DNA methylation characteristics associated with chemotherapy resistance in epithelial ovarian cancer.

Objective: The high mortality rate of epithelial ovarian cancer (EOC) is often attributed to the frequent development of chemoresistance. DNA methylation is a predictive biomarker for chemoresistance. Methods: This study utilized DNA methylation profiles and relevant information from GEO and TCGA to identify different methylated CpG sites (DMCs) between chemoresistant and chemosensitive patients. Subsequently, we constructed chemoresistance risk models with DMCs. The genes corresponding to candidate DMCs in chemoresistance risk models were further analyzed to identify different methylated gene symbols (DMGs) associated with chemoresistance. The DMGs that showed a strong correlation with the corresponding DMCs were analyzed through immunohistochemistry. Results: Compared to chemosensitive EOC patients, chemoresistant patients showed 423 hypermethylated CpGs and 1445 hypomethylated CpGs. The chemoresistance risk models based on DMCs have shown the improved predictive ability for chemoresistance in EOC (AUC = 65.0-76.2%). The methylations of cg25510164, cg13154880, cg15362155 and cg08665359 were strongly associated with decreased risk of chemoresistance. Conversely, the methylation of cg08872590 and cg14739437 significantly increased the risk. We identified 13 DMGs, from 47 DMCs corresponding genes, between chemosensitive and chemoresistant samples. Among the DMGs, the expression levels of DDR2 and OPCML exhibited strong correlations with the corresponding DMCs. DDR2 and OPCML both showed enhanced expression in chemoresistant ovarian microarray tissue. Conclusions: Hypomethylated CpGs may play a significant role in DNA methylation associated with chemoresistance in EOC. The epigenetic modification of DDR2 could have important implications for the development of chemoresistance. Our study provides valuable insights for future research on DNA methylation in the chemoresistance of EOC.

Association Between Serum Ferritin Levels in Early Pregnancy and Thyroid Function and Pregnancy Outcomes in Chinese Population.

Background: The relationship of iron deficiency and thyroid hormone has been researched a lot among pregnant or other healthy population. However, invisible iron deficiency, namely shortage of serum ferritin (sFer) level, has been barely investigated among Chinese pregnant women. This study aimed to explore the effects of sFer status on thyroid function and pregnancy outcomes in a population-based upper first-class hospital. Methods: A total of 781 singleton pregnant women of gestation in Shanghai General Hospital took part in this retrospective cohort study. The participants were divided into four groups by quartiles of serum ferritin levels (Q1-4). Binary logistic regressions were used to examine the strength of association between the different traits and the serum ferritin (sFer) quartiles separately, where Q1 (lowest ferritin quartile) was taken as the base reference. One-way ANOVA was adopted to compare the averages of the different variables across sFer quartiles. Categorical measures were compared by Fisher exact test or chi-square test. Results: As the sFer concentration rises, incidence of premature birth (15.8%vs 12.3% vs 9.20% vs 6.20% p = 0.016) as well as threatened miscarriage (14.8% vs 7.2% vs 8.70% vs 6.70% p = 0.021) presented a downward trend. Compared with the other sFer group, subjects of the low sFer group were older, more often to be found to have lower serum γT3 and FT4 levels in early pregnancy but not in middle pregnancy. Conclusion: sFer concentration in the first trimester can affect thyroid function. The correction of invisible iron deficiency with inadequate sFer status prior to pregnancy or during early pregnancy is imperative, not only to prevent anemia, but also for maintaining optimum thyroid function and normal fetal development. For clinicians, sFer status of pregnant women should be attached great importance apart from attention to iron level.

PFMT relevant strategies to prevent perineal trauma: a systematic review and network meta-analysis.

BACKGROUND: Most women suffer from perineal trauma during childbirth, whether it is natural tears or episiotomy. OBJECTIVES: To perform a systematic review and network meta-analysis investigating the effectiveness of different PFMT relevant strategies in the prevention of perineal trauma. SEARCH STRATEGY: PubMed, Embase, the Cochrane Library, CINAHL, CNKI, CBM, WANFANG DATABASE, and ClinicalTrials.gov were searched for citations published in any language from inception to 1 July 2021. SELECTION CRITERIA: Randomized controlled trials (RCTs) of PFMT relevant prevention strategies for preventing perineal trauma during childbirth. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers. Relative treatment effects were estimated using network meta-analysis (NMA). MAIN RESULTS: Of 12 632 citations searched, 21 RCTs were included. Comparing with usual care, "PFMT combine with perineal massage" and PFMT alone showed more superiority in intact perineum (RR = 5.37, 95% CI: 3.79 to 7.60, moderate certainty; RR = 2.58, 95% CI 1.34-4.97, moderate certainty, respectively), episiotomy (RR = 0.26, 95% CI 0.14-0.49, very low certainty; RR = 0.63, 95% CI 0.45-0.90, very low certainty, respectively), and OASIS (RR = 0.35, 95% CI 0.16-0.78, moderate certainty; RR = 0.49, 95% CI 0.28-0.85, high certainty, respectively). "PFMT combine with perineal massage" showed superiority in reducing perineal tear (RR = 0.41, 95% CI 0.20-0.85, moderate certainty). CONCLUSIONS: In view of the results, antenatal "PFMT combine with perineal massage" and PFMT were effective strategies for the prevention of perineal trauma.

Lubricant for reducing perineal trauma: A systematic review and meta-analysis of randomized controlled trials.

AIM: To assess the effect of lubricants on reducing perineal trauma during vaginal delivery. METHODS: PubMed, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, China Biology Medicine disc, WanFang databases, and ClinicalTrials.gov, were searched for literature up to 25 June 2021. Randomized controlled trials published in English or Chinese that compared the vaginal application of lubricant with standard care for women were included. Two reviewers independently performed study screening, data extraction, risk of bias assessment, and certainty of evidence assessment. Pooled effect sizes and corresponding 95% confidence intervals (CI) were calculated using meta-analysis. RESULTS: Nineteen trials enrolling 5445 pregnant women were included. Compared with standard care, women using lubricants had a lower incidence of perineal trauma (risk ratio [RR] 0.84, 95% CI 0.76-0.93; low certainty evidence), second-degree perineal laceration (RR 0.72, 95% CI 0.64-0.82; moderate certainty evidence) and episiotomy (RR 0.77, 95% CI 0.62-0.96; very low certainty evidence), and had a shorter duration of the second-stage labor (MD -13.72 min, 95% CI -22.68 to -4.77; very low certainty evidence). CONCLUSION: Lubricants might reduce the incidence of perineal trauma, especially second-degree perineal laceration, and shorten the duration of the second-stage labor. More well-designed studies will continue developing high-quality evidence in this field.

Efficacy and safety of immune checkpoint inhibitors combined anti-angiogenic therapy in patients with unresectable hepatocellular carcinoma: A meta-analysis.

BACKGROUND: This study aimed to compare the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with antiangiogenic agents in patients with unresectable hepatocellular carcinoma (HCC). METHODS: We conducted a systematic literature search of articles published between the establishment of the database and February 2022. Data were extracted and analyzed using STATA 14.0. RESULTS: Six randomized controlled trials (RCTs) (980 patients for combination therapy and 565 patients for monotherapy) and 5 single-arm studies (246 patients for ICIs combination therapy) were enrolled. The objective response rate (ORR) and disease control rate (DCR) were 26% and 70%, respectively, after ICIs combination therapy. Compared with monotherapy in RCTs, ICIs combination therapy resulted in higher progression-free survival (PFS) and overall survival (OS), but also increased the incidence of adverse events (AEs). Increased incidences of fatigue, hypertension, hyperbilirubinemia, proteinuria, and nausea were more common after ICIs combination therapy. CONCLUSION: The analysis results reveal that ICI-combined anti-angiogenesis therapy has higher efficacy than either ICIs or anti-angiogenesis options for unresectable HCC, but it is necessary to manage the AEs.

Serum miRNA-204-5p as a potential non-invasive biomarker for the diagnosis of endometrial cancer with sentinel lymph node mapping.

The lymph node status is one of the most critical prognostic factors used in determining adjuvant treatment in endometrial cancer (EC). Lymphadenectomy is associated significant surgical and postoperative risks. The use of sentinel lymph node mapping (SLNM) has emerged as an alternative method to complete lymphadenectomy in EC. However, there remains controversy surrounding the use of SLNM in high-risk disease and its false-negative rate (3%). The authors previously identified miR-204-5p as a tumor-suppressor miRNA associated with lymph node metastasis in EC tissues. The present study demonstrated that serum miR-204-5p in patients with EC has the potential for use as an early diagnostic biomarker combined with SLNM to assess the lymph node status prior to surgery. The present study also aimed to identify the optimal cut-off value of serum miR-204-5p. The relative expression levels of miR-204-5p were detected using reverse transcription-quantitative PCR in the serum of 52 patients with EC (total SLNM). A total of 20 patients diagnosed with ovarian cysts, 20 patients diagnosed with myoma, and 20 participants diagnosed with endometrial polyps or endometrial hyperplasia were included as the control group. miR-204-5p expression was also detected in lymph node tissues using in situ hybridization. The results revealed that serum miR-204-5p expression was downregulated in patients with EC compared with its expression in patients with benign ovarian cysts, myoma and endometrial hyperplasia/polyps (P<0.01). In accordance with the final pathological evaluation, patients with EC with a positive SLN status had a significantly lower level of miR-204-5p compared with those with a negative SLN status (P<0.01). The area under the ROC curve of miR-204-5p was 0.923, 95% CI (0.847-1.000), and the diagnostic value had a sensitivity of 87.2% and specificity of 80.0%, with an optimal cut-off value of 0.253. On the whole, it was demonstrated that a lower miR-204-5p expression is associated with lymph node metastasis in these SLN(+) EC tissues, indicating that the downregulation of serum miR-204-5p in patients with EC has potential for use as an early diagnostic biomarker combined with SLNM. In addition, with a cut-off value of 0.253, it appeared optimal for the prediction of lymph node metastasis in EC.

Influence of painless delivery on the maternal and neonatal outcomes under the guidance of new concept of labor.

OBJECTIVE: To explore the possible influence of painless delivery on the maternal and neonatal outcomes under the guidance of new concept of labor. METHODS: Primiparas who received painless delivery in our hospital were selected for this retrospective clinical study. They were divided into two groups, the experimental group and the control group. The experimental group received painless delivery with the application of new labor management, while the control group received painless delivery with the application of routine labor management. The maternal and neonatal outcomes (postpartum hemorrhage, postpartum urinary retention, fetal distress and neonatal asphyxia), the duration of first and second stages of labor, the total duration of labor, medical intervention during first stage of labor such as artificial rupture of membranes or the use of oxytocin, visual analog scale (VAS) scores upon complete cervical dilation, delivery method and maternal satisfaction rate were compared between the two groups. RESULTS: Among the 208 primiparas, 112 cases were enrolled in the control group and 96 cases in the experimental group. There were no significant differences in the incidences of postpartum hemorrhage, postpartum urinary retention, fetal distress and neonatal asphyxia between the two groups (all P>0.05). The duration of first and second stages of labor and the total duration of labor in the control group were shorter than those in the experimental group (all P<0.001). The rates of artificial rupture of membranes and intravenous use of oxytocin in the control group were higher than those in the experimental group (both P<0.05). The VAS scores upon complete cervical dilation in the control group were significantly higher than those in the experimental group (P<0.05). The vaginal delivery and maternal satisfaction rates were significantly lower in the control group than in the experimental group (both P<0.05). CONCLUSION: Painless delivery under the guidance of new concept of labor has no significant influence on the maternal and neonatal outcomes. Instead, it can prolong the labor process, provide more delivery time for pregnant women, reduce the intervention measures during delivery, decrease the delivery pain and finally increase the natural delivery rate and their satisfaction with delivery, which is worth wide promotion in clinical practice.

Inhibition of Expression of the S100A8 Gene Encoding the S100 Calcium-Binding Protein A8 Promotes Apoptosis by Suppressing the Phosphorylation of Protein Kinase B (Akt) in Endometrial Carcinoma and HEC-1A Cells.

BACKGROUND The aim of this study was to investigate the expression and silencing of the S100A8 gene, which encodes the S100 calcium-binding protein A8 (S100A8), and apoptosis and phosphorylation of protein kinase B (Akt) in tissue samples of endometrial carcinoma and HEC-1A endometrial adenocarcinoma cells in vitro. MATERIAL AND METHODS Immunohistochemistry (IHC) was used to detect expression of the S100A8 protein in 74 tissue samples of endometrial cancer and 22 normal endometrial tissue samples. A stable S100A8 gene knockdown cell line was constructed using lentiviral packing short hairpin RNA (shRNA) transfected into HEC-1A cells. S100A8 mRNA and S100A8 protein levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. The effects of expression of the S100A8 gene by endometrial cancer cells was investigated by the MTT assay, cell cycle and apoptotic assays, qRT-PCR, and Western blotting. RESULTS IHC showed high levels of expression of S100A8 protein in endometrial carcinoma tissues, and HEC-1A adenocarcinoma cells (in G1 and G2). Increased expression of S100A8 protein was found endometrial cancer tissues compared with normal endometrial tissues (79.7% vs. 4.5%). S100A8 gene knockdown reduced cell proliferation in the HEC-1A cells compared with control cells, induced cell apoptosis, inhibited the phosphorylation of protein kinase B (Akt), and induced the expression of pro-apoptotic genes, including the cytochrome C gene, CYCS, BAD, BAX, FOXO1, FOXO3, CASP9, and CASP3. CONCLUSIONS In endometrial carcinoma cells, down-regulation of the S100A8 gene induced cell apoptosis via inhibition of the phosphorylated or active form of protein kinase B (Akt).

Role of endometrial cancer abnormal MMR protein in screening Lynch-syndrome families.

OBJECTIVE: To identify patients with endometrial cancer with potential Lynch-related DNA mismatch repair (MMR) protein expression defects and to explore the role of these defects in screening for LS. METHODS: Endometrial cancers from 173 patients recruited to the Nanchong Central Hospital were tested for MMR (MLH1, MSH2, PMS2, and MSH6) protein expression using immunohistochemistry (IHC). RESULTS: In the 173 tumor tissue samples, the expression loss rates of MSH6, MSH2, PMS2 and MLH1 protein were 16.18% (28/173), 12.14% (21/173), 7.51% (13/173) and 5.78% (10/173), respectively. The total loss rate of MMR protein was 29.89% (27/87). There were 19 patients with a family history of cancer, of which 18 patients demonstrated loss of expression of MMR protein. In the 22 abnormal MMR patients without family history, five families were found to have Lynch-associated cancer (colorectal cancer, endometrial cancer, ovarian cancer, stomach cancer) after follow-up for two years. CONCLUSION: MMR proteins play an important role in the progress of endometrial cancer. The routine testing of MMR proteins in endometrial cancer can contribute to the screening of LS families, especially small families.