Effects of rosuvastatin on serum asymmetric dimethylarginine levels and incidence of long-term cardiovascular events in patients with hyperlipidaemia and H-type hypertension.

Aims/Background Rosuvastatin is a common lipid-lowering statin on the market, but its impact on the incidence of long-term cardiovascular events is not well clarified. This study aimed to explore the effects of rosuvastatin on serum asymmetric dimethylarginine (ADMA) levels and the incidence of long-term cardiovascular events in patients with hyperlipidaemia and H-type hypertension. Methods This retrospective study included 158 patients with hyperlipidaemia and H-type hypertension who were treated in the Hebei Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine from August 2015 to August 2016. The patients were divided into an occurrence group and a non-occurrence group according to the occurrence of long-term cardiovascular events following the resuvostatin treatment. The changes in blood lipids, blood pressure, serum ADMA levels and vascular endothelial function indexes before and after treatment were compared, and the effect of ADMA on the occurrence of long-term cardiovascular events and its predictive efficacy were analysed using the Spearman correlation test and receiver operating characteristics (ROC) curve. Results After treatment, the levels of serum total cholesterol, low-density lipoprotein cholesterol, triglyceride, serum ADMA and blood pressure became significantly lower (p < 0.001), with high-density lipoprotein cholesterol exhibiting no significant difference. Twenty-two cases developed long-term cardiovascular events after the treatment, with an incidence of 13.92%. The occurrence group had significantly higher serum ADMA levels than the non-occurrence group (p < 0.001). The rosuvastatin treatment also lowered the levels of endothelin-1 and high-sensitivity C-reactive protein and increased the nitric oxide level (p < 0.001). Spearman correlation analysis showed that serum ADMA levels were positively correlated with the occurrence of long-term cardiovascular events (r=0.462, p < 0.001). Meanwhile, according to the ROC curve, serum ADMA had a good predictive efficacy for long-term cardiovascular events, with an area under the curve of 0.885 (95% confidence interval 0.808-0.963; p < 0.001). Conclusion Rosuvastatin can reduce ADMA levels and exert vascular protective effects. The increase in serum ADMA levels is closely related to the occurrence of long-term cardiovascular events in patients with hyperlipidaemia and H-type hypertension, serving as a potential clinical predictor to guide disease prevention and treatment.

Identification and analysis of biomarkers associated with oxidative stress and ferroptosis in recurrent miscarriage.

Recurrent miscarriage (RM) has a huge impact on women. Both oxidative stress and ferroptosis play an important role in the pathogenesis of RM. Hence, it was vital to screen the ferroptosis oxidation-related biomarkers for the diagnosis and treatment of RM. We introduced transcript data to screen out differentially expressed genes (DEGs) in RM. Ferroptosis oxidation-related differentially expressed genes were obtained by overlapping DEGs and oxidative stress related genes with correlations >0.9 with ferroptosis-related genes. Least Absolute Shrinkage and Selectionator operator regression and support vector machine based recursive feature elimination algorithm were implemented to screen feature genes. The biomarkers associated with ferroptosis oxidation were screened via receiver operating characteristic curve analysis. We finally analyzed the competing endogenous RNAs regulatory network and potential drugs of biomarkers. We identified 1047 DEGs in RM. Then, 9 ferroptosis oxidation-related differentially expressed genes were obtained via venn diagram. Subsequently, 8 feature genes (PTPN6, GJA1, HMOX1, CPT1A, CREB3L1, SNCA, EPAS1, and TGM2) were identified via machine learning. Moreover, 4 biomarkers associated with ferroptosis oxidation, including PTPN6, GJA1, CPT1A, and CREB3L1, were screened via receiver operating characteristic curve analysis. We constructed the '227 long noncoding RNAs-4 mRNAs-36 microRNAs' network, in which hsa-miR-635 was associated with CREB3L1 and PTPN6. There were 11 drugs with therapeutic potential on 3 biomarkers associated with ferroptosis oxidation. We also observed higher expression of CPT1A and CREB3L1 in RM group compared to the healthy control group by quantitative real-time reverse transcription polymerase chain reaction. Overall, we obtained 4 biomarkers (PTPN6, GJA1, CPT1A, and CREB3L1) associated with ferroptosis and oxidative stress, which laid a theoretical foundation for the diagnosis and treatment of RM.

Characteristics of Different Obesity Metabolic Indexes and their Correlation with Insulin Resistance in Patients with Polycystic Ovary Syndrome.

This study is aimed to investigate the characteristics of different obesity metabolic indexes [body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), cardiometabolic index (CMI), body roundness index (BRI), visceral adiposity index (VAI), and lipid aggregation products (LAP)] and their correlation with insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS). The study was conducted on 140 subjects with PCOS and 133 control subjects aged 18-44 years. According to insulin resistance index (HOMA-IR) ≥ 2.69 and HOMA-IR < 2.69, PCOS group members were divided into insulin resistance group and non-insulin resistance group. Anthropometric and serological characteristics of the population with PCOS focused on calculating different obesity metabolic indexes and HOMA-IR. BMI, WC, WHR, WHtR, CMI, BRI, VAI, and LAP were significantly higher in PCOS patients than in the control group, and the differences were all statistically significant (P < 0.05); In the insulin resistance group of PCOS patients, BMI, WC, WHR, WHtR, CMI, BRI, VAI, and LAP were significantly higher than in the non-insulin resistance group (P < 0.05). In PCOS patients, BMI (r = 0.658, P < 0.001), WC (r = 0.0.662, P < 0.001), WHR (r = 0.377, P < 0.001), WHtR (r = 0.660, P < 0.001), CMI (r = 0.698, P < 0.001), BRI (r = 0.757, P < 0.001), VAI (r = 0.640, P < 0.001), and LAP (r = 0.767, P < 0.001) were positively correlated with IR. Obesity metabolic indexes associated with PCOS were elevated in the PCOS group compared to the control group, and in the PCOS insulin-resistant group compared to the non-insulin resistant group. Novel obesity metabolic indexes, especially CMI, BRI and LAP, might be more appropriate for evaluating the risk of concurrent IR in PCOS.

The Relationship Between Anti-Müllerian Hormone and Body Composition Components in Patients With Polycystic Ovary Syndrome of Reproductive Age.

To investigate and analyze the relationship between body composition components, including Body Mass Index (BMI), body fat percentage, waist-to-hip ratio, and visceral fat index, and Anti-Müllerian Hormone (AMH) levels in patients diagnosed with Polycystic Ovary Syndrome (PCOS), The study aims to provide a comprehensive understanding of how various aspects of body composition impact AMH levels. This study enrolled 167 women with PCOS of reproductive age. Serum AMH level and body composition were measured, and the correlation between body composition elements and AMH levels was analyzed. AMH level was negatively correlated with body weight, BMI, fat-free mass, body fat percentage, waist-hip ratio, and visceral fat level (P < 0.01). And negatively correlated with skeletal muscle ratio ( P = 0.003). AMH level remained significantly associated with BMI ( P = 0.028), body fat percentage ( P = 0.040), waist-hip ratio (P = 0.003), and visceral fat level ( P = 0.040) after age was included and a multiple linear regression model was established. After adjusting for age, BMI was still significantly associated with AMH (P = 0.029). At the same time, there was no obvious linear correlation between BSA and AMH. The results showed that AMH levels were significantly different among the three groups (9.53 ± 5.12 vs 6.98 ± 3.35 vs 6.38 ± 3.38, P < 0.001; ng/mL). The level of AMH in the non-central obesity group was higher than that in the central obesity group (9.68 ± 5.22vs7.09 ± 3.83, P < 0.001; ng/mL). In PCOS patients, those who are more obese have lower AMH levels, indicating poorer Ovarian Reserve. BMI may independently affect AMH levels, apart from age, BSA, and other factors. Ovarian function in centrally obese patients is poorer than in those with non-central obesity.

Dehydroepiandrosterone with a high-fat diet treatment at inducing polycystic ovary syndrome in rat model.

OBJECTIVE: This study aimed to evaluate the effects of dehydroepiandrosterone (DHEA) and DHEA combined with a high-fat diet (HFD) treatment of reproductive and endocrine metabolism in rats and then identify an ideal model of polycystic ovary syndrome (PCOS). METHODS: Three-week-old female Sprague-Dawley rats were injected subcutaneously with DHEA or oil, fed with or without a HFD, for 21 days, during which body weight, feed intake, and estrous cycle monitoring were carried out. Fasting blood glucose was measured, and serum fasting insulin, testosterone, dihydrotestosterone (DHT), estradiol, progesterone, luteinizing hormone (LH), anti-Müllerian hormone (AMH), and follicle-stimulating hormone (FSH) were estimated by ELISA. Serum total cholesterol (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by colorimetric assay. Whereas, histologic changes in rat ovaries were evaluated by H&E staining. Ovarian steroid hormone synthases and their protein levels (StAR, 3ß-HSD2, 17ß-HSD1, CYP11A1, CYP17A1, and CYP19A1) were examined by Western blotting. RESULTS: Both DHEA and DHEA + HFD-treated rats lost a regular estrous cycle; had polycystic ovarian changes, significantly higher serum fasting insulin and testosterone levels; and increased ovarian StAR, 3ß-HSD2, and CYP11A1 protein levels. Additionally, rats in the DHEA + HFD-treated group were obese; had elevated fasting blood glucose, TG, DHT, AMH levels and LH:FSH ratios; increased ovarian 17ß-HSD1 protein levels. CONCLUSION: DHEA combined with HFD treatment is more effective at inducing PCOS than DHEA alone. The reproductive and endocrine metabolic aspects of this method are more consistent with the clinical characteristics of PCOS patients.

Relationship between serum apelin, visfatin levels, and body composition in Polycystic Ovary Syndrome patients.

OBJECTIVE: To investigate the relationship between body composition and serum visfatin and apelin levels in patients with polycystic ovary syndrome (PCOS). METHODS: In this prospective observational study, the differences in body composition, levels of gonadal hormone concentrations, glucose metabolism, apelin, and visfatin were compared between PCOS patients and the control group. PCOS patients were further divided into different subgroups according to different obesity criteria and the differences between serum visfatin and apelin levels in different subgroups were compared. Finally, the correlation of serum visfatin levels and apelin levels with body composition, and metabolism-related indicators in PCOS patients was explored. RESULTS: A total collected 178 cases of PCOS patients and 172 cases of healthy women (control group) between 2020 July and 2021 November. In PCOS patients, their weight, Body Mass Index (BMI), Waist Hip Rate (WHR), Fat-Free Mass Index (FFMI), Percent Body Fat (PBF), Fat mass index (FMI), PBF of Arm, PBF of Leg, PBF of the Trunk, Visceral Fat Level (VFL), fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Luteinizing hormone (LH) were significantly higher than in the control group (all P < 0.001), Percent Skeletal Muscle (PSM), PSM of Leg, and PSM of the Trunk were significantly decreased than in the control group (all P < 0.001). The PCOS patients had significantly higher serum visfatin levels and apelin levels compared with the control group (all P < 0.001). In PBF > 35 % PCOS patients, the apelin and visfatin levels were significantly higher than the PBF ≤ 35 % PCOS patients. In WHR ≥ 0.85 and BMI ≥ 24 kg/m2 PCOS patients, the visfatin levels were significantly higher than the WHR < 0.85 and BMI < 24 kg/m2 PCOS patients. Serum apelin and visfatin positively correlated with BMI level, WHR, FFMI, PBF, FMI, PBF of arms, PBF of legs, PBF of the trunk, VFL, FBG, HOMA-IR index and negatively correlated with PSM, PSM of legs, and PSM of the trunk (all P < 0.001). CONCLUSIONS: Compared with healthy women, Patients with PCOS have an increased fat content in various parts of the body, reduced skeletal muscle content, and are often complicated by metabolic abnormalities. Serum visfatin and apelin correlated not only with obesity, fat mass, and fat distribution but also with muscle mass and distribution. It may be possible to reduce the long-term risk of metabolic disease in PCOS through the monitoring and management of the body composition in PCOS patients or to reflect the therapeutic effect of PCOS.

Autoantibodes to GP210 are a metric for UDCA responses in primary biliary cholangitis.

Objectives: Antibodies to gp210 and sp100 are specific and unique anti-nuclear autoantibodies (ANAs) associated with primary biliary cholangitis (PBC). Importantly the presence of anti-gp210 and anti-sp100 responses is indicative of poor clinical outcomes. However, the utility of measuring titers of these antibodies remains unclear. Materials and methods: Using the in-house purified gp210 (HSA108-C18) and sp100 (amino acid position 296-386), we quantitatively measured serum autoantibodies to gp210 and sp100 using chemiluminescence immunoassay (CLIA) in a very large cohort of 390 patients with PBC, including 259 cases with no prior ursodesoxycholic acid (UDCA) treatment and 131 cases with UDCA treatment. We also analyzed serial changes in anti-gp210 and anti-sp100 levels in 245 sequential samples from 88 patients. Results: In our cross-sectional analysis, we detected anti-gp210 immunoglobulin G (IgG) and anti-sp100 IgG autoantibodies in 129 out of 390 (33.1%) and 80 out of 390 (20.5%) PBC patients, respectively. Multivariate analysis revealed that serum IgG (st.ß = 0.35, P = 0.003) and gamma-glutamyltransferase (GGT) (st.ß = 0.23, P = 0.042) levels at baseline were independently associated with anti-gp210 concentrations. In serial testing, we observed significant fluctuations in anti-gp210 antibody levels. These fluctuations reflected responsiveness to UDCA therapy, particularly in anti-gp210-positive patients with initially lower concentrations in the stages of disease. Conclusions: Our study reflects that quantitative changes of anti-gp210 antibody are indicative of UDCA responses. There is a great need for newer metrics in PBC and we suggest that a more detailed and longer study of these unique ANAs is warranted.

Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis.

BACKGROUND: Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C. butyricum on PNS inflammation through the gut-kidney axis. METHOD: BALB/c mice were randomly divided into 4 groups: normal control group (CON), C. butyricum control group (CON+C. butyricum), PNS model group (PNS), and PNS with C. butyricum group (PNS+C. butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C. butyricum for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated. RESULTS: Since the successful modeling of the PNS, the 24 h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN), urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C. butyricum treatment. The crucial Th17/Tregs axis in PNS inflammation also was proved to be effectively regulated by C. butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C. butyricum could regulate the composition of the intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C. butyricum treatment increased the contents of acetic acid, propionic acid, butyric acid in feces, acetic acid, and valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota, and associated metabolic SCFAs in the gut-kidney axis. CONCLUSION: C. butyricum regulates Th17/Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a safe and inexpensive therapeutic agent for PNS.

TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.

Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.

Butyrate alleviates alcoholic liver disease-associated inflammation through macrophage regulation and polarization via the HDAC1/miR-155 axis.

BACKGROUND: We recently found that butyrate could ameliorate inflammation of alcoholic liver disease (ALD) in mice. However, the exact mechanism remains incompletely comprehended. Here, we examined the role of butyrate on ALD-associated inflammation through macrophage (Mψ) regulation and polarization using in vivo and in vitro experiments. METHODS: For in vivo experiments, C57BL/6J mice were fed modified Lieber-DeCarli liquid diets supplemented with or without ethanol and sodium butyrate (NaB). After 6 weeks of treatment, mice were euthanized and associated indicators were analyzed. For in vitro experiments, lipopolysaccharide (LPS)-induced inflammatory murine RAW264.7 cells were treated with NaB or miR-155 inhibitor/mimic to verify the anti-inflammatory effect and underlying mechanism. RESULTS: The administration of NaB alleviated pathological damage and associated inflammation, including LPS, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß levels in ALD mice. NaB intervention restored the imbalance of macrophage polarization by inhibiting inducible nitric oxide synthase (iNOS) and elevating arginase-1 (Arg-1). Moreover, NaB reduced histone deacetylase-1 (HDAC1), nuclear factor kappa-B (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and miR-155 expression in ALD mice, but also increased peroxisome proliferator-activated receptor-γ (PPAR-γ). Thus, MiR-155 was identified as a strong regulator of ALD. To further penetrate the role of miR-155, LPS-stimulated RAW264.7 cells co-cultured with NaB were treated with the specific inhibitor or mimic. Intriguingly, miR-155 was capable of negatively regulated inflammation with NaB intervention by targeting SOCS1, SHIP1, and IRAK-M genes. CONCLUSION: Butyrate suppresses the inflammation in mice with ALD by regulating macrophage polarization via the HDAC1/miR-155 axis, which may potentially contribute to the novel therapeutic treatment for the disease.

Oncological and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection: A systematic review and meta-analysis.

INTRODUCTION: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR). MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR). RESULTS: Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth). CONCLUSIONS: Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement.

Association of CCR6 functional polymorphisms with Primary Biliary Cholangitis.

The biliary epithelial cells release CC chemokine receptor 6 (CCR6) ligand 20 (CCL20), leading to recruitment of CCR6+ T cells and subsequent infiltration into the biliary epithelium in primary biliary cholangitis patients. Previous genome-wide multi-national meta-analysis, including our Han Chinese cohort, showed significant association of CCR6 and CCL20 single nucleotide polymorphisms (SNP) with PBC. We report here that significantly associated SNPs, identified in the CCR6 locus based on our Han Chinese genome-wide association study, can be separated into "protective" and "risk" groups, but only "risk" SNPs were confirmed using a separate Han Chinese PBC cohort. Only weak association of CCL20 SNPs was observed in Han Chinese PBC cohorts. Fine-mapping and logistical analysis identified a previously defined functional variant that, leads to increased CCR6 expression, which contributed to increased genetic susceptibility to PBC in Han Chinese cohort.

The Hippo pathway in endometrial cancer: a potential therapeutic target?

Endometrial cancer, one of the most prevalent malignant cancers tumors of the female reproductive tract, has been increasing in incidence and mortality rates around the world. The Hippo pathway, one of the eight traditional human cancer signaling pathways, is an intricate signaling network that regulates cell proliferation, differentiation, and migration as well as restricting organ size in response to a range of intracellular and extracellular signals. Inhibiting the Hippo pathway results in aberrant activation of its downstream core component YAP/TAZ, which can enhance cancer cells' metabolism and maintain their stemness. Additionally, the Hippo pathway can modulate the tumor microenvironment and induce drug resistance, where tumorigenesis and tumor progression occur. However, the Hippo pathway has been little researched in endometrial cancer. Here, we aim to review how the Hippo pathway contributes to the onset, development and the potential treatment of endometrial cancer with the aim of providing new therapeutic targets.

Compound AC1Q3QWB upregulates CDKN1A and SOX17 by interrupting the HOTAIR-EZH2 interaction and enhances the efficacy of tazemetostat in endometrial cancer.

Endometrial cancer (EC) is a common malignancy of the female reproductive system, with an escalating incidence. Recurrent/metastatic EC presents a poor prognosis. The interaction between the long non-coding RNA (lncRNA) HOTAIR and the polycomb repressive complex 2 (PRC2) induces abnormal silencing of tumor suppressor genes, exerting a pivotal role in tumorigenesis. We have previously discovered AC1Q3QWB (AQB), a small-molecule compound targeting HOTAIR-EZH2 interaction. In the present study, we unveil that AQB selectively hampers the interaction between HOTAIR and EZH2 within EC cells, thus reversing the epigenetic suppression of tumor suppressor genes. Furthermore, our findings demonstrate AQB's synergistic effect with tazemetostat (TAZ), an EZH2 inhibitor, significantly boosting the expression of CDKN1A and SOX17. This, in turn, induces cell cycle arrest and impedes EC cell proliferation, migration, and invasion. In vivo experiments further validate AQB's potential by enhancing TAZ's anti-tumor efficacy at lower doses. Our results advocate AQB, a recently discovered small-molecule inhibitor, as a promising agent against EC cells. When combined with TAZ, it offers a novel therapeutic strategy for EC treatment.

Rapid identification of endometrial hyperplasia and endometrial endometrioid cancer in young women.

PURPOSE: We investigated endometrial hyperplasia (EH) and endometrial endometrioid cancer (EEC) and developed a nomogram model to predict the EH/EEC risk and improve patients' clinical prognosis. METHODS: Data were collected from young females (age: ≤ 40 years) who complained of abnormal uterine bleeding (AUB) or abnormal ultrasound endometrial echoes. The patients were randomly divided into training and validation cohorts at a 7:3 ratio. The risk factors for EH/EEC were determined through the optimal subset regression analysis and a prediction model was developed. We used the concordance-index (C-index), and calibration plots in the training and validation sets to assess the prediction model. We drew the ROC curve in the validation set and calculated the area under the curve (AUC), as well as its accuracy, sensitivity, specificity, negative predictive value, and positive predictive value, and finally, converted the nomogram into a web page dynamic nomogram. RESULTS: Predictors included in the nomogram model were body mass index (BMI), polycystic ovary syndrome (PCOS), anemia, infertility, menostaxis, AUB type, and endometrial thickness. The C-index of the model in the training and validation sets were 0.863 and 0.858. The nomogram model had good discriminatory power and was well-calibrated. According to the prediction model, the AUC of EH/EC, EH without atypia, and AH/EC were 0.889, 0.867, and 0.956, respectively. CONCLUSIONS: The nomogram of EH/EC is significantly associated with risk factors, namely BMI, PCOS, anemia, infertility, menostaxis, AUB type, and endometrial thickness. The nomogram model can be used to predict the EH/EC risk and rapidly screen risk factors in a women population with high risk.

A delayed spontaneous second-trimester tubo-abdominal pregnancy diagnosed and managed by laparotomy in a "self-identified" infertile woman, a case report and literature review.

BACKGROUND: Abdominal pregnancy, a rare form of ectopic pregnancy, is associated with high morbidity and adverse consequences for future fertility. Early recognition and management reduce mortality and allow minimal invasive and conservative treatment. In modern medicine, primitive prevention to unexpected fatal pregnancies is crucial. CASE PRESENTATION: A divorced 33-year-old "self-identified" infertile polycystic ovary woman diagnosed as repeated implantation failure in previous in vitro fertilization with her ex-husband ever presented in surgery department with a history of 15-day abdominal pain, nausea, and vomiting and 3-h worsening abdominal pain. The serum beta-human chorionic gonadotropin value was more than 10,000 m-international units per milliliter. Sonogram findings were significant for the absence of intrauterine gestation; a placenta and well-formed living fetus of second-trimester gestation were seen in the abdomen, accompanied by hemoperitoneum. A unique spontaneously second-trimester tubo-abdominal pregnancy was confirmed in emergent laparotomy by gynecologists, she received a removing of the living fetus, a right total salpingectomy, resection of partial omentum and blood transfusion. The patient recovered uneventfully and her serum beta-human chorionic gonadotropin returned to normal range on the 30th postoperative day, till now, she has weak fertility awareness because of her catastrophic experiences in the unexpected abdominal pregnancy. CONCLUSIONS: This case highlights woman with a previous in vitro fertilization history may be in is a high risk to be delayed or missed in diagnosis in an intended ectopic pregnancy due to a fixed belief in infertility. Educational interventions and contraceptive care should be provided by fertility and healthcare practitioner. The possibility of abdominal pregnancy must always be suspected and dealt with promptly and appropriately by the astute clinician.

Expression and Correlation of MIF and ERK1/2 in Liver Cirrhosis and Hepatocellular Carcinoma Induced by Hepatitis B.

Objective: To detect expression and phosphorylation level of macrophage migration inhibitor (MIF) and extracellular-regulated kinases 1 and 2 (ERK1/2) in hepatitis B-induced liver cirrhosis (HBILC) and hepatocellular carcinoma (HCC) with a background of HBILC and analyze the correlation of MIF and ERK1/2 with HBILC and HCC. Methods: Twenty cases of normal liver tissues were collected as a control group, and 48 specimens of HBILC tissues and 48 specimens of HCC tissues were collected as the experimental group, which were assigned as the HBILC group and HCC group, respectively. All tissue specimens were processed into tissue chips. The expressions of MIF, ERK1/2, and their phosphorylated proteins were detected via immunohistochemistry, and MIF and ERK1/2 nucleic acid expressions were detected by in situ hybridization. The results were statistically analyzed using the chi-square test. Results: Proteins and nucleic acids of MIF and ERK1/2 presented low expression in the control group and high expression in the HBILC group and HCC group. MIF expression in the three groups was 25.0%, 75.0%, and 79.17%, respectively, while that of the nucleic acids was 25.0%, 70.83%, and 68.75%, respectively. Expression of ERK1/2 in the three groups was 40.0%, 60.42%, and 81.25%, respectively, and that of nucleic acids was 40.0%, 79.17%, and 77.08%. Expression of pERK1/2 was low in the control and HBILC group and high in the HCC group. Expression of pERK1/2 in the three groups was 20%, 45.83%, and 75%, respectively. Expression of pERK1/2 in the HCC group was significantly different from that in the HBILC and control group (P<0.05), but the difference between the HBILC group and control group was not statistically significant (P>0.05). Conclusion: Occurrence and development of HBILC and HCC are not only related to the high expression of MIF but also closely related to the activation of the ERK1/2 signaling pathway.

Excessively Increased Skeletal Muscle Mass of the Bilateral Lower Limbs is Associated with Hyperuricemia in Females with Polycystic Ovarian Syndrome.

This study is aimed at evaluating the correlation between the skeletal muscle mass index (SMI) of different body parts and hyperuricemia in females with polycystic ovary syndrome (PCOS), thus, providing scientific guidance on lifestyle self-management for patients with PCOS. The cross-sectional study included 171 patients with PCOS, which were divided into two distinct sub-groups based on the presence or absence of hyperuricemia. Anthropometric and serological characteristics of the population with PCOS focusing on skeletal muscle mass were conducted. PCOS patients with hyperuricemia had significantly greater SMI in different body parts. Further binary logistic regression analysis revealed that SMI of the bilateral lower limbs was positively associated with hyperuricemia with an adjusted odds ratio (95% confidence interval) of 1.235 (1.103 - 1.384), p < 0.001. The optimal cut-off value of SMI of the bilateral lower limbs in predicting hyperuricemia was 5.11 (Youden index = 0.490). Combined with the mean value of SMI in the bilateral upper limbs, the safe range of SMI of the bilateral lower limbs in patients with PCOS was calculated as 3.64 - 5.11, with the sensitivity and negative predictive values being 83.9% and 65.1%, respectively. Excessively increased SMI of the bilateral lower limbs was correlated with hyperuricemia in patients with PCOS.

CCNE1 is a predictive and immunotherapeutic indicator in various cancers including UCEC: a pan-cancer analysis.

BACKGROUND: CCNE1 plays an important oncogenic role in several tumors, especially high-stage serous ovarian cancer and endometrial cancer. Nevertheless, the fundamental function of CCNE1 has not been explored in multiple cancers. Therefore, bioinformatics analyses of pan-cancer datasets were carried out to explore how CCNE1 regulates tumorigenesis. METHODS: A variety of online tools and cancer databases, including GEPIA2, SangerBox, LinkedOmics and cBioPortal, were applied to investigate the expression of CCNE1 across cancers. The pan-cancer datasets were used to search for links between CCNE1 expression and prognosis, DNA methylation, m6A level, genetic alterations, CCNE1-related genes, and tumor immunity. We verified that CCNE1 has biological functions in UCEC cell lines using CCK-8, EdU, and Transwell assays. RESULTS: In patients with different tumor types, a high mRNA expression level of CCNE1 was related to a poor prognosis. Genes related to CCNE1 were connected to the cell cycle, metabolism, and DNA damage repair, according to GO and KEGG enrichment analyses. Genetic alterations of CCNE1, including duplications and deep mutations, have been observed in various cancers. Immune analysis revealed that CCNE1 had a strong correlation with TMB, MSI, neoantigen, and ICP in a variety of tumor types, and this correlation may have an impact on the sensitivity of various cancers to immunotherapy. CCK-8, EdU and Transwell assays suggested that CCNE1 knockdown can suppress UCEC cell proliferation, migration and invasion. CONCLUSION: Our study demonstrated that CCNE1 is upregulated in multiple cancers in the TCGA database and may be a promising predictive biomarker for the immunotherapy response in some types of cancers. Moreover, CCNE1 knockdown can suppress the proliferation, migration and invasion of UCEC cells.