The Fractional CO2 Laser for the Treatment of Genitourinary Syndrome of Menopause: A Prospective Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: Genitourinary syndrome of menopause (GSM) is a common condition affecting of most postmenopausal women, which greatly impacks the quality of life,and need to treat. This prospective multicenter cohort study aimed to compare the efficacy and safety of the fractional carbon dioxide (CO2 ) laser with that of topical estrogen for vaginal treatment and relieving symptoms of genitourinary syndrome of menopause (GSM). STUDY DESIGN/MATERIALS AND METHODS: This study included 162 postmenopausal patients who received vaginal laser or topical Estriol cream therapy between January 2017 and May 2019 at eight study centers in China. The degree of GSM-related symptoms (vaginal burning, dryness, and dyspareunia) was evaluated using the Vaginal Health Index score (VHIS) and Visual Analog Scale (VAS) at baseline, 1, 3, 6, and 12 months posttreatment. The primary endpoint was the improvement in vaginal burning, dryness, and dyspareunia at 6 months after treatment. Multivariate logistic regression was used to compare the rate of improvement in the two groups. RESULTS: At baseline, the laser and control groups showed no significant difference in the mean age, time after menopause, and the VHIS (all P > 0.05). In the laser group, compared with baseline, significant differences were seen in the VHIS after the first or second treatment session and at 1, 3, 6, and 12 months posttreatment (P < 0.01). In the control group, compared with baseline, the VHIS showed significant differences after 1, 3, and 6 months of treatment (P < 0.05). However, there was no significant difference after 3 and 6 months of follow-up between the two groups (P > 0.05). The VHIS scores were significantly higher after 1 month (16.63 ± 2.79 vs. 15.57 ± 2.43) and 12 months (15.72 ± 2.59 vs. 12.12 ± 4.08) of treatment in both the groups (P < 0.05). At 6 months after treatment, both groups showed improvement in vaginal burning, vaginal dryness, and dyspareunia (P > 0.05). The VAS findings at 6 months posttreatment were significantly different when compared with the pretreatment findings (P < 0.001). There were no significant adverse effects in the two groups. CONCLUSIONS: Fractional CO2 laser vaginal treatment could be a safe and effective option for treating symptoms of GSM, including vaginal burning, dryness, and dyspareunia. The improvement in symptoms was comparable with that seen with topical estrogen therapy and lasted for at least 6-12 months posttreatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Severe cervical inflammation and high-grade squamous intraepithelial lesions: a cross-sectional study.

PURPOSE: Inflammation has been reported as a facilitator in cervical oncogenesis, but the correlation between inflammation and cytological abnormality remains uncertain. The aim of this study was to investigate the correlation between inflammation and cytological abnormality. METHODS: ThinPrep cytological test (TCT) was used to detect cervical cytological abnormalities and inflammation degrees of 46,255 women in this prospective cross-sectional study. Histopathological examination was used to define the cervical intraepithelial neoplasia (CIN) in patients with cervical cytological abnormalities. RESULTS: The study revealed that 8.87% (4102/46,255) of TCT results had cytological abnormalities. The 4102 included cases were classified as the case group, including atypical squamous cells (ASC), low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). Women with negative intraepithelial lesion or malignancy (NILM) were classified as the control group. About 88.83% (3644/4102) of women with cytological abnormalities showed inflammations. The rate of severe inflammation was significantly higher in the case group than the control group (23.86% vs. 2.0%, P = 0.000). Our results also showed that patients with severe inflammation had a significantly increasing incidence of cytological abnormality by 12.598 times and elevated the risk of HSIL by 756.47 times, compared to the inflammation negative group. CONCLUSION: Severe inflammation was positively related to HSIL. Patients with severe cervical inflammation should be given more follow-ups and regular examinations and treated more carefully than those with mild or no inflammation.

[A case-control study of correlation between serum adiponectin levels and polycystic ovary syndrome].

OBJECTIVE: To compare the difference of serum adiponectin levels between polycystic ovary syndrome (PCOS) patients and age, boby mass index (BMI) and insulin-resistance index matched controls, and explore its influence factors. METHODS: Case-control study, involving 97 women with PCOS and 116 age, BMI, fasting plasma glucose and insulin levels, homeostasis model assessment-insulin resistance index (HOMA-IR) matched controls. Hormone profiles, and serum adiponectin levels were measured and compared. Hormone profiles and serum adiponectin levels were compared among the four PCOS phenotypes. Multiple regression analysis was used to evaluate the factors affecting serum adiponectin levels. RESULTS: (1) Serum adiponectin level was significantly lower in PCOS group [(21±16) mg/L] than controls [(25±13) mg/L, P=0.038], and the same result in stratified analysis on weight height ratio (WHR, ≥0.8 and <0.8). (2) There was statistical differences in testosterone among different four PCOS phenotypes (P=0.001), there were no statistical differences in FSH, LH, WHR and serum adiponectin levels among four PCOS phenotypes (P>0.05). (3) WHR and PCOS status were independent determinants of serum adiponectin levels (P<0.05). CONCLUSIONS: Low serum adiponectin levels in the women with PCOS is correlated with PCOS per se, independent of insulin resistance and obese. This fact supports the further study of the effect of adiponection in the pathophysiology of PCOS and its log-term impact.

Empirics on linking industrial agglomeration, energy consumption, residential construction sector growth, and environmental sustainability.

We looked at the long-term and short-term diversified relationships between industrial agglomeration, aggregate energy consumption, residential construction sector growth, and air pollution in China's 30 provincial units from 2004 through 2020. We contributed to the existing knowledge by calculating a holistic air pollution index (API) and applying advanced methods. We also augmented the Kaya identity by including industrial agglomeration and residential construction sector growth in the baseline framework. Based on empirical results: First, we revealed long-term stability among our covariates through panel cointegration analysis. Second, we uncovered a positive bilateral relationship between residential construction sector growth and industrial agglomeration in the long and short term. Third, we unfolded a unilateral positive correlation emerging from aggregate energy consumption to API, displaying the greatest influence in the east zone of China. Fourth, we observed a unilateral positive connection stemming from industrial agglomeration and residential construction sector growth to aggregate energy consumption and API in the long- and short-term dimensions. Finally, the linking nature was homogeneously prevailing across the long term and short term; however, the long-term impact size outweighed that of the short term. Given our empirical results, useful policy insights are discussed to provide the readers with a take-home message for substantiating sustainable development goals.

Risk Factors for Urinary Incontinence in Chinese Women: A Cross-sectional Survey.

OBJECTIVE: Urinary incontinence is highly prevalent among women, with a substantial effect on health-related quality of life. This article aimed to investigate the independent factors for urinary incontinence (UI) and the relative importance of each factor. METHODS: This study was a cross-sectional survey of Chinese women in Guangzhou. Female 20 years and older were invited to participate. The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form was used to determine whether respondents are experiencing UI. Univariate and multivariate unconditional logistic regression analyses were performed to determine the significant risk factors associated with UI. RESULTS: A total of 2626 women were invited to participate in the survey. The response rate was 80.5% (2114/2626). The prevalence of UI among the study population was 31.2%. Old age, increased body mass index, childbirth, family history of any female pelvic floor disorders, symptoms of chronic cough or rhinitis, wearing a corset, and often drinking were independent risk factors for UI. CONCLUSIONS: Urinary incontinence is common among Chinese women in Guangzhou. Among the factors that we are concerned with, old age and vaginal delivery are the two with greatest impact. Moreover, wearing a corset and drinking are the 2 lifestyle factors associated with UI.

[Plasma metastin in adolescent polycystic ovary syndrome.].

OBJECTIVE: This study was designed to investigate the correlationship between plasma metastin and pathogenesis of adolescent women with polycystic ovary syndrome (PCOS). METHODS: From Jan. 2006 to Jun. 2006, 42 PCOS patients including 19 adolescent women and 23 adults with syndrome were treated in Second Affiliated Hospital of Sun Yat-Sen University. According to the range of age, those patients were divided into 19 cases in adolescent group ( 19 years). Meanwhile, 20 adolescent women were matched as controls. Blood samples were collected between day 1 and day 5 of a spontaneous bleeding episode in the PCOS groups and a menstrual cycle of the controls. The levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), free T (FT), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), insulin, glucose, and metastin were detected from day 1 to day 5 of spontaneous bleeding or withdrawal bleeding by progesterone. On the next day, oral glucose tolerance test (75 g) and insulin release test were performed on those above patients and controls. The area under curve (AUC), the ratio of fasting blood glucose to insulin (GIR) and homeostasis model assessment insulin resistance index (HOMA-IR) were calculated. RESULTS: (1) The level of hormone: the level of LH was in (12 +/- 7) U/L in adult group and (12 +/- 8) U/L in adolescent PCOS group, which were significantly higher than (6 +/- 4) U/L in controls (P < 0.05). The level of FT was (2.3 +/- 1.2) pmol/L in adult group, which was significantly higher than (1.3 +/- 0.8) pmol/L in adolescent group and (1.1 +/- 0.5) pmol/L in control group (P < 0.05). It was observed that the level of (3.1 +/- 2.7)micromol/L in adolescent group was significantly lower than (6.3 +/- 2.7) micromol/L in control group (P < 0.05). Meanwhile, the level of FAI of 5.6 +/- 4.1 in adult group was significantly higher than 3.0 +/- 1.3 in control group (P < 0.05). No significant difference in FSH, T and SHBG levels among three groups were observed (P > 0.05). (2) Metastin and metabolism: Both the levels of fasting blood insulin, 2-hour insulin and AUC of insulin were (13 +/- 7) mU/L, (88 +/- 59) mU/L and (133 +/- 80) mUxL(-1)xmin(-1) in adolescent group, which were significantly higher than (7 +/- 3) mU/L, (57 +/- 29) mU/L and (82 +/- 34) mUxL(-1)xmin(-1) in control group. The fasting blood insulin of (13 +/- 7) mU/L in adolescent group was significantly higher than (9 +/- 5) mU/L in adult group. The level of fasting blood glucose and 2-hour glucose were (5.01 +/- 0.44) mmol/L and (6.48 +/- 1.16) mmol/L in adult group, which were significantly higher than (4.68 +/- 0.29) mmol/L and (5.44 +/- 0.83) mmol/L in control group and (4.67 +/- 0.30) mmol/L and (5.93 +/- 1.44) mmol/L in adolescent group. The glucose AUC of (9.99 +/- 1.85) mmolxL(-1)xmin(-1) in adult group was significantly higher than (8.42 +/- 1.53) mmolxL(-1)xmin(-1) in control group (P < 0.05). HOMA-IR of 2.6 +/- 2.0 in adolescent group was significantly higher than 1.4 +/- 0.7 in control group. GIR of 10 +/- 8 in adolescent group was significantly lower than 16 +/- 10 in control group (P < 0.05). The metastin level of (0.25 +/- 0.19) pmol/L in adolescent group and (0.29 +/- 0.29) pmol/L in adult group were all significantly higher than (0.18 +/- 0.23) pmol/L in control group (PPh glucose were observed (r = 0.256, 0.286 and 0.267. P = 0.044, 0.025 and 0.043). CONCLUSIONS: The expression of metastin in adolescent PCOS women was significantly higher that of normal adolescent women. The increased level of metastin might be associated with pathogenesis of adolescent women with PCOS.

[Effect of anti-Müllerian hormone on P450 aromatase mRNA expression in cultured human luteinized granulose cells].

OBJECTIVE: To investigate the effect of anti-Müllerian hormone (AMH) on hormone secretion and P450 aromatase mRNA expression from cultured human luteinized granulosa cells. METHODS: Human luteinized granulose cells were derived from 10 patients treated by in vitro fertilization-embryo transplantation (IVF-ET) in the Second Affiliated Hospital of Sun Yat-sen University from June to December 2006. Granulose cells were divided into group A, B, C, D, E depending on different concentration of AMH, testosterone group and blank group. 1x10(-7) mol/L testosterone and 1, 5, 10, 20, 50 microg/L AMH were added into the culture medium of group A, B, C, D and E. 1x10(-7) mol/L testosterone was added into the culture medium of testosterone group while no other ingredient was added into the medium of blank group. Estrogen levels in supernates were measured at 24, 48, 72 hours after cell incubation. RT-PCR was performed to detect the P450 aromatase mRNA expression in group B, C, D, E and testosterone group at 72 hours after cell incubation. RESULTS: (1) Estrogen levels in supernates of granulose cell culture at 24, 48, 72 hours were (8.529+/-0.381)x10(4), (10.977+/-0.436)x10(4), (13.309+/-0.506)x10(4) pmol/L in group A, (7.027+/-0.276)x10(4), (9.167+/-0.300)x10(4), (10.794+/-0.555)x10(4) pmol/L in group B, (6.039+/-0.226)x10(4), (7.585+/-0.548)x10(4), (8.797+/-0.518)x10(4) pmol/L in group C, (5.118+/-0.460)x10(4), (5.716+/-0.496)x10(4), (6.205+/-0.667)x10(4) pmol/L in group D, (4.932+/-0.148)x10(4), (5.323+/-0.184)x10(4), (5.629+/-0.212)x10(4) pmol/L in group E. When compared with blank group [(0.001+/-0.001)x10(4), (0.006+/-0.003)x10(4), (0.029+/-0.011)x10(4) pmol/L], the statistical differences were observed in group A, B, C, D, E (P<0.01); when compared with testosterone group [(8.418+/-0.569)x10(4), (10.841+/-0.689)x10(4), (13.301+/-0.637)x10(4) pmol/L], the statistical differences were observed in group B, C, D and E (P<0.01); statistical differences were also observed in group C, D and E when compared with group B, and also group D and E when compared with group C (P<0.01). No significant difference was observed between group D and E (P>0.05). In group A, B, C, D, E and testosterone group, the estrogen levels at 24 hours after cell culture were significantly lower than those at 48 and 72 hours (P<0.01); statistical difference was observed between estrogen levels at 48 and 72 hours (P<0.01). No significant difference was observed among 24, 48 and 72 hours in blank group (P>0.05). (2) Relative ratios of intensity of P450 aromatase/beta-actin at 72 hours of cell culture in group B, C, D and E were 0.6148+/-0.0046, 0.5156+/-0.0012, 0.4698+/-0.0027 and 0.4282+/-0.0017, respectively, which were statistically lower than that in testosterone group (0.8224+/-0.0021, P<0.01); statistical differences were also observed in group C, D and E when compared with group B, and also group D and E when compared with group C (P<0.01). No significant difference was observed between group D and E (P>0.05). CONCLUSION: It is suggested that AMH might affect estrogen synthesis by inhibiting P450 aromatose activity so that lead to hyperandrogenism microenvironment in local ovary.

Could semiquantitative analysis of real-time ultrasound elastography distinguish more liver parenchyma alterations of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome?

OBJECTIVE: Nonalcoholic fatty liver disease is the commonest diffuse liver disease, of which women with polycystic ovary syndrome are at an increased risk. The aim of the present study was to assess the diagnostic value of the semiquantitative strain parameters of real-time ultrasound elastography for nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. SUBJECTS AND METHODS: Thirty-five polycystic ovary syndrome patients with nonalcoholic fatty liver disease, 70 polycystic ovary syndrome patients without nonalcoholic fatty liver disease, and 70 healthy female controls of reproductive age were included. All participants underwent ultrasonic examination and semiquantitative analysis of real-time ultrasound elastography of the liver. RESULTS: Main semi quantitative strain parameters, such as average strain value, differed significantly among groups polycystic ovary syndrome with nonalcoholic fatty liver disease, polycystic ovary syndrome without nonalcoholic fatty liver disease, and control (87.02 ± 10.16 vs. 96.31 ± 11.44 vs. 104.49 ± 7.28, p < 0.001). Clinical and laboratory parameters differed significantly between the two subgroups with low or high average strain value. For diagnostic value of average strain value for elevated aminotransferase, the area under the curve was 0.808 (range 0.721-0.895). In multiple linear regression analysis, polycystic ovary syndrome, waist circumference, and metabolic syndrome were stand-alone independent factors associated with average strain value among subjects without nonalcoholic fatty liver disease. CONCLUSION: Semiquantitative real-time ultrasound elastography analysis could distinguish liver parenchyma alterations in patients with polycystic ovary syndrome more sensitively. The diagnostic value of the proposed method for nonalcoholic fatty liver disease need further research.

Prevalence of polycystic ovary syndrome in unselected women from southern China.

OBJECTIVE: The objective was to determine the prevalence and metabolic parameters of polycystic ovary syndrome (PCOS) in southern China. STUDY DESIGN: The study was observational with a parallel study. Participants were studied in a medical examination center. A population of 915 women of reproductive age was investigated at the time of their annual physical examination to determine the prevalence of PCOS in unselected women from southern China. RESULTS: Our results demonstrated a 2.2% (20/915) prevalence of PCOS. Women with PCOS had higher levels of luteinizing hormone and higher luteinizing hormone/follicle-stimulating hormone ratios than those in the other groups. Women with PCOS had higher fasting insulin levels and lower fasting glucose/fasting insulin ratios than women in any of the other groups. CONCLUSIONS: Some clinical and biochemical characteristics were apparent in PCOS patients in our population, and ethnic differences may be considered when studying the clinical and metabolic features of PCOS in China.

Clinical and metabolic features of polycystic ovary syndrome.

OBJECTIVE: To explore the clinical and metabolic features of Chinese women with polycystic ovary syndrome (PCOS). METHODS: The clinical data of 273 Chinese women diagnosed as having PCOS were retrospectively studied. RESULTS: Of these women 34.8% had hirsutism, 45.1% had acne, 94.1% had some menstrual abnormality, and 96.7% had typical appearances of polycystic ovaries on ultrasonographic examination. The prevalence of overweight women was 30.4%, and the prevalence of insulin resistance was 12.8% using the glucose to insulin ratio (GIR) and 21.6% using the homesostasis model assessment (HOMA). Body mass index was significantly correlated with fasting insulin level (r=0.50), GIR (r=0.37) and HOMA (r=0.53). CONCLUSION: Menstrual abnormality and polycystic ovaries were the main clinical manifestations in this cohort of Chinese women with PCOS. The prevalence of hyperandrogenism, obesity, and insulin resistance was lower in this cohort than in women from other races with the same condition. Ethnic differences needs to be considered when studying the clinical and metabolic features of women with PCOS.

[Diagnostic value of ovarian morphology by ultrasonography in pubertal polycystic ovary syndrome].

OBJECTIVE: To explore the ovarian morphological characteristics by ultrasonography as diagnostic criteria for pubertal polycystic ovary syndrome (PCOS). METHODS: Sixty-six adolescent PCOS patients and 27 controls were involved in this study. They underwent transrectal ultrasound during the early follicular phase or amenorrheal period (dominant follicle excluded by ultrasonography). t test and receiver operating characteristic (ROC) curve analysis were mainly used for statistical analysis. RESULTS: The mean ovarian volume (MOV), maximal ovarian volume (MaxOV) and mean follicle number (MFN) in PCOS group were all significantly greater than control group (P = 0.000). ROC curve analysis showed a satisfactory diagnostic potency for both ovarian volume and follicle number. The area under the ROC curve (AUC) was 0.914, 0.884 and 0.838 for MOV, MaxOV and MFN respectively with no statistical difference among them (P > 0.05). Setting the threshold of MOV at 6.4 cm(3) offered the best compromise between sensitivity (84.8%) and specificity (87.5%), and setting the threshold of MaxOV at 8.6 cm(3) offered the best compromise between sensitivity (75.8%) and specificity (95.2%) and setting the threshold of MFN at 8 offered the best compromise between sensitivity (86.7%) and specificity (78.3%). CONCLUSIONS: Ovarian morphology by ultrasonography yields satisfactory diagnostic accuracy for adolescent PCOS. Taking MOV >or= 6.4 cm(3) or MaxOV >or= 8.6 cm(3) or MFN >or= 8 as an ultraphonic criterion for pubertal PCOS offer the best compromise between sensitivity and specificity.

Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome.

This study aimed to detect serum microRNAs (miRNAs) differentially expressed between polycystic ovary syndrome (PCOS) patients with impaired glucose metabolism (IGM), PCOS patients with normal glucose tolerance (NGT), and healthy controls. A TaqMan miRNA array explored serum miRNA profiles as a pilot study, then selected miRNAs were analyzed in a validation cohort consisting of 65 PCOS women with IGM, 65 PCOS women with NGT, and 45 healthy women The relative expression of miR-122, miR-193b, and miR-194 was up-regulated in PCOS patients compared with controls, whereas that of miR-199b-5p was down-regulated. Furthermore, miR-122, miR-193b, and miR-194 were increased in the PCOS-IGM group compared with the PCOS-NGT group. Multiple linear regression analyses revealed that miR-193b and body mass index contributed independently to explain 43.7 % (P < 0.0001) of homeostasis model assessment-insulin resistance after adjustment for age. Investigation of diagnostic values confirmed the optimal combination of BMI and miR-193b to explore the possibility of IGM in PCOS women with area under the curve of 0.752 (95 % CI 0.667-0.837, P < 0.001). Bioinformatics analysis indicated that the predicted target functions of these miRNAs mainly involved glycometabolism and ovarian follicle development pathways, including the insulin signaling pathway, the neurotrophin signaling pathway, the PI3K-AKT signaling pathway, and regulation of actin cytoskeleton. This study expands our knowledge of the serum miRNA expression profiles of PCOS patients with IGM and the predicted target signal pathways involved in disease pathophysiology.

UHPLC/Q-TOFMS-based plasma metabolomics of polycystic ovary syndrome patients with and without insulin resistance.

Polycystic ovary syndrome (PCOS), characterized with menstrual irregularities, hyperandrogenism and ovulatory abnormalities, is usually companied with insulin resistance (IR) and accounts for one of the most prevalent reproductive dysfunction of premenopausal women. Despite accumulating investigations, diagnostic standards of this pathological condition remain obscure. The aim of present study is to characterize the plasma metabolic characteristics of PCOS patients with and without IR, and subsequently identify the potential biomarkers for the diagnosis of PCOS and its IR complication. A total of 59 plasma samples from eligible healthy controls (CON, n=19), PCOS patients without IR (non-IR PCOS, n=19) and PCOS patients with IR (IR PCOS, n=21) were profiled by an ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOFMS) followed by multivariate statistical analysis. Compared to the healthy controls, significant decrease in the levels of phosphocholines (PCs) and lyso PC (18:2), and increase in trilauric glyceride level were observed in the plasma of IR PCOS. Meanwhile, the significant increase in the levels of saturated fatty acids (palmitic acid and stearic acid) and decanoylcarnitine, and decrease in PC (36:2) and PS (36:0) were found in non-IR PCOS patients. Trilauric glyceride and decanoylcarnitine were identified as the potential biomarkers with the highest sensitivity and specificity for the diagnosis of PCOS patients with and without IR, respectively. Furthermore, based on these alterations of metabolites, MetPA network pathway analysis suggested a profound involvement of the abnormalities of glycerophospholipid, glycerolipid and fatty acid metabolisms in the pathogenesis of PCOS and IR complications. Collectively, LC-MS-based metabolomics provides a promising strategy for complementary diagnosis of PCOS and its IR complication and offers a new insight to understand their pathogenesis mechanisms.

MicroRNA-93 promotes ovarian granulosa cells proliferation through targeting CDKN1A in polycystic ovarian syndrome.

CONTEXT: MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression post-transcriptionally. Whether differently expressed miRNAs contribute to promoting granulosa cell proliferation in polycystic ovarian syndrome disease (PCOS) remains unknown. OBJECTIVE: We explored whether certain miRNAs are involved in the ovarian dysfunction of PCOS and the mechanism of increased granulosa cells proliferation. Patients and Cells: miRNA expression was analyzed in excised ovarian cortexes from 16 women with PCOS and 8 non-PCOS. An immortalized human granulosa (KGN) cell was used for the mechanism study. MAIN OUTCOME MEASURES: Expressions of miRNAs in ovarian cortexes were measured using qRT-PCR and KGN granulosa cells were cultured for proliferation assays after overexpression or inhibition of miR-93 or after insulin treatment. Bioinformatics were used to identify the potential miRNA targets. Protein expression analysis, luciferase assays, and rescue assays were used to confirm the substrate of miR-93. RESULTS: MiR-93 expression was higher in PCOS ovarian cortex and its identified target, CDKN1A, was downregulated. MiR-93 overexpression promoted cell proliferation and G1 to S transition. Knocking down CDKN1A promoted cell growth and cell cycle progression in granulosa cells, and CDKN1A re-introduction reversed the promotional role of miR-93. High concentrations of insulin induced upregulation of miR-93, stimulated KGN cells proliferation and reduced CDKN1A expression. CONCLUSIONS: miR-93 was increased in PCOS granulosa cells and targeted CDKN1A to promote proliferation and cell cycle progression. Insulin could upregulate the expression of miR-93 and stimulate cell proliferation. This might provide a new insight into the dysfunction of granulosa cells in PCOS.

Characterizing plasma phospholipid fatty acid profiles of polycystic ovary syndrome patients with and without insulin resistance using GC-MS and chemometrics approach.

Polycystic ovary syndrome (PCOS), a heterogeneous endocrine and metabolic disorder, is the leading cause of infertility in women of reproductive age. Insulin resistance (IR) occurs in 50-70% of women with PCOS. In this study, we aimed to characterize the plasma phospholipid fatty acid profile for PCOS patients with and without IR, as well as for the early prognosis of PCOS and its IR complication. A gas chromatography-mass spectrometry (GC-MS) followed by multivariate statistical analysis was established to globally characterize the phospholipid fatty acid profiles in plasma from non-IR PCOS, IR PCOS, and eligible healthy controls, and subsequently discovered fatty acid biomarkers. A total of 22 fatty acids were identified and quantified. Their proportions varied among three groups, suggesting each group has its own fatty acid pattern. Orthogonal partial least squares discriminant analysis (OPLS-DA) according to their fatty acid profiles showed that 29 tested samples could be clearly differentiated according to groups. More importantly, nervonic acid (C24:1 n-9) and dihomo-γ-linolenic acid (C20:3 n-6) were identified as the potential fatty acid biomarkers of PCOS and its IR complication, respectively, for their most contribution to group separation. Pearson correlation analysis indicated that C24:1 n-9 and C20:3 n-6 were well correlated with clinical characteristics of PCOS and IR indicators, respectively. These findings demonstrated that GC-MS-based plasma phospholipid fatty acid profile might provide a complementary approach for clinical diagnosis of PCOS and its IR complication.

Could semiquantitative analysis of real-time ultrasound elastography distinguish more liver parenchyma alterations of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome?

ABSTRACT Objective: Nonalcoholic fatty liver disease is the commonest diffuse liver disease, of which women with polycystic ovary syndrome are at an increased risk. The aim of the present study was to assess the diagnostic value of the semiquantitative strain parameters of real-time ultrasound elastography for nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. Subjects and methods: Thirty-five polycystic ovary syndrome patients with nonalcoholic fatty liver disease, 70 polycystic ovary syndrome patients without nonalcoholic fatty liver disease, and 70 healthy female controls of reproductive age were included. All participants underwent ultrasonic examination and semiquantitative analysis of real-time ultrasound elastography of the liver. Results: Main semi quantitative strain parameters, such as average strain value, differed significantly among groups polycystic ovary syndrome with nonalcoholic fatty liver disease, polycystic ovary syndrome without nonalcoholic fatty liver disease, and control (87.02 ± 10.16 vs. 96.31 ± 11.44 vs. 104.49 ± 7.28, p < 0.001). Clinical and laboratory parameters differed significantly between the two subgroups with low or high average strain value. For diagnostic value of average strain value for elevated aminotransferase, the area under the curve was 0.808 (range 0.721-0.895). In multiple linear regression analysis, polycystic ovary syndrome, waist circumference, and metabolic syndrome were stand-alone independent factors associated with average strain value among subjects without nonalcoholic fatty liver disease. Conclusion: Semiquantitative real-time ultrasound elastography analysis could distinguish liver parenchyma alterations in patients with polycystic ovary syndrome more sensitively. The diagnostic value of the proposed method for nonalcoholic fatty liver disease need further research.

Determining the normal cut-off levels for hyperandrogenemia in Chinese women of reproductive age.

OBJECTIVE: To determine the normative cut-off levels of free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS) and total testosterone (TT) among reproductive age women in China. STUDY DESIGN: A total of 450 reference subjects without known factors affecting androgen levels were selected from a total study population of 904 presumably healthy women undergoing annual check-ups. The upper limits of normal levels of biochemical androgens were computed by k-means cluster analysis, with the results categorized by age and expressed as both concentrations and percentiles. RESULTS: The upper limits (cut-off levels) of normal FT, DHEAS and TT levels as determined by k-means cluster analysis are 26 pmol/L, 4.92 µmol/L and 2.39 nmol/L, respectively, in the selected reference subjects. The corresponding percentiles of the cut-off levels of FT (91.8th vs. 87.9th), DHEAS (69.8th vs. 67.6th) and TT (90.0 th vs. 83.8th) were all higher in the reference subjects than in the total study population, suggesting that there were fewer abnormal subjects with elevated androgens in the healthier reference population than in the total study population. The level of DHEAS significantly declined by age (P < 0.05), whereas there was no significant difference in the mean FT or TT levels between age groups among these women of reproductive age. CONCLUSIONS: The normal hyperandrogenism cut-off values for FT, DHEAS and TT are 26.00 pmol/L, 4.92 µmol/L and 2.39 nmol/L, respectively, among women of reproductive age in China who are without factors that might affect androgen levels. The cut-off levels in percentiles are 91.8th for FT, 69.8th for DHEAS and 90.0 th for TT.

Elevated serum anti-mullerian hormone in adolescent and young adult Chinese patients with polycystic ovary syndrome.

PURPOSES: To explore the serum anti-mullerian hormone (AMH) level in adolescent and young adult Chinese patients with polycystic ovary syndrome (PCOS), and to evaluate its diagnostic value for PCOS. STUDY DESIGN: Serum AMH was measured in a cohort of 47 adolescent and young adult Chinese patients with PCOS and 40 age-matched controls. Its diagnostic potential was evaluated by Receiver Operating Characteristic (ROC) curves. RESULTS: The serum AMH level was higher in PCOS patients than in controls (9.85 ± 4.93 ng/mL vs. 7.13 ± 3.02 ng/mL, P = 0.002), and positively related to the mean ovarian volume in PCOS patients (r = 0.319, P = 0.029). The area under the ROC curve for AMH reached a value of 0.664 (0.551-0.778, 95% confidence interval). The best compromise between specificity (70%) and sensitivity (61.7%) was obtained with a cut-off value of 8 ng/mL. CONCLUSIONS: Serum AMH levels are elevated in adolescent and young adult Chinese patients of PCOS. Serum AMH measurement offers a relatively poor diagnostic potency with a sensitivity of 61.7% and a specificity of 70% at 8 ng/mL.

Increased plasma metastin levels in adolescent women with polycystic ovary syndrome.

OBJECTIVE: This study was designed to: (1) measure metastin levels in women with polycystic ovary syndrome (PCOS) and in adolescent controls; (2) investigate the possible correlations between metastin and PCOS-related reproductive and metabolic disturbances. STUDY DESIGN: The study was a clinical study. Nineteen adolescent women with PCOS, twenty-three adult women with the syndrome, and twenty adolescent controls were selected. Blood samples were collected between day 1 and day 5 of a spontaneous bleeding episode in the PCOS groups and of a menstrual cycle of the controls at 9 a.m. after an overnight fast. Circulating levels of LH, FSH, prolactin, testosterone (T), free testosterone, DHEAS, sex hormone-binding globulin, insulin, glucose and metastin were measured. RESULT(S): Plasma metastin levels are increased in adolescent women with PCOS compared to adolescent controls. Plasma metastin levels were positively correlated with LH levels, 2-h glucose levels and T levels. CONCLUSION(S): These results indicate that metastin is increased in adolescent PCOS women. The increased metastin levels were positively correlated with LH and T levels, and may affect the development of PCOS in adolescents.