Association between Body Mass Index and Serum Uric Acid: mediation analysis involving liver enzymes indicators.

BACKGROUND: Numerous studies have indicated a growing prevalence of hyperuricemia. Elevated levels of serum uric acid (SUA) have been established as influential factors in conditions such as obesity, metabolic syndrome, diabetes mellitus, gout, and cardiovascular disease. Overweight and obesity are closely related to an increase in SUA. Our objective is to demonstrate the mediating role of liver enzyme in the correlation between body mass index (BMI) and SUA. METHODS: A total of 5925 adults aged 18 to 65 were included in this cross-sectional study. Logistic regression and mediation analysis were used to investigate the relationship between BMI and hyperuricemia as well as liver enzyme levels. Standard methods were used to determine the biochemical indexes, including SUA, liver enzymes, and blood lipids in the collected samples. RESULTS: The study revealed that the prevalence of hyperuricemia was 28.0%. Furthermore, the prevalence of overweight and obesity was as high as 48.5%, with 70.7% of this subgroup presenting with hyperuricemia. There was a positive correlation between BMI and hyperuricemia, and elevated levels of liver enzymes (ALT, AST, GGT) were associated with a higher risk of hyperuricemia. The study also observed a positive correlation between BMI and liver enzymes (ALT, AST, GGT). The study findings suggested that ALT, AST, and GGT played significant mediating roles in the relationship between BMI and SUA. Specifically, the unadjusted model revealed that ALT and GGT accounted for 22.12% and 18.13% of the mediation effects, respectively. CONCLUSIONS: The study found that BMI is associated with hyperuricemia, where liver enzyme abnormalities may have a mediating role. It is suggested that being overweight or obese may affect liver enzyme levels, leading to increased SUA levels. Controlling weight and liver enzyme levels may help prevent and treat hyperuricemia.

Effect of nicastrin on hepatocellular carcinoma proliferation and apoptosis through PI3K/AKT signalling pathway modulation.

BACKGROUND: Increasing evidence has proven that the γ-secretase complex plays significant roles in the carcinogenesis of malignancies. However, the independent effect of nicastrin (NCSTN), the largest constituent of the γ-secretase complex, on the progression of hepatocellular carcinoma (HCC) remains to be discovered. METHODS: In our study, we used open online databases, including the Oncomine database, GEPIA and KMPlotter, to analyse the expression of 4 genes and their correlation with prognosis in HCC. NCSTN expression in 60 HCC patients from our centre was determined by immunohistochemical staining and qRT-PCR. The clinical and prognostic significance of NCSTN expression were analysed statistically. Stable Sk-hep1 cell lines with NCSTN overexpression were established using lentivirus-based vectors, and RNAi technology was used to transiently downregulate NCSTN expression in HepG2 cell lines. Cell growth and apoptosis were assessed by using EdU, clone formation, flow cytometry and Western blotting assays. RESULTS: Bioinformatics analysis showed that NCSTN mRNA expression was generally higher in HCC tissues than in normal tissues according to a meta-analysis of 9 HCC datasets, excluding PS-1, PEN-2 and APH-1. Moreover, NCSTN was associated with a poor prognosis in HCC patients from The Cancer Genome Atlas (TCGA). Although the relationship between NCSTN levels and the clinicopathological features of HCC patients was not significant, a survival analysis of HCC patients from TCGA indicated that overall and disease-free survival were significantly associated with NCSTN expression. NCSTN expression in HCC cell lines regulated cell growth and apoptosis in vitro. NCSTN downregulation in HepG2 cells inhibited tumour growth ability in vivo. In addition, NCSTN downregulation in HepG2 cell lines decreased p-PI3K and p-Akt expression, and IGF1, a PI3K/Akt activator, neutralized the effects on PI3K and Akt phosphorylation. Moreover, NCSTN overexpression in Sk-hep1 cells activated the PI3K/Akt signalling pathway, and MK-2206, a PI3K/Akt inhibitor, reversed this activation according to Western blotting analysis. CONCLUSIONS: We suggest that NCSTN serves as an oncogene in HCC by promoting growth and inhibiting apoptosis via the PI3K/Akt pathway, providing a potential novel therapeutic target for HCC treatment.

Effective treatment for hypertrophic scar with dual-wave-length PDL and Nd:YAG in Chinese patients.

There are several ways to prevent and treat hypertrophic scars. In recent years, lasers have been quite extensively used in treating scars. For example, Pulsed Dye Laser (PDL) and Intense Pulsed Light (IPL) can accelerate mutation of scar, whereas non-ablative and ablative fractional laser can improvescar texture. Dual-wave-length laser treatment is extensively used for blood vessel diseases but is rarely used and less reported for treatment of hypertrophic scars. Our study focuses on the efficacy and safety of dual-wave-length PDL and Nd:YAG in treatment of hypertrophic scars. Twenty-five patients in our study complaining of hypertrophic scars were treated with combined PDL/Nd:YAG laser at 4-6 weeks intervals. Following this, the patients and observers assessed these scars by using Patient Scar Assessment Scale (PSAS) and Observer Scar Assessment Scale (OSAS). The resultsshowed that hypertrophic scar was significantly improved after several laser treatments, and no severe adverse effects were observed. Considering the safety and satisfactory effects of dual-wave-length laser treatment, it can be regarded as a good method for treating hypertrophic scars. This study clearly demonstrates that combined PDL/Nd:YAG laser treatment is an effective, safe and well-tolerated treatment option for hypertrophic scars.

Progesterone maintains the status of granulosa cells and slows follicle development partly through PGRMC1.

Progesterone receptor membrane component 1 (PGRMC1) mediates antimitotic and antiapoptotic actions of progesterone in granulosa cells, which indicates that PGRMC1 may play a key role in maintaining the status of granulosa cells. The current study investigated the effects of progesterone on intracellular signaling involved in differentiation, follicle development, inflammatory responses, and antioxidation, and determined the role of PGRMC1 in these processes. Our results demonstrated that progesterone slowed follicle development and inhibited p-ERK1/2, p-p38, caspase-3, p-NF-κB, and p-IκB-α signals involved in differentiation, steroidogenesis, and inflammatory responses in granulosa cells. Progesterone inhibited the steroidogenic acute regulatory protein and the cholesterol side-chain cleavage enzyme and decreased pregnenolone production. A PGRMC1 inhibitor and a PGRMC1 small interfering RNA ablated these inhibitory effects of progesterone. Interfering with PGRMC1 functions also decreased cellular antioxidative effects induced by an oxidant. These results suggest that PGRMC1 might play a critical role in maintaining the status of granulosa cells and balancing follicle numbers.

Health Disparities Among Family Decision-Makers in China: An Ordered Probit Analysis of the China Family Panel Studies.

Purpose: The family decision-makers serve as the backbone of the family, and their health status warrants consideration. This study aims to explore how the health status of this group of people, namely the family decision-making group, is affected, and to delve into the mechanisms of influence based on this. The goal is to provide reliable evidence and strategies for the health management of the family decision-makers group, contributing to the achievement of the "Healthy China 2030" Planning Outline. Patients and Methods: Drawing on data from the China Family Panel Studies (CFPS), this study utilizes an Ordered Probit Model to analyze and compare the health status of family decision-makers and non-decision-makers. Results: The findings indicate that decision-makers tend to experience poorer health outcomes than other family members, with increased pressure related to decision-making identified as a significant contributor to their declining health. Heterogeneity analysis reveals that the negative effect is less pronounced in households with higher net worth but more pronounced in those with more significant housing, education, and medical spending pressures. Moreover, this study analysis highlights that enhancing individual or family socioeconomic status can alleviate the adverse health effects experienced by family decision-makers. Conclusion: The study reveals the presence of certain health adverse effects among family decision-makers. The implications drawn from this research hold significance for the health management of this demographic, underscoring the necessity for tailored interventions aimed at addressing the distinctive challenges confronted by this group.

Awareness and preparedness level of medical workers for radiation and nuclear emergency response.

Radiological science and nuclear technology have made great strides in the twenty-first century, with wide-ranging applications in various fields, including energy, medicine, and industry. However, those developments have been accompanied by the inherent risks of exposure to nuclear radiation, which is a source of concern owing to its potentially adverse effects on human health and safety and which is of particular relevance to medical personnel who may be exposed to certain cancers associated with low-dose radiation in their working environment. While medical radiation workers have seen a decrease in their occupational exposure since the 1950s thanks to improved measures for radiation protection, a concerning lack of understanding and awareness persists among medical professionals regarding these potential hazards and the required safety precautions. This issue is further compounded by insufficient capabilities in emergency response. This highlights the urgent need to strengthen radiation safety education and training to ensure the well-being of medical staff who play a critical role in radiological and nuclear emergencies. This review examines the health hazards of nuclear radiation to healthcare workers and the awareness and willingness and education of healthcare workers on radiation protection, calling for improved training programs and emergency response skills to mitigate the risks of radiation exposure in the occupational environment, providing a catalyst for future enhancement of radiation safety protocols and fostering of a culture of safety in the medical community.

Protective effects of functional Nano-Selenium supplementation on spleen injury through regulation of p38 MAPK and NF-κB protein expression.

Selenium (Se) is a trace element necessary for humans to maintain normal physiological activities, and Se deficiency may lead to splenic injury, while Se supplementation can alleviate splenic injury. However, the mechanism is unclear. In this study, we constructed a Se deficiency animal model by feeding Sprague-Dawley (SD) rats with low Se feed. Meanwhile, we observed the repairing effect of Se supplementation on splenic injury with two doses of novel nano-selenium (Nano-Se) supplement by gavage. We measured the Se content in the spleens of the rats by atomic fluorescence spectroscopy (AFS) method and combined the results of hematoxylin-eosin (HE) and Masson staining to observe the splenic injury, comprehensively evaluating the construction of the animal model of low selenium-induced splenic injury. We measured the mRNA and protein expression levels of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa-B (NF-κB), and interleukin-6 (IL-6) in the spleen by Real-time quantitative polymerase chain reaction (qPCR), western blot (WB), and immunohistochemistry (IHC). We found that the Se deficiency group exhibited lower Se content, splenic fibrosis, and high expression of p38 MAPK, NF-κB, and IL-6 compared to the normal group. The Se supplement groups exhibited higher Se content, attenuated splenic injury, and down-regulated expression of p38 MAPK, NF-κB, and IL-6 relative to the Se deficiency group. This study suggests that Se deficiency leads to splenic injury in rats, and Se supplementation may attenuate splenic injury by inhibiting the expression of p38 MAPK, NF-κB and IL-6.

Exploring configurations of social determinants for enhancing older adult health in China: an fuzzy-set qualitative comparative analysis based on 31 provinces in China.

With China's aging population on the rise, addressing population aging has become a national priority, particularly focusing on improving older adult health. This study employs the social determinants of health framework, considering China's unique macro-social, economic, policy, healthcare, and family cultural factors, to develop a framework for understanding the social determinants of health for older adult in China. Using the fsQCA method and a configurational perspective, the complex relationship between social determinants of health and older adult health status is examined. The findings indicate that individual social determinants alone are insufficient for achieving high levels of older adult health. Instead, three configurations of social determinants have been identified as conducive to high older adult health: Economic Development-Environment - Cultural Dominant Type, Socio-Economic Development - Older Adult Security - Environment - Cultural Dominant Type, and Economic Development Dominant Type. These configurations offer diverse pathways for enhancing older adult health. Conversely, the study identifies two configurations associated with low older adult health levels, exhibiting an asymmetric relationship with the configurations resulting in high older adult health levels. Moreover, economic development consistently emerges as a core condition across all three configurations associated with high older adult health levels, while two configurations associated with low older adult health lack this core condition. These findings underscore the universal contribution of enhancing economic development to improving older adult health.

The geographical pension gap: Understanding the causes of inequality in China's pension funds.

The sustainability of social pension insurance is of great significance in guaranteeing the essential life of the elderly and promoting social stability. Based on the provincial panel data from 2012 to 2020, this study uses non-spatial measurement methods, ArcGIS visualization research methods, and geographic detectors to study the regional differences in China's pension fund balances and the underlying influencing factors. Compared with the traditional way of establishing regression equations to explore the correlation of influencing factors, geographic detectors can quantify the strength of each influencing factor and detect the interaction of different influencing factors. This study found that: First, the growth rate of China's overall pension fund balances has been declining yearly, with the fastest decline in northeast China, the middle in the Western and Central regions of China, and the slowest decline in Eastern China. Second, the spatial distribution of pension fund balances shows agglomeration characteristics, with high-value areas mainly distributed in Eastern China and low-value regions distributed primarily in Western and Northeastern China. Third, the overall Theil index for pension fund balances is trending down, but the Theil index for the Eastern region is on the rise. Fourth, seven factors, including the working-age population, the population aged 65 and above, and regional GDP, are the main factors that lead to regional differences in the balance of urban and rural residential insurance funds. Finally, the superimposed effects of each element are reflected in double-factor enhancement or non-linear enhancement relation.

Regulation of telomerase towards tumor therapy.

Cancer is an aging-related disease, while aging plays an important role in the development process of tumor, thus the two are inextricably associated. Telomere attrition is one of the recognized hallmark events of senescence. Hence, targeting telomerase which could extends telomere sequences to treat tumors is widely favored. Cancer cells rely on high activity of telomerase to maintain a strong proliferative potential. By inhibiting the expression or protein function of telomerase, the growth of cancer cells can be significantly suppressed. In addition, the human immune system itself has a defense system against malignant tumors. However, excessive cell division results in dramatic shortening on telomeres and decline in the function of immune organs that facilitates cancer cell evasion. It has been shown that increasing telomerase activity or telomere length of these immune cells can attenuate senescence, improve cellular viability, and enhance the immunosuppressive microenvironment of tumor. In this paper, we review the telomerase-targeting progress using different anti-tumor strategies from the perspectives of cancer cells and immune cells, respectively, as well as tracking the preclinical and clinical studies of some representative drugs for the prevention or treatment of tumors.

T cells and their products in diabetic kidney disease.

Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease and has gradually become a public health problem worldwide. DKD is increasingly recognized as a comprehensive inflammatory disease that is largely regulated by T cells. Given the pivotal role of T cells and T cells-producing cytokines in DKD, we summarized recent advances concerning T cells in the progression of type 2 diabetic nephropathy and provided a novel perspective of immune-related factors in diabetes. Specific emphasis is placed on the classification of T cells, process of T cell recruitment, function of T cells in the development of diabetic kidney damage, and potential treatments and therapeutic strategies involving T cells.

A FITM1-Related Methylation Signature Predicts the Prognosis of Patients With Non-Viral Hepatocellular Carcinoma.

Although great progress has been made in treatment against hepatitis virus infection, the prognosis of hepatocellular carcinoma (HCC) remains unsatisfied. Therefore, there is an unmet need to explore biomarkers or prognostic models for monitoring non-viral hepatocellular carcinoma. Accumulating evidence indicates that DNA methylation participates in carcinogenesis of malignancies. In the present study, we analyzed 101 non-viral HCC patients from TCGA database to figure out methylation-driven genes (MDGs) that might get involved in non-viral HCC pathogenesis using MethyMix algorithm. Then we picked out 8 key genes out of 137 MDGs that could affect the overall survival (OS) of both methylation and expression level. Using PCA, Uni-variate, Multi-variate, and LASSO cox regression analyses, we confirmed the potential prognostic value of these eight epigenetic genes. Ultimately, combined with immunohistochemistry (IHC), ROC, OS, and GSEA analyses, fat storage-inducing transmembrane protein1 (FITM1) was identified as a novel tumor suppressor gene in non-viral HCC and an applicable FITM1-methylation-based signature was built in a training set and validated in a testing set. Briefly, our work provides several potential biomarkers, especially FITM1, as well as a new method for disease surveillance and treatment strategy development.

Up-Regulation of hsa_circ_0000517 Predicts Adverse Prognosis of Hepatocellular Carcinoma.

Although huge progress has been made in therapeutics against hepatocellular carcinoma (HCC) over the decades, the prognosis of this lethal disease remains poor. To find out risk factors for HCC-related outcome and better predict the prognosis, there is an unmet need to identify novel biomarkers of HCC. Accumulating evidence suggests that circRNAs play pivotal roles in carcinogenesis of several malignancies. In this study, we analyzed two datasets (GSE 94508 and GSE 97332) to examine differentially expressed circRNAs markedly related to HCC pathogenesis. Using Limma package in R and WGCNA analysis, hsa_circ_0000517 was significantly up-regulated in HCC (adjusted P < 0.01). Thereafter, a hsa_circ_0000517-related regulatory network was built based on application of databases including CSCD, TargetScan, miRDB, and miRTarBase. We uncovered the potential function of hsa_circ_0000517 through bioinformatics approaches, such as PPI network, GO, and KEGG pathway analyses. Specifically, functional analysis unveiled that hsa_circ_0000517 was likely to regulate the MAPK and Ras pathway through sponging several miRNAs and having an impact on the expression of TP53, MYC, and AKT1. To verify our initial finding, the expression of hsa_circ_0000517 in 60 HCC patients was detected by qRT-PCR and the expression in cancer tissues was higher compared with the paracarcinoma tissues. Survival analysis suggests high hsa_circ_0000517 expression was associated with adverse prognosis in HCC patients. Furthermore, this circRNA was significantly up-regulated in worse TNM stage, consistent with the progressive-stage-specific characteristic of circRNAs. A prognostic nomogram built on AFP and has_circ_0000517 showed significant diagnostic value. In all, we concluded that hsa_circ_0000517, a promising molecular in underlying mechanism of HCC, is a potent valuable biomarker for prognosis prediction.

Residual levels of rare earth elements in freshwater and marine fish and their health risk assessment from Shandong, China.

The total concentrations of rare earth elements (ΣREE) were quantified in 251 samples from 10 common species of freshwater and marine fish in seventeen cities of Shandong, China. ΣREE obtained from the freshwater fish ranged from 34.0 to 37.9ngg(-1) (wet weight) and marine fish from 12.7 to 37.6ngg(-1). The ratio of LREE to HREE was 13.7:1 and 10:1 for freshwater and marine fish, respectively. This suggests that freshwater fish exhibit greater REE concentrations than marine fish and the biological effects of LREE are higher than HREE. Results revealed a similar REE distribution pattern between those fish and coastal sediments, abiding the "abundance law". The health risk assessment demonstrated the EDIs of REEs in fish were significantly lower than the ADI, indicating that the consumption of these fish presents little risk to human health.

Effects of Air Pollution on Hospital Emergency Room Visits for Respiratory Diseases: Urban-Suburban Differences in Eastern China.

A study on the relationships between ambient air pollutants (PM2.5, SO2 and NO2) and hospital emergency room visits (ERVs) for respiratory diseases from 2013 to 2014 was performed in both urban and suburban areas of Jinan, a heavily air-polluted city in Eastern China. This research was analyzed using generalized additive models (GAM) with Poisson regression, which controls for long-time trends, the "day of the week" effect and meteorological parameters. An increase of 10 µg/m³ in PM2.5, SO2 and NO2 corresponded to a 1.4% (95% confidence interval (CI): 0.7%, 2.1%), 1.2% (95% CI: 0.5%, 1.9%), and 2.5% (95%: 0.8%, 4.2%) growth in ERVs for the urban population, respectively, and a 1.5% (95%: 0.4%, 2.6%), 0.8% (95%: -0.7%, 2.3%), and 3.1% (95%: 0.5%, 5.7%) rise in ERVs for the suburban population, respectively. It was found that females were more susceptible than males to air pollution in the urban area when the analysis was stratified by gender, and the reverse result was seen in the suburban area. Our results suggest that the increase in ERVs for respiratory illnesses is linked to the levels of air pollutants in Jinan, and there may be some urban-suburban discrepancies in health outcomes from air pollutant exposure.

T-2 toxin induces cardiac fibrosis by causing metabolic disorders and up-regulating Sirt3/FoxO3α/MnSOD signaling pathway-mediated oxidative stress.

T-2 toxin, an omnipresent environmental contaminant, poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity. This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin. Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0, 10, and 100 nanograms per gram body weight per day (ng/(g·day)), respectively. Morphological, pathological, and ultrastructural alterations in cardiac tissue were meticulously examined. Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites. The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected. The results showed that exposure to T-2 toxin elicited myocardial tissue disorders, interstitial hemorrhage, capillary dilation, and fibrotic damage. Mitochondria were markedly impaired, including swelling, fusion, matrix degradation, and membrane damage. Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiac metabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway. T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress. In conclusion, the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway. This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.