Evaluating trophinin associated protein as a biomarker of prognosis and therapy response in renal cell carcinoma.

BACKGROUND: Trophinin Associated Protein (TROAP) has been implicated in some tumors, yet its role in renal cell carcinoma (RCC) remains underexplored. This study aims to elucidate the prognostic and therapeutic implications of TROAP in RCC, encompassing different subtypes. METHODS: Firstly, we identified the expression patterns of TROAP across various tumors within the TCGA pan-cancer cohort. Subsequently, the prognostic significance of TROAP was validated in three TCGA RCC cohorts and a local cohort. Finally, we conducted functional enrichment analysis, somatic mutations and copy number variations, assessed therapeutic response cohorts, and performed in vitro experiments to explore the biological characteristics of TROAP. RESULTS: TROAP serves as an unfavorable factor in both the TCGA RCC datasets and our local cohort. Functional enrichment analysis and in vitro experiments have demonstrated its oncogene effect in promoting tumor progression. Additionally, the relationship between TROAP expression and gene mutations in RCC appears to be limited. Furthermore, elevated TROAP expression is associated with reduced efficacy of RCC therapies, including nivolumab and everolimus. CONCLUSIONS: Our findings illustrate TROAP as a pivotal biomarker for prognosis and therapeutic response in RCC. Elevated TROAP expression is indicative of aggressive tumor behavior and resistance to conventional therapies, making it a valuable target for personalized treatment strategies in RCC management.

Revealing the closed pore formation of waste wood-derived hard carbon for advanced sodium-ion battery.

Although the closed pore structure plays a key role in contributing low-voltage plateau capacity of hard carbon anode for sodium-ion batteries, the formation mechanism of closed pores is still under debate. Here, we employ waste wood-derived hard carbon as a template to systematically establish the formation mechanisms of closed pores and their effect on sodium storage performance. We find that the high crystallinity cellulose in nature wood decomposes to long-range carbon layers as the wall of closed pore, and the amorphous component can hinder the graphitization of carbon layer and induce the crispation of long-range carbon layers. The optimized sample demonstrates a high reversible capacity of 430 mAh g-1 at 20 mA g-1 (plateau capacity of 293 mAh g-1 for the second cycle), as well as good rate and stable cycling performances (85.4% after 400 cycles at 500 mA g-1). Deep insights into the closed pore formation will greatly forward the rational design of hard carbon anode with high capacity.

The interactive effects of family violence and peer support on adolescent depressive symptoms: The mediating role of cognitive vulnerabilities.

BACKGROUND: Family violence as an inducing factor of depressive symptoms has been confirmed in previous studies. However, the mechanisms underlying this association are not well understood, particularly in Chinese adolescents. Guided by the social-ecological diathesis-stress model, this three-wave longitudinal study aimed to examine the effects of an individual's cognitive vulnerabilities (rejection-sensitivity anxiety and negative cognitive error) and positive societal contexts (peer support) on the link between family violence and depressive symptoms in Chinese society. METHODS: A total of 859 Chinese adolescents (44.35 % female; Mage = 12.73, SD = 0.43 at baseline) completed self-reporting surveys that assessed variables associated with study and peer-nominated peer support. RESULTS: The results showed that family violence increased the incidence of depressive symptoms in adolescents after two years, resulting in rejection-sensitivity anxiety and negative cognitive error. Surprisingly, higher self-reported peer support, although not peer-nominated support, exacerbated rather than mitigated this indirect effect, supporting the reverse stress-buffering model and extending the healthy context paradox. LIMITATIONS: Most of the measures were based on participants' self-reports. CONCLUSIONS: These results emphasize the importance of individual cognition and societal contexts in adolescents with traumatic experiences and provide empirical evidence for the intervention and clinical treatment of depressive symptoms.

Examining the Mechanisms of Huachansu Injection on Liver Cancer through Integrated Bioinformatics Analysis.

OBJECTIVE: The objective of this study is to explore the potential anti-liver cancer mechanism of Huachansu injection through integrated bioinformatics analysis. METHODS: Active ingredients of Huachansu injection (extraction of toad skin) were obtained, and their potential drug targets were predicted via SwissTargetPrediction database. Liver cancer disease targets were identified from the GEO (Gene Expression Omnibus) dataset and four public databases. Then Protein-Protein Interaction (PPI) network of toad skin was constructed. GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were performed subsequently. Finally, molecular docking was performed using Auto Dock Vina. RESULTS: In the search for therapeutic targets, twenty active components of toad skin were screened for further study, five hundred and sixty-eight targets of components were identified. In the search for disease targets, three thousand two hundred and twenty-seven genes were identified after removal of duplicated genes, one hundred and fifty-nine genes were up-regulated in liver cancer samples while two hundred and seventy-eight were down-regulated in liver cancer patients. After predicting the therapeutic targets of the components, the results were cross-checked with the disease targets, thirteen up-regulated targets and ten down-regulated targets were obtained. Finally, in the results of molecular docking, seven targets (CDK1, AKR1B1, MMP12, AURKB, CHEK1, AURKA, TTK) were potential up-regulated targets, three targets (SHBG, SRD5A2, NR1I2) were potential down-regulated targets, all of which have the best binding energy and molecular interactions. CONCLUSION: CDK1, AKR1B1, MMP12, AURKB, CHEK1, AURKA, and TTK could be potential upregulated target proteins of Huachansu injection for treating liver cancer. The mechanism of Huachansu injection in the treatment of liver cancer through these up-regulated targets is related to cell cycle, cellular senescence, viral carcinogenesis, p53 signaling pathway. SHBG, SRD5A2, and NR1I2 could be potential down-regulated target proteins of Huachansu injection in treating liver cancer.

N6-methylandenosine-related immune genes correlate with prognosis and immune landscapes in gastric cancer.

Objectives: This study aimed to probe into the significance of N6-methyladenosine (m6A)-related immune genes (m6AIGs) in predicting prognoses and immune landscapes of patients with gastric cancer (GC). Methods: The clinical data and transcriptomic matrix of GC patients were acquired from The Cancer Genome Atlas database. The clinically meaningful m6AIGs were acquired by univariate Cox regression analysis. GC patients were stratified into different clusters via consensus clustering analysis and different risk subgroups via m6AIGs prognostic signature. The clinicopathological features and tumor microenvironment (TME) in the different clusters and different risk subgroups were explored. The predictive performance was evaluated using the KM method, ROC curves, and univariate and multivariate regression analyses. Moreover, we fabricated a nomogram based on risk scores and clinical risk characteristics. Biological functional analysis was performed based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The connectivity map was used to screen out potential small molecule drugs for GC patients. Results: A total of 14 prognostic m6AIGs and two clusters based on 14 prognostic m6AIGs were identified. A prognostic signature based on 4 m6AIGs and a nomogram based on independent prognostic factors was constructed and validated. Different clusters and different risk subgroups were significantly correlated with TME scores, the distribution of immune cells, and the expression of immune checkpoint genes. Some malignant and immune biological processes and pathways were correlated with the patients with poor prognosis. Ten small molecular drugs with potential therapeutic effect were screened out. Conclusions: This study revealed the prognostic role and significant values of m6AIGs in GC, which enhanced the understanding of m6AIGs and paved the way for developing predictive biomarkers and therapeutic targets for GC.

Ten-year Time-trend Analysis of Dyslipidemia Among Adults in Wuhan.

OBJECTIVE: Dyslipidemia is associated with an increased risk of cardiovascular disease, the major cause of death in an aging population. This study aimed to estimate the prevalence of dyslipidemia for the past decade among adults in Wuhan, China. METHODS: We performed a serial cross-sectional study that recruited 705 219 adults from the Health Management Center of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2010 to 2019. The diagnosis of dyslipidemia was based on the 2016 Chinese Guidelines for the Management of Dyslipidemia in Adults. Fixed effects and random effects models were applied to adjust the confounding variables (gender and age). RESULTS: The overall prevalence of dyslipidemia was 33.1% (46.2% in men and 14.7% in women) in 2019. The prevalence of dyslipidemia was significantly increased over 10 years [from 28.6% (95% CI: 28.2%-29.1%) in 2010 to 32.8 % (95% CI:32.6%-33.1%) in 2019;. P-0.001], especially for hypo-high-density lipoprotein cholesterolemia [from 18.4% (95% CI: 18.0%-18.8%) in 2010 to 24.5% (95% CI: 24.3%-24.7%) in 2019; P-0.001]. In 2019, the prevalence of dyslipidemia was higher in participants with comorbidities, including overweight/obesity, hypertension, diabetes, hyperuricemia, or chronic kidney disease, and dyslipidemia was the most significant among participants aged 30-39 years. CONCLUSION: This study demonstrated that dyslipidemia is on the rise in men, and more emphasis should be provided for the screening of dyslipidemia in young males for the primary prevention of cardiovascular and renal diseases.

Exploration of Potential Roles of m5C-Related Regulators in Colon Adenocarcinoma Prognosis.

Objectives: The purpose of this study was to investigate the role of 13 m5C-related regulators in colon adenocarcinoma (COAD) and determine their prognostic value. Methods: Gene expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) datasets. The expression of m5C-related regulators was analyzed with clinicopathological characteristics and alterations within m5C-related regulators. Subsequently, different subtypes of patients with COAD were identified. Then, the prognostic value of m5C-related regulators in COAD was confirmed via univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The prognostic value of risk scores was evaluated using the Kaplan-Meier method, receiver operating characteristic (ROC) curve. The correlation between the two m5C-related regulators, risk score, and clinicopathological characteristics were explored. Additionally, Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Gene Ontology (GO) analysis were performed for biological functional analysis. Finally, the expression level of two m5C-related regulators in clinical samples and cell lines was detected by quantitative reverse transcription-polymerase chain reaction and through the Human Protein Atlas database. Results: m5C-related regulators were found to be differentially expressed in COAD with different clinicopathological features. We observed a high alteration frequency in these genes, which were significantly correlated with their mRNA expression levels. Two clusters with different prognostic features were identified. Based on two independent prognostic m5C-related regulators (NSUN6 and ALYREF), a risk signature with good predictive significance was constructed. Univariate and multivariate Cox regression analyses suggested that the risk score was an independent prognostic factor. Furthermore, this risk signature could serve as a prognostic indicator for overall survival in subgroups of patients with different clinical characteristics. Biological processes and pathways associated with cancer, immune response, and RNA processing were identified. Conclusion: We revealed the genetic signatures and prognostic values of m5C-related regulators in COAD. Together, this has improved our understanding of m5C RNA modification and provided novel insights to identify predictive biomarkers and develop molecular targeted therapy for COAD.

Structure units oriented approach towards collective synthesis of sarpagine-ajmaline-koumine type alkaloids.

Sarpagine-Ajmaline-Koumine type monoterpenoid indole alkaloids represent a fascinating class of natural products with polycyclic and cage-like structures, interesting biological activities, and related biosynthetic origins. Herein we report a unified approach towards the asymmetric synthesis of these three types of alkaloids, leading to a collective synthesis of 14 natural alkaloids. Among them, akuammidine, 19-Z-akuammidine, vincamedine, vincarine, quebrachidine, vincamajine, alstiphylianine J, and dihydrokoumine are accomplished for the first time. Features of our synthesis are a new Mannich-type cyclization to construct the key indole-fused azabicyclo[3.3.1]nonane common intermediate, a SmI2 mediated coupling to fuse the aza-bridged E-ring, stereoselective olefinations to install either the 19-E or 19-Z terminal alkenes presented in the natural alkaloids, and an efficient iodo-induced cyclization to establish the two vicinal all-carbon quaternary centers in the Koumine-type alkaloids.

Electrode-Electrolyte Interfacial Chemistry Modulation for Ultra-High Rate Sodium-Ion Batteries.

Sodium-ion batteries capable of operating at rate and temperature extremes are highly desirable, but elusive due to the dynamics and thermodynamics limitations. Herein, a strategy of electrode-electrolyte interfacial chemistry modulation is proposed. The commercial hard carbon demonstrates superior rate performance with 212 mAh g-1 at an ultra-high current density of 5 A g-1 in the electrolyte with weak ion solvation/desolvation, which is much higher than those in common electrolytes (nearly no capacity in carbonate-based electrolytes). Even at -20 °C, a high capacity of 175 mAh g-1 (74 % of its room-temperature capacity) can be maintained at 2 A g-1 . Such an electrode retains 90 % of its initial capacity after 1000 cycles. As proven, weak ion solvation/desolvation of tetrahydrofuran greatly facilitates fast-ion diffusion at the SEI/electrolyte interface and homogeneous SEI with well-distributed NaF and organic components ensures fast Na+ diffusion through the SEI layer and a stable interface.

Ferroptosis Patterns Correlate with Immune Microenvironment Characterization in Gastric Cancer.

OBJECTIVE: We aimed to build a ferroptosis-based classifier to characterize the molecular features of gastric cancers (GC) and investigate the relationship between different ferroptosis patterns and GC tumor microenvironment (TME). METHODS: Based on the genomic and clinical information from TCGA portal and GEO database, non-negative matrix factorization (NMF) was used to identify ferroptosis subtypes in GC patients. In order to estimate the ferroptosis levels, we established ferroptosis subtype score (FSS) to quantify ferroptosis patterns and ferroptosis potential index (FPI) by principal component analysis (PCA). The correlations of different ferroptosis patterns with TME cell-infiltrating characteristics (including immune cell infiltration, immune checkpoints expression levels, tumor mutational burden (TMB) and immunotherapy response) were systematically analyzed. RESULTS: Two ferroptosis subtypes, C1 (with lower FSS) and C2 (with higher FSS), were determined. C2 displayed a significantly lower FPI than C1. Besides, C2 was associated with diffuse subtype while C1 with intestinal subtype. As for TME characteristics, C2 was in accordance with the immune-excluded phenotype as it showed more active immune and stromal activities but lower TMB, less probability of immunotherapy response and poorer prognosis. C1 was linked to immune-inflamed phenotype as it had lower stromal activities but increased neoantigen load, enhanced response to immunotherapy and relatively better prognosis. CONCLUSION: The systematic assessment of ferroptosis patterns and ferroptosis levels presented in our study implied that ferroptosis serves as an important factor in the formation of TME, which may expand the understanding of TME and provide a novel perspective for the development of targeted immunotherapeutic strategies for GC patients.

CXCR4 is a Novel Biomarker Correlated With Malignant Transformation and Immune Infiltrates in Gastric Precancerous Lesions.

Background: As early gastric cancer (EGC) has a far better prognosis than advanced gastric cancer (GC), early diagnosis and treatment are essential. However, understanding the mechanism of the process from gastric precancerous lesion (GPL) becoming EGC has made little advances. Besides, biomarkers that can monitor the progression of GPL-to-GC are still much insufficient. Methods: Key gene modules associated with GPL progression to EGC were identified by integrating two GPL-related data sets, GSE55696 and GSE130823, using the WGCNA method. Combining with the TCGA-STAD cohort, hub genes were identified. Immunofluorescence was conducted to validate the expression. To explore the implication of hub genes in GPL malignant transformation, a correlation test was conducted to identify their co-expression genes, co-expression cytokines, and co-expression immune cells. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to shrink CXCR4-related predictors and construct a prognostic model. Functional enrichment was applied for exploring the potential mechanism. Results: The green module in GSE55696 and the yellow module in GSE130823 were regarded as key gene modules associated with GPL progression to EGC, and 219 intersection genes from them were mainly enriched in critical immune biological processes. Combining with the TCGA-STAD cohort, CXCR4 was identified as a novel biomarker correlated with the malignant transformation of GPL, the positive rate of which was increased with GPL progression according to immunofluorescence. CXCR4 co-expression genes were found mainly involved in regulation of actin. CXCR4 co-expression cytokines were enriched in regulation of chemotaxis, cell chemotaxis, mononuclear cell migration, leukocyte chemotaxis, etc. As for co-expression immune cells, the expression level of CXCR4 was positively correlated with the abundance of macrophages but negatively correlated with that of effector memory T cells and NKT cells during GPL malignant transformation. In addition, the CXCR4-related prognostic model was able to predict the prognosis of GC and serve as an independent predictor for overall survival (OS). Conclusions: CXCR4 was a novel biomarker correlated with malignant transformation of GPL and played a vital role in the control of tumor immunity. CXCR4 is possible to serve as a therapeutic target for malignant transformation of GPL.

Identification of N6-Methylandenosine-Related lncRNAs for Subtype Identification and Risk Stratification in Gastric Adenocarcinoma.

OBJECTIVES: The purpose of this study was to investigate the role of m6A-related lncRNAs in gastric adenocarcinoma (STAD) and to determine their prognostic value. METHODS: Gene expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) database. Correlation analysis and univariate Cox regression analysis were conducted to identify m6A-related prognostic lncRNAs. Subsequently, different clusters of patients with STAD were identified via consensus clustering analysis, and a prognostic signature was established by least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The clinicopathological characteristics, tumor microenvironment (TME), immune checkpoint genes (ICGs) expression, and the response to immune checkpoint inhibitors (ICIs) in different clusters and subgroups were explored. The prognostic value of the prognostic signature was evaluated using the Kaplan-Meier method, receiver operating characteristic curves, and univariate and multivariate regression analyses. Additionally, Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Ontology (GO) analysis were performed for biological functional analysis. RESULTS: Two clusters based on 19 m6A-related lncRNAs were identified, and a prognostic signature comprising 14 m6A-related lncRNAs was constructed, which had significant value in predicting the OS of patients with STAD, clinicopathological characteristics, TME, ICGs expression, and the response to ICIs. Biological processes and pathways associated with cancer and immune response were identified. CONCLUSIONS: We revealed the role and prognostic value of m6A-related lncRNAs in STAD. Together, our finding refreshed the understanding of m6A-related lncRNAs and provided novel insights to identify predictive biomarkers and immunotherapy targets for STAD.

Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG.

OBJECTIVE: The aim of this study was to integrate the serum exosomal miRNA miR-122-5p with canonical serological biomarkers for the non-invasive screening of chronic atrophic gastritis (CAG) patients. METHODS: miR-122-5p and U6 were amplified by the quantitative reverse transcription polymerase chain reaction (RT-qPCR), gastrin (GAS), pepsinogen I (PG-I), and PG-II and were measured by ELISA. The area under the receiver operating characteristic (ROC) curves and their correlation were analyzed. RESULTS: In the present study, GAS level and PG-I/PG-II ratio (PGR) were increased in CAG group, but there was no significant difference in PG-I or PG-II levels between CAG group and chronic non-atrophic gastritis (CNAG) group. Only GAS level and PG-I/PG-II ratio were significantly correlated with atrophy, and not any other clinicopathologic factors. Expression of hsa-miR-122-5p positively correlated with GAS level, PG-I level, and PGR, while it negatively correlated with PG-II level; however, none of them had significant difference. The combination of GAS, PGR, and hsa-miR-122-5p presented as a better model for non-invasive screening of CAG compared to others. CONCLUSION: These results suggested that serum exosomal hsa-miR-122-5p combined with GAS and PGR would elevate accuracy and specificity in non-invasive screening of CAG.

High Endothelin Receptor Type A Expression as an Independent Prognostic Biomarker and Correlated with Immune Infiltrates in Stomach Adenocarcinoma.

BACKGROUND: Stomach adenocarcinoma (STAD) is the most common gastrointestinal cancer and is associated with high mortality worldwide. Endothelin receptor type A (EDNRA) is associated with guanine-nucleotide-binding (G) proteins and plays important roles in cellular processes and various diseases. PURPOSE: To investigate the prognosis value of EDNRA expression and its correlation with immune infiltrates in patients with STAD. METHODS: The association between clinical characteristics and EDNRA expression in STAD was analyzed using the Wilcoxon signed-rank test and logistic regression. The Kaplan-Meier plotter analysis and Cox regression were constructed to evaluate the influence of EDNRA on prognosis, and a receiver operating characteristic (ROC) curve and nomogram were constructed. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were conducted to analyze the correlation between EDNRA and immune infiltrates. In addition, Oncomine, TIMER databases and qRT-PCR of STAD cell lines were used to verify the EDNRA expression in STAD. RESULTS: Our results revealed that EDNRA expression was significantly higher in patients with STAD than normal gastric tissues, and the results have been confirmed by RT-qPCR. KM-plotter analysis revealed that patients with STAD had shorter OS, FP, and PPS (P<0.001). Multivariate Cox analysis further confirmed that high EDNRA expression was an independent risk factor for OS in patients with STAD. Moreover, other clinicopathologic features were related with worse prognosis in STAD, including age, lymph nodes metastases and primary outcome. More importantly, ROC analysis also confirmed the diagnostic value, and a prognostic nomogram involving age, T, M, N classification, pathologic stage, residual tumor and EDNRA was constructed. GSEA revealed that high EDNRA expression was correlated with immunoregulatory interactions between lymphoid and non lymphoid cells pathways, natural killer cell activation involved in immune response, interleukin 1 receptor binding and pathways in cancer, and ssGSEA showed that EDNRA is correlated with macrophages and NK cells. CONCLUSION: Collectively, EDNRA can be an independent prognostic biomarker and correlated with immune infiltration in stomach adenocarcinoma.

AURKB, CHEK1 and NEK2 as the Potential Target Proteins of Scutellaria barbata on Hepatocellular Carcinoma: An Integrated Bioinformatics Analysis.

OBJECTIVE: We aim to explore the potential anti-HCC mechanism of Scutellaria barbata through integrated bioinformatics analysis. METHODS: We searched active ingredients and related targets of Scutellaria barbata via TCMSP database, PubChem and SwissTargetPrediction database. Then, we identified HCC disease targets from GEO dataset by WGCNA. Next, the intersected targets of disease targets and drug targets were input into STRING database to construct PPI networking in order to obtain potential therapeutic targets of Scutellaria barbata. Cytoscape software was used to carry out network topology analysis of potential targets. We used the R package for GO analysis and KEGG analysis. Finally, we used AutoDock vina and PyMOL software for molecular docking. RESULTS: Sixteen active components from Scutellaria barbata were lastly selected for further investigation. A total of 442 component targets were identified from 16 active ingredients of Scutellaria barbata after the removal of duplicate targets. GSE45436 was selected for construction of WGCNA and screening of differentially expressed genes. A total of 354 genes were up-regulated in HCC samples and 100 were down-regulated in HCC patients. Twenty-one common genes were obtained by intersection and 10 critical targets were filtered for further investigation. The enrichment analysis showed that cell cycle, DNA replication, p53 signaling pathway were mainly involved. The molecular docking results showed that 4 potential combinations were with the best binding energy and molecular interactions. CONCLUSION: AURKB, CHEK1 and NEK2 could be the potential target proteins of Scutellaria barbata in treating HCC. Cell cycle, DNA replication, p53 signaling pathway consist of the fundamental regulation cores in this mechanism.

The role of systemic inflammation in the association between serum 25-hydroxyvitamin D and type 2 diabetes mellitus.

BACKGROUND & AIMS: The association between serum 25-hydroxyvitamin D [25(OH)D] and type 2 diabetes mellitus (T2DM) remains inconclusive. Moreover, whether inflammatory biomarkers are involved in this association has not been explored. This study aims to investigate serum 25(OH)D in relation to T2DM in a Chinese population and provide clues for the inflammatory mechanism whereby serum 25(OH)D deficiency increases T2DM risk. METHODS: A cross-sectional study of 47,803 participants aged 18-96 years was performed in a health management center in 2017. Multivariate linear or logistic regression models and mediation analysis were used to examine the relationships between serum 25(OH)D, inflammatory biomarkers (white blood cell counts and mean platelet volume), and T2DM. RESULTS: Of the 47,803 participants included, 5.2% were diabetic and 51.4% were serum 25(OH)D deficient. The study revealed a significant inverse association between serum 25(OH)D and T2DM risk after adjustment for potential confounders (P for trend = 0.002); the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) across serum 25(OH)D levels (sufficiency, insufficiency, and deficiency) were 1.00 (reference), 1.17 (1.03-1.33), and 1.25 (1.09-1.43), respectively. This study also showed a significant indirect effect of serum 25(OH)D on T2DM risk through total white blood cell count, neutrophil count, lymphocyte count, and monocyte count (P values < 0.05); the proportions mediated were 9.89%, 7.51%, 2.94%, and 2.82%, respectively. CONCLUSIONS: Serum 25(OH)D deficiency was independently associated with an elevated risk of T2DM in a Chinese adult population and low-grade systemic inflammation might be one of its biological mechanisms.

Identifying Dendritic Cell-Related Genes Through a Co-Expression Network to Construct a 12-Gene Risk-Scoring Model for Predicting Hepatocellular Carcinoma Prognosis.

The prognostic prediction of hepatocellular carcinoma (HCC) is still challenging. Immune cells play a crucial role in tumor initiation, progression, and drug resistance. However, prognostic value of immune-related genes in HCC remains to be further clarified. In this study, the mRNA expression profiles and corresponding clinical information of HCC patients were downloaded from public databases. Then, we estimated the abundance of immune cells and identified the differentially infiltrated and prognostic immune cells. The weighted gene co-expression network analysis (WGCNA) was performed to identify immune-related genes in TCGA cohort and GEO cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied to establish a risk-scoring model in the TCGA cohort. HCC patients from the GSE14520 datasets were utilized for risk model validation. Our results found that high level of dendritic cell (DC) infiltration was associated with poor prognosis. Over half of the DC-related genes (58.2%) were robustly differentially expressed between HCC and normal specimens in the TCGA cohort. 17 differentially expressed genes (DEGs) were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. A 12-gene risk-scoring model was established to evaluate the prognosis of HCC. The high-risk group exhibits significantly lower OS rate of HCC patients than the low-risk group. The risk-scoring model shows benign predictive capacity in both GEO dataset and TCGA dataset. The 12-gene risk-scoring model may independently perform prognostic value for HCC patients. Receiver operating characteristic (ROC) curve analysis of the risk-scoring model in GEO cohort and TCGA cohort performed well in predicting OS. Taken together, the 12-gene risk-scoring model could provide prognostic and potentially predictive information for HCC. SDC3, NCF2, BTN3A3, and WARS were noticed as a novel prognostic factor for HCC.

Temporal trends in hyperuricaemia among adults in Wuhan city, China, from 2010 to 2019: a cross-sectional study.

OBJECTIVES: Hyperuricaemia is a risk factor for gout attacks, kidney damage and cardiovascular events. Evidence on the trends in hyperuricaemia burden in Wuhan city, China, was limited. The present study aimed to estimate the prevalence of and a decade trend in hyperuricaemia in Wuhan city. DESIGN: Cross-sectional study. SETTING: Health Management Center of Tongji Hospital. PARTICIPANTS: A total of 732 527 adult participants from the general population who took a physical examination in the Health Management Center between 2010 and 2019. MAIN OUTCOME MEASURES: Prevalence of and trends in hyperuricaemia. RESULTS: The overall prevalence of hyperuricaemia was 25.8% (36.6% in men and 10.8% in women) in 2019. The hyperuricaemia prevalence and serum uric acid (SUA) levels were significantly higher in young men, old women and participants with obesity, hypertension, diabetes or dyslipidaemia (p<0.05). SUA levels among men and women gradually increased from 358.0 (313.0-407.0) umol/L and 250.0 (217.0-288.0) umol/L in 2010 to 388.0 (338.0-445.2) umol/L and 270.0 (233.0-314.0) umol/L in 2019, respectively, p<0.05. From 2010 through 2019, hyperuricaemia prevalence significantly increased in each age category and it increased most sharply among participants aged 20-39 years. The multivariate-adjusted prevalence among men was 26.1% (25.4% to 26.7%) in 2010, 30.9% (30.4% to 31.4%) in 2015 and 34.4% (34.1% to 34.8%) in 2019, while among women it was 5.8% (5.4% to 6.2%) in 2010, 7.2% (6.9% to 7.5%) in 2015 and 10.1% (9.9% to 10.3%) in 2019. CONCLUSIONS: Hyperuricaemia was highly prevalent among adults in Wuhan city. More attention should be paid to the increasing burden of hyperuricaemia, especially for those at higher risks.

Construction and Validation of a Ferroptosis-Related Prognostic Model for Gastric Cancer.

BACKGROUND: Gastric cancer (GC), an extremely aggressive tumor with a very different prognosis, is the third leading cause of cancer-related mortality. We aimed to construct a ferroptosis-related prognostic model that can be distinguished prognostically. METHODS: The gene expression and the clinical data of GC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). The ferroptosis-related genes were obtained from the FerrDb. Using the "limma" R package and univariate Cox analysis, ferroptosis-related genes with differential expression and prognostic value were identified in the TCGA cohort. Last absolute shrinkage and selection operator (LASSO) Cox regression was applied to shrink ferroptosis-related predictors and construct a prognostic model. Functional enrichment, ESTIMATE algorithm, and single-sample gene set enrichment analysis (ssGSEA) were applied for exploring the potential mechanism. GC patients from the GEO cohort were used for validation. RESULTS: An 8-gene prognostic model was constructed and stratified GC patients from TCGA and meta-GEO cohort into high-risk groups or low-risk groups. GC patients in high-risk groups have significantly poorer OS compared with those in low-risk groups. The risk score was identified as an independent predictor for OS. Functional analysis revealed that the risk score was mainly associated with the biological function of extracellular matrix (ECM) organization and tumor immunity. CONCLUSION: In conclusion, the ferroptosis-related model can be utilized for the clinical prognostic prediction in GC.

Clinical observation and analysis on the significance of quick sequential organ failure assessment in 74 non-ICU patients with sepsis.

BACKGROUND: Sepsis is an important disease that endangers human health and is the main cause of death in ICU patients, which has been a focus of clinical treatment. This study aims to evaluate the significance of the readily available quick sequential organ failure assessment (qSOFA) score in clinical cases of sepsis. METHODS: A retrospective cross-sectional study of patients with sepsis treated in the Department of Infectious Diseases, the Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology from January 2015 to December 2016 was conducted, and the patients were divided into a high-score group (≥2 points) and the low-score group (<2 points) according to the diagnostic criteria for sepsis (Sepsis 3.0). The differences in disease outcome and inflammatory indicators were compared between groups. RESULTS: A total of 74 patients with sepsis were included in this study. When the cutoff qSOFA score was 2 points, the patients in the high-score group showed a higher mortality rate (71.43%), and the patients in the low-score group showed a higher improvement rate (87.76%). The inflammatory indicators did not show statistically significant differences between the two groups. CONCLUSIONS: The qSOFA score can better predict the prognoses of non-ICU patients with sepsis compared with traditional inflammatory indicators. Clinicians should raise their awareness about qSOFA and improving its accuracy.