time of diagnosis of ADCK4-associated glomerulopathy, requiring renal replacement therapy, such as dialysis and kidney transplantation. However, long-term NS recurrence risk of kidney transplantation in patients with ADCK4-associated glomerulopathy is unknown. Methods The clinical data and mutations in ADCK4 of two siblings with steroid-resistant NS were collected. The long-term prognosis of the two siblings who received kidney transplantation was evaluated. Results We describe two siblings with ADCK4-associated glomerulopathy who received deceased donor kidney transplantation and showed no clinical evidence of recurrence of NS during more than 10 years of follow-up. Conclusions This suggests that long-term NS recurrence risk of kidney transplantation is low in patients with ADCK4-associated glomerulopathy who progress to ESRD.

As they age, adult stem cells become more prone to functional decline, which is responsible for aging‐associated tissue degeneration and diseases. One goal of aging research is to identify drugs that can repair age‐associated tissue degeneration. Multiple organ development‐related signaling pathways have recently been demonstrated to have functions in tissue homeostasis and aging process. Therefore, in this study, we tested several chemicals that are essential for organ development to assess their ability to delay intestinal stem cell (ISC) aging and promote gut function in adult Drosophila. We found that taurine, a free amino acid that supports neurological development and tissue metabolism in humans, represses ISC hyperproliferation and restrains the intestinal functional decline seen in aged animals. We found that taurine represses age‐associated ISC hyperproliferation through a mechanism that eliminated endoplasmic reticulum (ER) stress by upregulation of the target genes of unfolded protein response in the ER (UPRER) and inhibiting the c‐Jun N‐terminal kinase (JNK) signaling. Our findings show that taurine plays a critical role in delaying the aging process in stem cells and suggest that it may be used as a natural compound for the treatment of age‐associated, or damage‐induced intestinal dysfunction in humans., In young Drosophila, taurine activates the UPRER target genes in ISCs, which in turn attenuates ER stress and prevents the over‐activation of JNK signaling. When flies get old, the abundance of taurine dramatically reduces, which causes an increase in ER stress, and the activation of UPRER sensors in ISCs. Ultimately, this leads to the hyperproliferation of ISCs with age.

Objectives: To observe the induction efficacy of mycophenolate mofetil and cyclophosphamide under different complete remission (CR) criteria in children with proliferative lupus nephritis, and to further explore the factors influencing the judgment of remission. Methods: From 2003 to 2019, children who diagnosed proliferative lupus nephritis underwent induction therapy of MMF or CYC in three hospitals were consecutively collected. Based on this population, we compared CR rates between two groups under six CR criteria selected from related recommendations and clinical trials. Then degrees and impact factors of disagreement among CR rates evaluated by selected criteria would be analyzed by Kappa test and multivariable logistic-regression models. Results: A total of 161 children were included in this study, 27 patients received induction therapy of mycophenolate mofetil (MMF) and 134 patients recieved cyclophosphamide (CYC). Under different CR criteria, CR rates in MMF group fluctuated between 18.5%-74.1% and that in CYC group ranged from 16.4%-73.9%. Moreover, comparison between the two drugs in induction treatment under different criteria showed an opposite trend in efficacy. The results of six criteria were inconsistent, with pair-to-pair Kappa values ranging from 0.118 to 0.858. The most important factors leading to disagreement in judgment were urinary protein and urinary red blood cells. Conclusions: The definition of complete response, especially the factors of the urinary protein and urinary red blood cells, significantly impacts the clinical judgment of children with lupus nephritis.

In recent years, there has been increasing interests in energy Internet. This paper mainly contributes to the energy router, the core device in the energy Internet. This article adopts AC/DC/AC three-stage structure, which is composed of modular multilevel converter (MMC), dual active bridge (DAB) converter, and three-phase full bridge inverter through the public DC bus to form the main topology of the energy router. And it contains multiple ports of high-voltage DC, low-voltage DC, and low-voltage AC, which is convenient for various forms of load access and realizes plug-and-play function. Research and design a hierarchical decoupling control scheme to simplify the control architecture while achieving independent and flexible control at all stages. In addition, for the input stage MMC structure, the capacitor voltage balance control of each sub-module, the bridge arm energy balance control strategy and the circulating current suppression strategy are designed to achieve the stability of the MMC output DC voltage and suppress the circulating current to a certain extent. Aiming at the topological structure in which multiple DAB units adopted input in series and output in parallel to the intermediate isolation stage, a parallel current sharing control strategy is designed to reduce the impact of parameter differences. Finally, the simulation results are verified by Matlab/Simulink.

Real-time information about vehicle mass and road grade is important for vehicle handling and stability control. This paper establishes the longitudinal kinematics model of vehicles, using the recursive least squares method with adaptive forgetting factors and extended Kalman filter algorithm to estimate the vehicle mass and road grade respectively. The experimental results indicate that the algorithm can estimate the vehicle mass and road grade well without adding sensors, and the convergence and steady-state error meet the requirements of the actual vehicle control system.

Papillorenal syndrome (PRS), an autosomal dominant inherited condition, is clinically featured by renal hypoplasia and optic nerve dysplasia. Based on current knowledge of genotype-phenotype correlations in PRS, mutations in the Paired box 2 (PAX2) gene have been recognized as a critical pathogenesis of typical renal and optic disease manifestations. However, little information is currently available on the skeletal abnormalities of PRS and the potential contribution of PAX2 mutations. Here, we present a case of a 10-year-old female PRS patient with the typical features of chronic renal failure and severe myopia, but was unexpectedly discovered camptodactyly of her left middle finger which affects the proximal interphalangeal joint. Pathologically, the camptodactyly was further indicated by radiology as a skeletal deformity, demonstrating a decline of bone mineral density and disappearance of joint space. Molecular diagnostics revealed a heterozygous mutation, 220_225dup, in the exon 3 of her PAX2 gene, which is de novo considering the lack of this mutation in her non-consanguineous parents. This mutation leads to duplication of glutamic acid at position 74 and tyrosine at position 75 in PAX2 protein, which may influence the DNA-binding function. Besides, the absence of Spalt like transcription factor 4 (SALL4) mutation excluded the diagnosis of acro-renal-ocular syndrome (AROS), of which clinical characteristics are similar to our patient's. This case unravels a previously unrecognized phenotype of camptodactyly due to a significant skeletal deformity of PRS with a heterogeneous PAX2 mutation of hexanucleotide duplication. This report challenges against the current belief of genotype-phenotype correlations in PRS.

Unsatisfied dielectric properties and inferior mechanical properties have become the main obstacles limiting the application of polybenzoxazole (PBO) in the field of microelectronics. Herein, a novel nanocomposite film was successfully developed by introducing fluorinated graphene (FG) into fluorinated PBO (FPBO). Interestingly, the FG/FPBO composite films showed an ultra-low dielectric constant of 2.02 at 1 MHz. Meanwhile, the tensile strength of the composite films increased up to 103.5 MPa, which was 25% higher than that of the pristine FPBO. Moreover, the 5% weight loss temperature of FG/FPBO composites were as high as 525 °C, displayed an outstanding heat resistance. The water absorption of FG/FPBO films have also dropped from 1% to 0.5% due to the high hydrophobicity of FG. In short, our work provides a simple and efficient approach for the preparation of high-performance films with low dielectric constant and water absorption, as well as high mechanical strength and thermal stability.

The aim of this study was to elucidate whether genetic screening test results of pediatric patients with steroid-resistant nephrotic syndrome (SRNS) vary with ethnicity.Using high-throughput DNA sequencing, 28 nephrotic syndrome-related genes were analyzed in 110 chil-dren affected by SRNS and 10 children with isolated proteinuria enrolled by 5 centers in China (67 boys, 53 girls). Their age at disease onset ranged from 1 day to 208 months (median, 48.8 months). Patients were excluded if their age at onset of disease was over 18 years or if they were diagnosed as having Alport syndrome.A genetic etiology was identified in 28.3% of our cohort and the likelihood of establishing a genetic diagnosis decreased as the age at onset of nephrotic syndrome increased. The most common mutated genes were ADCK4 (6.67%), NPHS1 (5.83%), WT1 (5.83%), and NPHS2 (3.33%), and the difference in the frequencies of ADCK4 and NPHS2 mutations between this study and a study on monogenic causes of SRNS in the largest international cohort of 1,783 different families was significant. A case of congenital nephrotic syndrome was attributed to a homozygous missense mutation in ADCK4, and a de novo missense mutation in TRPC6 was detected in a case of infantile nephrotic syndrome.Our results showed that, in the first and the largest multicenter cohort of Chinese pediatric SRNS reported to date, ADCK4 is the most common causative gene, whereas there is a low prevalence of NPHS2 mutations. Our data indicated that the genetic testing results for pediatric SRNS patients vary with different ethnicities, and this information will help to improve management of the disease in clinical practice.

Epithelial-repair-dependent mucosal healing (MH) is associated with a more favorable prognosis for patients with inflammatory bowel disease (IBD). MH is accomplished via repair and regeneration of the intestinal epithelium. However, the mechanism underlying MH is ill defined. We found a striking upregulation of peroxisomes in the injured crypts of IBD patients. By increasing peroxisome levels in Drosophila midguts, we found that peroxisome elevation enhanced RAB7-dependent late endosome maturation, which then promoted stem and/or progenitor-cell differentiation via modulation of Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT)-SOX21A signaling. This in turn enhanced ISC-mediated regeneration. Importantly, RAB7 and SOX21 were upregulated in the crypts of IBD patients. Moreover, administration of drugs that increased peroxisome levels reversed the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. This study demonstrates a peroxisome-mediated epithelial repair mechanism, which opens a therapeutic avenue for the enhancement of MH in IBD patients.

Background Studies have identified mutations in >50 genes that can lead to monogenic steroid-resistant nephrotic syndrome (SRNS). The NUP160 gene, which encodes one of the protein components of the nuclear pore complex nucleoporin 160 kD (Nup160), is expressed in both human and mouse kidney cells. Knockdown of NUP160 impairs mouse podocytes in cell culture. Recently, siblings with SRNS and proteinuria in a nonconsanguineous family were found to carry compound-heterozygous mutations in NUP160 . Methods We identified NUP160 mutations by whole-exome and Sanger sequencing of genomic DNA from a young girl with familial SRNS and FSGS who did not carry mutations in other genes known to be associated with SRNS. We performed in vivo functional validation studies on the NUP160 mutations using a Drosophila model. Results We identified two compound-heterozygous NUP160 mutations, NUP160 R1173× and NUP160 E803K . We showed that silencing of Drosophila NUP160 specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by expression of the wild-type human NUP160 gene in nephrocytes. By contrast, expression of the NUP160 mutant allele NUP160 R1173× completely failed to rescue nephrocyte phenotypes, and mutant allele NUP160 E803K rescued only nuclear pore complex and nuclear lamin localization defects. Conclusions Mutations in NUP160 are implicated in SRNS. Our findings indicate that NUP160 should be included in the SRNS diagnostic gene panel to identify additional patients with SRNS and homozygous or compound-heterozygous NUP160 mutations and further strengthen the evidence that NUP160 mutations can cause SRNS.

Genetic mutations in dozens of monogenic genes can lead to serious podocyte dysfunction, which is a major cause of steroid-resistant nephrotic syndrome (SRNS). The NUP160 gene is expressed in both human kidney and mouse kidney. However, whether knockdown of NUP160 impairs podocytes has not yet been established. Therefore, we knocked down NUP160 by targeted short hairpin RNA (shRNA) in conditionally immortalized mouse podocytes and observed the effect of NUP160 knockdown on the proliferation, apoptosis, autophagy and cell migration of podocytes. We also investigated the effect of NUP160 knockdown on the expression and localization of podocyte associated molecules, such as nephrin, podocin, CD2AP and α-actinin-4. The knockdown of NUP160 significantly inhibited the proliferation of podocytes by decreasing the expression of both cyclin D1 and CDK4, increasing the expression of p27, and inducing S phase arrest. The knockdown of NUP160 promoted the apoptosis and autophagy of podocytes, and enhanced cell migration. The knockdown of NUP160 decreased the expression of nephrin, podocin and CD2AP in podocytes, and increased the expression of α-actinin-4. The knockdown of NUP160 also altered the subcellular localization of nephrin, podocin and CD2AP in podocytes. These results suggest that the knockdown of NUP160 impairs mouse podocytes, i.e. inhibiting cell proliferation, inducing apoptosis, autophagy and cell migration of mouse podocytes, and altering the expression and localization of podocyte associated molecules, including nephrin, podocin, CD2AP and α-actinin-4.

In Chinese children with steroid-resistant nephrotic syndrome (SRNS), it was reported that NPHS2 mutation was detected in 4.3%, which was lower than that in Caucasians (10-30%). However, there were no data on WT1 mutation in nephrotic syndrome (NS), especially in early-onset NS of Chinese children. Thus, a study, which enrolled 36 Chinese children with early-onset (before 3 y old) NS and steroid resistance if failing steroid therapy (early-group), was conducted. As control, 35 children with SRNS and with disease onset age after 3 y old were also analyzed (control-group). WT1 gene was examined by PCR and direct sequencing. The result showed that in the early-group 6/36 (16.7%) were detected with WT1 mutations. Further analysis according to different onset age revealed that the mutation detection rates of WT1 were 26.3% (5/19), 6.3% (1/16), and 0 (0/1) in children younger than 1 y, 1-2 y, and 2-3 y, respectively. In control-group, no WT1 (0/35) mutation was detected. WT1 mutation combined with NPHS2 variant was detected in a girl. In conclusion, WT1 mutations seemed more common in Chinese children with early-onset NS.

A lot of mutations of podocin, a key protein of podocyte slit diaphragm (SD), have been found both in hereditary and sporadic focal segmental glomeruloscleorosis (FSGS). Nevertheless, the mechanisms of podocyte injury induced by mutant podocins are still unclear. A compound heterozygous podocin mutation was identified in our FSGS patient, leading to a truncated (podocin (V165X)) and a missense mutant protein (podocin (R168H)), respectively. Here, it was explored whether and how both mutant podocins induce podocyte injury in the in vitro cultured podocyte cell line. Our results showed that podocin (R168H) induced more significant podocyte apoptosis and expression changes in more podocyte molecules than podocin (V165X). Podocyte injury caused by the normal localized podocin(V165X) was effectively inhibited by TRPC6 knockdown. The abnormal retention of podocin(R168H) in endoplasmic reticulum (ER) resulted in the mis-localizations of other critical SD molecules nephrin, CD2AP and TRPC6, and significantly up-regulated ER stress markers Bip/grp78, p-PERK and caspase-12. These results implicated that podocin (R168H) and podocin (V165X) induced different degrees of podocyte injury, which might be resulted from different molecular mechanisms. Our findings provided some possible clues for further exploring the pharmacological targets to the proteinuria induced by different mutant podocins.

Previous studies have demonstrated that two homozygous missense MYO1E mutations are associated with childhood autosomal recessive focal segmental glomerulosclerosis in steroid-resistant nephrotic syndrome (SRNS) families from Italy and Turkey. Non-disease-causing heterozygous MYO1E variants were also found in other SRNS patient cohorts. However, the role of MYO1E mutations in Chinese sporadic SRNS has not been established.Peripheral blood samples were collected for genetic analysis from 54 children with sporadic SRNS in Chinese Han ethnic group and a normal control group of 59 healthy adult volunteers. None of the patients carried mutations in NPHS2 or WT1. Genomic DNA was extracted from peripheral blood leukocytes. Twenty-eight exons and exon-intron boundaries of the MYO1E gene were amplified by polymerase chain reaction. Mutational analysis was performed by direct DNA sequencing and restriction endonuclease digestion.Fifty-one variants in the MYO1E gene were identified in 54 children with sporadic SRNS. Among them, 10 MYO1E mutations of IVS1-11TC, IVS2-86TA, 279TC (D93D), IVS6-181GA, 718CT (L240F), 1678AG (T560A), IVS16-35AG, IVS18+48TA, IVS19+38GA and IVS25+13CT were detected in 11 patients, whereas they were absent in the 59 normal Chinese controls. Forty-one variants in MYO1E were identified and all of them were published in single nucleotide polymorphism database from national center for biotechnology information. Furthermore, all the 10 MYO1E mutations were in heterozygous states.MYO1E mutations are not a major cause of Chinese children with sporadic SRNS in the study.

Mutations in the WT1 gene can lead to Denys-Drash syndrome or Frasier syndrome and can also cause isolated nephrotic syndrome (NS). Most patients with isolated NS caused by WT1 mutations present as 46, XX phenotypic females. There have been two cases with an onset age younger than 3 years with isolated NS caused by WT1 mutations presenting as 46, XY phenotypic males. We present a 46, XY phenotypic male patient with isolated NS and end-stage renal disease (ESRD) at the age of 6.3 years. He had normal male external genitalia with normal penis length and soft and normal volume of both testes. A mutation, 1051A>G (K351E), in exon 8 of WT1 was identified in the patient. After starting hemodialysis, manifestations of hypertension and renal failure improved, but he died at 6.8 years of age as a result of respiratory failure and heart failure. Our study supports the necessity of searching for mutations in WT1 in 46, XY phenotypic male patients with isolated NS and ESRD.

The dynamic processes of the mode-locked laser based on a nonlinear auxiliary cavity containing a nonlinear frequency-doubling crystal have been studied systematically in this paper. The formulae for the output pulse width of this mode-locked laser in a dynamic equilibrium state are given, and our experimental results are shown to be in agreement with the theoretical calculations. Finally, we have also reported the dependence of laser output characteristics on some parameters.

Sufficient tissue yield is essential for renal biopsy. We have developed a simple automated renal biopsy device (Chen device) that constantly obtains more tissue. Since the Bard device is extensively used around the world, we compared our device with the Bard device. Pediatric patients were biopsied with either the Chen (n=247) or Bard (n=200) devices. No major complications were encountered and the incidence of minor complications was comparable between two devices. However, the average length of tissue obtained by the Chen device per biopsy (1.78±0.73 cm) was significantly longer than that obtained by the Bard device (1.23±0.45 cm). Accordingly, 61.94% of biopsies with the Chen device had 20 or more glomeruli, whereas only 18% of biopsies with the Bard device had this number (p

In this Letter we show that the power of stimulated Rayleigh wing scattering (SRWS) generated in bulk liquid of anisotropic molecules is reduced by a simultaneous presence of stimulated four-photon interaction (SFPI) because the combined effect of SRWS and SFPI results in a walk-off between the pump beam and the generated signal in the nonguided system and this shortens the nonlinear interaction length. The SRWS may be greatly enhanced in a hollow waveguide filled with a liquid of higher index of refraction than that of the waveguide cladding as the long interaction length is maintained for the whole length of the waveguide. The enhanced SRWS results in a considerable red-shifted frequency super-broadening of an intense optical pulse that passes through the waveguide, and which can be experimentally observed.

Previous studies have demonstrated that the genetic variations of glucocorticoid receptor gene (NR3C1) are associated with both familial steroid resistance and acquired steroid resistance in some diseases, such as Cushing's disease, leukemia, lupus nephritis, and female pseudohermaphroditism. In this study, we examined the genetic variations of NR3C1 in 35 children with sporadic steroid-resistant nephrotic syndrome (SRNS), and in 83 cases with sporadic steroid-sensitive NS (SSNS) using polymerase chain reaction, denaturing high-performance liquid chromatography and DNA sequencing, and analyzed possible associations between NR3C1 variants and steroid resistance in sporadic NS. No causative mutations were found; however, six previously identified and six novel polymorphisms, 1206C > T, 1374A > G, 2382C > T, 2193T > G, IVS7-68_-63delAAAAAA, and IVS8-9C > G, were detected. Two novel haplotypes, [1374A > G; IVS7-68_-63delAAAAAA; IVS8-9C > G; 2382C > T] and [1896C > T; 2166C > T; 2430T > C], of NR3C1 were also identified in sporadic NS and controls. The odds ratios (95% Confidence Interval) for the two novel NR3C1 haplotypes in the sporadic nephrotic children at risk of steroid resistance were 4.970 (0.889-27.788) and 2.194 (0.764-6.306), respectively, but the association between NR3C1 haplotypes and steroid resistance was not significant. Further studies on the possible association between the two novel NR3C1 haplotypes and steroid resistance in sporadic NS in larger cohorts are required.

Using the new negative pressure biopsy technology, the automatic negative pressure gun and the specific puncture needle for the biopsy have been developed. Renal biopsies were conducted in 1136 cases, with the success rate being 99.9%, and 29 cases gross hematuria while the hepatic biopsies were conducted in 16 cases, mass biopsies in 3 cases with the success rates being 100% respectively. The biopsy gun has the advantages of easy manipulation, higher success rate and lower incidence of complications.

Background. Since the identification of the NPHS2 gene, various investigators have demonstrated that an NPHS2 mutation is a frequent cause of sporadic steroid-resistant nephrotic syndrome (SRNS), and occurs in 10.5–28% of children with the syndrome. Idiopathic nephrotic syndrome (INS) is also the most frequent glomerular disease in Chinese children, of which � 20% of cases show steroid resistance. To our knowledge, however, whether or not NPHS2 is the causative gene in Chinese sporadic SRNS has not been established. This study aims to examine mutations in NPHS2 in Chinese children with sporadic SRNS. Methods. We examined 23 Chinese children with sporadic SRNS for mutations in NPHS2. The mutational analysis of NPHS2 was performed by polymerase chain reaction, denaturing high-performance liquid chromatography and DNA sequencing. Results. A heterozygous missense mutation of L361P in exon 8 of NPHS2 was detected in one of 23 children with sporadic SRNS, whereas it was not found in 53 controls. We also identified seven NPHS2 polymorphisms, � 51G>T, 288C>T, IVS3-46C>T, IVS321C>T, IVS7-74G>C, 954T>C and 1038A>G, in some patients and controls. There was no significant difference in the genotypic and allelic frequencies of these polymorphisms between the patients and controls. Conclusion. The results demonstrate that NPHS2 mutations are also present in Chinese sporadic SRNS. Our investigation supports the necessity of searching for mutations in NPHS2 in Chinese children with sporadic SRNS.

Since the identification of the NPHS2 gene, which encodes podocin, several groups from European, Middle Eastern, and North American countries have reported NPHS2 mutations in families with steroid-resistant nephrotic syndrome (SRNS) or focal segmental glomerulosclerosis (FSGS). Families with SRNS have also been reported in China with a population of more than 1.3 billion. However, to our knowledge, there is no mutational analysis of the NPHS2 gene in familial SRNS or FSGS in China. We identified a novel mutation of NPHS2 (467_468insT and 503G>A) in a Chinese family with autosomal recessive SRNS using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing techniques. The results demonstrate that there is also NPHS2 mutation in Chinese familial SRNS. Therefore, Chinese SRNS patients with a familial history of NS should also be screened for possible mutations of NPHS2. We also detected clearly decreased staining with a specific podocin C-terminal antibody (P35) and negative staining with a specific podocin N-terminal antibody (P21). These results were contrary to those predicted from the mutated sites. Further studies are needed to explore the mechanism and impact of the mutant gene on the expression and localization of the relevant protein.

Mutations in the WT1 gene, leading to Denys-Drash syndrome and Frasier syndrome, can also cause isolated steroid-resistant nephrotic syndrome (ISRNS). Previous studies have reported six pairs of monozygotic twins with WT1 mutations, including one presenting with discordant phenotypes with identical WT1 mutations being of paternal origin and five pairs of monozygotic twins presenting the same phenotype with identical WT1 mutations. In this study, we report on female monozygotic twins showing discordant phenotypes with an identical de novo WT1 mutation, R394W, and presenting incomplete Denys-Drash syndrome and ISRNS.