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OBJECTIVES@#Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women with reproductive age, which is associated with hyperandrogenism, insulin resistance, and ovulatory dysfunction. Progesterone receptor membrane component 1 (PGRMC1) can mediate progesterone to inhibit the apoptosis of ovarian granulosa cells and the growth of follicles, and to induce glucolipid metabolism disorder in ovarian granulosa cells, which is closely related to the occurrence and development of PCOS. This study aims to determine the expression of PGRMC1 in serum, ovarian tissue, ovarian granulosa cells, and follicular fluid in PCOS patients and non-PCOS patients, analyze the value of PGRMC1 in diagnosis and prognosis evaluation of PCOS, and investigate its molecular mechanism on ovarian granulosa cell apoptosis and glucolipid metabolism.@*METHODS@#A total of 123 patients were collected from the Department of Obstetrics and Gynecology in Guangdong Women and Children Hospital (hereinafter referred to as "our hospital") from August 2021 to March 2022 and divided into 3 groups: a PCOS pre-treatment group (n=42), a PCOS treatment group (n=36), and a control group (n=45). The level of PGRMC1 in serum was detected by enzyme linked immunosorbent assay (ELISA). The diagnostic and prognostic value of PGRMC1 was evaluated in patients with PCOS by receiver operating characteristic (ROC) curve. Sixty patients who underwent a laparoscopic surgery from the Department of Obstetrics and Gynecology in our hospital from January 2014 to December 2016 were collected and divided into a PCOS group and a control group (n=30). The expression and distribution of PGRMC1 protein in ovarian tissues were detected by immunohistochemical staining. Twenty-two patients were collected from Reproductive Medicine Center in our hospital from December 2020 to March 2021, and they divided into a PCOS group and a control group (n=11). ELISA was used to detect the level of PGRMC1 in follicular fluid; real-time RT-PCR was used to detect the expression level of PGRMC1 mRNA in ovarian granulosa cells. Human ovarian granular cell line KGN cells were divided into a scrambled group which was transfected with small interfering RNA (siRNA) without interference and a siPGRMC1 group which was transfected with specific siRNA targeting PGRMC1. The apoptotic rate of KGN cells was detected by flow cytometry. The mRNA expression levels of PGRMC1, insulin receptor (INSR), glucose transporter 4 (GLUT4), very low density lipoprotein receptor (VLDLR), and low density lipoprotein receptor (LDLR) were determined by real-time RT-PCR.@*RESULTS@#The serum level of PGRMC1 in the PCOS pre-treatment group was significantly higher than that in the control group (P<0.001), and the serum level of PGRMC1 in the PCOS treatment group was significantly lower than that in the PCOS pre-treatment group (P<0.001). The areas under curve (AUC) of PGRMC1 for the diagnosing and prognosis evaluation of PCOS were 0.923 and 0.893, respectively, and the cut-off values were 620.32 and 814.70 pg/mL, respectively. The positive staining was observed on both ovarian granulosa cells and ovarian stroma, which the staining was deepest in the ovarian granulosa cells. The average optical density of PGRMC1 in the PCOS group was significantly increased in ovarian tissue and ovarian granulosa cells than that in the control group (both P<0.05). Compared with the control group, the PGRMC1 expression levels in ovarian granulosa cells and follicular fluid in the PCOS group were significantly up-regulated (P<0.001 and P<0.01, respectively). Compared with the scrambled group, the apoptotic rate of ovarian granulosa cells was significantly increased in the siPGRMC1 group (P<0.01), the mRNA expression levels of PGRMC1 and INSR in the siPGRMC1 group were significantly down-regulated (P<0.001 and P<0.05, respectively), and the mRNA expression levels of GLUT4, VLDLR and LDLR were significantly up-regulated (all P<0.05).@*CONCLUSIONS@#Serum level of PGRMC1 is increased in PCOS patients, and decreased after standard treatment. PGRMC1 could be used as molecular marker for diagnosis and prognosis evaluation of PCOS. PGRMC1 mainly localizes in ovarian granulosa cells and might play a key role in regulating ovarian granulosa cell apoptosis and glycolipid metabolism.
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Criança , Gravidez , Humanos , Feminino , Síndrome do Ovário Policístico , Apoptose , Células da Granulosa , Metabolismo dos Lipídeos , Proteínas de Membrana , Receptores de ProgesteronaRESUMO
OBJECTIVE To evaluate the efficacy and safety of dydrogesterone in the treatment of dysmenorrhea. METHODS The prospective ，random-controlled，open-labeland multicenter clinical study was adopted. A total of 108 women with dysmenorrhea were randomly assigned into dydrogesterone group and control group according to the ratio of 1∶1，with 54 patients in each group. Dydrogesterone group was treated with dydrogesterone 10 mg orally ，twice a day ，on the 5th-25th day of menstrual cycle ，for 3 menstrual cycles. Control group received Guizhi fuling capsule 0.93 g orally ，three times a day，since the end of menstrual bleeding to the third day of the next menstruation ，for 3 menstrual cycles. Main results were the changes of visual analogue scale （VAS）scores in 2 groups after 3 menstrual cycles ；secondary results were the changes of COX menstrual symptom scale （CMSS），quality life of 36-item short form （SF-36），levels of carbohydrate antigen 125（CA125）and interleukin 6（IL-6）after 3 menstrual cycles ；other findings included additional benefits and drug safety. RESULTS The results of intention to analysis data set and the follow-up study protocol analysis data set showed that VAS scores of 2 groups after treatment of dysmenorrhea for 1，2 and 3 menstrual cycles were lower than those before treatment ，the longer the treatment time ，the more obvious the decrease of VAS score （P＜0.05），and VAS score decline of dydrogesterone group was better than that of control group（P＜0.05）. After 3 menstrual cycles ，both the two group showed significant reduction in the severity and duration scores of CMSS（P＜0.05）；and the decrease of the above scores in the dydrogesterone group was superior than in the control group （P＜ 0.05）. After 3 menstrual cycles ，among 8 dimensions of SF- 36 scale，the scores of 7 dimensions in dydrogesterone group were significantly higher than those before treatment ，such as the scores of physiological function ，physical role ，physical pain ， emotional function ，social function ，general health status and energy （P＜0.05）；the increase of the scores of four dimensions were higher than those in the control group ，such as physical pain ，social function ，general health status ，energy（P＜0.05）. There was no significant difference in the levels of CA 125 and IL- 6 between 2 groups before and after treatment （P＞0.05）. After 3 menstrual cycles，the menstrual cycle and menstrual period in the dydrogesterone group were shorter than those before treatment ，and the menstrual volume decreased （P＜0.05）；but there was no significant change in the above indexes of control group （P＞0.05）. After 3 menstrual cycles ，the incidence of adverse drug events and adverse reactions in dydrogesterone group was 32.69％（17/52）and 28.85％（15/52）；no serious adverse drug events or adverse reactions such as thrombosis occurred in both groups. CONCLUSIONS Dydrogesterone can effectively reduce the VAS score ，also relieve dysmenorrhea-related symptoms ，and improve the quality of life. The efficacy of dydrogesterone is superior than that of Guizhi fuling capsule in treatment for dysmenorrheal ，without serious adverse reactions. It is well tolerated.
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Objective:To investigate the effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on targeted therapy of prostate cancer and its effect on tumor microenvironment. Methods:125I-RSOAds-hTERT/PSA ( 125I-virus complex) oncolytic adenovirus was constructed by PCR amplification and double restriction enzyme ligation. TUNEL staining, flow cytometry and Caspase-3 immunoblotting assay were used to detect the killing effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on prostate cancer cells in vitro and in vivo, respectively. To explore the effect of 125I-virus complex on tumor tissue cytokine secretion levels, interleukin 2 (IL-2), IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the culture supernatant of human prostate cancer cell line PC3, mouse prostate adenocarcinoma cell line RM-1, and mice serum were detected by ELISA. We explored the regulation of 125I-virus complex on the expression of CD24, CD44 and prostate stem cell antigen (PSCA) in prostate tumor tissues and tumor cells through immunohistochemistry. Meanwhile, the expression levels of CD32 and vascular endothelial growth factor (VEGF), as well as CD4+ , CD8+ and macrophage infiltration in tumor tissue were detected through immunofluorescence experiments. Results:125I-virus complex oncolytic adenovirus significantly increased tumor cell apoptosis in vitro and in vivo that was significantly higher than that of 125I group and virus complex group. Meanwhile, IL-2 ( t=-183.30, -38.20, P<0.05), IL-10 ( t=113.80, 92.71, P<0.05), TNF-α ( t=-73.20, -73.91, P<0.05), IFN-γ ( t=-65.37, -139.70, P<0.05) increased in vitro and in vivo. 125I-virus complex reduced the expression of CD24, CD44 and PSCA in tumor cells and tumor tissue, reduced the weight of tumor tissue, inhibited angiogenesis of tumor tissue ( t=8.55, P<0.05), and regulated the immune response in tumor tissue. Conclusions:125I-virus complex targeting prostate cancer can significantly kill cancer cells, reduce the weight and angiogenesis of tumor, and improve tumor microenvironment.
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To explore an appropriate treatment for patients with upper ureteral stone (＞ 15 mm in size) by comparing the therapeutic outcomes for those undergoing retroperitoneoscopic ureterolithotomy (RPUL) and percutaneous nephrolithotomy (PCNL).A total of 62 patients with large upper ureteral stone were divided randomly into 2 groups.RPUL was performed in group A (n =30) and PCNL in group B (n =32).No significant inter-group difference existed in age,gender,stone location and size,operative duration or surgical success rate (P ＞ 0.05).Blood loss volume,rate of postoperative analgesic usage,time of hospital stay and incidence of postoperative complications in group A were significantly lower than those of group B (P ＜ 0.05).Thus RPUL offers more advantages and better efficacies.