1.Effectiveness of the artificial intelligence image recognition system in diagnosing endometrial cytopathology
Jing AN ; Panyue YIN ; Bin WANG ; Guizhi SHI ; Dexing ZHONG ; Jianliu WANG ; Qiling LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(2):343-347
		                        		
		                        			
		                        			【Objective】 To explore the effectiveness of an image recognition system based on artificial intelligence (AI) in diagnosing benign and malignant endometrial cell clumps. 【Methods】 We selected endometrial cytological specimens from The First Affiliated Hospital of Xi’an Jiaotong University and Xi’an Daxing Hospital from August 2021 to February 2023; histopathology was used as the gold standard. We compared and analyzed the sensitivity, specificity, positive predictive value, negative predictive value, accuracy and diagnostic time of AI image recognition system (AI diagnosis) and professional pathologists’ manual diagnosis (manual diagnosis) of benign and malignant endometrial cell clumps. 【Results】 Among the 126 patients included in the analysis, the overall coincidence rate of AI diagnosis and histological diagnosis was 92.1% (116/126), which was highly consistent with histopathological results (Kappa=0.841). The overall coincidence rate of manual diagnosis and histological diagnosis was 94.4% (119/126), which was highly consistent with histopathological results (Kappa=0.889). There was no statistically significant difference between AI diagnosis and manual diagnosis methods (χ2=0.568, P=0.451). The sensitivity, specificity, positive predictive value, and negative predictive value of AI diagnosis were 91.8%, 92.3%, 91.8%, and 92.3%, respectively. There were 126 cytology sections, each of which required 6.67 minutes for manual diagnosis and 5.00 minutes for AI diagnosis. 【Conclusion】 The AI image recognition system has high diagnostic accuracy, sensitivity and specificity, which is equivalent to the manual diagnosis level of professional pathologists. Therefore, this system has application value in the diagnosis of benign and malignant endometrial cell clumps.
		                        		
		                        		
		                        		
		                        	
2.Clinical significance of lympho-vascular space invasion in different molecular subtypes of endometrial carcinoma
Yimeng LI ; Zhuoyu ZHAI ; He LI ; Liwei LI ; Zhihui SHEN ; Xiaobo ZHANG ; Zhiqi WANG ; Jianliu WANG
Chinese Journal of Obstetrics and Gynecology 2024;59(8):617-627
		                        		
		                        			
		                        			Objective:To analyze the lympho-vascular space invasion (LVSI) in different molecular subtypes of the cancer genome atlas (TCGA) molecular subtypes of endometrial cancer (EC) and to evaluate the prognostic value of LVSI in EC patients with different molecular subtypes.Methods:A total of 258 patients diagnosed EC undergoing surgery in Peking University People′s Hospital from January 2016 to June 2022 were analyzed retrospectively. Among 258 patients, 14 cases were classified as POLE-ultramutated subtype, 43 as high-microsatellite instability (MSI-H) subtype, 155 as copy-number low (CNL) subtype, and 46 as copy-number high (CNH) subtype. Fifty-four patients were positive for LVSI, while 203 tested negative.Results:(1) The incidence of LVSI was found to be highest in the CNH subtype (32.6%,15/46), followed by the MSI-H subtype (27.9%, 12/43), the CNL subtype (16.9%, 26/154), and the POLE-ultramutated subtype (1/14), with statistically significant differences ( χ2=7.79, P=0.044). (2) Staging and deep myometrial invasion were higher in the LVSI positive group than those in the LVSI negative group (all P<0.05), except for the POLE-ultramutated subtype. The grade, lymph node metastasis, and the expression of nuclear antigen associated with cell proliferation (Ki-67) were significantly higher in LVSI positive patients than those in LVSI negative EC patients with both MSI-H and CNL subtypes (all P<0.05). In CNL subtypes patients, LVSI was also associated with age, histology subtype,and progesterone receptor (PR; all P<0.05). (3) Of the 257 EC patients, 25 cases recurred during the follow-up period, with a recurrence rate of 9.7% (25/257); among them, the recurrence rate of LVSI positive patients was 22.2% (12/54), which was significantly higher than those with LVSI negative (6.4%, 13/203; χ2=12.15, P<0.001). During the follow-up period, none of the 14 patients with POLE-ultramutated had recurrence; among CNL patients, the recurrence rate was 19.2% (5/26) in LVSI positive patients, which was significantly higher than that in LVSI negative ones (5.5%, 7/128; χ2=3.94, P=0.047); where as no difference were found in both MSI-H [recurrence rates in LVSI positive and negative patients were 2/12 and 9.7% (3/31), respectively] and CNH subtype [recurrence rates between LVSI positive and negative patients were 5/15 and 9.7% (3/31), respectively] EC patients (both P>0.05). After log-rank test, the 3-year recurrence free survival (RFS) rate were significantly lower in LVSI positive patients from CNL subtype and CNH subtype than those in LVSI negative patients (CNL: 80.8% vs 94.5%; CNH: 66.7% vs 90.3%; both P<0.05). (4) Lymph node metastasis ( HR=6.93, 95% CI: 1.15-41.65; P=0.034) had a significant effect on the 3-year RFS rate of EC patients with MSI-H subtype. Multivariate analysis revealed that PR expression ( HR=0.04, 95% CI: 0.01-0.14; P<0.001) was significantly associated with the 3-year RFS rate of CNL subtype patients. Conclusions:LVSI has the highest positivity rate in CNH subtype, followed by MSI-H subtype, CNL subtype, and the lowest positivity rate in POLE-ultramutated subtype. LVSI is significantly associated with poor prognosis in CNL subtype patients and may affect the prognosis of CNH subtype patients. However, LVSI is not an independent risk factor for recurrence across all four TCGA molecular subtypes.
		                        		
		                        		
		                        		
		                        	
3.Diagnostic significance and predictive efficiency of metabolic risk score for fertility-sparing treatment in patients with atypical endometrial hyperplasia and early endometrial carcinoma
Xingchen LI ; Yiqin WANG ; Jiaqi WANG ; Jingyi ZHOU ; Jianliu WANG
Journal of Gynecologic Oncology 2024;35(4):e42-
		                        		
		                        			 Objective:
		                        			This study aims to assess the impact of the metabolic risk score (MRS) on time to achieve complete remission (CR) of fertility-sparing treatments for atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) patients. 
		                        		
		                        			Methods:
		                        			Univariate and multivariate cox analyses were employed to identify independent risk factors affecting the time to CR with patients at our center. These factors were subsequently incorporated into receiver operator characteristic curve analysis and decision curve analysis to assess the predictive accuracy of time to CR. Additionally, Kaplan–Meier analysis was utilized to determine the cumulative CR rate for patients. 
		                        		
		                        			Results:
		                        			The 173 patients who achieved CR following fertility preservation treatment (FPT) were categorized into three subgroups based on their time to CR (<6, 6–9, >9 months). Body mass index (hazard ratio [HR]=0.20; 95% confidence interval [CI]=0.03, 0.38; p=0.026), MRS (HR=0.31; 95% CI=0.09, 0.52; p=0.005), insulin resistance (HR=1.83; 95% CI=0.05, 3.60; p=0.045), menstruation regularity (HR=3.77; 95% CI=1.91, 5.64; p=0.001), polycystic ovary syndrome (HR=−2.16; 95% CI=−4.03, −0.28; p=0.025), and histological type (HR=0.36;95% CI=0.10, 0.62; p=0.005) were identified as risk factors for time to CR, with MRS being the independent risk factor (HR=0.29; 95% CI=0.02, 0.56; p=0.021). The inclusion of MRS significantly enhanced the predictive accuracy of time to CR (area under the curve [AUC]=0.789 for Model 1, AUC=0.862 for Model 2, p=0.032). Kaplan–Meier survival curves revealed significant differences in the cumulative CR rate among different risk groups. 
		                        		
		                        			Conclusion
		                        			MRS emerges as a novel evaluation system that substantially enhances the predictive accuracy for the time to achieve CR in AEH and early EC patients seeking fertility preservation. 
		                        		
		                        		
		                        		
		                        	
4.Diagnostic significance and predictive efficiency of metabolic risk score for fertility-sparing treatment in patients with atypical endometrial hyperplasia and early endometrial carcinoma
Xingchen LI ; Yiqin WANG ; Jiaqi WANG ; Jingyi ZHOU ; Jianliu WANG
Journal of Gynecologic Oncology 2024;35(4):e42-
		                        		
		                        			 Objective:
		                        			This study aims to assess the impact of the metabolic risk score (MRS) on time to achieve complete remission (CR) of fertility-sparing treatments for atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) patients. 
		                        		
		                        			Methods:
		                        			Univariate and multivariate cox analyses were employed to identify independent risk factors affecting the time to CR with patients at our center. These factors were subsequently incorporated into receiver operator characteristic curve analysis and decision curve analysis to assess the predictive accuracy of time to CR. Additionally, Kaplan–Meier analysis was utilized to determine the cumulative CR rate for patients. 
		                        		
		                        			Results:
		                        			The 173 patients who achieved CR following fertility preservation treatment (FPT) were categorized into three subgroups based on their time to CR (<6, 6–9, >9 months). Body mass index (hazard ratio [HR]=0.20; 95% confidence interval [CI]=0.03, 0.38; p=0.026), MRS (HR=0.31; 95% CI=0.09, 0.52; p=0.005), insulin resistance (HR=1.83; 95% CI=0.05, 3.60; p=0.045), menstruation regularity (HR=3.77; 95% CI=1.91, 5.64; p=0.001), polycystic ovary syndrome (HR=−2.16; 95% CI=−4.03, −0.28; p=0.025), and histological type (HR=0.36;95% CI=0.10, 0.62; p=0.005) were identified as risk factors for time to CR, with MRS being the independent risk factor (HR=0.29; 95% CI=0.02, 0.56; p=0.021). The inclusion of MRS significantly enhanced the predictive accuracy of time to CR (area under the curve [AUC]=0.789 for Model 1, AUC=0.862 for Model 2, p=0.032). Kaplan–Meier survival curves revealed significant differences in the cumulative CR rate among different risk groups. 
		                        		
		                        			Conclusion
		                        			MRS emerges as a novel evaluation system that substantially enhances the predictive accuracy for the time to achieve CR in AEH and early EC patients seeking fertility preservation. 
		                        		
		                        		
		                        		
		                        	
5.Diagnostic significance and predictive efficiency of metabolic risk score for fertility-sparing treatment in patients with atypical endometrial hyperplasia and early endometrial carcinoma
Xingchen LI ; Yiqin WANG ; Jiaqi WANG ; Jingyi ZHOU ; Jianliu WANG
Journal of Gynecologic Oncology 2024;35(4):e42-
		                        		
		                        			 Objective:
		                        			This study aims to assess the impact of the metabolic risk score (MRS) on time to achieve complete remission (CR) of fertility-sparing treatments for atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) patients. 
		                        		
		                        			Methods:
		                        			Univariate and multivariate cox analyses were employed to identify independent risk factors affecting the time to CR with patients at our center. These factors were subsequently incorporated into receiver operator characteristic curve analysis and decision curve analysis to assess the predictive accuracy of time to CR. Additionally, Kaplan–Meier analysis was utilized to determine the cumulative CR rate for patients. 
		                        		
		                        			Results:
		                        			The 173 patients who achieved CR following fertility preservation treatment (FPT) were categorized into three subgroups based on their time to CR (<6, 6–9, >9 months). Body mass index (hazard ratio [HR]=0.20; 95% confidence interval [CI]=0.03, 0.38; p=0.026), MRS (HR=0.31; 95% CI=0.09, 0.52; p=0.005), insulin resistance (HR=1.83; 95% CI=0.05, 3.60; p=0.045), menstruation regularity (HR=3.77; 95% CI=1.91, 5.64; p=0.001), polycystic ovary syndrome (HR=−2.16; 95% CI=−4.03, −0.28; p=0.025), and histological type (HR=0.36;95% CI=0.10, 0.62; p=0.005) were identified as risk factors for time to CR, with MRS being the independent risk factor (HR=0.29; 95% CI=0.02, 0.56; p=0.021). The inclusion of MRS significantly enhanced the predictive accuracy of time to CR (area under the curve [AUC]=0.789 for Model 1, AUC=0.862 for Model 2, p=0.032). Kaplan–Meier survival curves revealed significant differences in the cumulative CR rate among different risk groups. 
		                        		
		                        			Conclusion
		                        			MRS emerges as a novel evaluation system that substantially enhances the predictive accuracy for the time to achieve CR in AEH and early EC patients seeking fertility preservation. 
		                        		
		                        		
		                        		
		                        	
6.Role of steroid receptor-associated and regulated protein in tumor progression and progesterone receptor signaling in endometrial cancer.
Jie LIU ; Zhiqi WANG ; Jingyi ZHOU ; Jiaqi WANG ; Xiangjun HE ; Jianliu WANG
Chinese Medical Journal 2023;136(21):2576-2586
		                        		
		                        			BACKGROUND:
		                        			Steroid receptor-associated and regulated protein (SRARP) suppresses tumor progression and modulates steroid receptor signaling by interacting with estrogen receptors and androgen receptors in breast cancer. In endometrial cancer (EC), progesterone receptor (PR) signaling is crucial for responsiveness to progestin therapy. The aim of this study was to investigate the role of SRARP in tumor progression and PR signaling in EC.
		                        		
		                        			METHODS:
		                        			Ribonucleic acid sequencing data from the Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium, and Gene Expression Omnibus were used to analyze the clinical significance of SRARP and its correlation with PR expression in EC. The correlation between SRARP and PR expression was validated in EC samples obtained from Peking University People's Hospital. SRARP function was investigated by lentivirus-mediated overexpression in Ishikawa and HEC-50B cells. Cell Counting Kit-8 assays, cell cycle analyses, wound healing assays, and Transwell assays were used to evaluate cell proliferation, migration, and invasion. Western blotting and quantitative real-time polymerase chain reaction were used to evaluate gene expression. The effects of SRARP on the regulation of PR signaling were determined by co-immunoprecipitation, PR response element (PRE) luciferase reporter assay, and PR downstream gene detection.
		                        		
		                        			RESULTS:
		                        			Higher SRARP expression was significantly associated with better overall survival and disease-free survival and less aggressive EC types. SRARP overexpression suppressed growth, migration, and invasion in EC cells, increased E-cadherin expression, and decreased N-cadherin and Wnt family member 7A ( WNT7A ) expression. SRARP expression was positively correlated with PR expression in EC tissues. In SRARP -overexpressing cells, PR isoform B (PRB) was upregulated and SRARP bound to PRB. Significant increases in PRE-based luciferase activity and expression levels of PR target genes were observed in response to medroxyprogesterone acetate.
		                        		
		                        			CONCLUSIONS
		                        			This study illustrates that SRARP exerts a tumor-suppressive effect by inhibiting the epithelial-mesenchymal transition via Wnt signaling in EC. In addition, SRARP positively modulates PR expression and interacts with PR to regulate PR downstream target genes.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Receptors, Progesterone/metabolism*
		                        			;
		                        		
		                        			Proteomics
		                        			;
		                        		
		                        			Cell Line, Tumor
		                        			;
		                        		
		                        			Endometrial Neoplasms/metabolism*
		                        			;
		                        		
		                        			Cell Proliferation/genetics*
		                        			;
		                        		
		                        			Luciferases/pharmacology*
		                        			;
		                        		
		                        			Gene Expression Regulation, Neoplastic/genetics*
		                        			
		                        		
		                        	
7.Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma
Nan KANG ; Yinli ZHANG ; Shichao GUO ; Ran CHEN ; Fangzhou KONG ; Shuchun WANG ; Mingming YUAN ; Rongrong CHEN ; Danhua SHEN ; Jianliu WANG
Cancer Research and Treatment 2023;55(3):978-991
		                        		
		                        			 Purpose:
		                        			The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients. 
		                        		
		                        			Materials and Methods:
		                        			A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored. 
		                        		
		                        			Results:
		                        			TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion. 
		                        		
		                        			Conclusion
		                        			This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy. 
		                        		
		                        		
		                        		
		                        	
8.Construction of core indicators for entrustable professional activities in specialists in obstetrics and gynecology
Fang AN ; Sha DOU ; Honglan ZHU ; Huaqin CHENG ; Xiuli SUN ; Jianliu WANG
Chinese Journal of Medical Education Research 2023;22(10):1441-1445
		                        		
		                        			
		                        			Objective:To construct the core indicators for entrustable professional activities in specialists in obstetrics and gynecology.Methods:A study group was formed by the specialists in obstetrics and gynecology and the experts in medical education. The core indicators for entrustable professional activities were constructed for the specialists in obstetrics and gynecology based on literature review and clinical practice, and then the Delphi method was used to conduct two rounds of expert letter consultation for screening and optimization from March 2021 to January 2023 to further identify the core indications.Results:The expert positive coefficient was 100% for the two rounds of consultation, with an expert authority coefficient of 0.82, and the Kendall's coefficient of concordance was 0.221 and 0.213, respectively (both P<0.01). Ten core indicators and their content descriptions were constructed for entrustable professional activities in obstetrics and gynecology specialists, and the experts had a degree of recognition of more than 80% for the importance of these ten entrustable professional activities, with a coefficient of variation of <0.25. This study determined the expected entrustable level of each indicator for specialists at the completion of the course, which ranged from grade 3 to 5; the highest level of 4.48 was observed for the diagnosis and treatment of outpatients, which was between the levels of mastery and expert; the lowest level of 3.52 was observed for laparoscopic hysterectomy, which was between the levels of competency and mastery. Conclusion:This study preliminarily constructs the core indicators for entrustable professional activities in specialists in obstetrics and gynecology, which provides a new exploration for the standardized training of specialists.
		                        		
		                        		
		                        		
		                        	
9.Fertility and prognosis assessment between bleomycin/etoposide/cisplatin and paclitaxel/carboplatin chemotherapy regimens in the conservative treatment of malignant ovarian germ cell tumors: a multicenter and retrospective study
Ran CHU ; Penglin LIU ; Jingying CHEN ; Xiaodong CHENG ; Kezhen LI ; Yanci CHE ; Jianliu WANG ; Li LI ; Xi ZHANG ; Shu YAO ; Li SONG ; Ying ZHAO ; Changzhen HUANG ; Ying XUE ; Xiyu PAN ; Junting LI ; Zhongshao CHEN ; Jie JIANG ; Beihua KONG ; Kun SONG
Journal of Gynecologic Oncology 2023;34(2):e12-
		                        		
		                        			 Objective:
		                        			To evaluate the impact of bleomycin/etoposide/cisplatin (BEP) and paclitaxel/carboplatin (PC) chemotherapy regimens on the fertility and prognostic outcomes in malignant ovarian germ cell tumor (MOGCT) patients who underwent fertility-sparing surgery (FSS). 
		                        		
		                        			Methods:
		                        			A propensity score matching algorithm was performed between the BEP and PC groups. The χ2 test and the Kaplan-Meier method were used to compare the fertility outcome, disease-free survival (DFS) and overall survival (OS). The Cox proportional hazards regression analysis was used to identify risk factor of DFS. 
		                        		
		                        			Results:
		                        			We included 213 patients, 185 (86.9%) underwent BEP chemotherapy, and 28 (13.1%) underwent PC chemotherapy. The median age was 22 years (range, 8–44 years), and the median follow-up period was 63 months (range, 2–191 months). Fifty-one (29.3%) patients had a pregnancy plan, and 35 (85.4%) delivered successfully. In the before and after propensity score matching cohorts, there were no significant differences in spontaneous abortion, selective termination of pregnancy, during-pregnancy status, and live birth between the BEP and PC groups (p>0.05). Fourteen (6.6%) patients experienced recurrence, including 11 (5.9%) in the BEP group and 3 (10.7%) in the PC group. Four (1.9%) patients in the BEP group died. Kaplan-Meier analysis revealed no significant differences in DFS (p=0.328) and OS (p=0.446) between the BEP and PC groups, and the same survival results were observed in the after matching cohort. 
		                        		
		                        			Conclusion
		                        			The PC regimen is as safe as the BEP regimen for MOGCT patients with fertility preservation treatment, and no differences were observed in fertility and clinical prognosis. 
		                        		
		                        		
		                        		
		                        	
10.Development and validation of a prognostic model based on metabolic risk score to predict overall survival of endometrial cancer in Chinese patients
Xingchen LI ; Xiao YANG ; Yuan CHENG ; Yangyang DONG ; Jingyuan WANG ; Jianliu WANG
Journal of Gynecologic Oncology 2023;34(6):e69-
		                        		
		                        			 Objective:
		                        			Metabolic syndrome (MetS) is closely related to the increased risk and poor prognosis of endometrial cancer (EC). The purpose of this study was to analyze the relationship between metabolic risk score (MRS) and EC, and establish a predictive model to predict the prognosis of EC. 
		                        		
		                        			Methods:
		                        			A retrospective study was designed of 834 patients admitted between January 2004 to December 2019. Univariate and multivariate Cox analysis were performed to screen independent prognostic factors for overall survival (OS). A predictive nomogram is built based on independent risk factors for OS. Consistency index (C-index), calibration plots and receiver operating characteristic curve were used to evaluate the predictive accuracy of the nomogram. 
		                        		
		                        			Results:
		                        			The patients were randomly divided into training cohort (n=556) and validation cohort (n=278). The MRS of EC patients, ranging from −8 to 15, was calculated. Univariate and multivariate Cox analysis indicated that age, MRS, FIGO stage, and tumor grade were independent risk factors for OS (p<0.05). The Kaplan–Meier analysis demonstrated that EC patients with low score showed a better prognosis in OS. Then, a nomogram was established and validated based on the above four variables. The C-index of nomogram were 0.819 and 0.829 in the training and validation cohorts, respectively. Patients with high-risk score had a worse OS according to the nomogram. 
		                        		
		                        			Conclusion
		                        			We constructed and validated a prognostic model based on MRS and clinical prognostic factors to predict the OS of EC patients accurately, which may help clinicians personalize prognostic assessments and effective clinical decisions. 
		                        		
		                        		
		                        		
		                        	
            
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