Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective:To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi).Methods:Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate.Results:(1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.

Objective:To establish a niraparib-resistant ovarian cancer cell line and preliminarily explore its biological characteristics and metabolic signatures.Methods:(1) Using ovarian adenocarcinoma cell line A2780 as parental cells, the niraparib-resistant cell line A2780-NiraR was established by the method of concentration gradient increased induction, and its morphological characteristics were observed using inverted phase-contrast microscope. The half-inhibitory concentration (IC 50) of niraparib was determined by cytotoxicity assay. (2) Cell proliferation was determined by cell count kit-8 (CCK-8) assay and direct cell counting assay, cell cycle distribution was analyzed by flow cytometry. (3) The differential metabolites between A2780 and A2780-NiraR cells were detected by non-target metabolomics based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC/HRMS). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted on the above differential metabolites to explore related metabolic pathways. Results:(1) Compared with the parental A2780 cells, A2780-NiraR cells exhibited predominantly short-spindle or oval morphology with reduced cellular projections and indistinct cell borders. The IC 50 values of niraparib were 3.17 and 26.19 μmol/L against A2780 cells and A2780-NiraR cells, respectively ( F=98.50, P<0.001). (2) A2780-NiraR cells had a slower proliferation rate compared with A2780 cells ( F=146.80, P<0.001). The doubling time of A2780-NiraR cells [(37.5±1.9) hours] was significantly longer than that of A2780 cells [(14.5±1.0) hours; t=10.50, P<0.001]. Compared with the parental A2780 cells, A2780-NiraR cells had a significantly lower S phase fraction [(44.5±0.7)% in A2780 cells, (30.2±2.9)% in A2780-NiraR cells; t=4.78, P<0.001] and higher G 0/G 1 phase fraction [(35.4±1.2)% in A2780 cells, (52.2±3.1)% in A2780-NiraR cells; t=5.10, P<0.001]. (3) The metabolites of A2780 and A2780-NiraR cells were analyzed by non-target metabolomics. Forty-four differential metabolites between A2780 and A2780-NiraR cells were screened using the orthogonal partial least squares-discriminant analysis (OPLS-DA) model, the majority of which were significantly increased, such as pyrrolidone carboxylic acid, L-lysine and 1-pyrroline-4-hydroxy-2-carboxylate. Pathway enrichment analysis indicated that the arginine metabolism, purine metabolism, and pyrimidine metabolism were the most significantly enriched pathways. Conclusion:A2780-NiraR cells have acquired a stable niraparib resistance phenotype, and metabolic pathways including arginine metabolism may serve as potential therapeutic targets for enhancing niraparib efficacy in ovarian cancer.

Objective:To investigate the clinical efficacy of cervical cerclage in singleton pregnancy with different degrees of short cervix.Methods:The clinical data of singleton pregnant women who underwent transvaginal ultrasound examination at 18-24 +6 weeks of gestation and found cervical dilation with cervical length (CL) ≤20 mm, and without history of spontaneous preterm delivery or late abortion in Women′s Hospital, Zhejiang University School of Medicine from January 2021 to September 2023 were collected and retrospectively analyzed. According to the case control matching, 78 pregnant women in the cerclage group and 78 women in the conservative treatment group were finally included. The pregnancy outcomes and neonatal prognosis of the two groups were compared. Meanwhile, the two groups of pregnant women were divided into three subgroups for stratification (CL≤10, 11-15, 16-20 mm). Multivariate logistic regression analysis and Kaplan-Meier curve were used to evaluate the effect of cervical cerclage on pregnancy outcomes in different subgroups. Results:(1) Compared with the conservative treatment group, the gestational age at delivery (median: 36 vs 37 weeks) and the duration of pregnancy extension (median: 90 vs 97 days) in the cerclage group were not significantly prolonged (all P>0.05). There was no significant difference in the cumulative non-delivery rate between the cerclage group and the conservative treatment group ( P=0.143). The rate of neonatal intensive care unit (NICU) admission in the cerclage group was significantly higher than that in the conservative treatment group (46.1% vs 31.2%, P<0.001), but there were no significant differences in other neonatal outcomes between the two groups (all P>0.05). (2) CL 16-20 mm subgroup: compared with the conservative treatment group (28 cases), the cerclage group (18 cases) had a significantly higher rate of preterm birth before 37 weeks of gestation (3.6% vs 6/18, P<0.001) and a significantly lower neonatal birth weight (median: 3 370 vs 2 925 g, P<0.001). There was no significant difference in the cumulative non-delivery rate between the cerclage group and the conservative treatment group ( P=0.168). (3) CL 11-15 mm subgroup: compared with the conservative treatment group (26 cases), the gestational age of delivery in the cerclage group (32 cases) was later (median: 36 and 37 weeks, respectively), and the difference was statistically significant ( P<0.05). The cumulative non-delivery rate in the cerclage group was significantly higher than that in the conservative treatment group ( P=0.001). (4) CL≤10 mm subgroup: compared with the conservative treatment group (24 cases), the pregnant women in the cerclage group (28 cases) had a later gestational age at delivery (median: 34 vs 37 weeks), a longer duration of pregnancy (median: 74 vs 97 days), and a larger newborn birth weight (median: 2 300 vs 3 165 g). The rates of preterm birth before 34 weeks of gestation (45.8% vs 14.3%) and before 37 weeks of gestation (83.3% vs 39.3%) were lower, and the differences were all statistically significant (all P<0.05). The cumulative non-delivery rate of pregnant women in the cerclage group was significantly higher than that in the conservative treatment group ( P<0.001). Conclusion:Cervical cerclage could significantly prolong the gestational weeks and improve the perinatal outcomes for singleton pregnant women with cervical internal orifice dilation and CL≤15 mm without a history of spontaneous preterm delivery or late abortion.

Objective:To investigate whether elevated serum uric acid (UA) in early pregnancy was an independent risk factor for pre-eclampsia (PE) and its potential predictive value.Methods:This retrospective nested case-control study analyzed clinical data from pregnant women who delivered at Beijing Friendship Hospital, Capital Medical University, between January 2022 and March 2025. With the occurrence of PE as the outcome variable, the observation objects were divided into UA-elevated group and UA-normal group according to whether the UA level in the first trimester was higher than the 75th percentile ( P75) of the total population. After balancing confounders via propensity score matching (PSM), logistic regression, subgroup analysis and sensitivity analysis were performed to evaluate the association between UA and PE risk. Results:(1) In the initial cohort, the serum UA levels of PE women (327 cases) and non-PE women (8 919 cases) in the first trimester were (264.4±64.4) and (237.1±57.9) μmol/L, respectively, and the difference was statistically significant ( t=-4.74, P<0.001). The P75 of serum UA was 264.8 μmol/L, and based on this cut-off value, 7 169 cases (77.5%, 7 169/9 246) were in the UA-normal group and 2 077 cases (22.5%, 2 077/9 246) in the UA-elevated group. After PSM matching, the two groups were balanced in age, body mass index and other covariates. The incidence of PE in the UA-normal group and the UA-elevated group was 2.76% (198/7 169) and 6.21% (129/2 077); the incidence of severe PE was 1.21% (87/7 169) and 3.42% (71/2 077), respectively; the incidence of early-onset PE was 0.49% (35/7 169) and 1.44% (30/2 077), respectively; and the differences between the two groups were statistically significant (all P<0.001). (2) Logistic regression analysis showed that indirect bilirubin, low-density lipoprotein cholesterol, plateletcrit and UA (categorical and continuous variable forms) were independent risk factors for PE (all P<0.05), among which UA had the most significant risk effect with dose-effect trend. (3) For every 10 μmol/L increase in UA level, the risk of early-onset PE increased by 3% ( OR=1.03, 95% CI: 1.00-1.06; P=0.023), and the risk of severe PE increased by 5% ( OR=1.05, 95% CI: 1.01-1.09; P=0.012). (4) Multivariate logistic analysis showed that taking P70, P75 and P80 as cut-off values, the risk of PE increased by 40% ( OR=1.40, 95% CI: 1.02-2.13; P=0.047), 86% ( OR=1.86, 95% CI: 1.08-3.22; P=0.026), 87% ( OR=1.87, 95% CI: 1.21-2.91; P=0.005), respectively. Conclusion:Elevated UA level in the first trimester of pregnancy is an independent risk factor for PE, which can be used as one of the early screening indicators to assist in identifying high-risk groups of PE.

Objective:To investigate whether continued low-dose aspirin (LDA) intervention affects the incidence of pre-eclampsia (PE) and adverse pregnancy outcomes in pregnant women with high-risk PE screening in the first trimester and reassessed as low risk at 28 weeks of gestation.Methods:This study was a prospective observational cohort study. From April 2022 to April 2024, a total of 106 pregnant women who underwent prenatal examination in the Affiliated Jiangyin Hospital of Nantong University were enrolled. They were assessed as high risk of PE by multiple indicators combined screening at 11-13 +6 weeks of gestation, received LDA intervention, and were reassessed as low risk of PE at 28 weeks of gestation. The patients were divided into withdrawal group (49 cases) and continuation group (57 cases). The incidence of PE and adverse pregnancy outcomes were compared between the two groups. Results:(1) There were no statistically significant differences in general conditions and the incidence of pregnancy complications between the two groups (all P>0.05). During the PE risk screening at 11-13 +6 weeks of gestation, there were no statistically significant differences in mean arterial pressure (MAP) and ultrasound uterine artery pulsation index (UtPI) between the two groups (all P>0.05), but the placental growth factor (PlGF) level in the withdrawal group was significantly lower than that in the continuation group ( P=0.023). There was no significant difference in the proportion of pregnant women with high risk of PE before 32 weeks and 34 weeks of pregnancy between the two groups (all P>0.05). (2) There were 7 cases (14%, 7/49) of PE in the withdrawal group, including 1 case (2%, 1/49) of early-onset PE and 3 cases (6%, 3/49) of PE before 37 weeks of pregnancy. There were 11 cases (19%, 11/57) of PE in the continuation group, including 2 cases (4%, 2/57) of early-onset PE and 4 cases (7%, 4/57) of PE before 37 weeks of pregnancy. There were no significant differences in the incidence of PE (including early-onset PE and PE before 37 weeks of pregnancy), gestational hypertension, severe PE, chronic hypertension complicated with PE and chronic hypertension complicated with pregnancy between the two groups (all P>0.05). (3) There were no significant differences in cesarean section rate, preterm birth rate, placental abruption, postpartum hemorrhage, fetal growth restriction, fetal distress rate, neonatal birth weight, neonatal asphyxia, and 1-minute and 5-minute Apgar scores between the two groups (all P>0.05). No stillbirth occurred in the two groups. Conclusion:For pregnant women with high risk of PE screening in the first trimester and taking LDA intervention, there is no difference in the incidence of PE and adverse pregnancy outcomes whether to continue LDA or not after being reassessed as low risk at 28 weeks of gestation.

Objective:To investigate the effect of altitude on the risk of pre-eclampsia (PE).Methods:This cross-sectional study included 19 246 pregnant women who delivered in Gansu Provincial Hospital from January 2016 to December 2020. General clinical data, pregnancy outcomes and neonatal outcomes were collected. The diagnosis of PE was based on the disease diagnosis coding of medical record information system and the Chinese guidelines for the diagnosis and treatment of hypertensive disorders in pregnancy (2020). According to the altitude of residence, the subjects were divided into low altitude group (9 931 cases), middle altitude group (9 068 cases) and high altitude group (247 cases). Univariate and multivariate logistic regression analyses were used to evaluate the relationship between altitude and the risk of PE, after adjusting for confounding factors such as age, ethnicity, mode of conception, gestational diabetes mellitus, and hemoglobin level.Results:(1) Among the 19 246 pregnant women, 752 (3.91%, 752/19 246) were diagnosed with PE. The incidence of PE in the low altitude group, middle altitude group and high altitude group was 2.95% (293/9 931), 4.91% (445/9 068) and 5.67% (14/247), respectively. With the increase of living altitude, the incidence of PE increased significantly ( P<0.001). (2) The results of univariate logistic analysis showed that compared with the low altitude area, the risk of PE in pregnant women living in the middle altitude area and high altitude area increased by 70% ( OR=1.70, 95% CI: 1.46-1.97; P<0.001) and 98% ( OR=1.98, 95% CI: 1.14-3.43; P=0.016). (3) The results of multivariate logistic regression analysis showed that after fully adjusting for confounding factors, the risk of PE increased by 40% for every 500 meters of elevation ( OR=1.40, 95% CI: 1.25-1.57; P<0.001). Compared with those living in low altitude areas, the risk of PE in pregnant women living in middle altitude and high altitude areas increased by 72% ( OR=1.72, 95% CI: 1.47-2.00; P<0.001) and 100% ( OR=2.00, 95% CI: 1.07-3.74; P=0.030). Conclusion:In the high-altitude environment of Gansu Province, the risk of PE gradually increases with the increase of altitude.

Objective:To investigate the relationship between postpartum hemorrhage (PPH) volume and the risk of adverse clinical outcomes in pregnant women.Methods:This was a retrospective cohort study of 41 494 deliveries at Peking University Third Hospital from 2012 to 2020. With PPH volume as the main exposure, the outcome indicators included: (1) Severe adverse outcomes: shock or embolism, abnormal coagulation function, abnormal liver function, and kidney injury; (2) General adverse outcomes: moderate to severe anemia, hypoalbuminemia, postpartum blood transfusion. Robust Poisson regression was employed to calculate the risk of each outcome index in pregnant women with different PPH volumes under the condition of controlling confounding factors, and to analyze the risk trends of each outcome index with the change of PPH volumes.Results:A total of 41 494 pregnant women were included in the study, including 9 959 cases (24.00%, 9 959/41 494), 23 974 cases (57.78%, 23 974/41 494), 5 235 cases (12.62%, 5 235/41 494), 1 144 cases (2.76%, 1 144/41 494), 508 cases (1.22%, 508/41 494), 208 cases (0.50%, 208/41 494), 207 cases (0.50%, 207/41 494) and 259 cases (0.62%, 259/41 494) pregnant women with PPH volume <250, 250-499, 500-749, 750-999, 1 000-1 249, 1 250-1 499, 1 500-1 999 and ≥2 000 ml, respectively. The risk of any serious adverse outcome, such as shock or embolism, abnormal coagulation function, abnormal liver function and kidney injury, showed a "J-shaped" relationship with PPH volume: risks remained stable (0.26%-0.59%) below 1 500 ml but increased significantly to 3.38% ( RR=3.43, 95% CI: 1.14-10.35) at 1 500-1 999 ml and 5.02% ( RR=4.53, 95% CI: 1.49-13.75) at ≥2 000 ml (all P<0.05). Moderate-to-severe anemia showed threshold effects at 750 ml ( RR ranging from 7.21 to 8.53) and hypoalbuminemia at 1 250 ml ( RR ranging from 3.24 to 3.83), with risks plateauing beyond these thresholds (all P<0.05). Conclusion:It is suggested that 750 ml, 1 250 ml and 1 500 ml should be used as the key intervention thresholds, corresponding to the initiation thresholds of anemia, hypoalbuminemia management and multidisciplinary intensive care, respectively, so as to provide a new reference for optimizing the clinical diagnosis and treatment strategy of PPH.

Humans ; Female ; Pregnancy ; Cesarean Section/standards* ; China ; Consensus ; Postoperative Complications/prevention & control* ; Obstetric Labor Complications/surgery*

Humans ; Female ; Hysteroscopy/methods* ; Endometrial Neoplasms/therapy* ; Fertility Preservation/methods* ; Consensus ; China ; Endometrium/surgery* ; Hysterectomy