Association between atherogenic indexes and erectile dysfunction: a cross-sectional analysis of the National Health and Nutrition Examination Survey 2001-2004.

PURPOSE: Elevated blood lipids are considered a risk factor for atherosclerosis, which can lead to erectile dysfunction. This study aimed to explore the relationship between the atherogenic index of plasma (AIP), atherogenic coefficient (AC), Castelli's risk index-I (CRI-I), Castelli's risk index-II (CRI-II), and erectile dysfunction. METHODS: Based on the National Health and Nutrition Examination Survey (NHANES) data from 2001-2004, multivariable-adjusted logistic regression models were used to evaluate the association between AIP, AC, CRI-I, and CRI-II with ED. Smooth curve fitting was employed to assess the linear association. RESULTS: A total of 1806 male participants with complete data were enrolled in the study. In Model 1, those in the highest tertile of AIP had a 49% increased risk of ED compared to the lowest tertile (OR 1.49; 95% CI 1.15-1.91 p = 0.0021). After adjusting for the variables of age, race, education, body mass index, and poverty income ratio (PIR), significant positive correlations were found between ED and AIP, with each 1-unit increase in AIP associated with a 65% increase in the risk of developing ED (OR 1.65; 95% CI 1.03-2.64 p = 0.0361). CONCLUSIONS: AIP is positively associated with the development of ED in US adults. More prospective cohort studies are needed to confirm the link between AIP and ED.

Cancer-associated fibroblasts impair the cytotoxic function of NK cells in gastric cancer by inducing ferroptosis via iron regulation.

As the predominant immunosuppressive component within the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) inhibit Natural Killer cell (NK cell) activity to promote tumor progression and immune escape; however, the mechanisms of cross-talk between CAFs and NK cells in gastric cancer (GC) remain poorly understood. In this study, we demonstrate that NK cell levels are inversely correlated with CAFs abundance in human GC. CAFs impair the anti-tumor capacity of NK cells by inducing ferroptosis, a cell death process characterized by the accumulation of iron-dependent lipid peroxides. CAFs induce ferroptosis in NK cells by promoting iron overload; conversely, decreased intracellular iron levels protect NK cells against CAF-induced ferroptosis. Mechanistically, CAFs increase the labile iron pool within NK cells via iron export into the TME, which is mediated by the upregulated expression of iron regulatory genes ferroportin1 and hephaestin in CAFs. Moreover, CAF-derived follistatin like protein 1(FSTL1) upregulates NCOA4 expression in NK cells via the DIP2A-P38 pathway, and NCOA4-mediated ferritinophagy is required for CAF-induced NK cell ferroptosis. In a human patient-derived organoid model, functional targeting of CAFs using a combination of deferoxamine and FSTL1-neutralizing antibody significantly alleviate CAF-induced NK cell ferroptosis and boost the cytotoxicity of NK cells against GC. This study demonstrates a novel mechanism of suppression of NK cell activity by CAFs in the TME and presents a potential therapeutic approach to augment the immune response against GC mediated by NK cells.

Calponin 1 increases cancer-associated fibroblasts-mediated matrix stiffness to promote chemoresistance in gastric cancer.

The mechanical microenvironment regulated by cancer-associated fibroblasts (CAFs) influence tumor progression. Chemotherapeutic interventions including 5-Fluorouracil (5-Fu) are commonly used for primary treatment of patients with advanced gastric cancer (GC), and the development of acquired resistance to 5-Fu limits the clinical efficacy of these chemotherapies. However, if and how the interplay between CAFs and the mechanical microenvironment regulates GC response to 5-Fu is poorly understood. In this study, we demonstrate that high-level expression of calponin 1(CNN1) in gastric CAFs predicts poor clinical outcomes of GC patients, especially for those treated with 5-Fu. CNN1 knockdown in CAFs improves the effectiveness of 5-Fu in reducing tumor growth in a mouse GC model and confers increased sensitivity to 5-Fu in a 3D culture system. Furthermore, CNN1 knockdown impairs CAF contraction and reduces matrix stiffness without affecting the expression of matrix proteins. Mechanistically, CNN1 interacts with PDZ and LIM Domain 7 (PDLIM7) and prevents its degradation by the E3 ubiquitin ligase NEDD4-1, which leads to activation of the ROCK1/MLC pathway. The increased matrix stiffness, in turn, contributes to 5-Fu resistance in GC cells by activating YAP. Taken together, our data reveal a critical role of the mechanical microenvironment in 5-Fu resistance, which is modulated by CNN1hi CAFs-mediated matrix stiffening, indicating that targeting CAFs may provide a novel option for overcoming drug resistance in GC.

Risk factors associated with splenic hilar lymph node metastasis in patients with advanced gastric cancer in northwest China.

There are plenty of risk factors associated with splenic hilar lymph node metastasis (SHLNM) in patients with advanced gastric cancer (AGC). Whereas, their main influencing factors have not reached a consensus yet. The aim of the study is to investigate the related clinicopathological factors influencing SHLNM in AGC. A retrospective study was performed to investigate 150 patients who underwent D2 curative partial or total gastrectomy for gastric carcinoma from January 2007 to November 2012. Clinicopathological factors were analyzed by univariate and multivariate analysis. A total of 10.7% (16/150) of the patients had SHLNM. The overall ratio of metastatic lymph node (positive lymph nodes/lymph nodes harvested) in the splenic hilum was 17.5% (38/217). Univariate analysis results showed SHLNM was related with depth of invasion, tumor grade, tumor size, tumor location and Bormann type, with significant difference (P<0.05); Multivariate analysis demonstrated that SHLNM was related with depth of invasion and tumor size, with significant difference (P<0.05). Consequently, depth of invasion, tumor grade, tumor size, tumor location and Bormann type were associated with SHLNM in AGC, meanwhile depth of invasion and tumor size are independent risk factors. Preoperative predicting risk factors of SHLNM greatly benefits making more rational surgical scheme of treating AGC.

[Insect community structure and its dynamics in Chinese prickly ash plantations at different altitudes in Yunnan Province].

With community character indices and principal component analysis, this paper studied the variation of insect community composition and structure in Chinese prickly ash plantations at four altitudes in Yunnan Province, and analyzed the temporal patterns of the variation and its affecting factors. The results showed that with the increase of altitude, the species diversity, abundance and evenness of the community decreased gradually, while the population number had a certain increase. Such a variation was more obvious with time. The factor dominating the variation was the gradual change of the species and individuals numbers of natural enemy sub-community to those of pest sub-community.