Isochlorogenic acid A attenuates progression of liver fibrosis through regulating HMGB1/TLR4/NF-κB signaling pathways

OBJECTIVE Liver fibrosis is a chronic damage process related to the further progression of hepatic cirrhosis and has yet no truly effective treatment is available.This study aimed to investigate the effects of isochlorogenic acid A(ICQA)on liver fibrosis induced by carbon tetrachloride(CCl4)and clarify the underlying mechanism.METHODS Rats were treated with CCl4 for eight weeks in order to induce liver fibrosis and simultaneously orally administered with ICQA(10,20 and 40 mg·kg-1).RESULTS ICQA had significant protective effect on liver injury,inflammation,and fibrosis in rats.Meanwhile,ICQA prevented the activation of hepatic stellate cells(HSC)as indicated by inhibiting the overexpres⁃sion of a-smooth muscle actin(a-SMA).In addition,reduced fibrosis was found to be associated with decreased protein expression of high-mobility group box 1(HMGB1)and toll like receptor(TLR)4.Moreover,ICQA supressed the cytoplasmic translocation of HMGB1 in rat liver.Further investigations indicated that ICQA treatment significantly attenuated nuclear translocation of the nuclear factor-κB(NF-κB)p65 and inhibited degradation of IkBa expression in the liver of rats with liver fibrosis.CONCLUSION ICQA has hepatoprotective and anti-fibrotic effects in rats with liver fibrosis through modulating the HMGB1/TLR4/NF-κB signaling pathways.

Resveratrol and fenofibrate ameliorate fructose-induced nonalcoholic steatohepatitis by modulation of genes expression

AIM: To evaluate the effect of resveratrol, alone and in combination with fenofibrate, on fructose-induced metabolic genes abnormalities in rats.METHODS: Giving a fructose-enriched diet (FED) to rats for 12 wk was used as a model for inducing hepatic dyslipidemia and insulin resistance. Adult male albino rats (150-200 g) were divided into a control group and a FED group which was subdivided into 4 groups, a control FED, fenofibrate (FENO) (100 mg/kg), resveratrol (RES) (70 mg/kg) and combined treatment (FENO + RES) (half the doses). All treatments were given orally from the 9th week till the end of experimental period. Body weight, oral glucose tolerance test (OGTT), liver index, glucose, insulin, insulin resistance (HOMA), serum and liver triglycerides (TGs), oxidative stress (liver MDA, GSH and SOD), serum AST, ALT, AST/ALT ratio and tumor necrosis factor-α (TNF-α) were measured. Additionally, hepatic gene expression of suppressor of cytokine signaling-3 (SOCS-3), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), malonyl CoA decarboxylase (MCD), transforming growth factor-β1 (TGF-β1) and adipose tissue genes expression of leptin and adiponectin were investigated. Liver sections were taken for histopathological examination and steatosis area were determined.RESULTS: Rats fed FED showed damaged liver, impairment of glucose tolerance, insulin resistance, oxidative stress and dyslipidemia. As for gene expression, there was a change in favor of dyslipidemia and nonalcoholic steatohepatitis (NASH) development. All treatment regimens showed some benefit in reversing the described deviations. Fructose caused deterioration in hepatic gene expression of SOCS-3, SREBP-1c, FAS, MDA and TGF-β1 and in adipose tissue gene expression of leptin and adiponectin. Fructose showed also an increase in body weight, insulin resistance (OGTT, HOMA), serum and liver TGs, hepatic MDA, serum AST, AST/ALT ratio and TNF-α compared to control. All treatments improved SOCS-3, FAS, MCD, TGF-β1 and leptin genes expression while only RES and FENO + RES groups showed an improvement in SREBP-1c expression. Adiponectin gene expression was improved only by RES. A decrease in body weight, HOMA, liver TGs, AST/ALT ratio and TNF-α were observed in all treatment groups. Liver index was increased in FENO and FENO + RES groups. Serum TGs was improved only by FENO treatment. Liver MDA was improved by RES and FENO + RES treatments. FENO + RES group showed an increase in liver GSH content.CONCLUSION: When resveratrol was given with half the dose of fenofibrate it improved NASH-related fructose-induced disturbances in gene expression similar to a full dose of fenofibrate.

2D-QSAR Studies on Anthranilic Acid Derivatives: A Novel Class of Allosteric Inhibitors of Hepatitis C NS5B Polymerase

Quantitative structure activity relationship （QSAR） studies were performed on 45 anthranilic acid derivatives for their potent allosteric inhibition activities of HCV NSSB polymerase. Genetic algorithm based genetic function approximation （GFA） method of variable selection was used to generate the model. Highly statistically significant model with r^2 = 0.966 and r^2cv = 0.951 was obtained when the number of descriptors in the equation was set to 5. High r^2pred value of 0.884 indicates the good predictive power of the best model. Spatial descriptors of radius of gyration （RadOfGration）, molecular volume （Vm）, length of molecule in the z dimension （Shadow-Zlength）, thermodynamic descriptors of the octanol/water partition coefficient （LogP） and molecular refractivity index （MR） showed enormous contributions to HCV NS5B polymerase inhibition. The validation of the model was done by leave-one-out （LOO） test, randomization tests and external test set prediction. The model gives insight on indispensable structural requirements for the activity and can be used to design more potent analogs against HCV NSSB polymerase.

血清BNP、hs-CRP、UA与cTnT联合检测对心力衰竭的诊断价值研究

目的分析血清B型钠尿肽(BNP)、超敏C反应蛋白(hs-CRP)、尿酸(UA)、心肌肌钙蛋白T(cTnT)联合检测对心力衰竭(HF)的诊断价值。方法回顾性分析103例HF患者的资料并将其作为研究组,另回顾性分析体检的98例健康者的资料并将其作为对照组。两组研究对象均接受血清BNP、hs-CRP、UA与cTnT检测。比较两组研究对象血清BNP、hs-CRP、UA与cTnT水平;比较美国纽约心脏病学会(NYHA)分级Ⅰ~Ⅱ级、Ⅲ~Ⅳ级HF患者的血清BNP、hs-CRP、UA与cTnT水平;比较单独血清BNP、hs-CRP、UA、cTnT检测与四项指标联合检测对HF的检出率。结果研究组血清BNP、hs-CRP、UA、cTnT分别为(290.95±45.68)pg/ml、(5.12±1.02)mg/L、(432.26±30.58)μmol/L、(17.03±3.52)pg/ml,均高于对照组的(47.56±15.00)pg/ml、(1.36±0.46)mg/L、(285.65±35.44)μmol/L、(6.45±2.02)pg/ml(P<0.05)。NYHA分级Ⅲ~Ⅳ级HF患者血清BNP、hs-CRP、UA、cTnT分别为(336.52±50.66)pg/ml、(6.02±0.98)mg/L、(460.46±40.49)μmol/L、(19.56±3.00)pg/ml,均高于Ⅰ~Ⅱ级患者的(236.65±45.88)pg/ml、(4.05±1.00)mg/L、(398.65±35.45)μmol/L、(14.02±3.02)pg/ml(P<0.05)。血清四项指标联合检测对HF的检出率88.35%高于单独血清BNP、hs-CRP、UA、cTnT检测的72.82%、67.96%、60.19%、56.31%(P<0.05)。结论血清BNP、hs-CRP、UA与c TnT水平联合检测可以有效提高HF的检出率,具有临床应用价值。

血清hs-CRP、apoA1/apoB、UA水平与急性心肌梗死合并2型糖尿病患者血管病变支数、狭窄程度的相关性

目的:分析血清超敏C反应蛋白(hs-CRP)、载脂蛋白A1/载脂蛋白B(apoA1/apoB)、尿酸(UA)水平与急性心肌梗死(AMI合并2型糖尿病(T_(2)DM)患者血管病变支数、狭窄程度的相关性。方法:选取2021年5月至2023年5月该院收治150例AMI患者进行前瞻性研究,设为研究组,根据是否合并2型糖尿病(T_(2)DM)将其分为合并组(n=100)、未合并组(n=50),另选取同期50名健康体检者,设为对照组。比较三组血清hs-CRP、apoA1/apoB、UA水平,合并组不同Gensini评分患者hs-CRP、apoA1/apoB、UA水平,合并组不同动脉病变支数患者hs-CRP、apoA1/apoB、UA水平,并采用Spearman相关性分析血清hs-CRP、apoA1/apoB、UA水平与AMI合并T_(2)DM患者血管病变支数、狭窄程度的相关性。结果:合并组hs-CRP、UA水平均高于未合并组、对照组,且未合并组高于对照组,合并组apoA1/apoB低于未合并组、对照组,且未合并组低于对照组,差异有统计学意义(P<0.05);Gensini评分>40分患者hs-CRP、UA水平均高于Gensini评分为21~40分、0~20分患者,且Gensini评分为21~40分患者高于Gensini评分为0~20分患者,Gensini评分>40分患者的apoA1/apoB低于Gensini评分为21~40分、0~20分患者,且Gensini评分为21~40分患者低于Gensini评分为0~20分患者,差异有统计学意义(P<0.05);血管病变支数为3支患者的hs-CRP、UA水平均高于血管病变支数为2支、1支的患者,且2支高于1支,血管病变支数为3支患者的apoA1/apoB低于血管病变支数为2支、1支,且2支低于1支,差异有统计学意义(P<0.05);合并组血清hs-CRP、UA水平与血管病变支数、Gensini评分均呈正相关(r>0,P<0.05),apoA1/apoB与血管病变支数、Gensini评分均呈负相关(r<0,P<0.05)。结论:血清hs-CRP、UA水平与AMI合并T_(2)DM患者血管病变支数、Gensini评分等均呈正相关,血清apoA1/apoB与AMI合并T_(2)DM患者动脉病变支数、Gensini评分等均呈负相关。

丹酚酸B调控pSmad3C/pSmad3L发挥抗肝纤维化-肝细胞癌作用

目的观察丹酚酸B(salvianolic acid B,Sal B)对二乙基亚硝胺(diethylnitrosamine,DEN)诱导小鼠肝纤维化-肝细胞癌进程的影响,并探讨Sal B经由p Smad3C/p21介导的抑癌信号、p Smd3L/PAI-1/c-Myc介导的促肝纤维化-肝癌信号转换机制。方法昆明种♂小鼠100只,随机分组,DEN诱导小鼠肝纤维化-肝细胞癌模型,不同剂量Sal B(15、30mg·kg^(-1)·d^(-1),ig)及阳性药秋水仙碱(0.2 mg·kg^(-1)·d^(-1),ig)干预。于造模第12周、第16周分批处死小鼠,肝脏活检,苏木精-伊红(HE)染色、Van Gieson(VG)染色观察肝组织病理学特征,Western blot法检测肝组织中p Smad3C、p S-mad3L、p21、纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor 1,PAI-1)及c-Myc蛋白表达。结果正常组肝脏表面光滑、质地柔软,模型组第12周时肝脏表面粗糙、质地变硬,第16周时肝脏表面可见弥漫性结节、质地坚硬;而丹酚酸B干预组以上病变明显改善。HE及VG染色显示,正常组肝组织结构正常,模型组第12周时肝组织炎细胞浸润、胶原纤维增生,形成假小叶结构;第16周时肝小叶结构紊乱,细胞核变大、分裂相增多、异型性明显;Sal B干预组肝组织病变程度明显减轻。Western blot结果显示,正常组肝组织中p Smad3C、p Smad3L、PAI-1表达均较少,p21、c-Myc几乎不表达;模型组第12周时肝组织中p Smad3C无明显变化,p S-mad3L、PAI-1、p21表达增多,第16周时p Smad3C、p Smad3L、p21、PAI-1、c-Myc表达皆有增加;而Sal B干预组第12周时p Smad3C、p21表达明显增加,p Smad3L、PAI-1蛋白水平明显降低,第16周时p Smad3C表达明显增加,p21几乎无变化,p Smad3L、PAI-1、c-Myc表达明显降低。结论Sal B延缓DEN诱导的小鼠肝纤维化-肝细胞癌进程,其机制可能与调控p Smad3C/p21、p Smad3L/PAI-1/c-Myc信号转换有关。

Chinese Prescription Kangen-karyu as Potential Anti-Alzheimer’s Disease Therapeutic:Analyses of BACE1 and GSK-3βInhibitory Activities

Inhibition ofβ-site amyloid precursor protein-cleaving enzyme 1(BACE1)or glycogen synthase kinase-3β(GSK-3β)is estimated to be the central therapeutic approach for Alzheimer’s disease(AD).In this study,water extract of Kangenkaryu,its crude drug and chemical composition used in oriental medicine were evaluated regarding their BACE1 and GSK-3βinhibitory activities.Fluorescence resonance energy transfer was used to characterize the BACE1 inhibitory effect of Kangen-karyu,its crude drug and chemical composition.GSK-3βactivity was determined using the Kinase-Glo Luminescent Kinase Assay Platform.The water extract of Kangen-karyu inhibited BACE1 and GSK-3βin concentration-dependent manners when compared with reference drugs,quercetin and luteolin.Among six components of Kangen-karyu,the water extracts of Salviae Miltiorrhizae Radix or Cyperi Rhizoma exhibited significant inhibitory effects on BACE1 and GSK-3β.Among the constituents of Salviae Miltiorrhizae Radix extract,salvianolic acid C,salvianolic acid A,rosmarinic acid,and magnesium lithospermate B significantly inhibited BACE1.In addition,they inhibited GSK-3βwith an IC50 value range of 6.97 to 135.35μM.From these results,one of the effectiveness and its mechanisms of action of Kangen-karyu against AD may be the inhibition of BACE1 and GSK-3β,and one of the active ingredients of Kangen-karyu is Salviae Miltiorrhizae Radix and its constituents.

Overview of the microbiota in the gut-liver axis in viral B and C hepatitis

Viral B and C hepatitis are a major current health issue,both diseases having a chronic damaging effect on the liver and its functions.Chronic liver disease can lead to even more severe and life-threatening conditions,such as liver cirrhosis and hepatocellular carcinoma.Recent years have uncovered an important interplay between the liver and the gut microbiome:the gut-liver axis.Hepatitis B and C infections often cause alterations in the gut microbiota by lowering the levels of‘protective’gut microorganisms and,by doing so,hinder the microbiota ability to boost the immune response.Treatments aimed at restoring the gut microbiota balance may provide a valuable addition to current practice therapies and may help limit the chronic changes observed in the liver of hepatitis B and C patients.This review aims to summarize the current knowledge on the anatofunctional axis between the gut and liver and to highlight the influence that hepatitis B and C viruses have on the microbiota balance,as well as the influence of treatments aimed at restoring the gut microbiota on infected livers and disease progression.

丹酚酸B预适应对缺氧/复氧损伤的心脏微血管内皮细胞蛋白激酶C mRNA表达的影响

[目的]探讨丹酚酸B对心脏微血管内皮细胞(CMEC)抗缺氧损伤的保护机制。[方法]基于缺氧预适应的保护机制 ,通过缺氧/复氧的CMEC损伤模型 ,采用分子生物学方法 ,观察蛋白激酶CmRNA表达情况。[结果]丹酚酸B预适应可促进缺氧/复氧损伤的CMEC的蛋白激酶CmRNA表达增强 ,且明显优于缺氧预适应(HPC)。[结论]丹酚酸B预适应与HPC具有相类似的细胞保护效应 ,可增强细胞对随后较长时间缺氧/复氧损伤的耐受性 ,其机制可能是通过增强蛋白激酶CmRNA表达实现的。

CHF患者血浆NT-proBNP、UA和hs-CRP的变化及其临床意义

目的研究慢性心力衰竭(CHF)患者血浆N末端B型钠尿肽(NT-pro BNP)、血清尿酸(UA)、超敏C反应蛋白(hs-CRP)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)与低密度脂蛋白胆固醇(LDL-C)联合检测在CHF患者的临床应用价值。方法分别检测2013年5月至2014年5月于武汉大学人民医院心血管内科住院的319例CHF患者和102例正常对照者血液中NT-pro BNP、UA、hs-CRP及血脂相关指标(TC、TG、HDL-C、LDL-C)的水平,CHF组与正常对照组之间NT-pro BNP、UA、hs-CRP及血脂相关指标比较采用成组t检验,不同心功能之间各指标比较用单因素方差分析,而两两之间比较采用LSD法,NT-pro BNP与其他生化指标均进行Logistic回归分析。结果 CHF组患者的NT-pro BNP、UA和hs-CRP水平与正常对照组比较均升高[(5 224.03±8 119.83)pg/m L vs(139.46±96.75)pg/m L,(428.06±168.33)μmol/L vs(244.45±67.74)μmol/L,(15.60±24.81)mg/L vs(1.58±0.69)mg/L],而TC、HDL-C和LDL-C的水平均降低[(3.90±1.12)mmol/L vs(4.07±1.25)mmol/L,(1.01±0.95)mmol/L vs(1.59±0.54)mmol/L,(2.03±0.76)mmol/L vs(2.44±0.53)mmol/L];且随着NYHA心功能分级的增加,NT-pro BNP、UA和hs-CRP水平都升高(F=28.755,P<0.001;F=6.573,P<0.001;F=3.676,P=0.007),而TC、HDL-C和LDL-C水平都降低(F=3.052,P=0.029;F=2.479,P=0.045;F=2.947,P=0.021);Logistic回归分析显示,NT-pro BNP、UA和hs-CRP为CHF的独立危险因素(OR=2.98,P<0.001;OR=1.03,P=0.011;OR=1.39,P=0.021)。结论 NT-pro-BNP、UA、hs-CRP、TC、HDL-C、LDL-C等标志物与CHF密切相关,这些生化指标的联合检测有助于监测和控制CHF的发生和发展。

FibroScan在慢性病毒性肝病中的临床应用评估

目的将肝脏瞬时弹性扫描仪(FibroScan)检测应用在慢性病毒性肝病中,评估其临床应用价值。方法选取2015年8月—2017年5月我院门诊及住院的300例慢性病毒性肝病患者作为研究对象。对比不同类型患者的肝脏硬度值(LSM)、透明质酸(HA)测定值。结果乙肝病毒携带者、丙肝自愈患者、慢性乙型肝炎患者、慢性丙型肝炎患者、乙型肝炎肝硬化患者、丙型肝炎肝硬化患者的LSM值、HA测定值存在一定差异性。结论在慢性病毒性肝病中应用FibroScan具有重要价值。

血清BNP、hs-CRP、cTnI及UA联合检测对心力衰竭的临床价值

目的评价联合检测血清B型钠尿肽(BNP)、高敏C反应蛋白(hs-CRP)、心肌肌钙蛋白I(cTnI)及尿酸(UA)在心力衰竭(HF)患者中的表达及对预后评估的临床价值。方法选择我院2011年1月～2012年12月心内科住院HF患者70例,检测血清BNP、hs-CRP、cTnI及UA水平,并观察随访HF患者住院期间和出院后6个月内的不良心脏事件发生率、再住院率以及死亡率。结果Ⅱ级、Ⅲ级、Ⅳ级HF患者血清BNP分别为(192.4±89.8)、(387.4±172.7)、(764.8±286.1)pg/mL,三组比较差异有统计学意义,P<0.01。hs-CRP、cTnI及UA比较,差异均有统计学意义,(P<0.05)。且血清BNP、hs-CRP、cTnI及UA水平随着NYHA分级上升,水平越高。不同分组HF患者在住院期间和出院后6个月不良心血管事件发生率、再住院及死亡率比较差异有统计学意义。结论 HF患者血清BNP、hs-CRP、cTnI及UA水平随着NYHA分级上升,水平越高,对全面评估HF患者危险程度、疗效预后及转归,有重要的临床价值。

血清hs-CRP、BNP、cTnI及UA水平检测在心力衰竭患者诊治中的临床意义

目的:探讨血清高敏C反应蛋白(hs-CRP)、B型钠尿肽(BNP)、心肌肌钙蛋白I(cTnI)、尿酸(UA)水平检测在心力衰竭(HF)患者诊治中的临床意义。方法:回顾性分析2016年2月至2018年2月收治的129例HF患者的临床资料,将其设为观察组。同期在蚌埠医学院第一附属医院进行健康体检的50名健康者作为对照组。比较观察组各心功能分级患者与对照组的血清hs-CRP、BNP、cTnI及UA检测水平,并分析在HF诊治中的意义。结果:观察组血清hs-CRP、BNP、cTnI及UA水平随NYHA分级的增加而增高;NYHAⅠ级患者的血清hs-CRP、BNP水平明显高于对照组,差异有统计学意义(P<0.05);NYHAⅠ级患者的血清cTnI及UA水平与对照组比较,差异无统计学意义(P>0.05)。结论:联合检测血清hs-CRP、BNP、cTnI及UA水平对心力衰竭患者诊治具有临床参考意义。

Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis

Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease.A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis.Due to the obesity epidemic,fatty liver is now a significant problem in clinical practice.Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes.An association between hepatitis C virus (HCV) infection,steatosis and the onset of insulin resistance has been reported.Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections.Moreover,hyperinsulinemia has a deleterious effect on the management of chronic HCV.Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin.The underlying mechanisms of this complex interaction are not fully understood.A direct cytopathic effect of HCV has been suggested.The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides),lipid metabolism,the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated.

冠心病病变程度与U ACRP IL-6及BNP水平的相关性分析

目的探讨冠心病（CHD）病变程度与尿酸（UA）、C-反应蛋白（CRP）、白细胞介素-6（IL-6）32．B型脑钠肽（BNP）的相关性。方法200例CHD患者和同期100例对照者纳入研究，CHD患者分为急性心肌梗死组（AMI），不稳定性心绞痛组（UAP），稳定心绞痛组（SAP）。根据冠脉造影结果分为单支病变组、双支病变组和三支病变组。计算冠脉病变积分，对患者进行心功能分级，测定血浆UA、CRP、IL-6及BNP和LVEF水平，分析与冠脉病变程度、心功能的相关性。结果AMI、UAP、SAP和对照组的UA、CRP、IL-6及BNP水平依次下降（P〈0．05），同时UA、CRP、IL-6及BNP水平随病变支数增多、Gensini积分增加而增大（P〈0．05）。冠脉病变支数、冠脉病变积分和心功能级别与UA、CRP、IL-6、BNP均呈正相关（P〈0．05）。结论血浆UA、CRP、IL-6及BNP水平与CHD相关，可作为患者心脏功能、冠脉病变程度及危险分层的指标。

HBV、HCV、HIV血筛多中心研究免疫学灰区的核酸检测分析与临床特征研究

目的分析化学发光灰区标本的临床特征及核酸检测对化学发光灰区标本结果判断的指导性意义。方法收集2021年7月—12月全国不同地区的5家综合医院入院患者术前/输血前血源性传播疾病样本检测结果,对化学发光灰区检测结果的标本进行核酸检测结果及临床特征分析。结果5723例样本中总计检出HBV免疫灰区样本28例(占比0.49%),HCV灰区样本20例(占比0.35%)。经核酸检测验证,28例HBV灰区样本中,15例HBV样本核酸检测为阳性(占比53.5%),其HBcAb也均为阳性;13例HBV样本核酸检测为阴性(占比46.5%),其中HBcAb阳性4例。HBV与HCV免疫检测灰区在临床各个科室均有发现,出现HBV灰区样本最多的前三科室为骨科、妇科、泌尿科,灰区样本核酸验证假阳性最多的临床科室为妇科与骨科。HCV灰区样本最多的前三科室为泌尿、肾内、外科,且均为假阳性。HBV灰区样本患者临床诊断结果有35.7%(10/28)为肿瘤类疾病,HCV灰区样本患者临床诊断结果有40%(8/20)为肿瘤类疾病。结论化学发光法容易造成假阳性结果,应注意复检验证,且设置灰区并非必要。灰区样本可见于多个临床科室,具有一定的临床分布特征。核酸检测可以提高检测灵敏度并且更大限度保证结果的准确性,能够验证免疫检测灰区。

血清Cys-C、TBA及血常规指标在乙肝肝硬化失代偿期患者中的应用价值分析

目的探讨血清Cys-C、TBA及血常规指标在乙肝肝硬化失代偿期患者中的应用价值。方法选择2019年1月至2020年12月本院收治的134例乙肝肝硬化失代偿期患者纳入肝硬化组,另择同期收治的80例乙型肝炎患者及100例查体的健康体检者纳入肝炎组及对照组。测定各组受试者白细胞计数(WBC)、血红蛋白(Hb)、血小板计数(PLT)、白蛋白(ALB)、国际标准化比值(INR)及谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、TBA、Cys-C、肾小球滤过率(eGFR)水平,评估肝硬化患者治疗效果。结果(1)肝硬化组患者Cys-C、TBA、ALT、AST、TBIL、INR显著高于肝炎组、对照组,Hb、PLT、ALB、eGFR显著低于肝炎组、对照组(P<0.05);肝硬化Child-Pugh-C级患者Cys-C、TBA、ALT、AST、TBIL、INR显著高于肝硬化Child-Pugh-B级患者,Hb、PLT、ALB、eGFR显著低于肝硬化Child-Pugh-B级患者(P<0.05)。(2)Pearson相关性分析示,Cys-C、TBA与ALT、AST、TBIL等肝功能指标呈正相关,Hb、PLT与ALT、AST、TBIL等肝功能指标呈负相关(P<0.05)。(3)肝硬化失代偿期治疗有效组患者Cys-C、TBA、ALT、AST、TBIL、INR显著低于治疗无效组患者,Hb、PLT、eGFR显著高于治疗无效组患者(P<0.05)。(4)受试者特征工作曲线显示,Cys-C、TBA、WBC、Hb、PLT、INR、ALB、eGFR预测临床治疗效果的曲线下面积分别为0.729、0.800、0.557、0.693、0.788、0.702、0.609、0.815。结论乙肝肝硬化失代偿期患者存在血清Cys-C、TBA及Hb、PLT等血常规指标的变化,且其水平与肝功能及治疗效果密切相关,可能可作为病情评估、预后预测的参考指标。

利用牛乳腺细胞和小鼠乳腺组织分析异绿原酸C通过NF-κB信号通路对乳腺炎症反应的抑制效应

旨在探究异绿原酸C(ICAC)对乳腺炎及NF-κB炎性通路的抑制作用。本研究以脂多糖(LPS)分别刺激牛乳腺上皮细胞(MAC-T)和小鼠乳腺组织建立体外和体内炎性模型,采用MTT方法筛选ICAC处理MAC-T细胞的适宜浓度,ELISA检测炎性因子(IL-1β、IL-6和TNF-α)和炎性介导因子(COX-2和iNOS)的表达水平,Western blot方法检测NF-κB信号通路关键蛋白(IκB和p65)的表达水平和磷酸化水平。结果发现:1)ICAC在20~100 mg·L^(-1)的浓度下对MAC-T细胞没有显著的生长抑制作用(P>0.05);2)1 mg·L^(-1)的LPS处理引起MAC-T细胞中IL-1β、IL-6的蛋白质表达量极显著高于对照组(P<0.01),ICAC处理(20、50、80 mg·L^(-1))极显著下调了MAC-T细胞中IL-1β、IL-6、TNF-α、COX-2和iNOS的表达量(P<0.01);3)小鼠腹腔注射的ICAC(60、80、100 mg·kg^(-1))均降低了LPS诱导的CD3的表达,小鼠乳腺组织T淋巴细胞浸润减少;4)ICAC显著降低了LPS诱导的MAC-T细胞和小鼠乳腺组织中p65和IκB的磷酸化水平(P<0.05),抑制了p65的核转移。上述结果说明,异绿原酸C通过NF-κB炎性通路抑制MAC-T细胞和小鼠乳腺组织的炎性反应,但是异绿原酸C在奶牛乳腺炎防治中的应用有待进一步研究。

Rapid and sensitive HPLC-MS/MS method for quantitative determination of isochlorogenic acid B in rat plasma and its application in pharmacokinetic study

A sensitive LC-ESI-MS/MS method for determination of isochlorogenic acid B in rat plasma was developed and validated in the present study. Plasma samples were prepared by a simple protein precipitation with methanol containing resveratrol as internal standard (IS). The chromatographic separation was performed on a Zorbax SB-Cjg column (3.5 pm, 2.1 mmx 100 mm, Agilent, USA) at a flow rate of 0.2 mL/min using methanol/water containing 0.1% formic acid (v/v) as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with Electronic Spray Ion by selected reaction monitoring (SRM) of the transitions at m/z 515.3->352.9 for isochlorogenic acid B and m/z 227.1-143.1 for IS, respectively. The calibration curve of the method was linear over the range of 5-2500 ng/mL (r^2= 0.9982). The intra- and inter-day precisions (R.S.D.%) were less than 12.46%, and the accuracy (R.E.%) was within ±5.80%. Isochlorogenic acid B was sufficiently stable under all relevant analytical conditions. The validated method was successfully applied to the plasma pharmacokinetic studies of isochlorogenic acid B in rats. It was found that isochlorogenic acid B had non-linear pharmacokinetic characteristics in rats within the dosage ranges from 5 to 20 mg/kg.

Pd-B-P/C高效催化甲酸分解制氢的研究

甲酸(FA)分解制氢是解决能源问题的有效途径,而开发一类高效、稳定、廉价的催化剂是FA分解制氢在未来得到广泛应用的关键.联合使用一水合次亚磷酸钠(NaH2PO2·H2O)和二甲胺硼烷(DMAB)作为还原剂,成功制备了一类B、P共掺杂的Pd基催化剂,其对FA分解制氢具有较高的活性和选择性.在303K、反应混合液为1 mol/L FA和3mol/L甲酸钠(SF)的条件下,前1h反应的平均转化频率(TOF)达到798h-1,通过气相色谱检测发现分解后的气体产物中CO的体积分数小于0.01%,保证了分解得到氢气的清洁.