Phenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy.

BACKGROUND: Nephronophthisis-related ciliopathies (NPHP-RC) account for the majority of cases of monogenetically caused end-stage renal disease (ESRD) in children. Exploring the correlation between the phenotype and genotype of NPHP-RC is helpful for early diagnosis and management. We investigated the phenotype and genotype spectra of NPHP-RC in a Chinese multicentre cohort. METHODS: Crosss-ectional and longitudinal data of 60 patients from 57 families with pathogenic NPHP-RC gene mutations distributed in 22 regions of China were collected into a unified, anonymous database. The mean observation time of this cohort was 3.5±3.1 years. RESULTS: Mutations in NPHP1 and NPHP3 were the most common genetic defects. Overall, 45% of patients presented with isolated nephronophthisis (NPH), and 55% exhibited the extrarenal phenotype, which frequently involved the liver (41.7%, n=25), central nervous system (26.7%, n=16), eyes (26.7%, n=16) and skeletal system (11.7%, n=7). Accidental detection of elevated serum creatinine and non-specific symptoms caused by chronic kidney disease occurred in 65% of patients. Patients carrying NPHP1 mutations mainly presented with isolated NPH (90%, 18/20) and progressed to ESRD at a mean age of 12.9±0.5 years. The mean age of ESRD onset in the non-NPHP1 group was lower than that in the NPHP1 group (6.2±1.4 years, p<0.001), especially for patients carrying NPHP3 mutations (3.1±1.2 years), showing a heterogeneous phenotype characterised by Bardet-Biedl syndrome (12.5%, n=5), Joubert syndrome (7.5%, n=3), COACH syndrome (2.5%, n=1), Mainzer-Saldino syndrome (2.5%, n=1), short-rib thoracic dysplasia (2.5%, n=1) and unclassified symptoms (32.5%, n=13). CONCLUSIONS: The Chinese Children Genetic Kidney Disease Database registry characterised the spectrum of the phenotype and genotype of NPHP-RC in the Chinese population. NPHP1 and NPHP3 were the most common pathogenic genes. Rapid progression to ESRD and liver involvement were noted in patients with NPHP3 mutations.

[Clinical phenotype characteristics and genetic analysis in children with nephronophthisis and related syndromes caused by different gene mutations]. / ä¸åŒåŸºå› çªå˜è‡´è‚¾å•ä½è‚¾ç—¨åŠç›¸å ³ç»¼åˆå¾æ‚£å„¿ä¸´åºŠè¡¨åž‹ç‰¹ç‚¹åŠåŸºå› åˆ†æž.

OBJECTIVES: To improve the understanding of the clinical phenotypes and genetic characteristics of nephronophthisis (NPHP) and related syndromes in children. METHODS: A retrospective analysis was performed on the medical data of eight children with NPHP and related syndromes who were diagnosed and treated in the Department of Pediatrics of the Second Hospital of Hebei Medical University, from January 2018 to November 2022. The clinical characteristics and genetic testing results were analyzed. RESULTS: Among these eight children, there were five boys and three girls, with an age of onset ranging from 15 months to 12 years. All 8 children exhibited different degrees of renal function abnormalities when they attended the hospital. Among the eight children, two had the initial symptom of delayed development, two had the initial symptom of anemia, and two were found to have abnormal renal function during physical examination. The extrarenal manifestations included cardiovascular abnormalities in two children, skeletal dysplasia in two children, liver dysfunction in one child, retinitis pigmentosa in one child, and visceral translocation in one child. All eight children had renal structural changes on ultrasound, and four children had mild to moderate proteinuria based on routine urine test. Of all eight children, five had NPHP1 gene mutations and one each had a gene mutation in the NPHP3, IFT140, and TTC21B genes, and four new mutation sites were discovered. CONCLUSIONS: Children with NPHP and related syndromes often have the initial symptom of delayed development or anemia, and some children also have extrarenal manifestations. NPHP and related syndromes should be considered for children with unexplained renal dysfunction, and high-throughput sequencing may help to make a confirmed diagnosis.

Clinicopathologic comparisons of IgA nephropathy and IgA vasculitis nephropathy in children: a ten-year single-center experience.

BACKGROUND: To investigate the similarities and differences of renal clinical and renal pathology between IgA nephropathy (IgAN) and IgA vasculitis nephritis (IgAVN) in children. METHODS: A total of 237 children with IgAN and 190 children with IgAVN were included. The general conditions, clinical characteristics, final diagnosis, clinical and pathological classification of the children were intercepted at the time of admission, and the retrospective comparative analysis was carried out. RESULTS: The results showed that the median course of disease in IgAN group was longer than that in IgAVN group (p = 0.02). Patients with IgAN had a significantly higher duration of infection than the patients with IgAVN (p = 0.03). The white blood cell count (WBC), hemoglobin (HGB) in IgAN group were significantly lower than that in IgAVN group (p = 0.02). The serum creatinine in IgAN group was higher than that in IgAVN group (p = 0.02). Patients with IgAN and IgAVN had statistically significant differences in pathological typing between clinical types: hematuria and proteinuria, nephrotic syndrome and chronic nephritis (p = 0.004). DISCUSSION: The clinical manifestations of IgAN and IgAVN were similar, but the onset of IgAN was hidden and the clinical manifestations were relatively serious. Renal pathology was mainly glomerulosclerosis and renal tubular atrophy. IgAVN was characterized by acute onset and good renal function. Renal pathology was dominated by endothelial hyperplasia and crescent formation. These differences did not support the hypothesis that the two diseases are the same.

Facet and d-band center engineering of CuNi nanocrystals for efficient nitrate electroreduction to ammonia.

Electrocatalytic nitrate reduction offers a sustainable route to ammonia synthesis and wastewater treatment. However, the nitrate-to-ammonia conversion remains inefficient due to the sluggish kinetics and diverse side reactions. Herein, well-faceted CuNi nanocrystals with Ni-rich surfaces and favorable d-band centres were synthesized with the assistance of γ-cyclodextrin via a solvothermal process. When used as catalysts for nitrate electroreduction, they delivered an ammonia yield of 1.374 mmol h-1 mg-1 (0.5496 mmol h-1 cm-2) at -0.3 V with the faradaic efficiency and selectivity reaching 94.5% and 65.0%, respectively, surpassing pure Cu or Ni nanocrystals and most reported catalysts. Such excellent performances originated from the optimal geometric and electronic structures and special element distribution, which optimized the adsorption behaviors and accelerated the reaction kinetics. A NO3--NO2--NH3 pathway was proposed with the chemical process following the initial electron transfer process as the rate-determining step. This work sheds light on the design of efficient catalysts to achieve carbon neutrality through simultaneous geometric and electronic structure modulation.

Elevating the p-band centre of SnO2 nanosheets through W incorporation for promoting CO2 electroreduction.

SnO2 is one of the most promising catalysts for CO2 electroreduction. However, the intrinsic low electrical conductivity and weak CO2 adsorption and activation capability have rendered the reaction kinetically sluggish and inefficient. To surmount these hurdles, herein, W was incorporated into SnO2 nanosheets to modulate the electronic structures. Compared with pristine SnO2, the p-band centre of W-doped SnO2 was elevated towards the Fermi level, accompanied by the reduction in the band gap and work function. As a result, both the CO2 adsorption and the electron transfer process were promoted, thus lowering the activation energy barrier for CO2 reduction. Benefitting from these, a maximum faradaic efficiency of 87.8% was achieved for HCOOH at -0.9 V vs. the RHE. Meanwhile, the current density and energy efficiency approached 20.92 mA cm-2 and 60%, respectively. Such performances could sustain for 14 h without obvious fading and exceeded pristine SnO2 and most reported Sn-based catalysts. Tafel slope and reaction order analyses further suggested that the reaction proceeded following a stepwise electron-proton transfer pathway with the formation of CO2˙- as the rate determining step. This work demonstrated the effectiveness of electronic structure tuning in promoting the catalytic performances of p-block metal oxides and contributed to the development of efficient catalysts for sustainable energy conversion and carbon neutrality.

Stormorken Syndrome Caused by a Novel STIM1 Mutation: A Case Report.

Objective: To identify the gene mutation of Stormorken syndrome and review the published Stromal Interaction Molecule 1 (STIM1) mutation phenotype. Methods: We described the clinical and molecular aspects of a Chinese female with Stormorken syndrome by laboratory tests, muscle biopsies, and genetic analysis. We used this information to summarize all the mutation sites reported in the literature. We also reviewed the clinical features of published cases with a gain of function mutations of STIM1. Results: A 12-year-old Chinese female presented with skin purpura in the lower limbs and stroke-like episodes. Muscle biopsy and microscopic examination revealed atrophy in her skeletal muscle. Genetic analysis identified a novel heterozygous missense mutation, a c.1095G>C transition (NM_003156.3), which caused a p.K365N amino acid substitution in the protein and affected a STIM1-orai1-activation region (SOAR). Conclusions: The novel variant c.1095G>C transition (NM_003156.3) was located in the SOAR, which expands the phenotypic spectrum of STIM1 variants in human disorders and may define the molecular basis of Stormorken syndrome.

Changes of Peripheral Blood Lymphocyte Subsets and Immune Function in Children with Henoch-Schonlein Purpura Nephritis.

BACKGROUND: Purpuric nephritis is the most common secondary glomerular disease in childhood. Its prevalence in children has been steadily rising in recent years. OBJECTIVE: To explore the characteristics and pathogenesis of changes in peripheral blood lymphocyte subsets and immune function in children with Henoch-Schonlein purpura nephritis. METHODS: The study included 104 children with Henoch-Schonlein purpura, divided into nephritis (HSPN) group (68 cases) and non-nephritis (NHSPN) group (36 cases), and 15 normal children. The rate-scatter turbidimetric method was utilized to determine the immunoglobulins IgA, IgG, IgM, C3 and C4, and the flow cytometry technique was employed to detect the levels of lymphocyte subsets including CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, NK, etc. RESULTS: Compared with the control group, the CD3+, CD4+, CD8+ and NK cell levels of peripheral blood mononuclear cells significantly decreased (P<0.05), and the CD19+ level significantly elevated (P<0.05) in the HSPN group and the NHSPN group whereas the HSPN group had a more significant change than the NHSPN group (P<0.05). Compared with the control group, the serum immunoglobulin IgA and IgG of the HSPN group and the NHSPN group significantly increased, and the IgM, C3, and C4 significantly decreased (P<0.05); while the HSPN group had a more significant change than the NHSPN group (P<0.05). CONCLUSION: Immune dysfunction in children with HSPN is specifically manifested as low cellular immune function, which leads to increased secretion of inflammatory mediators, activates B cells, and further increases the secretion of immunoglobulins, leading to the occurrence of small vasculitis.

Effect of Sirolimus on the Level of Peripheral Blood Lymphocyte Autophagy in Children With Systemic Lupus Erythematosus.

Background: To observe the changes of autophagy-related protein levels in peripheral blood lymphocytes before and after sirolimus treatment in children with systemic lupus erythematosus (SLE). Methods: Children with SLE were randomly divided into two groups, 28 in the traditional treatment group and 28 in the sirolimus group. Fifteen healthy children who were in the same period were collected as the normal control group. Clinical laboratory indexes, the percentage of routine lymphocytes, complement C3, complement C4, serum Anti-dsDNA and SLEDAI were detected. Results: At 3 and 6 months after treatment, compared with the traditional treatment group, the percentage of routine lymphocytes in the sirolimus group increased (P = 0.03), SLEDAI score and positive rate of Anti-dsDNA decreased (P = 0.01). Compared with normal children, the expression of microtubule-associated protein 1 light chain 3 (LC3) protein in peripheral blood lymphocytes was significantly higher (P = 0.006); peripheral blood expression of P62/SQSTM1 (sequestosome 1) protein in lymphocytes decreased (P = 0.02). Conclusion: Sirolimus can play a role in the treatment of systemic lupus erythematosus by regulating the level of autophagy.