ABSTRACT
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.
ABSTRACT
A dysregulated immune response against the SARS-CoV-2 virus plays a critical role in severe COVID-19. However, the molecular and cellular mechanisms by which the virus causes lethal immunopathology are poorly understood. Here, we utilize multiomics single-cell analysis to probe dynamic immune responses in patients with stable or progressive manifestations of COVID-19, and assess the effects of tocilizumab, an anti-IL-6 receptor monoclonal antibody. Coordinated profiling of gene expression and cell lineage protein markers reveals a prominent type-1 interferon response across all immune cells, especially in progressive patients. An anti-inflammatory innate immune response and a pre-exhaustion phenotype in activated T cells are hallmarks of progressive disease. Skewed T cell receptor repertoires in CD8+ T cells and uniquely enriched V(D)J sequences are also identified in COVID-19 patients. B cell repertoire and somatic hypermutation analysis are consistent with a primary immune response, with possible contribution from memory B cells. Our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19, which may contribute to delayed virus clearance and has implications for therapeutic intervention.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the association between homocysteine level and prethrombotic status and long-term thromboembolic events in patients with primary hypertension.</p><p><b>METHODS</b>Results between 110 hypertensive patients with elevated homocysteine (HCY) level were compared with 110 hypertensive patients with normal HCY level which were enrolled from October 2003 to November 2009. Fibrinogen (FIB), viscosity, thrombomodulin (TM), granule membrane protein (GMP-140), prethrombin F1+2 fragment (F1+2), D-dimer fragment (D-Dimer) and antithrombin III (AT-III) were measured and correlated to HCY and prethrombotic state. The endpoints of the study were arterial and venous thromboembolic events. The variables linked with arterial and venous thromboembolic events were included in Cox proportional hazard models. The event-free survival was illustrated with Kaplan-Meier survival curves and compared by the Log-rank test.</p><p><b>RESULTS</b>The patients were followed up for 8-122 months (median follow-up time was 85 months). Compared with hypertensive patients with normal HCY, the plasma level of TM ((4.8±1.2) µg/L vs. (4.5±1.0) µg/L, P = 0.045), GMP-140 ((18.8±3.2) µg/L vs. (17.1±4.3) µg/L, P = 0.001), F1+2 ((1.2±0.4) nmol/L vs. (1.0±0.6) nmol/L, P = 0.004) were significantly higher while the plasma level of AT-III ((95.3±10.4) % vs. (98.6±10.6)%, P = 0.021) was significantly lower in hypertensive patients with elevated HCY level. FIB, viscosity of plasma and D-dimer were similar between the two groups. Multiple regression analyses indicated that HCY level was negatively correlated with AT-III (β = -0.199, P = 0.011) and positively correlated with age (β = 0.217, P = 0.04), female gender (β = 5.667, P = 0.001) and TM (β = 2.341, P = 0.003). Cox multivariate analysis revealed that age and HCY level were independent prognostic risk factors of thromboembolic events (OR 1.046, 95% CI 1.013-1.082, OR 1.052, 95% CI 1.027-1.078, respectively) (all P < 0.05). Kaplan-Meier curves showed that there was a significant difference in the event-free survival between the two groups (Log-rank test, P = 0.027).</p><p><b>CONCLUSIONS</b>Compared with normal HCY hypertensive patients, the levels of plasma prothrombin activators such as TM, GMP-140 and F1+2 were significant increased and anti-thrombin factor such as AT-III was significant decreased in hypertensive patients with elevated HCY. Old age and high HCY level were independent prognostic risk factors of thromboembolic events. The event-free survival in hypertensive patients with elevated HCY is lower than in hypertensive patients with normal HCY level.</p>
Subject(s)
Female , Humans , Case-Control Studies , Essential Hypertension , Fibrin Fibrinogen Degradation Products , Homocysteine , Blood , Hypertension , Kaplan-Meier Estimate , P-Selectin , Prognosis , Proportional Hazards Models , Regression Analysis , Risk Factors , ThromboembolismABSTRACT
Objective To investigate the clinical efficacy,safety and the correlation factors of recurrence of radiofrequency catheter ablation in treatment of atrial fibrillation.Methods The clinical data of 127 patients with atrial fibrillation having underwent circumferential pulmonary vein ablation guided by 3-D mapping system were analyzed retrospectively.Then they were followed up for 12 months.The status of patients after ablation and the success rate of ablation was recorded,then the relationship between the factors and the recurrence after ablation of atrial fibrillation was analyzed.Results After a follow up of 12 months,94 patients maintained sinus rhythm,and atrial fibrillation recurred in 33 cases.The first clinical success rate was 74.02％(94/127).Thirty-three patients with recurred atrial fibrillation received ablation again and 11 patients got success.The total clinical success rate was 82.68％ (105/127).The success rate of paroxysmal atrial fibrillation was 88.46％ (92/104) and success rate of persistent atrial fibrillation was 56.52％ (13/23).Univariate analysis showed that the type,the course,the diameters of left atrial,the early recurrence,the body mass index were related to the recurrence of atrial fibrillation,and multivariable Logistic analysis revealed only the type and the diameters of left atrial were independent risk factors responsible for the recurrence of atrial fibrillation (P ＜ 0.05).Conclusion Radiofrequency catheter ablation in treatment of atrial fibrillation is effective and safe,and the type and the diameters of left atrial are independent risk factors responsible for the recurrence of atrial fibrillation.
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Objective: To observe the therapeutic effect of acupuncture therapy for treatment of chronic atrophic gastritis. Methods: According to the theory of TCM, 36 cases of chronic atrophic gastritis were differentiated and treated by acupuncture. Gastroscopy and electrogastrograph (EGG) of the body surface, gastric acid and pepsin, blood gastrin, blood prostaglandin E (PGE), gastric mucosal cells and G cells are recorded. Results: Acupuncture therapy had a better effect in improving clinical symptoms, the markedly effective rate was 97.2% and the disappearing rate of clinical manifestations 97.02%;after acupuncture treatment,blood PGE concentration increased; gastric acid secretion increased; gastric dynamics was enhanced and the amplitude of EGG rose; acupuncture could significantly facilitate secretion of gastrin. Conclusion: Acupuncture is a convenient treatment method for atrophic gastritis with quick effect and without side effects.
