云南边境地区登革1型病毒非结构蛋白编码区序列测定及进化分析

登革病毒有4个血清型,可引起登革热和登革出血热/登革休克综合征.登革病毒包括5'和3'非编码区(UTR)及一个单一的开放阅读框(ORF),该ORF编码一个聚蛋白前体,经蛋白酶裂解加工成3种结构蛋白(C、PrM和E)和7种非结构蛋白(NS1、NS2A、NS2B、NS3、NS4A、NS4B和NS5)[1].     

云南边境地区登革1型病毒非结构蛋白编码区序列测定及进化分析

登革病毒有4个血清型,可引起登革热和登革出血热/登革休克综合征.登革病毒包括5'和3'非编码区(UTR)及一个单一的开放阅读框(ORF),该ORF编码一个聚蛋白前体,经蛋白酶裂解加工成3种结构蛋白(C、PrM和E)和7种非结构蛋白(NS1、NS2A、NS2B、NS3、NS4A、NS4B和NS5)[1].     

云南边境地区登革1型病毒非结构蛋白编码区序列测定及进化分析

登革病毒有4个血清型,可引起登革热和登革出血热/登革休克综合征.登革病毒包括5'和3'非编码区(UTR)及一个单一的开放阅读框(ORF),该ORF编码一个聚蛋白前体,经蛋白酶裂解加工成3种结构蛋白(C、PrM和E)和7种非结构蛋白(NS1、NS2A、NS2B、NS3、NS4A、NS4B和NS5)[1].     

《中国医师进修杂志》2007年第8期外科版继续医学教育试题

(从下列多选题中选出一个正确答案)1.下列哪一项为肾癌中最常见的类型:A.移行细胞癌B.肾细胞癌C.肾母细胞瘤D.囊腺癌2.下列哪一项为能降解Ⅳ型胶原三螺旋部位的酶:A.明胶酶B.蛋白酶C.蛋白酶抑制剂D.解旋酶3.下列哪一项为肿瘤细胞侵袭转移的关键:A.蛋白酶对细胞外基质的降解B.蛋白酶的表达C.蛋白酶抑制剂的表达D.明胶酶的表达4.下列哪一项不是蛋白激酶C不同功能的主要表现方面:A.细胞增殖、分化、凋亡B.肿瘤发生C.血管发生D.肿瘤抑制5.下列哪一项在泌尿系肿瘤中的发病率最高:A.肾细胞癌B.膀胱癌C.前列腺癌D.肾囊肿《中国医师进修杂…     

丙型肝炎病毒MHC-Ⅱ类抗原表位预测

目的预测各型丙型肝炎病毒(HCV)的MHC-Ⅱ类抗原表位,为HCV的疫苗研发提供理论依据。方法从NCBI数据库中检索出10条包含6种基因型的HCV完整氨基酸序列,使用在线MHC-Ⅱ类抗原表位分析工具NetMHCⅡpan-2.1 Server,从MHC-Ⅱ类抗原表位在6种HCV型别之间的保守性及与MHC-Ⅱ类分子亲和力两方面评价HCV携带的潜在MHC-Ⅱ类抗原表位。结果位于NS3和NS5B蛋白的3段表位核心序列具有较好的保守性,其中尤以NS3蛋白携带的表位核心序列保守性最好;高亲和力的MHC-Ⅱ类抗原表位主要位于E2、NS5A、NS4A和NS5B蛋白,其中E2和NS5A蛋白携带的高亲和力抗原表位较为丰富。结论 NS5B蛋白所携带的MHC-Ⅱ类抗原表位兼顾了各个HCV基因型之间的保守性及与MHC-Ⅱ类分子的高亲和力,具有较好的疫苗应用前景;NS3、E2、NS5A和NS4A蛋白有可能成为HCV多表位肽疫苗的备选组分。     

原发性高血压伴发颈动脉粥样硬化患者基质金属蛋白酶不同基因型血脂分析

目的 分析携带不同基质金属蛋白酶（MMP）基因型的原发性高血压（EH）伴发颈动脉粥样硬化（CAS）患者血脂情况.方法 纳入维、汉两个民族488例EH患者,采用聚合酶链反应-限制性片段长度多态性技术测定MMP-2-735 C/T和MMP-3-1171 5A/6A基因多态性,依据是否存在CAS分为CAS组（293例,其中汉族171例,维族122例）和颈动脉正常组（NS组,195例,其中汉族105例,维族90例）,对不同基因型携带者进行血脂分析.结果 对于MMP-2基因,汉族CAS组CT＋TT基因型低密度脂蛋白胆固醇（LDL-C）高于CC基因型（P＜0.05）,高密度脂蛋白胆固醇低于CC基因型（P＜0.05）;维族MMp-2 CT＋ TT基因型三酰甘油均高于CC基因型（P＜0.05）.对于MMP-3基因,汉族NS组6A/6A基因型总胆固醇、LDL-C高于5A/5A＋5A/6A基因型（P＜0.05）.结论 MMP不同基因型患者血脂水平存在差异,与CAS发生机制可能相关.     

上海市浦东新区注射吸毒者HCV的进化分析与正选择位点研究

目的 了解上海市浦东新区注射吸毒者分离的HCV的基因分型,分析其病毒种群的增长演化过程与选择压力。方法 采集美沙酮门诊注射吸毒者血清200份,扩增HCV NS5B 377-nt核苷酸片段。结合同期当地的志愿献血者、MSM、法定报告丙型病毒性肝炎（丙肝）病例的分离序列,使用BEAST软件包分析主要基因型的进化速率和种群演变过程。采用Datamonkey在线软件包对注射吸毒者分离序列分析选择压力,并与直接抗病毒药物（Direct-acting antiviral,DAA）结合位点进行比对。结果 美沙酮门诊注射吸毒者HCV RNA阳性检出率19.5%（39/200）,其中基因分型分为3a亚型（14份）、3b亚型（13份）、1b亚型（7份）、6a亚型（4份）和6n亚型（1份）。注射吸毒者分离序列与其他人群序列同源性均较高。进化分析表明,HCV 1b亚型的理论感染人数于20世纪90年代开始增加且增速较快,3a与3b亚型则从90年代中期呈逐渐上升趋势。选择压力分析显示,注射吸毒者NS5B 377-nt片段确认有2个正选择位点,在7个DAA结合位点的突变率为2.2%。结论 HCV 3a和3b亚型是上海浦东注射吸毒者丙肝感染的主导基因型。而1b亚型在各人群中普遍分布,进化速率较快,其导致的感染数将持续上升。注射吸毒者HCV NS5B基因片段的DAA结合位点突变率低,预计药物结合效果较好。     

丙型肝炎病毒与宿主蛋白相互作用研究进展

宿主蛋白在丙型肝炎病毒(HCV)的复制、翻译以及致肝脏病变等过程中发挥着重要作用,本文就宿主蛋白与HCV 5′非编码区、3′编码区以及结构蛋白(核心蛋白C、包膜蛋白E1、E2)、非结构蛋白(NS3、NS4、NS5A和NS5B)之间的相互作用进行综述。     

HCV准种复杂性与干扰素疗效关系的初步探讨

目的　探讨丙型肝炎病毒 (HCV) 1b型患者HVR1 ,NS5A区准种复杂性与干扰素疗效的关系。方法　应用单链构象多态性聚合酶链反应 (SSCP)法检测慢性丙型肝炎患者干扰素治疗前后HCV准种的动态变化。结果　治疗前HCVHVR1准种的SSCP条带数 (复杂性 )≤ 3者在经干扰素治疗后HCVRNA阴转率为 71 .4 3% ,>3者HCVRNA阴转率为 1 5 .38% ,两者相比 ,差异有显著性 (P <0 .0 5 ) ;治疗有效组SSCP条带数为 2 .4 3± 0 .98( x±s) ,无效组为 4 .4 6± 0 .88,两者相比 ,差异亦具显著性 (P <0 .0 1 )。而NS5A区SSCP条带数则无差异。结论　HCV1b型慢性丙型肝炎患者HVR1区准种的复杂性与干扰素疗效有关 ;而NS5A区准种的复杂性与干扰素疗效无关。     

丙型肝炎病毒与宿主蛋白相互作用研究进展

宿主蛋白在丙型肝炎病毒（HCV）的复制，翻译以及致肝脏病变等过程中发挥着重要作用。本文就宿主蛋白与HCV5′非编码区，3′非编码区以及结构蛋白（核心蛋白C，包膜蛋白E1，E2），非结构蛋白（NS3，NS4，NS5A和NS5B）之间的相互作用进行综述。     

Tyler’s Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies.

Many believe that excessive intake of refined carbohydrates (CHO) plays a major role in the development of obesity/overweight, type 2 diabetes mellitus and insulin resistance, a collection of events commonly referred to as “diabesity,” and have sought natural means to overcome these linked perturbations. As a first approach, planned diets with low portions of refined CHO have become popular. However, these diets do not satisfy everyone; and many are concerned over replacing CHO with more fats. As a second option, addition of soluble fiber to the diet can slow absorption of refined CHO, i.e., lower the glycemic index of foods and overcome or at least ameliorate many of the adverse reactions resulting from increased refined CHO ingestion. Unfortunately, the general public does not favor diets high in fiber content, and various fibers can lead to gastrointestinal problems such as gas and diarrhea. A third choice to favorably influence CHO absorption is to use natural dietary supplements that block or slow CHO absorption in the gastrointestinal tract via inhibiting enzymes necessary for CHO absorption –amylase and alpha-glucosidases. Although a number of natural supplements with anti-amylase activity have been recognized, the most studied and favored one is white kidney bean extract. Animal and human studies clearly show that this agent works in vivo and has clinical utility. This paper reviews many aspects of diabesity and the use of “carb blockers” to prevent and ameliorate the situation. In many respects, carb blockers mimic the beneficial effects of fibers.     

Obesity-related heart failure with preserved ejection fraction: new treatment strategies

Objectives: Obesity has risen in the US and worldwide, and has become a major risk factor for type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease, and mostly HF with preserved ejection fraction (HFpEF). Also, the prevalence of HF is quite high in the US accounting for 6.6 million adults at present and is projected to reach 8.5 million by the year 2030 and is equally divided between HFpEF and heart failure reduced ejection fraction (HFrEF). Patients with HFpEF are resistant to treatment with drugs usually used for the treatment of HFrEF, but the reasons for this resistance are not clearly known.

Methods: In order to get a better perspective on the current status of the underlying pathophysiology and treatment of patients with HFpEF, a Medline search of the English language literature was conducted between 2015 and 2018 using the terms obesity, HFpEF, diabetes, treatment, SGLT2 inhibitors, and neprilysin inhibitors and 24 pertinent papers were selected.

Results: The review of these papers revealed that patients with HFpEF have expanded plasma volume, restricted left ventricular distension with increased end-diastolic volume and depressed natriuretic peptide levels. In this respect, drugs that cause increased diuresis and natriuresis should a reasonable choice to treat these patients. The recently FDA approved sodium-glucose cotransporter-2 (SGLT2) inhibitors for the treatment of T2DM, are a good choice, for the treatment of HFpEF, since they cause osmotic diuresis from glucose excretion and increase salt and water excretion and decrease plasma volume. In addition, they produce loss of calories leading to weight and blood pressure reduction and have shown to prevent the new onset HFpEF and decrease hospitalizations and death from this disease.

Conclusion: The results of this analysis has shown that HFpEF has different pathophysiology from HFrEF and is difficult to treat. Drugs that block renal tubular glucose reabsorption and cause osmotic diuresis and natriuresis could be a good choice to treat patients with HFpEF alone or in combination with diuretics and other drugs.     

When To Hospitalize The Emphysema Patient

With emphysema now ranking second among causes of disability in men past 40, Dr. Haas believes that careful reappraisal of the criteria for hospitalization in this disease is indicated. Critical to this reappraisal, he maintains, is recognition that many patients now “written oil'” as hopeless cripples may be returned to “the dignity of economic and social independence.”     

Stenotrophomonas maltophilia susceptibility to ceftazidime-avibactam combination versus ceftazidime alone

ObjectiveTo compare the minimum inhibitory concentrations (MIC) of the ceftazidime-avibactam (CZA) combination versus ceftazidime alone (TZ) for Stenotrophomonas maltophilia.Patients and methodsMIC comparison was performed by E-tests. We assumed that CZA was more effective in vitro than TZ alone when CZA led to a category change from “Resistant” with TZ alone to “Susceptible” or “Intermediate” with CZA, or if the MIC of CZA was at least 4-fold lower than the MIC of TZ for TZ-susceptible isolates.ResultsFor the 54 clinical isolates included in the study, CZA showed better results in terms of the proportion of susceptible isolates (66.7% vs. 38.9%, P < 0.01), MIC₅₀ (2 μg/mL vs. 12 μg/mL, P < 0.05), and MIC distribution. According to our definition, CZA was also more effective in vitro than TZ alone for 50% of the isolates.ConclusionUsing CZA for empirical treatments in severe or polymicrobial infections with S. maltophilia seems appropriate.     

波利特、达克普隆和Nexium对幽门螺杆菌的体外抑菌效果比较

目的：观察、比较质子泵抑制剂(PPI)波利特(雷贝拉唑肠溶衣片)、达克普隆(兰索拉唑胶囊)和Nexium对幽门螺杆菌(Hp)的抑制作用，初步解释近期临床流行病学资料所显示的不同PPI用于Hp根除治疗所表现的明显效果差异现象。方法：使用Hp国际标准株NCTC11637、NCTC11639和国内分离菌株CAPMN62，应用平板掺入法测定三种PPI对Hp的体外抑菌作用。结果：波利特在体外对Hp具有明显的抑制作用(MIC99为2．25mg／L)，其次为达克普隆(MIC99为42.5mg／L)，而Nexium抑菌作用不明显(MIC99为360mg／L)。结论：不同PPI对Hp的直接抑菌作用存在明显差异，其作用除本身化学结构的差异因素外，制剂中的其他复合成分的影响也不容忽视；亟待对体外抑菌效果与用于Hp感染治疗效果的相关性进行分析，以便更好地指导临床用药和相关幽门螺杆菌病的防治。     

6分钟步行试验评价老年高血压心力衰竭疗效的探讨

目的探讨6分钟步行试验(6MWT)评价老年高血压心力衰竭疗效的价值。方法采用缬沙坦治疗老年高血压心力衰竭患者20例,比较治疗前后6MWT的变化,并以纽约心脏病学会(NYHA)心功能分级作为对比。结果治疗后患者的大多数患者的收缩压、舒张压及心率均较治疗前明显下降(p<0.05);治疗后NYHA分级构成较治疗前有统计学差异(Z=-3.416,p=0.001);治疗前患者6MWT为(198.67±87.51)米,治疗后上升为(451.20±73.77)米,显著高于治疗前(t=2.664,p=0.011);相关性分析显示6MWT与NYHA分级呈显著负相关性(r=-0.658,p=0.016)。结论 6MWT评价心衰疗效具有客观化及量化的优势,适合于评价老年高血压心力衰竭的疗效。     

国产与进口帕罗西汀治疗抑郁症的疗效及安全性

目的评价国产与进口帕罗西汀治疗抑郁症的临床疗效及安全性。方法随机选择门诊、住院抑郁症病人138例，分为试验组69例，男性28例，女性41例，年龄（42.50±12.43）岁（21-66岁），病程0.04-3.5a。对照组69例，男性30例，女性39例，病程0.04-4a。年龄（42.25±11.38）岁（17-63岁）。2组分别口服国产及进口帕罗西汀20-40mg／d，治疗12周。疗效评定采用汉米斯顿抑郁量表（HAMD）和临床总体印象量表（CGI），安全性评价应用不良反应量表（TESS）。结果试验组痊愈率为70％，有效率为86％，对照组痊愈率为74％，有效率为90％，2组间疗效差异无统计学意义（P〉0.05）。试验组和对照组不良反应发生率分别为32％和28％，2组的不良反应轻微，安全性好，常见的有恶心、头痛、出汗、失眠，嗜睡。结论国产帕罗西汀的抗抑郁作用疗效肯定.使用安wg ,与进口帕罗西汀疗效相似。     

MET抑制剂在晚期肝癌中的应用进展

目前晚期肝细胞癌的标准药物治疗是索拉菲尼,但其临床效果是有限的,而且副作用较大。但除索拉菲尼以外,在所有完成的Ⅲ期临床对照研究中,没有药物在作为一线或二线用药时能明显提高生存率。最近一项Ⅱ期随机对照研究结果的亚组分析显示,一种选择性MET抑制剂ARQ197,在全身治疗失败或不耐受全身治疗的伴有MET扩增的晚期肝细胞癌患者中应用,能明显提高总生存率。在本文中,我们对所有目前正在进行及已经完成临床试验的MET抑制剂做一综述。旨在进一步了解MET抑制剂在肝癌中的应用情况,为晚期肝癌的药物治疗提供新的策略。     

Nutrition and cancer: state of the art relationship of several nutrients to the development of cancer.

Nutrition and cancer interact in a number of important ways and nutritional factors are increasingly recognized as relevant to both the prevention and treatment of cancer. The role of several nutrients in cancer development is considered briefly here. Deficiency of riboflavin (Vitamin B2) prolongs the survival of tumor-bearing animals, but may accelerate carcinogenesis caused by certain agents, as flavin cofactors are involved in drug and carcinogen metabolism. Deficiency of Vitamin A may enhance the development of tumors of epithelial origin, particularly lung. Evidence is accumulating that Vitamin A and/or its precursors, the B-carotenes, may possibly have an effect in chemoprevention of certain of these epithelial cancers both in animals and in man. The consumption of dietary fat among various nations is correlated closely with increased development of cancers of the breast, colon, and prostate, and possibly of other organs. Studies of migrant populations from Japan to the United States show changes in prevalence of stomach and colon cancer in the direction of the native United States population. Sources of nitrites are of concern because of their potential conversion to carcinogenic nitrosamines. Limitation of the delivery of nitrites may be difficult to accomplish so investigators are exploring the blockade of conversion of nitrites to nitrosamines. Nutrition should not be viewed as the sole means of cancer prevention and treatment but rather as a vital component of any treatment plan.     

芳香化酶抑制剂与他莫昔芬治疗Luminal型绝经后乳腺癌疗效的系统评价

目的 评价芳香化酶抑制剂与他莫昔芬治疗Luminal型绝经后乳腺癌的疗效.方法 通过检索1993年1月1日至2013年1月1日PubMED、Science Direct、EBSCO Host、EMbase、The Cochrane Library、中国学术期刊全文数据库、万方数据库、维普中文科技期刊全文数据库,对纳入研究的方法学进行评价.对纳入文献的质量进行严格评价和资料提取,使用Review Manager 5.0软件对符合质量标准的随机临床试验（RCT）行系统评价.结果 12篇RCT共纳入2634例患者,其中治疗组1354例（使用芳香化酶抑制剂）,对照组1280例（使用他莫昔芬）,系统评价结果显示：相比对照组,治疗组可显著提升患者1年的无瘤生存率（RR值为1.10,95％ CI为1.01～1.19）、可显著提升患者3年的无瘤生存率（RR值为1.09,95％ CI为1.05～ 1.13）、可显著提升患者1年的总体有效率（RR值为1.21,95％ CI为1.12～1.30）、可显著降低患者3年的心血管疾患发生率（RR值为0.47,95％ CI为0.27～0.83）,患者3年的骨关节疾患发生率比较差异无统计学意义（RR值为0.99,95％ CI为0.61～ 1.61）.结论 相比于他莫昔芬,芳香化酶抑制剂治疗Luminal型绝经后乳腺癌的疗效显著,值得推广.