Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Familial male-limited precocious puberty due to Asp578His mutations in the LHCGR gene: clinical characteristics and gene analysis in an infant / 中国当代儿科杂志

The aim of the study was to provide a descriptive analysis of familial male-limited precocious puberty (FMPP), which is a rare inherited disease caused by heterozygous constitutively activating mutations of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR). The patient was a ten-month-old boy, presenting with penile enlargement, pubic hair formation, and spontaneous erections. Based on the clinical manifestations and laboratory data, including sexual characteristics, serum testosterone levels, GnRH stimulation test, and bone age, this boy was diagnosed with peripheral precocious puberty. Subsequently the precocious puberty-related genes were analyzed by direct DNA sequencing of amplified PCR products from the patient and his parents. Genetic analysis revealed a novel heterozygous missense mutation c.1732G>C (Asp578His) of the LHCGR gene exon11 in the patient, which had never been reported. His parents had no mutations. After combined treatment with aromatase inhibitor letrozole and anti-androgen spironolactone for six months, the patient's symptoms were controlled. The findings in this study expand the mutation spectrum of the LHCGR gene, and provide molecular evidence for the etiologic diagnosis as well as for the genetic counseling and prenatal diagnosis in the family.

Association between acanthosis nigricans and metabolic syndrome in children with obesity / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate adipokines levels in obese children with acanthosis nigricans (AN) and to explore the relationship between AN and metabolic syndrome (MS).</p><p><b>METHODS</b>A cross-sectional study was performed on 109 obese children and 47 age- and gender-matched normal controls. The obese children were divided into two groups with AN and without AN. Serum levels of adiponectin, leptin, TNF-α and retinol-binding protein 4 (RBP4) were measured using ELISA. Multiple logistic regression analysis was performed to estimate the association of clinical parameters with MS.</p><p><b>RESULTS</b>Waist-hip ratio, systolic blood pressure, triglyceride, fasting insulin and insulin resistance index (HOMA-IR) were significantly higher in obese children with AN than in those without AN and normal controls (P<0.05). The obese children with AN and without AN had lower adiponectin levels than normal controls (P<0.05), on the contrary, the obese children with AN had higher leptin levels than those without AN and normal controls (P<0.05). Multiple logistic regression analysis revealed that AN (OR=3.469, 95%CI: 1.518-7.929) and BMI (OR=7.108, 95%CI: 2.359-21.416) were independent risk factors for MS.</p><p><b>CONCLUSIONS</b>As a visible marker of insulin resistance, AN is associated with abnormal adipokines secretion. Reducing the incidence of AN and losing weight may prevent obesity associated MS.</p>

Research advances on CIDEC in insulin resistance / 中国当代儿科杂志

Childhood obesity has been rising dramatically in recent years and most patients are insulin resistant. Recent studies have indicated that cell death-inducing DFF45-like effector C (CIDEC) is responsible for the development of insulin resistance. CIDEC regulates adipogenesis, lipid storage and lipolysis, thus protecting insulin target tissues from lipotoxity. This paper reviews current findings on the structure and function of CIDEC, its transcriptional and post-translational regulations, and the underlying mechanism of CIDEC causing insulin resistance. As a novel lipid droplet protein, CIDEC may be a drug target for treatment of insulin resistance and relevant metabolic disorders.

Screening of differentially expressed genes during adipocyte differentiation by suppression subtractive hybridization technique / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To screening differentially expressed genes related to adipocyte differentiation.</p><p><b>METHODS</b>Total RNA extracted from the preadipocyte cell line SW872 was taken as the Driver and the total RNA from the differentiated adipocytes SW872 as the Tester. Suppression subtractive hybridization (SSH) was used to isolate the cDNA fragments of differentially expressed genes. The products of SSH were inserted into pGM-T vector to establish the subtractive library. The library was amplified through E.coli transformation and positive clones of the transformants were screened. Positive clones were sequenced. Nucleic acid similarity was subsequently analyzed by comparing with the data from GenBank.</p><p><b>RESULTS</b>There were 135 white clones in the cDNA library, 64 positive clones were chosen randomly and sequenced and similarity search revealed 34 genes which expressed differentially in adipocyte differentiation.</p><p><b>CONCLUSION</b>The subtracted cDNA library for differentially expressed in adipocyte differentiation has been successfully constructed and the interesting candidate genes related to adipocyte differentiation have been identified.</p>

Effect of early high fat diet on pancreatic β cellularity and insulin sensibility in young rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of early high fat diet on sugar metaboliam, insulin sensibility and pancreatic β cellularity in young rats.</p><p><b>METHODS</b>Sixty male weaned young rats were randomly fed with high fat diet (high fat group) and normal diet (control group). The body weight, viscus fattiness and fasting plasma glucose (FPG) were measured after 3, 6 and 9 weeks. Serum insulin level was measured with radioimmunoassay. The ultrastructure of pancreas was observed under an electricmicroscope.</p><p><b>RESULTS</b>The high fat group had significantly higher body weight and visceral fat weight than the control group after 3 weeks. There were no significant differences in the FPG level between the two groups at all time points. The levels of fasting insulin and HOMAIR in the high fat group were significantly higher than those in the control group after 3, 6 and 9 weeks (P<0.01). Dilation of rough endoplasmic reticulum and mild swelling of mitochondria of islet β-cells were observed in the high fat group after 6 weeks.</p><p><b>CONCLUSIONS</b>Early high fat diet may induce a reduction in insulin sensitivity and produce insulin resistance in young rats. Endoplasmic reticulum expansion in β-cells may be an early sign of β-cell damage due to obesity.</p>

Effect of As(2)O(3) on expressions of COX-2 and matrix metalloproteinases in SGC7901 and K562 cells / 中国实验血液学杂志

This study was aimed to investigate on effect of As(2)O(3) on expressions of COX-2, MMP-2 and MMP-9 in SGC7901 and K562 cells. SGC7901 and K562 cells were cultured in RPMI 1640 medium and were inoculated in culture medium with different concentrations of As(2)O(3) and at different times. Expressions of COX-2, MMP-2 and MMP-9 in SGC7901 and K562 cells were measured by using Western blot, while the levels of COX-2 mRNA and MMP-2 mRNA were measured with fluorescence quantitative RT-PCR. The results showed that the expression of COX-2, MMP-2 and MMP-9 decreased in dose- and time-dependent manners after treating with As(2)O(3). The levels of COX-2 mRNA and MMP-2 mRNA reduced in groups treated with As(2)O(3). In conclusion, As(2)O(3) inhibits expressions of COX-2, MMP-2 and MMP-9 in K562 and SGC7901 cells, suggesting that As(2)O(3) inhibits tumor development through its effect on angiogenesis involved in solid and hematologic malignancies.

Effect of arsenic trioxide on vascular endothelial growth factor-C and its receptor (VEGFR-3) in nude mice with gastric cancer / 中国实验血液学杂志

This study was aimed to investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 in gastric cancer in order to clarify the role of As2O3 in lymphangiogenesis and metastasis of tumor. The gastric cancer model was established in nude mice by using gastric cancer cell line SGC-7901. As2O3 was injected to the two treatment groups (2.5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected to the control group. Expression of VEGF-C and VEGFR-3 were detected by immunohistochemistry and were analyzed with QWin550cW image Acquiring & Analysis System. The results showed that the expression of VEGF-C and VEGFR-3 in cancer cells significantly reduced in the arsenic -treated groups. The expression of VEGF-C and VEGFR-3 in 5 mg/kg group was significantly less than that in 2.5 mg/kg group. The gray ratio analysis confirmed that there were significant difference between control group and two treated group, as well as between 2.5 mg/kg-treated group and 5 mg/kg-treated group. It is concluded that As2O3 can inhibit expression of VEGF-C and VEGFR-3 of human gastric cancer xenografts in nude mice, which suggests that As2O3 may inhibit the lymphangiogenesis by suppressing the expression of VEGF-C and VEGFR-3.

Exploring of Interaction Teaching Model on Improving Pediatric Probation Quality / 中华医学教育探索杂志

Interaction teaching model of teaching and studying exchanging,simulation scenes,and clinical scientific research training were developed in medical interns.With the helps of such teaching model,rapid progresses of studying interests,activi- ties,and abilities were found in such pediatric interns.Under grasping basic pediatrics knowledge according to teaching program, they all have multiple abilities of clinical practices,medical teaching,and scientific research to a degree.The interaction teaching model which regards student as principal part plays a very important role in the development of pediatric probation quality.

Effect of realgar on expression of survivin in leukemia cell lines and its significance / 中国实验血液学杂志

To study the effect of realgar on expression of survivin in leukemia cell lines, HL-60 and Jurket cell lines were used as in vitro models. The expression of survivin was detected by Western blot analysis and immunofluorescence, and the expressions of Fas and caspase-3 were examined by immunohistochemistry. The results showed that the expression of survivin was positive in the two cell lines. HL-60 cells did not express Fas and caspase-3, and Jurket cells were Fas-positive and caspase-3 was negative. Realgar induced a dose- and time-dependent down-regulation of survivin expression in Jurket cells, and especially in HL-60. Caspase-3 expression changed from negative to positive in HL-60 cell, but there still was no expression in Jurket cell. It is concluded that survivin expression level decreased during leukemia cell apoptosis induced by Realgar. The down-regulation of survivin expression may be an important mechanism in leukemia cell apoptosis induced by realgar through mitochondrial pathway.

Expression of Survivin, Anti Apoptosis Gene in Leukemia and Correlation between Expression of Survivin,Fas and Caspase / 实用儿科临床杂志

Objective To explore the relation ship between expression of survivin gene in leukemia cells and its clinical effects, and to study the mechanism of survivin resist-apoptosis function in leukemia.Methods Survivin expression was detected by Western blots analysis and expressions of Fas and Caspase were examined by immunohistochemistry in 18 leukemia patients.Results Thirteen cases in peripheral blood mononuclear cell survivin positive expression was detected in 18 leukemia patients(72.2%), but no survivin expression in 10 normal persons. There were significant difference of survivin expression in ALL/ANLL patients groups and different WBC groups(P