Correlation between Toll-like Receptor Gene Polymorphisms and Idiopathic Nephrotic Syndrome in Chinese Children.

OBJECTIVE: Idiopathic nephrotic syndrome (INS) is the most common glomerular disease in children. Toll-like receptors (TLRs) have been reported to be associated with response to steroid treatment in children with INS. Nevertheless, the correlation between TLR genes and the progression of INS has not yet been clarified. The present study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) in TLR2, TLR4, and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS. METHODS: A total of 183 pediatric inpatients with INS were included and given standard steroid therapy. Based on their clinical response to steroids, the patients were classified into three groups: steroid-sensitive nephrotic syndrome (SSNS), steroid-dependent nephrotic syndrome (SDNS), and steroid-resistant nephrotic syndrome (SRNS). A total of 100 healthy children were employed as controls. The blood genome DNA was extracted from each participant. Six SNPs (rs11536889, rs1927914, rs7869402, rs11536891, rs352140, and rs3804099) in TLR2, TLR4, and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms. RESULTS: Among the 183 patients with INS, 89 (48.6%) had SSNS, 73 (39.9%) had SDNS, and 21 (11.5%) had SRNS. No significant difference was found in the genotype distribution between healthy children and patients with INS. However, the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS. Compared with patients with the C allele and CC genotype, patients with the T allele and CT genotype had an increased risk of SRNS. CONCLUSION: TLR4 rs7869402 affected the steroid response in Chinese children with INS. It might be a predictor for the early detection of SRNS in this population.

Prognostic factors of pediatric pelvic and genitourinary rhabdomyosarcoma: An analysis based on SEER database.

Background: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcomas in children. This study aimed to investigate the prognostic factors of pelvic and genitourinary RMS in children and evaluate the survival outcomes of these children treated with or without radiation therapy (RT). Methods: The Surveillance, Epidemiology, and End Results Program (SEER) database was required for children with pelvic and genitourinary RMS. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. Results: For the 262 patients analyzed, the most common biological subtypes were embryonic (n=209, 79.8%) and alveolar (n=29, 11.1%). Patients with alveolar RMS had the worst prognosis (P < 0.05). The testis (n=122, 46.6%) was the most common location, followed by the urinary bladder (n=57, 21.8%) and prostate (n=48, 18.3%). Uterus RMS had the highest survival rate, followed by testis, urinary bladder, and prostate RMS. Favorable prognostic factors were age at diagnosis < 15 years, non-alveolar histological subtype, early tumor stage (localized/regional), specific sites (uterus and testis), and treatment (cancer-directed surgery and chemotherapy) (P < 0.05). Propensity score-matched analyses comparing the cohorts of patients treated with or without RT demonstrated no significant differences in prognostic survival (OS: P=0.872, CSS: P=0.713). Conclusion: The nomogram constructed based on independent prognostic factors may accurately predict survival rates at 1 and 5 years. Surgery and adjuvant chemotherapy can be effective treatments, but RT fails to guarantee a survival benefit. Therefore, prospective trials evaluating RT for pediatric pelvic and genitourinary RMS are warranted.

Epidemiological Study on Mycoplasma pneumoniae and Chlamydia pneumoniae Infection of Hospitalized Children in a Single Center During the COVID-19 Pandemic.

Background: Since the outbreak of COVID-19, a series of preventive and control measures in China have been used to effectively curb the spread of COVID-19. This study aimed to analyze the epidemiological characteristics of Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP) in hospitalized children with acute respiratory tract infection during the COVID-19 pandemic. Methods: MP IgM antibody and CP IgM antibody were detected in all hospitalized children due to acute respiratory tract infection in the Children's Hospital Affiliated to Zhejiang University from January 2019 to December 2020. These data were compared between 2019 and 2020 based on age and month. Results: The overall detection rate of MP and CP in 2020 was significantly lower than that in 2019 (MP: 21.5% vs 32.9%, P<0.001; CP: 0.3% vs 0.9%, P<0.001). This study found a 4-fold reduction in the number of children positive for MP and a 7.5-fold reduction in the number of children positive for CP from 2019 to 2020. The positive cases were concentrated in children aged >1 year old. In 2019, the positive rate of MP was detected more commonly in children 3 years of age or older than in younger children. In 2020, the higher positive rate of MP reached a peak in the 3- to 6-year age group (35.3%). CP was detected predominantly in children aged 6 years older in 2019 and 2020, with positive rates of 4.8% and 2.6%, respectively. Meanwhile, the positive rates of MP in 2019 were detected more commonly in July, August and September, with 47.2%, 46.7% and 46.3%, respectively. Nevertheless, the positive rates of MP from February to December 2020 apparently decreased compared to those in 2019. The positive rates of CP were evenly distributed throughout the year, with 0.5%-1.6% in 2019 and 0.0%-2.1% in 2020. Conclusions: A series of preventive and control measures for SARS-CoV-2 during the COVID-19 pandemic can not only contain the spread of SARS-CoV-2 but also sharply improve the infection of other atypical pathogens, including MP and CP.

Urinary Sediment mRNA Level of CREBBP and CYBA in Children With Steroid-Resistant Nephrotic Syndrome.

Background: This study aimed to evaluate gene expression patterns in urinary sediment samples of children with steroid-resistant nephrotic syndrome (SRNS). Methods: The messenger RNA (mRNA) levels of 770 immune-related genes were detected using a NanoString nCounter platform. To verify the NanoString results, quantitative analysis of nine gene mRNAs was performed using real-time RT-PCR in more samples. Results: Firstly, compared with the steroid-sensitive nephrotic syndrome (SSNS) group (n=3), significant changes were observed in the mRNA level of 70 genes, including MAP3K14, CYBA, SLC3A2, CREB-binding protein (CREBBP), CD68, forkhead box P1 (FOXP1), CD74, ITGB2, IFI30, and so forth, in the SRNS group (n=3). A total of 129 children with idiopathic nephrotic syndrome (INS), 15 with acute glomerulonephritis, and 6 with immunoglobulin A nephropathy (IgAN) were enrolled to verify the NanoString results. Compared with patients with IgAN, those with INS had significantly lower levels of FOXP1 (P=0.047) and higher levels of CREBBP (P=0.023). Among SSNS, the mRNA level of ITGB2 was significantly lower in the non-relapse group than in the non-frequent relapse and frequent-relapse groups (P=0.006). Compared with the SSNS group, CREBBP was significantly elevated in the SRNS group (P=0.02). Further, CYBA significantly decreased in the SRNS group (P=0.01). The area under the curve (AUC) for CREBBP and CYBA was 0.655 and 0.669, respectively. CREBBP had a sensitivity of 83.3% and a specificity of 49.4% and CYBA had a sensitivity of 58.3% and a specificity of 83.1% to rule out SSNS and SRNS. The diagnosis value was better for CREBBP+CYBA than for CREBBP or CYBA alone, indicating that the combination of CREBBP and CYBA was a more effective biomarker in predicting steroid resistance (AUC=0.666; sensitivity=63.9%; specificity=76.4%). Conclusions: This study was novel in investigating the urinary sediment mRNA level in children with INS using high-throughput NanoString nCounter technology, and 70 genes that may relate to SRNS were found. The results revealed that the urinary sediment mRNA level of ITGB2 was significantly lower in the non-relapse group than in the non-frequent relapse and frequent-relapse groups. Meanwhile, CREBBP was significantly elevated and CYBA was significantly lowered in the SRNS group compared with the SSNS group.

Non-fluoroscopic percutaneous transcatheter closure of atrial septal defects in children under transesophageal echocardiographic guidance.

BACKGROUND: This study sought to investigate the feasibility, safety and effectiveness of transcatheter closure of atrial septal defects (ASDs) under the guidance of transesophageal echocardiography (TEE) in children. METHODS: We reviewed the medical records of patients who underwent percutaneous ASD closure at our center from August 2016 to December 2017. For a total of 88 patients who were identified as having a single-hole defect and were undergoing percutaneous transcatheter ASD closure, a procedure completely guided by TEE was performed. There were 31 male patients and 57 female patients. The patients' mean age was 60.09 ± 36.42 months (13-182 months), and their mean body weight was 20.16 ± 10.04 kg (9-77 kg). Patients were followed up by performing transthoracic echocardiography and obtaining chest X-rays and electrocardiograms. RESULTS: The transcatheter closure of ASDs was successful in all patients. The mean ASD size was 11.58 ± 5.31 mm (3-28 mm), and the mean size of the occlusion device was 16.07 ± 5.29 mm (6-36 mm). The mean procedural times were 13.33 ± 2.82 minutes (6-16 minutes). The mean hospitalization costs were 27,259.66 ± 2507.04 RMB (25,200.00-33,911.45 RMB). The mean postoperative hospital stay was 3.22 ± 0.53 days (3-5 days). Residual shunt, occlusion device shedding or displacement, and pericardial effusion were not observed during or after the operation. CONCLUSION: Percutaneous transcatheter ASD closure completely guided by TEE is a feasible, safe, non-invasive and easy procedure.