Expression of PGRMC1 in patients with polycystic ovary syndrome and its molecular mechanism for regulating ovarian granulosa cell apoptosis and glucolipid metabolism / 中南大学学报(医学版)

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.

MDCT in diagnosis of double outlet right ventricle / 中国医学影像技术

Objective To observe the value of MDCT in diagnosis of double outlet right ventricle (DORV). Methods Clinical and imaging data of 36 patients with DORV confirmed with operation or cardioangiography were retrospectively analyzed. The preoperative results of MDCT and echocardiography (Echo) were compared with surgical findings. Results MDCT definitely diagnosed 34 patients with DORV, while 2 patients were misdiagnosed, and the accurate diagnostic rate was 94.44% (34/36).The accurate diagnostic rate of Echo was 75.00% (27/36), and the difference was statistically significant (P=0.022). Moreover, in the relationship of ventricular septal defect (VSD) with large artery and the special relationship of the large artery in DORV, the diagnostic accuracy of MDCT was 100% (36/36), of Echo was 80.56% (29/36), and the difference was statistically significant (P=0.017). For totally 119 intracardiac and extracardiac malformations in all 36 patients, no significant statistical difference of diagnostic accuracy for detecting intracardiac malformation was found between MDCT and Echo (P=0.474), whereas for extracardiac malformations, the diagnostic accuracy of MDCT (98.72% [77/78]) was higher than that of Echo (69.23% [54/78], P<0.001). Conclusion MDCT could diagnose DORV and combined malformation definitely, therefore providing important guidance for surgical planning.

Current status of surgical treatment of gastric gastrointestinal tumors: a national multi-center retrospective study / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the clinicopathology of patients with gastric gastrointestinal stromal tumor(gGIST) who underwent radical excision within 18 years in 10 domestic medical centers in order to understand the status of domestic surgical treatment of gGIST.</p><p><b>METHODS</b>Clinicopathological data of gGIST patients undergoing radical excision in 10 medical centers from January 1998 to January 2016 were collected, and their operational conditions, postoperative adjuvant therapy, gene detection and survival were analyzed retrospectively.</p><p><b>RESULTS</b>A total of 1 846 cases were recruited in this study, including 246 cases from Guangdong General Hospital, 331 cases from Sun Yat-sen University Cancer Center, 374 cases from Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 342 cases from Nanfang Hospital of Southern Medical University, 265 cases from Fujian Medical University Union Hospital, 148 cases from Fudan University Shanghai Cancer Center, 49 cases from West China Hospital of Sichuan University, 43 cases from Peking University Cancer Hospital and Institute, 28 cases from the 81st Hospital of Pepole's Liberation Army(PLA), 20 cases from Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute. There were 918 male (49.7%) and 928 female patients (50.3%) with median onset age of 59(18 to 95) years old. Fundus(735 cases, 39.8%) and body (781 cases, 42.3%) of stomach were the common sites of lesions. The average size of tumor was (5.3±4.6) cm. There were 1 421 cases with mitotic count ≤5(77.0%). According to the operation procedure, 924 cases (50.1%) underwent laparoscopic surgery, 759 cases (41.1%) laparotomy, 120 cases (6.5%) endoscopic surgery, and 20 cases (1.1%) laparoscopic combined with endoscopic surgery, 6 cases (0.3%) laparoscopic excision surgery through gastric wall and cavity, and 17 cases (0.9%) laparoscopy and then were transferred to laparotomy. Wedge excision were performed in 1 308 cases (70.9%), proximal gastric excision in 226 cases(12.2%), distal gastric excision in 92 cases (5.0%), total gastrectomy in 94 cases (5.1%), and local gastrectomy in 126 cases(6.8%). Multi-visceral excision was performed in 138 cases, and the splenectomy was performed in 83 cases(60.1%)with the highest ratio. According to modified NIH classification, 399 cases(21.6%) were extreme low risk, 580 cases(31.4%) were low risk, 424 cases(23.0%) were moderate risk, 443 cases (24.0%) were high risk. A total of 461 cases received postoperative imatinib adjuvant therapy, accounting for 53.2%(461/867) of patients with moderate and high risk. Among 1 846 cases, 1 402 cases (75.9%) had complete follow-up data and the median follow-up time was 33.6 (0.1 to 158) months. The 5-year survival rates of extreme low risk, low risk, moderate risk and high risk were 100%, 98.5%, 92.5%, and 79.2% with significant difference(P=0.000).</p><p><b>CONCLUSIONS</b>Gastric GIST occurs mostly in fundus and body of stomach in China. Wedge excision is the main operational procedure and laparoscopic operation is over 50%. General prognosis of gastric GIST is quite good.</p>

Changes of diagnosis and treatment for gastrointestinal stromal tumors during a 18-year period in four medical centers of China / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To elucidate the historic and current diagnosis and treatment status of gastrointestinal stromal tumor (GIST) in the Chinese population based on four high volume databases.</p><p><b>METHODS</b>Clinicopathological data of GIST patients with follow-up information between January 1998 and December 2015 from Sun Yat-sen University Cancer Center, Union Hospital of Huazhong University of Science and Technology, Southern Medical University Nanfang Hospital and Guangdong General Hospital were retrospectively analyzed. Kaplan-Meire method was used to draw survival curve. The accumulative survival rate was calculated by life table method. Comparison of survival rate among groups was examined by Log-rank test.</p><p><b>RESULTS</b>A total of 2 610 cases were enrolled into the study, including 667(25.6%) cases from Sun Yat-sen University Cancer Center, 754(28.9%) cases from Union Hospital of Huazhong University of Science and Technology, 692(26.5%) cases from Southern Medical University Nanfang Hospital and 497 (19.0%) cases from Guangdong General Hospital. There were 1 394 male and 1 216 female cases with the ratio of 1.15 to 1.00. The age of patients was from 18 to 95 (median 58.0) years old. Three-year was used as a time stage, then 18 years were divided into 6 stages. New GIST patients increased gradually year by year. There were 13(0.5%) cases during 1998 to 2000, 68(2.6%) cases during 2001 to 2003, 256(9.8%) cases during 2004 to 2006, 517 (19.8%) cases during 2007 to 2009, 814(31.2%) cases during 2010 to 2012, and 942 (36.1%) cases during 2013 to 2015. Primary GIST sites were esophagus in 50(1.9%) cases, stomach in 1 686(64.6%) cases, duodenum in 206 (7.9%) cases, jejunum and ileum in 446 (17.1%) cases, colon and rectum in 133 (5.1%) cases, and non-gastrointestinal tract in 89 (3.4%) cases. GIST lesions of 2 404(92.1%) cases located in the primary sites and relapse/metastasis occurred in 206 cases when consulting. Among 206 relapse/metastasis cases, liver metastasis was found in 126 (61.2%) cases, abdominal cavity/pelvic cavity metastasis in 64 (31.1%) cases, liver plus abdominal cavity/pelvic cavity metastasis in 12 (5.8%) cases, and other site metastasis in 4 (1.9%) cases. Among all the patients, 352 received gene detection, including 1 (0.4%) during 2004 to 2006, 7 (1.4%) during 2007 to 2009, 150 (18.4%) during 2010 to 2012, and 194 (20.6%) during 2013 to 2015. Most of the primary oncogenic mutational site occurred in c-Kit, including 30 (8.5%) cases in exon 9, 242 (68.8%) cases in exon 11, 4 (1.1%) cases in exon 13, 2 (0.6%) cases in exon 17, while 3 (0.9%) cases in PDGFRA exon 12 and 20 (5.7%) cases in PDGFRA 18, besides, no mutations of KIT and PDGFRA were detected in 51 (14.5%) cases. A total of 2 202 cases underwent operation, including 2 038 (92.6%) of radical resection and 164 (7.4%) of palliative resection. Among 2 038 patients undergoing radical resection, 450 (22.1%) cases were very low risk, 593 (29.1%) cases were low risk, 283 (13.9%) cases were moderate risk and 712 (34.9%) cases were high risk according to NIH risk classification. Of 995 patients with moderate and high risk, 550(55.3%) cases received postoperative imatinib adjuvant therapy, whose ratio in above 6 time stages was as follows: 0, 42.8%(12/28), 19.8%(20/101), 9.8% (21/215), 65.7% (176/268) and 85.6% (321/375). Of 206 relapse/metastasis patients, 200 (97.1%) cases received imatinib as the first-line therapy, and 22 (10.7%) received sunitinib as the second-line therapy. A total of 1 743 patients had complete follow-up data and median follow-up time was 35.9 (0.1 to 173.8) months. The 5-year overall survival rates in very low, low, moderate and high risk patients were 100%, 97%, 95% and 78% respectively.</p><p><b>CONCLUSION</b>This retrospective study provides the largest data of GIST and indicates the historic changes of clinicopathological characteristics, diagnosis and treatment of GIST for further domestic GIST research.</p>