[Clinical, genetic, and pathological analysis in 165 children with disorders of sex development]. / 165ä¾‹å„¿ç«¥æ€§å‘è‚²å¼‚å¸¸ç–¾ç— çš„ä¸´åºŠã€é—ä¼ å­¦ä¸Žç— ç†å­¦åˆ†æž.

OBJECTIVES: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). METHODS: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. RESULTS: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. CONCLUSIONS: Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.

Lack of association between vitamin D receptor genes BsmI as well as ApaI polymorphisms and osteoporosis risk: A pooled analysis on Chinese individuals.

BACKGROUND: As for the association between vitamin D receptor (VDR) gene polymorphisms and osteoporosis, the current results have yielded conflicts. Therefore, we performed a pooled analysis based on Chinese individuals to provide comprehensive data on the association between VDR BsmI, ApaI, Tru9I polymorphisms and osteoporosis risk. METHODS: Studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine databases through to January 2017. Studies were screened according to the predefined inclusion and exclusion criteria. The association between VDR BsmI, ApaI, Tru9I polymorphisms and osteoporosis was evaluated by calculating pooled odds ratios (ORs) based on the individual ORs. The significance of the pooled OR was evaluated by a Z-test. All statistical analyses were conducted using Stata 12.0 software (StataCorp, College Station, TX, USA). RESULTS: A total of 13 studies with 1141 osteoporosis cases and 1263 controls were included in this meta-analysis. It revealed that VDR Tru9I polymorphism was associated with an increased risk of osteoporosis in a common model (OR = 2.67, CI 95% = 1.59-4.49). No significant association was observed between VDR BsmI, ApaI and osteoporosis. CONCLUSION: In conclusion, this meta-analysis suggests that VDR Tru9I polymorphism may be associated with osteoporosis risk in Chinese individuals, while BsmI, ApaI polymorphisms might not be a risk factor for osteoporosis.

Primary culture of lung fibroblasts from hyperoxia-exposed rats and a proliferative characteristics study.

Lung fibrosis is an ultimate consequence of bronchopulmonary dysplasia (BPD) which shows the excessive proliferation of lung fibroblasts (LFs). To find a better model for studying the role of LFs in hyperoxia-induced lung fibrosis at the cellular level, we isolated LFs from the lung tissue of hyperoxia- and normoxia-exposed rat lungs on postnatal days 7, 14 and 21 for primary culture to study their proliferative behavior. In the present study, the LF predominance was > 95% in our culture method. The LFs isolated from rats exposed to hyperoxia in vivo showed significantly greater proliferation than that from normoxia-exposed rats. Flow cytometry revealed that percentage of LFs in S and G2/M stage increased, and proportion in the G0/G1 stage declined at the same time. A greater presence of myofibroblasts in LFs isolated from rats exposed to hyperoxia compared with those exposed to normoxia. In addition, elevated collagen level, transforming growth factor-ß and connective tissue growth factor protein expression in conditioned medium were also found in hyperoxia LFs. These data demonstrate that hyperoxia promotes LFs proliferation, myofibroblast transdifferentiation and collagen synthesis in a time-dependent manner. The primary culture of LFs from hyperoxia-exposed rats is a feasible method for studying the pathogenesis and treatment of lung fibrosis caused by BPD at the cellular level.

5-aza-2'-deoxycytidine, a DNA methylation inhibitor, attenuates hyperoxia-induced lung fibrosis via re-expression of P16 in neonatal rats.

BackgroundP16 methylation plays an important role in the pathogenesis of hyperoxia-induced lung fibrosis. 5-aza-2'-deoxycytidine (5-aza-CdR) is a major methyltransferase-specific inhibitor. In this study, the effects of 5-aza-CdR on a hyperoxia-induced lung fibrosis in neonatal rats were investigated.MethodsRat pups were exposed to 85% O2 for 21 days of and received intraperitoneal injections of 5-aza-CdR or normal saline (NS) once every other day. Survival rates and lung coefficients were calculated. Hematoxylin-eosin staining was performed to analyze the degree of lung fibrosis. Collagen content and TGF-ß1 levels were determined. A methylation-specific polymerase chain reaction and western blotting were performed to determine P16 methylation status and P16, cyclin D1, and E2F1 protein expression.Results5-aza-CdR treatment during hyperoxia significantly improved the survival rate and weight gain, while it decreases the degree of lung fibrosis and levels of hydroxyproline and TGF-ß1. Hyperoxia induced abnormal P16 methylation and 5-aza-CdR effectively reversed the hypermethylation of P16. Expression of the P16 protein in lung tissues was enhanced, while cyclin D1 and E2F1 protein were reduced by 5-aza-CdR treatment during hyperoxia.ConclusionThese data show that 5-aza-CdR attenuated lung fibrosis in neonatal rats exposed to hyperoxia by lowering hydroxyproline and TGF-ß1 expression and via re-expression of P16 in neonatal rats.

Autophagy regulates hyperoxia-induced intracellular accumulation of surfactant protein C in alveolar type II cells.

Surfactant protein C (SP-C) deficiency is a risk factor for hyperoxia-induced bronchopulmonary dysplasia in newborn infants. However, the role of SP-C deficiency in the process is unclear. Here, using neonatal rat BPD model and MLE-12, mouse alveolar epithelial type II cell, we examined the changes of SP-C levels during hyperoxia. Immunohistochemistry, immunofluorescence, and ELISA analysis showed SP-C accumulation in alveolar epithelial type II cells. Electron microscopy further demonstrated the accumulation of lamellar bodies and the co-localization of lamellar bodies with autophagosomes in the cytoplasm of alveolar epithelial type II cells. The inhibition of autophagy with 3-Methyladenine and knockdown of Atg7 abolished hyperoxia-induced SP-C accumulation in the cytoplasm. Furthermore, inhibition of JNK signaling with SP600125 suppressed hyperoxia-induced Atg7 expression and SP-C accumulation. These findings suggest that hyperoxia triggers autophagy via JNK signaling-mediated Atg7 expression, which promotes the accumulation of SP-C within alveolar epithelial type II cells. Our data provide a potential approach for hyperoxic lung injury therapy by targeted pharmacological inhibition of autophagic pathway.

[Genetic polymorphism of surfactant protein A in neonatal respiratory distress syndrome].

OBJECTIVE: To investigate the characteristics of gene expression of surfactant protein A in Chinese premature infants and the association between surfactant protein A and the risk of neonatal respiratory distress syndrome (RDS). METHODS: Vein-blood samples (2 mL) from 18 Chinese premature infants with RDS and 28 controls were assayed for SP-A genotypes 6A2, 6A3, 1A0 and 1A1 by SSCP. RESULTS: The frequency of allele distribution of SP-A1 allele 6A2 and 6A3 was 0.50 and 0.056 respectively in the RDS group and was 0.214 and 0.107 in the control group. Compared with the controls, SP-A1 allele 6A2 was over-represented in the RDS group (P<0.05). In contrast, SP-A1 allele 6A3 tended to be under-represented in the RDS group but there was no statistical difference when compared with the controls. The frequency of allele distribution of SP-A2 allele 1A0 and 1A1 was 0.722 and 0.667 respectively in the RDS group and was 0.679 and 0.821 respectively in the control group. There were no significant differences in the distribution frequency of SP-A2 allele 1A0 and 1A1 between the two groups. In the infants born at gestation >32 weeks, SP-A1 allele 6A2 was over-represented in the RDS group compared with the control group (frequency: 0.56 vs 0.15; P<0.05). CONCLUSIONS: The frequency of SP-A1 allele 6A2 and 6A3 was low, in contrast, the frequency of SP-A2 allele 1A0 and 1A1 was high in normal Chinese premature infants. SP-A1 allele 6A2 may be a susceptible gene for RDS.