三个新的PAH基因短串联重复序列多态性及其在苯丙酮尿症产前诊断中的应用

目的提高经典型苯丙酮尿症的产前诊断的成功率。方法在苯丙氨酸羟化酶（phenylalanine hydroxylase，PAH）基因附近选择了3个新的短串联重复序列（short tandem repeat，STR）位点（PAH26、PAH32和PAH9），进行扩增长度片段多态性分析，确定它们在中国人群的分布及在诊断中的应用价值。结果3个新的STR位点的多态信息含量分别为0．518（PAH26）、0．413（PAH32）和0．362（PAH9）。这3个位点之间，PAH9与第3内含子中的STR位点（TCTA）n之间存在连锁不平衡，其他位点组合不存在连锁不平衡。联合第3内含子中的STR位点（TCTA）n和2个新的位点，可以对家系中突变基因标记进行95％N断，并成功地用于4例产前诊断中。结论选择性地应用PAH基因中的3个STR位点组合，可以95％地区分经典型苯丙酮尿症家系中父母的两个基因，从而准确地进行快速产前诊断。     

从氧自由基、一氧化氮探讨四逆汤抗急性失血性休克的肝脏机制

目的:从氧自由基、一氧化氮探讨四逆汤抗急性失血性休克的肝脏机制。方法:复制急性失血性休克大鼠模型, 分为假手术对照组;单纯休克模型组;休克+生理盐水复苏组;休克+四逆注射液复苏组。四逆注射液(浓度1000g生药/L), 剂量0.1mL/200g大鼠。用生理盐水或四逆注射液治疗3h后处死动物并取组织。测定各组肝脏超氧化物歧化酶(SOD)活性、丙二醛(MDA)水平, 一氧化氮(NO)水平。采用免疫组化染色法, 观察诱导型一氧化氮合酶(iNOS)在肝细胞中的变化特点。RT-PCR观测肝细胞iNOS和内皮源性一氧化氮合酶(eNOS)基因表达的变化。结果:模型组在休克1h后SOD活性明显低于对照组(P＜0.01)、MDA水平明显高于对照组(P＜0.01)。四逆汤组复苏3h后肝组织SOD明显高于生理盐水组(P＜0.01)、MDA低于生理盐水组(P＜0.01)、NO水平明显高于生理盐水组(P＜0.01)。生理盐水组iNOS在肝细胞中染色阳性单位明显高于四逆汤组(P＜0.05)。生理盐水组促进iNOSmRNA的表达。四逆汤组eNOSmRNA的表达增强。结论:四逆汤通过清除氧自由基, 升高NO, 改善肝组织微循环, 减少诱导型iNOS表达的各种因素, 理论上减轻了NO与氧自由基生成的ONOO的细胞毒作用和血管的低反应性, 并对肝脏起到保护作用。     

Corticofugal amplification of facilitative auditory responses of subcortical combination-sensitive neurons in the mustached bat

Recent studies on the bat's auditory system indicate that the corticofugal system mediates a highly focused positive feedback to physiologically "matched" subcortical neurons, and widespread lateral inhibition to physiologically "unmatched" subcortical neurons, to adjust and improve information processing. These findings have solved the controversy in physiological data, accumulated since 1962, of corticofugal effects on subcortical auditory neurons: inhibitory, excitatory, or both (an inhibitory effect is much more frequent than an excitatory effect). In the mustached bat, Pteronotus parnellii parnellii, the inferior colliculus, medial geniculate body, and auditory cortex each have "FM-FM" neurons, which are "combination-sensitive" and are tuned to specific time delays (echo delays) of echo FM components from the FM components of an emitted biosonar pulse. FM-FM neurons are more complex in response properties than cortical neurons which primarily respond to single tones. In the present study, we found that inactivation of the entire FM-FM area in the cortex, including neurons both physiologically matched and unmatched with subcortical FM-FM neurons, on the average reduced the facilitative responses to paired FM sounds by 82% for thalamic FM-FM neurons and by 66% for collicular FM-FM neurons. The corticofugal influence on the facilitative responses of subcortical combination-sensitive neurons is much larger than that on the excitatory responses of subcortical neurons primarily responding to single tones. Therefore we propose the hypothesis that, in general, the processing of complex sounds by combination-sensitive neurons more heavily depends on the corticofugal system than that by single-tone sensitive neurons.     

Detection of factor Ⅷ intron 1 inversion in severe haemophilia A

Objective Screening the intron 1 inversion of factor Ⅷ (FⅧ) in the population of severe haemophilia A(HA) in China and performing carrier detection and prenatal diagnosis. Methods Using LD-PCR to detect intron 22 inversions and multiple-PCR within two tubes to intron 1 inversions in sereve HA patients. Carrier detection and prenatal diagnosis were performed in affected families. Linkage analysis and DNA sequencing were used to verify these tests. Results One hundred and eighteen patients were seven diagnosed as intron 22 inversions and 7 were intron 1 inversions out of 247 severe HA patients. The prevalence of the intron 1 inversion in Chinese severe haemophilia A patients was 2. 8% (7/247). Six women from family A and 2 from family B were diagnosed as carriers. One fetus from family A was affected fetus. Conclusion Intron 1 inversion could be detected directly by multiple-PCR within two tubes. This method made the strategy more perfective in carrier and prenatal diagnosis of haemophilia A.     

一种新型的脱细胞组织工程血管支架的构建和评价

本研究的目的是制备一种免疫原性较小、生物相容性较好、力学性能优良的组织工程血管支架。新鲜获得的犬主动脉,置于三蒸水中4℃过夜，使血管细胞由于渗透压差较大而破裂；随后经过多聚环氧化合物家族的乙二醇缩水甘油醚（EX-810）的作用。进一步促进细胞破裂的同时。对血管支架的纤维结构起交联作用；最后应用物理超声的方法清除支架内的细胞碎片残留。用这种方法处理的犬主动脉内几乎没有可见的核染，基本消除了血管支架的免疫原性。同新鲜的血管相比较。这种组织工程血管支架的各种力学指标与新鲜的犬主动脉没有显著差异。说明处理后的支架仍然保持新鲜血管的力学特征。同时它还表现出极低的细胞毒性。分别在支架上种植内皮细胞和平滑肌细胞，扫描电镜检测结果表明，两种细胞在支架上生长良好，且局部已经融合成片。 相容性     

丹参提取物对氧自由基引起的化学发光的抑制作用

观察了经调理的酵母多糖（ＯＺ）、Ｎ－ｆｏｒｍｙｌｍｅｔｈｉｏｎｙｌ－Ｌｅｕｃｙｌ－ｐｈｅｎｙｌａｌａｎｉｎｅ（ｆＭＬＰ）Ｃａｌｃｉｕｍ ｉｎｏｐｈｏｒｅ（Ａ２３１８７），等几种白细胞激动剂引起的大鼠腹腔中性粒细胞（ＰＭＮｓ）的化学发光和次黄嘌呤－黄嘌呤氧化酶系统（ＨＯ－ＸＯ）产生的化学发光。观察到了具有抗炎作用的中药单体７６４－３对ＰＭＮ吞噬ＯＺ引起的化学发光及ＨＯ－ＸＯ系统产生的化学发光具有明显     

of the carcinogenic mechanism for polycyclic aromatic hydrocarbons - extended bay region theory and its quantitative model

With the help of results on the metabolism and the carcinogenicactivities of polycyclic aromatic hydrocarbons (PAH), the comprehensivemetabolic process in vivo is discussed. It is thought that thecarcinogenic activity exhibited by a PAH is determined by thecompetition between the carcinogenesis and detoxification inwhich it participates. It is suggested that the essential agentof carcinogenesis should be, as a rule, the highest delocalizationenergy (ß unit) of the carbonium ion at the aromaticangular ring (A region), which is obtained by the perturbationalmolecular orbit (PMO) method. Since there are no essential distinctionsin the molecular geometry and delocalization energy states betweentwo carbonium ions of the aromatic angular ring and of the bayregion, the A region can be looked upon as the extended bayregion. On the basis of discussion of the overall metabolism,evaluation of the detoxification efficacy of each kind of thecompeting carcinogenic factors, including the biological factorB and three structural factors of the PAH molecule: K, A andL, was made. After making necessary approximation, K=0.228,A=0.5, L=1.22 and B=0.7 are obtained. It can be seen from thesevalues that the L region plays the most important role in detoxificationprocesses, and the K region plays the least important role.The effect of biological factor B is approximately the sum ofthe K region and the A region. This paper suggests the conceptof a carcinogenic constant. For the PAHs with the same numberof aromatic rings (N), C is a constant. The curve of functionC=f(N), including the extensional line, is an isosceles triangle.The author suggests that it should be called the ‘PyramidRule’. The final form of the quantitative equation is. The values for 50 PAHs which had been tested by animal experiments were calculated. Of these, 92% of thePAHs are in agreement with experiments on carcinogenic activities.     

2011—2020年郑州市二七区居民恶性肿瘤死亡趋势及减寿分析

目的了解郑州市二七区居民2011—2020年恶性肿瘤死亡流行趋势及对居民寿命的影响情况,为制定恶性肿瘤防治对策提供科学依据。方法对2011—2020年郑州市二七区居民恶性肿瘤死亡资料进行分析,计算恶性肿瘤死亡率、潜在减寿年数(potential years of life lost,PYLL)、标化潜在减寿年数(standardized potential years of life lost,SPYLL)、标化潜在减寿率(standardized potential years of life lost rate,SPYLLR)和人均减寿年数(average years of life lost,AYLL)等指标,采用年度变化百分比(annual percent change,APC)分析率的时间变化趋势。结果2011—2020年郑州市二七区居民恶性肿瘤年均死亡率为114.68/10万,标化死亡率为103.52/10万,男性年均死亡率(146.09/10万)高于女性(84.56/10万)。恶性肿瘤前5位死因依次为肺癌、肝癌、胃癌、结直肠癌和食管癌,共占恶性肿瘤死亡构成的65.36%。2011—2020年该区居民恶性肿瘤死亡率呈上升趋势(APC=3.70%,P<0.001)。0~44岁年龄组恶性肿瘤死亡率处于较低水平,45岁后随年龄增长逐渐升高,75岁以后迅速升高。恶性肿瘤总PYLL为39067人年,SPYLLR为6.73‰,AYLL为12.59年。结论肺癌、肝癌、胃癌、结直肠癌和食管癌是二七区恶性肿瘤预防控制的重点工作,同时宫颈癌和乳腺癌对女性健康的影响不可忽视,应针对主要恶性肿瘤和重点人群开展综合防控措施,以降低恶性肿瘤的死亡率。     

以重点监控药品管理促进合理用药水平提升

通过开展以“合理用药”为核心的重点监控药品管理,促进合理用药水平提升。采取事后处方点评及处方前置审核,建立和完善重点监控药品管理方案,对不合理用药进行拦截、宣教、绩效处罚、限量采购、约谈等,实现了重点监控药品规范化管理。实践后,不合理医嘱减少,处方点评合格率提升,辅助用药种类减少。认为建立重点监控药品管理的相关制度及流程,对提升合理用药水平有一定促进作用。