Association between serum sphingolipids and necroinflammation of liver tissue pathology in chronic hepatitis B

Background & Aims: Accurately identifying liver necroinflammation was essential for the timely implementation of antiviral therapy in chronic hepatitis B(CHB) patients. The sphingolipids were involved in various chronic inflammatory processes. This study aimed to evaluate the association between serum sphingolipids and liver necroinflammation in CHB patients.Methods: The study prospectively enrolled patients with a diagnosis of chronic hepatitis B who were subsequently treated with nucleos(t)ide analogs (NAs). Liver biopsy was performed at baseline and 5-year follow-up, and serum sphingolipid levels were measured by ultra-high-performance liquid chromatography tandem mass spectrometry.Results: A total of 70 CHB patients were enrolled with baseline liver necroinflammation of 27(38.6%) G1, 23(32.9%) G2, and 20(28.6%) G ≥ 3, respectively. A total of 126 liver biopsies were performed on the study population over a 5-year period, of which 80 (63.5%) G<2 and 46 (36.5%) G≥2. Serum ALT, ALP, SM d16:0/16:1, SM d16:0/17:1, SM d18:0/17:0 and Cer d18:2/22:0 showed significant differences between two groups (P<0.01). Multivariate analysis showed that serum ALT (OR 1.006, 95% CI: 1.000-1.011), SM d16:0/16:1 (OR 1.552, 95% CI: 1.150-2.093), Cer d18:2/22:0 (OR 0.003, 95% CI: 0.000-0.173) were associated with G ≥ 2. In the subgroup of patients with normal serum ALT, serum Cer d18:2/22:0 was lower in patients with G ≥ 2 than that with G < 2. After 5 years, alleviated inflammation was accompanied by decreased serum SM d16:0/16:1 and increased serum Cer d18:2/22:0 in patients with baseline G ≥ 2.Conclusions: Lower serum Cer d18:2/22:0 could reflect hepatic necroinflammation (G ≥ 2) in CHB patients including those with normal serum ALT, and its elevation predicts the inflammation improvement after NAs treatment.     

TCDD宫内暴露致雄性子代大鼠生殖毒性研究

目的：探讨2-3-7-8四氯二苯并二噁英（2-3-7-8 Tetrachlorodibenzo-p-Dioxin,TCDD）宫内暴露对雄性子代生殖毒性的影响及机制。方法：成功交配后,将母鼠随机分组。高剂量组（0.5 μg/kg）、低剂量组（0.1 μg/kg）和溶剂对照组,每组各6只,TCDD组及对照组于孕8~14 d（gestation day 8-14,GD8-14）采用灌胃方式分别给予TCDD及玉米油处理。孕鼠自然分娩,测量雄性仔鼠肛门至生殖器的距离（anal to genital distance,AGD）;计算睾丸的脏器系数;利用精子质量分析仪对仔鼠精子的质量及数量进行分析测定;酶联免疫吸附法对雄性子代血清睾酮（testosterone,T）水平进行测定;测定凋亡相关蛋白Bax、Bcl2、Caspase-3的表达水平。结果：0.1 μg/kg组、0.5 μg/kg组仔鼠与对照组仔鼠相比,AGD[（1.49±0.04） cm、（1.32±0.01） cm和（1.21±0.02） cm]有所缩短（P=0.000）,精子数目[（72.33±4.46）×106个/mL、（63.67±3.44）×106个/mL、（45.33±5.47）×106个/mL]与精子活率[（78.53±1.26）%、（64.40±3.14）%、（53.87±3.65）%]明显降低,精子畸形率[（2.17±0.75）%、（4.83±0.75）%、（8.00±1.10）%]升高（P=0.000）,血清中T水平[（2.68±0.06） ng/mL、（2.38±0.08） ng/mL和（2.10±0.09） ng/mL]明显下降（P=0.000）,差异均有统计学意义,0.5 μg/kg TCDD组雄性仔鼠的睾丸质量（P=0.001）和睾丸脏器系数（P=0.004）降低的差异有统计学意义;睾丸组织细胞Bax蛋白相对表达量（0.836±0.004、1.185±0.004、1.414±0.001）随染毒剂量的递增而上升（P=0.000）,Bcl-2（1.368±0.053、1.108±0.040、0.751±0.022）则相反（P=0.001）,同时,0.5 μg/kg TCDD染毒组Pro-Caspase-3蛋白表达明显降低,但Cleaved-Caspase-3蛋白表达明显增加（P=0.000）。结论：宫内暴露TCDD可使雄性仔鼠出现雌性化特征,影响雄性仔鼠生育能力,对雄性子代具有生殖毒性,其机制可能与仔鼠睾丸组织细胞增殖-凋亡失衡和细胞凋亡的线粒体通路被激活有关。     

血府逐瘀汤对心血管疾病炎症介质影响的Meta分析

目的：评价血府逐瘀汤对心血管疾病相关炎症介质的影响。方法：通过Pubmed、Embase、Cochrane Library、国家知识基础设施数据库(CNKI)、中国学术期刊数据库(CSPD)及中文科技期刊数据库(CCD)进行文献检索,应用主题词结合自由词的方式制定检索策略,获取血府逐瘀汤对心血管疾病炎症介质影响的随机对照试验(RCT),根据Cochrane手册对纳入的RCT进行文献质量评价,整理并提取相关数据资料,应用RevMan 5.3软件进行Meta分析。结果：共纳入23项RCT,包括2 274例患者。Meta分析结果显示,血府逐瘀汤可显著降低炎症介质C反应蛋白(SMD=-2.04,95%CI为-2.82～-1.26,P<0.000 01)、超敏C反应蛋白(SMD=-1.46,95%CI为-1.96～-0.96,P<0.000 01)、肿瘤坏死因子-α(SMD=-1.25,95%CI为-1.68～-0.83,P<0.000 01)和白细胞介素-6(SMD=-1.08,95%CI为-1.45～-0.70,P=0.003)的水平。结论：血府逐瘀汤可通过降低炎症介质的表...     

DPPH法测定芒果叶中总黄酮提取物的抗氧化活性

目的 研究芒果叶中不同含量总黄酮提取物的抗氧化活性。方法 采用DPPH法测定芒果叶中以芒果苷为指标的不同含量的总黄酮提取物的抗氧化活性。结果 抗氧化活性由大到小依次为:VC＞芒果苷含量为78.48 %的总黄酮提取物＞芒果苷对照品＞芒果苷含量为52.13 %的总黄酮提取物＞芒果苷含量为38.65 %的总黄酮提取物＞芒果苷含量为15.24 %的总黄酮提取物＞BHT。结论 不同含量的总黄酮提取物对DPPH自由基的清除作用呈现一定的线性关系。     

氮素不同形态配比对夏枯草苗期生长 及光合特性的影响

目的:探讨不同氮素形态对夏枯草生长及光合特性的影响,为夏枯草氮肥的合理施用提供一定依据.方法:采用水培法,测定在等氮水平(15mmol·L-1)不同铵硝比处理下,夏枯草叶面积、生物量、叶绿素含量及光合相关参数.结果:随着铵硝比的下降,夏枯草叶面积先增加后下降,全铵营养(NH+4-N:N0-3-N为100:0)下最小,当NH+4-N:NO-3-N为25:75时最大;随硝态氮比例的提高,夏枯草全株鲜重不断增加,在全硝处理时达到最大,是全铵处理的5.11倍;而全株干重则以NH+4-N:NO-3-N为25:75的最大,且与全硝处理无显著差异.铵硝比为50:50时叶片中总叶绿素、类胡萝卜素含量最高.铵硝比为25:75时,夏枯草净光合速率(Pn)最大,全铵处理下最低.结论:在总氮水平为15mmol·L-1下,适量增加硝态氮比例,有利于促进夏枯草苗期生长、提高干物质积累和净光合速率.     

大肠癌中医辨证分型研究进展

回顾了近年来大肠癌中医病因病机及辨证分型方面的研究进展,应统一中医证型及其标准,加强对大肠癌四诊客观化的相关研究尤为重要。     

特利加压素联合白蛋白输注治疗肝肾综合征患者疗效及尿NGAL和KIM-1对疗效的预测价值

目的 探讨尿中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）和肾损伤因子-1（uKIM-1）对特利加压素联合白蛋白输注治疗肝肾综合征患者疗效的预测价值。方法 2017年5月1日~2018年4月30日就诊于北京佑安医院的肝硬化并发I型HRS患者19例,应用特利加压素联合白蛋白输注治疗,采用ELLSA法测定尿NGAL和KIM-1水平。结果 经特利加压素联合白蛋白输注治疗4 d后,应答12例（63.2%）,未应答7例（36.8%）;两组患者年龄和性别比较,差异无统计学意义（P=0.605和P=0.386）,两组自发性细菌性腹膜炎（SBP）和上消化道出血发生率比较,差异无统计学意义（P=0.526和P=0.525）,两组血清ALT、AST、TBIL、DBIL、BUN、ALB和血小板计数、血红蛋白、白细胞计数等基线资料比较,差异无统计学意义（P>0.05）;应答组患者PTA显著高于非应答组（P=0.006）,血肌酐水平显著低于非应答组（P=0.043）;应答组患者uNGAL/Cr 为21.8（7.8~65.5） μg/g,uKIM-1/Cr水平4.9（2.0~7.7） μg/g,均显著低于非应答组【分别为97.8（27.1~358.2） μg/g（P=0.010）和9.1（5.5~13.6） μg/g,P=0.001】;早期应答组患者90 d生存率为75.0%,非应答组为42.9%,差异无统计学意义（P=0.182）;血肌酐与uNGAL/Cr呈正相关（r=0.549,P=0.022）,而与uKIM-1/Cr无显著相关（r=0.213,P=0.411）。结论 基线血肌酐、PTA和尿NGAL水平可以预测特利加压素联合白蛋白输注治疗的肝硬化并发HRS患者的疗效,值得进一步研究。     

载艾塞那肽介孔二氧化硅纳米粒的研制及其药动学

制备了孔径（6.0±0.2）nm、孔容（0.94±0.03）cm3/g、比表面积（701.4±0.70）m2/g的SBA-15型介孔二氧化硅纳米粒,平均粒径为（920±120）nm,以其为载体负载艾塞那肽。所得SBA-15型介孔二氧化硅纳米粒因具有较大比表面积和比孔容,可提高载药量至（15.2±2.0）%。体外释放试验表明,该纳米粒在p H 7.4磷酸盐缓冲液中d1释出近35%,d14时缓慢释出40%。将艾塞那肽的水溶液和SBA-15型介孔二氧化硅纳米粒分别皮下注射给予SD大鼠。结果两组的t1/2为0.60和14.53 h,AUC0→t为1.71和8.60 ng·ml^-1·h,MRT为1.14和21.30 h,可见该载体可显著增加药物的半衰期和MRT,有望成为艾塞那肽皮下注射给药的理想载体。     

阿托伐他汀钙片在人及Beagle犬体内药动学差异的对比

采用液相色谱-串联质谱法分别测定人和Beagle犬口服阿托伐他汀钙片后血浆中的阿托伐他汀(1)及其活性代谢物,包括邻位羟基化物(2)和对位羟基化物(3),计算并对比人和Beagle犬血浆中1、2、3的药动学参数.结果显示,药物在人体内主要以原型1的形式存在,检测不到代谢物3;而在Beagle犬体内主要以代谢物2的形式存在,另检测到原型药物占约30％,代谢物3约占5％.原型药物1在人体内的消除半衰期约为Beagle犬的3倍,而清除率仅约为Beagle犬的65％.可见,人与犬口服药物的药动学存在显著的种属间差异,Beagle犬对原型药物的代谢速度和程度均显著高于人体.     

Terminal aspartic acids promote the self-assembly of collagen mimic peptides into nanospheres

The development of novel strategies to construct collagen mimetic peptides capable of self-assembling into higher-order structures plays a critical role in the discovery of functional biomaterials. We herein report the construction of a novel type of amphiphile-like peptide conjugating the repetitive triple helical (GPO)_m sequences characteristic of collagen with terminal hydrophilic aspartic acids. The amphiphile-like collagen mimic peptides containing a variable length of (Gly-Pro-Hyp)_m sequences consistently generate well-ordered nanospherical supramolecular structures. The C-terminal aspartic acids have been revealed to play a determinant role in the appropriate self-assembly of amphiphile-like collagen mimic peptides. Their presence is a prerequisite for self-assembly, and their lengths could modulate the morphology of final assemblies. We have demonstrated for the first time that amphiphile-like collagen mimic peptides with terminal aspartic acids may provide a general and convenient strategy to create well-defined nanostructures in addition to amphiphile-like peptides utilizing β-sheet or α-helical coiled-coil motifs. The newly developed assembly strategy together with the ubiquitous natural function of collagen may lead to the generation of novel improved biomaterials.

Amphiphile-like collagen mimic peptides with terminal aspartic acids may provide a general and convenient strategy to create well-defined nanostructures.