The CXCLs-CXCR2 axis modulates the cross-communication between tumor-associated neutrophils and tumor cells in cervical cancer.

OBJECTIVE: This study aimed to check the expression profile of the C-X-C motif chemokine ligands (CXCLs)-C-X-C motif chemokine receptor 2 (CXCR2) axis in cervical cancer and to explore the cross-talk between cervical cancer cells and neutrophils via CXCLs-CXCR2 axis. METHODS: Available RNA-sequencing data based on bulk tissues and single-cell/nucleus RNA-sequencing data were used for bioinformatic analysis. Cervical cancer cell lines Hela and SiHa cells were utilized for in vitro and in vivo studies. RESULTS: Except for neutrophils, CXCR2 mRNA expression is limited in other types of cells in the cervical tumor microenvironment. CXCLs bind to CXCR2 and are mainly expressed by tumor cells. CXCL1, 2, 3, 5, 6, and 8, which are consistently associated with neutrophil infiltration, are also linked to poor prognosis. SB225002 (a CXCR2 inhibitor) treatment significantly impairs SiHa cell-induced neutrophil migration. CXCL1, CXCL2, CXCL5, or CXCL8 neutralized conditioned medium from SiHa cells have weaker recruiting effects. The conditioned medium of neutrophils from healthy donors can slow cancer cell proliferation. Conditioned medium of tumor-associated neutrophils (TANs) can drastically enhance cervical cancer cell growth in vitro and in vivo. CONCLUSIONS: The CXCLs-CXCR2 axis is critical in neutrophil recruitment and tumor cell proliferation in the cervical cancer microenvironment.

CXCL8 Promotes Endothelial-to-Mesenchymal Transition of Endothelial Cells and Protects Cells from Erastin-Induced Ferroptosis via CXCR2-Mediated Activation of the NF-κB Signaling Pathway.

CXCL8-CXCR1/CXCR2 signaling pathways might form complex crosstalk among different cell types within the ovarian tumor microenvironment, thereby modulating the behaviors of different cells. This study aimed to investigate the expression pattern of CXCL8 in the ovarian tumor microenvironment and its impact on both endothelial-to-mesenchymal transition (EndMT) and ferroptosis of endothelial cells. The human monocytic cell line THP-1 and the human umbilical vein endothelial cell line PUMC-HUVEC-T1 were used to conduct in vitro studies. Erastin was used to induce ferroptosis. Results showed that tumor-associated macrophages are the major source of CXCL8 in the tumor microenvironment. CXCL8 treatment promoted the nucleus entrance of NF-κB p65 and p65 phosphorylation via CXCR2 in endothelial cells, suggesting activated NF-κB signaling. Via the NF-κB signaling pathway, CXCL8 enhanced TGF-ß1-induced EndMT of PUMC-HUVEC-T1 cells and elevated their expression of SLC7A11 and GPX4. These trends were drastically weakened in groups with CXCR2 knockdown or SB225002 treatment. TPCA-1 reversed CXCL8-induced upregulation of SLC7A11 and GPX4. CXCL8 protected endothelial cells from erastin-induced ferroptosis. However, these protective effects were largely canceled when CXCR2 was knocked down. In summary, CXCL8 can activate the NF-κB signaling pathway in endothelial cells in a CXCR2-dependent manner. The CXCL8-CXCR2/NF-κB axis can enhance EndMT and activate SLC7A11 and GPX4 expression, protecting endothelial cells from ferroptosis.

Gestational diabetes mellitus: The optimal time of delivery.

Gestational diabetes mellitus (GDM) is a common pregnancy complication strongly associated with poor maternal-fetal outcomes. Its incidence and prevalence have been increasing in recent years. Women with GDM typically give birth through either vaginal delivery or cesarean section, and the maternal-fetal outcomes are related to several factors such as cervical level, fetal lung maturity, the level of glycemic control still present, and the mode of treatment for the condition. We categorized women with GDM based on the latter two factors. GDM that is managed without medication when it is responsive to nutrition- and exercise-based therapy is considered diet- and exercise-controlled GDM, or class A1 GDM, and GDM managed with medication to achieve adequate glycemic control is considered class A2 GDM. The remaining cases in which neither medical nor nutritional treatment can control glucose levels or patients who do not control their blood sugar are categorized as class A3 GDM. We investigated the optimal time of delivery for women with GDM according to the classification of the condition. This review aimed to address the benefits and harms of giving birth at different weeks of gestation for women with different classes of GDM and attempted to provide an analytical framework and clearer advice on the optimal time for labor.

The COmprehensive Score for financial Toxicity in China: Validation and Responsiveness.

CONTEXT: Financial toxicity is a priority concern faced by cancer patients and oncology providers. A validated instrument is important to measure this toxicity and improve health-related quality of life of patients. OBJECTIVES: To assess the validity and responsiveness of the Chinese version of the COmprehensive Score for financial Toxicity (COST) and to measure financial toxicity using the COST instrument in Chinese health care systems. METHODS: A longitudinal observational study was performed at three cancer centers from March 2017 to October 2018 for eligible patients. Construct validity was assessed by exploratory and confirmatory factor analysis. The convergent and discriminant validity was tested by examining the correlation coefficient. Responsiveness was tested using the standardized response mean and effect size. Associations between the financial toxicity and variables were assessed by multivariable linear analysis. RESULTS: There were 440 participants at baseline and 268 participants at 6-month follow up. A two-factor solution better represented the Chinese version of COST structure with good internal consistency and test-retest reliability. Convergent validity showed mild to moderate correlations between the domains of COST and the similar domains of Self-Perceived Burden Scale and Quality of Life Discriminant validity showed a low correlation between the COST and the subjective support of Social Support Rate Scale. Sensitivity to change at the sixth month showed effect sizes with global COST scores of 0.3. Multivariable analysis showed that age, household income, and health insurance were significantly associated with financial toxicity. CONCLUSIONS: The Chinese version of COST is a valid and clinically responsive instrument. The identified baseline variables can be used to provide evidence for a financial toxicity intervention study.

[Spatial Distributions of Transferable Nitrogen Forms and Influencing Factors in Sediments from Inflow Rivers in Different Lake Basins].

It is necessary to investigate the distribution of nitrogen forms in river sediments to recognize the water environment quality. In this study, ion exchangeable form nitrogen(IEF-N), weak acid extractable form nitrogen (WAEF-N), strong alkali extractable form nitrogen (SAEF-N) and strong oxidation extractable form nitrogen (SOEF-N) in sediments were obtained by means of sequential extraction procedures.We analyzed the spatial variations of nitrogen forms in sediments from Taihu watershed (Dongtiaoxi River and Xitiaoxi River) and Hongzehu watershed (Anhe River and Suihe River), and expounded the influence factors of nitrogen form distribution. The results showed that the physicochemical properties of sediments from different watersheds varied in space. The concentrations of total nitrogen and nitrogen fractions also showed obvious changes in river sediments. As a whole, the concentrations of total nitrogen and transferable nitrogen in Taihu rivers were higher than those in Hongzehu rivers, but the former showed smaller spatial changes. Sediments from Taihu rivers showed the different concentration order of total nitrogen and transferable nitrogen comparing with those from Hongzehu rivers. The former followed the order of SOEF-N > SAEF-N > IEF-N > WAEF-N, and the latter followed the order of SOEF-N > SAEF-N > WAEF-N > IEF-N.The spatial varitions of transferable nitrogen fractions in Hongzehu rivers were prominent, which was associated with nitrogen sources. The spatial distributions of transferable nitrogen in sediments were obviously affected by their physicochemical properties, especially for organic matter and grain size.

[Relationship between methylenetetrahydrofolate reductase gene C677T polymorphism and susceptibility of ischemic stroke: a meta-analysis].

OBJECTIVE: To evaluate the relationship between the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and the susceptibility of ischemic stroke among different ethnic populations. METHODS: The databases of MEDLINE, EMBASE, Cochrane Library and others were searched. And a total of 17 studies published in English between 2000 and October 2010 on the association of MTHFR gene C677T polymorphism with ischemic stroke were selected. A comprehensive quantitative analysis was performed by meta-analysis. RESULTS: The results showed that the pooled OR values of ischemic stroke with TT and CC genotype were 1.30 (95%CI: 1.11 to 1.52) and 0.88 (95%CI: 0.79 to 0.98) respectively. And when sub-grouped by ethnic populations, the Caucasians were more likely than other populations to suffer ischemic stroke. There was a low probability of publication bias. CONCLUSION: The presence of MTHFR TT gene is associated with an elevated risk of developing ischemic stroke, especially in Caucasians.