Chinese Medical Sciences Journal最新文献

Objective

To explore the potential biological functions and prognostic prediction values of non-apoptotic regulated cell death genes (NARCDs) in lung adenocarcinoma.

Methods

Transcriptome data of lung adenocarcinoma were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. We identified differentially expressed NARCDs between lung adenocarcinoma tissues and normal tissues with R software. NARCDs signature was constructed with univariate Cox regression analysis and the least absolute shrinkage and selection operator Cox regression. The prognostic predictive capacity of NARCDs signature was assessed by Kaplan-Meier survival curve, receiver operating characteristic curve, and univariate and multivariate Cox regression analyses. Functional enrichment of NARCDs signature was analyzed with gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. In addition, differences in tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion score, and chemotherapeutic drug sensitivity were analyzed between the high and low NARCDs score groups. Finally, a protein-protein interaction network of NARCDs and immune-related genes was constructed by STRING and Cytoscape software.

Results

We identified 34 differentially expressed NARCDs associated with the prognosis, of which 16 genes (ATIC, AURKA, CA9, ITGB4, DDIT4, CDK5R1, CAV1, RRM2, GAPDH, SRXN1, NLRC4, GLS2, ADRB2, CX3CL1, GDF15, and ADRA1A) were selected to construct a NARCDs signature. NARCDs signature was identified as an independent prognostic factor (P < 0.001). Functional analysis showed that there were significant differences in mismatch repair, pS3 signaling pathway, and cell cycle between the high NARCDs score group and low NARCDs score group (all P < 0.05). The NARCDs low score group had lower tumor mutational burden, higher immune score, higher tumor immune dysfunction and exclusion score, and lower drug sensitivity (all P < 0.05). In addition, the 10 hub genes (CXCL5, TLR4JUN, IL6, CCL2, CXCL2, ILA, IFNG, IL33, and GAPDH) in protein-protein interaction network of NARCDs and immune-related genes were all immune-related genes.

Conclusion

The NARCDs prognostic signature based on the above 16 genes is an independent prognostic factor, which can effectively predict the clinical prognosis of patients of lung adenocarcinoma and provide help for clinical treatment.

Background

Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.

Methods

We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.

Results

We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.

Conclusions

We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.

Kidney stone is a highly recurrent disease in the urinary tract system. Most kidney stones are calcium stones, usually consisting of either calcium oxalate or calcium phosphate. Supersaturation of soluble calcium, oxalate, phosphate, and citrate in the urine is the basis for calcium stone formation. Genetics, diet, low physical activity, and individual habits contribute to the formation of kidney stones. In this review, the associations of the risk of kidney stones with oxalate consumption and some individual habits, such as smoking, alcohol drinking, and opium consumption, are summarized.

Despite declines in morbidity and mortality in recent years, ischemic stroke (IS) remains one of the leading causes of death and disability from cerebrovascular diseases. Addressing the controllable risk factors underpins the successful clinical management of IS. Hypertension is one of the most common treatable risk factors for IS and is associated with poor outcomes. Ambulatory blood pressure monitoring has revealed that patients with hypertension have a higher incidence of blood pressure variability (BPV) than those without hypertension. Meanwhile, increased BPV has been identified as a risk factor for IS. The risk of IS is higher and the prognosis after infarction is worse with higher BPV, no matter in the acute or subacute phase. BPV is multifactorial, with alterations reflecting individual physiological and pathological changes. This article reviews the current research advances in the relationship between BPV and IS, with an attempt to raise awareness of BPV among clinicians and IS patients, explore the increased BPV as a controllable risk factor for IS, and encourage hypertensive patients to control not only average blood pressure but also BPV and implement personalized blood pressure management.

Objective

To explore the effects and mechanisms of a traditional Chinese medicine (TCM) prescription, “Fang-gan Decoction” (FGD), in protecting against SARS-CoV-2 spike protein-induced lung and intestinal injuries in vitro and in vivo.

Methods

Female BALB/c mice and three cell lines pretreated with FGD were stimulated with recombinant SARS-CoV-2 spike protein (spike protein). Hematoxylineosin (HE) staining and pathologic scoring of tissues, cell permeability and viability, and angiotensin-converting enzyme 2 (ACE2) expression in the lung and colon were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of inflammatory factors in serum and cell supernatant. The expression of NF-κB p65, p-NF-κB p6S, p-IκBα, p-Smad2/3, TGF-β1, Caspase3, and Bel-2 was evaluated by Western blotting.

Results

FGD protected against the damage to the lung and colon caused by the spike protein in vivo and in vitro according to the pathologic score and cell permeability and viability (P<0.05). FGD up-regulated ACE2 expression, which was reduced by the spike protein in the lung and colon, significantly improved the deregulation of inflammatory markers caused by the spike protein, and regulated the activity of TGF-β/Smads and NF-κB signaling.

Conclusion

Traditional Chinese medicine has a protective effect on lung and intestinal tissue injury stimulated by the spike protein through possible regulatory functions of the NF-κB and TGF-β1/Smad pathways with tissue type specificity.

Background

Hospitalizations for asthma and chronic obstructive pulmonary disease (COPD) exacerbations frequently occur in Thailand. National trends in hospital outcomes are essential for planning preventive strategies within the healthcare system. We examined temporal trends in in-hospital outcomes, including mortality rate, length of stay (LOS), and expenses for reimbursement in adults hospitalized for asthma and COPD exacerbations in southern Thailand.

Methods

A retrospective, population-based study on adults hospitalized for exacerbations of asthma and COPD was carried out using data from the National Health Security Office in southern Thailand. Baseline demographic and in-hospital outcome assessments were conducted on 19,459 and 66,457 hospitalizations for asthma and COPD, respectively, between 2017 and 2021.

Results

Significant reductions in hospital admissions for exacerbations of asthma and COPD were observed over time, particularly in 2020/2021. From 2017 to 2021, the in-hospital mortality rate for asthma rose from 3.2 to 3.7 deaths per 1,000 admissions (P<0.05). The rates for COPD admissions, on the other hand, reduced from 20.3 to 16.4 deaths per 1,000 admissions between 2017 and 2020, but subsequently increased to 21.8 in 2021 (P<0.05). The prominent contributor to the higher mortality rate was found to be increasing age. Nonetheless, the average LOS for both asthma and COPD decreased slightly over the study period. The total expenses for reimbursing exacerbations of asthma and COPD per hospitalisation have risen significantly each year, with a particularly notable increase in 2020/2021.

Conclusion

During 2017-2021, exacerbations of asthma and COPD in Thailand continued to account for significant in-hospital mortality rates and reimbursement expenses, despite the overall decrease in hospitalizations and slight fluctuations in the LOS.