Prognostic value of myocardial injury in patients with COVID-19 / 中华心血管病杂志

Objective: To analyze the prognostic value of myocardial injury in patients with COVID-19. Method: Confirmed cases of COVID-19 patients admitted from January 31st to February 5th at isolation ward of Renmin Hospital of Wuhan University were divided into non-survival group （33 cases）and survival group (169 cases)according to the clinical outcomes 5 weeks after admission. Data including demographics, comorbidities, vital signs, laboratory results were obtained. Cardiac injury was defined as serum concentration of high sensitivity cardiac troponin I (hs-cTnI) above 0.04 μg/L. Univariate and multivariate Cox regression were used to analyze the prognostic value of myocardial injury in patients with COVID-19. Kaplan-Meier analysis was used to plotted survival curve and analyze the impact of myocardial injury on the survival outcome of COVID-19 patients. Results: A total of 202 patients were included, the age was 63 (51, 70) years old, 88 (43.6%) of them were male, 85 (42.1%) of them had comorbidities, 125 (61.9%) of them were severely to critically ill. Till March 11, 33 patients died, all of them were critically ill patients. The age, proportion of males, comorbidities, respire rate, serum levels of hs-cTnI and incidence of heart failure in the non-survival group were significantly higher than those in the survival group (all P<0.05). The hospitalization time of non-survival group was significantly shorter than that of survival group (6(4, 9) vs. 32(23, 36), P<0.001). Myocardial injury was an important prognostic factor of COVID-19 (HR=5.382, 95%CI 2.404-12.050, P<0.001). Kaplan-Meier survival analysis showed that the presence of myocardial injury was significantly associated with the reduced survival rate among COVID-19 patients (P<0.001). Conclusion: Myocardial injury is an important prognostic factor of COVID-19, COVID-19 patients with myocardial injury face a significantly higher risk of death.

Gonadotropin-releasing hormone-antagonist up-regulate the proportion of uterine natural killer cells and enhance their toxicity during the implantation window period of mice / 上海交通大学学报（医学版）

Objective: To investigate the effects of gonadotropin-releasing hor-mone-antagonist (GnRH-ant) on the proportion and toxicity of mice uterine nature killer (uNK) cells during implantation window. Methods: Sixteen C57BL/6 mice were randomly divided into GnRH-ant group and control group, with 8 mice in each group. From the 3rd day of the estrous cycle, GnRH-ant (1.5 μg/100 g) was injected intraperitoneally into the mice of the GnRH-ant group for 7 days continuously, and the control group was injected with the same volume of normal saline at the same time point. On the 7th day, the mice of the two groups were injected with human menopausal gonadotropin (40 U/100 g). The next day, they were injected with human chorionic gonadotropin (100 U/100 g) and sacrificed after 48 h. The uterus tissues were taken out for primary digestion to obtain single-cell suspension. Flow cytometry was used to analyze the proportion of uNK cells and the expression levels of toxicity molecules perforin (Pf) and granzyme B (Gz-B). Results: Compared with the control group, the proportion of uNK cells in GnRH-ant group increased (P=0.000), the proliferation level increased (P=0.000), the apoptosis level decreased (P=0.004), and the expression of toxicity molecules Pf (P=0.000) and Gz-B (P=0.034) were up-regulated. Conclusion: GnRH-ant may up-regulate the proportion of uNK cells and enhance their toxicity in the implantation window period of mice.

Role of saliva proteinase 3 in dental caries / 国际口腔科学杂志·英文版

Salivary analysis can be used to assess the severity of caries. Of the known salivary proteins, a paucity of information exists concerning the role of proteinase 3 (PR3), a serine protease of the chymotrypsin family, in dental caries. Whole, unstimulated saliva was collected from children with varying degrees of active caries and tested using a Human Protease Array Kit and an enzyme-linked immunosorbent assay. A significantly decreased concentration of salivary PR3 was noted with increasing severity of dental caries (P<0.01); a positive correlation (r=0.87; P<0.01; Pearson's correlation analysis) was also observed between salivary pH and PR3 concentration. In an antibacterial test, a PR3 concentration of 250 ng·mL⁻¹ or higher significantly inhibited Streptococcus mutans UA159 growth after 12 h of incubation (P<0.05). These studies indicate that PR3 is a salivary factor associated with the severity of dental caries, as suggested by the negative relationship between salivary PR3 concentration and the severity of caries as well as the susceptibility of S. mutans to PR3.

Endothelial cell injury with inflammatory cytokine and coagulation in patients with sepsis / 世界急诊医学杂志（英文）

@#BACKGROUND: Current studies on CD62P have focused mainly on cardiovascular diseases, while only few studies have evaluated the effects of CD62P on the development of sepsis and the association between endothelial cell injury with inflammation and coagulation. This study attended to explore the association between endothelial cell injury with inflammation and coagulation by evaluating the expression of soluble CD62P (s-CD62P) in plasma and its mechanism in patients with sepsis, thus to provide the evidence of effective treatment of sepsis with anti-adhesion therapy targeted CD62P. METHODS: A total of 70 critically ill patients with systemic inflammatory response syndrome (SIRS) admitted to intensive care unit (ICU) between September 2009 and February 2010 were enrol ed for a prospective and control study. According to the diagnostic criteria of sepsis/SIRS, the patients were divided into two groups: a sepsis group (n=38) and a SIRS group (n=32). Another 20 healthy volunteers served as a control group. Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure, diabetes and its complications. The demographics of the patients including age, sex, body mass index (BMI), smoking and alcohol addict were compared among the groups. Six mL peripheral blood samples were collected within 24-hour admission in ICU for enzyme-linked immunosorbent assay (ELISA) to detect the plasma levels of s-CD62P, TNF-α, and hs-CRP. And variables of coagulation function such as platelet (PLT), prothrombin (PT), activated partial thromboplastin time (APTT), D-dimer and antithrombin-III (AT-III) were analyzed during 24 hours after admission to ICU. Meanwhile sequential organ failure assessment (SOFA) score of critically ill patients was evaluated. Data were expressed as mean±standard deviation and were statistical y analyzed by using SPSS 17.0 statistical software. The differences in plasma levels of s-CD62P of patients in each group were analyzed by ANOVA and the Kruskal-Wallis test. The relations between s-CD62P and inflammatory cytokines as well as with coagulation were determined by Pearson's product moment correlation coefficient analysis. Changes were considered as statistically significant if P value was less than 0.05. RESULTS: Compared with the control group and SIRS group, the sepsis group demonstrated significantly higher levels of s-CD62P, TNF-α and highly sensitive C-reactive protein (hs-CRP) (P<0.05). The plasma levels of D-dimer, PT, and APTT in the sepsis and SIRS groups were significantly higher than those in the control group, while the platelet count and the activity of AT-III were obviously lower (P<0.05). In the sepsis group, the plasma levels of hs-CRP and TNF-α were positively correlated with PT, APTT, and D-dimer, and negatively correlated with AT-III and PLT (P<0.05). The plasma levels of s-CD62P were significantly correlated with the plasma levels of TNF-α, hs-CRP, D-dimer, PT, and APTT, whereas they were correlated negatively well with PLT and AT-III (P<0.05). CONCLUSIONS: The concentration of plasma s-CD62P is elevated as a early biomarker in patients with sepsis, and it serves as one of the pathogenic factors responsible for endothelial cell damage. Coagulation and mediators of inflammation promote each other, aggravating the severity of sepsis. Plasma s-CD62P may be an important factor for the development of coagulation and inflammatory reaction.

High mobility group box 1 protein: possible pathogenic link to atrial fibrillation / 中华医学杂志(英文版)

Atrial fibrillation (AF) is the most common sustained dysrhythmia in clinical practice. The bulk of evidence suggests that inflammatory processes, oxidative stress and matrix metalloproteinase are associated with development of AF. However, these agents may be involved in high mobility group box 1 protein (HMGB1). We hypothesized that HMGB1 may be a possible pathogenic link to AF. A growing body of evidence supports these hypotheses. First, the level of serum HMGB1 is significantly increased in patients with AF including paroxysmal and persistent AF. Second, HMGB1 has been identified as a new pro-inflammatory cytokine in cardiovascular diseases, along with tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C-reactive protein, and there is cross-talk between HMGB1 and inflammatory cytokines. Third, oxidative stress is involved in the release of the pro-inflammatory cytokine, HMGB1, indicating there is cross-talk between oxidative stress and inflammation, and oxidative stress may reinforce the effect of inflammation on the pathogenesis of AF and inflammation may play a more important role in the pathogenesis of AF. Fourth, HMGB1 can promote matrix metalloproteinase-9 upregulation and activation. Fifth, HMGB1 receptors (receptor for advanced glycation end products, Toll-like receptor-2,4) may mediate the atrial structural remodeling or be up-regulated in patients with non-valvular AF. These results suggest that HMGB1 may participate in the pathogenesis of AF and provide a potential target for pharmacological interruption of AF.