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Context While the associations between thyroid markers and gestational diabetes mellitus (GDM) have been extensively studied, the results are inconclusive and the mechanisms remain unclear. Objective We aimed to investigate the prospective associations of thyroid markers in early gestation with GDM risk, and examine the mediating effects through lipid species. Methods This study included 6068 pregnant women from the Tongji-Shuangliu Birth Cohort. Maternal serum thyroid markers (free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody) were measured before 15 weeks. Deiodinase activity was assessed by fT3/fT4 ratio. Plasma lipidome were quantified in a subset of 883 participants. Results Mean age of the participants was 26.6 ± 3.7 years, and mean gestational age was 10.3 ± 2.0 weeks. Higher levels of fT4 were associated with a decreased risk of GDM (OR = 0.73 comparing the extreme quartiles; 95% CI 0.54, 0.98, Ptrend = .043), while higher fT3/fT4 ratio was associated with an increased risk of GDM (OR = 1.43 comparing the extreme quartiles; 95% CI 1.06, 1.93, Ptrend = .010) after adjusting for potential confounders. Multiple linear regression suggested that fT3/fT4 ratio was positively associated with alkylphosphatidylcholine 36:1, phosphatidylethanolamine plasmalogen 38:6, diacylglyceride 18:0/18:1, sphingomyelin 34:1, and phosphatidylcholine 40:7 (false discovery rate [FDR] adjusted P < .05). Mediation analysis indicated 67.9% of the association between fT3/fT4 ratio and GDM might be mediated through the composite effect of these lipids. Conclusion Lower concentration of serum fT4 or higher fT3/fT4 ratio in early pregnancy was associated with an increased risk of GDM. The association of fT3/fT4 ratio with GDM was largely mediated by specific lipid species.

The impact of para-aortic lymphadenectomy (PALD) on prognosis and quality of life (QoL) for IB2-IIA2 cervical cancer patients remain controversial. And whether intraoperative frozen pathology exam on common iliac lymph nodes could help predict para-aortic lymph node (PALN) metastasis was unanswered with high-level evidence.A multi-center, randomized controlled study is intended to investigate the effect of PALD on the prognosis and QoL in cervical cancer patients and to assess the value of intraoperative frozen pathological evaluation of common iliac nodes metastasis for the prediction of PALN metastasis. After choosing whether to receive intraoperative frozen pathological examination of bilateral common iliac lymph nodes, eligible patients will be randomly assigned (1:1) to receive PALD or not. The primary end point is 2-year progression-free survival (PFS). The secondary end points include 5-year PFS, 2-year overall survival (OS), 5-year OS, adverse events (AEs) caused by PALD, AEs caused by radiotherapy and QoL. A total of 728 patients will be enrolled from 8 hospitals in China within 3-year period and followed up for 5 years.Chinese Clinical Trial Register Identifier: ChiCTR2000035668.

Aims We aimed to assess the association between gut bacterial biomarkers during early pregnancy and subsequent risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. Methods Within the Tongji-Shuangliu Birth Cohort study, we conducted a nested case-control study among 201 incident GDM cases and 201 matched controls. Fecal samples were collected during early pregnancy (at 6-15 weeks), and GDM was diagnosed at 24 to 28 weeks of pregnancy. Community DNA isolated from fecal samples and V3-V4 region of 16S rRNA gene amplicon libraries were sequenced. Results In GDM cases versus controls, Rothia, Actinomyces, Bifidobacterium, Adlercreutzia, and Coriobacteriaceae and Lachnospiraceae spp. were significantly reduced, while Enterobacteriaceae, Ruminococcaceae spp., and Veillonellaceae were overrepresented. In addition, the abundance of Staphylococcus relative to Clostridium, Roseburia, and Coriobacteriaceae as reference microorganisms were positively correlated with fasting blood glucose, 1-hour and 2-hour postprandial glucose levels. Adding microbial taxa to the base GDM prediction model with conventional risk factors increased the C-statistic significantly (P < 0.001) from 0.69 to 0.75. Conclusions Gut microbiota during early pregnancy was associated with subsequent risk of GDM. Several beneficial and commensal gut microorganisms showed inverse relations with incident GDM, while opportunistic pathogenic members were related to higher risk of incident GDM and positively correlated with glucose levels on OGTT.

Ions or charged vacancies drift induced by electric fields in organic–inorganic halide perovskites (OIHPs) generally contributes to distinct current–voltage hysteresis, which drives the development of resistive switching memory (RSM) devices. Here, the two-dimensional (2D) OIHP films are adopted as the switching layer to fabricate the RSM devices with a simplified photovoltaic structure. The device displays stable and low voltage resistive switching (RS) characteristics, with an on/off ratio greater than 106 and a switching voltage as low as 0.4 V. After adding a NiOx hole transport layer in a completed photovoltaic device, the fabricated RSM devices without encapsulation show reliable RS behavior with an endurance over 4 × 102 cycles and a retention time of 103 s in atmospheric conditions. Both Ag ions and iodine vacancies conductive filaments are responsible for the RS properties. This work provides a perspective for appvlication in high-performance 2D OIHP RSM devices compatible with photovoltaic behavior.

Objective Cervical cancer diagnosed during pregnancy is a rare event, and data regarding efficacy of cancer treatment during pregnancy is limited. This study aimed to assess the safety of continuation of the pregnancy for mother and fetus when concomitantly diagnosed with cervical cancer. Methods This study retrospectively analyzed all cervical cancer patients diagnosed while pregnant or immediately postpartum, inclusive from Jan 2010 to June 2019 at our institute. Patient clinical details and follow-up were obtained from hospital records. Results The study comprised 40 patients with clinical cancer stages of IA1 (1/40, 2.5%); IB1 (15/40, 37.5%); IB2 (10/40, 25%); IIA (12/40, 30%); and IIB (2/40, 5%). There were 38 patients diagnosed during pregnancy, and 2 diagnosed in the postpartum period. Of the 38 patients, 17 were diagnosed in the first trimester, 13 in the second trimester, and 8 in the third trimester. 10 of 38 patients (26.3%) continued their pregnancy after learning of their diagnosis; 7 (70%) in the third trimester and 3 (30%) in the second trimester. The mean time from diagnosis to surgery in the patients who continued their pregnancy was 52.7 days, which was statistically significantly greater than the termination of pregnancy group (52.7 vs. 16.3 days, P P = 0.54), and none of the pregnant women who ultimately died had delayed treatment due to pregnancy. Similarly, the surgical estimated blood loss and operative duration comparison in the 2 groups were not significantly different. Conclusions In the present study, the gestational age of pregnancy at the time of initial diagnosis of cervical cancer was an important determinant in the disease management. Continuation of the pregnancy when diagnosed with cervical cancer may not affect the oncologic outcome of the mother nor increase either surgical or obstetric complications. Additionally, the use of neoadjuvant chemotherapy did not threaten the health of the fetus. These results may be useful in counseling patients facing the diagnosis of cervical cancer during pregnancy.

LncRNA-MIR210HG plays crucial roles in the progression of diverse cancers. However, the expression and function of MIR210HG in ovarian cancer remains unclear. In the present study, we aimed to determine the expression and function of lncRNA-MIR210HG in ovarian cancer under hypoxic conditions. MIR210HG expression in ovarian cancer cells under hypoxic conditions was determined by qPCR analysis, and the distribution was determined by FISH and qPCR analysis based on cell nucleus and cytosol RNA extraction. Epithelial-Mesenchymal Transition (EMT) assay and human umbilical vein endothelial cell-based tube formation and migration assays were employed to determine the potential function of MIR210HG in vitro, followed by establishment of a subcutaneous tumor model in mice. The direct target of MIR210HG was determined by RNA pull-down and western blotting. Furthermore, the expression and clinical correlation of MIR210HG was determined based on malignant tissues from ovarian cancer patients. Our results indicated that MIR210HG was induced by hypoxia, which is HIF-1α dependent and mainly located in the cytosol of ovarian cancer cells. Knockdown of MIR210HG significantly inhibited EMT and tumor angiogenesis in vitro and impaired tumor growth in mice. Molecular investigations indicated that MIR210HG directly targets HIF-1α protein and inhibits VHL-dependent HIF-1α protein degradation in ovarian cancer. Further results demonstrated that MIR210HG was upregulated in ovarian cancer tissues and correlated with tumor progression and poor prognosis of ovarian cancer patients. Our study suggests that hypoxia-induced MIR210HG promotes cancer progression by inhibiting HIF-1α degradation in ovarian cancer, which could be a therapeutic target for ovarian cancer.

Context Fetuin-A was reported to be associated with risk of type 2 diabetes, but its association with incident gestational diabetes mellitus (GDM) was less studied. Objective We aimed to examine the association between fetuin-A levels in early pregnancy and risk of incident GDM and to evaluate whether this association was causal. Methods A total of 332 pregnant women with GDM and 664 matched controls were included in this nested case-control study. Multivariable conditional logistic regression was applied to investigate the prospective association between serum fetuin-A in early pregnancy and subsequent risk of GDM. Two-sample Mendelian randomization (MR) analysis was used to examine the causal association, using summary statistics from the CHARGE Consortium and the FinnGen consortium. Results The mean age of the participants was 28.0 years, and the mean gestational age was 11.0 weeks (range 6-15) at enrollment. In the final model, the odds ratio (OR) for GDM comparing the extreme quartiles of fetuin-A levels was 1.78 (95% CI 1.06, 2.98; P for trend = 0.009), and the restricted cubic spline analysis indicated a linear association (P for nonlinearity = 0.83). This positive association was found in women with waist circumference Conclusions Serum fetuin-A levels in early pregnancy were positively associated with risk of GDM, particularly in those with normal waist circumference. However, we found no genetic evidence for a causal association.

Ovarian cancer (OC) remains the leading cause of mortality due to gynecological malignancies. Epidemiological studies have demonstrated that steroid hormones released from the hypothalamic-pituitary-ovarian axis can play a role in stimulating or inhibiting OC progression, with gonadotropins, estrogens and androgens promoting OC progression, while gonadotropin-releasing hormone (GnRH) and progesterone may be protective factors in OC. Experimental studies have indicated that hormone receptors are expressed in OC cells and mediate the growth stimulatory or growth inhibitory effects of hormones on these cells. Hormone therapy agents have been evaluated in a number of clinical trials. The majority of these trials were conducted in patients with relapsed or refractory OC with average efficacy and limited side-effects. A better understanding of the mechanisms through which hormones affect cell growth may improve the efficacy of hormone therapy. In the present review article, the role of hormones (GnRH, gonadotropins, androgens, estrogens and progestins) and their receptors in OC tumorigenesis, and hormonal therapy in OC treatment is discussed and summarized.

AIMS We prospectively evaluated the association of circulating retinol-binding protein 4 (RBP4) levels in early pregnancy and risk of incident gestational diabetes mellitus (GDM) in pregnant women. METHODS A nested case-control study was conducted among 332 women who developed GDM and 664 matched controls based on the Tongji-Shuangliu Birth Cohort. GDM was diagnosed during 24-28 weeks of gestation according to the International Association of Diabetes and Pregnancy Study Group criteria. Serum RBP4 levels in early pregnancy (6-15 weeks of gestation) were determined by ELISA assay. Multivariable conditional logistic regression models were used to analyse the association and generated the odds ratio (OR) and 95% confidence interval (CI). EMBASE and PubMed were searched up to 30 November 2020 to identify studies investigating the association between blood RBP4 levels in early pregnancy and incident GDM. RESULTS In the multivariable model with adjustment of potential risk factors, the OR comparing the extreme quartiles of serum RBP4 levels was 2.26 (95% CI: 1.34, 3.81; p for trend

Accurate fetal weight estimation is important for both fetuses and their mothers. The low birth weight (LBW, birth weight

To examine the associations of serum concentrations of adiponectin and leptin and leptin/adiponectin ratio (LAR) in early pregnancy with risk of gestational diabetes mellitus (GDM) in Chinese women. The predictive ability of those biomarkers for GDM was also assessed.Within the Tongji-Shuangliu Birth Cohort, a nested case-control study was established with 332 GDM cases and 664 matched controls at 1:2 ratio on age (±3 years) and gestational age (±4 weeks). Serum adiponectin and leptin levels were measured in early pregnancy (median gestational week, 11; range, 6-15). Conditional logistic regression models with adjustment for potential covariates were used to evaluate the associations.Multivariable-adjusted odds ratios (ORs) comparing extreme quartiles of adiponectin, leptin and LAR were 0.55 (95 % CI, 0.35, 0.85), 1.96 (95 % CI, 1.19, 3.24), and 2.72 (95 % CI, 1.63, 4.54) for GDM, respectively (All P-trend 0.02). Adding adiponectin and leptin to a conventional prediction model (including traditional risk factors and fasting glucose) increased the C-statistics from 0.708 (95 % CI, 0.674, 0.741) to 0.728 (95 % CI, 0.695, 0.760), and achieved a net reclassification improvement of 0.292.Our findings indicate that adiponectin is inversely associated with GDM, while leptin and LAR are positively associated with GDM in Chinese pregnant women.

Background: Woman with advanced-stage high-grade serous ovarian cancer (HGSOC) is likely to have a bad prognosis. Relapses are common in patients even with no evidence of disease after primary treatment. We aimed to identify the prognostic factors for disease recurrence in these patients. Methods: A nested case-control study was conducted in a large medical center in Southwest China. The primary outcome was recurrence of disease within 3 years after CR. Cox regression was used to calculate the time to event analysis in different groups.Results: Ninety- seven patients were finally included. Fifty-seven patients (58.8%) relapsed within 3 years after CR. Among all the variables, the difference in posttreatment CA-125 level was statistically significant (P ＜0.05) between the recurrent group and the progression-free group in both univariate and multivariable analysis . A cutoff value was set at the median level in the recurrent group (10 U/ml) to categorize patients into two arms. In Cox regression, the posttreatment CA-125 level was identified as a prognostic factor for recurrence with an OR of 1.05 (95% CI: 1.02-1.10, P=0.033). The median time (from initiation of treatment) until relapse was 25 months for patients whose posttreatment CA-125 levels were higher than 10 U/ml, while it was undefined for patients whose posttreatment CA-125 level were ≤ 10 U/ml. Patients with a higer posttreatment CA-125 level showed a increased risk for OC relapse compared to those with a lower posttreatment CA-125 level. Furthermore, as shown in line graphs recording serum CA-125 levels during follow-up in each recurrent case, the increments of serum CA-125 levels were delayed in recurrent OC patients who had a posttreatment CA125 level ≤ 10 U/ml compared with those with a higher CA-125 level. Conclusion: A low serum CA-125 level after primary treatment was a potential prognostic factor in women with advanced HGSOC.

Background Lipid metabolism plays an important role in the pathogenesis of diabetes. There is little evidence regarding the prospective association of the maternal lipidome with gestational diabetes mellitus (GDM), especially in Chinese populations. Objectives We aimed to identify novel lipid species associated with GDM risk in Chinese women, and assess the incremental predictive capacity of the lipids for GDM. Methods We conducted a nested case-control study using the Tongji-Shuangliu Birth Cohort with 336 GDM cases and 672 controls, 1:2 matched on age and week of gestation. Maternal blood samples were collected at 6-15 wk, and lipidomes were profiled by targeted ultra-HPLC-tandem MS. GDM was diagnosed by oral-glucose-tolerance test at 24-28 wk. The least absolute shrinkage and selection operator is a regression analysis method that was used to select novel biomarkers. Multivariable conditional logistic regression was used to estimate the associations. Results Of 366 detected lipids, 10 were selected and found to be significantly associated with GDM independently of confounders: there were positive associations with phosphatidylinositol 40:6, alkylphosphatidylcholine 36:1, phosphatidylethanolamine plasmalogen 38:6, diacylglyceride 18:0/18:1, and alkylphosphatidylethanolamine 40:5 (adjusted ORs per 1 log-SD increment range: 1.34-2.86), whereas there were inverse associations with sphingomyelin 34:1, dihexosyl ceramide 24:0, mono hexosyl ceramide 18:0, dihexosyl ceramide 24:1, and phosphatidylcholine 40:7 (adjusted ORs range: 0.48-0.68). Addition of these novel lipids to the classical GDM prediction model resulted in a significant improvement in the C-statistic (discriminatory power of the model) to 0.801 (95% CI: 0.772, 0.829). For every 1-point increase in the lipid risk score of the 10 lipids, the OR of GDM was 1.66 (95% CI: 1.50, 1.85). Mediation analysis suggested the associations between specific lipid species and GDM were partially explained by glycemic and insulin-related indicators. Conclusions Specific plasma lipid biomarkers in early pregnancy were associated with GDM in Chinese women, and significantly improved the prediction for GDM.

Background Prophylactic uterine artery embolization (UAE) combined with subsequent curettage is suggested as an effective and minimally invasive treatment strategy for cesarean scar pregnancy (CSP) with a high bleeding risk. However, the timing of curettage after UAE remains to be studied. Thus, we aimed to identify the optimal time interval to perform curettage after UAE in patients with CSP. Methods We conducted a retrospective cohort study in a large medical center for women and children in Southwest China. CSP patients treated by UAE combined with subsequent curettage were included and grouped by the treatment time interval between these two procedures. The clinical outcomes among arms were compared by univariate and multivariable analysis. Results Our study included 314 CSP patients who received this combination treatment in our department from January 2014 to December 2019. The median time interval between UAE and curettage was 48 h, with a range of 12-168 h among all participants. Thirty-two patients (10.2%) experienced intraoperative hemorrhage (blood loss ≥200 mL). Intrauterine balloon tamponade was used in 17 cases (5.4%). In 14 cases (4.5%), the procedure was converted to laparoscopy (or laparotomy). In the cohort study, patients with longer treatment intervals had more intraoperative blood loss and a higher incidence of complications than those with shorter intervals (P 72 h had an adjusted odds ratio of 3.37 (95% confidence interval: 1.40-8.09). Conclusion We suggest that curettage not be delayed longer than 72 h after UAE in this combined treatment of CSP.

Objective We aimed to examine prospective associations between circulating fatty acids in early pregnancy and incident gestational diabetes mellitus (GDM) among Chinese pregnant women. Methods Analyses were based on two prospective nested case-control studies conducted in western China (336 GDM cases and 672 matched controls) and central China (305 cases and 305 matched controls). Fasting plasma fatty acids in early pregnancy (gestational age at enrollment: 10.4 weeks(s.d., 2.0)) and 13.2 weeks (1.0), respectively) were determined by gas chromatography-mass spectrometry, and GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Groups criteria during 24–28 weeks of gestation. Multiple metabolic biomarkers (HOMA-IR (homeostatic model assessment for insulin resistance), HbA1c, c-peptide, high-sensitivity C-reactive protein, adiponectin, leptin, and blood lipids) were additionally measured among 672 non-GDM controls at enrollment. Results Higher levels of saturated fatty acids (SFAs) 14:0 (pooled odds ratio, 1.41 for each 1-s.d. increase; 95% CI: 1.25, 1.59) and 16:0 (1.19; 1.05, 1.35) were associated with higher odds of GDM. Higher levels of n-6 polyunsaturated fatty acid (PUFA) 18:2n-6 were strongly associated with lower odds of GDM (0.69; 0.60, 0.80). In non-GDM pregnant women, higher SFAs 14:0 and 16:0 but lower n-6 PUFA 18:2n-6 were generally correlated with unfavorable metabolic profiles. Conclusions We documented adverse associations of 14:0 and 16:0 but a protective association of 18:2n-6 with GDM among Chinese pregnant women. Our findings highlight the distinct roles of specific fatty acids in the onset of GDM.

Advanced and recurrent gynecological cancers are associated with poor prognosis and lack of effective treatment. The developments of the molecular mechanisms on cancer progression provide insight into novel targeted therapies, which are emerging as groundbreaking and promising cancer treatment strategies. In gynecologic malignancies, potential therapeutic targeted agents include antiangiogenic agents, poly (ADP-ribose) polymerase (PARP) inhibitors, tumor-intrinsic signaling pathway inhibitors, selective estrogen receptor downregulators, and immune checkpoint inhibitors. In this article, we provide a comprehensive review of the clinical evidence of targeted agents in gynecological cancers and discuss the future implication.

Orlistat possesses anti-tumor capacity by inducing apoptosis in ovarian cancer cells. However, the mechanism is not clearly understood. Emerging evidence indicates the overlaps between autophagy and apoptosis. In this study, we have investigated the role of autophagy in orlistat-induced apoptosis in ovarian cancer (OC) cells. The effect of orlistat on apoptosis was evaluated in SKOV3 and A2780 cell lines by MTT and TUNEL assay. The formations of autophagosomes were observed by acridine orange and GFP-LC3 fluorescence. In addition, conversions of LC3-I to LC3-II were analyzed by western blot, as well as other autophagy-related proteins. 3-Methyladenine (3-MA) was used as an autophagy inhibitor in combined treatment with orlistat. Western blot was further conducted to investigate the molecular mechanisms of orlistat-affected apoptosis and autophagy on protein level. The proliferation activities of OC cells were inhibited by orlistat in a dose-dependent manner. The expressions of cleaved-caspase 3 and 9 in orlistat-treated cells were increasing, which suggested that orlistat-induced apoptosis was caspase-dependent. At the same time, the average number of GFP-LC3 dots per cell was increased after 48 h of orlistat treatment. The expression levels of LC3-II were significantly up-regulated, as well as other autophagy-related proteins such as Vsp34, Atg7 and UVRAG. These results suggested orlistat-induced autophagy flux, which was further found involved in inhibiting the Akt/mTOR/p70S6K signaling pathway. However, combined treatment of orlistat and 3-MA significantly suppressed the cell viability, which indicated a pro-survival role of autophagy in OC cells. We suggested that orlistat had anti-cancer effect in OC cells. In addition, autophagy played a pro-survival role, suppressing which the orlistat-induced anti-cancer effect would be more significant.

An acidophilic chemolithoautotrophic bacterium named TST3 was isolated from an acid drainage of Daye Tongshankou copper mines in China. The isolate TST3 was a motile, Gram-negative, rod-shaped bacterium and could utilize elemental sulfur, thiosulfate and tetrathionate as energy sources for autotrophic growth. The phylogenetic analysis based on 16S rDNA gene sequence and amino acid sequence of sulfur oxygenase reductase indicated that strain TST3 is most closely related to Acidithiobacillus caldus. The strain exhibited unusual physiological characteristics with optimal growth at 37 °C and at an initial pH of 1.5–2.0. The dissolution of rock phosphates by A. caldus TST3 was explored in a series of bio-leaching experiments without and with pre-cultivation of the microorganism. The results showed that phosphorous was more efficiently bio-solubilized under the condition without pre-incubation in comparison to that obtained with pre-cultivation when strain TST3 was cultured in a phosphorous-limited environment. The presence of RPs exerted a positive effect on the expression of sulfur oxidation genes, bio-oxidative activity of elemental sulfur and bacterial growth. Bio-solubilization of rock phosphates was a pH-dependent phenomenon. The larger amount of phosphorous dissolved from rock phosphates without pre-cultivation coincided with the increased generation of gypsum crystals due to the relatively lower pH values from the enhanced bio-oxidization of sulfur.

Rationale Despite the development of human papillomavirus vaccines and significant improvement in cervical cancer screening over the past few years, cervical cancer remains the fourth most common cancer in women of childbearing age after breast cancer, melanoma, and thyroid cancer. Patient concerns In this case report, the patients are all cervical cancer with stage IB2 and IB3 during pregnancy, the management constitutes a major medical challenge related to the impact of treatment on both maternal and fetal outcomes. Neoadjuvant chemotherapy (NACT) is an innovative option for cervical cancer patients with stage IB2 and IB3 before cesarean delivery and radical hysterectomy, and many chemotherapeutic agents are available, cisplatin plus paclitaxel yielded good maternal and fetal outcomes to the authors' knowledge. Diagnoses Masses were discovered in the cervix of 4 pregnant women with a history of vaginal bleeding. Biopsy examination of the masses revealed cervical carcinoma, which was staged in accordance with the International Federation of Gynecology and Obstetrics (i.e., FIGO) system. Interventions The patients were treated with paclitaxel plus cisplatin, followed by cesarean delivery and radical hysterectomy. Outcomes The 4 patients were treated successfully, with no recurrence during follow-up periods of 14 to 56 months, and all of the children were doing well with no anomalies. Lessons Although further data are required, in pregnant women with invasive cervical cancer, NACT with cisplatin plus paclitaxel followed by cesarean delivery and radical hysterectomy was a practical treatment option.

The role of microRNA-18a (miRNA/miR-18a) as a tumor suppressor or promoter in a number of different types of cancer has been reported. However, to date, the expression and the effects of miR-18a in epithelial ovarian cancer (EOC) remain elusive. In the present study, the expression of miR-18a in patient EOC tissues and ovarian cancer cell lines was investigated using the reverse transcription-quantitative polymerase chain reaction. Luciferase assays and western blotting were performed to detect the potential direct targets of miR-18a. An A2780cp intraperitoneal mouse model, and Cell Counting Kit 8, flow cytometry and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assays, were used to investigate the effect of miR-18a on tumor growth in vivo and in vitro. The results indicated that the expression of miR-18a was reduced in EOC tissue and in the investigated ovarian cancer cell lines compared with non-malignant (normal) ovarian tissues and the human ovarian epithelium cell line, respectively. Overexpression of miR-18a in the A2780s and A2780cp cell lines significantly induced cell cycle arrest and apoptosis. It was demonstrated that miR-18a directly targets tumor protein p53-regulating inhibitor of apoptosis gene 1 and inositol phosphate multikinase, hence regulating the expression of downstream targets. The A2780cp intraperitoneal mouse model was employed and the results indicated that miR-18a may inhibit A2780cp intraperitoneal tumor growth in vivo by inhibiting proliferation and inducing apoptosis. Together, the results of the present study demonstrated that miR-18a has a role as a tumor suppressor by inhibiting proliferation and inducing apoptosis. Assessment of miR-18a expression may provide a novel method for diagnosis and be a therapeutic target for EOC.

Rationale: Post-hysterectomy collision tumors of the vulva has rarely been reported. Though long-term HPV infection may induce vulva tumor, but the relationship between HPV infection and collision vulva tumor is not clear. And there are no clear rules of the post-hysterectomy cancer surveillance for human papilloma virus (HPV) long-term infections. So here we first report a case of post-hysterectomy rare collision vulva tumor with long-term HPV infection composed of squamous cell carcinoma of the labia major and adenosquamous carcinoma of bartholin gland and hope to bring new direction to our future research. Patient concerns: A 48-year-old woman with long-term HPV infection, 3 years after hysterectomy, gravida 3, para 2, was admitted to our hospital with complaints of a 4-month history of an itching vulva ulceration. An anabrosis was located on the surface of the solid mass of the bartholin gland at the posterior part of the right labium and the right inguinal lymph nodes were palpable. Result of the incisional biopsy of the ulcer area at local hospital was atypical squamous cells couldn’t exclude high-grade squamous intraepithelial lesion (ASC-H). Subsequently more authoritative pathological consultation results suggested squamous cell carcinoma of the vulva. Diagnoses: Post-hysterectomy collision vulva tumor with long-term HPV infection composed of squamous cell carcinoma of the labia major and adenosquamous carcinoma of bartholin gland. Interventions: The extensive excision of the vulva, bilateral inguinal lymph nodes dissection, and local skin flap transposition surgeon was done to this patient. The final certificate diagnosis was: vulvar tumor T1bM0N0 composed of squamous cell carcinoma of the labia major and adenosquamous carcinoma of bartholin gland; HPV infection; post hysterectomy, and bilateral salpingectomy. Outcomes: The patient recovered well after surgery, and consequently received 6 courses of TC (paclitaxel + carboplatin) chemotherapy, and 9 months and 13 days followed up. So far patient recorded as complete response (CR). Lessons: Collision vulva tumor occurred post-hysterectomy is extremely rare. It is most likely related to long-term HPV infection, which suggests us should to modify the manner of the post-hysterectomy cancer surveillance for HPV long-term infections. For patients with high-risk HPV infection, even if the cytology results are negative, we may should perform colposcopy and vulva biopsy more positively to prevent the disease from progressing into cancer. And the pathogenesis of relationship between HPV infection and collision vulva tumor is still need further investigation.

Human papillomavirus (HPV) is the most common sexually transmitted infection, exhibiting a tropism for the epidermis and mucosae. The link between persistent HPV infection and malignancies involving the anogenital tract as well as the head and neck has been well‑established, and it is estimated that HPV‑related cancers involving various anatomical sites account for 4.5% of all human cancers. Current prophylactic vaccines against HPV have enabled the prevention of associated malignancies. However, the sizeable population base of current infection in whom prophylactic vaccines are not applicable, certain high‑risk HPV types not included in vaccines, and the vast susceptible population in developing countries who do not have access to the costly prophylactic vaccines, put forward an imperative need for effective therapies targeting persistent infection. In this article, the life cycle of HPV, the mechanisms facilitating HPV evasion of recognition and clearance by the host immune system, and the promising therapeutic strategies currently under investigation, particularly antiviral drugs and therapeutic vaccines, are reviewed.

To analyze risk factors associated with heterotopic pregnancy and the uterine pregnant outcome of those patients after surgery.We retrospectively analyzed 22 patients diagnosed as HP after in vitro fertilization (IVF) between January 2015 and December 2018.HP was diagnosed at gestation age of 55.4 ± 11.8 days. HP were presented as irregular vaginal bleeding, abdominal pain, and sometimes no symptoms. 81.8% of ectopic lesion in HP occurred at fallopian tubes, especially ampullary; cornual pregnancy takes up 13.6%. Compared with clinical intrauterine pregnancy (IUP), IVF with tubal infertility factors had higher risks of HP (OR 4.185, 95% CI 1.080- 16.217); IVF with pelvic adhesion also had higher risks of HP (OR 5.552 95% CI 1.677-18.382); IVF with more than 2 embryos transferred increased risks of HP (OR 23.253, 95% CI 1.804-299.767). The abortion rates of surgery-treated HP and IUP after IVF were 27.8% versus 10.3% (P = .042).These results demonstrate IVF with tubal infertility, pelvic adhesion or multiembryos transfer are risk factors of HP. Furthermore, surgery could induce abortion.