1.Clinical outcomes of fresh and frozen embryos transfer after in vitro fertilization in spouses of patients with severely low sperm concentration and motility
Xiaoxiao HU ; Lijuan ZHAO ; Lingying JIANG ; Songying ZHANG
Journal of Zhejiang University. Medical sciences 2024;53(3):368-375
		                        		
		                        			
		                        			Objective:To compare the pregnancy and neonatal outcomes of in vitro fertilization-embryo transfer(IVF-ET)with fresh or frozen embryos in spouses of patients with severely low sperm concentration and motility.Methods:A total of 2300 patients whose spouses have severely low sperm concentration and motility underwent IVT-ET in the Reproduction Medicine Center,Sir Run Run Shaw Hospital from April 2018 to April 2022.After applying the propensity score matching(PSM),473 fresh embryo transferred cycles and 473 frozen embryo transferred cycles were selected for the study,and the pregnancy and neonatal outcomes were compared between the two groups.Results:There were no significant differences in pregnancy outcomes and neonatal outcomes between fresh and frozen embryo groups(all P>0.05).In the stratification analysis,the number of retrieved oocytes in the fresh good-quality embryo transfer group was significantly increased compared with the fresh poor-quality embryo group(P<0.05),but the very early pregnancy loss rates were similar between the two groups(P>0.05),while the rate in fresh good-quality embryo transfer group was significantly higher than that in the frozen good-quality embryo transfer group(P<0.05).Among different age groups of women,the number of retrieved oocytes and the level of estrogen in the fresh embryo transfer group was significantly higher in the 20 to<30 years old group than that in the 30 to<35 years old group(both P<0.05),but the clinical pregnancy rate was lower in the 20 to<30 years old group than that in the 30 to<35 years old group(P>0.05).Additionally,the very early pregnancy loss was significantly increased in the fresh embryo group compared with the frozen embryo group in the 20 to<30 years age group(P<0.05).Conclusions:There were no significant differences in pregnancy and neonatal outcomes between fresh and frozen embryo transfer in spouses of patients with severely low sperm concentration and motility undergoing IVF-ET.Due to the shorter transfer times,less embryo freezing damage and reduced costs,fresh embryo transfer can be considered as the first choice.However,it is not necessary to pursue fresh embryo transfer if maternal oestrogen levels are too high and there is a tendency of overstimulation.
		                        		
		                        		
		                        		
		                        	
2.MAPK4 Accelerates Progression of Cervical Squamous Cell Carcinoma by Positively Regulating SLC3A2 Expression
Jing YU ; Lu DENG ; Yuting ZHAO ; Zhenlong YUAN ; Lingying WU
Cancer Research on Prevention and Treatment 2024;51(10):803-812
		                        		
		                        			
		                        			Objective To explore the role of MAPK4 in cervical squamous cell carcinoma(CSCC)for the identification of candidate prognostic prediction biomarkers and molecular therapeutic targets.Methods The TCGA cohort was subjected to Kaplan-Meier survival analysis.Immunohistochemistry experiments were conducted on clinical samples to explore the correlation between MAPK4 and patient prognosis.A nomogram was constructed based on MAPK4 mRNA levels.Western blot,CCK-8,colony formation,and Transwell cell function experiments were performed to clarify the abnormal expression and role of MAPK4 in CSCC.DIA proteome sequencing was used to identify effector molecules regulated by MAPK4.Combined with the above cell function experiments,the knockdown of MAPK4 and the overexpression of effector molecules revealed that MAPK4 regulated effector molecules to mediate tumor progression.Results CSCC patients with elevated MAPK4 mRNA levels and high protein expression have a worse prognosis.The constructed nomogram based on MAPK4 can accurately predict the 1-,3-,and 5-year survival rates of patients.Compared with that in normal cervical tissues,MAPK4 protein expre-ssion was up-regulated in tumors.MAP-K4 knockdown substantially inhibited the proliferation,colony formation,mig-ration,and invasion of CSCC ME180 and SiHa cells.SLC3A2 is a downs-tream effector molecule of MAPK4.Overexpression SLC3A2 can weaken the inhibitory effect of MAPK4 knockdown on cell proliferation,colony formation,migration,and invasion.Conclusion MAPK4 is a candidate prognostic biomarker for patients with CSCC.MAPK4 positively regulates SLC3A2 protein expression and accelerates tumor progression,making it a potential molecular therapeutic target for patients with CSCC.
		                        		
		                        		
		                        		
		                        	
3.Analysis of factors for serious early complications after primary debulking surgery in elderly patients with advanced epithelial ovarian cancer
Yiran CHEN ; Hongwen YAO ; Ying CUI ; Yuxi ZHAO ; Qian HU ; Guihua SHEN ; Lingying WU
Chinese Journal of Geriatrics 2023;42(6):689-695
		                        		
		                        			
		                        			Objective:To investigate the factors for serious complications within 30 days after surgery in elderly patients with advanced epithelial ovarian cancer(EOC)who undertook primary debulking surgery(PDS).Methods:The clinical data of International Federation of Gynecology and Obstetrics(FIGO)stage ⅢC/Ⅳ EOC patients aged≥60 years who received PDS in gynecological department of National Cancer Center and National Center of Gerontology between January 2014 and December 2018 were retrospectively analyzed.Clavien-Dindo scoring system was applied to grade the complications within 30 days after surgery.The serious early postoperative complications were those of grade Ⅲ or above occurred within 30 days after surgery.Multivariate Logistic regression analysis was used to screen the independent risk factors of serious complications within 30 days after surgery.Results:A total of 133 patients were included in this study and serious complications rated 11.3%(15/133). The mean age of patients in severe complication group was significantly higher than that in the control group[(69.80±6.56) vs.(65.87±5.14), t=2.699, P=0.008]. The proportion of patients with preoperative ECOG score≥2 was significantly higher in the severe complication group than that in the control group[26.7%(4/15) vs.5.9%(7/118), χ2=4.985, P=0.026], and the proportion of preoperative hypoalbuminemia(<35 g/L)was significantly higher in the severe complication group[20.0%(3/15) vs.3.4%(4/118), χ2=4.897, P=0.027]. However, there was no significant difference in intraoperative bleeding, R0 resection rate as well as surgical complexity( χ2=1.964, 0.330, 4.637, all P>0.05)between the two groups.Multivariate Logistic regression analysis showed that the independent factors for serious early postoperative complications were age≥70 years( OR=4.345, P=0.028), ECOG score≥2( OR=25.619, P=0.008)and preoperative albumin <35 g/L( OR=6.733, P=0.040). Conclusions:In the elderly ovarian cancer patients, individualized perioperative management should be strengthened for the patients with factors associated with serious early postoperative complications, in order to reduce severe complications and improve the prognosis.
		                        		
		                        		
		                        		
		                        	
4.Research Progress on Antitumor Mechanism of Apatinib
Lingying ZHAO ; Wenqing ZHANG ; Cunxi LI ; Tianhui HU
Cancer Research on Prevention and Treatment 2021;48(1):7-11
		                        		
		                        			
		                        			In recent years, antiangiogenic drugs based on VEGF and VEGFRs signaling pathway have been widely used in the treatment of malignant tumors. Apatinib is an orally bioavailable small-molecule antiangiogenic agent and can specifically inhibit the tyrosine kinase activity of VEGFR, thereby inhibiting tumor angiogenesis. Apatinib is the first-level recommendation of third-line treatment of gastric cancer in CSCO Guidelines for the Diagnosis and Treatment of Gastric Cancer published in 2018. Apatinib has been proved to be effective and safe in gastric, lung and breast cancers. In addition, the drug shows great potential in the treatment of a variety of solid tumors. This article reviews the recent progress on the mechanism, clinical efficacy, related efficacy predictors of apatinib and its combination with other antitumor drugs.
		                        		
		                        		
		                        		
		                        	
5.Efficiency comparison of Kwak and ACR ( 2017 ) Thyroid Imaging Reporting and Data System ( TI‐RADS) classification :a polycentric retrospective study
Yu LIANG ; Linxian YUE ; Qin CHEN ; Jie LIN ; Daoning GUO ; Peng HE ; Fang YANG ; Wensheng YUE ; Hong ZHENG ; Jiaquan RUAN ; Haijun LIU ; Jianqiong SONG ; Lingying YANG ; Juan WANG ; Chengting ZHOU ; Yutian WU ; Siyi WANG ; Yanqiong TANG ; Mengxia YUAN ; Yan ZHAO
Chinese Journal of Ultrasonography 2019;28(5):419-424
		                        		
		                        			
		                        			Objective To evaluate the diagnostic efficacy of Kwak and ACR( 2017 ) thyroid imaging reporting and data systems ( T I‐RADS ) for thyroid nodules . Methods Cases of thyroid nodule who underwent surgery from January 2015 to M arch 2018 in 15 hospitals in Sichuan province were collected and the ultrasonographic features of thyroid nodules were retrospectively analyzed by trained senior ultrasound physicians using Kwak and ACR T I‐RADS classification methods . Totally ,12 712 thyroid nodules were observed ,7 023 thyroid nodules in 7 023 cases with complete ultrasound and surgical and pathological data were eventually enrolled in the study . T hyroid nodules with solid ,hypoechoic or very hypoechoic ,tall/wide ratio ≥ 1 , margin ill‐defined and microcalcification were classified as malignant signs of ultrasound . M alignant percentage was calculated and diagnostic tests were performed . Results ① T here was a statistical difference between the benign and malignant nodules in the two types of T I‐RADS classification ( P<0 .01) . ② T he area under ROC curve of Kwak and ACR in the diagnosis of malignant nodules were 0 .89 and 0 .84 ,respectively . T he Youden index of Kwak and ACR were 0 .66 and 0 .57 ,respectively . ③Taking Kwak T I4B and ACR T R4 as critical points for malignancy ,the sensitivity ,specificity ,positive predictive value and negative predictive value of Kwak T I 4B were 75 .0% ,90 .9% ,83 .2% ,and 85 .9% , respectively . T he accuracy of Kwak T I4B was 84 .9% ; T he sensitivity ,specificity ,positive predictive value and negative predictive value of ACR T R4 were 88 .2% ,68 .9% ,62 .9% ,and 90 .8% ,respectively . T he accuracy of ACR T R4 was 76 .2% . T he Kappa value of Kwak TI4B and ACR T R4 was 0 .52 . T he χ2 value of Kwak T I4B and ACR T R4 was 2 174 .6 ( P < 0 .01 ) . Conclusions T he diagnostic values of two T I‐RADS classification methods for thyroid malignant nodules are high . T he overall efficiency of Kwak T I‐RADS classification method is better than that of ACR TI‐RADS classification method .
		                        		
		                        		
		                        		
		                        	
6. Analysis of effects and postoperative clinicopathological prognosis factors of neoadjuvant chemotherapy in patients with stage Ⅰb2 and Ⅱa2 squamous cell carcinoma of the cervix
Jusheng AN ; Yuxi ZHAO ; Yan SONG ; Ning LI ; Manni HUANG ; Xiaoguang LI ; Bin LI ; Rong ZHANG ; Lingying WU
Chinese Journal of Obstetrics and Gynecology 2019;54(10):673-679
		                        		
		                        			 Objective:
		                        			To explore the effects and postoperative prognostic factors in cervical cancer patients received neoadjuvant chemotherapy combined with surgery and post-operative adjuvant therapy.
		                        		
		                        			Methods:
		                        			A total of 177 patients with cervical cancer at International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ b2, Ⅱ a2 who underwent neoadjuvant chemotherapy (NACT) followed by surgery with and without adjuvant therapy in Cancer Hospital, Chinese Academy of Medical Sciences were included. Univariate and multivariate analyses of 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were performed.
		                        		
		                        			Results:
		                        			Of 177 patients, 133 (75.1%) had stage Ⅰb2 and 44 (24.9%) had Ⅱa2 cancers. After NACT, overall response rate was 63.3% (112/177) including 12 cases of complete response (CR), 100 of partial response (PR) and no progressive disease (PD) case. At a median follow-up of 59.2 months, the 5-year DFS rate was 73.6% and the 5-year OS rate was 86.8%. Univariate analysis revealed that lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year DFS rate (
		                        		
		                        	
7.Analysis of effects and postoperative clinicopathological prognosis factors of neoadjuvant chemotherapy in patients with stageⅠb2 andⅡa2 squamous cell carcinoma of the cervix
Jusheng AN ; Yuxi ZHAO ; Yan SONG ; Ning LI ; Manni HUANG ; Xiaoguang LI ; Bin LI ; Rong ZHANG ; Lingying WU
Chinese Journal of Obstetrics and Gynecology 2019;54(10):673-679
		                        		
		                        			
		                        			Objective To explore the effects and postoperative prognostic factors in cervical cancer patients received neoadjuvant chemotherapy combined with surgery and post-operative adjuvant therapy. Methods A total of 177 patients with cervical cancer at International Federation of Gynecology and Obstetrics (FIGO) stageⅠb2, Ⅱa2 who underwent neoadjuvant chemotherapy (NACT) followed by surgery with and without adjuvant therapy in Cancer Hospital, Chinese Academy of Medical Sciences were included. Univariate and multivariate analyses of 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were performed. Results Of 177 patients, 133 (75.1%) had stageⅠb2 and 44 (24.9%) hadⅡa2 cancers. After NACT,overall response rate was 63.3% (112/177) including 12 cases of complete response (CR), 100 of partial response (PR) and no progressive disease (PD) case. At a median follow-up of 59.2 months, the 5-year DFS rate was 73.6% and the 5-year OS rate was 86.8%. Univariate analysis revealed that lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year DFS rate (P<0.05). Lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year OS rate (P<0.05). The multivariate analysis showed that, stromal invasion (outer 1/3 or outer 1/2) was independent risk factor of 5-year DFS rate (P<0.05), and 5-year OS rate was significantly affected by tumor size >3 cm after NACT (P<0.05). Conclusions The effect of NACT in Ⅰb2, Ⅱa2 squamous carcinoma of the uterined cervix is confirmed. The independent risk factor for 5-year DFS rate in patients received NACT and hysterectomy is deep stromal invasion of the cervix. The presence of tumor size>3 cm after NACT adversely affect 5-year OS rate.
		                        		
		                        		
		                        		
		                        	
8.Analysis of prognostic factors and therapeutic patterns of recurrent stage Ⅰb-Ⅱa cervical squamous carcinoma treated with radical hysterectomy
Zhengjie OU ; Dan ZHAO ; Jusheng AN ; Chunyang SUN ; Manni HUANG ; Bin LI ; Lingying WU
Chinese Journal of Obstetrics and Gynecology 2019;54(6):399-405
		                        		
		                        			
		                        			Objective To analyze the prognosis and appropriate treatment modalities of the patients with recurrence of early stage (Ⅰb-Ⅱa) cervical squamous cancer primarily treated with radical hysterectomy. Methods This retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰb and Ⅱa recurrent cervical squamous cancer who underwent radical hysterectomy primarily from January 2007 to July 2015. Kaplan-Meier method and Cox regression analysis were performed to analyze related prognostic factors of overall survival and progression-free survival, which included age, postoperative therapy, the site of recurrence, therapy-free interval (TFI) and treatment modality. The patients who were treated with palliative chemotherapy after recurrence were selected as a subgroup. The responses of palliative chemotherapy were evaluated and analyzed among different factors, included TFI, the site of recurrence and chemotherapy regime. Results Of the 2 071 patients, 116 relapsedⅠb-Ⅱa cervical squamous cancer were included in the study with the average age of (45.6±7.2) years old. 3-year progression-free survival rate and 3-year overall survival rate after recurrence were 30.2% and 42.2%, respectively. Univariate analysis implied that postoperative radiotherapy, recurrence site, TFI and treatment modality were associated with progression-free survival (P<0.05), while postoperative radiotherapy, TFI and treatment modality with overall survival (P<0.05). Multivariate analysis showed that TFI and treatment modality were independent prognostic factors for progression-free survival (P<0.05), while postoperative radiotherapy at initial treatment, TFI and treatment modality were independent prognostic variables for overall survival (P<0.05). In the analysis of treatment modality, 3-year progression-free survival rate and 3-year overall survival rate of 47 patients who were treated with definitive local therapy were significantly higher than that of 69 patients who were treated with palliative chemotherapy (P<0.01). In the subgroup analysis of palliative chemotherapy, 15 patients achieved complete response (21.7%) and 16 displayed partial response (23.2%). The overall response rate (ORR) was 44.9%. TFI (P<0.01) and chemotherapy regime (P<0.05) were significant factors associated with ORR. The ORR of TFI≥12 months was significantly higher than that of TFI <12 months. Besides, the ORR of paclitaxel plus platinum chemotherapy was prominently higher than that of other regimens, while there was no significant difference between the ORR of paclitaxel plus cisplatin and other platinum (P=0.408). Conclusions For recurrent stageⅠb-Ⅱa cervical squamous carcinoma treated with radical hysterectomy, use of definitive local therapy for suitable patients is advised to achieve better prognosis. In terms of palliative chemotherapy, longer TFI may mean better ORR and the combination of paclitaxel plus platinum is preferred.
		                        		
		                        		
		                        		
		                        	
9.Development of health care needs assessment tool for the elderly
Lingying WANG ; Yipu ZHAO ; Xiuying HU
Chinese Journal of Modern Nursing 2019;25(23):2905-2910
		                        		
		                        			
		                        			Objective? To develop a health care needs assessment tool for the elderly at home, which is in line with China's national conditions. Methods? Guided by Zuluaga-Raysmith model theory, a health care needs assessment tool for the elderly was developed through literature review, theoretical analysis, expert review, expert consultation and pre-survey. Results? An item pool of 10 first-level items and 72 second-level items, which were suitable for home-based elderly health care needs assessment tools was initially formed. Through three rounds of national expert consultation and pre-survey, an elderly health care needs assessment tool consisting of 7 first-level items, 10 second-level items and 61 third-level items was formed. The expert authority coefficient was 0.791, the expert positive coefficient was 100%, and the expert coordination coefficient was 0.935 (P< 0.05). Conclusions The pool of items for the assessment tool is reasonably formed, the results of Delphi expert consultation are reliable. The scale can be widely used after adjustment. It can help medical staff quickly and comprehensively understand the current situation of health care needs of the elderly, provide support for the accurate construction of long-term care service system for the elderly, and support the development of community/home care for the elderly.
		                        		
		                        		
		                        		
		                        	
10.Up-regulation of soluble vascular endothelial growth factor receptor 1 expression in co-culture of human umbilical cord-derived mesenchymal stem cells and rheumatoid arthritis fibroblast-like synoviocytes
Yu WEI ; Xiaojun TANG ; Lingyu GENG ; Lingying NIU ; Chun WANG ; Yue SUN ; Bingzhu HUA ; Cheng ZHAO
Chinese Journal of Rheumatology 2018;22(10):691-694
		                        		
		                        			
		                        			Objective To investigate the expression of soluble vascular endothelial growth factor receptor 1 (sFlt1) in human umbilical cord-derived mesenchymal stem cells (HUCMSC) under the condition of inflammatory cytokine and co-culture with rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs).Methods ① HUCMSC were cultured alone or stimulated by Tumour necrosis factor (TNF)-αt,interferon (IFN)-γor the combination of TNF-α and IFN-γ.The sFh1 levels of each group were detected by enzyme-linked immunosorbent assay (ELISA) at 24 h,48 h and 72 h respectively.② RA-FLSs and HUCMSC were cocultured in a transwell system with both of them cultured alone as control for 72 hours.ELISA was used to detect sFlt1 levels in each group.T test was used for comparison between two groups,and ANOVA was used to compare multi-group variables.Results ① The sFlt1 levels of TNF-α + IFN-γ group were significantly higher than those of the control group at 24 h and 48 h (24 h (5.4±0.4) ng/ml vs (2.8±1.7) ng/ml,t=0.942,P=0.026;48 h (7.2±0.8) vs (4.3±1.0) ng/ml,t=4.285,P=0.005),while that at 72 h was not significantly different [(9.1±1.7) ng/ml vs (7.0±1.4) ng/ml,t=0.683,P=0.52].And no significant difference in sFlt1 levels between control group and TNF-α group or IFN-γ stimulation group were observed.② Compared with RA-FLSs,the expression of sFlt1 in HUCMSC was significantly higher (8.19±3.64) ng/ml vs (0.19±0.08) ng/ml,t=7.280,P<0.01].After co-cultured with RA-FLSs and HUCMSC,the sFlt1 concentration of the co-culture group was significantly higher than that of HUCMSC group [(17.26±6.92) ng/ml vs (8.19±3.64) ng/ml,t=3.985,P=0.000 7].Conclusion The sFlt1 expression of HUCMSC is up-regulated by inflammatory cytokine TNF-α combined with IFN-γ.RA FLSs may promote the co-cultured HUCMSC to increase sFlt1 expression by secreting inflammatory factors.
		                        		
		                        		
		                        		
		                        	
            
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