Assessment of the Effect of Leonurine Hydrochloride in a Mouse Model of PCOS by Gene Expression Profiling.

Polycystic ovary syndrome (PCOS) is an endocrine disease commonly associated with metabolic disorders in females. Leonurine hydrochloride (Leo) plays an important role in regulating immunity, tumours, uterine smooth muscle, and ovarian function. However, the effect of Leo on PCOS has not been reported. Here, we used dehydroepiandrosterone to establish a mouse model of PCOS, and some mice were then treated with Leo by gavage. We found that Leo could improve the irregular oestros cycle of PCOS mice, reverse the significantly greater serum testosterone (T) and luteinising hormone (LH) levels, significantly reduce the follicle-stimulating hormone (FSH) level, and significantly increase the LH/FSH ratio of PCOS mice. Leo could also change the phenomenon of ovaries in PCOS mice presented with cystic follicular multiplication and a lacking corpus luteum. Transcriptome analysis identified 177 differentially expressed genes related to follicular development between the model and Leo groups. Notably, the cAMP signalling pathway, neuroactive ligand-receptor interactions, the calcium signalling pathway, the ovarian steroidogenesis pathway, and the Lhcgr, Star, Cyp11a, Hsd17b7, Camk2b, Calml4, and Phkg1 genes may be most related to improvements in hormone levels and the numbers of ovarian cystic follicles and corpora lutea in PCOS mice treated by Leo, which provides a reference for further study of the mechanism of Leo.

Value of the modified Patient-Generated Subjective Global Assessment in indicating the need for nutrition intervention and predicting overall survival in patients with malignant tumors in at least two organs.

BACKGROUND: Although the Patient-Generated Subjective Global Assessment (PG-SGA) is a reference standard used to assess a patient's nutrition status, it is cumbersome to administer. The aim of the present study was to estimate the value of a simpler and easier-to-use modified PG-SGA (mPG-SGA) to evaluate the nutrition status and need for intervention in patients with malignant tumors present in at least two organs. METHODS: A total of 591 patients (343 male and 248 female) were included from the INSCOC study. A Pearson correlation analysis was conducted to assess the correlation between the mPG-SGA and nutrition-related factors, with the optimal cut-off defined by a receiver operating characteristic curve (ROC). The consistency between the mPG-SGA and PG-SGA was compared in a concordance analysis. A survival analysis was used to determine the effects of nutritional intervention among different nutrition status groups. Univariable and multivariable Cox analyses were applied to evaluate the association of the mPG-SGA with the all-cause mortality. RESULTS: The mPG-SGA showed a negative association with nutrition-related factors. Individuals with an mPG-SGA ≥ 5 (rounded from 4.5) were considered to need nutritional intervention. Among the malnourished patients (mPG-SGA ≥ 5), the overall survival (OS) of those who received nutrition intervention was significantly higher than that of patients who did not. However, the OS was not significantly different in the better-nourished patients (mPG-SGA < 5). CONCLUSION: Our findings support that the mPG-SGA is a feasible tool that can be used to guide nutritional interventions and predict the survival of patients with malignant tumors affecting at least two organs.

Effect of economic inequality on generosity: A social norm perspective.

Economic inequality has been found to reduce individuals' generosity in western contexts. However, whether this effect is cross-culturally consistent and its internal mechanism remain unclear, as well as how to mitigate this impact. Hence, we explored whether and why economic inequality may erode generosity in a sample of Chinese adults from the social norm perspective and introduced the equal allocation norm to mitigate this effect. Four online studies were conducted: two were correlational (Study 1: n = 300; Study 2: n = 568) and two were experimental (Study 3: n = 289; Study 4: n = 500). Results showed that economic inequality predicted less generosity in the dictator game, and perceived unequal allocation norm accounted for this effect. Moreover, introducing the equal allocation norm could buffer this negative effect. Findings suggest economic inequality impairs generosity, and making the equal allocation norm more salient may guide people to act more generously.

Eosinophil extracellular traps in asthma: implications for pathogenesis and therapy.

Asthma is a common, chronic inflammatory disease of the airways that affects millions of people worldwide and is associated with significant healthcare costs. Eosinophils, a type of immune cell, play a critical role in the development and progression of asthma. Eosinophil extracellular traps (EETs) are reticular structures composed of DNA, histones, and granulins that eosinophils form and release into the extracellular space as part of the innate immune response. EETs have a protective effect by limiting the migration of pathogens and antimicrobial activity to a controlled range. However, chronic inflammation can lead to the overproduction of EETs, which can trigger and exacerbate allergic asthma. In this review, we examine the role of EETs in asthma.

Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients.

Background: Cervical cancer is the second most lethal malignancy among women, and histone modification plays a fundamental role in most biological processes, but the prognostic value of histone modification in cervical cancer has not been evaluated. Methods: A total of 594 cervical cancer patients from TCGA-CESC, GSE44001, and GSE52903 cohorts were enrolled in the current study, along with the corresponding clinicopathological features. Patients with a follow-up time less than one month were removed. A total of 122 histone modification-associated signaling pathways were obtained from the MSigDB. The activation scores of these pathways were evaluated using the "GSVA" package, differentially expressed genes were identified by the "limma" package, and pathway enrichment was conducted using the "clusterProfiler 4.0" package. The subsequent least absolute shrinkage and selection operator (LASSO) regression analysis was performed using the "glmnet" package, and a prognostic nomogram was established using the "regplot" package. For the prediction of potential therapeutic drugs, we used the data from GDSC2016 and visualized them via "MOVICS". Results: Nine of 23 histone modification-associated prognostic genes were identified to construct the prognostic signature by LASSO analysis, named the histone modification-associated gene (HMAG) signature. Cervical patients with HMAG-H in TCGA-CESC cohort showed a 2.68-fold change of death risk, with the 95% CI from 1.533 to 4.671 (p < 0.001), as well as the increased death risk of HMAG-H in the GSE44001 cohort (HR: 2.83, 95% CI: 1.370-5.849, p = 0.005) and GSE44001 cohort (HR: 4.59, 95% CI: 1.658-12.697, p = 0.003). We observed the preferable AUC values of the HMAG signature in TCGA-CESC cohort (1-year: 0.719, 3-year: 0.741, and 5-year: 0.731) and GSE44001 cohort (1-year: 0.850, 3-year: 0.781, and 5-year: 0.755). The C-index of the nomogram showed a prognostic value as high as 0.890, while the C-index for age was only 0.562, and that for grade was only 0.542. Patients with high HMAG scores were more suitable for the treatment of CHIR-99021, embelin, FTI-277, JNK-9L, JQ12, midostaurin, PF-562271, pyrimethamine, and thapsigargin, and patients with low HMAG scores were more suitable for the treatment of BMS-536924, CP466722, crizotinib, PHA-665752, rapamycin, and TAE684. Conclusion: We comprehensively evaluated the histone modification status in cervical cancer patients and revealed histone modification-associated prognostic genes to construct the HMAG signature, aiming to provide a new insight into prognosis prediction and precise clinical treatment.

Exports Widen the Regional Inequality of Health Burdens and Economic Benefits in India.

Both the ever-complex international and subnational supply chains could relocate health burdens and economic benefits across India, leading to the widening of regional inequality. Here, we simultaneously track the unequal distribution of fine particle matter (PM2.5) pollution, health costs, and value-added embodied in inter- and intranational exports for Indian states in 2015 by integrating a nested multiregional input-output (MRIO) table constructed based on EXIOBASE and an Indian regional MRIO table, Emissions Database for Global Atmospheric Research (EDGAR), the Community Multi-Scale Air Quality (CMAQ) model, and a concentration-response function. The results showed that the annual premature deaths associated with PM2.5 pollution embodied in inter- and intranational exports were 757,356 and 388,003 throughout India, accounting for 39% and 20% of the total premature deaths caused by PM2.5 pollution, respectively. Richer south and west coastal states received around half of the national Gross Domestic Product (GDP) induced by exports with a quarter of the health burden, while poorer central and east states bear approximately 60% of the health burden with less than a quarter of national GDP. Our findings highlight the role of exports in driving the regional inequality of health burdens and economic benefits. Therefore, tailored strategies (e.g., air pollution compensation, advanced technology transfer, and export structure optimization) could be formulated.

Fat mass assessment using the triceps skinfold thickness enhances the prognostic value of the Global Leadership Initiative on Malnutrition criteria in patients with lung cancer.

The present study evaluated whether fat mass assessment using the triceps skinfold (TSF) thickness provides additional prognostic value to the Global Leadership Initiative on Malnutrition (GLIM) framework in patients with lung cancer (LC). We performed an observational cohort study including 2672 LC patients in China. Comprehensive demographic, disease and nutritional characteristics were collected. Malnutrition was retrospectively defined using the GLIM criteria, and optimal stratification was used to determine the best thresholds for the TSF. The associations of malnutrition and TSF categories with survival were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HR). Malnutrition was identified in 808 (30·2 %) patients, and the best TSF thresholds were 9·5 mm in men and 12 mm in women. Accordingly, 496 (18·6 %) patients were identified as having a low TSF. Patients with concurrent malnutrition and a low TSF had a 54 % (HR = 1·54, 95 % CI = 1·25, 1·88) greater death hazard compared with well-nourished individuals, which was also greater compared with malnourished patients with a normal TSF (HR = 1·23, 95 % CI = 1·06, 1·43) or malnourished patients without TSF assessment (HR = 1·31, 95 % CI = 1·14, 1·50). These associations were concentrated among those patients with adequate muscle mass (as indicated by the calf circumference). Additional fat mass assessment using the TSF enhances the prognostic value of the GLIM criteria. Using the population-derived thresholds for the TSF may provide significant prognostic value when used in combination with the GLIM criteria to guide strategies to optimise the long-term outcomes in patients with LC.