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.

Objective: The aim of this study was to determine the poly (ADP-ribose) polymerase inhibitors (PARPis) response and outcome of ovarian cancer (OC) patients with BRCA1/2 germline mutation and a history of breast cancer (BC). Methods: Thirty-nine OC patients with BRCA1/2 germline mutation and a history of BC were included. The clinicopathological characteristics, PARPis response and prognosis were analyzed. Results: The median interval from BC to OC diagnosis was 115.3 months (range=6.4–310.1).A total of 38 patients (38/39, 97.4%) received platinum-based chemotherapy after surgical removal. The majority of these patients were reported to be platinum sensitive (92.1%, 35/38).21 patients (53.8%) received PARPis treatment with 16 patients (76.2%) for maintenance treatment and 5 patients (5/21, 23.8%) for salvage treatment. The median duration for PARPis maintenance and salvage treatment was 14.9 months (range=2.0–56.9) and 8.2 months (range=5.2–20.7), respectively. In the entire cohort, 5-year progression-free survival (PFS) and overall survival (OS) rate was 33.1% and 78.9%, respectively. Patients with BRCA1 mutation had a non-significantly worse 5-year PFS (28.6% vs. 45.8%, p=0.346) and 5-year OS (76.9% vs.83.3%, p=0.426) than those with BRCA2 mutation. In patients with stage III–IV (n=31), first line PARPis maintenance treatment associated with a non-significantly better PFS (median PFS: NR vs. 22.4 months; 5-year PFS: 64.3% vs. 21.9%, p=0.096). Conclusion The current study shows that these patients may have a good response to platinum-based chemotherapy and a favorable survival. And these patients can benefit from PARPis treatment and will likely be suitable candidates for PARPis.

Objective: The aim of this study was to determine the poly (ADP-ribose) polymerase inhibitors (PARPis) response and outcome of ovarian cancer (OC) patients with BRCA1/2 germline mutation and a history of breast cancer (BC). Methods: Thirty-nine OC patients with BRCA1/2 germline mutation and a history of BC were included. The clinicopathological characteristics, PARPis response and prognosis were analyzed. Results: The median interval from BC to OC diagnosis was 115.3 months (range=6.4–310.1).A total of 38 patients (38/39, 97.4%) received platinum-based chemotherapy after surgical removal. The majority of these patients were reported to be platinum sensitive (92.1%, 35/38).21 patients (53.8%) received PARPis treatment with 16 patients (76.2%) for maintenance treatment and 5 patients (5/21, 23.8%) for salvage treatment. The median duration for PARPis maintenance and salvage treatment was 14.9 months (range=2.0–56.9) and 8.2 months (range=5.2–20.7), respectively. In the entire cohort, 5-year progression-free survival (PFS) and overall survival (OS) rate was 33.1% and 78.9%, respectively. Patients with BRCA1 mutation had a non-significantly worse 5-year PFS (28.6% vs. 45.8%, p=0.346) and 5-year OS (76.9% vs.83.3%, p=0.426) than those with BRCA2 mutation. In patients with stage III–IV (n=31), first line PARPis maintenance treatment associated with a non-significantly better PFS (median PFS: NR vs. 22.4 months; 5-year PFS: 64.3% vs. 21.9%, p=0.096). Conclusion The current study shows that these patients may have a good response to platinum-based chemotherapy and a favorable survival. And these patients can benefit from PARPis treatment and will likely be suitable candidates for PARPis.

Objective: The aim of this study was to determine the poly (ADP-ribose) polymerase inhibitors (PARPis) response and outcome of ovarian cancer (OC) patients with BRCA1/2 germline mutation and a history of breast cancer (BC). Methods: Thirty-nine OC patients with BRCA1/2 germline mutation and a history of BC were included. The clinicopathological characteristics, PARPis response and prognosis were analyzed. Results: The median interval from BC to OC diagnosis was 115.3 months (range=6.4–310.1).A total of 38 patients (38/39, 97.4%) received platinum-based chemotherapy after surgical removal. The majority of these patients were reported to be platinum sensitive (92.1%, 35/38).21 patients (53.8%) received PARPis treatment with 16 patients (76.2%) for maintenance treatment and 5 patients (5/21, 23.8%) for salvage treatment. The median duration for PARPis maintenance and salvage treatment was 14.9 months (range=2.0–56.9) and 8.2 months (range=5.2–20.7), respectively. In the entire cohort, 5-year progression-free survival (PFS) and overall survival (OS) rate was 33.1% and 78.9%, respectively. Patients with BRCA1 mutation had a non-significantly worse 5-year PFS (28.6% vs. 45.8%, p=0.346) and 5-year OS (76.9% vs.83.3%, p=0.426) than those with BRCA2 mutation. In patients with stage III–IV (n=31), first line PARPis maintenance treatment associated with a non-significantly better PFS (median PFS: NR vs. 22.4 months; 5-year PFS: 64.3% vs. 21.9%, p=0.096). Conclusion The current study shows that these patients may have a good response to platinum-based chemotherapy and a favorable survival. And these patients can benefit from PARPis treatment and will likely be suitable candidates for PARPis.

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.

Over the last decade, clinical trials using various poly ADP ribose polymerase (PARP) inhibitors on patients with ovarian cancer have shown promising results. The introduction of PARP inhibitors has changed the treatment landscape and improved outcomes for patients with ovarian cancer. Fuzuloparib, developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd., is a novel orally available small molecule PARP inhibitor. By introducing the trifluoromethyl group into chemical structure, fuzuloparib exhibits higher stability and lower inter-individual variability than other PARP inhibitors. Several clinical trials (FZOCUS series and others) have been carried out to assess the efficacy and safety of fuzuloparib through different lines of treatments for advanced or recurrent ovarian cancer in both treatment and maintenance. Here, we present the most recent data from these studies, discuss current progress and potential future directions.

Objective:To explore the clinical features of poly ADP-ribose polymerase (PARP) inhibitor-related anemia in advanced and relapsed epithelial ovarian cancer (EOC).Methods:Patients diagnosed with advanced or relapsed EOC and treated with PARP inhibitor at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 to October 2020 were accrued. The data included PARP inhibitors, treatment details, and lab tests before treatment and during treatment were collected and the clinical characteristics of PARP inhibitor-related anemia were analyzed.Results:(1) A total of 98 patients with a median age of 56.5 years old (30-82 years old) were enrolled in this study. All patients were treated with PARP inhibitor (65 cases of olaparib, 17 cases of niraparib, and 16 cases of fluzoparib). The median treatment duration was 37.5 weeks (4-119 weeks). (2) The anemia rate was 40% (39/98), including 5% (5/98) of grade Ⅰ, 14% (14/98) of grade Ⅱ, 11% (11/98) of grade Ⅲ, and 9% (9/98) of grade Ⅳ. Fourteen patients with pre-treatment grade Ⅰ anemia had a higher rate of anemia events than the 80 patients without pre-treatment anemia, 7/14 vs 35% (28/80; χ2=4.281, P=0.039). (3) The median anemia occurrence time was 7.0 weeks (1-52 weeks), including 41% (16/39) of anemia cases occurred in 1-4 weeks, 26% (10/39) occurred in 5-8 weeks, 13% (5/39) occurred in 9-12 weeks, 3% (1/39) occurred in 13-16 weeks, 10% (4/39) occurred in 17-20 weeks, 8% (3/39) occurred ≥21 weeks. At the time of the lowest hemoglobulin tested, the median value of mean corpuscular volume (MCV) was 106 fl,which was higher than the up limit of normal range (100 fl), 74% (29/39) of anemia patients had an elevated MCV level; the median value of mean corpuscular hemoglobin (MCH) was 36 pg, 54% (21/39) of anemia patients had an elevated MCH level; the median value of mean corpuscular hemoglobin concentration (MCHC) was 320 g/L, 69% (27/39) of anemia patients had a higher MCHC level; 92% (36/39) of anemia patients had a normal level of serum iron; 79% (31/39) of anemia patients had a normal level of transferrin. 74% (29/39) of the anemia patients were macrocytic orthochromatic anemia. (4) Among the 39 patients with anemia, 20 patients (51%, 20/39) withhold the treatment of PARP inhibitor due to grade Ⅲ or Ⅳ anemia, including 10 patients (50%, 10/20) who resumed the PARP inhibitor treatment by suppling iron, folate, and vitamin B 12. The median stopping time of PARP inhibitor was 5.5 weeks (2-10 weeks), while the other 10 patients terminated the PARP inhibitor treatment for not recovering from severe anemia. Conclusions:One of the common adverse effects of PARP inhibitors is anemia, which mostly happened in the first 3 months of treatment. In the treatment of EOC, PARP inhibitor-related anemia mainly manifest as macrocytic orthochromatic anemia, and most patients with normal serum iron and transferrin.

Objective:To analyze the characteristics of patients with Takayasu arteritis (TA) in the east China Takayasu arteritis (ECTA) cohort and their subgroups, and evaluate the disease characteristics.Methods:Patients diagnosed with TA in ECTA cohort from January 2009 to October 2019 were enrolled and their data were analyzed. The characteristics were analyzed and compared within subgroups using t-test or Wilcoxon rank sum test or Chi-square test. Results:A total of 454 patients were included, with the male to female ratio of 1∶4.75(79/375), and the main complaint were dizziness/headache, fatigue, and chest tightness/pain. The type Ⅴ and Ⅰ were the most common angiographic pattern, among which the subclavian artery and carotid artery were most vulnerable, manifested as vascular stenosis. Hypertension, tuberculosis and hepatitis B were common complications. In subgroup comparison, symptoms and inflammation index were much more evident in the active group, female group, <40 years old, and newly diagnosed group. C-reactive protein (CRP)[10(2, 33) mg/L vs 3(1, 14) mg/L, Z=-4.49, P<0.01), erythrocyte sedimentation rate (ESR) [(45±33) mm/1 h vs (25±23) mm/1 h, t=-5.82, P<0.01), in the active group were significantly higher than those in the inactive group, while the ESR in female patients was only higher than that in males, but without statistical significant difference. SAA in the young age group, ESR in the newly diagnosed group was significantly higher than that in the other subgroups [19(6, 95) mg/L vs 10(4, 39) mg/L, Z=2.06, P<0.05] [(44±34) mm/1 h vs (32±28) mm/1 h, t=3.77, P<0.01]. Conclusion:The TA patients are mainly young women, and are in active disease when first being diagnosed. The type Ⅴ and Ⅰ are the most common artery involve-ment pattern. Hypertension and tuberculosis are the most frequent complications.

Objective:To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer.Methods:A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis.Results:The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy ( P<0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P<0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P<0.01). Conclusion:Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.

Objective:To analyze the clinicopathological features and prognostic factors of patients with uterine clear cell carcinoma (UCCC).Methods:UCCC patients who underwent surgery and complete follow-up at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis.Results:The study included 34 patients. Only 18 patients (52.9%) were diagnosed with UCCC preoperatively and 8 patients (23.5%) underwent UCCC standard comprehensive staging surgery. Among the 34 patients, stage ⅠA was 17 cases (50.0%), stage ⅠB was 1 case (2.9%), stage Ⅱ was 4 cases (11.8%), stage ⅢA was 2 cases (5.9%), stage ⅢB was 1 case (2.9%), stage ⅢC1 was 5 cases (14.7%) and stage ⅣB was 4 cases (11.8%). The median follow-up period was 72 months, 5-years disease-free survival (DFS) rate and overall survival (OS) rates for all patients were 79.1% and 81.3%, respectively. Univariate analysis result showed that preoperative CA125 level, range of lymphadenectomy, tumor stage and peritoneal cytology were significantly associated with DFS ( P<0.05). Preoperative CA125 level, range of lymphadenectomy, tumor stage, peritoneal cytology and lymph vascular space invasion were significantly associated with OS ( P<0.05). Multivariate analysis result showed that peritoneal cytology was the only independent prognostic factor for DFS, the relapse risk of peritoneal cytology positive patients was 11.47 folds higher than that of the negative patients ( P=0.009). Tumor stage was the only independent prognostic factor for OS, the death risk of ⅣB stage patients was 25.29 folds higher than that of theⅠA stage ( P=0.009). Conclusions:The preoperative pathological diagnosis of UCCC is difficult, which results in incomplete surgical staging. Peritoneal cytology and tumor stage are independent prognostic factors for DFS and OS of UCCC patients, which deserve much more attention in clinical practice.