莲子心总生物碱的毒性试验研究

摘要 目的： 探讨莲子心总生物碱的毒副作用,以对莲子心总生物碱作出安全性评价。方法 ：小鼠急性毒性试验中一次性给予最大灌胃量5000mg/kg莲子心总生物碱,观察小鼠中毒症状。长期口服毒性实验,Sprague-Dawley(SD)大鼠随机分为四组,分别按照400mg/kg?d、200 mg/kg?d、100 mg/kg?d的剂量给予SD大鼠灌胃实验室自制莲子心总生物碱,对照组给予等量体积0.3%羧甲基纤维素钠,连续服用30天。结果 ：在急性毒性试验中给予5000mg/kg莲子心总生物碱对小鼠不产生毒性作用。在长期毒性试验中,除不同剂量给药组SD大鼠血清尿素氮与对照组具有显著性差异(P<0.05),高、中剂量组SD大鼠血糖含量与对照组有明显差异(P<0.05)外余下指标与对照组相比均无明显差异。高、中、低剂量组大鼠肝组织病理切片与对照组相比均明显异常,表现为肝小叶结构正常。结论 ： 莲子心总生物碱对小鼠最大耐受剂量为5000mg/kg,同时灌胃给药400mg/kg/天莲子心总生物碱对大鼠无毒副作用。     

重症急性呼吸综合征患者中重症者早期预警指标研究

目的　探讨重症急性呼吸综合征 (SARS)患者中与重症发生相关的危险因素 ,寻找发生重症的早期预警指标。方法　对北京市SARS临床诊断病例数据库中转院资料完整 ,且在 2周内发生重症的 35 5例和始终未发生重症的 84 1例SARS患者进行单因素和多因素分析。结果　高龄、有基础病的患者发生重症的危险性明显增加。重症患者发生重症前表现出以下特点 :体温下降缓慢、脉搏加快、淋巴细胞计数持续 <0 9× 10 9/L、中性粒细胞高于 7 1× 10 9/L(80 % )、X线胸片异常进展较快等。采用Cox多元逐步回归发现 ,具有统计学显著性的早期预警重症发生的独立因素包括 :年龄偏大、有基础疾病、住院 2d后体温仍不能降至正常、住院 3d后中性粒细胞比值持续在 80 %以上、住院 4d后淋巴细胞计数仍持续 <0 9× 10 9/L和病程中出现脉搏持续加快达到 10 0次 /min。结论　根据SARS患者的年龄和基础病情况 ,结合临床对体温、脉搏、淋巴细胞绝对值以及中性粒细胞绝对值 (百分比 )的密切观察能够对重症SARS的发生进行早期预警。     

Association of the angiotensin-converting enzyme gene polymorphism with chronic heart failure in Chinese Han patients

BACKGROUND: An insertion/deletion (I/D) polymorphism is present in the 16th intron of the angiotensin-converting enzyme (ACE) gene and is associated with serum and tissue ACE level. Some studies have shown that the DD genotype is associated with some cardiovascular diseases; while ACE polymorphism's effect on chronic heart failure (CHF) remains uncertain. AIM: To investigate the association of the ACE gene I/D polymorphism with CHF in the Chinese Han population. METHODS: The genotype was determined by polymerase chain reaction in 102 normal controls and in 79 patients with CHF. Plasma angiotensin (Ang) levels were assessed by radio-immunity assay. Left ventricular end-diastolic diameters (LVDD) and left ventricular ejection fractions were assessed by echocardiography. RESULTS: The ACE gene polymorphism distribution was similar in patients and control subjects. However, ACE gene DD polymorphism was associated with a more severe condition, greater LVDD [mm: DD: 71+/-7, ID: 62+/-5, II: 60+/-5, P<0.001 DD vs. ID, P<0.001 DD vs. II] and higher plasma Ang II level [pg/ml DD: 92+/-19, ID: 79+/-21, II: 65+/-17 P<0.05 DD vs. ID, P<0.001 DD vs. II]. CONCLUSION: In Chinese Han patients with CHF, ACE gene DD polymorphism might be a marker of a more severe condition, and a higher level of activation of the renin-angiotensin system.     

万古霉素等十种抗生素对耐苯唑西林葡萄球菌的体外活性比较

为了比较万古霉素等１０种抗生素对１９９５年分离的９５株耐苯唑西林的金黄色葡萄球菌和７２株凝固酶阴性葡萄球菌的体外活性，用ＮＣＣＬＳ颁布的琼脂稀释法测ＭＩＣ。结果受检的１０种抗生素中万古霉素的活性最好，其ＭＩＣ５０及ＭＩＣ９０分别为１ｍｇ／Ｌ及２ｍｇ／Ｌ，平均值为１２４ｍｇ／Ｌ；耐药率为０％。其次为壁霉素，其ＭＩＣ５０及ＭＩＣ９０分别为２ｍｇ／Ｌ及８ｍｇ／Ｌ，平均值为２５１ｍｇ／Ｌ；耐药率为２％。利福平ＭＩＣ５０及ＭＩＣ９０分别为０１２５ｍｇ／Ｌ及３２ｍｇ／Ｌ，平均值为０２２ｍｇ／Ｌ；耐药率为１４％。其它依ＭＩＣ９０的大小排序，为氧氟沙星，甲氧苄啶，红霉素，庆大霉素，磷霉素，磺胺甲恶唑等。用柱状图显示了前三种药的ＭＩＣ值的分离，万古霉素具有良好的分散性，全部落在敏感区，且为单峰。结果表明万古霉素对ＭＲＳＡ和ＭＲＳＣｏＮ有良好的抗菌活性。     

前S2合成肽对肝癌组织中浸润T淋巴细胞亚群表达的影响

目的通过前S2合成肽对肝细胞癌(HCC)组织中浸润T淋巴细胞亚群表达状况的分析,探讨前S2合成肽是否能改变乙型肝炎病毒(HBV)导致的HCC组织中浸润T淋巴细胞亚群表达的百分数和CD4+/CD8+比值,达到特异性治疗HCC. 方法用Merrifield固相化学合成法合成HBV中前S2抗原性最强的P120～146多肽段.测序后,用0.01mol/L磷酸盐缓冲液溶解除菌后作为抗原.选择12例术后病理诊断为HCC,术前血清经酶联免疫吸附法测得HBsAg、HBeAg、抗-HBC阳性和HBV DNA阳性,且HBsAg在HCC组织中表达为阳性病例作为研究对象.在96孔培养板上,每孔加入经密梯度离心获得的单个核细胞悬液100μl(1×106细胞),设每孔含量为1μg、5μg、10μg、白细胞介素-2 500U和阴性对照共5组,每组均设3复孔,作用7d后制片,采用APAAP法观察CD3+、CD4+、CD8+的百分数和CD4+/CD8+的比值变化. 结果 发现在含有前S2合成肽5μg/孔组中,CD4+表达明显增加(34.1±3.2),与自身对照(29.3±3.5)相比差异有显著性 (t＝3.508,P<0.01),CD4+/CD8+比值(1.19±0.43)与自身对照(0.81±0.41)相比差异有显著性(t＝2.235,P＜0.05).在白细胞介素-2组中,CD3+表达有增加,与自身对照相比有差异,其它各组T淋巴细胞亚群几乎处于不变化的状态. 结论在适当的剂量下,前S2合成肽能够改变HCC组织中T淋巴细胞亚群的表达,使CD4+增加,并能改变CD8+静息状态,使二者互为达到杀伤肿瘤细胞的目的,为特异性运用前S2蛋白提供客观依据.     

Tnhibition of hepatitis B virus by a novel L-nucleoside, β-L-D4A and related analogues

AIM: To explore the inhibition of β-L-D4A on hepatitis B virus (HBV) in 2.2.15 cells derived from HepG2 cells transfected with HBV genome.METHODS: 2.2.15 cells were plated at a density of 5×104per well in 12-well tissue culture plates, and treated with various concentrations of β-L-D4A for 6 days. In the end,5 μl of medium was used for the estimation of HBsAg and HBeAg, the other medium was processed to obtain virions by a polyethlene glycol precipitation method. At the same time, intracellular DNA was also extracted and digested with HindⅢ. Both DNAs were subjected to Southern blot,hybridized with a 32P-labeled HBV probe and autoradiographed.Intensity of the autoradiographic bands was quantitated by densitometric scans of computer and ED50 was calculated. Then Hybond-N membrane was washed and rehybridized with a 32P-labeled mtDNA-specific probe, and effect of β-L-D4A on mitochondrial DNA was studied. 2.2.15 cells were also seeded in 24-well tissue culture plates,and cytotoxicity with different concentrations was examined by MTT method. ID50 was calculated. Structureactivity relationships between D2A and D4A were also studied as above.RESULTS: Autoradiographic bands were similar between supernatant and intracellular HBV DNA. Episomal HBV DNA was inhibited in a dose-dependent manner. ED50 was 0.2μM. HBsAg or HBeAg was not apparently decreased, and inhibition of mitochondrial DNA was not obvious. The experiment of cytotoxicity gained ID50 at 200 μM.CONCLUSION: β-L-D4A possesses potent inhibitory effects on the replication of HBV in vitro with little cytotoxicity and mitochondrial toxicity, TI value is 1000. It is expected to be developed as a new clinically anti-HBV drug.     

Comparison of accuracy of mitral valve area in mitral stenosis by real-time, three-dimensional echocardiography versus two-dimensional echocardiography versus Doppler pressure half-time

Mitral valve area (MVA) in 30 patients with mitral stenosis (MS) and 34 normal controls was calculated by real-time, 3-dimensional echocardiography (RT3DE); MVA in patients with MS correlated well with the mitral area determined by 2-dimensional echocardiography (r = 0.98) and by pressure half-time (r = 0.90). MVA in normal controls on RT3DE correlated well with MVA on 2-dimensional echocardiography (r = 0.94) and pressure half-time (r = 0.91). There were significant differences between the orifice areas in patients with MS and normal controls. RT3DE can provide not only the anatomic structure of mitral valve apparatus, but also the optimal plane of the smallest mitral valve orifice, and can thus accurately measure the MVA.     

An evaluation of the response to neoadjuvant chemotherapy for osteosarcoma of extremities: PERCIST versus RECIST 1.1 criteria after long-term follow-up

Annals of Nuclear Medicine - The aim of this study was to compare the recent Positron emission tomography (PET) Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid...