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.

Objective:To develop and verify a nomogram to predict disease-free survival(DFS)and overall survival(OS)for patients undergoing cervical cancer surgery,which may provide reference for evaluating the prognosis of cervical cancer patients undergoing surgery.Methods:The clinical,pathological and follow-up data of patients who underwent radical operation for cervical cancer in Xijing Hospital,Air Force Medical University from March 2013 to October 2018 were analyzed retrospectively.Based on Cox regression analysis,Bayesian Informa-tion Criterion(BIC)backward stepwise selection method and R square screening variables,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were used to compare the predictive efficiency of the model,and a nomogram with better predictive efficiency was selected.The consistency index(C-index)and the receiver operating characteristic curve(ROC)were used to test the efficiency of the nomogram.Results:A total of 950 patients with cervical cancer were enrolled in this study.The risk factors for constructing the DFS nomogram were FIGO stage(2018),parametrium invasion,invasion depth,and maximum tumor diameter.The C-index for DFS in the training cohort and the verification cohort were 0.754 and 0.720,respectively.The area under ROC of the training cohort for 1-,3-and 5-years was 0.74(95%CI 0.65-0.82),0.77(95%CI 0.71-0.83)and 0.79(95%CI0.74-0.85),and the areas under ROC of verification cohort 1-,3-and 5-years were 0.72(95%CI 0.58-0.87),0.75(95%CI 0.64-0.86)and 0.72(95%CI 0.61-0.84),respectively.The risk factors for con-structing the OS nomogram were FIGO stage(2018),histological type,LVSI,parametrium invasion,surgical mar-gin,and invasion depth.The C-index for OS in the training cohort and the verification cohort were 0.737 and 0.759,respectively.The area under ROC of the 3-and 5-year training cohort were 0.76(95%CI 0.69-0.83)and 0.78(95%CI 0.72-0.84),and the areas under ROC of verification cohort 3-and 5-years were 0.76(95%CI 0.65-0.87)and 0.79(95%CI 0.69-0.88),respectively.Conclusions:This study is based on real-world big data to construct nomogram of DFS for 1,3,and 5 years and OS for 3,and 5 years for cervical cancer,which have ideal predictive effects and help clinical physicians correctly evaluate the prognosis of cervical cancer surgery patients.It provides strong reference basis for diagnosis,treatment,and prognosis evaluation.

Objective: This study aimed to identify the risk factors for genitourinary fistulas and delayed fistula recognition after radical hysterectomy for cervical cancer. Methods: This study was a retrospective analysis of data collected in the Major Surgical complications of Cervical Cancer in China (MSCCCC) database from 2004–2016. Data on sociodemographic characteristics, clinical characteristics, and hospital characteristics were extracted. Differences in the odds of genitourinary fistula development were investigated with multivariate logistic regression analyses, and differences in the time to recognition of genitourinary fistula were assessed by Kruskal–Wallis test. Results: In this study, 23,404 patients met the inclusion criteria. Surgery in a cancer center, a women’s and children’s hospital, a facility in a first-tier city, or southwest region, stage IIA, type C1 hysterectomy, laparoscopic surgery and ureteral injury were associated with a higher risk of ureterovaginal fistula (UVF) (p<0.050). Surgery in southwest region, bladder injury and laparoscopic surgery were associated with greater odds of vesicovaginal fistula (VVF) (p<0.050). Surgery at cancer centers and high-volume hospitals was associated with an increase in the median time to UVF recognition (p=0.016; p=0.005). International Federation of Gynecology and Obstetrics (FIGO) stage IIA1-IIB was associated with delayed recognition of VVF (p=0.040). Conclusion Intraoperative urinary tract injury and surgical approach were associated with differences in the development of UVFs and VVFs. Patients who underwent surgery in cancer centers and high-volume hospitals were more likely to experience delayed recognition of UVF. Patients with FIGO stage IIA1-IIB disease were more likely to experience delayed recognition of VVF.

Objective:To summarize our institutional experiences of screening and selecting potential recipients and living donors for uterine transplantation at a single center.Methods:A total of 102 patients were diagnosed as absolute uterine factor infertility (AUFI). Depending upon the outcomes of previous trials, 8 modules were selected for surveying. A registration form was distributed for subjects at outpatient clinics or through telephone consultations for clinical trials of uterus transplantation between November 2018 and October 2019. The relevant information was collected and entered into a dedicated system for data processing.Results:The number of eligible subjects was 84 and the number of recipients with potential donors 37. The average age of potential recipients was 26.0(18-47) years. Among potential recipients, 76(90.5%) had congenital AUFI and 8(9.5%) acquired AUFI. For potential donors with available organs, the average age was 47.5(32-64) years and the proportion of menopausal or peri-menopausal status 56.8%.Conclusions:Currently large demands and sufficient supports for conducting clinical trials of uterine transplantation are available in China. However, inherent deficiencies persist in organ donor population reserves and preoperative screening protocols, such as donor age and subjective/objective factors of participants. During clinical trials of uterine transplantation, preoperative screening should be performed for expanding the screening scope, extending the screening time and popularizing the screening knowledge to boost the success rate.

Objective:To analyze the epidemiological, clinical characteristics and treatment of coronavirus disease 2019 (COVID-19) in Northeastern Sichuan, and summarize experience in time to provide reference for clinical diagnosis and treatment.Methods:A retrospective study was conducted. Fifty-nine patients with COVID-19 admitted to Bazhong Central Hospital and Dazhou Central Hospital from January 27th to February 9th, 2020 were selected as the subjects. The data of demography, epidemiology, laboratory examination, chest CT and related clinical treatment were collected. According to the severity of the disease, the patients were divided into three types: mild, general and severe types, and the differences of the above indices among different clinical types were compared.Results:① General information and epidemiology: 31 cases (52.5%) were male, 28 cases (47.5%) were female, the average age was (42.0±16.4) years old, and the patients over 40 years old accounted for the largest proportion (35 cases, 59.3%). The proportion of clinical type was 72.9% (43 cases) in general type, and 62.7% (37 cases) were imported type. With the increase of disease severity, the average age of patients also showed a significant increase trend [the age of the mild, general and severe patients were (30.9±13.6), (42.7±15.3), (55.8±18.9) years old, P < 0.01]. The proportion of patients with more than one basic disease in severe patients was significantly higher than those in mild and general patients [66.7% (4/6) vs. 20.0% (2/10), 9.3% (4/43), both P < 0.05]. In the distribution of clinical symptoms, the proportion of severe patients with chest distress/dyspnea was significantly higher than those in mild and general patients [66.7% (4/6) vs. 10.0% (1/10), 11.6% (5/43), both P < 0.05]. ② Laboratory examination index: the total number of white blood cell count (WBC), neutrophils count (NEU), C-reactive protein (CRP) in severe patients were higher than those in mild patients and general patients [WBC (×10 9/L): 7.21±4.35 vs. 5.85±1.69, 5.43±2.04; NEU (×10 9/L): 6.09±4.43 vs. 3.95±1.45, 3.54±1.83; CRP (mg/L): 16.00 (8.20, 46.43) vs. 5.00 (0.00, 16.13), 15.00 (3.13, 28.58)], the albumin (Alb) level in severe patients was lower than those in mild and general patients (g/L: 38.00±5.35 vs. 49.23±5.27, 39.81±2.15, both P < 0.05), while the hemoglobin (Hb) level in mild patients was higher than that in severe and general patients (g/L:155.2±12.1 vs. 141.3±6.8, 131.1±11.7, both P < 0.05). ③ Chest imaging: the CT manifestations of typical cases were single or multiple ground glass shadows. With the progress of the disease, the focus gradually increased, the scope gradually expanded, and multiple solid shadows of lung lobes were involved. ④ Treatment: all patients received at least 2 kinds of antiviral therapy, and the application rate of Interferon and Ribavirin in severe patients were higher than those in mild and general patients [100.0% (6/6) vs. 80.0% (8/10), 97.7% (42/43); 83.3% (5/6) vs. 0% (0/10), 20.9% (9/43); all P < 0.05]. ⑤ Prognosis: until March 6th 2020, 50 patients (84.8%) were discharged from the hospital after rehabilitation, and the remaining 9 patients were still under treatment, none deaths. Conclusions:The proportion of severe patients with chest distress/dyspnea is higher, the older the patients are and the more basic diseases are, the more likely they are to develop into severe type. High resolution chest CT could be considered for suspected cases or even fever patients, which may show the progress of the disease.

Objective:To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI +）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods:Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results:(1) A total of 4 891 patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.367, 95% CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS ( HR=1.420, 95% CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS ( P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups ( P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.705, 95% CI: 1.088-2.674, P=0.020). Conclusions:For patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

Objective: To explore the therapeutic feasibility of uterus transplantation for uterine infertility. Methods: Retrospective analysis was performed for the diagnosis, treatment and pregnancy course of the first domestic case of uterus transplantation and the relevant literature reviewed. The recipient was a 22-year-old woman with a congenital absence of uterus and vagina. Previously she underwent vaginal reconstruction and the donor was her mother. The specific procedures included donor/recipient screening, ethical argumentation, assisted reproductive technology of obtaining frozen embryos, Vinci robot-assisted uterine procurement, orthotopic replacement & fixation of retrieved uterus, revascularization; immunoregulation & monitoring of transplanted uterine recipient, assisted reproductive technology after transplantation and gestational management. Results: The durations of donor and recipient surgeries were 360 and 530 min respectively. No complications of recipient or donor occurred during the perioperative period. First menstruation occurred at 40 days post-transplantation and regularly thereafter. Pregnancy occurred after embryo transfer at 31 months post-transplantation. No rejection episodes occurred after transplantation or during gestation. Caesarean delivery occurred near gestational week 34. The boy weighed 2000 grams at birth and the mother remained well. Conclusions In conjunctions with literature review, uterine infertility may be treated by modified uterus transplantation. And a new path is paved for healthy pregnancy of women with uterine infertility.

Objective To investigate the changes of peripheral blood tacrolimus concentration and lymphocyte subsets in the uterus transplant recipient,and provide the evidence for monitoring the immune status after uterus transplantation.Methods The peripheral blood tacrolimus concentrations of the uterus transplant recipient during 1 year after transplantation were measured with the microparticle enzyme immunoassay (MEIA).Meanwhile,the whole blood cell counts and lymphocyte subsets were determined by the blood analyzer and flow cytometer,respectively.Results The blood tacrolimus concentrations of the uterus transplant recipient in the first month and second month after transplantation were (13.51 ± 3.92) ng/mL and (15.58 ± 1.19) ng/mL,respectively.The lymphocyte absolute counts were normal before transplantation.At the fifth day after transplantation,the counts of CD3 + T lymphocytes,CD4 + T lymphocytes,CD8 + T lymphocytes and NK cells and the ratio of CD4/CD8 were significantly decreased.One week after transplantation,the counts of CD4 + T lymphocytes were recovered to the normal range and maintained,but its recovery was slower than that of CD8 + T lymphocytes.The ratio of CD4/CD8 ranged from 0.4 to 0.8 during 10 days after transplantation,and increased and maintained between 0.8 and 1.1 after that.The counts of NK cells increased gradually from the 10th day after transplantation,but still did not recover to the level before transplantation even at the 20th day after transplantation.However,the counts and percentages of B lymphocytes did not decrease but increased at the fifth day after transplantation,and recovered to normal gradually from the 10th day after transplantation.There was no significant correlation between the CD3 + T lymphocyte count and blood tacrolimus concentration.Conclusion The dynamic changes of blood lymphocyte subsets and tacrolimus concentration exist in the uterus transplant recipient,which need to be further verified by a large amount of clinical data.

Objective To analysis the clinical high risk factors for fetal chromosomal abnormalities.Methods Amniocentesis,chromosomal karyotype analysis and other related methods were performed on 4829 pregnant women,who presented sole indication of prenatal diagnosis such as advanced age,high risk factors and fetal ultrasound abnormalities,for analyzing the correlations of those women to the incidence of fetal chromosomal abnormalities.Results The detection rates of abnormal karyotype were 5.0％ (57/1143),1.7％ (40/2367) and 4.3％ (57/1319) in the older women group (age＞35),abnormal maternal serological screening group and abnormal fetal ultrasound finding group,respectively.The detection rats of karyotype abnormality were 6.9％ (23/333) in women with fetal congenital heart diseases,8.5％ (20/234) in those with abnormal amniotic fluid,1.1％ (1/89) in those with fetal ventriculomegaly,1.1％ (10/898) in those with fetal intracardiac hyperechogenicity,5.9％ (2/34) in those with fetal choroid cyst and 5.6％ (1/18) in those with fetal renal pelvis broadening.Conclusion The pregnant women with age＞35,fetal sonographic structural anomalies or two or more soft marker abnormalities should be prenatally diagnosed and doing the genetic counseling combined with the family history.

OBJECTIVETo optimize the methods for genetic detection and prenatal diagnosis of Duchenne muscular dystrophy (DMD).

METHODSDenaturing high-performance liquid chromatography (DHPLC), multiplex PCR (mPCR), sequencing and other molecular techniques were used in combination for molecular diagnosis of 8 cases diagnosed as DMD.

RESULTSAmong the 8 cases, 4 have carried large deletions, 3 have point mutations, among which 6 were of de novo type. Prenatal diagnosis were offered for 5 families, the results showed that none of the fetuses had carried large deletions or point mutations. The pregnancies had continued and healthy babies were born.

CONCLUSIONCombined use of short tandem repeat, DHPLC, mPCR and sequencing can improve the detection of DMD gene mutations. By establishing and optimizing genetic and prenatal diagnostic methods, accurate genetic counseling can be provided for families affected with DMD.

Adult ; Base Sequence ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genetic Testing ; Humans ; Molecular Sequence Data ; Muscular Dystrophy, Duchenne ; diagnosis ; embryology ; genetics ; Pedigree ; Point Mutation ; Pregnancy ; Prenatal Diagnosis ; Sequence Deletion ; Young Adult