Polycystic ovary syndrome patients with high BMI tend to have functional disorders of androgen excess:a prospective study

Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome （PCOS）. There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index （BMI）, total testosterone （TT）, modified Ferriman-Gallwey hirsutism score, sex hormone binding globulin （SHBG）, homeostasis model assessment-estimated insulin resistance （HOMA-IR） and free androgen index （FAI） between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyper- androgenism had significantly higher BMI （P 〈 0.05）, but differences in TT, SHBG, FAI and waist/hip ratio were insignificant. The odds ratio of overweight was calculated for all PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong pre-dictor of hyperandrogenism in PCOS.

The remedial effect of soluble interleukin-1 receptor type Ⅱ on endometriosis in the nude mouse model

Objective： Recent studies have shown that the local expression of soluble interleukin （IL） -1 receptor type Ⅱ （slL-1 R Ⅱ ） in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 R Ⅱ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of slL-1-R Ⅱ administration on endometriosis in the nude mouse model. Methods： Nineteen nude model mice with endometriosis were randomly divided into three groups： group A was treated by intraperitoneal administration with only slL-1 R Ⅱ for two weeks, group B was similarly treated with only IL- 1, and group C （control） was administered saline. After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor （VEGF） and B-cell lymphoma leukemia-2 （Bcl- 2） were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid （PF） and serum were also measured by enzyme-linked immunosorbent assay （ELISA）. Results： The mean size of ectopic endometrial lesion did not differ between the three groups （P 〉 0.05）. Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion： slL-1 R Ⅱ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.

Follicular hyperandrogenism and insulin resistance in polycystic ovary syndrome patients with normal circulating testosterone levels

Polycystic ovary syndrome（PCOS） is a common reproductive disease with high heterogeneity. The role of excess androgen in PCOS etiology remains disputed, since around 20%-50% of PCOS women do not display hyperandrogenemia. The microenvironment of the ovary critically influences follicular development. In the present study, we assessed the role of androgen in PCOS by investigating whether excessive follicular fluid androgen was present in PCOS patients with normal serum androgen levels and influenced by follicular fluid insulin resistance（IR）.Follicular fluid samples of 105 women with PCOS and 105 controls were collected. Levels of steroid hormones,glucose and insulin in the follicular fluid were examined and compared with data from serum biochemistry tests. We found that 64.9%（63/97） of PCOS patients with normal serum androgen levels displayed abnormally high follicular fluid androgen level. The follicular fluid androgen level was positively correlated with follicular fluid IR within a certain range and follicular fluid estrogen-to-testosterone（E2/T） ratio was significantly reduced in these patients.These results indicated that there existed a subgroup of PCOS patients who displayed excessive follicular fluid androgen and IR despite their normal circulating testosterone（T） levels. Our study highlights the importance of ovary hyperandrogenism and IR in the etiology of PCOS.

Association of Single Nucleotide Polymorphisms in IRF6 and TGFA Genes With Nonsyndromic Cleft Lip With Or Without Cleft Palate in Chinese Patients

Objective： Nonsyndromic cleft lip with or without cleft palate（NSCL/P） is a common birth defect with unclear etiology. Both genetic and environmental factors may contribute to NSCL/P. Many genes have been identified as candidate genes associated with this disease. Interferon regulatory factor 6（IRF6） gene and transforming growth factor-a（TGFA） gene seem to be crucial in the predisposition of NSCL/ P. Here we evaluated some single nucleotide polymorphisms（SNPs） loci of TGFA and IRF6 genes in Chinese nuclear families consisting of fathers, mothers and affected offspring with NSCL/P. Methods：Fifty patients of NSCL/P were confirmed by the plastic surgeons. They and their parents were included in the study, all with the informed consents. SNPs loci of TGFA and IRF6 genes were analyzed by microarray technology. Some PCR products were randomly chosen and sequenced to check microarray results. The distribution of gene type and allele frequency between patient group and parents group were compared. Then a Haplotype Relative Risk（HRR） and Transmission Disequilibrium Test（TDT） were performed. Results：The sequences of randomly selected PCR products were all consistent with the microarray results. All loci were in Hardy-Weinberg equilibrium. There were no significant differences in the distribution of genotypes and alleles between patients and their parents. Using HRR and TDT analyses the V274I of IRF6 was associated with NSCL/P, while another SNP locus oflRF6 was not. Strong evidence of linkage disequilibrium was found between the 2 SNP loci of TGFA and disease with the HRR analysis, but not with the TDT analysis. Conclusion：Our study confirms the contribution of IRF6 in the etiology of NSCL/P in populations of Asian ancestry. The association of TGFA with NSCL/P requires further research.

A novel long-term intravenous combined with local treatment with human amnion-derived mesenchymal stem cells for a multidisciplinary rescued uremic calciphylaxis patient and the underlying mechanism

Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progressive skin ischemia,large areas of painful malodorous ulcers,and mummified legs.Because of the worsening symptoms and signs refractory to conventional therapies,treatment with human amnion-derived mesenchymal stem cells(hAMSCs)was approved.Preclinical release inspections of hAMSCs,efficacy,and safety assessment,including cytokine secretory ability,immunocompetence,tumorigenicity,and genetics analysis in vitro,were introduced.We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats,abnormal immune response tests in C57BL/6 mice,and tumorigenicity tests in neonatal Balbc-nu nude mice.After the preclinical research,the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers.When followed up to 15 months,the blood-based markers of bone and mineral metabolism improved,with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells.Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis,and 20 months later,the re-epithelialization restored the integrity of the damaged site.No infusion or local treatment-related adverse events occurred.Thus,this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,anti-inflammatory and immune modulation,multidifferentiation,re-epithelialization,and restoration of integrity.