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Objective This study aimed to investigate the factors influencing the personal burden rate incerebral ische-mic patients,compare the difference in the burden rate among the patients with varying degrees of cerebral ischemia,provide a reference for establishing a personal burden rate evaluation,and propose suggestions for control its increase.Methods The medi-cal insurance data were collected from 8164 discharged patients in a tertiary hospital in Tianjin between January and December 2022.With the data,the Generalized Linear Model was utilized to analyze the factors affecting the personal burden rate across different Diagnosis Related Groups(DRGs).Results Statistically significant differences were observed in the cost structure a-mong different DRGs.Age,length of hospital stays,total hospitalization cost,hospital admission mode,number of hospitaliza-tions,and type of medical insurance significantly impacted the personal burden rate.The personal burden rate was inversely cor-related with age and length of hospital stays,but directly correlated with the total hospitalization cost.The patients admitted from emergency,first-time hospitalization,and those covered by the basic medical insurance program for urban employees had a lower personal burden rate.Conclusion Hospitals should establish diverse personal burden rate performance evaluation standards for patients with different types of medical insurance,incorporating factors such as average length of hospital stays and average hospi-talization cost.A more equitable hospital internal assessment plan should be developed by considering patients admitted to differ-ent departments and aligning with the characteristics of clinical pathways.Medical institutions should minimize self-funded pro-jects under declared medical insurance,increase the enrollment of cases in DRGs,and promote tiered diagnosis and treatment to reduce the personal burden rate for patients.
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This article reviewed the present situation of the research on the relationship between the number of nursing staff, education level, skill combination and patient safety at home and abroad, as well as the indirect mechanism of nursing manpower factors on patient safety through intermediary factors such as working environment, attendance, nursing lack and so on. In view of the problems existing in domestic research, some suggestions were put forward, such as carrying out longitudinal and intervention research on patient safety, optimizing the allocation of nursing human resources and patient safety indicators, exploring the mechanism of multiple nursing factors and patient safety and conducting empirical analysis. To provide reference for hospital managers to improve nursing quality and ensure patient safety.
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Objective:A kinetic model of the clearance of protein-bound uremic toxins (PBUTs) in maintenance hemodialysis patients is established to evaluate the effects of adding sorbents with different sorption efficiency to dialysate on the clearance rate of PBUTs, and to predict the sorption efficiency of sorbents using the model.Methods:The kinetic model was established by integrating the parameters of plasma flow rate ( Qp), dialysate flow rate ( Qd), free plasma fraction of PBUTs ( f1), free dialysate fraction of PBUTs ( f2), mass transfer coefficient of dialyzer ( K) and surface area of dialysis membrane ( A), and using the mass balance equation and Fick's first law. The model was also used to evaluate the relationship between the clearance rate of different PBUTs and the parameters of dialyzer and the sorption efficiency of sorbents. Results:The kinetic model of PBUTs clearance (CL): ?CL=Qp1-f1-f2γφf1-f2γ,?γ=QpQd,?φ=eKAf1Qp-f2Qd. The model was used to analyze the dialysis parameters of indoxyl sulfate and p-cresol sulfate dialysis.The clearance rate of PBUTs increased with the decrease of its binding capacity to albumin in plasma and the increase of plasma flow rate in dialyzer, dialysate flow rate, mass transfer coefficient of dialyzer, surface area of dialysis membrane, and sorption capacity of sorbents in dialysate. The increasing trend of PBUTs clearance rate was particularly obvious after applying sorbents. Further analysis of the dialysate flow rate and the sorption efficiency of sorbents in the dialysate showed that the increase of the dialysate flow rate could make up for the difference of the sorption efficiency of sorbents. When the dialysate flow rate tended to be infinite, the sorption efficiency of sorbents in the dialysate had no effect on the clearance rate of PBUTs. Conclusion:Adding sorbents of PBUTs to the dialysate during dialysis can significantly improve the clearance rate of PBUTs, suggesting a promising clinical application value.
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Paget disease of the vulva is the most common type of extramammary Paget disease and is a rare clinical malignancy occurring in the vulva. At present, the specific pathogenesis is not clear, and the lesions mainly involve areas rich in apocrine sweat glands, such as the external genitalia. The clinical manifestations show no obvious heterogeneity, and may be characterized by erythema, pruritus, scurf and tingling in the lesion area, with erosion and exudation in severe cases. Diagnosis requires histopathological examination and immunohistochemistry. Paget disease of the vulva is often misdiagnosed as eczema or dermatitis due to the lack of knowledge about this disease in clinicians. This article reviews the current research progress of Paget disease of the vulva, in order to deepen clinicians' understanding of this disease and effectively improve clinical diagnosis and treatment abilities.
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Rheumatoid arthritis (RA) is a systemic chronic auto-inflammatory disease, characterized by infiltration of inflammatory cells, pannus formation, articular cartilage destruction, and bone matrix destruction. Therefore, improving articular cartilage destruction has an important impact on the treatment of RA. Chinese medicine has a good application effect in improving cartilage destruction of RA due to its characteristics of multiple components, multiple targets, high activity and low side effects. Based on this, the author reviewed relevant literature to summarize the relevant research and mechanism of Chinese medicine and its active components in improving RA cartilage destruction. The results showed that Chinese medicine and its active components can improve RA cartilage destruction by regulating inflammatory factors, phosphatidylinositol 3-kinase/protein kinase B, Wnt/β- catenin, nuclear factor-κB, mitogen-activated protein kinase, Janus kinase 2/signal transduction and activator of transcription 3/ vascular endothelial growth factor, microRNAs, fibroblastic synovial cells.
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The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Subject(s)
Animals , Male , Testis , Sertoli Cells/metabolism , Transcriptome , Spermatogenesis/genetics , Primates , Aging/genetics , Stem CellsABSTRACT
Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Subject(s)
Animals , Humans , Sarcopenia/metabolism , Forkhead Box Protein O3/metabolism , Muscle, Skeletal/metabolism , Aging/metabolism , Primates/metabolismABSTRACT
Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Subject(s)
Mice , Animals , Transcriptome , Aging/metabolism , Cochlea , Stria Vascularis , PresbycusisABSTRACT
Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Subject(s)
Aged , Animals , Humans , Aging/genetics , Forkhead Transcription Factors/metabolism , Myocytes, Cardiac/metabolism , Primates/metabolism , Repressor Proteins/metabolism , Transcriptome , Macaca fascicularis/metabolismABSTRACT
Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Subject(s)
Mice , Animals , Quercetin/pharmacology , Endothelial Cells , Hair , Hair Follicle , AlopeciaABSTRACT
Acupuncture for Benign prostatic hyperplasia (BPH) pays attention to the syndrome differentiation theory, but also emphasizes the differentiation of the meridians, to obtain the better effective. At present, the clinical treatment of BPH is mainly based on deep acupuncture with filiform needle, electroacupuncture, warm acupuncture and moxibustion and comprehensive treatment of acupuncture and moxibustion, especially the comprehensive treatment of warm acupuncture combined with needle, Traditional Chinese Medicine and western medicine. Acupuncture treatment of BPH can reduce the prostate volume of patients, improve their lower urinary tract symptoms, improve their quality of life, without sever adverse events. BPH patients are often accompanied by emotional problems. It is suggested that acupuncture "treating spirit" should be further developed in clinical treatment to promote the application of acupuncture in the treatment of this disease.
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Objective:To establish a more suitable and practicable criterion of metabolically healthy overweight/obesity (MHO/O) in Chinese, a comparison study on different criteria of MHO/O was conducted in subjects aged over 45-year-old in Shanghai Changfeng Community.Method:A total of 3 301 overweight/obese subjects over 45 years old (men 1 521, women 1 789) in Shanghai Changfeng Community was included in the study. According to the inclusion or exclusion of waist circumference (WC), homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.5, and numbers of abnormal metabolic components, the MHO/O criteria were divided into 7 types: Adult Treatment Panel Ⅲ (ATP-Ⅲ) (with WC)<1 component, ATP-Ⅲ (with WC)<2 components, ATP-Ⅲ (with WC)<3 components, ATP-Ⅲ (without WC)<1 component, ATP-Ⅲ (without WC)<2 components, adjusted metabolic associated fatty liver disease (MAFLD) criteria<1 component, and adjusted MAFLD criteria<2 components. The prevalence of MHO/O and its relationship with the changes of body mass index (BMI), and the differences of the characteristics of MHO/O among the 7 types of metabolic health standards were compared.Result:The prevalence of MHO/O according to the ATP-Ⅲ (with WC)<1, ATP-Ⅲ (with WC)<2, ATP-Ⅲ (with WC)<3, ATP-Ⅲ (without WC)<1, ATP-Ⅲ (without WC)<2, adjusted MAFLD criteria<1, and adjusted MAFLD criteria<2 was 2.85%, 15.48%, 39.87%, 8.00%, 33.66%, 2.33%, 12.24%, respectively. The prevalence of MHO/O decreased as BMI increased. When BMI ≥ 28 kg/m 2, the prevalence of MHO/O by ATP-Ⅲ (with WC)<1 and adjusted MAFLD criteria<1 dropped to 0. Conclusion:The adjusted MAFLD criterion without abnormal metabolic components is the most practicable definition of MHO/O.
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Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Subject(s)
Animals , Mice , Aging , Autoimmune Diseases , Disease Models, Animal , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Mice, Inbred C57BL , Th17 Cells/metabolism , Uveitis/pathology , VirulenceABSTRACT
Vascular calcification is a common pathological process in patients with diabetes, chronic kidney disease, and cardiovascular disease, manifested by the deposition of hydroxyapatite on the walls of blood vessels. Hydrogen sulfide is the third gas signal molecule found in mammals after nitric oxide and carbon monoxide, which has anti-inflammatory, antioxidant stress and other effects in the cardiovascular system. In recent years, it has been recognized that hydrogen sulfide has an anti-vascular calcification effect, and supplementation with hydrogen sulfide and its donors can alleviate vascular calcification. In this review, we discussed the various evidence of the protective effect of hydrogen sulfide on vascular calcification, and highlighted the hydrogen sulfide metabolism changes and the potential regulatory mechanisms of hydrogen sulfide on the pathophysiological changes in vascular calcification.
Subject(s)
Animals , Humans , Hydrogen Sulfide/metabolism , Cardiovascular Diseases , Carbon Monoxide , Antioxidants , Nitric Oxide , Mammals/metabolismABSTRACT
Objective:To predict the pathogens of bloodstream infection (BSI) in hematopoietic stem cell transplantation (HSCT) patients by plasma microbial cell-free DNA (mcfDNA) sequencing with and without additional amplification.Methods:A total of 978 HSCT patients were enrolled in Peking University People′s Hospital from March to July 2021, and the 7 428 blood samples were prospectively collected from pretransplant conditioning period to 4 months after transplantation. The plasma samples were separated and then cryopreserved. According to blood culture results and whether there were plasma samples before BSI onset, twenty-eight HSCT patients with positive blood culture (39 plasma samples within 1-8 days before BSI onset) and 9 HSCT patients with negative blood culture (9 plasma samples) were filtered. The 39 samples were performed with mcfDNA additional and non-additional amplification sequencing, and the 9 samples were only performed with additional amplification sequencing. With the blood culture results as the gold standard, the consistency between the sequencing and the blood culture results was observed. Student t test and Wilcoxon test were used for statistical analysis. Results:Without additional amplification sequencing, only 7 samples sequencing results were consistent with the blood culture results, and the total pathogen detection rate was 17.95% (7/39). The rates within 3 days and 4-8 days were 23.81% (5/21) and 2/18, respectively. The main pathogenic type detected was gram-negative bacteria (5/7). With additional amplification sequencing, the total pathogen detection rate was 59.26% (16/27) and the rate within 3 days was 8/13. The number of gram-positive bacteria detected was elevated (13/16) and the number of additional microorganisms in additional amplification sequencing was increased significantly ( P=0.001 0), compared with non-additional amplification sequencing. Moreover, additional sequencing analysis of 9 samples from patients with negative culture result showed that no pathogen was detected in six samples, and the common Torque teno virus in HSCT patients was detected in only three samples. Conclusion:The pathogen detection rate of plasma mcfDNA additional amplification sequencing was better than that of non-additional amplification sequencing in HSCT patients before BSI onset, especially in the first three days, which has the potential to predict BSI pathogens.
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Objective:To analyze the clinical characteristics of acute drug poisoning, and provide better management for poisoned patients in Emergency Department.Methods:We retrospectively enrolled 197 patients diagnosed as acute drug poisoning in Emergency Department of Beijing Chaoyang Hospital from January 1, 2019 to December 31, 2019. Medical records included age, gender, baseline diseases, medication time, visit time, kinds of drugs, drug concentrations, accompanying symptom, hospitalization duration, treatment, fluid resuscitation and outcomes. The inclusion criteria were as follows: age≥ 14 years old, and met the criteria of acute poisoning. The exclusion criteria were as follows: age<14 years old; incomplete clinical data; pesticide poisoning; toxic gas poisoning; and other non-drug poisoning. All patients were divided into the survival group and death group according to their outcomes at the discharge. Clinical characteristics, laboratory parameters and treatments were compared using the Student’s t test, Mann-Whitney U test, as appropriate. Results:The mean age of all the patients was 38.9±20.4 years. The majority were young patients, accounting for 134 cases (68.0%). The accompanying symptoms included consciousness disturbance (106 cases), dizziness (56 cases), fatigue (38 cases), and nausea and/or vomiting (42 cases). The duration of medication-to-visit time was 0.5-96 h, with an average of 7.17±0.89 h. The types of drugs included 105 (53.2%) sedatives and hypnotics, 73 antipsychotics (37.1%), 17 antibiotics (8.6%), and 20 antipyretic analgesics (10.2%). The Glasgow comascale (GCS) score of patients in the survival group was higher than that of the death group (12.47±3.05 vs 7.60±4.43, P<0.01). In the death group, the alanine aminotransferase, urea nitrogen, creatinine, cardiac troponin I, prothrombin time, activated partial thromboplastin time, plasma fibrinogen and D-dimer were higher than those of the survival group (all P<0.05). One hundred and eighty-seven patients were cured, while 10 patients died. One hundred and fifty-nine patients were treated with gastric lavage, and 23 patients were treated with blood purification. The concentrations of toxic drugs before and after treatment in 134 poisoned patients were compared. The concentration of drugs after treatment was significantly lower than that before treatment. Conclusions:Acute non-pesticide poisoning in Emergency Department is mainly caused by sedatives, hypnotics, antipsychotics, and antipyretics and analgesics. It is important to conduct laboratory examinations for toxic medications to provide better management for poisoned patients. It is necessary to establish a standardized monitoring system and management path for acute drug poisoning.
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The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.
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Objective@#The mitotic count of gastrointestinal stromal tumors (GIST) is closely associated with the risk of planting and metastasis. The purpose of this study was to develop a predictive model for the mitotic index of local primary GIST, based on deep learning algorithm. @*Materials and Methods@#Abdominal contrast-enhanced CT images of 148 pathologically confirmed GIST cases were retrospectively collected for the development of a deep learning classification algorithm. The areas of GIST masses on the CT images were retrospectively labelled by an experienced radiologist. The postoperative pathological mitotic count was considered as the gold standard (high mitotic count, > 5/50 high-power fields [HPFs]; low mitotic count, ≤ 5/50 HPFs). A binary classification model was trained on the basis of the VGG16 convolutional neural network, using the CT images with the training set (n = 108), validation set (n = 20), and the test set (n = 20). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at both, the image level and the patient level. The receiver operating characteristic curves were generated on the basis of the model prediction results and the area under curves (AUCs) were calculated. The risk categories of the tumors were predicted according to the Armed Forces Institute of Pathology criteria. @*Results@#At the image level, the classification prediction results of the mitotic counts in the test cohort were as follows:sensitivity 85.7% (95% confidence interval [CI]: 0.834–0.877), specificity 67.5% (95% CI: 0.636–0.712), PPV 82.1% (95% CI: 0.797–0.843), NPV 73.0% (95% CI: 0.691–0.766), and AUC 0.771 (95% CI: 0.750–0.791). At the patient level, the classification prediction results in the test cohort were as follows: sensitivity 90.0% (95% CI: 0.541–0.995), specificity 70.0% (95% CI: 0.354–0.919), PPV 75.0% (95% CI: 0.428–0.933), NPV 87.5% (95% CI: 0.467–0.993), and AUC 0.800 (95% CI: 0.563–0.943). @*Conclusion@#We developed and preliminarily verified the GIST mitotic count binary prediction model, based on the VGG convolutional neural network. The model displayed a good predictive performance.
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Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , TranscriptomeABSTRACT
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.