抗炎-中药治疗动脉粥样硬化的有效途径

动脉粥样硬化发病机制的“炎症-损伤-反应”学说得到广泛支持和认可。炎性反应贯穿于动脉粥样硬化发生、发展的整个过程，并与急性心脑血管事件的发生密切相关；干预AS炎症反应可能是中药治疗动脉粥样硬化的有效途径。本文从动脉粥样硬化发生、发展过程的病理基础角度，总结了炎性反应在动脉粥样硬化形成早期、进展期、成熟期、破裂期的重要作用，并提出了从抗炎角度研究、筛选、治疗动脉粥样硬化中药的思路和方法。     

翁维良老师治疗酒精性心肌病经验

翁维良教授从事中西医内科临床工作50余年,擅用活血化瘀治疗心血管病及各种慢性疑难疾病。结合多年临床经验,翁老认为酒精性心肌病病机多属以心气(阳)亏虚为主,湿热、瘀血、痰饮、毒热内蕴为标的虚实夹杂证。治疗时,在完全戒酒的基础上,配合中药益气温阳扶助正气,同时辨证应用健脾、祛湿、活血、祛痰、解毒等祛除实邪治法,疗效肯定。文章旨在介绍翁维良教授辨治酒精性心肌病的临证经验。     

108例支气管哮喘患者舌脉象特征分析

目的：探讨对支气管哮喘临床辨证有意义的舌脉象客观指标,以辅助临床诊断。方法：应用TP—I型中医舌脉象数字化分析仪检测108例患者舌脉象参数,分析支气管哮喘发作期与缓解期的舌脉象特征。结果：108例支气管哮喘患者的舌象中,舌色以淡红舌、淡紫舌多见,舌苔以白苔、黄苔、薄苔为多见;脉象以弦脉、滑脉、弦滑脉为多见;舌脉象参数中舌色指数、苔色指数、厚苔指数、胖瘦指数在哮喘发作期各证型中有显著性差异（P〈0．05）;RPSR1、RPSR3、RPSR4、RBF、RLMS2、PLMP2、RLMS3、RLMP3在哮喘发作期与缓解期有显著性差异（P〈0．05）。结论：支气管哮喘患者的脉象参数、舌色指数、苔色指数、厚苔指数、胖瘦指数、RPSR1、RPSR3、RPSR4、RBF、RLMS2、PLMP2、RLMS3、RLMP3对其辨证分型有重要参考价值。     

JAK2/STAT3信号通路介导灯盏花乙素抗人心脏微血管内皮细胞缺氧-复氧损伤

Objective: To investigate the antagonistic cell injury effect and molecular mechanism of scutellarin(SCU)in hypoxia reoxygenation(HR) treated human cardiac microvascular endothelial cells(HCMECs).Methods: The method of 12 h hypoxia following by 12 h reoxygenation was used to culture HCMECs in vitro to built cell injury model. The groups were divided into control group, model(HR) group, and HR + SCU(0.1 μmol/L, 1 μmol/L, and 10 μmol/L) group. The cell viability was determined by MTT, and oxidative stress was detected by malondialdehyde(MDA) levels by biochemical assay kit. Protein expression of JAK2/p-JAK2 and STAT3/p-STAT3 were evaluated by Western blot.Results: The results of MTT and MDA showed that HR decreased the cell viability(P 0.05) and increased MDA level significantly(P 0.05), SCU played a contrary role in these processes. Western blot analysis indicates that, the expression of JAK2 and p-JAK2, STAT3, and p-STAT3 were increased in model group when compared with control group(P 0.05); Compared with model group, their expression were reduced by SCU(P 0.05).Conclusion: SCU took a protective effect on HR-treated HCMECs, and the molecular mechanism may be associated with the inhibition of JAK2/STAT3 signal transduction pathway.     

Antioxidative and in vitro hepatoprotective activity of Bupleurum kaoi leaf infusion

The roots of Bupleurus spp. have been used in traditional Chinese herbal medicine for curing liver diseases. Although bioactive saikosaponins have been detected in the leaves as well as in the roots, the aerial parts of the plants are discarded as waste. In the present study, a leaf infusion of B. kaoi Liu, Chao et Chuang, an indigenous Bupleurus species in Taiwan, was prepared and the antioxidant properties and in vitro hepatoprotective activity were demonstrated. The results show that the leaf infusion exerted DPPH free radical scavenging activity, inhibitory capacity on superoxide anion formation and superoxide anion scavenging activity. The hepatotoxicity of acetaminophen (APAP) and carbon tetrachloride (CCl4) on the rat liver cells were also decreased by the leaf infusion.     

Visual targeted therapy of hepatic cancer using homing peptide modified calcium phosphate nanoparticles loading doxorubicin guided by T1 weighted MRI

Effective treatment and real-time monitoring of hepatic cancer are essential. A multifunctional calcium phosphate nanoparticles loading chemotherapeutic agent doxorubicin and magnetic resonance imaging contrast agent diethylenetriaminepentaacetic acid gadolinium (A54-CaP/Gd-DTPA/DOX) was developed for visual targeted therapy of hepatic cancer via T1-weighted MRI in real-time. A54-CaP/Gd-DTPA/DOX exhibited a higher longitudinal relaxivity (6.02?mM^?1?s^?1) than commercial MR contrast agent Gd-DTPA (3.3765?mM^?1?s^?1). The DOX release from the nanoparticles exhibited a pH dependent behavior. The cellular uptake results showed that the internalization of A54-CaP/Gd-DTPA/DOX into BEL-7402 cells was1.9-fold faster than that of HepG2 cells via A54 binding. In vivo experiments presented that A54-CaP/Gd-DTPA/DOX had higher distribution and longer retention time in tumor tissue than CaP/Gd-DTPA/DOX and free DOX, and also displayed great antitumor efficacy (95.38% tumor inhibition rate) and lower toxicity. Furthermore, the Gd-DTPA entrapped in the nanoparticles could provide T1-weighted MRI for real-time monitoring the progress of tumor treatment.     

Nano carriers for drug transport across the blood–brain barrier

Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood–brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug–carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully discussed.     

心脏不停跳心内直视手术113例

目的探讨不停跳心内直视手术的方法和意义。方法浅低温（31℃-34℃）不停跳心脏直视手术共113例,男59例,女54例。年龄4-73岁,平均31.4岁。其中房间隔缺损（atrial septal defect,ASD）22例,室间隔缺损（ventricular septal defect,VSD）32例,法乐氏三联征（triad of Fallot,F3）3例,双腔右心室1例,Ebstein畸形3例,二尖瓣置换手术（mitral valve replacement,MVR）36例,主动脉瓣置换手术（aortic valve replacement,AVR）9例,双瓣置换手术（double valves replacemnet,DVR）7例。结果1例二尖瓣置换手术因术中暴露极差而被迫降温心脏停跳操作外,其余全为非停跳手术,全组手术顺利,无死亡,术后恢复良好。结论心脏不停跳手术简化了手术操作程序,方便手术后管理,减少了心脏停跳后的负面影响。     

IL-1 receptor-associated kinase 1 participates in the modulation of the NLRP3 inflammasome by tumor-associated macrophages in hepatocellular carcinoma

BackgroundHepatocellular carcinomas (HCCs) occur frequently in the digestive system and are associated with high mortality. This current study examined the regulatory relationship between interleukin (IL)-1 receptor-associated kinase 1 (IRAK1), NLR family pyrin domain-containing 3 (NLRP3) inflammasomes, and tumor-associated macrophages (TAMs) in the growth and metastasis of HCC.MethodsThe expression of IRAK1 and NLRP3 was assessed in tissues and cells via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Immunohistology was performed to detect the macrophage markers CD68, CD163, and CD168 in tumor tissues. Small interfering (si)RNA targeting IRAK1 (si-IRAK1) was designed to silence IRAK1 expression. Following si-IRAK1 transfection and/or co-culture with TAMs, HCC cell viability, proliferation, migration, and invasion, as well as the expression of NLRP3 and pro-inflammatory cytokines IL-1 β, IL-18, and monocyte chemotactic protein 1 (MCP-1) were assessed.ResultsHCC tissues showed elevated expression of IRAK1 and NLRP3, as well as increased expression of the macrophage markers CD68, CD163, and CD168, compared to adjacent healthy tissues. Silencing of IRAK1 expression in HepG2 and Huh7 cells resulted in suppression of cell proliferation, migration, and invasion, and also reduced expression of NLRP3 and the pro-inflammatory cytokines IL-1β, IL-18, and MCP-1. Moreover, TAMs promoted HepG2 and Huh7 cell proliferation, migration, and invasion, and elevated the expression of NLRP3, IL-1β, IL-18, and MCP-1. Furthermore, IRAK1 silencing reversed the effects of TAMs on HepG2 and Huh7 cells.ConclusionsThe expression of IRAK1 was associated with HCC growth and metastasis, as well as NLRP3 inflammasome activation. The ability of TAMs to promote HCC growth and metastasis may be activated by NLRP3 inflammasomes and regulated by IRAK1.     

Decreased expression of claudin-18.2 in alpha-fetoprotein-producing gastric cancer compared to conventional gastric cancer

BackgroundAlpha-fetoprotein-producing gastric cancer (AFPGC) is a subtype of gastric cancer (GC) with more aggressive biological behavior. As a highly specific tight junction component exclusively present in gastric mucosa and gastric adenocarcinomas, claudin-18.2 (CLDN18.2) has become an emerging target in GC. In this study, we aimed to provide insight into AFPGC and investigate the expression and the clinical implications of CLDN18.2 in AFPGC.MethodsWe retrospectively collected 98 cases of AFPGC and reviewed their clinical, morphological, and immunohistochemical features. Another 356 patients with stage-matched conventional GC (cGC) were enrolled as a control group. We further surveyed CLDN18.2 expression by immunohistochemistry (IHC) in 51 AFPGC tissues and explained its association with the clinicopathological parameters of AFPGC.ResultsOur results showed that AFPGC was a unique GC type with elevated serum alpha-fetoprotein (AFP), which was a predictor of a worse prognosis. AFPGC showed typical morphological features and positive staining of at least 1 hepatocytic or enteroblastic marker. The expression rate of CLDN18.2 was low, with a positivity rate of 21.6%, which was much lower than that observed in cGC tissues (38.5%). A significant correlation was found between CLDN18.2 expression and the differentiation of AFPGC. CLDN18.2 expression was negatively correlated with the serum AFP level of AFPGC. We also found that AFPGC with a hepatoid type (HPT) component showed a significantly lower CLDN18.2 expression than those without.ConclusionsThis study demonstrated that CLDN18.2 was significantly decreased in AFPGC and was negatively correlated with the patient’s preoperative serum AFP level. The negative correlation between AFP and CLDN18.2 could be explained by retro-differentiation of AFPGC. Special treatment strategies might be needed for this unique tumor type.