Metformin enhances the survival ability of ovarian granulosa cells in polycystic ovary syndrome by promoting LINC00548 to suppress androgen receptor/klotho pathway.

BACKGROUND: Metformin (Met) has been reported to play the key role in the pathogenesis of polycystic ovary syndrome (PCOS). However, the precise mechanisms underlying the actions of Met in PCOS remain incompletely understood. This study aimed to confirm the mechanism of Met interacting with a long non-coding RNA LINC00548 in PCOS. METHODS: Ovarian granulosa cells (OGCs) were incubated 500 nM dihydrotestosterone (DHT) to construct PCOS in vitro model and then were treated 20 µM Met. A series of cell experiments including Cell Counting Kit-8, Terminal uridine nucleotide end labeling, and flow cytometry were performed to confirm the changes of OGC survival ability. Quantitative real-time polymerase chain reaction was conducted to determine the levels of LINC00548, whereas Western blotting was applied to determine the levels of androgen receptor (AR) and klotho. RESULTS: Met improved the cell viability and suppressed cell apoptosis in DHT-treated OGCs. LINC00548 downregulated in DHT-treated OGCs was upregulated by Met, and its overexpression further enhanced the positive effects of Met on the survival ability of DHT-treated OGCs. In addition, Met could induce the upregulation of LINC00548 to suppress the activation of AR/klotho pathway in DHT-treated OGCs. CONCLUSION: Overall, this study discovers that Met enhances the survival ability of OGCs in PCOS by elevating LINC00548 expression to suppress AR/klotho pathway.

Association of endometriosis with asthma: a study of the NHANES database in 1999-2006.

OBJECTIVE: Asthma is a chronic inflammatory disease of the airways with a gender differences in the prevalence after puberty. Recent studies have reported a relationship between asthma and endometriosis, possibly related to the immune response mechanisms, but the evidences are limited and inconsistent. Herein, this research aimed to investigate the association of endometriosis with asthma based on the representative population in the United States (U.S.) to provide some reference for further exploration on mechanism of gender difference in asthma. METHODS: In this cross-sectional study, data of women aged ≥ 20 years old were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 1999-2006. Weighted univariate and multivariate logistic regression analyses were utilized to explore the association of endometriosis with asthma. The multivariate models adjusted for covariates including age, race, education level, marital status, poverty income ratio (PIR), body mass index (BMI), waist circumference, smoking, estrogen and progesterone hormones use, uterine fibroids, at least one ovary removed, and birth control pills intake. The evaluation indexes were odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses of age, race, BMI, and pregnancy history were also performed. RESULTS: Among 5,556 eligible women, 782 had asthma, and 380 had endometriosis. The average age of participants was 37.19 years old, and more than half of them were non-Hispanic White (68.44%). After adjusting for covariates, endometriosis was associated with higher odds of asthma compared with non-endometriosis [OR = 1.48, 95%CI: (1.10-1.99)]. This relationship was also found in 40-49 years old [OR = 2.26, 95%CI: (1.21-4.23)], BMI of 25-29.9 kg/m2 [OR = 2.87, 95%CI: (1.52-5.44)], and pregnancy history [OR = 1.44, 95%CI: (1.01-2.06)] subgroups. CONCLUSION: Endometriosis had a positive association with asthma in adult women. Females aged 40-49 years old, with BMI of 25-29.9 kg/m2 and had a history of pregnancy should take care about monitoring endometriosis to reduce the potential risk of asthma. Further studies are still needed to clarify the causal association between endometriosis and asthma.

A Fifteen-Gene Classifier to Predict Neoadjuvant Chemotherapy Responses in Patients with Stage IB to IIB Squamous Cervical Cancer.

Neoadjuvant chemotherapy (NACT) remains an attractive alternative for controlling locally advanced cervical cancer. However, approximately 15-34% of women do not respond to induction therapy. To develop a risk stratification tool, 56 patients with stage IB-IIB cervical cancer are included in 2 research centers from the discovery cohort. Patient-specific somatic mutations led to NACT non-responsiveness are identified by whole-exome sequencing. Next, CRISPR/Cas9-based library screenings are performed based on these genes to confirm their biological contribution to drug resistance. A 15-gene classifier is developed by generalized linear regression analysis combined with the logistic regression model. In an independent validation cohort of 102 patients, the classifier showed good predictive ability with an area under the curve of 0.80 (95% confidence interval (CI), 0.69-0.91). Furthermore, the 15-gene classifier is significantly associated with patient responsiveness to NACT in both univariate (odds ratio, 10.8; 95% CI, 3.55-32.86; p = 2.8 × 10-5) and multivariate analysis (odds ratio, 17.34; 95% CI, 4.04-74.40; p = 1.23 × 10-4) in the validation set. In conclusion, the 15-gene classifier can accurately predict the clinical response to NACT before treatment, representing a promising approach for guiding the selection of appropriate treatment strategies for locally advanced cervical cancer.

What Changed on the Folliculogenesis in the Process of Mouse Ovarian Aging?

There are about 1-2 million follicles presented in the ovary at birth, while only around 1000 primordial follicles are left at menopause. The ovarian function also decreases in parallel with aging. Folliculogenesis is vital for ovarian function, no matter the synthesis of female hormones or ovulation, yet the mechanisms for its changing with increasing age are not fully understood. Early follicle growth up to the large preantral stage is independent of gonadotropins in rodents and relies on intraovarian factors. To further understand the age-related molecular changes in the process of folliculogenesis, we performed microarray gene expression profile analysis using total RNA extracted from young (9 weeks old) and old (32 weeks old) mouse ovarian secondary follicles. The results of our current microarray study revealed that there were 371 (≥2-fold, q-value ≤0.05) genes differentially expressed in which 174 genes were upregulated and 197 genes were downregulated in old mouse ovarian secondary follicles compared to young mouse ovarian secondary follicles. The gene ontology and KEGG pathway analysis of differentially expressed genes uncovered critical biological functions such as immune system process, aging, transcription, DNA replication, DNA repair, protein stabilization, and apoptotic process were affected in the process of aging. The considerable changes in gene expression profile may have an adverse influence on follicle quality and folliculogenesis. Our study provided information on the processes that may contribute to age-related decline in ovarian function.

Benign Prostatic Hyperplasia Treatment by Transurethral Enucleation of the Prostate Using a 2-µm Laser.

This study investigates the efficacy of benign prostatic hyperplasia (BPH) treatment by prostate transurethral enucleation using a 2-µm laser. A total of 107 patients with BPH were treated by prostate transurethral enucleation using a RevoLix 2-µm laser surgery system. Bleeding volume, operation time, catheterization time, voiding situation, maximum urinary flow rate, and hospital stay were observed. The mean operation time was 74 min ± 12 min (range 45 to 150 min), the mean follow-up period was 2 to 6 months, the mean catheter time was 5 days, and the mean peak urinary flow rate increased from 6.3 ± 0.6 to 17.5 ± 1.5 mL/s. The International Prostate Symptom Score and quality of life significantly declined (p < 0.01). No significant differences were observed in the hemoglobin and blood electrolytes before and after operation. Prostate transurethral enucleation using a 2-µm laser is safe and efficient for BPH treatment.

Long-term follow-up on the effects of sigmoid-rectal pouch for urinary diversion.

PURPOSE: The aim of this study was to investigate the long-term clinical effects of sigmoidrectal pouch for urinary diversion. MATERIALS AND METHODS: A total of 45 patients, including 40 males and 5 females, underwent sigmoid-rectal pouch procedure. The patients aged from 38 to 70 years with a mean age of 59 years. The postoperative follow-up ranged from 6 months to 19 years with an average of 6 years. Postoperative continence and voiding were analyzed, urinary reservoir pressure was measured and the complications of upper urinary tract were determined. The index of quality of life (QoL) in the International Prostate Symptom Score (IPSS) was used to evaluate the degree of satisfaction to urinate. RESULTS: Forty patients had slight incontinence in the early postoperative stage and could control urination well 30 days postoperatively. The volume of pouch was 270-600 mL with an average of 375 mL. The basic pressure during filling period was 6-20 cmH2O with an average 15 cmH2O, the maximum filling pressure was 15-30 cmH2O with an average 26 cmH2O. The compliance of sigmoid-rectal pouch was fine with an average of 30 (range 18-40) mL/ cmH2O. There were no severe complications such as hyperchloremic acidosis or retrograde pyelonephritis. Six patients had slight hydronephrosis. The index of QoL were 0-2 in 20 patients, 3 in five patients and 4 in two patients. CONCLUSION: The sigmoid-rectal pouch operation was simple and acceptable by surgeons and patients. It may be an ideal urinary diversion for patients with muscle-invasive bladder cancer, especially for patients on whom urethrectomy should be done.