Qijuan Zang

The early diagnosis of infections in acute-on-chronic liver failure (ACLF) is still difficult. mNGS(metagenomic next-generation sequencing) is a no-bias, s

Introduction The early diagnosis of infections in acute-on-chronic liver failure (ACLF) is still difficult. mNGS(metagenomic next-generation sequencing) is a no-bias, sensitive pathogen diagnosis method, and further research on mNGS in ACLF is needed. Methods A total of 275 ACLF patients with suspected or confirmed infections were recruited and divided into the mNGS group and the non-mNGS group. Differences between the two groups were assessed. Results The 1:1 Propensity score matching (PSM) for balancing the baseline variables produced 86 patients in each group. From these 86 patients in the mNGS group, 134 samples were collected and analyzed. The overall microbiological positive rate (103/134, 76.9%) detected by mNGS was higher than that detected by culture (24/134, 17.9%), particularly for fungi (14.9% vs. 2.2%). The etiological diagnosis rates for pulmonary and thoracoabdominal infections detected by the mNGS method were higher than those of the culture method (47.9% vs. 11.4%; 52.0% vs. 18.4%, respectively). The etiological diagnosis can be confirmed 22.83 ± 26.27 hours ahead of time. mNGS testing did not significantly improve 90-day transplant-free survival in the overall cohort (sHR 0.96, 95% CI 0.72–1.27; P = 0.76). In the subgroup where mNGS guided therapy, numerically higher resolution rates were observed for pulmonary (53.8% vs 37.1%), abdominal (63.2% vs 52.6%), and bloodstream infections (66.7% vs 50.0%), though these differences were not statistically significant. Conclusions mNGS is a valuable diagnostic tool for ACLF with infections, especially for viruses and fungi. mNGS allows for precise and earlier pathogen diagnosis, enabling timely and targeted anti-infective therapy. mNGS may be associated with improved clinical outcomes in ACLF patients with co-infections, though this potential association requires further validation.

There is evidence that allergic diseases are associated with carcinogenesis. According to translational and epidemiological data, it appears that different cancer types yield different associations. We investigated the relationship between allergic diseases and 28 cancers by Mendelian randomization. Quantitative trait locus analysis was utilized to determine genes expressed in kidney tissue that were affected by allergy-related loci. We further explored the underlying molecular mechanism between allergic diseases and renal cell carcinoma (RCC) with bioinformatics. Of the 28 cancers, evidence suggested that allergies specifically suppressed kidney cancer. Seventy single nucleotide polymorphisms associated with allergic diseases affected the expression of 134 genes in kidney tissue. These 134 genes were enriched in immune-related pathways represented by the major histocompatibility complex class II antigen presentation pathway. Among them, seven core genes were significantly positively correlated with T helper 2 cells. Allergic diseases specifically suppressed RCC through multiple immune pathways. Among them, the major histocompatibility complex class II antigen presentation pathway and T helper 2 cells were the most critical. Our study sheds light on the underlying mechanisms of allergic diseases and RCC and provides therapeutic targets for RCC.

The Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) identifies nutritional risk in patients with liver disease, an important factor in cirrhosis outcomes. Recognizing the gap in existing prognostic models, which often overlook malnutrition, we developed and validated an RFH-NPT-based model for predicting outcomes of patients with cirrhosis. This study included inpatients with cirrhosis from a single center between February and July 2016 (training cohort) and patients from six other medical centers admitted between December 2011 and May 2022 (validation cohort). RFH-NPT assessment was conducted at admission, followed by a 5-year follow-up. A nomogram was created using prognostic variables from Cox modeling, best subset regression (BSR), and least absolute shrinkage and selection operator (LASSO) regression. Its performance was evaluated using various statistical methods and compared with that of existing models such as the Child‒Pugh, MELD, and MELD-Na. A total of 152 patients were included in the training cohort. The nutritional risk was significantly greater in nonsurvivors (81.1%) than in survivors (46.5%). The nomogram showed better accuracy in predicting 1-, 3-, and 5-year survival than traditional methods. The nomogram's effectiveness was confirmed in the validation cohort of 320 patients. This study re-emphasizes the critical role of malnutrition in patients with liver cirrhosis and establishes an effective RFH-NPT-based model for outcome prediction. This study is registered at Clinicaltrials.gov (NCT05513651).

Recent studies suggest that dyslipidaemia may play a critical role in the progression of cardiovascular disease in Takayasu arteritis (TA), although the exact relationship between dyslipidaemia and TA disease activity remains unclear, which is the focus of this study. We evaluated dyslipidaemia and atherosclerosis in a cohort of untreated female patients. Fifty untreated female patients with TA (median age 30 years) and 98 healthy controls matched for age and body mass index (median age 30 years) were assessed for lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), ApoB, ApoE, lipoprotein(a)], inflammatory markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)], and atherosclerotic plaque frequency. TA patients exhibited significantly higher levels of TG and the non-HDL-C/HDL-C ratio than the control group, whereas TC, HDL-C, LDL-C, and ApoA1 levels were significantly lower. Pearson's correlation analysis indicated a positive correlation between CRP and ApoB, as well as the non-HDL-C/HDL-C ratio, and negative correlations with TG, HDL-C, and ApoA1. Atherosclerotic plaques were detected in 14.3% of the TA patients. Multivariate regression analysis revealed that the presence of atherosclerotic plaques was associated only with age, independent of inflammatory markers and lipoprotein levels. The results of this study indicate that untreated female TA patients exhibit a markedly dysregulated serum lipid profile. Atherosclerosis in early TA was not related to lipids or markers of inflammation.

Background Skin cutaneous melanoma (SKCM) is an aggressive and life-threatening skin cancer. G-protein coupled receptor 143 (GPR143) belongs to the superfamily of G protein-coupled receptors. Methods We used the TCGA, GTEx, CCLE, and the Human Protein Atlas databases to examine the mRNA and protein expression of GPR143. In addition, we performed a survival analysis and evaluated the diagnostic efficacy using the Receiver-Operating Characteristic (ROC) curve. Through CIBERSORT, R programming, TIMER, Gene Expression Profiling Interactive Analysis, Sangerbox, and Kaplan-Meier plotter database analyses, we explored the relationships between GPR143, immune infiltration, and gene marker expression of immune infiltrated cells. Furthermore, we investigated the proteins that potentially interact with GPR143 and their functions using R programming and databases including STRING, GeneMANIA, and GSEA. Meanwhile, the cBioPortal, UALCNA, and the MethSurv databases were used to examine the genomic alteration and methylation of GPR143 in SKCM. The Connectivity Map database was used to discover potentially effective therapeutic molecules against SKCM. Finally, we conducted cell experiments to investigate the potential role of GPR143 in SKCM. Results We demonstrated a significantly high expression level of GPR143 in SKCM compared with normal tissues. High GPR143 expression and hypomethylation status of GPR143 were associated with a poorer prognosis. ROC analysis showed that the diagnostic efficacy of the GPR143 was 0.900. Furthermore, GPR143 expression was significantly correlated with immune infiltration in SKCM. We identified 20 neighbor genes and the pathways they enriched were anabolic process of pigmentation, immune regulation, and so on. Genomic alteration analysis revealed significantly different copy number variations related to GPR143 expression in SKCM, and shallow deletion could lead to high expression of GPR143. Ten potential therapeutic drugs against SKCM were identified. GPR143 knockdown inhibited melanoma cell proliferation, migration, and colony formation while promoting apoptosis. Conclusions Our findings suggest that GPR143 serves as a novel diagnostic and prognostic biomarker and is associated with the progression of SKCM.

Background. Skin cutaneous melanoma is one of most aggressive type of cancers worldwide. Therefore, the identification of SKCM biomarkers is of great importance. FLG gene is one of the genes that encode proteins involved in epidermal formation. This was the first time to study the role of FLG in the prognosis and immune infiltrates of skin cutaneous melanoma. Methods. We downloaded the somatic mutation data of 471 SKCM patients from the Cancer Genome Atlas (TCGA) database and analyzed the mutation profiles with MafTools package. The expression of FLG and the overall survival in SKCM were analyzed by GEPIA. Additionally, univariate and multivariate Cox analyses were used to compare several clinical features with survival rates. We used TIMER to investigate FLG expression and collection of immune infiltration levels in SKCM, as well as cumulative survival in SKCM. Meanwhile, we also used CIBERSORT to investigate the association between FLG and cancer immune infiltration. In addition, gene set enrichment analysis (GSEA) was performed using the TCGA dataset. Furthermore, data from GEO and HPA was used to validate the results. Results. Single nucleotide polymorphism (SNP) happened more frequently than insertion or deletion, and CT was the most common of SNV in SKCM. We selected the first 15 mutated genes by analyzing 471 melanoma samples, and the prognosis analysis showed that only the high expression of mutated FLG gene was significantly correlated with the poor prognosis of SKCM. Multivariate Cox analysis showed that age, the worse tumor status, less lymph node metastasis, and FLG expression were independent factors for prognosis. Specifically, lower infiltration levels of B cell, CD8+ T cells, neutrophils, and dendritic cells correlated with poor survival outcomes in SKCM. GSEA revealed that FLG is closely related to cancer pathways and epidermal cell proliferation. In addition, the previous conclusions can be verified from external data from GEO and HPA. Conclusion. The discovery of mutant gene FLG as a biomarker of SKCM helps elucidate how changes in the immune environment promote the occurrence of cutaneous melanoma. Further analysis suggested that FLG might be a new predictor of SKCM prognosis.