Weiguo Lü

Women's Hospital, School of Medicine, Zhejiang University

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Xing Xie

Women's Hospital, School of Medicine, Zhejiang University

Xiaodong Cheng

Women's Hospital, School of Medicine, Zhejiang University

Xinyu Wang

Union Hospital

Xiao Li

Chinese PLA General Hospital

Yunfeng Fu

Women's Hospital, School of Medicine, Zhejiang University

Da-feng Ye

Beijing Haidian Hospital

Jiale Qin

The First Affiliated Hospital, Sun Yat-sen University

Bingjian Lü

Women's Hospital, School of Medicine, Zhejiang University

Bei Cheng

Huazhong University of Science and Technology

Xing Xie

Peking University

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Women's Hospital, School of Medicine, Zhejiang University

102

Zhejiang University

Sun Yat-sen University

Peking University

Chinese Academy of Medical Sciences & Peking Union Medical College

Chinese Academy of Sciences

Central South University

Sichuan University

Huazhong University of Science and Technology

Shanghai Jiao Tong University

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OP20.01: An independent predictor for methotrexate resistance in low-risk gestational trophoblastic neoplasia with myometrial invasion: a prospective study

Ultrasound in Obstetrics and Gynecology (2017)

Jiale Qin Jiahui Luo Xiaodong Wu J. Wang Weiguo Lü

In Doppler ultrasound, GTN shows great change in uterine hemodynamics, especially in the cases with myometrial invasion. Low-risk GTN is a highly curable, however, approximately 30% cases will be resistant to the initial chemotherapy MTX. MTX resistance will require salvage drug leading to prolong the overall duration of treatment and accumulate more side effects. This study aimed to explore the relationship between the sonographic parameters and MTX-R in order to find sonographic predictor. It was a prospective research recruited 120 LR-GTN patients (FIGO score 0-6) treated with MTX between September 2012 and Match 2017 in our hospital. Before therapy, patients underwent a Doppler ultrasound to detect the presence of myometrial invasion. In the myometrial invasion cases, uterine size, tumour size and hemodynamic parameters (PS, ED, TAmax, TAmean, S/D, PI and RI) in both intratumour and uterine artery were assessed. Otherwise, only uterine artery hemodynamic parameters were measured. The relationships between sonographic parameters and MTX-R were analysed. The cases with myometrial invasion (96 cases) showed statistically higher PS, ED, TAmax, TAmean and lower S/D, PI and RI of uterine artery comparing with those indices in the cases without myometrial invasion (24 cases). Moreover, Univariable logistic regression analysis identified uterine artery hemodynamics were the significant predictors for MTX-R in the cases with myometrial invasion (p<0.05). Among them, TAmean was an independent factor indicated by multivariable logistic regression analysis with 0.806 AUC. It had 73.5% sensitivity and 74.2% specificity at the cut-off value of 25.9cm/s. However, those indices were no predictive power in the case without myometrial invasion. TAmean in uterine artery obtained prior to chemotherapy could be used as an independent factor for predicting MTX-R in LR-GTN with myometrial invasion. Conversely, ultrasound hemodynamics could be not useful to GTN without myometrial invasion.

10.1002/uog.17882

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The performance of human papillomavirus DNA detection with type 16/18 genotyping by hybrid capture in primary test of cervical cancer screening: a cross-sectional study in 10,669 Chinese women

Clinical Microbiology and Infection (2018)

Xinghong Zhao Qi Wu X. Wang Yunfeng Fu X. Zhang

We aimed to assess the performance of DH3 human papillomavirus (HPV) assay, a newly developed hybrid capture technique that detects 14 high-risk HPVs with type 16/18 genotyping, as a primary test in cervical cancer screening.In total 11,356 Chinese women aged 21-65 years participated in a cervical cancer screening programme using cytology (Thinprep, Hologic) and HPV testing (Cobas 4800 Test, Roche). Residual samples were used to detect HPV by DH3 HPV.In total 10,669 women with valid results were included in the study. Of those, 135 were diagnosed as CIN2+, and 83 were diagnosed as CIN3+; 1056 women (9.9%) were DH3 HPV-positive and 255 (2.4%) of those were 16/18-positive, while 990 (9.3%) women were Cobas HPV-positive and 243 (2.3%) of those were 16/18-positive. DH3 HPV was non-inferior to Cobas HPV in identifying CIN1- and CIN2+ using predetermined thresholds (both p < 0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of DH3 HPV were 93.3% (95% confidence interval [CI] = 87.7-96.9), 91.2% (95%CI = 90.6-91.7), 12.0% (95%CI = 10.1-14.1) and 99.9% (95%CI = 99.8-100), respectively, similar to those of Cobas HPV (91.1%, 95%CI = 85.0-5.3; 91.8%, 95%CI = 91.2-92.3; 12.5%, 95%CI = 10.5-14.7; and 99.9%, 95%CI = 99.8-99.9, respectively), in identifying CIN2+ (all p > 0.05). When DH3 HPV and Cobas HPV were respectively used as primary testing in screening strategy, the performance of two strategies were similar in identifying CIN2+. The results were similar in identifying CIN3+.Our data suggest that DH3 HPV performs similarly to Cobas HPV in identifying high-grade CIN in cervical cancer screening.

Hybrid capture

10.1016/j.cmi.2018.02.027

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[Evaluation of P16(INK4α) expression in Thinprep cervical specimens for the predication of high-grade cervical intraepithelial neoplasia].

Yuanying Ma Feng Ye Xiaoduan Chen Liqian Qiu Weiguo Lü

Objective To explore the value of P16 in the predication of high-grade cervical intraepithelial (HGCIN) by P16 expression in cervical specimens. Methods One hundred ninety-two residual ThinPrep samples were collected and detected by HPV DNA test and P16 detected by immunocytochemistry. All women underwent colposcopy and histological examination of biopsy specimen if needed. P16 test, cytology and HR-HPV DNA (HC2) test were compared based on histological examination of colposcopic biopsies. Results (1)The expression of P16 showed 16.3% in normal or inflammatory cases, 46. 7% in CIN 1,93. 8% in CIN 2, 91.1% in CIN 3 and 100. 0% in carcinoma. A positive relation between P16 and the grade of cervical lesions was observed by Spearman analysis ( P ＜ 0. 05, r = 0. 900).(2)By P16 test, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for ≥CIN 2 were 94. 1%, 78.5% , 77.7%, 94.4% and 85.4% respectively. By HR-HPV DNA test, the sensitivity, specificity, PPV, NPV and accuracy for ≥ CIN 2 were 95.3%,56. 1%, 63. 3%, 93. 8% and 73.4% respectively. By cytological test, the sensitivity, specificity, PPV,NPV and accuracy for ≥ CIN 2 were 82.4%, 92. 5%, 89. 7%, 86. 8% and 88.0% respectively. There were significant difference of specificity, PPV and accuracy between P16 and HR-HPV DNA ( P ＜ 0. 05 ).And no significant difference of accuracy was found between P16 and cytology( P ＞ 0. 05). Conclusion The specificity, PPV and accuracy of P16 are significantly higher than those of HR-HPV DNA. Thus P16 test is valuable to diagnose HGCIN in ThinPrep specimens. Key words: P16 ; Human papillomavirus ; Cervix neoplasm ; CIN ;

10.3760/cma.j.issn.0376-2491.2010.43.005

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The effect of prophylactic chemotherapy on treatment outcome of postmolar gestational trophoblastic neoplasia

BMC Women s Health (2023)

Yuanyuan Liu Yaqiong Ye Xiaodong Cheng Weiguo Lü Xing Xie

Abstract Objective To evaluate whether prophylactic chemotherapy (P-chem) increased the drug resistance rate of postmolar GTN and whether the first-line chemotherapy should be different from P-chem. Methods Postmolar GTN received P-Chem was defined as P-Chem group. Postmolar GTN without P-chem was randomly selected as control group according to the ratio of 1:3 (P-chem:control) and matched by age for low risk and high risk GTN separately. Results Totally 455 low-risk and 32 high-risk postmolar GTN patients were included. WHO risk score, chemotherapy cycles to achieve hCG normalization and resistant rate were similar between P-chem (27 cases) and control (81 cases) group. Among low-risk GTN patients, interval from hydatidiform mole to GTN was significantly longer in P-chem group than control (44 vs 69 days, P = 0.001). Total chemotherapy cycles and resistant rate were similar between low-risk GTN treated with same agent as P-chem (group A) and alternative agent (group B). But group A needed more chemotherapy cycles to achieve hCG normalization than group B. Conclusions P-chem delayed the time to GTN diagnosis, but didn’t increase risk score or lead to drug resistance of postmolar GTN. Alternative agent different from P-chem had the potential of enhancing chemotherapy response in low- risk postmolar GTN.

Gestational trophoblastic neoplasia

10.1186/s12905-022-02134-w

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SURF4 maintains stem-like properties via BIRC3 in ovarian cancer cells

Journal of Gynecologic Oncology (2020)

Yongfang Yue Lili Xia Shanshan Xu Conghui Wang Xinyu Wang

Objective: As cancer stem cells (CSCs) are considered as the origin of tumor development, recurrence, and drug resistance, we aimed to explore the mechanism related to modulating stemness in CSCs, thus facilitating to search for new therapeutic strategy for ovarian cancer.Methods: In this study, ovarian cancer stem cells (OCSCs) induced from cell line 3AO and A2780 were enriched in serum-free medium (SFM).The effect of SURF4 on CSC-like properties was evaluated by sphere-forming assays, re-differentiation assays, quantitative real-time polymerase chain reaction, flow cytometry, Western blotting, cell viability assays and in vivo xenograft experiments.The downstream molecule participating in SURF4 maintaining stemness was screened by RNA-sequencing and identified by the experiments of gene function.Results: SURF4 was upregulated expressed in OCSCs.Knockdown of SURF4 reduced the expression of the related stem markers (SOX2 and c-MYC), inhibited self-renewal ability, and improved the sensitivity to chemotherapeutic drugs (paclitaxel and cisplatin) in OCSCs.SURF4 knockdown also inhibited tumorigenesis in nonobese diabetic/severe combined immunodeficiency mice.BIRC3 expression was controlled by SURF4, and BIRC3 showed the similar effect as SURF4 did, and BIRC3 overexpression partially recovered stem-like properties abolished by SURF4 knockdown.Conclusion: Our findings suggest that SURF4 possesses the ability to maintain stemness of OCSCs via BIRC3, and may serve as a potential target in stem cell-targeted therapy for ovarian cancer.

Stem cell marker

10.3802/jgo.2020.31.e46

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Appreciation of the Combined Detection of Sero-enzyme and Total Bile Acids (TBA) in Infect of the Hepatitis B virus

Journal of Practical Medical Techniques (2008)

Weiguo Lü

Objective To discuss the combined detection of total bile acids (TBA) and sero-enzyme in infect of the Hep-atitis B virus.Methods grouping according to type of the disease and integrated mode of HBV,appreciation of TBA、ALT、 AST、GGT、TB、TP、ALB and PA use chisquare test.Results TBA is more sensitivity in hepatic cirrhosis and hepatoma as ALT, AST.Conclusion The detection of sero-enzyme, total bile acids and combined detection is important to diagnosis of hepar and gall disease, antidiastole and prognosis.

Liver enzyme

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Human papillomavirus 16E6/E7 activates autophagy via Atg9B and LAMP1 in cervical cancer cells

Cancer Medicine (2019)

Tingting Chen Shizhou Yang Songfa Zhang Junfen Xu Weiguo Lü

Although the role of high-risk human papillomavirus (HPV) E6 and E7 in cellular malignant transformation has been elucidated， the function of both genes in cellular homeostasis is still unknown. Autophagy functions in maintenance of cellular homeostasis play a key role in the initiation and development of cancer and infectious disease.Cervical cancer cell lines SiHa and CaSki were utilized in this study.We found that HPV 16E6/E7 (16E6/E7) downregulation inhibited autophagy, and consequently suppressed cell proliferation and promoted early apoptosis. Transcriptome sequencing demonstrated that Atg9B and LAMP1 were downregulated in 16E6/E7 knockdown cells. Gene function experiments revealed that 16E6/E7 downregulation depressed Atg9B and LAMP1, and Atg9B and LAMP1 overexpression compensated, at least partially, autophagy blockage induced by 16E6/E7 knockdown. Immunoprecipitation assay showed that 16E7 interacted with Atg9B and dual-luciferase reporter system revealed that 16E6 most likely regulated -1750 to -2000 nt in Atg9B and -1800 to -2000 nt in LAMP1 promoter region.Our findings verified that 16E6/E7 activated autophagy via accelerating autophagosome formation and degradation, and Atg9B and LAMP1 were involved in the process of 16E6/E7 modulating autophagy, suggesting that targeting autophagy may be a potential approach in cervical cancer therapeutics.

LAMP1

10.1002/cam4.2351

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Toxic effects of Tong Bi Composition on testicle tissue in rats.

Zhonghua zhongyiyao xuekan (2010)

Hui Chen Jifan Chen Huang Sheng-guang Guangxing Chen Qingping Liu

Objective:To study the toxic effects of Tong Bi Composition on reproduct ive organs in male rats.Methods:27 male SD rats were randomly divided into 3 groups,9 in each group.The control group were given by normal saline at a dose of 10mL.kg-1.d-1,while the Composition-one group were given Tong Bi Composition at a dose of 30g.kg-1.d-1,the Com-position-two group at a dose of 10g.kg-1.d-1.After 60 days,the rats were sacrificed.The weight,relative testis weight,sperm density as well as the total activity were comparatively analyzed.The pathological changes in testicular and epididymides tissue were observed by optical microscope.Results:Compared with the control group,a significant decrease in relative testis weight and sperm density were seen in the Composition-one group(P 0.01),but not in the Composition-two group(P 0.05).In two experiment groups the motility of sperm from caudal epididymides dropped to zero,and diastrophic sperms were seen,especially many in the Composition-one group.The testicular lesion in rats caused by Tong Bi Composition Was observed in Composition-one group much more seriously than that in Composition-two group.Conclusion:In male rats,Tong Bi Compo-sition has obvious anti-reproductive effects,which are dose-dependent.

Testicle

Adult male

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Effects of health promotion combined with psychological guidance on prevention and therapy of hypertension in communities

Weiguo Lü

Objective To investigate the effects of health promotion combined with psychological guidance on preven tion and therapy of hypertension in community population.Methods 200 hypertension patients from 6 Community Health Service Centers in Lunjiao Town of Shunde District in Foshan City were included for follow-up of 2 years(2011-2012 year).Before and 2 years after health promotion combined with psychological guidance intervention,changes in blood pressure,rates of awareness about hypertension and life style changes were analyzed.Results After the comprehensive intervention of health promotion combined with psychological guidance for 2 years,average blood pressures of the patients decreased markedly,the systolic blood pressures decreased from(153.50 ±18.00) mm Hg to(130.95±13.56) mm Hg,and the diastolic blood pressures decreased from(83.46 ±11.05) mm Hg to(69.21±9.30) mm Hg respectively,the differences were statistically significant(P 0.05).After intervention the awareness rates of hypertension knowledge were higher,and hypertension-related behaviors improved than before intervention(P 0.05).The score of Hamilton depression scale decreased from(12.37±1.22) points before intervention to(5.46±0.91) points after intervention,with the scores of cardiovascular symptoms,respiratory symptoms,gastrointestinal symptoms,autonom ic nerve symptoms and sensing system symptoms decreased more significantly(P 0.05).Conclusion Psychological guidance using group counseling,in addition to health promotion,are significantly effective in the prevention and ther apy of hypertension in communities.

Depression

Community Health

Promotion (chess)

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Risk stratification for cervical precancer and cancer by DH3‐HPV partial genotyping and cytology in women attending cervical screening: A retrospective cohort study

Journal of Medical Virology (2023)

Yunfeng Fu Ying Li Xiao Li Xinyu Wang Weiguo Lü

To evaluate the effect of DH3-human papillomavirus (HPV) partial genotyping for risk stratification in cervical cancer screening, we conducted a post hoc analysis within a retrospective cohort of 7263 Chinese women aged 21-71 years who participated in population-based screening. The residual cytological samples at baseline were retested with DH3-HPV and Hybrid Capture 2 (HC2) assay after 3-year follow-up. Risk values with 95% confidence intervals (CIs) of cervical intraepithelial neoplasia (CIN) grade 3/2 or worse (CIN3+/CIN2+) were estimated based on HPV and cytology results. The report complies with the STROBE statement. Across every cytological result, risk estimates obtained from DH3-HPV and HC2 were similar or almost identical. By DH3-HPV partial genotyping, risks of CIN3+/CIN2+ were invariably higher for HPV16/18 than other high-risk HPV (hrHPV). Among women with normal cytology, immediate CIN3+ risks were 8.16% (95% CI = 4.19%-15.28%) for HPV16/18 positive and 0.48% (95% CI = 0.13%-1.73%) for other hrHPV positive. Among women with any abnormal cytology, immediate CIN3+ risks were 33.33% (95% CI = 22.24%-46.64%) for HPV16/18, and 13.33% (95% CI = 8.37%-20.56%) for other hrHPV. Among 5840 women completed 3-year follow-up, the cumulative CIN3+ risk was 25.56% (95% CI = 18.91%-33.59%) for HPV16/18 and 8.22% (95% CI = 6.02%-11.13%) for other hrHPV. Women with an HPV-negative result with DH3-HPV or HC2 test had very low cumulative 3-year CIN3+ risk (0.06%, 95% CI = 0.02%-0.17%), which was about one-tenth of women with normal cytology at baseline (0.62%, 95% CI = 0.45%-0.86%). Similar patterns were observed for the endpoint of CIN2+. These findings suggest that partial genotyping of DH3-HPV performs well in risk stratification, which can better balance the benefits and harms of cervical cancer screening.

Cervical screening

Papillomaviridae

10.1002/jmv.28482

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