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Objective: Hydrogen sulfide (H2S), an endogenous gaseous transmitter, was found to protect the heart from various forms of injury, but the underlying mechanism is not known. H2S can open the KATP channel on vascular smooth muscle cells, and the objective of this study was to determine whether H2S can open the KATP channel on myocardiocytes. Methods: The whole-cell patch-clamp technique was used to record IK,ATP and action potentials of atrial and ventricular myocytes isolated from the hearts of male Wistar rats. Sodium hydrogen sulfide (NaHS) was used as a donor of H2S to observe the effect of exogenous H2S on IK,ATP. DL-propargylglycine (PPG), an inhibitor of the synthesis of H2S, was used at a concentration of 200 μM to observe the effect of endogenous H2S on IK,ATP. Results: NaHS at concentrations (in μM) of 9.375, 18.75, 37.5, 75 and 150 increased IK,ATP by 12.8% (p > 0.05), 28.4% (p < 0.05), 38.8% (p < 0.01), 51.2% (p < 0.01) and 58.6% (p< 0.01) on ventricular myocytes, respectively, and by 6.8% (p > 0.05), 10.4% (p > 0.05), 18.9% (p < 0.01), 24.8% (p < 0.01) and 37.2% (p < 0.01) on atrial myocytes, respectively. The H2S-induced decrease in the duration of action potentials (APD90) of ventricular myocytes was concentration-dependent, although only NaHS at a concentration of 150 μM decreased the APD90 significantly (15%, p < 0.05). The H2S-induced decrease in APD90 on atrial myocytes was concentration dependent, but the statistical difference was not significant. Inhibition of IK,ATP by PPG was time dependent and the level of inhibition was: ventricular myocytes, 7% (p > 0.05), 10% (p < 0.05), 15.3% (p < 0.01), 24.0% (p < 0.01) and 28.9% (p < 0.01); atrial myocytes, 15.8% (p > 0.05), 21.3% (p > 0.05), 26.5% (p < 0.01), 34.0% (p < 0.01) and 43.2% (p < 0.01) measured at 5, 10, 15, 20 and 25 min, respectively. The increase in the APD90, by PPG was time dependent for ventricular myocytes [increased by 12.8% (p < 0.05) at 25 min]. The same was true for atrial myocytes, although only the value at 25 min was significant (15%, p < 0.05). Conclusions: H2S decreased the APD90,and both the endogenous and exogenous H2S-induced increase in IK,ATP on both atrial and ventricular myocytes was concentration dependent. These results may help to explain, at least in part, how H2S protects heart cells from various forms of injury. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim The inconsistent effects of lopinavir--ritonavir (LPV/r) on COVID-19 seem to be caused by the therapeutic window. In the present study, we aim to present the effects of early LPV/r treatment on patients with severe COVID-19. Methods The demographics, characteristics, treatments, SARS-CoV-2 test results and outcomes of 19 patients with severe COVID-19 treated with LPV/r within 12 days of onset of symptoms were retrospectively assessed. Results Within 3 days of admission, three (15.79%) patients received noninvasive ventilation, and 16 (84.21%) patients received high- flow oxygen support. The median duration between the onset of symptoms and initiating LPV/r therapy was 9 (range 2-12) days. The median course of LPV/r treatment was 11 (range 7-17) days. One of the 19 patients (5.26%) died. Of the 18 patients discharged, the median hospital stay was 17 (range 11-45) days. At day 6 after LPV/r therapy was initiated, 68.42% of patients were virologically cured, increasing to 84.22% at day 12. Conclusion In this cohort of patients with severe COVID-19 who were treated with LPV/r within 12 days of the onset of symptoms, clinical improvement was observed in 18/19 patients (94.74%). Randomised controlled trials are urgently needed to further evaluate this strategy. [ABSTRACT FROM AUTHOR]

Nine tumor and various potential biomarkers were measured and combined the information to diagnose disease, all patients accepted fiber bronchoscopy brush liquid based cytologyand histopathology examination in order to reliably detect lung cancer. The samples from 314 Chinese lung cancer patients were obtained and CK5/6, P63, P40, CK7, TTF-1, NapsinA CD56, Syn and CgA were measured with the immunohistochemical SP method and analyzed correlation of the expression of these markers with pathological and clinical features of squamous cell carcinoma, adenocarcinoma, and small cell lung carcinoma. Squamous cell carcinoma, adenocarcinoma and small cell carcinoma were 61 cases, 114 cases and 139 cases,CK5/6 and P63 expression were more frequent in squamous cell carcinoma, with sensitivity and specificity of 77.05 % and 96.44 %, 83.61 % and 88.93 %, and compared with adenocarcinoma and small cell carcinoma difference was statistically significant (P<0.05), The incidences of a positive P40 expression were 100 % in squamous cell carcinoma, with specificity of 98.81 %.CK7, TTF-1 and NapsinA expression were more frequent in adenocarcinoma, with sensitivity and specificity of 85.09 % and 78.69 %, 79.82 % and 93.44 %, 56.14 % and 95.08 %, and compared with squamous cell carcinoma and small cell carcinoma difference was statistically significant (P<0.05). TTF-1, Syn, CgA and CD56 expression were more frequent in adenocarcinoma, with sensitivity and specificity of 86.33 % and 93.44 %, 89.21 % and 98.36 %, 74.10 % and 100 %, 96.40 % and 96.72 %. The combined detection of CK5/6, P63 and P40 were more useful and specific in differentiating squamous cell carcinoma. CK7, TTF-1 and NapsinA were more useful and specific in differentiating lung adenocarcinoma. The impaired CD56, TTF-1, Syn and CgA reflects the progression of small cell lung cancer. [ABSTRACT FROM AUTHOR]

Aberrant activation of Wnt/β-catenin signaling pathways is closely involved in the occurrence and progression of several types of human malignancies. However, as a fundamental component in this cascade, Wnt3 has not been well understood for the expression level and pathogenic mechanism in gastric carcinogenesis. Here, this research was undertaken to elucidate the important role of Wnt3 in gastric cancer. Wnt3 expression in gastric carcinomas and their respective normal tissues was examined by immunoblotting and immunohistochemistry. In all cases, Wnt3 expression was significantly elevated in gastric carcinomas compared with normal tissues. Knocking down Wnt3 in MGC-803 gastric cancer cells by small interfering RNAs transfection led to an obvious decrease in both transcript and protein levels. Silence of Wnt3 expression in gastric cancer cells inhibited the expression of β-catenin and cyclin D1 genes in Wnt/β-catenin pathway, significantly blocked cellular proliferation, delayed cell cycle, suppressed cell invasion and metastasis, accompanied by a higher apoptosis rate. Together, we conclude that upregulation of Wnt3 plays a crucial role in gastric tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells, and Wnt3 might be a potential target for the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Background The presence of diabetes and plasma glucose concentration on admission are associated with adverse outcomes after an acute myocardial infarction (AMI), as high glucose can induce vascular endothelial cell apoptosis. This study explored the relative associations among admission plasma glucose level, soluble Fas (sFas) concentration, and long-term survival in patients with acute ST-elevation myocardial infarction (STEMI). Methods This prospective cohort study include 83 patients with acute STEMI. Based on their admission plasma glucose levels (7.8 and 11.1 mmol/L as the limits for low and high levels, respectively), patients were allocated into one of three groups: normal glucose (n = 33), median glucose (n = 24), and high glucose (n = 26). The admission plasma level of sFas was measured with a sandwich enzyme-linked immunosorbent assay (ELISA). Patients were followed up for an average of 89 ± 20 months for all causes of death and cardiovascular death. Results sFas levels were significantly higher in the high glucose group compared to the normal glucose group (5.87 ± 1.70 mmol/L vs. 3.07 ± 0.93 mmol/L, respectively, P < 0.05). The sFas level was positively associated with the admission plasma glucose level. The correlation coefficient (R) was 0.747, and R2 was 0.559. Mortality was significantly higher in the high glucose group compared to the normal glucose group (19.2% vs. 3.0%, respectively, P < 0.05). Conclusions In patients with acute STEMI, plasma glucose level was high on admission, and sFas apoptosis levels were increased. Long-term follow-up revealed that a high admission plasma glucose level was associated with higher mortality compared to a normal admission glucose level. [ABSTRACT FROM AUTHOR]