The relaxant effects of protopine (Pro) on smooth muscles were studied by recording isotonic contraction and radioimmunoassay. Pro relaxed the contraction of rabbit thoracic aorta, mesenteric artery, portal vein and guinea pig ileum and taenia colon induced by high K+ (70 mmol.L-1). Pro also inhibited the contraction of rabbit thoracic aorta, mesenteric artery, portal vein induced by NE (0.3 mumol.L-1) and guinea pig taenia colon induced by BaCl2 (1 mmol.L-1). Pro inhibited the intracellular Ca2+ release, but did not inhibit Ca2+ influx induced by NE. These results suggested that the smooth muscle relaxant mechanism of action of Pro may be the inhibition of intracellular Ca2+ release.
CD4+ T cells play critical roles in directing immunity, both as T helper and as regulatory T (Treg) cells. Here, we demonstrate that hepatocytes can modulate T cell populations through engulfment of live CD4+ lymphocytes. We term this phenomenon enclysis to reflect the specific enclosure of CD4+ T cells in hepatocytes. Enclysis is selective for CD4+ but not CD8+ cells, independent of antigen-specific activation, and occurs in human hepatocytes in vitro, ex vivo, and in vivo. Intercellular adhesion molecule 1 (ICAM-1) facilitates T cell early adhesion and internalization, whereas hepatocytes form membrane lamellipodia or blebs to mediate engulfment. T cell internalization is unaffected by wortmannin and Rho kinase inhibition. Hepatocytes engulf Treg cells more efficiently than non-Treg cells, but Treg cell-containing vesicles preferentially acidify overnight. Thus, enclysis is a biological process with potential effects on immunomodulation and opens a new field for research to fully understand CD4+ T cell dynamics in liver inflammation.
The association between P2Y12 receptor inhibitors reloading and in-hospital outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS) patients who were on chronic P2Y12 receptor inhibitors therapy remained underdetermined.The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS project) is a national registry active from November 2014 to December 2019. 4790 NSTEACS patients on chronic P2Y12 receptor inhibitors therapy were included. Cox proportional hazard models, Kaplan-Meier curves, and subgroup analyses were conducted.The NSTEACS patients who received reloading of P2Y12 receptor inhibitors were younger and had fewer comorbid conditions. The reloading group had a lower risk of major adverse cardiac events (MACE) (0.51% vs. 1.43%, P = 0.007), and all-cause death (0.36% vs. 0.99%, P = 0.028), the risks of myocardial infarction and major bleeding were not significantly different between patients with and without reloading. In survival analysis, a lower cumulative risk of MACE could be identified (Log-rank test, P = 0.007) in reloading group. In the unadjusted Cox model, reloading P2Y12 receptor inhibitors was associated with a decreased risk of MACE [HR, 0.35; 95% CI 0.16-0.78; (P = 0.010)] and all-cause death [HR, 0.37; 95% CI 0.14-0.94; (P = 0.036)]. Reloading of P2Y12 receptor inhibitors was associated with a decreased risk of MACE in most of the subgroups.In NSTEACS patients already taking P2Y12 receptor inhibitors, we observed a decreased risk of in-hospital MACEs and all-cause mortality and did not observe an increased risk of major bleeding, with reloading. The differential profile in the two groups might influence this association and further studies are warranted.https://www.gov (Unique identifier: NCT02306616, date of first registration: 03/12/2014).
C-C motif chemokine ligand 14 (CCL14) is a chemokine promoting the activation of immune cells. However, the relationship between CCL14 expression, tumor immunity, and prognosis in Hepatocellular Carcinoma (HCC) remain unclear. CCL14 expression and its influence on tumor prognosis were analyzed by the ONCOMINE, Tumor Immune Estimation Resource (TIMER) and Kaplan-Meier plotter. The relationship between CCL14 expression and tumor immunity were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). CCL14 expression was significantly lower in several human cancers, including HCC, than in corresponding normal tissues. CCL14 expression in HCC tissues correlated with prognosis. Low CCL14 expression associated with poorer overall survival, disease-specific survival, progression-free survival, and relapse-free survival in multiple cohorts of HCC patients, particularly at early disease stages (stage 1+2 or grade 2). CCL14 showed strong correlation with tumor-infiltrating B cells, CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells. CCL14 expression in HCC negatively correlated with expression of several immune cell markers, including exhausted T cell markers, PD-1, TIM-3 and CTLA-4, suggesting its role in regulating tumor immunity. These findings demonstrate that CCL14 is a potential prognostic biomarker that determines cancer progression and correlated with tumor immune cells infiltration in HCC.
Sixteen genera of soil moniliaceous hyphomycetes were isolated from 40 soil samples collected from the southern and northern slopes of Taibai Mountain, and the indices Shannon-Wiener diversity index, evenness, niche breadth, and niche overlap were used to analyze the community structure and niche of soil moniliaceous hyphomycetes in different forest types on the southern and northern slopes of Taibai Mountain. The results showed that the distribution of soil moniliaceous hyphomycetes on the study area had an obvious environmental gradient pattern. Altitude and forest type were the main determinants of the fungal community distribution. The species richness and diversity index of soil moniliaceous hyphomycetes decreased significantly with increasing altitude, but the community evenness represented an increasing trend. Among the genera of soil moniliaceous hyphomycetes, Penicillium, Aspergillus, Verticillium, Paecilomyces and Acremonium had larger niche width and greater niche overlap with other genera, suggeting that these genera had wide distribution on the southern and northern slopes of Taibai Mountain. As for Trichothecium, Gliocladium and Metarhizium, their niche width was narrower, and their niche overlap with other genera was smaller, indicating that the distribution of these genera was more affected by altitude and vegetation, with the occurrence only in special forest types.
Bmi1 is overexpressed in multiple human cancers. We previously reported the oncogenic function and the transcription regulation mechanisms of Bmi1 in nasopharyngeal carcinoma (NPC). In this study, we observed that the mRNA and the protein levels of Bmi1 were strictly inconsistent in NPC cell lines and cancer tissues. The inhibitors of proteasome and lysosome could not enhance the protein level of Bmi1, indicating that Bmi1 may be post-transcriptionally regulated. The IRESite analysis showed that there were two potential internal ribosome entry sites (IRESs) in the 5'-untranslated region (5'-UTR) of Bmi1. The luciferase assay demonstrated that the 5'-UTR of Bmi1 has IRES activity, which may mediate cap-independent translation. The IRES activity of the Bmi1 5'-UTR was significantly reduced after the mutation of the two IRES elements. Taken together, these results suggested that the IRES elements mediating translation is a novel post-transcriptional regulation mechanism of Bmi1.
Despite advances in the treatment of ST-segment elevation myocardial infarction (STEMI), little is known about how this evolving knowledge is applied in current clinical practice in China.
Objective
To evaluate hospital performance and temporal trends in the management of STEMI.
Design, Setting, and Participants
This study used data from the Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome Project, a nationwide quality improvement registry, in collaboration with the American Heart Association and the Chinese Society of Cardiology. Participants included patients with STEMI admitted to 143 tertiary hospitals across China from November 2014 to July 2019, and data were analyzed from November 2020 to December 2021.
Main Outcomes and Measures
Levels, hospital-level variations, and trends for utilization rates of the 9 management strategies with Class I recommendations in Chinese and US guidelines.
Results
A total of 57 560 hospitalizations with STEMI were included. Overall, 20.0% of patients received all the care according to the 9 guideline-recommended strategies. The performance rate of quality measures was low for reperfusion therapy (61.0%, 35 115/57 560 patients), β-blocker at discharge (68.3%, 37 750/55 285 patients), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at discharge (55.1%, 2524/4578 patients), and smoking cessation counseling (36.5%, 9586/26 265 patients) among those who were eligible. Of 25 563 patients who underwent primary percutaneous coronary intervention (PCI), 66.8% underwent this procedure within 90 minutes of hospital arrival. Of 1128 patients who underwent fibrinolysis therapy, 253 (22.4%) underwent this treatment within 30 minutes of hospital arrival. Measures with high performance rates included receipt of dual antiplatelet therapy within 24 hours (95.5%, 54 263/56 848 patients) and at discharge (91.8%, 51 452/56 019 patients) and receipt of statin at discharge (93.0%, 52 214/56 141 patients) for those eligible. There was significant variation between hospitals in all-or-none score (ranging from 0 to 61.9%) and performance of individual measures. The quality of care improved during the study period, especially for reperfusion therapy, primary PCI within the first 90 minutes of hospital arrival, and smoking cessation counseling.
Conclusions and Relevance
The quality of care for patients hospitalized with STEMI does not meet guideline-recommended strategies in China, with only 1 in 5 patients receiving all the care according to the 9 guideline-recommended strategies. Large disparities in the quality of care exist across hospitals.
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