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.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

In order to investigate the effect of curcumin combined with all-trans retinoid acid (ATRA) on differentiation of ATRA-resistant acute promyelocytic leukemia (APL) cells and its molecular mechanism, the NB4-R1, an ATRA-resistant APL cells, was used as a model, counting of NB4-R1 and cell morphologic observation were performed, the effect of curcumin alone or combined with ATRA on proliferation, differentiation of NB4-R1 cells was detected by flow cytometry (FCM), the change of AKT phosphorylation in cell differentiation was detected by Western blot. The results showed that ATRA had no influence on NB4-R1 cell proliferation, but enhanced the inhibitory effect of curcumin on NB4-R1 cell growth; the curcumin or ATRA alone did not affect NB4-R1 differentiation; curcumin combined with ATRA could obviously induce CD11b expression; the cell morphology showed obvious differentiation characteristics. ATRA could promote phosphorylation of AKT in NB4 cells at short time, but not had effect on phosphorylation of AKT in NB4-R1 cells; the curcumin could enhance the phosphorylation of AKT in NB4-1R cells, the curcumin combined with ATRA could further enhance the phosphorylation of AKT. It is concluded that PI3K/AKT pathway inactivation may be one of the factors of drug resistance in APL and curcumin promotes differentiation of NB4-R1 through activating PI3K/AKT pathway.
Cell Differentiation ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Curcumin ; pharmacology ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Leukemia, Promyelocytic, Acute ; pathology ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; Tretinoin ; pharmacology

Objective To evaluate the efficacy of parecoxib sodium for prevention of post-thoracotomy pain syndrome.Methods Ninety ASA physical status Ⅰ or Ⅱ patients,aged 40-64 yr,weighing 50-80 kg,scheduled for elective thoracotomy,were equally and randomly divided into 3 groups using a random number table:control group (group C) and two different treatments with parecoxib sodium groups (P1 and P2 groups).At 20 min before skin incison,parecoxib sodium 40 mg was injected intravenously in P1 and P2 groups,while the equal volume of normal saline was given in group C.An increment of parecoxib sodium 40 mg was given every 12 h for 6 times after surgery in group P2.General anesthesia combined with epidural anesthesia was used during surgery and patient-controlled epidural analgesia was used for postoperative analgesia in the three groups.Morphine was used as rescue analgesic to maintain VAS score ≤ 3.The consumption of morphine within 72 h after operation,development of adverse effects and development and duration of pain (VAS score ＞ 3) within 6 months after operation were recorded.The blood coagulation was measured at 72 h after operation.Results Morphine was not used within 72 h after operation in P2 group.The abnormality of blood coagulation at 72 h after operation was not observed in the three groups.Compared with group C,no significant changes were found in the incidence and duration of pain within 6 months after operation in P1 group (P ＞ 0.05),the incidence of pain was significantly decreased and duration of pain was shortened within 6 months after operation in P2 group,and the incidence of nausea,vomiting and pruritus was decreased in P1 and P2 groups (P ＜ 0.05 or 0.01).The incidence of nausea,vomiting and pruritus was significantly lower in P2 group than in P1 group (P ＜ 0.01).Conclusion Continuous application of parecoxib sodium for 72 h can decrease the development of post-thoracotomy pain syndrome without increasing the incidence of adverse effects.

Objective To evaluate the quality of new nurses' extrathoracic compression in CPR by feedback system,and provide basis for standard training.Methods Totals of 71 new nurses were trained with theory and operation in accordance with "2010 CPR guide",focusing on the key and difficulty of link quality.Laerdal model was also used for training and test the effect of extrathoracic compression.Results The average compression frequency was 124.23 times/min,the pressing depth above 5cm was 40.3％,the positioning accuracy rate was 91.30％,the chest wall sufficient recoil was 97.41％,the pressing and loosening ratio was 0.85,and the all indicators up to standard was 37.39％.Conclusions Training of link quality should be paid attention to,and keys and difficulties should be strengthened,so that new nurses can receive basic first aidskills of the post qualification.

Objective To explore the personal guidance application effect of CPR training on new recruit nurses.Methods A total of 25 new nurses received CPR training by the personal guidance,and they were practiced on the Laerdal ACLS advanced life support model before and after the training,then compared the respective data collected by Laerdal computer skill report system.Results It revealed that significant difference in each indicator of chest compression,before and after the individualized guidance (P ＜ 0.05),such as the incidence of displaying error after individualized guidance was 17.6％ higher than before (41.4％) ; the incidence of chest compression that deeply enough was 92.7％ higher than before (65.2％),and the proportion of incorrect hand position was 1.3％,which was lower than before (7.7％).No statistical difference in tidal volume of artificial ventilation,before and after the individualized guidance (P ＞ 0.1).Conclusions The individualized guidance showed favorable results in new recruit nurses,which could be generalized in the clinical practice.Besides,the proper compression frequency requires further investigation.