Pathogenic gene screening in 91 Chinese patients with short stature of unknown etiology with a targeted next-generation sequencing panel.

BACKGROUND: Dwarfism is a common severe growth disorder, but the etiology is unclear in the majority of cases. Recombinant human growth hormone may be a treatment option, but it has limited efficacy. The currently known laboratory assays do not meet the precision requirements for clinical diagnosis. Here, we have constructed a targeted next-generation sequencing (NGS) panel of selected genes that are suspected to be associated with dwarfism for genetic screening. METHODS: Genetic screening of 91 children with short stature of unknown etiology was performed with the help of the NGS panel. All the coding regions and exon-intron boundaries of 166 genes were included in the panel. To clarify the pathogenicity of these mutations, their clinical data were reviewed and analyzed. RESULTS: The assay identified p.A72G, p.I282V, and p.P491S variants of the PTPN11 gene and a p.I437T variant of the SOS1 gene in 4 cases with Noonan syndrome. A frameshift mutation (p.D2407fs) of the ACAN gene was identified in a case of idiopathic short stature with moderately advanced bone age. A p.R904C variant of the COL2A1 gene was found in a patient, who was accordingly diagnosed with Stickler syndrome. Severe short stature without limb deformity was associated with a p.G11A variant of HOXD13. In addition, we evaluated evidence that a p.D401N variant of the COMP gene may cause multiple epiphyseal dysplasia. CONCLUSIONS: Our findings suggest that syndromes, particularly Noonan syndrome, may be overlooked due to atypical clinical features. This gene panel has been verified to be effective for the rapid screening of genetic etiologies associated with short stature and for guiding precision medicine-based clinical management.

Economic burden attributable to healthcare-associated infections at western China hospitals: 6 Year, prospective cohort study.

OBJECTIVES: Healthcare-associated infections (HAIs) represent a major threat to patient safety and are associated with significant economic burden. Calculating the costs attributable to HAIs is challenging given the various sources of bias. Although HAIs as a reasonably preventable medical harm should have been closely linked to medical insurance incentives, there was little linkage between HAIs and medicare in western China owing to the lack of economic evaluation data. The present study aimed to generate estimates of the attributable costs associated with HAIs and the magnitude of costs growth. METHODS: In this cohort study designed horizontally and vertically from 2016 to 2022, we compared outcomes of randomly sampling patients with HAIs and individually matched patients without HAIs in two cohorts at a 6-year interval at 34 hospitals in western China. The primary outcome was the direct medical cost for the entire hospital stay, converted to US dollars ($ for the benchmark year), discounted at 3% annually, and estimated separately in the full analysis set (FAS) and the per protocol set (PPS). We used multiple linear regression to adjust the discounted costs and to assess subgroups effects within each cohort. We nested a dynamic vertical comparison of costs attributable to HAIs between the front and rear cohorts. RESULTS: A total of 230 patients with HAIs in 2016 and 204 patients with HAIs in 2022 were enrolled. After a 1:1 match, all 431 pairs were recruited as FAS, of which 332 pairs as PPS met all matching restrictions. Compared to the 2016 cohort in FAS, the patients with HAIs in 2022 had a significantly older age (64.40 ± 16.45 years), higher repeat hospitalization rate (65 [32.02%] of 203), and lower immune function (69 [33.99%] of 203). The discounted costs and adjusted-discounted costs for patients with HAIs in the 2022 cohort were found to be significantly higher than those of patients without HAIs (discounted costs: $5484.60 [IQR 8426.03] vs $2554.04(4530.82), P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3040.21(1823.36), P < 0.001, respectively), and also higher than those of patients with HAIs in the 2016 cohort (discounted costs: $5484.60 [8426.03] vs $3553.00 [6127.79], P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3703.82 [3159.14], P < 0.001, respectively). In vertical comparison of PPS, the incremental costs of the 2022 cohort are 1.48 times higher than those of the 2016 cohort ($964.63(4076.15) vs $652.43 [2533.44], P = 0.084). CONCLUSIONS: This meticulously designed study in western China has successfully and accurately examined the economic burden attributable to HAIs. Their rapidly increasing tendency poses a serious challenge to patients, hospitals, and the medical insurance. A closer linkage between HAIs and ongoing motivating system changes is urgently needed in western China.

An SNP of the ZBTB38 gene is associated with idiopathic short stature in the Chinese Han population.

OBJECTIVE: Idiopathic short stature (ISS) refers to extreme short stature without any diagnostic explanation. Recently, three genome-wide association studies discovered associations between the ZBTB38 and adult height in different populations. Therefore, variations in the ZBTB38 might contribute to ISS. Furthermore, one study in Korean population showed that ZBTB38 gene was significantly associated with adult height, but not with ISS. We want to examine whether the variants in ZBTB38 are associated with ISS in Chinese Han. METHODS: A case-control association study was performed in 268 ISS patients and 513 healthy controls from Chinese Han population. Fourteen tag SNPs were selected and genotyped using SNaPshot method. Furthermore, expression of mRNA was quantified by RT-qPCR, and assessment of allelic expression imbalance was conducted with SNaPshot method. RESULTS: Seven ZBTB38 SNPs were significantly associated with ISS by allele tests (rs724016, rs1582874, rs11919556, rs6440006, rs7612543, rs62282002, rs18651435). And five loci were associated with ISS according to genotype (rs11919556, rs16851419, rs6440006, rs62282002, rs18651435). Notably, after applying the stringent Bonferroni correction for multiple testing, one SNP, rs16851435, remained significantly associated by allele and genotype (P = 5·30 × 10⁻4 for allele and P = 0·002 for genotype). Furthermore, the rs16851435 alleles were investigated association with ZTBT38 mRNA expression levels. The G allele showed a higher transcriptional activity than the T allele (P = 0·002). CONCLUSIONS: Our study indicated that the nonsynonymous SNP (rs16851435:T > G,p.Ser319Ala) of ZBTB38 was contributed to susceptibility of ISS in the Chinese Han population.

Measurement of amino-terminal propeptide of C-type natriuretic peptide in patients with idiopathic short stature or isolated growth hormone deficiency.

OBJECTIVE: To explore the value of amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) in evaluating the effectiveness of therapy with recombinant human growth hormone (rhGH) in patients with idiopathic short stature (ISS) and isolated growth hormone deficiency (IGHD). METHODS: Forty-eight prepubertal children (IGHD = 25, ISS = 23) treated for at least 1 year with rhGH were included. Insulin growth factor-1 (IGF-I) and NTproCNP serum levels were measured before starting treatment and again 6 months later. Twelve months after starting treatment, all patients were assessed and annual growth velocity (GV), height standard deviation score (HTSDS), and gain HTSDS (deltaHTSDS) were recorded. RESULTS: In the GHD group, positive relationships between GV and change of IGF-I(SDS) (deltaIGF-I(SDS)), GV and change of NTproCNP concentrations (deltaNTproCNP) were found. GH peak value was also positively associated with IGF-I(SDS) and NTproCNP before therapy and deltaIGF-I(SDS) and deltaNTproCNP were positively associated. In the ISS group, GV was associated with only deltaNTproCNP. CONCLUSIONS: NTproCNP is a novel biomarker of growth as levels increase during growth-promoting treatment. Furthermore, IGF-I is also valuable in evaluating the efficacy of rhGH therapy in short stature patients.

[Relationship between the polymorphism of growth hormone receptor Ex3 and the efficacy of rhGH treatment in children with idiopathic short stature].

OBJECTIVE: To assess the influence of growth hormone receptor (GHR) Ex3 genotype on the short-term response to recombinant human growth hormone (rhGH) therapy in children with idiopathic short stature (ISS). METHODS: Thirty prepubertal children with ISS receiving rhGH treatment [0.116±0.02 IU/(kg/d)] were randomly recruited. The GHR Ex3 locus was genotyped using a PCR multiplex assay. The growth data including growth velocity, height SDS for chronological age (HtSDSCA), height SDS for bone age (HtSDSBA) and predict final height were compared in children with different GHR genotypes 6 months after rhGH treatment. RESULTS: After 6 months of rhGH treatment, the children with ISS carrying d3/d3 alleles showed a significantly higher increment in growth velocity than those carrying fl/fl alleles (6.3±1.6 cm/year vs 3.4±0.5 cm/year; P<0.05). CONCLUSIONS: The polymorphism in GHR Ex3 is associated with the responsiveness to rhGH treatment, showing that the growth velocity in ISS children with d3/d3 genotype is significantly higher than those with fl/fl genotype.

ß-Caryophyllene inhibits high glucose-induced oxidative stress, inflammation and extracellular matrix accumulation in mesangial cells.

ß-Caryophyllene (BCP) is a bicyclic sesquiterpene compound that has anti-diabetic activity. However, the effect of BCP on diabetic nephropathy (DN) remains unclear. Here, we aimed to evaluate the potential role of BCP in high glucose (HG)-induced glomerular mesangial cells (MCs). MCs were maintained under HG condition to simulate DN in vitro. Our results showed that BCP inhibited HG-induced cell proliferation, ROS production and NADPH oxidase (NOX) 2/4 expression. BCP exhibited anti-inflammatory activity with decreased levels of TNF-α, IL-1ß, IL-6 in HG-induced MCs. Moreover, BCP treatment suppressed the HG-induced secretion of fibronectin (FN) and collagen IV (Col IV) in MCs. Furthermore, BCP suppressed the NF-κB activation and enhanced the Nrf2 activation in HG-induced MCs. However, inhibition of Nrf2 attenuated the protective effects of BCP on HG-induced MCs, while inhibition of NF-κB enhanced the nephro-protective effects of BCP on MCs. In conclusion, these findings demonstrated that BCP executed protective effects on HG-induced MCs via regulating NF-κB and Nrf2 signaling pathways.

Modelling the effects of media coverage and quarantine on the COVID-19 infections in the UK.

A new COVID-19 epidemic model with media coverage and quarantine is constructed. The model allows for the susceptibles to the unconscious and conscious susceptible compartment. First, mathematical analyses establish that the global dynamics of the spread of the COVID-19 infectious disease are completely determined by the basic reproduction number R0. If R0 ≤ 1, then the disease free equilibrium is globally asymptotically stable. If R0 > 1, the endemic equilibrium is globally asymptotically stable. Second, the unknown parameters of model are estimated by the MCMC algorithm on the basis of the total confirmed new cases from February 1, 2020 to March 23, 2020 in the UK. We also estimate that the basic reproduction number is R0 = 4.2816(95%CI: (3.8882, 4.6750)). Without the most restrictive measures, we forecast that the COVID-19 epidemic will peak on June 2 (95%CI: (May 23, June 13)) (Figure 3a) and the number of infected individuals is more than 70% of UK population. In order to determine the key parameters of the model, sensitivity analysis are also explored. Finally, our results show reducing contact is effective against the spread of the disease. We suggest that the stringent containment strategies should be adopted in the UK.

Identification of gene variants in 130 Han Chinese patients with hypospadias by targeted next-generation sequencing.

BACKGROUND: Hypospadias is a common congenital malformation of male external genitalia, which mainly manifests as an abnormal urethral opening on the ventral side of the penis. The etiology and clinical phenotype of hypospadias is highly heterogeneous, and its clinical diagnosis is challenging. Currently, over 70% of patients have an unknown etiology. Here, we performed a targeted analysis of gene mutations in 130 patients with hypospadias of unknown etiology to find the precise genetic cause. METHODS: We developed a targeted next-generation sequencing (NGS) panel, encompassing the exon coding regions of 105 genes involved in external genitalia and urogenital tract development and performed sequencing analysis on 130 children with hypospadias of unknown etiology. RESULTS: In total, 25 patients with hypospadias (19.2%) were found to have 20 mutations among the nine genes involved in external genitalia and urogenital tract development, including 16 reported and four novel mutation sites. Twenty-two patients (16.9%) had diagnostic variants. Multiple genetic mutations were identified in three of the 25 patients. Hypospadias combined with micropenis was the most common phenotype (68%) in 25 patients. CONCLUSIONS: Higher frequency mutations were identified in SRD5A2 (52%) and AR (24%) in our patient cohort. Middle or posterior hypospadias with micropenis may be significant indicators of genetic variations. Polygenic inheritance may be a rare genetic cause of hypospadias.

[Effects of dietary fat on onset of gestational diabetes mellitus].

OBJECTIVE: To explore the effects of dietary fat on gestational diabetes mellitus (GDM). METHODS: Nulliparous pregnant women with GDM (GDM group, n = 85) were compared with normal pregnant women (normal pregnant group, NP group, n = 159). A 24 hours recall dietary assessment was obtained before dietary intervention. From the dietary record a list of the amount of foods consumed, were entered into a software program. The analysis was focused on three nutrients (carbohydrate, protein and fat), especially on dietary fat and fat subtypes. RESULTS: (1) Total calorie per day in GDM group (8970 +/- 2115) kJ was higher than that in NP group (8799 +/- 1785) kJ, but there was no significant difference between two groups (P > 0.05). (2) Carbohydrate, protein and fat intake in GDM group (as % kJ) was 51.9 +/- 7.2, 17.5 +/- 0.9 and 30.6 +/- 1.3, respectively. Carbohydrate, protein and fat intake in NP group (as % kJ) was 53.6 +/- 8.1, 18.3 +/- 1.1 and 28.1 +/- 2.3 respectively. Fat intake (as % kJ) in GDM group was significantly higher than that in NP group (P < 0.05), while carbohydrate and protein intake (as % kJ) in GDM group was not significantly different compared with NP group (P > 0.05). (3) Polyunsaturated fatty acids (PUFA) in GDM group (as % kJ) (8.3 +/- 0.5) was lower than that in NP group (10.1 +/- 0.4) (P < 0.05), but saturated fatty acids (SFA) in GDM group (as % kJ) (15.2 +/- 0.4) was higher than that in NP group (11.7 +/- 0.6) (P < 0.05). Although monounsaturated fatty acids (MUFA) in GDM group (as % kJ) (7.1 +/- 0.5) was higher than that in NP group (6.3 +/- 0.3), there was no significant difference between two groups. CONCLUSION: High dietary fat, high SFA and low PUFA may be one of the high-risk factors triggering GDM.

Effect of Placenta Previa on Preeclampsia.

BACKGROUND: The correlation between gestational hypertension-preeclampsia (GH-PE) and placenta previa (PP) is controversial. Specifically, it is unknown whether placenta previa has any effect on the various types of preeclampsia (PE), and the role PP with concurrent placenta accreta (PA) play in the occurrence of GH-PE are not well understood. OBJECTIVE: The aim of this study was to identify the effects of PP on GH, mild and severe preeclampsia (MPE and SPE), and early- and late-onset preeclampsia (EPE and LPE). Another aim of the study was to determine if concurrent PA impacts the relationship between PP and GH-PE. METHODS: A retrospective single-center study of 1,058 patients having singleton pregnancies with PP was performed, and 2,116 pregnant women were randomly included as controls. These cases were collected from a tertiary hospital and met the inclusion criteria for the study. Clinical information, including PP and the gestational age at the onset of GH-PE were collected. Binary and multiple logistic regression analyses were conducted after the confounding variables were controlled to assess the effects of PP on different types of GH-PE. RESULTS: There were 155 patients with GH-PE in the two groups. The incidences of GH-PE in the PP group and the control group were 2.5% (26/1058) and 6.1% (129/2116), respectively (P = 0.000). Binary and multiple regression analyses were conducted after controlling for confounding variables. Compared to the control group, in the PP group, the risk of GH-PE was reduced significantly by 78% (AOR: 0.216; 95% CI: 0.135-0.345); the risks of GH and PE were reduced by 55% (AOR: 0.451; 95% CI: 0.233-0.873) and 86% (AOR: 0.141; 95% CI: 0.073-0.271), respectively; the risks of MPE and SPE were reduced by 73% (AOR: 0.269; 95% CI: 0.087-0828) and 88% (AOR: 0.123; 95% CI: 0.055-0.279), respectively; and the risks of EPE and LPE were reduced by 95% (AOR: 0.047; 95% CI: 0.012-0.190) and 67% (AOR: 0.330; 95% CI: 0.153-0.715), respectively. The incidence of concurrent PA in women with PP was 5.86%; PP with PA did not significantly further reduce the incidence of GH-PE compared with PP without PA (1.64% vs. 2.51%, P>0.05). Binary logistic regression analyses were conducted after controlling for confounding variables, compared with the non-PP + GH-PE group, and the AOR of FGR in the non-PP + non-GH-PE group was 0.206 (0.124-0.342). Compared with the PP + GH-PE group, the AOR of FGR in the PP + non-GH-PE group was 0.430 (0.123-1.500). CONCLUSION: PP is not only associated with a significant reduction in the incidence of GH-PE, but also is associated with a reduction in incidence of various types of PE. Concurrent PA and PP do not show association with a reduction in incidence of GH-PE.

Maternal TSH level and TPOAb status in early pregnancy and their relationship to the risk of gestational diabetes mellitus.

Subclinical hypothyroidism is common in pregnant women and often related to adverse pregnancy outcomes, but its relationship with gestational diabetes remains controversial. In particular, the impact of thyroperoxidase antibodies status on the relationship between subclinical hypothyroidism and gestational diabetes is not clear. We investigated the association between combined thyroid stimulating hormone (TSH) level and thyroperoxidase antibodies status in early pregnancy (<20 weeks of gestation) and gestational diabetes mellitus. A total of 7084 pregnant women met the inclusion criteria, which included thyroperoxidase antibodies-positive subclinical hypothyroidism [TSH(H)TPOAb(+)] (n = 78), thyroperoxidase antibodies-negative subclinical hypothyroidism [TSH(H)TPOAb(-)] (n = 281), thyroperoxidase antibodies-positive euthyroidism [TSH(N)TPOAb(+)] (n = 648), and thyroperoxidase antibodies-negative euthyroidism [TSH(N)TPOAb(-)] (n = 6077). Of the 7084 cases included in our study, 1141 cases were diagnosed with gestational diabetes mellitus at 24-28 weeks of pregnancy. The prevalence of gestational diabetes mellitus in TSH(N)TPOAb(-), TSH(H)TPOAb(-), TSH(N)TPOAb(+), and TSH(H)TPOAb(+) was 14.65, 19.57, 24.85, and 46.15 %, respectively. Compared with TSH(N)TPOAb(-) women, the risk of gestational diabetes mellitus was increased in all other groups of women in early pregnancy. After dividing early pregnancy into first and second trimesters, we found that TSH(H)TPOAb(-) women in the first trimester do not show this increase. Our study suggests that subclinical hypothyroidism and thyroperoxidase antibodies-positive euthyroidism in early pregnancy are associated with an increased risk of gestational diabetes mellitus.

[Preliminary study on prenatal diagnosis from coelomic cells using polymerase chain reaction].

OBJECTIVE: To evaluate the number of cells in coelomic fluid by DNA quantitation with picogreen and to establish a new method of prenatal diagnosis for sex-linked disorders in early pregnancy. METHODS: Coelomic fluid and chorionic villi were obtained from 25 women undergoing planned termination of pregnancy. DNA of coelomic fluid was extracted by boiling method and DNA concentration was measured with picogreen, and fetal gender was determined by X and Y-sequence-specific PCR. The results of PCR were compared with traditional cytogenetic analysis of chorionic villi. RESULTS: There were 750-6270 cells in 0.5-3 ml coelomic fluid. Two amplified bands of X and Y were identified simultaneously in the coelomic fluid of male-fetus. Only one band was detected in that of female-fetus. Eleven out of 25 coelomic fluids showed X and Y bands, and the others were one band (X). The overall concordance rate of gender determination between coelomic fluid and chorionic villi was 100%. CONCLUSION: The number of cells in 0.5-3 ml coelomic fluid can completely meet the needs of PCR reactions. Sex determination using cells in coelomic fluid and PCR is reliable, which can be used as a prenatal diagnostic test for sex-linked disorders and has the advantages of high sensitivity and rapidity.

Hormone Inhibition During Mini-Puberty and Testicular Function in Male Rats.

BACKGROUND: The mini-pubertal period of almost six hours in neonatal male rats is thought to be an important stage in sexual development. OBJECTIVES: The aim of this study was to investigate the effect of hormone inhibition during mini-puberty on testicular function in male rats. MATERIALS AND METHODS: We measured serum testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in male rats at different time points after birth by enzyme linked immunosorbent assay (ELISA) and established a "no mini-puberty" model by ether inhalation. The mRNA expression levels of testicular androgen receptor (AR), insulin-like growth factor 3 (INSL3), anti-Mullerian hormone (AMH), and ghrelin were determined by real-time polymerase chain reaction (PCR) assays on postnatal days 45 and 75. Testicular tissue biopsies were stained with hematoxylin and eosin (H & E) and the structure, number and maturity of testis cells (including spermatogenic, Sertoli, and Leydig cells) were observed under microscopy at the same time. RESULTS: Serum T and LH levels peaked at two hours after birth, while FSH peaked at hour 0, and bilateral testicular weight peaked at four hours after birth. The rats that underwent ether inhalation five minutes after birth had markedly reduced serum hormone levels. The mini-puberty model group revealed visible morphologic alterations in the tests on postnatal day 45. Then, on postnatal day 75, the mRNA expression level of AMH significantly decreased (P < 0.05) in the same group. CONCLUSIONS: The inhibition of mini-puberty period in male rats was demonstrated to have an effect on their testicular function to some extent.

Effects of China-made recombinant human growth hormone on the treatment of growth hormone deficiency.

OBJECTIVE: To evaluate the therapeutic effect of China-made recombinant human growth hormone (r-hGH) in children with growth hormone deficiency (GHD) and to investigate the utilities of various biochemical parameters in GHD diagnosis and treatment. METHODS: Our study comprises of 30 normal children and 71 GHD children treated with China-made r-hGH substitution therapy 0.1 IU x kg(-1) x d(-1) for 6 months. Serum insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), bone turnover markers (Ost, ICTP), and anti-growth hormone antibody (GHAb) were detected before and after r-hGH treatment. RESULTS: After the first 3 and 6 months of treatment, growth velocities of GHD children were significantly increased (13.1 +/- 3.7 and 12.6 +/- 3.6 cm/year) compared with pretreatment values (2.9 +/- 0.8 cm/year, P < 0.01). GHD Children had obviously reduced serum levels of IGF-1, IGFBP-3, and bone turnover markers (Ost, ICTP) compared with normal controls (P < 0.01), and these biochemical parameters improved significantly after treatment (P < 0.01). Growth hormone antibodies were positive in 17 of 45 cases after treatment by binding capacity detection. The binding percentage of growth hormone antibody which was increased more than 30% after the treatment showed a negative correlation with growth velocity (P < 0.01). CONCLUSIONS: (1) The growth stimulating effect and safety were confirmed in using China-made r-hGH in the treatment of GHD children for 6 months. (2) The measurements of serum IGF-1 and IGFBP-3 may serve as useful parameters in the diagnosis of GHD. (3) Serum Ost and ICTP are useful laboratory criteria for evaluating the effect of r-hGH therapy in the early stage. (4) It is necessary to monitor serum levels of GHAb during r-hGH therapy.

[Detection of fibroblast growth factor receptor 3 gene mutation at nucleotide 1138 site in congenita achondroplasia patients].

OBJECTIVE: [corrected] To investigate the mutation at the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) nucleotide 1138 site for identifying the major pathologic mechanism of achondroplasia (ACH) and to evaluate the efficacy of denaturing gradient gel electrophoresis(DGGE) method for screening the point mutations. METHODS: The genomic DNA from 17 clinically diagnosed ACH patients where analysed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) with Sfc I and Msp I restriction endonucleases and by PCR-DGGE technique for screening. RESULTS: G to A transition mutation at nucleotide 1138 was detected in 14/17 of the ACH patients as heterozygotes by PCR-RFLP with Sfc I digestion. No 1138 G to C transition was detected by Msp I digestion. All of the 14 samples with G to A mutation were also found to be positive for point mutation by PCR-DGGE. No mutation was detected in 3 negative samples by PCR-RFLP, implying that there was actually no point mutation in this amplified region. CONCLUSION: Nucleotide 1138 in transmembrane domain of FGFR3 gene is the hot point for mutation in ACH and hence its major pathologic cause. PCR-DGGE is a sensitive and reliable technique for point mutation screening, especially for the heterozygotes.

Mutation analysis of the SRD5A2, AR and SF-1 genes in 52 Chinese boys with hypospadias.

OBJECTIVES: To investigate the prevalence of genetic mutations in steroid 5α-reductase-2 (SRD5A2), androgen receptor (AR) and steroidogenic factor-1 (SF-1) in Chinese children with hypospadias, and to also explore the possible underlying molecular mechanisms of this disease. METHODS: A total of 52 boys with hypospadias were enrolled. Mutational analyses of the SRD5A2, AR and SF-1 genes were performed by direct sequencing. RESULTS: SRD5A2 gene mutations were found in 13.5% (7/52 cases), including five compound heterozygotic and two homozygotic mutations. One novel heterozygotic SF-1 gene mutation was identified in a patient with perineal hypospadias and cryptorchidism, the patient's mother also had the same mutation. No mutation was found in the AR gene. The clinical manifestations of patients with mutations in SRD5A2 or SF-1 varied. CONCLUSIONS: In Chinese patients, SRD5A2 gene mutations were, relatively, frequently associated with hypospadias. The SF-1 gene may be another candidate gene for hypospadias. In contrast, AR gene mutations are not commonly associated with this condition.

Use of early transverse annular compression sutures for complete placenta previa during cesarean delivery.

OBJECTIVE: To compare the difference in maternal outcomes between early and late use of transverse annular compression sutures (TACS) during cesarean delivery among women with complete placenta previa (CPP). METHODS: A retrospective study of 36 women with CPP was conducted. Percentiles of blood loss before TACS were calculated. The transfusion rate, sensitivity, specificity, Youden index, positive predictive value, and negative predictive value were also estimated. Patients were assigned to either the early TACS group or the late TACS group based on the highest Youden index. Maternal outcomes of the 2 groups were compared. RESULTS: The Youden index for transfusion rate was highest when blood loss before TACS reached 500 mL. Blood loss before intervention in the late TACS group was significantly higher than in the early TACS group (735.0 ± 123.7 mL versus 396.9 ± 76.3 mL; P<0.001). More women in the late TACS group than in the early TACS group required blood transfusion (60.0% versus 12.5%; P=0.004) and the volume of blood transfused was significantly lower in the early TACS group than in the late TACS group (137.5 ± 377.5 mL versus 806.7 ± 619.3 mL; P=0.001). CONCLUSION: Early implementation of TACS could lead to improved maternal outcomes.

[Association of 45, X/46, XY mosaicism with disorders of sex development: the clinical analysis of 5 cases].

OBJECTIVE: To analyze clinical characteristics of children with 45, X/46, XY mosaicism and explore effective managements for them. METHOD: Five children with 45, X/46, XY mosaicism were all in puberty period, of whom, three were female and two male. The standing height, weight and sexual development were measured. The levels of sex hormones, other endocrine parameters were also determined, and imaging examinations were performed. RESULT: All the patients had disorders of sex development, of whom, 4 had short stature, and the HtSDs was -2.8 ± 1.1. The results of laboratory indexes suggested that 4 had hypergonadotropic hypogonadism, with the average level of LH (13.5 ± 5.8) IU/L and FSH (56.8 ± 37.4) IU/L. Imaging examinations revealed that 2 cases had cryptorchidism, 1 had immature uterus, 1 had testicular dysgenesis and 1 had normal testis. Three patients received rhGH treatment and 1 took gender assignment into account. CONCLUSION: Patients with mosaic 45, X/46, XY karyotypes had a wide range of phenotypic manifestations, and disorders of sex development and short stature were the main clinical features. However, the disorders of sex development varied among these patients. And the management for them depends upon many factors and needs to be individualized based on the cooperation with different clinical departments.