ABSTRACT
Background: Coronary artery calcification (CAC) is a crucial marker for coronary atherosclerosis, and the extent of CAC is closely linked to the incidence and progression of cardiovascular diseases. The interleukin-2 (IL-2) receptor (IL-2R), which plays a critical role in mediating the proliferation and differentiation of immune cells, may also be involved in the development of CAC. The study aimed to investigate the relationship between IL-2R and CAC, with the goal of providing new insights into cardiovascular diseases. Methods: In this study, we enrolled 606 patients diagnosed with coronary artery disease to assess CAC. Based on coronary artery calcification score (CACS), patients were divided into two groups: the non-severe CAC group (CACS ≤ 400 Agatston units, AU) and the severe CAC group (CACS > 400 AU). Results: The results showed that IL-2R levels were significantly higher in patients with severe CAC compared to those with non-severe CAC (383 vs. 352 pg/mL, p = 0.002). Moreover, the level of IL-2R was positively correlated with the severity of CAC, independent of other clinical risk factors. According to Receiver Operating Characteristic (ROC) curve, the IL-2R prediction model demonstrated a good capability in distinguishing severe CAC with the Area Under the Curve (AUC) value of 0.726. Conclusions: Our study suggests that IL-2R is independently associated with the occurrence of severe CAC in coronary artery disease (CAD) patients. Additionally, IL-2R may play a crucial role in the development of advanced atherosclerosis. Consequently, therapeutic strategies targeting the IL-2/IL-2R pathway may be effective in preventing or treating CAD.
ABSTRACT
Microplastics (MPs) is an emerging pollutant potentially harmful to health. Medical practices using plastic devices, such as percutaneous coronary interventions (PCI), may result in MPs entering into the blood. The purpose of this study was to quantify the effect of PCI on microplastic levels in patients' blood. Laser direct infrared (LDIR) was used to detect MPs in the blood of 23 patients before and after PCI. MPs in the water in which devices used in PCI were washed were also examined. The concentration of MPs in the blood was significantly elevated (93.57 ± 35.95 vs. 4.96 ± 3.40 particles/10 mL of blood, P < 0.001) after PCI compared to before, and the increased MPs were polyamide (PA), polyethylene (PE), polyurethane (PU), and polyethylene terephthalate (PET), which was consistent with the types of MPs detected in the device washing water. The maximum diameter of MPs in blood before PCI was 50 µm, whereas after PCI it was 213 µm, and even 336 µm in device washing water. These findings indicated that PCI will cause MPs to enter the blood, and devices used during PCI were a major source, a range of medical practices that use plastic devices may be a new route for MPs to enter the human body.
Subject(s)
Microplastics , Percutaneous Coronary Intervention , Humans , Microplastics/analysis , Percutaneous Coronary Intervention/instrumentation , Male , Female , Aged , Middle Aged , Polyurethanes/chemistryABSTRACT
Objective: This bibliometric analysis and review aimed to examine the current research status and trends in the combination of nutrition and exercise training for sarcopenia. Additionally, it sought to provide researchers with future research directions in this field. Methods: Relevant publications were obtained from the Web of Science Core Collection (WoSCC) database, covering the period from January 1995 to October 2023. The collected publications were analyzed using CiteSpace, VOSviewer, Bibliometrix, and Review Manager. Results: Out of the 2528 retrieved publications, the United States emerged as the leading contributor in terms of publication volume. The University of Texas System was identified as the most productive institution. Luc J C van Loon emerged as the most published author in this field. Analysis of keywords revealed recent hot topics and emerging areas of interest, such as "gut microbiota" and "mechanisms". Upon further evaluation, resistance training (RT) and protein supplementation were identified as the most commonly employed and effective methods. Conclusion: RT and protein supplementation are widely recognized as effective strategies. Future research should focus on investigating the molecular aspects of sarcopenia. Moreover, the potential therapeutic role of gut microbiota in sarcopenia requires further comprehensive investigation in human subjects to establish its correlation.
ABSTRACT
Basal progenitor cells are crucial for maintaining foregut (the esophagus and forestomach) homeostasis. When their function is dysregulated, it can promote inflammation and tumorigenesis. However, the mechanisms underlying these processes remain largely unclear. Here, we employ genetic mouse models to reveal that Jag1/2 regulate esophageal homeostasis and foregut tumorigenesis by modulating the function of basal progenitor cells. Deletion of Jag1/2 in mice disrupts esophageal and forestomach epithelial homeostasis. Mechanistically, Jag1/2 deficiency impairs activation of Notch signaling, leading to reduced squamous epithelial differentiation and expansion of basal progenitor cells. Moreover, Jag1/2 deficiency exacerbates the deoxycholic acid (DCA)-induced squamous epithelial injury and accelerates the initiation of squamous cell carcinoma (SCC) in the forestomach. Importantly, expression levels of JAG1/2 are lower in the early stages of human esophageal squamous cell carcinoma (ESCC) carcinogenesis. Collectively, our study demonstrates that Jag1/2 are important for maintaining esophageal and forestomach homeostasis and the onset of foregut SCC.
Subject(s)
Carcinogenesis , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Esophagus , Homeostasis , Jagged-1 Protein , Jagged-2 Protein , Stem Cells , Animals , Jagged-1 Protein/metabolism , Jagged-1 Protein/genetics , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Neoplasms/metabolism , Esophagus/pathology , Esophagus/metabolism , Stem Cells/metabolism , Mice , Jagged-2 Protein/metabolism , Jagged-2 Protein/genetics , Humans , Carcinogenesis/genetics , Carcinogenesis/pathology , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/metabolism , Mice, Knockout , Signal Transduction , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Receptors, Notch/metabolism , Receptors, Notch/genetics , Cell Differentiation , Male , FemaleABSTRACT
The gut microbiota play a pivotal role in human health. Emerging evidence indicates that gut microbes participate in the progression of tumorigenesis through the generation of carcinogenic metabolites. However, the underlying molecular mechanism is largely unknown. In the present study we show that a tryptophan metabolite derived from Peptostreptococcus anaerobius, trans-3-indoleacrylic acid (IDA), facilitates colorectal carcinogenesis. Mechanistically, IDA acts as an endogenous ligand of an aryl hydrocarbon receptor (AHR) to transcriptionally upregulate the expression of ALDH1A3 (aldehyde dehydrogenase 1 family member A3), which utilizes retinal as a substrate to generate NADH, essential for ferroptosis-suppressor protein 1(FSP1)-mediated synthesis of reduced coenzyme Q10. Loss of AHR or ALDH1A3 largely abrogates IDA-promoted tumour development both in vitro and in vivo. It is interesting that P. anaerobius is significantly enriched in patients with colorectal cancer (CRC). IDA treatment or implantation of P. anaerobius promotes CRC progression in both xenograft model and ApcMin/+ mice. Together, our findings demonstrate that targeting the IDA-AHR-ALDH1A3 axis should be promising for ferroptosis-related CRC treatment.
Subject(s)
Colorectal Neoplasms , Ferroptosis , Gastrointestinal Microbiome , Humans , Animals , Mice , Ferroptosis/genetics , Carcinogenesis/genetics , Cell Transformation, Neoplastic , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathologyABSTRACT
INTRODUCTION: The present study aimed to examine the correlation between serum cytokine levels and the incidence of coronary artery disease (CAD), a leading cause of mortality globally, which is known to have a strong association with inflammatory factors. The study further sought to determine the predictors of CAD to distinguish patients with coronary artery lesions from those suspected of having CAD. METHODS AND RESULTS: In this study, 487 patients who underwent coronary angiography as a result of suspected CAD but without acute myocardial infarction (AMI) were recruited. The serum levels of the cytokines interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-α, interferon (IFN)-α, and IFN-γ were measured using a multiplexed particle-based flow cytometric assay technique. The results of the study revealed that the levels of IL-4, IL-12p70, IL-17, IFN-α, and IFN-γ in the CAD group were significantly lower compared to those in the non-CAD group. Multivariate logistic regression analysis indicated that two serum cytokines (IL-4 and IL-17), one protective factor (high-density lipoprotein cholesterol [HDL-C]), and three risk factors (sex, smoking, and diabetes) were independently predictive of CAD. The receiver operating characteristic curve analysis showed that the combined use of these predictors in a multivariate model demonstrated good predictive performance for CAD, as evidenced by an area under the curve value of 0.826. CONCLUSION: The results of the study indicated that serum IL-4 and IL-17 levels serve as independent predictors of CAD. The risk prediction model established in the research, which integrates these serum cytokines (IL-4 and IL-17) with relevant clinical risk factors (gender, smoking, and diabetes) and the protective factor HDL-C, holds the potential to differentiate patients with CAD from those suspected of having CAD but without AMI.
Subject(s)
Coronary Artery Disease , Diabetes Mellitus , Myocardial Infarction , Humans , Coronary Artery Disease/complications , Cytokines , Interleukin-17 , Interleukin-4 , Myocardial Infarction/complicationsABSTRACT
Background: Transcatheter aortic valve replacement (TAVR) potentially may be significantly simplified by using the single artery access (SA) technique, which does not require a secondary artery access. Nevertheless, the safety and efficacy of this technique remains unclear. Our goal was to determine if single artery access TAVR (without upgrading the sheath size) is a feasible, minimally invasive procedure. Methods: Patients with symptomatic severe aortic stenosis who underwent TAVR via the femoral artery were consecutively enrolled in this study. Eligible individuals were divided into 2 groups: the SA group and the dual artery access (DA) group. The primary end point was device success (defined by the valve academic research consortium 3, VARC 3). A 6-month follow-up and propensity score matching analyses were performed. Results: After propensity score matching analysis, a total of 130 patients were included: 65 in the SA group and 65 in the DA group. The SA procedure achieved similar device success (95.4% vs. 87.7%; P = 0.115) compared with the DA procedure. The SA procedure shortened the operating time (102â min vs. 125â min; P = 0.001) but did not increase the x-ray time or dose. Both a 20 Fr and a 22 Fr sheath (without upgrading the sheath size) could be used for the SA procedure. There was no major vascular complication occurred in both groups. The incidence of minor main vascular and access complications in the SA group was comparable to those of the DA procedure (0.0% vs. 3.1%; P = 0.156). Conclusions: The SA access procedure is a promising minimally invasive TAVR technique with a low incidence of vascular complications and a high incidence of device success. It is safe and possibly applicable in all TAVR procedures.
ABSTRACT
Psoriasis is a chronic inflammatory skin disease mediated by immune and complex genetic factors. The wingless-related integration site (Wnt) signaling pathway plays a critical role in psoriasis, but how the Wnt pathway is regulated in psoriatic skin and whether it can be exploited for therapeutic benefits is unclear. By comparing biopsies from healthy and psoriatic skin, we found that Wnt inhibitory factor 1 (WIF1), an inhibitor of Wnt signaling, showed reduced expression at both mRNA and protein levels in psoriatic skin. We then quantified methylation of the WIF1 gene promoter by DNA methylation sequencing and found that the WIF1 promoter region was hypermethylated. We further showed that recombinant WIF1 injection ameliorates the imiquimod (IMQ) mouse model of psoriasis. We also revealed that treatment with the DNA methylation inhibitor, decitabine, inhibited proliferation of immortalized human keratinocytes (HaCaT) in a psoriasis-like inflammatory environment. Finally, we applied decitabine to the IMQ mouse model and demonstrated that treatment of mice with decitabine ameliorates the disease. Therefore, our study reveals that methylation of the WIF1 gene is associated with the pathogenesis of psoriasis, and suggests that pharmacological targeting of DNA methylation is a potential treatment strategy for psoriasis.
Subject(s)
Psoriasis , Humans , Animals , Mice , Decitabine/pharmacology , Decitabine/therapeutic use , Decitabine/metabolism , Psoriasis/drug therapy , Psoriasis/genetics , Psoriasis/pathology , Skin/pathology , Keratinocytes , DNA Methylation , Imiquimod/therapeutic use , Promoter Regions, Genetic/genetics , Mice, Inbred BALB C , Disease Models, AnimalABSTRACT
Background: Limited data exist on the use of temporary permanent pacemaker (TPPM) to reduce unnecessary PPM in patients with high-degree atrioventricular block (HAVB) after transcatheter aortic valve replacement (TAVR). Objectives: This study aims to determine the feasibility of TPPM in patients with HAVB after TAVR to provide prolonged pacing as a bridge. Materials and methods: One hundred and eleven consecutive patients undergoing TAVR were screened from August 2021 to June 2022. Patients with HAVB eligible for PPM were included. TPPM were used in these patients instead of conventional temporary pacing or early PPM. Patients were followed up for 1 month. Holter and pacemaker interrogation were used to determine whether to implant PPM. Results: Twenty one patients met the inclusion criteria for TPPM, of which 14 patients were third-degree AVB, 1 patient was second-degree AVB, 6 patients were first degree AVB with PR interval > 240 ms and LBBB with QRS duration > 150 ms. TPPM were placed on the 21 patients for 35 ± 7 days. Among 15 patients with HAVB, 26.7% of them (n = 4) recovered to sinus rhythm; 46.7% (n = 7) recovered to sinus rhythm with bundle branch block. The remains of 26.7% patients (n = 4) still had third-degree AVB and received PPM. For patients with first-degree AVB and LBBB, PR interval shortened to < 200 ms in all 6 patients and LBBB recovered in 2 patients. TPPM were successfully removed from all patients and no procedure-related adverse events occurred. Conclusion: TPPM is reliable and safe in the small sample of patients with conduction block after TAVR to provide certain buffer time to distinguish whether a PPM is necessary. Future studies with larger sample are needed for further validation of the current results.
ABSTRACT
Emerging evidence reveals that amino acid metabolism plays an important role in ferroptotic cell death. The conversion of methionine to cysteine is well known to protect tumour cells from ferroptosis upon cysteine starvation through transamination. However, whether amino acids-produced metabolites participate in ferroptosis independent of the cysteine pathway is largely unknown. Here, the authors show that the tryptophan metabolites serotonin (5-HT) and 3-hydroxyanthranilic acid (3-HA) remarkably facilitate tumour cells to escape from ferroptosis distinct from cysteine-mediated ferroptosis inhibition. Mechanistically, both 5-HT and 3-HA act as potent radical trapping antioxidants (RTA) to eliminate lipid peroxidation, thereby inhibiting ferroptotic cell death. Monoamine oxidase A (MAOA) markedly abrogates the protective effect of 5-HT via degrading 5-HT. Deficiency of MAOA renders cancer cells resistant to ferroptosis upon 5-HT treatment. Kynureninase (KYNU), which is essential for 3-HA production, confers cells resistant to ferroptotic cell death, whereas 3-hydroxyanthranilate 3,4-dioxygenase (HAAO) significantly blocks 3-HA mediated ferroptosis inhibition by consuming 3-HA. In addition, the expression level of HAAO is positively correlated with lipid peroxidation and clinical outcome. Together, the findings demonstrate that tryptophan metabolism works as a new anti-ferroptotic pathway to promote tumour growth, and targeting this pathway will be a promising therapeutic approach for cancer treatment.
Subject(s)
Neoplasms , Tryptophan , Humans , Tryptophan/metabolism , Cysteine/metabolism , Serotonin/metabolism , Neoplasms/drug therapy , Lipid PeroxidationABSTRACT
Inherited genetic variations in the melanocortin-1 receptor (MC1R) responsible for human red hair color (RHC) variants are associated with impaired DNA damage repair and increased melanoma risk. MC1R signaling is critically dependent on palmitoylation, primarily mediated by the protein acyltransferase zinc finger DHHC-type palmitoyltransferase 13 (ZDHHC13). A better understanding of how ZDHHC13 is physiologically activated could help identify approaches to prevent melanomagenesis in redheads. Here, we report that AMP-activated protein kinase (AMPK) phosphorylates ZDHHC13 at S208 to strengthen the interaction between ZDHHC13 and MC1R-RHC, leading to enhanced MC1R palmitoylation in redheads. Consequently, phosphorylation of ZDHHC13 by AMPK increased MC1R-RHC downstream signaling. AMPK activation and MC1R palmitoylation repressed UVB-induced transformation of human melanocytes in vitro and delayed melanomagenesis in vivo in C57BL/6J-MC1R-RHC mice. The importance of AMPK to MC1R signaling was validated in human melanomas where AMPK upregulation correlated with expression of factors downstream from MC1R signaling and with prolonged patient survival. These findings suggest AMPK activation as a promising strategy to reduce melanoma risk, especially for individuals with red hair. SIGNIFICANCE: Phosphorylation of ZDHHC13 by AMPK at S208 promotes MC1R activation and suppresses melanocyte transformation, indicating activation of AMPK as a potential approach to prevent melanoma in people with red hair.
Subject(s)
AMP-Activated Protein Kinases , Cell Transformation, Neoplastic , Melanoma , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Enzyme Activation , Phosphorylation , Lipoylation , Melanocytes/enzymology , Melanocytes/radiation effects , Humans , Animals , Mice , Melanoma/genetics , Ultraviolet Rays , Gene Expression Regulation/genetics , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/radiation effectsABSTRACT
Understanding the heterogeneous intestinal microenvironment is critical to uncover the pathogenesis of inflammatory bowel disease (IBD). Recent advances in single-cell RNA sequencing (scRNA-seq) have identified certain cell types and genes that could contribute to IBD; however, a comprehensively integrated analysis of these scRNA-seq datasets is not yet available. Here we introduce scIBD, a platform for single-cell meta-analysis of IBD with interactive and visualization features, which combines highly curated single-cell datasets in a uniform workflow, enabling identifying rare or less-characterized cell types in IBD and dissecting the commonalities, as well as the differences between ulcerative colitis and Crohn's disease. scIBD also incorporates multifunctional information-including regulon activity, GWAS-implicated risk genes and genes targeted by therapeutics-to infer clinically relevant cell-type specificity. Collectively, scIBD is a user-friendly web-based platform for the community to analyze the transcriptome features and gene regulatory networks associated with the pathogenesis and treatment of IBD at single-cell resolution.
Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Humans , Inflammatory Bowel Diseases/genetics , Colitis, Ulcerative/etiology , Crohn Disease/diagnosis , TranscriptomeABSTRACT
It was to explore the application value of individualized nursing oriented by solution-focused nursing mode in postoperative nursing of patients with pelvic fractures. 90 patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI) were enrolled. They were randomly grouped into a control group and an experimental group, with 45 cases in each group. Patients in the general group were treated with conventional treatment, and patients in the enhancement group were treated with high-dose rosuvastatin based on conventional treatment. The experimental group was compared for indicators such as serum inflammatory factors, cardiac function, overall efficacy, and follow-up prognosis before and after the operation. After treatment, the total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the enhancement group were better as against the control group (P<0.05). Through treatment, the concentration of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the enhancement group was lower compared to the general group. The total effective rate of the enhancement group (95.56%) was higher relative to the general group (86.67%) (P<0.05). In patients with STEMI, preoperative intensive statin therapy can improve the efficacy of PCI, and reduce the inflammatory response and the incidence of cardiovascular events.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/surgery , C-Reactive Protein/metabolism , Cholesterol, LDL , Arrhythmias, Cardiac , Treatment OutcomeABSTRACT
The study aimed to explore the correlations of the results of the high-frequency ultrasound evaluation of the brachial artery endothelial dilatation and carotid atherosclerosis with glucose and lipid metabolism, inflammatory cytokines, the severity of coronary artery disease (CAD) and vascular endothelial function in elderly patients. 78 elderly patients with CAD in Beijing Anzhen Hospital were selected. The high-frequency ultrasonography was carried out to observe the flow-mediated dilatation (FMD) and intima-media thickness (IMT) and to analyze their correlations with inflammatory cytokines [C-reactive protein (CRP) and plasminogen activator inhibitor (PAI-1)], endothelial function [nitric oxide (NO) and endothelin-1 (ET-1)], glycolipid metabolism [high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG) and fasting blood glucose (FBG)] and the severity of CAD. FMD, NO and HDL-C: patients with single-vesselCAD> those with double-vessel CAD>those with multi-vessel CAD. IMT, CRP, PAI-1, FBG, ET-1, TC and TG: patients with single-vesselCAD< those with double-vessel CAD Subject(s)
Carotid Artery Diseases
, Coronary Artery Disease
, Aged
, Brachial Artery
, C-Reactive Protein
, Carotid Arteries
, Carotid Intima-Media Thickness
, Cholesterol
, Cytokines
, Dilatation
, Endothelium, Vascular
, Glucose
, Humans
, Lipid Metabolism
, Plasminogen Activator Inhibitor 1
, Triglycerides
, Ultrasonography
ABSTRACT
Endoplasmic reticulum (ER) stress is a cellular state that results from the overload of unfolded/misfolded protein in the ER that, if not resolved properly, can lead to cell death. Both acute lung infections and chronic lung diseases have been found related to ER stress. Yet no study has been presented integrating metabolomic and transcriptomic data from total lung in interpreting the pathogenic state of ER stress. Total mouse lungs were used to perform LC-MS and RNA sequencing in relevance to ER stress. Untargeted metabolomics revealed 16 metabolites of aberrant levels with statistical significance while transcriptomics revealed 1593 genes abnormally expressed. Enrichment results demonstrated the injury ER stress inflicted upon lung through the alteration of multiple critical pathways involving energy expenditure, signal transduction, and redox homeostasis. Ultimately, we have presented p-cresol sulfate (PCS) and trimethylamine N-oxide (TMAO) as two potential ER stress biomarkers. Glutathione metabolism stood out in both omics as a notably altered pathway that believed to take important roles in maintaining the redox homeostasis in the cells critical for the development and relief of ER stress, in consistence with the existing reports.
Subject(s)
Cresols/metabolism , Endoplasmic Reticulum Stress/physiology , Glutathione/metabolism , Lung Injury/diagnosis , Methylamines/metabolism , Sulfuric Acid Esters/metabolism , Animals , Biomarkers/analysis , Biomarkers/metabolism , Cresols/analysis , Endoplasmic Reticulum Stress/genetics , Gene Expression Profiling/methods , Lung/chemistry , Lung/metabolism , Lung/pathology , Lung Injury/genetics , Lung Injury/metabolism , Lung Injury/pathology , Male , Metabolomics/methods , Methylamines/analysis , Mice , Mice, Inbred C57BL , Oxidative Stress/genetics , Oxidative Stress/physiology , Sulfuric Acid Esters/analysis , Unfolded Protein Response/genetics , Unfolded Protein Response/physiologyABSTRACT
BACKGROUND: Revascularization for the treatment of coronary artery disease (CAD) is advancing rapidly and is used increasingly in old patients. This study aimed to compare the efficacy and safety of revascularization with drug therapy in CAD patients aged over 80 years at a real-world clinical setting. METHODS: A total of 501 CAD patients aged over 80 years were consecutively enrolled from January 2011 to January 2016 in Anzhen Hospital (Beijing, China), Capital Medical University. The patients were treated with percutaneous coronary intervention (PCI) (n=283), coronary artery bypass grafting (CABG) (n=106), or drug therapy (n=112). All-cause mortality, cardiovascular-related mortality, readmission rate, and Seattle Angina Questionnaire (SAQ) score were compared between the three treatment methods. RESULTS: A total of 411 patients (82.04%) were followed with a median duration of 25 months. All-cause mortality and cardiovascular-related mortality in the drug therapy group were significantly higher than the PCI and CABG groups (both P<0.05). Readmission rate for cardiovascular events in the CABG group was significantly lower than the PCI and drug therapy groups (both P<0.05). Scores of physical limitation, angina frequency, treatment satisfaction, and disease perception of the SAQ in the PCI and CABG groups were significantly higher than the drug therapy group (both P<0.05). Scores of angina stability did not differ significant between the three groups (P=0.127). CONCLUSIONS: Revascularization is superior to drug therapy in efficacy and safety in the treatment of oldest-old patients with CAD.
ABSTRACT
Melanoma is the deadliest form of skin cancer, and nearly 90% of melanomas are believed to be caused by ultraviolet radiation (UVR), mainly from sunlight. UVR induces DNA damage, forming products such as cyclobutane pyrimidine dimers (CPD) and 6-4-pyrimidone photoproducts (6-4PP) in a wavelength-dependent manner and causes oxidative DNA damage. These DNA lesions lead to DNA mutations and contribute to the formation of melanoma. In this review, we discuss the protective role of melanocytes against UV-induced DNA damage and how genetic variations, including those in p53 and melanocortin-1 receptor (MC1R), or epigenetic histone modifications in melanocytes result in a tendency toward melanoma. We also provide a summary of prevention and treatment strategies against melanoma, including the most recent immunotherapies. Collectively, this work contributes to the understanding of the molecular pathogenesis of UV-induced melanoma.
ABSTRACT
BACKGROUND: Coronary artery disease (CAD) in octogenarians (age of ≥80 years) has a high risk of mortality and high medical expenses. Research shows that the prevalence of CAD is higher among octogenarians than that among younger people, but few such patients undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study aimed to evaluate different treatments with respect to their clinical effects and impacts on quality of life of octogenarians with CAD. METHODS: Data of 519 octogenarians with CAD consecutively treated at Beijing Anzhen Hospital, Capital Medical University (Beijing, China) from January 2010 to January 2016 were collected in this study. The patients were categorized into three groups based on the treatments they received: the PCI group (nâ=â292), CABG group (nâ=â110), and medical treatment group (nâ=â117). The followings were recorded during follow-up: clinical data, death (all-cause and cardiovascular-related), re-hospitalization time, Seattle Angina Questionnaire (SAQ) score, and occurrence of hemorrhagic events (cerebral bleeding, gastrointestinal bleeding, and dermal ecchymosis). RESULTS: The median follow-up duration was 25.0 (25th, 75th percentile: 17.0, 55.5) months among 417 patients. The all-cause death rates (28.2% vs. 12.0% and 14.6%, respectively) and cardiovascular-related death rates (15.4% vs. 3.8% and 6.4%, respectively) were significantly higher in the medical treatment group than those in the PCI group and CABG group (all Pâ<â0.05). The re-hospitalization rate for cardiovascular events was significantly lower in the CABG group than those in the PCI group and medical treatment group (3.8% vs. 12.8% and 14.9%, respectively) (χâ=â8.238, Pâ=â0.018). The SAQ scores of physical limitation, angina frequency, treatment satisfaction, and disease perception were significantly higher in the PCI group and CABG group than those in the medical treatment group (all Pâ<â0.05). No significant difference in the angina stability score was observed among the three groups (Fâ=â3.179, Pâ=â0.204). CONCLUSION: PCI and CABG result in reduced mortality and better quality of life in octogenarians with CAD.
Subject(s)
Coronary Artery Disease/pathology , Coronary Artery Disease/physiopathology , Aged, 80 and over , Coronary Angiography , Coronary Artery Bypass , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Female , Humans , Male , Quality of LifeABSTRACT
Immunotherapy with checkpoint inhibitors has greatly prolonged the overall survival of cancer patients in melanoma and many other cancer types. However, only a subset of patients shows clinical responses from these interventions, which was predicated by the T cell-inflamed tumor microenvironment. T cell-inflamed phenotype is characterized by the infiltration of CD8+ T cells, CD8α/CD103-lineage dendritic cells (DCs), as well as high density of forkhead box P3 (FoxP3)+ regulatory T cells (Tregs) that are associated with the efficacy of immune checkpoint blockade. A number of regulators has been associated with T cell-inflammation in the tumor microenvironment, and WNT/ß-catenin signaling is one of the best characterized. The tumor-intrinsic WNT/ß-catenin signaling activation is frequently associated with poor spontaneous T cell infiltration across most human cancers. In this article, we review the essential roles of WNT/ß-catenin signaling in the T cell-inflamed and non-T cell-inflamed tumor microenvironment, including the development and function of immune cells, activation of immune exclusion of tumor cells, and cancer immunosurveillance. We also discuss the impact of this pathway in driving the non-T cell-inflamed tumor microenvironment in other tumor types. To improve immunotherapy efficacy, we argue that targeting Wnt/ß-catenin signaling should be a high priority for combinational cancer therapy to restore T cell infiltration.