1.E3 ubiquitin ligase FBXW11-mediated downregulation of S100A11 promotes sensitivity to PARP inhibitor in ovarian cancer
Ligang CHEN ; Mingyi WANG ; Yunge GAO ; Yanhong LV ; Lianghao ZHAI ; Jian DONG ; Yan CHEN ; Xia LI ; Xin GUO ; Biliang CHEN ; Yi RU ; Xiaohui LV
Journal of Pharmaceutical Analysis 2025;15(7):1652-1666
Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.
2.E3 ubiquitin ligase FBXW11-mediated downregulation of S100A11 promotes sensitivity to PARP inhibitor in ovarian cancer.
Ligang CHEN ; Mingyi WANG ; Yunge GAO ; Yanhong LV ; Lianghao ZHAI ; Jian DONG ; Yan CHEN ; Xia LI ; Xin GUO ; Biliang CHEN ; Yi RU ; Xiaohui LV
Journal of Pharmaceutical Analysis 2025;15(7):101246-101246
Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.
3.Clinical diagnostic value of NT-proBNP in peridialysis chronic kidney disease patients
Fayan YANG ; Yanhong GUO ; Lu YU ; Liuwei WANG ; Zihan ZHAI ; Lin TANG
Chinese Journal of Nephrology 2023;39(7):506-514
Objective:To explore the clinical value of N terminal pro B type natriuretic peptide (NT-proBNP) in diagnosing or predicting heart failure in peridialysis chronic kidney disease (CKD) population.Methods:It was a single-center retrospective study. Patients with peridialysis CKD who visited the Department of Nephrology, First Affiliated Hospital of Zhengzhou University from January 2021 to June 2021 were collected and divided into 4 groups according to the presence or absence of heart failure and the level of left ventricular ejection fraction (LVEF), namely the non-heart failure group, heart failure with reduced ejection fraction (HFrEF) group (LVEF<40%), heart failure with mid-range ejection fraction (HFmrEF) group (40%≤LVEF<50%), and heart failure with preserved ejection fraction (HFpEF) group (LVEF≥50%). The NT-proBNP, echocardiography and other indicators of the 4 groups were compared. The value of plasma NT-proBNP in diagnosing heart failure, HFpEF, HFmrEF and HFrEF was analyzed by drawing receiver operating characteristic curve (ROC curve). Logistic regression analysis was used to analyze the related factors of heart failure in peridialysis CKD patients.Results:A total of 508 patients were included, including 11 cases in the HFrEF group, 29 cases in the HFmrEF group, 152 cases in the HFpEF group, and 316 cases without heart failure. The differences in age, 24-h urine volume, hemodialysis proportion, non-dialysis proportion, serum creatinine, estimated glomerular filtration rate, hemoglobin, serum albumin, C-reactive protein, NT-proBNP, cardiac troponin I, left ventricular internal diameter, LVEF, pulmonary artery systolic pressure, left ventricular end-diastolic volume, E/A value, septal thickness, and left ventricular posterior wall thickness among the four groups were statistically significant ( P < 0.05, respectively). A two-pair comparison (all P values corrected by Bonferroni method) revealed that the 24-h urine volume was higher in the non-heart failure group than in the other three groups (corrected P<0.05, respectively), while the proportion of hemodialysis patients and the levels of NT-proBNP and C-reactive protein were lower in the non-heart failure group than in the other three groups (corrected P<0.001, respectively); the levels of hemoglobin and serum albumin were lower in the HFpEF group than in the non-heart failure group (corrected P<0.001, respectively); troponin I was lower in the non-heart failure group than in the HFpEF group (corrected P<0.001), HFmrEF group (corrected P=0.001) and HFrEF group (corrected P<0.001), and troponin I was lower in the HFpEF group than in the HFrEF group (corrected P=0.008); LVEF was higher in the non-heart failure group than in the other three groups (corrected P<0.001, respectively), and LVEF in the HFpEF group was higher than in the HFmrEF and HFrEF groups (corrected P<0.001, respectively). For patients with peridialysis CKD, the cut-off values of plasma NT-proBNP for diagnosing or predicting heart failure, HFpEF, HFmrEF and HFrEF were 4 943.33 ng/L, 4 976.83 ng/L, 14 964.5 ng/L and 17 847.55 ng/L, respectively. Multivariate logistic regression analysis showed that NT-proBNP (every 500 ng/L increase, OR=1.390, 95% CI 1.287-1.501, P<0.001), LVEF ( OR=0.747, 95% CI 0.656-0.851, P<0.001) and 24-h urine volume (every 100 ml increase, OR=0.842, 95% CI 0.763-0.929, P=0.001) were independently correlated with heart failure. Conclusions:The cut-off value of plasma NT-proBNP for diagnosing or predicting heart failure in peridialysis CKD patients is much higher than that in patients with normal renal function. NT-proBNP, LVEF and 24-h urine volume are independently associated with heart failure in peridialysis CKD patients.
4.Efficacy of noninvasive prenatal testing in fetal chromosome aneuploidy in cautious population
Na LI ; Duan JU ; Xiuyan WANG ; Chunya ZHAI ; Yingxia LONG ; Yanhong MA ; Qiuxia WANG ; Ying ZHANG ; Bibo YUAN ; Xiaozhou LI
Chinese Journal of Reproduction and Contraception 2023;43(7):697-702
Objective:To analyze the application value of noninvasive prenatal testing (NIPT) in screening fetal chromosome aneuploidy in cautious population.Methods:The data of 19 590 pregnant women who voluntarily received NIPT in the Department of Gynecology and Obstetrics, General Hospital of Tianjin Medical University from October 2016 to June 2020 were retrospectively analyzed. The patients were divided into groups according to age, type of pregnancy and number of fetuses. The screening efficiency of NIPT was compared among different groups. Meanwhile, the screening efficacy of second trimester serum screening (STSS), STSS combined with NIPT and direct NIPT screening was compared and analyzed.Results:The positive predictive values of NIPT for trisomy 21, trisomy 18 and trisomy 13 were 87.18%, 54.84% and 41.18%, respectively. In pregnant women with advanced age (≥35 years old), in vitro fertilization and embryo transfer (IVF-ET) and twin pregnancy, NIPT sensitivity was all 100%, specificity was 99.79%, 99.82% and 100%, positive predictive value was 85.25%, 50.00% and 100%, respectively. The positive predictive value of ≥35 years old patients was significantly higher than that of <35 years old patients (61.54%, P=0.003), and the other indicators were similar to those of the young (<35 years old), conceived naturally and singleton group (all P>0.05). Compared with STSS, combined screening and direct NIPT screening had higher positive predictive value (1.20%, 68.75%, 73.74%; all P<0.001) and lower false positive rate (27.83%, 0.19%, 0.17%; all P<0.001). Conclusion:NIPT has high sensitivity, specificity and positive predictive value for fetal chromosome aneuploidy screening in pregnant women with advanced age, STSS high risk, IVF-ET and twin pregnancy, which greatly relieves the pressure of prenatal diagnosis and reduces the birth rates of children with chromosome disease.
5.Efficacy of noninvasive prenatal testing in fetal chromosome aneuploidy in cautious population
Na LI ; Duan JU ; Xiuyan WANG ; Chunya ZHAI ; Yingxia LONG ; Yanhong MA ; Qiuxia WANG ; Ying ZHANG ; Bibo YUAN ; Xiaozhou LI
Chinese Journal of Reproduction and Contraception 2023;43(7):697-702
Objective:To analyze the application value of noninvasive prenatal testing (NIPT) in screening fetal chromosome aneuploidy in cautious population.Methods:The data of 19 590 pregnant women who voluntarily received NIPT in the Department of Gynecology and Obstetrics, General Hospital of Tianjin Medical University from October 2016 to June 2020 were retrospectively analyzed. The patients were divided into groups according to age, type of pregnancy and number of fetuses. The screening efficiency of NIPT was compared among different groups. Meanwhile, the screening efficacy of second trimester serum screening (STSS), STSS combined with NIPT and direct NIPT screening was compared and analyzed.Results:The positive predictive values of NIPT for trisomy 21, trisomy 18 and trisomy 13 were 87.18%, 54.84% and 41.18%, respectively. In pregnant women with advanced age (≥35 years old), in vitro fertilization and embryo transfer (IVF-ET) and twin pregnancy, NIPT sensitivity was all 100%, specificity was 99.79%, 99.82% and 100%, positive predictive value was 85.25%, 50.00% and 100%, respectively. The positive predictive value of ≥35 years old patients was significantly higher than that of <35 years old patients (61.54%, P=0.003), and the other indicators were similar to those of the young (<35 years old), conceived naturally and singleton group (all P>0.05). Compared with STSS, combined screening and direct NIPT screening had higher positive predictive value (1.20%, 68.75%, 73.74%; all P<0.001) and lower false positive rate (27.83%, 0.19%, 0.17%; all P<0.001). Conclusion:NIPT has high sensitivity, specificity and positive predictive value for fetal chromosome aneuploidy screening in pregnant women with advanced age, STSS high risk, IVF-ET and twin pregnancy, which greatly relieves the pressure of prenatal diagnosis and reduces the birth rates of children with chromosome disease.
6.Experience on prevention and control management of the pediatric emergency department during the pandemic of Omicron variant of novel coronavirus in Shanghai in 2022
Liming HE ; Yanhong ZHANG ; Yang CHEN ; Ye CHENG ; Xue YANG ; Jian MA ; Chuanqing WANG ; Jing HU ; Xiaobo ZHANG ; Xiaowen ZHAI ; Gongbao LIU ; Guoping LU
Chinese Pediatric Emergency Medicine 2022;29(10):773-778
Objective:To summarize the experience on accurate prevention and control of children′s emergency department during the epidemic of novel coronavirus Omicron variant.Methods:We retrospectively analyzed the strategies and management experience of emergency prevention and control of novel coronavirus infection in emergency department at Children′s Hospital of Fudan University from March to May 2022.Results:As a designated hospital for treating pediatric patients who contracted novel coronavirus in Shanghai, the emergency department in our hospital was confronted with the dual pressure of critical patients treatment and pandemic prevention and control.We carefully studied a series of laws and regulations, as well as the newest edition of Chinese clinical guidance for novel coronavirus pneumonia diagnosis and treatment, and combined with the characteristics of novel coronavirus infection in children, then formulated the independent emergency department, fever clinics and novel coronavirus clinics; Updated the emergency department pre-examination triage process, the precautions pratice of clinical stuffs and disfection strategy, and established the second emergency department.From the beginning of March to the end of May 2022, a total of about 12 000 patients were admitted to the emergency department in our hospital, including 704 patients in the resuscitation room, 652 patients in the observation room, and 164 patients in the emergency ward.There were six patients with novel coronavirus infection in the emergency department.Neither nosocomial infection nor occupational exposure occurred.Conclusion:After 3 months of practice, the results showed that it can fully guarantee the timely treatment of critically ill children and achieved zero cross-infection in the hospital, which has important reference significance for the treatment of children, epidemic prevention, control during the novel coronavirus epidemic.
8.Influence of home environment and social characteristics on breast feeding selection among hepatitis B virus carrying pregnant women
He CUI ; Juan ZHAI ; Jing WU ; Ke ZHAO ; Yanhong YANG ; Juan DING
Chinese Journal of Modern Nursing 2018;24(24):2875-2878
Objective To investigate the home environment and social characteristics among hepatitis B virus (HBV) carrying pregnant women and to analyze their influence on breast feeding selection. Methods From January 2016 to December 2016, we selected 77 HBV carrying delivery women with hospital delivery of the First Affiliated Hospital of Zhengzhou University by convenient chester sampling. All of them were divided into the group of breast feeding (n=31) and the group of non-breast feeding (n=46) according to whether to select breast feeding after delivery. Home environment and social characteristics of delivery women were assessed with the Family Environment Scale-Chinese Version (FES-CV) and we analyzed the influence factors of breast feeding. Results Among HBV carrying pregnant women, the scores of 10 aspects of FES-CV ranged from low to high including achievement orientation (3.16±1.14), active-recreational orientation (3.29±1.19), intellectual-cultural orientation (3.72±1.16), conflict (4.47±1.45), expressiveness (4.94±1.59), cohesion (5.11±1.49), independence (5.17±1.73), organization (5.47±1.76), control (5.92±2.05), ethics (6.70±2.18). The scores of cohesion, independence, achievement orientation, intellectual-cultural orientation and active-recreational orientation of group of breast feeding were higher than those of group of non-breast feeding (t=7.066, 6.193, 8.342, 7.302, 8.903; P<0.01); and the score of conflict was lower than that of group of non-breast feeding (t=-8.443, P<0.01). There were no statistical differences in scores of expressiveness, ethics, organization and control between two groups (t=-0.632, 0.528, 1.254, 1.951;P>0.05). Conclusions HBV carrying pregnant women still face with the high level of family and social pressure. HBV carrying pregnant women without breast feeding are with the low level of cohesion, independence, achievement orientation, intellectual-cultural orientation, active-recreational orientation and high conflict of home environment and social characteristics.
9.LC-MS/MS application in pain management
Zheng CAO ; Yanhong ZHAI ; He YANG
Chinese Journal of Laboratory Medicine 2017;40(10):829-834
Pain management is the monitoring of chronic pain patients under long-term treatment with controlled analgesic drugs via random or regular lab tests. Plenty of clinical data showed that pain management could not only improve the patient′s compliance to prescribed drugs and result in better outcome,but also greatly reduce the possibility of controlled analgesic drugs into the underground market illegally. Drugs that are usually internationally recommended in pain management include opiates, opioids, sedative drugs, stimulant, hallucinogens etc. Considering drug metabolism rates difference among individuals and ease of sampling,random urine is usually the first choice of specimen for drug testing in pain management. In terms of methodology,LC-MS/MS has become a"gold standard"approach due to its high sensitivity,high specificity and wide usability.
10.Comparison of two methods for testing anti-ABO IgG anibody titer in pregnant women
Shufa YANG ; Yangyuan LI ; Yanhong ZHAI ; Wenjuan WANG ; Juan ZHAO
International Journal of Laboratory Medicine 2014;(14):1916-1918
Objective To compare the 2 methods of the flow cytometry and the microcolumn gel agglutination assay for testing anti-ABO Ig G antibody.Methods The flow cytometry and the microcolumn gel agglutination assay were adopted to detect the an-ti-ABO IgG antibody in the O blood type pregnant women(experimental group)and the A/B blood type pregnant women (control group).The difference in the positive rates between the experimental and control groups and the correlation between these two methods were analysed.The different titers of samples were selected for detection on different days to compare their reproducibili-ty.Results 300 samples from the experimental goup and 300 samples from the control group were collected.The detection results of 2 methods showed that the positive rates of the experimental group was significantly higher than that of the control group with statistical difference(P <0.05).The correlation coefficients(rs )between these two methods were 0.694.The coefficient of variation in the flow cytometry was smaller than that in the microcolumn gel agglutination assay(P <0.05).Conclusion ABO blood type in-compatibility is more common in O type pregnant women.The flow cytometry and the microcolumn gel agglutination assay possess good correlation.The reproducibility of the flow cytometry is better than that of microcolumn gel agglutination assay.

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