甲型H1N1流感肺炎患儿潮气呼吸肺功能的改变

目的探讨甲型H1N1流感肺炎患儿的肺功能变化及其在临床诊断和治疗评估中的意义。方法测定53例甲型H1N1流感肺炎患儿(A组)潮气呼吸肺功能,并与87例同年龄段健康儿童(B组)对照。结果 A组潮气流速-容量环变窄,呼气曲线升枝陡峭,高峰提前,降枝呈波谷样凹陷。与B组比较,A组通气功能指标反映呼气功能障碍,尤其1个月~3岁年龄组患儿(P<0.05)。结论甲型H1N1流感肺炎患儿其急性期肺功能改变主要表现为气道阻塞性通气功能障碍;潮气呼吸肺功能测定可为甲型H1N1流感肺炎患儿评判病情程度及预后评估提供客观依据。     

黄金方防治甲型H_1N_1流感病毒感染小鼠肺炎的实验研究

目的:观察黄金方对甲型H1N1流感病毒FM1株和PR8株感染小鼠肺炎的防治作用。方法:采用滴鼻感染正常小鼠和免疫低下小鼠建立流感病毒感染肺炎模型,分别采用治疗和预防性给药,观察对小鼠肺指数、死亡率、生存时间的影响。结果:治疗给药试验中黄金方大剂量组(6 g.kg-1)、中剂量组(3g.kg-1)可明显降低正常小鼠感染流感病毒FM1株或PR8株后肺指数(与模型组比较,P<0.05),3个剂量组均可明显减少正常小鼠感染流感病毒FM1株或PR8株后死亡率并延长生存时间(与模型组比较,P<0.01);预防给药试验中黄金方大剂量组(6 g.kg-1)、中剂量组(3 g.kg-1)可明显降低免疫低下小鼠感染流感病毒FM1株或PR8株后肺指数(与模型组比较,P<0.05),3个剂量组均可减少正常小鼠感染流感病毒FM1株后死亡率并明显延长生存时间(与模型组比较,P<0.01)。结论:黄金方在体内对H1N1流感病毒感染有较好的治疗和预防作用。     

96例儿童甲型H1N1流感患者的临床分析

目的探讨儿童甲型H1N1流感的临床特征及疗效。方法回顾性分析我院2014年1月~2016年11月收治的儿童甲型H1N1流感患者96例,对患儿年龄、实验室检查、临床症状及病程转归进行重点分析。结果儿童甲型H1N1流感患者以婴幼儿多见(85.4%),临床表现以发热、咳嗽及流涕等呼吸道表现为主,外周血白细胞总数正常或减低,甲型H1N1流感病毒检测阳性;96例患儿均治愈出院,平均住院时间为(7.0±1.2)d;早期口服奥司他韦治疗组较晚期口服治疗组住院时间缩短,两组比较差异有统计学意义(P<0.05)。结论在甲型流感流行季节,对于外周血白细胞不高的发热患者,早期口服奥司他韦治疗可以减轻临床症状,缩短病程,避免呼吸衰竭等严重并发症的发生。     

儿童重症甲型H1N1流感的诊治体会

甲型H1N1流感是由变异后的新型甲型H1N1流感病毒感染所致的急性传染病,人群普遍易感,临床表现与季节性流感相似,病情轻重不一,多数为发热、轻度上呼吸道感染表现,也可发生致死病例.自2009年9月,我院开始收治甲型H1N1流感重症病例,本文将其中8例重症病例的临床治疗情况予以总结,报告如下.     

重症禽流感H7N9及重症甲型流感H1N1临床特点分析

目的:探讨重症禽流感H7N9与重症甲型流感H1N1的临床特点。方法:收集漳州市医院收治的7例重症禽流感H7N9(重症H7N9)与15例重症甲型流感H1N1(重症H1N1)病例,回顾性分析患者一般情况、基础病、临床症状、检验结果、影像学检查结果、治疗与预后等资料。结果:22例患者中,≥2种基础病的患者死亡率(72.73%)高于≤1种基础病患者死亡率(18.18%)(P<0.05);重症H7N9患者外周血淋巴细胞下降率(100%)高于重症H1N1患者(26.67%)(P<0.05);重症H7N9患者肺实变、胸腔积液与心包积液发生率分别为71.43%、85.71%、57.14%,高于重症H1N1患者的13.33%、13.33%、0(P<0.05);重症H7N9患者需要机械通气时间为(26.86±13.06)d,高于重症H1N1患者的(7.20±6.46)d(t=4.79,P<0.05);两组患者在出院后的随访中,重症H7N9患者在肺部影像上残留更多的纤维条索灶,吸收更慢。结论:与重症甲型流感H1N1相比,重症禽流感H7N9病情更重,预后更差。     

糖皮质激素雾化吸入治疗重症甲型H1N1流感患儿疗效及其对单核细胞、嗜碱性粒细胞、嗜酸性粒细胞的影响

目的:探究重症甲型H1N1流感患儿应用糖皮质激素雾化吸入治疗的疗效,并分析患儿单核细胞(MONO)、嗜碱性粒细胞(嗜碱性粒细胞,BASO)、嗜酸性粒细胞(EOS)的状况.方法:选取298例2019年2月—2021年2月期间在本院接受治疗的重症甲型H1N1流感患儿,随机抽签的方法将患儿均分到对照组(常规治疗)、研究组(糖皮质激素),每组149例患儿.比较两组治疗前后身体状况变化、治疗研究炎症细胞状况.结果:治疗前后相比,两组体温(T)、心率(HR)以及第1秒用力呼气容积(FEV1)均明显改善,但研究组T、HR更低,FEV1更大(t=12.82、1.85、5.59,P<0.05).研究组MONO、BASO以及EOS百分比均比对照组更低,且研究组EOS计数更小(t=6.96、10.06、13.54、8.00,P<0.05).结论:采取雾化吸入糖皮质激素的方式给予重症甲型H1N1流感患儿治疗,可以明显改善患儿身体状况,降低炎症细胞水平,治疗效果良好.     

大剂量静脉丙种球蛋白治疗重症甲型H1N1流感患儿的价值探讨

目的 探讨大剂量静脉丙种球蛋白治疗重症甲型H1N1流感患儿的临床价值.方法 回顾性总结本院2009年6-12月确诊的50例重症甲型H1N1流感病例,并依据是否使用大剂量静脉丙种球蛋白分为治疗组及对照组,总结两组患儿的临床资料,采用卡方检验统计两组患儿的临床改善情况,并结合文献进行分析.结果 当加用静脉丙种球蛋白静脉滴注后,治疗组经治疗后,体温下降10例,咳嗽11例,流涕8例,气促8例,肺部闻及啰音7例,喘鸣音8例,较治疗前及对照组有明显好转,各项指标比较差异有显著性（P〈0.05）.结论 大剂量静脉丙种球蛋白对重症甲型H1N1流感患儿临床症状改善方面具有明显疗效.     

磷酸奥司他韦与利巴韦林联用对甲型H1N1流感患儿的疗效及其对流感病毒转阴的影响

目的:评价磷酸奥司他韦与利巴韦林联用对甲型H1N1流感患儿的疗效与安全性及其对流感病毒转阴的影响。方法:选取2017年11月—2018年10月期间收治的甲型H1N1流感患儿100例资料,按治疗方法的不同将其分为治疗组和对照组,每组50例;对照组患儿给予利巴韦林治疗,治疗组患儿在对照组基础上加用磷酸奥司他韦治疗,比较两组患儿治疗后的总有效率和用药期间不良反应发生率差异,以及治疗3、5 d体温复常率与病毒转阴率的差异。结果:治疗组患者治疗后的总有效率(94.00%)高于对照组(78.00%()P<0.05),治疗3、5 d体温恢复率和病毒转阴率均高于对照组(P<0.05),不良反应发生率(4.00%)明显低于对照组(16.00%()P<0.05)。结论:采用磷酸奥司他韦与利巴韦林联用治疗甲型H1N1流感患儿的疗效较为明显,有效提高了甲型H1N1流感患儿的流感病毒转阴率,且安全性较高。     

32例甲型H1N1流感患者的影像学特点

目的总结分析甲型H1N1流感的胸部X线片与CT影像表现特点。方法对32例甲型H1N1流感患者的影像学特点及临床资料进行回顾性分析。结果 32例患者中有9例患者胸片或CT未见明显病变,其余23例出现斑片状阴影17例,两肺间质改变、肺纹理增粗4例,胸腔积液1例,合并存在磨玻璃样阴影5例。结论甲型H1N1流感患者的肺部影像学表现有一定特征性,重症甲型H1N1流感肺炎主要的胸部影像学表现为两肺多发斑片状实变影及磨玻璃样阴影,影像学检查对甲型H1N1流感特别是重型甲流H1N1流感诊断有重要的价值。     

甲型H1N1流感重症患儿4例临床救治经验总结分析

目的探讨甲型H1N1流感重症患儿的临床特点及救治体会。方法回顾性分析2009年11月25至2010年1月5日我院儿科病房诊治的4例甲型H1N1流感重症患儿的临床表现、实验室检查和影像学资料。用咽拭子取呼吸道标本,冰壶保存立即送市疾病预防控制中心病毒室,以实时逆转录核酸扩增聚合酶链反应法(Real-timeRT-PCR)检测甲型H1N1流感病毒核酸。结果 4例患儿发病早期均表现为流感样症状,无特异性表现。4例均有发热,轻微咳嗽,肺部炎症体征不明显。2例有咽痛。所有病例均无呕吐腹泻症状。从起病到临床症状加重的时间为2～4d,表现为呼吸困难。4例均有Ⅰ型呼吸衰竭,采用CPAP面罩无创通气。血常规起病时3例白细胞计数减少,仅1例明显增高。3例起病3～4d,胸片示一侧肺部片状阴影,2d后片状阴影大面积融合;1例起病第2天,胸片和肺部CT示左肺上叶肺不张、左中下肺炎、左侧胸腔积液。所有患儿均治愈出院。结论肥胖是容易发展成重症病例的重要的危险因素之一。5～9岁的患儿容易成为重症病例。提高认识,早期发现、早期诊治是降低甲型H1N1流感重症患儿病死率的关键。     

Preferential induction of CYP1A1 and CYP1B1 in CCSP-positive cells.

Both benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are potent ligands of aryl hydrocarbon receptors (AhR). Although animal studies indicate that both compounds induce pathological changes in the peripheral lung, the specific cell type involved remains unclear. Clara cells, expressing Clara cell specific protein (CCSP) and abundant in cytochrome P450, are nonciliated bronchiolar epithelial cells in the peripheral lung. Here we explore the hypothesis that CCSP-positive Clara cells are highly responsive to AhR ligands and are the primary cell type involved in BaP- and TCDD-induced toxicities. The responsiveness to AhR ligands was evaluated by measuring the respective mRNA and protein levels of cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) using real-time RT-PCR and immunocytochemistry assays. Two in vitro models were used: primary cultures of human small airway epithelial (SAE) cells and rat lung slice cultures. In the presence of calcium, human SAE cells differentiated into CCSP-positive cells. BaP- and TCDD-induced mRNA and protein levels of CYP1A1 and CYP1B1 levels were significantly elevated in CCSP-positive cell cultures. Similarly, AhR mRNA and protein levels were increased in CCSP-positive cell cultures, as determined by real-time RT-PCR and Western blot analysis. When rat lung slice cultures were treated with BaP or TCDD for 24 h, CYP1A1 and CYP1B1 proteins were strongly induced in Clara cells. These results indicate that, in the peripheral lung of both rats and humans, CCSP-positive cells (Clara cells) may be more sensitive to AhR ligands than other cell types.     

松江区开展1+1+1签约服务的SWOT分析

在上海市社区卫生服务综合改革中出台的《关于本市全面推广家庭医生制度的指导意见》中要求家庭医生与居民之间通过签约服务关系的建立,落实基本卫生服务项目与综合、全程的健康管理服务,提高居民健康水平。本文运用SWOT分析法,分析松江区开展1+1+1签约服务的主要优势、劣势以及面临的机遇和挑战,需要发挥政府主导作用,加强部门协调沟通,敢于突破瓶颈,才能够把1+1+1签约服务落到实处。     

Suppression of CYP1A1 expression by naringenin in murine Hepa-1c1c7 cells

Naringenin, dietary flavonoid, is antioxidant constituents of many citrus fruits. In the present study, we investigated the effect of naringenin on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible CYP1A1 gene expression in mouse hepatoma Hepa-1c1c7 cells. Naringenin alone did not affect CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity. In contrast, the TCDD-inducible EROD activities were markedly reduced upon concomitant treatment with TCDD and naringenin in a dose dependent manner. TCDD-induced CYP1A1 mRNA level was also markedly suppressed by naringenin. A transient transfection assay using dioxin-response element (DRE)-linked luciferase and electrophoretic mobility shift assay revealed that naringenin reduced transformation of the aryl hydrocarbons receptor(AhR) to a form capable of specifically binding to the DRE sequence in the promoter of the CYP1A1 gene. These results suggest the down regulation of the CYP1A1 gene expression by either naringenin in Hepa-1c1c7 cells might be antagonism of the DRE binding potential of nuclear AhR.     

CYP1A1 and CYP1B1 in blood-brain interfaces: CYP1A1-dependent bioactivation of 7,12-dimethylbenz(a)anthracene in endothelial cells.

Immunohistochemistry and autoradiography were used to identify sites of the cytochrome P450 enzymes (P450) 1A1 and 1B1 expression and activation of 7,12-dimethylbenz(a)anthracene (DMBA), in the brain of rodents pretreated with the aryl hydrocarbon receptor (AhR) agonists beta-naphthoflavone (BNF), 3,3',4,4',5-pentachlorobiphenyl or vehicle. Immunohistochemistry revealed that CYP1A1 was preferentially induced in endothelial cells (EC) in the choroid plexus, in veins in the leptomeninges, and in cerebral veins of AhR agonist-pretreated mice. No induction occurred in cerebral capillary EC. In vehicle-treated mice no localization of CYP1A1 in EC was observed. CYP1B1 was expressed in smooth muscle cells of arteries in the leptomeninges, in cerebral arteries/arterioles and to a low extent in ependymal cells of AhR agonist- and vehicle-treated mice. No CYP1B1 was detected in capillary loops of the choroid plexus or in cerebral capillaries. Following administration of [(3)H]DMBA to BNF-pretreated mice, a marked irreversible binding in EC of the choroid plexus and of veins in the leptomeninges was observed but not in cerebral capillaries. In vehicle-treated mice, there was no [(3)H]DMBA-binding at these sites. Furthermore, a high level of irreversibly bound [(3)H]DMBA occurred in EC at these sites in precision-cut mouse/rat brain slices and in excised blood-brain interfaces incubated with [(3)H]DMBA. Since [(3)H]DMBA binding sites corresponded with the sites of CYP1A1 induction, we conclude that rodents express a constitutively low but highly inducible and functional CYP1A1 in EC of some of the blood-brain interfaces. The role of CYP1A1/1B1 and environmental pollutants in the etiology of cerebrovascular disease needs further consideration.     

Immunobiological effects of AFB1 and AFB1-FB1 mixture in experimental subchronic mycotoxicoses in rats

Maize co-contamination with aflatoxin B1 (AFB1) and fumonisin B1 (FB1) is frequently found in several countries. Although the alterations on nutritional and immunologic parameters induced by these mycotoxins, when administered individually, are partially characterised, little is known about the effects induced in animals by a subchronic administration of both toxins mixtures. We have studied the nutritional and immunological alterations induced in rats fed during 90 days with a diet without mycotoxins, containing 40 ppb AFB1, and with a diet containing a mixture of 40 ppb AFB1 and 100 ppm FB1. Animals fed with the mixture of toxins obtained lower body weight than the control ones. The mitogenic response of spleen mononuclear cells (SMC) in vivo was higher in animals fed with AFB1. In in vitro studies, lower proliferations of SMC pre-exposed to AFB1 and to the mixture of toxins were detected. The SMC of animals fed with AFB1 produced lower levels of IL-2, higher of IL-4 and equal levels of IL-10. The SMC of animals fed with both toxins produced higher levels of IL-4, lower of IL-10 and equal levels of IL-2. The SMC preincubated with an AFB1-FB1 mixture produced higher concentrations of IL-4, lower of IL-10 and equal levels of IL-2. The peritoneal macrophages of animals that consumed AFB1 released less H(2)O(2), while animals fed with the mixture of toxins produced higher levels. In in vitro studies, macrophages pre-exposed to the mixture of toxins released less H(2)O(2). These results show different immunobiological effects produced by a mixture of mycotoxins in comparison to the individual action of the same toxins.     

Phenotype-genotype relationships of SULT1A1 in human liver and variations in the IC50 of the SULT1A1 inhibitor quercetin

Human sulfotransferases catalyze sulfate conjugation and 2 polymorphic genes, SULT1A1 and SULT1A2 in this family of transferases have been identified, encoding for 2 isoenzymes with very similar properties and substrate specificities. In order to test the hypothesis that variability in sulfation is due to genetic polymorphism in SULT1A1, the sulfation rate of 4-nitrophenol, a diagnostic substrate, was measured in 50 human liver samples and the genotype at the SULT1A1 locus was analyzed. The rate of 4-nitrophenol sulfation varied from 473 - 1,405 pmol/min/mg between the 5th and 95th percentiles, with a median and a mean +/- SD of 757 and 807 +/- 292 pmol/min/mg, respectively. The activities detected among the SULT1A1*2/*2 homozygotes (5 cases) were significantly lower than those of the other 2 genotypes, SULTA1*11/*1 and SULT1A1*1/*2 (5 and 40 cases, respectively), whereas there was no significant difference found between the SULT1A1*1/*1 and SULT1A1*1/*2 genotypes. To evaluate the possible influence of SULT1A2 polymorphism, genotype assays were also performed for this locus. No SULT1A2*2/*2 carrier, 26 SULT1A2*1/*1 and 24 SULT1A2*1/*2 were detected in the population sample under study. However, no correlation between the rate of 4-nitrophenol sulfation and the SULT1A2 genotype was detected. These results confirm that the variation in the rate of 4-nitrophenol sulfation in human liver is mainly due to SULT1A. Since SULT1A1*1/*2 polymorphism accounts for no more than 10% of the phenotypic variation seen in this cohort, other factors must also contribute to the variability in the rate of 4-nitrophenol sulfation in human liver. However, on the basis of the data obtained, variations in age, gender and liver function as possible causative factors can be excluded. The IC50 of quercetin, a potent inhibitor of 4-nitrophenol sulfation, was measured in the liver samples and ranged from 4.6 to 17.3 nM between the 5th and 95th percentiles. The median and the mean +/- SD were 7.7 nM and 8.3 +/- 2.5 nM, respectively. There was a weak but significant correlation between the IC50 value and age of the liver donors (r = 0.283, p = 0.046). The observed variation did not correlate with the genotypes at the SULT1A1 and SULT1A2 loci.     

安全性问题绝不能妥协——对话CDE甲流疫苗临床技术审评人员杨焕

Q.《中国处方药》：CDE在甲流疫苗审评时对临床急需和安全性的利弊权衡原则是如何考量的？ A杨焕：CDE审评任何药品都要遵循获益最大化和风险最小化原则,以获得良好的获益风险比。对于公共卫生紧急事件的药品审评,在安全性问题上更不能妥协。WHO发布的各类文件和建议中,也反复和重点地强调各国应高度关注新疫苗的安全性问题。我们在审评要点中也提醒各企业的临床研究必须高度重视疫苗的安全性。     

Enhanced expression of CYP1B1 in Escherichia coli

Conditions for the optimal expression of the human CYP1B1 hemoprotein in Escherichia coli have been investigated. CYP1B1 cDNA was prepared from a retinal cDNA template and used to generate cDNA fragments with modified 5'-sequences reported to allow enhanced expression in E. coli DH5alpha. Plasmids were constructed, using the pCWori+ expression vector and were used to examine necessity for thiamine, delta-aminolevulinic acid (ALA), and IPTG. The optimal shaking speed in an orbital incubator was 150 rpm at 30 degrees C. Higher speeds resulted in increased cell death and lower speeds resulted in lower expression of cytochrome P450. IPTG was necessary for this expression system, which makes use of the lac repressor, but levels above 0.5 mM were without additional benefit. We were able to show thiamine to be unnecessary in this expression system, although included by others expressing CYP1B1. ALA has been reported to enhance expression of several different forms of cytochrome P450. We examined the dependence of CYP1B1 expression on ALA. The expression proved to be highly dependent upon this heme precursor, with levels of CYP1B1 increasing approximately 20-fold, to 920 nmol/l in the presence of up to 2.5 mM ALA. The question of whether heme synthesis and apoprotein synthesis were coupled was then investigated. It could be shown that although heme synthesis was not limiting (CYP101 holoenzyme expression in the absence of ALA was four times higher than the ALA-supported CYP1B1 holoenzyme expression), it was necessary for optimal expression of CYP1B1. CYP1B1 protein synthesis appears to be coupled to heme precursor availability, as seen by SDS-PAGE, because in the absence of heme precursor apocytochrome P450 1B1 does not accumulate.