Role of ursolic acid chalcone,a synthetic analogue of ursolic acid,in inhibiting the properties of CD133+ sphere-forming cells in liver stem cells

The expression of CD133 decreases with differentiation of tumor cell, indicating that CD133 is a specific marker for isolation and identification of CSCs. In the present study the effect of Ursolic acid chalcone (UAC) on CD133⁺ hepatocellular carcinoma cell (HCC CSCs) differentiation, their self-renewal, tumorigenic capacity and sensitivity to chemotherapeutic drugs was studied. The results demonstrated that UAC inhibits the expression of CD133⁺ in a dose and time-dependent manner in PLC/PRF/5 and Huh7 HCC cells. The inhibition was significant at 50 μM and on day 8. The percentage of CD133⁺ cells decreased from an initial 59.3% in PLC/PRF/5 to 37.1% and 78.2% in Huh7 to 59.2% on treatment with UAC. There was inhibition of Oct4, Tert, Bmi1, β-catenin, ABCG2, and tumor sphere-related gene Ep300. In addition it also decreased number of CK19-positive cells and increased number of CK8/18-positive cells. UAC treatment caused a decrease in self-renewal capability and increase in sensitivity to doxorubicin and vincristine drugs in CD133⁺ HCC CSCs. Therefore, UAC can be a potent therapeutic agent to target differentiation of CSC in HCC.     

Antiarrhythmic Effect of Ischemic Preconditioning in Recent Unstable Angina Patients Undergoing Coronary Artery Bypass Grafting

Coronary artery bypass grafting (CABG) for unstable angina pectoris patients results in a higher incidence of arrhythmia and higher arrhythmic cardiac mortality. Ischemic preconditioning (IP) has proved effective in suppressing ischemia reperfusion arrhythmias in animals and in humans. The purpose of the present study was to investigate whether IP protects against postoperative arrhythmias in recent unstable angina patients undergoing urgent CABG. Forty-one patients with recent unstable angina and three-vessel coronary artery disease admitted for CABG were randomized into an IP group and a control group. The IP protocol involved twice occluding the ascending aorta with a cross-clamp for 2 minutes, followed by 3 minutes of reperfusion. Twenty-four-hour continuous electrocardiography (24-h ECG) was recorded from the preoperative day to the 2nd postoperative day. The incidences of supraventricular extrasystole (SVES), ventricular extrasystole (VES), supraventricular tachycardia (SVT), and ventricular tachycardia (VT) were 95.2%, 85.7%, 26.2%, and 26.2%, respectively, before surgery and 100.0%, 100.0%, 88.1%, and 76.2%, respectively, after surgery. IP significantly reduced the incidence of VT and the severity of SVES, VES, SVT, and VT after surgery. The period of mechanical ventilation and the length of stay in the intensive care unit were significantly shorter in the IP group. In summary, rhythm disturbances are common in CABG patients with recent unstable angina. IP significantly reduces rhythm disturbances, including SVES, VES, SVT, and VT after CABG. The findings indicate that IP could constitute an additional myocardial protective strategy in recently unstable angina patients undergoing CABG.     

Aortopulmonary window： a case diagnosed and surgery confirmed by ultrafast computed tomography

Aortopulmonary window (APW) is a rare congenital defect,found in 0.2% of patients with congenital heart disease,in which a communication exists between the ascending aorta and the pulmonary artery trunk with normal separation of the aortic and pulmonary valves.     

Ischemic Preconditioning in Cardiac Surgery

Murry and colleagues in 1986 described a paradoxical phenomenon that exposure of the heart to repeated brief ischemic episodes delayed the severity of myocardial infarction of a following prolonged myocardial ischemia and termed it myocardial ischemic preconditioning (IP). From then on, IP had been extensively studied in various kinds of experimental models as well as in humans. Besides delaying myocardial infarction, IP has been proved to be a potent endogenous factor in preserving high energy phosphates, suppressing arrhythmias and improving postischemic functional recovery. Delaying myocardial ultrastructure damage, reducing lactate, reducing the utilization of myocardial glycogen and protecting coronary endothelium after IP has also been found. Different experimental models and conditions resembling cardiac surgery have also been investigated. The mechanism of IP is not yet clear, however. The conclusions derived from animal studies could not totally stand for the situation in open heart surgery. IP was found effective in preserving high energy phosphate, improving heart performance and decreasing cardiac troponin T release during open heart surgery. Controversial exists because in same reports there were no effects of IP. The difference in IP protocol, myocardial protective method and study object might be the reason of the controversial results. Several clinical factors may affect IP effects during clinical practice. The purpose of the present study was to review the recent literature on IP, especially the IP mechanism, IP phenomenon in cardiac surgery and the possible influential factors, to summarize whether IP might prefer additional protection of current protective strategy in cardiac surgery.     

Synergistic effect of the anti-PD-1 antibody with blood stable and reduction sensitive curcumin micelles on colon cancer

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a potent anticancer drug with versatile biological activities, while the clinical translation of curcumin is severely limited due to its hydrophobicity, rapid elimination, and metabolism in the blood circulation. Herein, we aim to unravel the potential of curcumin as a synergistic agent with immunotherapy in the treatment of cancers. In an effort to minimize premature release and improve the systemic bioavailability, a superior blood stable and reduction sensitive curcumin micellar formulation, of which the release can be triggered by cancer cells, is rationally designed. We have synthesized a telodendrimer (mPEG-PLA-(LA)₄) capable of forming reversible disulfide crosslinked micelles (DCMs). The curcumin loaded DCMs (Cur/DCMs) are spherical with a uniform size of 24.6 nm. The in vitro release profile demonstrates that curcumin releases significantly slower from DCMs than that from non-crosslinked micelles (NCMs), while the release can be accelerated with the increasing concentration of reducing agent glutathione (GSH). Intravenous administration of Cur/DCMs stably retains curcumin in the bloodstream and efficiently improves the systemic bioavailability. Furthermore, Cur/DCMs exhibit synergistic anticancer efficacy when combined with the anti-PD-1 antibody in an MC-38 colon cancer xenograft model. Our results potentiate the integration of blood stable curcumin nanoformulation and immunotherapy for cancer treatment.     

不同方法处理的牛心包生物相容性和钙化结果分析

目的 观察脱细胞处理对牛心包体内生物相容性及钙化的影响并与戊二醛处理的牛心包进行比较；材料和方法对新鲜牛心包随机分为三组，A、戊二醛处理组：新鲜牛心包采用0．5％的戊二醛进行处理；B、新鲜牛心包组：新鲜牛心包保存于四联抗生素液中；C、脱细胞组：新鲜牛心包酶．去污剂联合脱细胞后保存于四联抗生素液中。上述处理后的牛心包经细菌培养，显示无细菌生长后，植入雄性昆明小鼠皮下三周观察炎性浸润及钙化情况。采用von Kossa钙染色检查进行定性分析；原子吸收光谱检查进行钙含量定量分析。同时体外对三组牛心包进行力学和热皱缩温度进行测试。结果 三组间炎性浸润程度明显不同，0．5％的戊二醛处理组钙化程度明显增高，每克干重牛心包平均含钙量71．2mg，较其他两组有明显差异（P〈0．001），新鲜牛心包组（平均2．12mg／g干重）和脱细胞组（1．41mg／g干重）间钙化程度方面亦有显著统计学意义（P〈0．001）。组织学钙染色光镜下检查显示三组间黑色颗粒有明显差异，支持三组间钙含量定量结果的差异。戊二醛处理组的力学性能与优于新鲜组和脱细胞处理组，热皱缩温度高于新鲜组和脱细胞处理组。结论 新鲜牛心包脱细胞处理后钙化显著降低，免疫源性降低，有很好的生物相容性。     

MicroRNA profiling of the intestine during hypothermic circulatory arrest in swine

AIM:To perform a profiling analysis of changes in intestinal micro RNA(mi RNA)expression during hypothermic circulatory arrest(HCA).METHODS:A total of eight piglets were randomly divided into HCA and sham operation(SO)groups.Under general anesthesia,swine in the HCA group were subjected to hypothermic cardiopulmonary bypass at 24?℃followed by 80 min of circulatory arrest,and the reperfusion lasted for 180 min after cross-clamp removal.The counterparts in the SO group were only subjected to median sternotomy.Histopathological analysis was used to detect mucosal injury,and Pickand-Mix custom mi RNA real-time polymerase chain reaction(PCR)panels containing 306 unique primer sets were utilized to assay unpooled intestinal samples harvested from the two groups.RESULTS:The intestinal mucosa of the animals that were subjected to 24?℃HCA exhibited representative ischemic reperfusion injury of grade 2 or 3 according to the Chiu score.Such intestinal mucosal injuries,with the subepithelial space and epithelial layer lifting away from the lamina propria,were accompanied by shortened and irregular villi.On the contrary,the intestinal mucosa remained normal in the shamoperated animals.In total,twenty-five mi RNAs were differentially expressed between the two groups(15upregulated and 10 downregulated in the HCA group).Among these,eight mi RNAs(mi R-122,mi R-221-5p,mi R-31,mi R-421-5p,mi R-4333,mi R-499-3p,mi R-542and let-7d-3p)were significantly dysregulated(four higher and four lower).The expression of mi R-122 was significantly(5.37-fold)increased in the HCA group vs the SO group,indicating that it may play a key role inHCA-induced mucosal injury.CONCLUSION:Exposure to HCA caused intestinal mi RNA dysregulation and barrier dysfunction in swine.These altered mi RNAs might be related to the protection or destruction of the intestinal barrier.     

High Postoperative Interleukin-8 Levels Related to Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Surgery

BACKGROUND: Atrial fibrillation (AF) is the most frequently encountered postoperative arrhythmic complication after coronary artery bypass graft (CABG). There is increasing evidence to support the influence of inflammation in the pathogenesis of AF. The aim of the present study was to investigate the relation of postoperative new AF and systemic inflammatory changes after CABG. METHODS: A total of 113 CABG patients were recruited in the present study. Holter data from 24-hour electrocardiography were collected from 1 day before the operation to postoperative day 2 (POD2). AF was registered as positive if any AF event occurred. Serum cytokine, including interleukin (IL)-6, IL-8, and IL-10 were analyzed before and after surgery. RESULTS: The overall incidences of postoperative AF and sustained AF were 36.3% and 31.9%, respectively. Patients with postoperative AF had longer respiratory treatment, intensive care unit treatment, and inotropic medication periods. Similar concentrations of serum IL-6 were found after surgery in patients with and without AF. The concentrations of serum IL-8 was significantly higher at 2 hours and on POD1 and POD2 in patients with postoperative AF. The concentration of serum IL-10 was significantly higher on POD1 in patients with postoperative AF. CONCLUSIONS: Postoperative AF in CABG patients is associated with a more complicated postoperative outcome. Higher concentrations of serum IL-8 in CABG patients with postoperative AF suggested that an influence of inflammation in the pathogenesis postoperative AF after open heart surgery.     

家兔内毒素休克时血浆及主动脉一氧化碳水平的变化

目的：探讨一氧化碳(CO)是否作为一种新的内源性介质参与内毒素休克发病机制。结果：血浆以及主动脉CO和一氧化氮（NO）水平在内毒素休克时均显著增高，使用血红素氧合酶抑制剂锌原叶啉和NO合酶抑制剂糖皮质激素地塞米松均可显著减轻内毒素林克中的血压下降和代谢性酸中毒程度，但是锌原卟啉仅能显著抑制血浆以及主动脉CO水平的增高，但对NO2／NO3水平无显著影响；而使用地塞米松则可显著抑制血浆以及主动脉NO2／NO3水平的增高，对CO水平无显著影响。结论：CO是在NO之外的又一个内源性介质，参与内毒素休克一系列病理生理过程。