Objective To explore the relationship of plasma NT-proBNP level and severity of chronic congestive heart failure (CHF) and investigate the curative effect and security of meglumine adenosine cyclophosphate (MAC) combined with perindopril on patients with CHF.Methods From June 2011 to June 2013,126 inpatients with chronic congestive heart failure were randomly divided into A group (42 cases,routine therapy),B group (41 cases,routine therapy and perindopril) and C group (43 cases,routine therapy and perindopril plus MAC),all cases treated for 14 days.The left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) by echocardiography and plasma NT-proBNP levels were evaluated before and after 14 days therapy.Results The plasma NT-proBNP levels in NYHA Ⅱ ～ Ⅳ classes were significantly difference compared each other between any two classes (P ＜0.05) and the levels was positively correlated with NYHA cardiac function class and LVEDD (r =0.617,P ＜ 0.01 ; r =0.412,P ＜ 0.01),negatively correlated with LVEF (r =-0.372,P ＜ 0.01).After 14 days therapy,compared with A group,the LVEF and LVEDD significantly improved (P ＜ 0.05) and NT-proBNP level significantly decreased (P ＜ 0.05) in B,C groups; Compared with B group,C group had lower NT-proBNP level (P ＜ 0.05) although no further improvement in cardiac function.Conclusions The plasma NT-proBNP level is correlated closely with the severity of CHF and it is a good examination of diagnose,therapy and evaluating prognosis of CHF.Perindopril may significantly decline plasma NT-proBNP level and improve cardiac function of CHF patients,combined with MAC may further decline plasma NT-proBNP level although not further improved LVEF.Giving MAC and perindopril to patients with CHF was secure and patients tolerated it well.

Objective To study the findings of 256‐slice CT angiography in atherosclerosis of the intracranial carotid arteary . Methods 402 cases of atherosclerotic lesions in the neck and brain were collected from 2013 to 2014 in our hospital ,in which there were 274 cases of male and 128 cases female .All patients underwent 256‐slice CT angiography of the head and neck .The incidence of atherosclerosis involvement in the intracranial carotid artery was analysed .The characteristics of carotid plaque on different sexes , age(≤60 years and >60 years) and location (right and left ) were observed .The length and property of plaque ,and stenostic rate of the artery were measured respectively .Results There were 164 cases (40 .80% ) of intracranial carotid artery athrosclerosis in 402 cases of atherosclerotic lesions of the neck and brain ,in which the incident rate of male was 38 .32% and female 46 .09% (χ2 =2 .182 ,P=0 .140) .The incident rate of >60 years group was more than that of ≤60 years group (χ2 <31 .105 ,P<0 .001)for both sexes . There were no differences on lesion location (right or left)for different sexes or age groups (χ2 <0 .035 ,P>0 .088) .And there were also no differences on lesion length (≤10 mm ,11-20 mm ,>20 mm) for different sexes or age groups (χ2 <0 .027 ,P>0 .091) . Calcified plaques were seen the most (79 .81% ) ,mixed plaques were seen more (15 .46% ) ,and lipid plaques (1 .58% ) and fibrous plaques (3 .15% ) were seen less .The mixed plaques were more seen on >60 years group than that on ≤60 years group for male pa‐tients (χ2 =12 .204 ,P=0 .001) ,but no other difference was found for plaque property in other different sexes or age groups .Mild stenosis of the corated artery was found in 54 .57% lesions ,moderate stenosis in 39 .75% and severe stenosis in 5 .68% ,and there were no any difference in different sexes or age groups (χ2 <2 .062 ,P>0 .151) .Conclusion CT angiography of the head and neck is of important significance for diagnosis of atherosclerosis in the intracranial carotid artery .

Porcine deltacoronavirus (PDCoV) is a newly emerging enteropathogenic swine coronavirus causing acute diarrhea and vomiting in pigs. The apoptosis of ST cells induced by PDCoV infection was studied in this research. In ST cells, caspase activity assay showed that the activity of caspase 3, caspase 8 and caspase 9 increased significantly with the infection of PDCoV, but not observed in UV irradiated PDCoV-infected cells, indicating that PDCoV infection activated both endogenous and exogenous apoptotic pathways in ST cells, and the induction of apoptosis depended on viral replication. To further investigate the endogenous apoptosis induced by PDCoV, cytochrome C and apoptosis-inducing factors in cytoplasm and mitochondria were detected. Compared with normal cells, the amount of cytochrome C released from mitochondria to cytoplasm increased significantly in PDCoV-infected cells, and the release increased with the prolongation of infection, while the apoptosis-inducing factor was always localized to mitochondria, suggesting that PDCoV induced apoptosis was initiated through caspase-dependent mitochondrial apoptosis pathway by promoting cytochrome C in the mitochondrial membrane gap into the cytosol. In conclusion, this study reveals the mechanism of PDCoV inducing apoptosis.
Animals ; Apoptosis ; Coronavirus ; Coronavirus Infections ; Mitochondria ; Swine ; Swine Diseases

The recent discovery of activator compounds binding to an allosteric site on the NAD

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.