苯丙氨酸负荷实验筛选苯丙酮尿症杂合子

目的初步建立口服苯丙氨酸负荷实验筛选苯丙酮尿症(PKU)杂合子的方法。方法采用病例对照研究,观察4例PKU杂合子(为已确诊PKU患儿的父母)和4例年龄、性别、体质量与前者相匹配的健康对照者,空腹、口服苯丙氨酸后1、2、3、4、6、24 h,血清苯丙氨酸(Phe)、酪氨酸(Tyr)浓度及其比值(Phe/Tyr)的变化。血清Phe、Tyr浓度采用高效液相色谱仪测定。结果口服Phe 2 h,PKU杂合子与对照者的Phe/Tyr均达到峰值,两者间血清Phe浓度和Phe/Tyr呈现显著差异(P<0.05);且两者之间的数值范围无重叠,其中Phe/Tyr的差距更大。结论口服苯丙氨酸负荷实验有助于筛选人群中的PKU杂合子。     

早期慢性肾脏病患者肾组织甲状旁腺激素的表达及其作用

目的 探讨早期慢性肾脏病(CKD)患者肾组织甲状旁腺激素(PTH)表达和分布,以及其在CKD进展中的可能作用.方法 选取2009年至2012年间本科收治并经肾活检确诊的CKD 1期及2期的肾小球肾炎患者82例为研究对象.另取8例肾移植配型不符或肾肿瘤患者的正常肾组织作对照.受试者均检测Scr、BUN、血钙、磷、PTH及25(OH) VitD3等.以Cockcroft-Gault (CG)公式计算肌酐清除率(Ccr),双血浆99mTc-DTPA清除率法检测GFR.根据肾间质炎性细胞浸润程度,将患者分为轻、中、重组,用免疫组化方法观察肾组织PTH表达和分布；用Image-Pro Plus图像分析软件计算各例肾组织PTH阳性染色吸光度(A)值,并比较PTH表达强度差异.结果CKD1期及2期的肾小球肾炎患者的外周血钙、磷、25(OH) VitD3及PTH水平均处于正常范围,PTH与上述其他指标间无相关.不同病理类型肾小球肾炎患者肾组织均可见PTH表达,主要位于肾小管,而肾小球及肾间质也有少量分布,其表达强度均显著高于对照组(P＜0.01),且随肾间质炎性细胞浸润增多,PTH表达增强.各病理类型间肾组织PTH表达强度差异无统计学意义.结论 早期CKD(1期及2期)患者肾组织PTH表达增强,且早于外周血PTH的改变及矿物质和骨代谢紊乱,可能与局部炎性反应程度相关.     

脑梗死超早期动脉溶栓后证候演变观察

目的探讨急性脑梗死超早期动脉溶栓后中医证候的演变。方法采用前瞻、对照方法,分析40例超早期脑梗死动脉溶栓后中医证候的动态演变。结果治疗14 d后,34例风证全部消失,气虚证由治疗前的0例变为8例,火证由治疗前的22例变为9例。瘀证在治疗前后的出现频率均为100%。急性脑梗死在超早期以实证为主,随着病程的发展,风证逐渐消失,实证的比例下降。而虚证,特别是气虚证的比例开始增加,瘀证在整个过程中则一直存在。治疗组证候的变化与保守治疗组没有明显差别。结论溶栓治疗对脑梗死超早期的证候演变没有产生明显的影响,治疗组的证候变化符合急性脑梗死超早期的总体证候演变规律。     

Clustered patterns of species origins of nature-derived drugs and clues for future bioprospecting

Many drugs are nature derived. Low drug productivity has renewed interest in natural products as drug-discovery sources. Nature-derived drugs are composed of dozens of molecular scaffolds generated by specific secondary-metabolite gene clusters in selected species. It can be hypothesized that drug-like structures probably are distributed in selective groups of species. We compared the species origins of 939 approved and 369 clinical-trial drugs with those of 119 preclinical drugs and 19,721 bioactive natural products. In contrast to the scattered distribution of bioactive natural products, these drugs are clustered into 144 of the 6,763 known species families in nature, with 80% of the approved drugs and 67% of the clinical-trial drugs concentrated in 17 and 30 drug-prolific families, respectively. Four lines of evidence from historical drug data, 13,548 marine natural products, 767 medicinal plants, and 19,721 bioactive natural products suggest that drugs are derived mostly from preexisting drug-productive families. Drug-productive clusters expand slowly by conventional technologies. The lack of drugs outside drug-productive families is not necessarily the result of under-exploration or late exploration by conventional technologies. New technologies that explore cryptic gene clusters, pathways, interspecies crosstalk, and high-throughput fermentation enable the discovery of novel natural products. The potential impact of these technologies on drug productivity and on the distribution patterns of drug-productive families is yet to be revealed.     

急性牙髓炎一次性根管治疗的临床疗效观察

目的分析一次性根管治疗急性牙髓炎的临床疗效。方法选择65例急性牙髓炎患者,随机分成观察组33例和对照组32例。观察组采用一次性根管治疗,对照组采用开髓后封失活剂,分次根管消毒、根管充填等常规根管治疗。结果治疗48 h后,有效率对照组高于观察组,差异有统计学意义(P<0.05)。1年后疗效综合评价,观察组高于对照组,但差异无统计学意义(P>0.05)。结论急性牙髓炎一次性根充治疗可以减少术者的操作程度和患者的痛苦、就诊次数和受感染几率。