Recurrence and survival of patients with stage III endometrial cancer after radical surgery followed by adjuvant chemo- or chemoradiotherapy: a systematic review and meta-analysis.

OBJECTIVE: To compare recurrence and survival in patients with stage III endometrial cancer after radical surgery, followed by either adjuvant chemoradiotherapy (ACR) or adjuvant chemotherapy (AC). METHODS: We searched for relevant studies in PubMed Central, Embase and the Cochrane Central Register of Controlled Trials. Data were pooled on rates of recurrence as well as rates of progression-free, disease-free and overall survival. Heterogeneity was evaluated using the I2 test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. RESULTS: Data from 18,375 patients in 15 retrospective studies and one randomized controlled trial were meta-analyzed. Compared to the AC group, the ACR showed significantly lower risk of local recurrence (OR 0.43, 95%CI 0.32-0.59) and total recurrence (OR 0.72, 95%CI 0.58-0.89). ACR was also associated with significantly better overall survival (HR 0.66, 95%CI 0.57-0.76), progression-free survival (HR 0.56, 95%CI 0.39-0.81) and disease-free survival (HR 0.66, 95%CI 0.53-0.83). CONCLUSIONS: Adding adjuvant radiotherapy to adjuvant chemotherapy after radical surgery may significantly reduce risk of local and overall recurrence, while significantly improving survival of patients with stage III endometrial cancer.

[RNA m 6A Modification and Its Roles in Immune Function Regulation].

N 6-methyladenosine (m 6A) is the most prevalent post-transcriptional RNA modification in eukaryotic cells. m 6A methyltransferase complexes and demethylases are involved in the dynamic and reversible regulation of m 6A modification, while m 6A binding proteins could specifically identify m 6A modification and regulate RNA metabolism, including splicing, translocation, stability, and translation. m 6A is found to play a vital role in all the fundamental biological processes, including the regulation of the immune system, from normal development to diseases. The normal development and functioning of the immune system rely on the precise regulation of the relevant gene expression, and m 6A modification is crucial to the regulation. Herein, we reviewed the concept, the functions, and the mechanism of m 6A modification, concentrating on its role in immune system function modulation. Furthermore, we highlighted present obstacles and future research directions in the field, intending to provide a theoretical foundation and reference for future study on how m 6A modification is involved in immune regulation.

Influence of lymph node involvement or lymphadenectomy on prognosis of patients with borderline ovarian tumors: A systematic review and meta-analysis.

OBJECTIVE: Borderline ovarian tumors (BOTs) account for about 15% of all epithelial tumors of the ovary, and around 75% of patients are diagnosed in early stages. Although many of these patients have lymph node involvement (LNI), whether LNI decreases their survival is controversial, raising the question of whether lymphadenectomy should be performed. We conducted a systematic review and meta-analysis of these questions. METHODS: We searched articles related to LNI and lymphadenectomy in patients with BOTs in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Data on rate of LNI, recurrence and survival were pooled and meta-analyzed using a random-effects model. Heterogeneity was evaluated using the I2 test. RESULTS: A total of 25 studies with 12,503 patients were meta-analyzed. The overall pooled rate of LNI was 10% [95% confidence interval (CI) 0.07-0.13]. LNI was associated with a higher risk of recurrence [odds ratio (OR) 2.23, 95% CI 1.13-4.40]. However, LNI did not significantly affect cause-specific survival [hazard ratio (HR) 1.73, 95% CI 0.99-3.02] or disease-free survival (HR 1.48, 95% CI 0.56-3.92). Similarly, lymphadenectomy did not significantly affect risk of recurrence (OR 0.91, 95% CI 0.57-1.46), overall survival (HR 0.90, 95% CI 0.58-1.40), disease-free survival (HR 0.95, 95% CI 0.61-1.50) or progression-free survival (HR 0.60, 95% CI 0.24-1.49). CONCLUSIONS: LNI appears to increase risk of recurrence in BOT patients, but neither it nor lymphadenectomy appears to influence prognosis. Therefore, lymphadenectomy should be considered only for certain BOT patients, such as those with suspected LNI based on imaging or surgical exploration.

RIP1 promotes proliferation through G2/M checkpoint progression and mediates cisplatin-induced apoptosis and necroptosis in human ovarian cancer cells.

Receptor-interacting protein 1 (RIP1, also known as RIPK1) is not only a tumor-promoting factor in several cancers but also mediates either apoptosis or necroptosis in certain circumstances. In this study we investigated what role RIP1 plays in human ovarian cancer cells. We showed that knockout (KO) of RIP1 substantially suppressed cell proliferation, accompanied by the G2/M checkpoint arrest in two human ovarian cancer cell lines SKOV3 and A2780. On the other hand, RIP1 KO remarkably attenuated cisplatin-induced cytotoxicity, which was associated with reduction of the apoptosis markers PARP cleavage and the necroptosis marker phospho-MLKL. We found that RIP1 KO suppressed cisplatin-induced ROS accumulation in both SKOV3 and A2780 cells. ROS scavenger BHA, apoptosis inhibitor Z-VAD or necroptosis inhibitor NSA could effectively suppress cisplatin's cytotoxicity in the control cells, suggesting that ROS-mediated apoptosis and necroptosis were involved in cisplatin-induced cell death. In addition, blocking necroptosis with MLKL siRNA effectively attenuated cisplatin-induced cytotoxicity. In human ovarian cancer A2780 cell line xenograft nude mice, RIP1 KO not only significantly suppressed the tumor growth but also greatly attenuated cisplatin's anticancer activity. Our results demonstrate a dual role of RIP1 in human ovarian cancer: it acts as either a tumor-promoting factor to promote cancer cell proliferation or a tumor-suppressing factor to facilitate anticancer effects of chemotherapeutics such as cisplatin.

Contraceptive practices among unmarried women in China, 1982-2017: systematic review and meta-analysis.

OBJECTIVE: Premarital sexual practices and contraceptive prevalence rate (CPR) among unmarried women in China remain unclear. We conducted a systematic review and meta-analysis to estimate CPR and analyse contraceptive methods used by unmarried women between 1982 and 2017. METHODS: Wanfang, The China National Knowledge Infrastructure Database, MEDLINE, PubMed and Web of Science were systematically searched. Data on CPR and use of major contraceptive methods were extracted and pooled using a DerSimonian-Laird random effects model. RESULTS: Of 188 articles retrieved from five databases, 22 studies met our inclusion criteria. Overall CPR based on a random effects meta-analysis was 32.2% (95% confidence interval [CI] 24.7%, 39.8%). Pooled rates of contraceptive use were 61.4% (95% CI 47.9%, 74.9%) for condoms, 25.9% (95% CI 14.5%, 37.4%) for pills, 19.8% (95% CI 8.9%, 30.8%) for the rhythm method and 25.4% (95% CI 14.2%, 36.7%) for the withdrawal method. CONCLUSIONS: The sexual and reproductive health situation of unmarried women in China seems to have improved little since the 1990s. Our findings may help to optimise reproductive health care programmes and thereby reduce the alarming rates of unplanned pregnancies and abortions among unmarried women in China.

[Effects of NF-kappaB inhibitor on cisplatin-induced apoptosis in cervical cancer].

OBJECTIVE: To observe whether cisplatin-induced apoptosis were increased when SiHa cells were preincubated with nuclear factor-kappa B (NF-kappaB) inhibitors [aspirin, sulindac, curcumin or pyrrolidine dithiocarbamate (PDTC)]. METHODS: SiHa cells were preincubated 2 hours with aspirin, sulindac, curcumin and PDTC respectively, then a further incubation were done with cisplatin, and Western blot analysis were applied to detect P65 level of nuclear extraction. MTT assay was done to detect relative cell viability. TUNEL was applied to detect apoptosis rates. Flow cytometryies with PI staining were also used to detect apoptosis as well as cell cycle. RESULTS: When SiHa cells were pretreated with aspirin, sulindac, curcumin or PDTC, Western blot showed that the expression of P65 was inhibited upon cisplatin stimulus (P < 0.05). MTT assay demonstrated that a preincubation with NF-kappaB inhibitor could signifianctly increase cisplatin-induced chemosensitivity (P < 0.05). When cells pretreated with aspirin, sulindac, curcumin, or PDTC, TUNEL and flow cytometries assay showed that the apoptotic rates were all increased after 24 hours cisplatin stimulus (P < 0.05). Results of flow cytometries were also showed that a pretreation with aspirin, sulindac, curcumin, or PDTC could significantly increase cisplatin-induced apoptosis. CONCLUSION: Aspirin, sulindac, curcumin and PDTC could all inhibit cisplatin induced NF-kappaB activiation, which could increase cispaltin-induced chemosensativity by augments of apoptosis.

Efficacy of Oral Medications or Intrauterine Device-Delivered Progestin in Patients with Endometrial Hyperplasia with or without Atypia: A Network Meta-Analysis.

The aim of this systematic review was to evaluate the efficacy of oral medication or intrauterine device-delivered progestins in patients with endometrial hyperplasia (EH) with or without atypia. We systematically examined PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov to identify studies reporting the regression rate of patients with EH who received progestins or non-progestins. The regression rates after different treatments were compared using a network meta-analysis in terms of the relative ratios (RRs) and 95% confidence intervals (CIs). Begg-Mazumdar rank correlation and funnel plots were performed to evaluate the publication bias. Five non-randomized studies and 21 randomized controlled trials involving 2268 patients were included in the network meta-analysis. The levonorgestrel-releasing intrauterine system (LNG-IUS) was associated with a higher regression rate than medroxyprogesterone acetate (MPA) (RR 1.30, 95% CI 1.16-1.46) in patients with EH. Among those without atypia, the LNG-IUS was associated with a higher regression rate than any of the three types of oral medications (MPA, norethisterone, or dydrogesterone (DGT)) (RR 1.35, 95% CI 1.18-1.55). According to the network meta-analysis, combining the LNG-IUS with MPA or metformin increased regression rate, while DGT was associated with the highest regression rate among all oral medications. The LNG-IUS may be the best choice for patients with EH, and combining it with MPA or metformin may further improve its efficacy. DGT may be the preferred choice for patients who are unwilling to use the LNG-IUS or who cannot tolerate its side effects.

Reproductive and oncological outcomes of fertility-sparing surgery in patients with stage I epithelial ovarian cancer: A systematic review and meta-analysis.

OBJECTIVE: We meta-analyzed available evidence on fertility, survival, and cancer recurrence in patients with stage I epithelial ovarian cancer (EOC) after fertility-sparing surgery (FSS). METHODS: We systematically reviewed PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials to identify studies reporting reproductive and oncological outcomes of patients with stage I EOC who underwent FSS. Random-effects models were used to calculate pooled rates of disease outcomes, along with 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to identify sources of heterogeneity in the data. RESULTS: We included 23 observational retrospective studies involving 1126 patients. The pooled pregnancy rate was 30% (95% CI, 0.26-0.34), while the pooled natural conception rate was 26% (95% CI, 0.20-0.33). The pooled live birth rate was 27% (95% CI, 0.22-0.32). The pooled rate of EOC recurrence was 12% (95% CI, 0.09-0.14), which did not differ significantly from the rate among patients who underwent radical surgery (odds ratio, 0.77; 95% CI, 0.45-1.33). CONCLUSIONS: FSS is associated with good oncological outcomes but less than satisfactory reproductive outcomes. All in all, the procedure appears to be a safe alternative to radical surgery for EOC patients who want to preserve fertility.

Cervical Cancer Recurrence and Patient Survival After Radical Hysterectomy Followed by Either Adjuvant Chemotherapy or Adjuvant Radiotherapy With Optional Concurrent Chemotherapy: A Systematic Review and Meta-Analysis.

Objective: To compare cervical cancer recurrence and patient survival after radical hysterectomy followed by either adjuvant chemotherapy (AC) or adjuvant radiotherapy with or without concurrent chemotherapy (AR/CCRT). Methods: We systematically searched PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov to identify studies reporting recurrence or survival of cervical cancer patients who received AC or AR/CCRT after radical hysterectomy. Data were meta-analyzed using a random-effects model, and heterogeneity was evaluated using the I2 test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. Results: The meta-analysis included 14 non-randomized studies and two randomized controlled trials, altogether involving 5,052 cervical cancer patients. AC and AR/CCRT groups did not differ significantly in rates of total or local recurrence or mortality. Nevertheless, AC was associated with significantly lower risk of distant recurrence [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.55-0.81] and higher rates of overall survival [hazard ratio (HR) 0.69, 95%CI 0.54-0.85] and disease-free survival rate (HR 0.77, 95%CI 0.62-0.92). Conclusions: AC may be an effective alternative to AR/CCRT for cervical cancer patients after radical hysterectomy, especially younger women who wish to preserve their ovaries and protect them from radiation damage. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021252518).

Internal Jugular Vein Thrombosis After Microwave Ablation of Cervical Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: A Case Report.

In this study, two patients with papillary thyroid carcinoma and lymph node metastasis were treated by Dr. Shurong Wang's team and are reported. The two patients refused surgery and underwent microwave ablation (MWA) of the thyroid and lymph node lesions. Ultrasound review 2 days after MWA revealed internal jugular vein thrombosis. Patient #1 received low molecular weight heparin calcium injection, Xueshuantong injection, Xiangdan injection, and rivaroxaban. Patient #2 was treated with enoxaparin sodium injection, Xueshuantong injection, urokinase, and warfarin sodium tablet. The thrombus was successfully managed in each patient using anticoagulant treatment. Such complication of MWA has not been reported in many cases before. According to the relevant literature, thrombosis after thyroid cancer ablation might be related to subclinical hypothyroidism, increased heme oxidase 1 (HO-1) levels in the blood of patients with papillary thyroid cancer, and increased platelet content and mean platelet volume in patients with thyroid cancer. No specific cause of thrombosis was identified in the two cases reported here. No recurrence was observed after 1 (patient #1) and 4 (#2) years of follow-up. In conclusion, patients with papillary thyroid carcinoma and lymph node metastasis should undergo color Doppler ultrasound of the neck after MWA of thyroid lesions and neck metastasis.

High expressions of bcl-2 and survivin, and decreased apoptosis in uterine cervical carcinosarcoma compared to cervical squamous cell carcinoma.

PURPOSES: Uterine cervical carcinosarcoma (CS) is very rare. To date, only 40 cases have been reported. It seems to have a more aggressive clinical behavior than does cervical squamous cell carcinoma (SCC). The purposes of our study were to characterize the clinicopathologic characteristics and human papillomavirus (HPV) status of the rare tumor and to analyze the molecular features in cervical CS that may account for its aggressive behavior. METHODS: Three patients were diagnosed with uterine cervical CS at West China Second Hospital of Sichuan University between 1995 and 2009. Data were retrospectively analyzed from available charts and pathological reports. Twelve patients with FIGO stage Ib-IIa cervical SCC were enrolled as the controls, and the expression profiling of p53, Ki-67, bcl-2, survivin and apoptosis index between cervical CS and SCC was compared. Immunohistochemical and apoptosis results were scored separately for the carcinomatous and sarcomatous components. RESULTS: All three patients were shown to be negative for HPV infection by Hybribio HPV genoarray assay. Expression of p53 was observed in one patient in both carcinomatous and sarcomatous components in a similar proportion; in contrast, the Ki67, bcl-2 and survivin expressions were higher in carcinomatous components than in sarcomatous components in all three cases. Compared to cervical SCC, stronger immunostaining for bcl-2, survivin and lower apoptosis was observed in cervical CS. CONCLUSIONS: Cervical CS is a peculiar tumor with many different clinicopathologic characteristics from cervical SCC. Dysregulation of apoptosis may confer tumor cells of cervical CS with survival and growth advantages, and thereby facilitate the aggressive behavior of cervical CS.

Ovarian metastasis in women with cervical carcinoma in stages IA to IIB: A systematic review and meta-analysis.

BACKGROUND: Cervical cancer is one of the common malignancies that afflict women worldwide. In rare cases, cervical cancer leads to ovarian metastasis (OM), resulting in poor outcomes. We conducted a systematic review and meta-analysis to evaluate the incidence and risk factors of OM in patients with adenocarcinoma (ADC) or squamous cell carcinoma (SCC) of the cervix. METHODS: We searched articles focused on OM in cervical carcinoma in PubMed, Embase, and the Cochrane Central Register of Controlled Trials. A meta-analysis was performed including selected publications. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using random-effects models. The heterogeneity was evaluated by the I test. I > 50% was considered high heterogeneity. RESULTS: A total of 12 studies with 18,389 patients with cervical cancer in International Federation of Gynecology and Obstetrics stages IA to IIB were included in the meta-analysis. The overall incidence of OM was 3.61% among patients with ADC and 1.46% among patients with SCC (ADC vs SCC: OR 3.89, 95% CI 2.62-5.78; P < .001). Risk factors for OM were age >40 years (OR 1.79, 95% CI 1.02-3.13), bulky tumor (OR 2.65, 95% CI 1.77-3.95), pelvic lymph node involvement (PLNI; OR 9.33, 95% CI 6.34-13.73), lymphovascular space involvement (LVSI; OR 4.38, 95% CI 1.86-10.31), parametrial invasion (PMI; OR 7.87, 95% CI 5.01-12.36), and corpus uteri invasion (CUI; OR 7.64, 95% CI 2.51-23.24). PLNI, LVSI, and PMI were the leading risk factors, contributing to OM with respective population attributable fractions of 64.8%, 58.8%, and 51.5%. CONCLUSION: The incidence of OM is relatively low in ADC and SCC patients. Risk factors for OM include PLNI, LVSI, PMI, bulky tumor, CUI, or age over 40 years, with the first 3 contributing more to risk of OM.

Contraceptive and reproductive health practices of unmarried women globally, 1999 to 2018: Systematic review and meta-analysis.

BACKGROUND: Premarital sex practices and contraceptive prevalence rate (CPR) among unmarried women worldwide remain unclear, even though unmarried women tend to have multiple sex partners over time, which makes their sexual behaviors particularly important to the sexual and reproductive health of society more broadly. METHODS: We searched the MEDLINE, PubMed, and Google Scholar databases for relevant articles published between January 1, 1999 and December 31, 2018. Data on prevalence of premarital sexual intercourse, use of highly prevalent contraceptive methods, as well as CPR overall and at first sexual intercourse were extracted and estimated using a DerSimonian- Laird random effects model. RESULTS: Of the 3918 articles identified, 37 covering 19 countries were included. The estimated overall prevalence of premarital sexual intercourse was 41.9% (95%CI 34.2-49.6%). Pooled CPR was 57.0% (95%CI 44.3-69.8%) overall and 57.6% (95% CI 39.5- 75.6%) at first intercourse. The overall prevalence of condom use was 51.2% (95%CI 42.7-59.7%), followed by oral contraceptives (20.5%, 95%CI 13.7-27.3%), withdrawal (12.7%, 95%CI 9.4-15.9%), and rhythm (12.1%, 95%CI 6.7-17.4%). CONCLUSION: The findings of this global study indicate worrying trends in unprotected intercourse and contraceptive practices, suggesting the need for greater attention and resources aimed at educating unmarried adolescent women about sexual and reproductive health. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42019132736.

Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy.

The immune cells within the tumor microenvironment (TME) play important roles in tumorigenesis. It has been known that these tumor associated immune cells may possess tumor-antagonizing or tumor-promoting functions. Although the tumor-antagonizing immune cells within TME tend to target and kill the cancer cells in the early stage of tumorigenesis, the cancer cells seems to eventually escape from immune surveillance and even inhibit the cytotoxic function of tumor-antagonizing immune cells through a variety of mechanisms. The immune evasion capability, as a new hallmark of cancer, accidently provides opportunities for new strategies of cancer therapy, namely harnessing the immune cells to battle the cancer cells. Recently, the administrations of immune checkpoint modulators (represented by anti-CTLA4 and anti-PD antibodies) and adoptive immune cells (represented by CAR-T) have exhibited unexpected antitumor effect in multiple types of cancer, bringing a new era for cancer therapy. Here, we review the biological functions of immune cells within TME and their roles in cancer immunotherapy, and discuss the perspectives of the basic studies for improving the effectiveness of the clinical use.

[Homocysteine decreases the invasion in cultured human trophoblasts: relationship between homocysteine and matrix metalloproteinase-2, -9 expression].

OBJECTIVE: To test the hypothesis that homocysteine can decrease MMP-2 and MMP-9 expression in cultured trophoblasts of early pregnancy and that homocysteine can prevent trophoblasts invasion in the early stage of preeclampsia. METHODS: Cytotrophoblasts from early pregnancy were isolated and cultured. Trophoblasts were treated with or without Hcy (1 mmol/L) for 48 hour, and real time RT-PCR and gelatin zymography were used to quantify the mRNA and protease activity of MMP-2, -9. RESULTS: Treatment with Hcy (1 mmol/L) induced a decrease in MMP-2 mRNA by 21% and MMP-9 mRNA by 11%. At protein level MMP-2 expression decreased 14% and MMP-9 expression decreased 52% compared with control. CONCLUSIONS: Homocysteine can decrease MMP-2, -9 expression in trophoblasts of early pregnancy and influence its invasion process.

[Differences between the expression of matrix metalloproteinase-2, 9 in preeclampsia and normal placental tissues].

OBJECTIVE: To study the possible relationships between expression of matrix metalloproteinase (MMP) 2, 9 and the pathogenesis of preeclampsia in which trophoblast invasion is impaired. METHODS: MMP-2, 9 expression were detected by immunohistochemistry streptavidin-biotin complex (SABC) method in 20 normal term placentae and 20 preeclampsia placentae, respectively. In addition, mRNAs for MMP-2, 9 were analyzed by real time PCR in both groups. RESULTS: The intensities of both MMP-2 and MMP-9 immunostaining in preeclampsia placentae were significantly declined compared to those of normal term placentae (P < 0.05). By using 2(-DeltaDeltaCt) as a relatively quantitative assay, mRNA expression of MMP-2 was significantly higher in 10 normal placentae than those in 13 preeclampsia placentae (7.6 +/- 2.8 vs 5.6 +/- 1.5, P < 0.05). Expression of MMP-9 mRNA was also significantly higher in normal placentae than those in preeclampsia placentae (2.2 +/- 2.6 vs -0.9 +/- 2.0, P < 0.05). Whereas, mRNA expression of MMP-2 was higher compared to MMP-9 in normal term placentae (P < 0.05). CONCLUSION: The decreased expression of MMP-2 and MMP-9 in preeclampsia placentae may lead to impaired invasion of trophoblast cells, causing abnormal placentation and occurrence of preeclampsia.

[Expression of keratinocyte growth factor and keratinocyte growth factor receptor and its impact on Hela cells].

OBJECTIVE: To identify the expression of keratinocyte growth factor (KGF) and keratinocyte growth factor receptor (KGFR) in Hela cells and the impact of keratinocyte growth factor on Hela cells. METHODS: Reverse transcriptase polymerase chainreaction (RT-PCR) method was employed to determine the gene expression of KGF and KGFR in Hela cells. The ELISA and Western blot methods were employed to determine the protein expression of the KGF and KGFR. The 3H-Thymidine incorporation method was employed to determine the impact of the KGF on the proliferation of Hela cells. RESULTS: The KGF and KGFR genes were expressed in the Hela cells. The KGF and KGFR proteins were expressed in the Hela cells. The Hela cells were stimulated to proliferate by the recombinant human KGF. The proliferation of the autocrine KGF in the Hela cells was neutralized by the KGF antibodies significantly (Dunnett's test, P