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Phthalates (PAEs), a group of environmental endocrine disruptors, are associated with oxidative stress and have adverse effects on female ovarian reserves. However, this association has been poorly investigated, particularly with respect to clinical evidence. In this study, we provided clinical evidence of a relationship between exposure levels of PAEs, oxidative stress and decreased ovarian reserve (DOR). Firstly, the urinary concentrations of metabolites of PAEs were measured by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), and the biomarkers of oxidative stress, malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), were determined. Finally, statistical analyses were conducted to describe the relationship between the PAEs exposure, oxidative stress and DOR. We found that the levels of monomethyl phthalate (MMP), monoisobutyl phthalate (MiBP), mono-(2-ethylhexyl) phthalate (MEHP), and mono-(2-ethyl-5-hydroxypentyl) phthalate (MECPP) in the DOR group were significantly higher than those in the control group. There was a significant negative association between AMH and MMP, MiBP levels. and a significant positive association between FSH and MMP levels. PAEs exposure was also associated with a significant increase in MDA levels and decrease in SOD levels. In conclusion, the exposure of PAEs was closely associated with DOR, potentially mediated by oxidative stress pathways; however, small sample size was a limitation in this study. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are typical persistent organic pollutants that have been associated with type 2 diabetes (T2DM) in cohort studies. This review aims to comprehensively assess the molecular mechanisms of PCBs‐induced T2DM. Recent progress has been made in the research of PCBs in liver tissue, adipose tissue, and other tissues. By influencing the function of nuclear receptors, such as the aryl hydrocarbon receptor (AhR), pregnancy X receptor (PXR), and peroxisome proliferator activated receptor γ (PPARγ), as well as the inflammatory response, PCBs disrupt the balance of hepatic glucose and lipid metabolism. This is associated with insulin resistance (IR) in the target organ of insulin. Through androgen receptor (AR), estrogen receptor α/β (ERα/β), and pancreato‐duodenal‐homeobox gene‐1 (PDX‐1), PCBs affect the secretion of insulin and increase blood glucose. Thus, this review is a discussion on the relationship between PCBs exposure and the pathogenesis of T2DM. It is hoped to provide basic concepts for diabetes research and disease treatment. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS), a common endocrine and metabolic disorder affecting women in their reproductive years. Emerging evidence suggests that the maternal-fetal immune system is crucial for proper pregnancy. However, whether immune function is altered at the end of pregnancy in PCOS women and the underlying molecular mechanisms is currently unexplored. Herein, the basic maternal immune system was investigated (n = 136 in the control group; n = 103 in the PCOS group), and whole-transcriptome sequencing was carried out to quantify the mRNAs, miRNAs, and lncRNAs expression levels in fetal side placental tissue of women with PCOS. GO, KEGG, and GSEA analysis were employed for functional enrichment analysis. The process of identifying hub genes was conducted utilizing the protein-protein interaction network. CIBERSORT and Connectivity Map were deployed to determine immune cell infiltration and predict potential drugs, respectively. A network of mRNA-miRNA-lncRNA was constructed and then validated by qRT-PCR. First, red blood cell count, neutrophil count, lymphocyte count, hypersensitive C-reactive protein, and procalcitonin were significantly elevated, while placental growth factor was hindered in PCOS women. We identified 308 DEmRNAs, 77 DEmiRNAs, and 332 DElncRNAs in PCOS samples. Functional enrichment analysis revealed that there were significant changes observed in terms of the immune system, especially the chemokine pathway. Eight genes, including FOS, JUN, EGR1, CXCL10, CXCR1, CXCR2, CXCL11, and CXCL8, were considered as hub genes. Furthermore, the degree of infiltration of neutrophils was dramatically decreased in PCOS tissues. In total, 57 ceRNA events were finally obtained, and immune-related ceRNA networks were validated. Some potential drug candidates, such as enalapril and RS-100329, could have a function in PCOS therapy. This study represents the inaugural attempt to evaluate the immune system at the end of pregnancy and placental ceRNA networks in PCOS, indicating alterations in the chemokine pathway, which may impact fetal and placental growth, and provides new therapy targets. [ABSTRACT FROM AUTHOR]

Nearly one-fifth of patients with non-small cell Lung Cancer (NSCLC) will develop liver metastases (LMs), and the overall treatment strategy of LMs will directly affect the survival of patients. However, some retrospective studies have found that patients receiving chemotherapy or targeted therapy have a poorer prognosis once LMs develop. In recent years, multiple randomised controlled trials (RCTS) have shown significant improvements in outcomes for patients with advanced lung cancer following the introduction of immune checkpoint inhibitors (ICIs) compared to conventional chemotherapy. ICIs is safe and effective in patients with LMs, although patients with LMs are mostly underrepresented in randomised clinical trials. However, NSCLC patients with LMs have a significantly worse prognosis than those without LMs when treated with ICIs, and the mechanism by which LMs induce systemic anti-tumour immunity reduction is unknown, so the management of LMs in patients with NSCLC is a clinical challenge that requires more optimised therapies to achieve effective disease control. In this review, we summarised the mechanism of ICIs in the treatment of LMs, the clinical research and treatment progress of ICIs and their combination with other therapies in patients with LMs from NSCLC. [ABSTRACT FROM AUTHOR]

Context: Polycystic ovary syndrome (PCOS) is a prevalent hormonal imbalance that predominantly affects women in their reproductive years. Previous studies have yielded conflicting conclusions., Objective: This is an updated meta-analysis aiming to explore the connection between flavonoid supplementation and PCOS., Data Sources: Seven databases were searched: Cochrane Library, PubMed, Web of Science, Embase, Wanfang, China Science and Technology Journal, and China National Knowledge Infrastructure, spanning from their inception to April 15, 2024., Data Extraction: Two authors independently searched the databases using the search terms., Data Analysis: Following strict inclusion criteria, 8 papers were ultimately included. This updated meta-analysis suggests that flavonoid supplementation could enhance follicular development, promote the proliferation and differentiation of follicular granulosa cells, elevate estradiol levels, and mitigate testosterone, C-reactive protein, and ovarian index levels., Conclusion: This analysis suggests that dietary flavonoids could potentially alleviate symptoms associated with PCOS., Systematic Review Registration: PROSPERO registration no. CRD42022382912., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

More than 1.9 million new colorectal cancer (CRC) cases and 935000 deaths were estimated to occur worldwide in 2020, representing about one in ten cancer cases and deaths. Overall, colorectal ranks third in incidence, but second in mortality. More than half of the patients are in advanced stages at diagnosis. Treatment options are complex because of the heterogeneity of the patient population, including different molecular subtypes. Treatments have included conventional fluorouracil-based chemotherapy, targeted therapy, immunotherapy, etc. In recent years, with the development of genetic testing technology, more and more targeted drugs have been applied to the treatment of CRC, which has further prolonged the survival of metastatic CRC patients., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior authors or other coauthors who contributed their efforts in this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: To compare the clinical characteristics of pregnant women with polycystic ovary syndrome (PCOS) and perinatal outcomes with or without preeclampsia (PE) and to factors that are potentially associated with the onset of PE., Material and Methods: This was a retrospective study of pregnant women diagnosed with PCOS from January 2017 to December 2021. Eligible patients were divided into two groups based on the presence or absence of preeclampsia: a PE group and a non-PE group. Demographics, clinical characteristics, maternal and perinatal outcomes, and potential factors linked to disease recurrence were analyzed., Results: In total, 616 patients were enrolled and respectively classified into the PE group (n = 51) and the non-PE group (n = 565). The incidence of PE in pregnant women with PCOS was 8.28%; this was significantly higher than that in non-PCOS pregnant women (3.22%, p < 0.001). Logistic regression analysis of the predictive factors for PE in women with PCOS revealed that the combination of maternal hyperandrogenism, a pre-pregnancy BMI ≥ 24 kg/m², and a family history of cardiovascular disease (CVD) and assisted reproductive techniques (ART) exhibited the steepest receiver-operating characteristic (ROC) curve value at 0.797 [95% confidence interval (CI): 0.733-0.862]., Conclusions: Patients with PCOS have a higher incidence of PE. We identified a series of significant and independent factors associated with PE in PCOS: maternal hyperandrogenism, a pre-pregnancy BMI ≥ 24 kg/m², and a family history of CVD and ART.