中医药的抗炎机制在治疗肝纤维化中的作用

肝脏是人体腹腔内最大的实体器官,对维持机体的基本生理功能起着至关重要的作用。肝脏疾病是威胁人类健康的常见病多发病。全球约有10%人口受到不同程度的肝脏疾病的危害,其中,肝纤维化往往成为这些疾病的晚期病理特征。由于肝纤维化的发病机制复杂,尚无有效的合成类药物能够治疗肝纤维化。中药治疗肝纤维化具有多靶点和副作用小的优势。本文综述了肝纤维化的病理特征与诱发炎症的关系,讨论了中药治疗肝纤维化的单味中药、传统配方及其化学活性成分的抗炎症机制。     

国产西罗莫司与原研品在体内外对细胞影响的比较实验

目的探讨国产西罗莫司与原研品对移植宿主外周血中免疫细胞的影响效果。方法体外实验:人膀胱癌T24细胞体外培养,分别加入国产西罗莫司和原研品,CKK-8法检测并比较细胞增殖活性受抑制的情况。体内实验:建立小鼠异位心脏移植模型,设立对照无手术组(对照组)、移植无治疗组(Tx组)、移植+国产西罗莫司组(Tx+YXK组)、移植+原研品组(Tx+RAPA组)。观察移植心脏搏动情况,受者脾脏的流式细胞学检测,以及脾脏及移植物中免疫细胞浸润的病理检查。流式细胞检测树突状细胞(DC),CD8+细胞和调节性T细胞(Treg),病理组织学检测及免疫组化染色比较两组免疫细胞浸润情况。两组间比较采用独立样本t检验,多组间比较采用单因素方差分析,两两比较采用LSD-t检验。结果体外实验结果显示,国产西罗莫司与原研品对T24细胞活力影响的差异无统计学意义(P>0.05)。体内实验结果显示,Tx组移植心脏于第7天停止搏动,Tx+YXK组和Tx+RAPA组在第10天心脏搏动仍有力、节律正常。(1)脾脏流式细胞检测显示,与对照组、Tx组比较,Tx+RAPA组、Tx+YXK组CD11c+I-A+CD86+DC细胞(15.88±4.73、22.90±3.86比4.51±1.57、5.40±2.54)、CD8+淋巴细胞数量(6.32±0.98、6.75±1.34比3.03±1.12、3.23±0.97)均降低,而Tx+RAPA组CD4+CD25+Foxp3+阳性细胞数量(15.06±3.42比7.87±1.95,10.88±2.08)升高(P均<0.05)。Tx+YXK组和Tx+RAPA组3种免疫细胞数量差异均无统计学意义(P>0.05)。(2)移植心脏病理免疫细胞组化染色灰度分析,Tx组、Tx+YXK组和Tx+RAPA组CD4,CD8,IDO和CD11b数量差异无统计学意义(P>0.05),与Tx组比较,Tx+RAPA组和Tx+YXK组CD11c(25143.52±3525.12比12936.30±766.94、14240.60±3124.67)、Foxp3阳性细胞浸润数量(500.78±238.33比46.05±68.16、49.22±25.82)降低(P均<0.05),Tx+YXK组和Tx+RAPA组比较差异无统计学意义(P>0.05)。(3)模型动物脾脏病理免疫细胞组化染色灰度分析,Tx组CD 4和CD8阳性细胞浸润数量较Tx+YXK组和Tx+RAPA组少,但差异无统计学意义(P>0.05),Tx+YXK组和Tx+RAPA组比较,各种细胞染色的IOD值差异均无统计学意义。结论使用国产西罗莫司与原研品两种药物后受者移植心脏和脾脏中的细胞浸润变化一致;在体外对细胞增殖、移植后抗排斥作用和体内免疫细胞的影响表现均一致。     

沙库巴曲缬沙坦钠片对高原地区慢性心力衰竭患者神经内分泌激素和心功能的影响

摘要 目的：探讨沙库巴曲缬沙坦钠片治疗高原地区慢性心力衰竭（CHF）患者的疗效及对神经内分泌激素和心功能的影响。方法：选取2017年3月~2019年6月期间我院接收的CHF患者109例。根据随机数字表法将患者随机分为对照组（n=54）和研究组（n=55）,对照组患者予以缬沙坦治疗,研究组患者则予以沙库巴曲缬沙坦钠片治疗,比较两组患者疗效、神经内分泌激素指标[去甲肾上腺素（NA）、醛固酮（ALD）、血管紧张素Ⅱ（AngⅡ）]和心功能指标[超敏心肌肌钙蛋白T（hs-cTnT）、N-末端脑钠肽前体（NT-proBNP）、左房内径（LAD）、左室舒张末期内径（LVEDD）以及左室射血分数（LVEF）]。记录两组患者心血管不良事件发生情况。结果：研究组患者治疗12周后总有效率为90.91%（50/55）,显著高于对照组患者的75.93%（41/54）（P<0.05）。两组治疗12周后ALD、NA、AngⅡ均下降,且研究组低于对照组（P<0.05）。两组治疗12周后hs-cTnT、NT-proBNP、LVEDD、LAD均下降,且研究组低于对照组（P<0.05）;LVEF升高,且研究组高于对照组（P<0.05）。两组心血管不良事件发生率对比无差异（P>0.05）。结论：沙库巴曲缬沙坦钠片治疗高原地区CHF患者,疗效显著,可有效改善神经内分泌激素水平和心功能,且不增加心血管不良事件发生率,临床应用价值较高。     

SGLT2抑制剂对2型糖尿病患者血糖、血尿酸水平及心脏功能的影响

摘要 目的：研究SGLT2抑制剂对2型糖尿病患者血糖、血尿酸水平及心脏功能的影响。方法：选取我院2019年1月~2020年6月收治的2型糖尿病合并稳定性心功能不全患者106例为研究对象,采用随机数字表法将患者分为两组,所有患者均给予2型糖尿病饮食控制治疗方案,并给予心功能不全对症药物治疗。对照组患者在此基础上给予二甲双胍,观察组在对照组的基础上给予SGLT2抑制剂达格列净。比较两组患者的血糖、血尿酸（uric acid,UA）、血清脑钠肽(brainnatriureticpeptide,BNP)水平、心脏功能及生活质量。结果：治疗前两组的餐后2 h血糖（2- hour postprandial glucose,2 h PBG）、空腹血糖（fasting blood glucose,FBG）及糖化血红蛋白（glycosylated hemoglobin,HbAIc）水平比较无差异（P＞0.05）,治疗后两组的上述指标均显著降低,且观察组显著低于对照组（P<0.05）;治疗前两组的UA和BNP水平比较无差异（P＞0.05）,治疗后两组的上述指标均显著降低,且观察组显著低于对照组（P<0.05）;治疗前两组的左室射血分数（left ventricular ejection fraction,LVEF）和左室舒张末期内径（left ventricular end diastolic diameter,LVEDD）水平比较无差异（P＞0.05）,治疗后观察组的LVEF水平显著升高,LVEDD水平显著降低（P<0.05）,但对照组治疗前后比较无差异（P＞0.05）;治疗前两组的SF-36健康调查量表(the SF-36 Health Survey,SF-36)评分比较无差异（P＞0.05）,治疗后两组的SF-36评分均显著上升,且观察组显著高于对照组（P<0.05）,两组的不良反应发生率比较无统计学差异（P＞0.05）。结论：达格列净可显著改善2型糖尿病合并稳定性心功能不全患者的血糖、血尿酸水平,还能够改善患者的心脏功能,值得临床借鉴。     

CT定量分析在冠心病介入治疗前后血流灌注改变的评估价值

摘要 目的：探讨CT定量分析在冠心病介入治疗前后血流灌注改变的评估价值。方法：2018年2月到2020年11月选择在本院诊治的冠心病患者95例作为研究对象,所有患者都给予经皮冠状动脉介入治疗,在介入前1 d与介入后1个月进行CT定量与超声检查,随访介入后6个月的冠状动脉再狭窄情况并进行相关性分析。结果：所有患者都顺利完成介入治疗,介入期无严重并发症发生。95例患者介入后1个月的左室射血分数(ejectionfraction,EF)、左室短轴缩短率(fractionalshortening,FS)高于介入前1 d(P<0.05),介入前后左室等容舒张时间(iso-volumicrelaxationtime,IVRT)对比差异无统计学意义(P>0.05)。95例患者介入后1个月的心肌血流量(Myocardialbloodflow,MBF)、心肌血容量(Myocardialbloodvolume,MBV)高于介入前1d(P<0.05),达峰时间(Timetopeak,TTP)低于介入前1 d(P<0.05)。介入后随访6个月,冠状动脉再狭窄14例,再狭窄率14.7 %,其中中度狭窄12例,重度狭窄2例;Pearson分析显示冠心病患者介入前1 d的MBF、MBV、TTP与FS、EF都存在相关性(P<0.05);Logistic回归分析显示MBF、MBV、TTP、FS、EF为影响冠心病患者介入后随访再狭窄率的重要因素(P<0.05)。结论：CT定量分析在冠心病介入前后的应用能有效反映血流灌注改变情况,且与患者的心功能存在相关性,也可有效预测患者介入随访冠状动脉再狭窄发生情况。     

目标剂量螺内酯联合曲美他嗪对老年慢性心力衰竭患者炎症因子、RAAS及心率变异性的影响

摘要 目的：探讨目标剂量螺内酯（20 mg/d）联合曲美他嗪对老年慢性心力衰竭（CHF）患者炎症因子、肾素-血管紧张素-醛固酮系统（RAAS）、及心率变异性的影响。方法：选取120例老年CHF患者,随机分为对照组和研究组,各60例,其中对照组给予曲美他嗪治疗,研究组给予曲美他嗪联合目标剂量螺内酯治疗,对比两组疗效、炎症因子[超敏C反应蛋白（hs-CRP）、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）]、RAAS指标 [肾素（PRA）、血管紧张素Ⅱ（AngⅡ）及醛固酮（ALD）]、心率变异性[24 h平均正常R-R间期标准差（SDNN）,24 h连续5 min节段平均正常R-R间期标准差（SDANN）,连续正常R-R间期差的均方根（rMSSD）]、心功能[左心室射血分数（LVEF）、左室收缩末期内径（LVESD）、左室舒张末期内径（LVEDD）]及安全性。结果：与对照组相比,研究组的总有效率更高（P<0.05）。治疗6个月后,两组hs-CRP、TNF-α、IL-6、LVESD、LVEDD、PRA、AngⅡ、ALD均较治疗前降低,且研究组上述指标低于对照组（P<0.05）。治疗6个月后,两组LVEF较治疗前升高,且研究组LVEF高于对照组（P<0.05）。治疗6个月后,研究组SDNN、SDANN、rMSSD均较治疗前升高,且研究组上述指标高于对照组（P<0.05）。两组不良反应发生率比较差异不明显（P>0.05）。结论：曲美他嗪联合目标剂量螺内酯治疗老年CHF患者疗效显著且安全性好,可明显改善患者的心功能、心率变异性,降低炎症因子水平,其可能是通过拮抗RAAS发挥作用。     

An Approach Based on Mutually Informed Neural Networks to Optimize the Generalization Capabilities of Decision Support Systems Developed for Heart Failure Prediction

Available clinical methods for heart failure (HF) diagnosis are expensive and require a high-level of experts intervention. Recently, various machine learning models have been developed for the prediction of HF where most of them have an issue of over-fitting. Over-fitting occurs when machine learning based predictive models show better performance on the training data yet demonstrate a poor performance on the testing data and the other way around. Developing a machine learning model which is able to produce generalization capabilities (such that the model exhibits better performance on both the training and the testing data sets) could overall minimize the prediction errors. Hence, such prediction models could potentially be helpful to cardiologists for the effective diagnose of HF. This paper proposes a two-stage decision support system to overcome the over-fitting issue and to optimize the generalization factor. The first stage uses a mutual information based statistical model while the second stage uses a neural network. We applied our approach to the HF subset of publicly available Cleveland heart disease database. Our experimental results show that the proposed decision support system has optimized the generalization capabilities and has reduced the mean percent error (MPE) to 8.8% which is significantly less than the recently published studies. In addition, our model exhibits a 93.33% accuracy rate which is higher than twenty eight recently developed HF risk prediction models that achieved accuracy in the range of 57.85% to 92.31%. We can hope that our decision support system will be helpful to cardiologists if deployed in clinical setup.     

Endogenous cardiac activity rhythms of continental slope Nephrops norvegicus (decapoda: nephropidae)

The endogenous cardiac activity rhythm of the Norway lobster Nephrops norvegicus was studied under constant conditions of darkness by means of a computer-aided monitoring system (CAPMON). Time series recordings of the heart rate (beats min^?1) were obtained from 47 adult males freshly collected from the continental slope (400–430?m) in the western Mediterranean. Periodogram analysis revealed the occurrence of circadian periodicity (of around 24?h) in most cases. A large percentage of animals showed significant ultradian periods (of around 12 and 18?h). The analysis of the circadian time series revealed the occurrence of peaks of heart rate activity during the expected night phase of the cycle. These results are discussed in relation to the emergence and locomotor activity rhythms of the species.     

A mixed finite element formulation for a non-linear,transversely isotropic material model for the cardiac tissue

In this paper we present a mixed finite element method for modeling the passive properties of the myocardium. The passive properties are described by a non-linear, transversely isotropic, hyperelastic material model, and the myocardium is assumed to be almost incompressible. Single-field, pure displacement-based formulations are known to cause numerical difficulties when applied to incompressible or slightly compressible material cases. This paper presents an alternative approach in the form of a mixed formulation, where a separately interpolated pressure field is introduced as a primary unknown in addition to the displacement field. Moreover, a constraint term is included in the formulation to enforce (almost) incompressibility. Numerical results presented in the paper demonstrate the difficulties related to employing a pure displacement-based method, applying a set of physically relevant material parameter values for the cardiac tissue. The same problems are not experienced for the proposed mixed method. We show that the mixed formulation provides reasonable numerical results for compressible as well as nearly incompressible cases, also in situations of large fiber stretches. There is good agreement between the numerical results and the underlying analytical models.     

Xanthine Oxidase is Not Responsible for Reoxygenation Injury in Isolated-Perfused Rat Heart

The massive leakage of intracellular enzymes which occurs during reoxygenation of heart tissue after hypoxic or ischemic episodes has been suggested to result from the formation of oxygen radicals. One purported source of such radicals is the xanthine oxidase-mediated metabolism of hypoxanthine and xanthine. Xanthine oxidase (O form) has been suggested to be formed in vivo by limited proteolysis of xanthine dehydrogenase (D form) during the hypoxic period (Granger el ai. Gastroenterology 81, 22 (1981)). We measured the activities of xanthine oxidase in both fresh and isolated-perfused (Langendorff) rat heart tissue. Approximately 32% of the total xanthine oxidase was in the O form in fresh and isolated-perfused rat heart. This value was unchanged following 60min of hypoxia and 30 minutes of reoxygenation. The infusion of 250/JM allopurinol throughout the perfusion completely inhibited xanthine oxidase activity but had no effect on the massive release of lactate dehydrogenase (LDH) into the coronary effluent upon reoxygenation of heart tissue subjected to 30 or 60min of hypoxia. Protection from 30min of hypoxia was also not obtained when rats were pretreated for 48 h with allopurinol at a dose of 30mg/kg/day and perfused with allopurinol containing medium. Superoxide dismutase (50 units/ml), catalase (200 units/ml), or the antioxidant cyanidanol (100μM) also had no effect on LDH release upon reoxygenation after 60 min of hypoxia. Xanthine oxidase activity was detected in a preparation enriched in cardiac endothelial cells while no allupurinol-inhibitable activity could be measured in purified isolated cardiomyocytes. It is concluded that xanthine dehydrogenase is not converted to xanthine oxidase in hypoxic tissue of the isolated perfused rat heart, and that the release of intracellular enzymes upon reoxygenation in this experimental model is mediated by factors other than reactive oxygen generated by xanthine oxidase.