HBeAg阳性慢性乙型肝炎患者红细胞补体受体Ⅰ型分子基因点突变与HBV DNA含量的关系

目的研究免疫应答和耐受HBeAg阳性慢性乙型肝炎患者红细胞补体受体Ⅰ型分子(CR1)基因点突变与HBV DNA含量变化的关系,探讨其临床意义。方法选择肝脏功能正常、血清HBV DNA大于106IU/ml的114例HBeAg阳性慢性乙型肝炎患者作为免疫耐受组研究对象,选择初次发生转氨酶高于正常值2倍以上伴或不伴有肝细胞性黄疸的110例HBeAg阳性慢性乙型肝炎患者为免疫应答组研究对象。采用PCR和HindⅢ酶切技术对红细胞CR1分子基因多态性进行分类。用细胞核酸释放剂(CNR)裂解细胞,释放HBV DNA,对白细胞HBV DNA进行实时荧光PCR检测。结果免疫应答组HBeAg阳性慢性乙型肝炎患者的红细胞CR1基因点突变率明显低于免疫耐受组和正常人群(P<0.05)。在免疫应答组中,CR1基因发生点突变患者的血清和白细胞HBV DNA含量均明显高于未发生点突变者(P<0.05);在免疫耐受组中,红细胞CR1基因发生点突变和无点突变的患者其血清和白细胞HBV DNA差异均无统计学意义。结论检测HBeAg阳性慢性乙型肝炎患者红细胞CR1基因点突变对了解乙型肝炎患者清除HBV的能力、评估病情发展、判断预后具有一定的指导意义。     

医院就诊人群HBsAg与抗HBs双阳性HBV感染者的流行病学与分子病毒学特征

目的探讨乙型肝炎病毒表面抗原(HBsAg)和抗HBsAg抗体(抗HBs)同时阳性的HBV感染者的流行病学及分子病毒学特征。方法分析52 070例医院就诊人群HBV血清学标志物检测结果,以HBsAg和抗HBs双阳性患者为实验组,HBsAg阳性、抗HBs阴性患者为对照组,比较2组患者的流行病学特征。半巢氏PCR扩增2组患者HBV S蛋白编码区并测序,比较2组间在不同基因区、基因型及临床诊断时的统计学差异。结果医院检测人群HBsAg阳性率为20.40%(10 621/52 070),其中HBsAg、抗HBs双阳性率为2.48%(263/10 621)。HBsAg、抗HBs双阳性在0~9岁和≥80岁人群流行率较高,而HBsAg阳性、抗HBs阴性则相反。实验组S蛋白氨基酸突变率显著高于对照组(1.52%vs 0.81%,P0.01),差异主要存在于主要亲水区(MHR)(1.68%vs 0.57%,P0.01)。实验组中除肝癌(HCC)患者外(1.97%vs 2.21%,P0.05),乙肝携带者、慢性乙型肝炎(CHB)患者和肝硬化(LC)患者的S蛋白突变率均显著高于对照组同疾病患者(分别为1.47%vs 0.65%,1.28%vs0.84%,2.21%vs 0.44%,P均0.05)。结论 HBsAg、抗HBs双阳性以0~9岁和≥80岁HBsAg阳性人群更多见。HBV感染者血清HBsAg和抗HBs共存可能与S蛋白(主要为MHR)的突变造成的免疫逃逸有关。HBsAg、抗HBs双阳性和HBsAg阳性、抗HBs阴性患者之间S蛋白的突变率差异与患者肝脏疾病所处的阶段有关。     

未治和经治慢性乙型肝炎患者的病毒基因型分析及其核苷酸类似物耐药突变的模式特征

目的 检测分析未治和经治慢性乙型肝炎患者病毒基因型及其核酸类似物耐药突变位点的模式特征,为慢性乙型肝炎患者的抗病毒治疗方案提供依据.方法 随机选取74例未治和66例经治的慢性乙型肝炎患者,PCR反向斑点杂交法检测其血清乙型肝炎病毒的基因型及核苷酸类似物耐药基因突变位点. 结果 未治患者与经治患者的血清乙型肝炎病毒基因型均以B型为主,两组差异无统计学意义(P＞0.05),未治患者HBV C型的比例低于经治患者(P＜0.05),B+C和B+D型的比例则高于经治患者(P＜0.05).未治患者同样存在耐药基因突变:尽管其B型和C型HBV的耐药突变比例均低于经治患者(P＜0.05),但其B+D型HBV的耐药突变比例高于经治患者(P＜0.05),且以236T单基因突变为主;经治组患者HBV耐药突变单位点180M、204V和204I例数均高于未治组,而且经治组患者比未治组患者有更多的多位点耐药突变(P＜0.05). 结论 HBV B基因型是本研究主要的基因型.未治患者亦存在耐药基因耐药突变,以B+D型HBV的耐药基因突变和236T单基因突变为特征;与未治患者相比,经治患者有更多的单基因位点和多基因位点的突变.未治和经治慢性乙型肝炎患者,均应在治疗过程中定期监测NAs耐药突变发生,以便及时选择最佳治疗方案.     

厦门地区乙型肝炎患者HBV RT基因耐药突变模式及临床分析

目的研究厦门地区乙型肝炎(简称乙肝)患者HBV RT基因耐药突变模式的临床特征及与乙肝进程之间的关系。方法收集2015年11月至2018年5月厦门市中医院433例乙肝患者HBV耐药检测数据,以其中167例有完整干扰素与核苷(酸)类似物(NAs)用药信息患者作为观察对象。扩增HBV RT基因经Sanger法测序后分析患者RT基因耐药突变模式、性别、年龄、HBsAg水平、DNA水平、丙氨酸氨基转移酶(ALT)水平及天门冬氨酸氨基转移酶(AST)水平、HBV基因型、HBeAg模式、感染持续时间及与乙肝疾病进程之间的相互关系。结果厦门地区B、C型HBV感染者分别占65.59%和34.41%。C型HBV感染者有较高的HBsAg水平(P=0.026);突变型HBV感染者的年龄、HBsAg、ALT及AST水平均明显高于野生型HBV感染者,差异均有统计学意义(P0.05);不同临床进程中,肝硬化和肝癌患者的年龄、C型HBV感染比例均高于慢性HBV感染者,差异均有统计学意义(P0.05),肝癌患者的HBV DNA水平高于慢性HBV感染者,差异有统计学意义(P=0.009)。整体耐药突变率为37.18%(161/433),最常见的3个(rtM204、rtL180和rtA181)耐药突变位点突变率均为C型高于B型。共检出19种突变模式,以单位点突变的rtM204I、rtV173L和rtA181T多见,分别占4.19%、3.59%、1.80%。结论厦门地区HBV RT基因的耐药突变率与基因型有关,B、C基因型在不同耐药位点的突变率存在差异,C型感染者与突变型感染者结局较差。建议HBV感染者使用高耐药屏障的NAs治疗。     

B和C基因型HBsAg~+/HBsAb~+双阳性患者S区基因的抗原表位及相关基因的突变

目的探讨B和C基因型的乙型肝炎表面抗原(HBsAg)~+/乙型肝炎表面抗体(HBsAb)+双阳性乙型肝炎患者S区基因抗原表位之间的差异及其与HBsAg~+/HBsAb~+双阳性现象之间的关系。方法选取5例HBsAg~+/HBsAb~+双阳性样本的51个S区克隆株作为研究对象,对其S区基因克隆测序并进行统计分析。结果 5例样本中C基因型3例,B基因型2例。C基因型的30个克隆株S区氨基酸变异率显著高于B基因型的21个克隆株,且在S区的N端、C端及MHR区均存在差异。C基因型样本的变异位点主要分布在194、68、3位点,B基因型样本的变异位点则集中在40、200、129、5位点。结论不同基因型的HBsAg+/HBsAb+双阳性乙型肝炎患者在S区内的氨基酸变异存在差异,主要表现为变异位点及频次的不同,提示不同基因型的HBsAg可能具有不同的抗原表位,即只有抗原表位区内的氨基酸序列改变方可导致HBsAg抗原性改变,从而使HBsAg不能被HBsAb中和,易出现HBsAg~+/HBsAb~+双阳性现象。     

乙型肝炎病毒基因变异及临床意义

HBV基因组各编码区都可发生变异。S区突变是苗免疫失败、肝移植后HBV再感染、形成HBsAg/抗-HBs双阳性HBV感染和HBsAg阴性/抗-HBs阳性慢性乙型肝炎的重要原因。P区突变可导致HBV复制缺陷；X区突变可能不利于HBV清除，前C突变引起的异型慢性乙型肝炎更倾向于病情进展和抗病毒治疗顽固化；C基因启动子突变可能与HBeAg阴性暴发性乙型肝炎有关。     

各类慢性乙型肝炎患者HBV前S2抗原与HBV感染血清标志物及HBVDNA的关系

目的探讨乙型肝炎病毒(HBV)前S2抗原(preS2Ag)与HBV感染5项标志物(HBV-M)、HBV DNA之间的关系及对慢性乙型肝炎分类诊断的临床意义。方法对584例各类慢性乙型肝炎患者血清采用放射免疫法(R IA)检测preS2Ag,用酶联免疫吸附试验(ELISA)检测HBV-M(HBsAg、抗HBs、HBeAg、抗HBe、抗HBc),用聚合酶链反应(PCR)检测HBV DNA。结果慢性乙型肝炎轻度、中度、重度及肝炎后肝硬化患者preS2Ag的检出率分别为45.98%、67.10%、83.87%及92.86%;preS2Ag在HBeAg阳性、HBV DNA>105拷贝/mL患者中检出率明显高于HBeAg阴性、HBV DNA<105拷贝/mL患者,差异有统计学意义(P<0.001)。结论preS2Ag的检出意味着病毒有复制或有传染性;开展preS2Ag的检测有助于慢性乙型肝炎的分类、慢性乙型肝炎急性发作和预后的判断。     

慢性乙型肝炎患者HBV前S1抗原及HBV-M和HBV-DNA与肝功能的关系

乙型肝炎病毒(HBV)基因组表面抗原(HBsAg)编码区(S区)由S、前S1和前S2基因组成，分别编码S、前S1和前S2三种主要蛋白，从而共同构成HBV外壳蛋白。作为一项新的HBV血清学检测指标，乙型肝炎病毒前S1抗原(HBV preS1-Ag)的检测已被普遍应用于乙型肝炎的实验室诊断和疗效观察。我们对310份慢性乙型肝炎患者血清进行了：HBV preS1-Ag、HBV-M、HBV-DNA及丙氨酸氨基转移     

乙肝患者血清HBsAg与HBsAb双阳性的特殊模式分析

目的报告乙肝表面抗原（HBsAg）与表面抗体（HBsAb）双阳性患者血清中这2种标志物波动情况及S区编码碱基序列变异特点。方法收集本院2005年7月收治的2例患者血清标本（经酶联免疫吸附试验定量检测HBsAg与HBsAb均阳性）并随访2月;PCR法扩增血清中HBV的S基因并测序。结果1例患者初始血清HBsAg与HBsAb分别为0.11IU/ml、18.44mIU/ml,2月后HBsAg消失;另1例患者初始血清HBsAg与HBsAb分别为24.09IU/Ml、840.06mIU/Ml,2月后HBsAb不能检出。在二者初始血清中扩增出完整HBV的S基因片段,序列分析显示为基因型D和血清亚型ayw,共同抗原决定簇α的aa145位甘氨酸编码序列未发生缺失或突变。结论2例HBsAg与HBsAb双阳性患者血清中仍存在HBV,其抗原决定簇α区未发生因aa145位甘氨酸突变导致的免疫原性改变。     

血清前S1蛋白在乙型肝炎病毒感染中的临床意义

目的 分析前S1蛋白与其他HBV检测指标的关系，并探讨其相应的临床意义。方法 采用ELISA方法对住院患者进行血清前S1蛋白检测，比较不同HBV指标组合模式中的前S1蛋白变化。结果 HBV高复制组(HBeAg、HBV DNA、HBcAb IgM阳性各组)中血清前S1蛋白阳性高，低复制组相对低。HBsAg、HBsAb阳性(18)及HBsAg、HBsAb、HBeAb阳性(7)和仅HBsAg阳性(21)患者中，其前S1蛋白均阴性。前S1蛋白阳性亦见于HBsAb阳性的大三阳(3／12)、HBsAb阳性的小三阳(5／20)、HBsAg、HBsAb、HBcAb阳性(1／3)和仅HBsAb阳性(1／439)及仅HBcAb阳性(1／3)患者中。结论 血清前S1蛋白不仅是一反映HBV复制状态和传染性的指标，而且还可能反映HBV颗粒状态和隐匿性HBV感染。     

Measurement of L-carnitine and acylcarnitines in body fluids and tissues in children and in adults

We have developed a reliable and validated radio-enzymatic method for the assay of L-carnitine and acylcarnitines, using a modification of existing methods. The sensitivity of the assay is 10 mumol/l using 10 microliters of plasma or urine. It is also suitable for measurements of carnitine in a 10 mg sample of liver or muscle obtained by percutaneous biopsy. The use of N-ethylmaleimide in the reaction mixture together with an excess of [1-14C]acetyl CoA ensures that the reaction proceeds to completion and a linear response is obtained. Using this method control ranges have been established for plasma and urine carnitine concentrations in healthy children and adults, and for the carnitine content of liver and muscle in adults. No significant difference was found between fasting and post-prandial plasma carnitine levels. An age-related increase was found in urinary total carnitine and acylcarnitine concentration throughout childhood. These data provide a reliable basis for studies of patients with abnormal carnitine and acylcarnitine metabolism, distribution and excretion.     

Rosamicin in Urethral and Vaginal Secretions and Tissues in Dogs and Rats

In animal studies we investigated the distribution of rosamicin in plasma and urethral and vaginal tissues in rats as well as in urethral and vaginal secretions in dogs. We found concentration ratios between urethral secretion and plasma of 1.9 and between vaginal secretion and plasma of 2.4. The rosamicin concentrations in urethral and vaginal tissue significantly exceeded the levels of all other tissues investigated. Because rosamicin could be valuable for the treatment of bacterial urethritis and the colonization of the vaginal introitus with fecal bacteria in women, it should be investigated clinically in this respect.     

Variations in atherosclerosis and remodeling patterns in aorta and carotids

Background

Atherosclerosis is a progressive disease that causes vascular remodeling that can be positive or negative. The evolution of arterial wall thickening and changes in lumen size under current "standard of care" in different arterial beds is unclear. The purpose of this study was to examine arterial remodeling and progression/regression of atherosclerosis in aorta and carotid arteries of individuals at risk for atherosclerosis normalized over a 1-year period.

Methods

In this study, 28 patients underwent at least 2 black-blood in vivo cardiovascular magnetic resonance (CMR) scans of aorta and carotids over a one-year period (Mean 17.8 ± 7.5 months). Clinical risk profiles for atherosclerosis and medications were documented and patients were followed by their referring physicians under current "standard of care" guidelines. Carotid and aortic wall lumen areas were matched across the time-points from cross-sectional images.

Results

The wall area increased by 8.67%, 10.64%, and 13.24% per year (carotid artery, thoracic aorta and abdominal aorta respectively, p < 0.001). The lumen area of the abdominal aorta increased by 4.97% per year (p = 0.002), but the carotid artery and thoracic aorta lumen areas did not change significantly. The use of statin therapy did not change the rate of increase of wall area of carotid artery, thoracic and abdominal aorta, but decreased the rate of change of lumen area of carotid artery (-3.08 ± 11.34 vs. 0.19 ± 12.91 p < 0.05).

Conclusions

Results of this study of multiple vascular beds indicated that different vascular locations exhibited varying progression of atherosclerosis and remodeling as monitored by CMR.     

Issues and challenges in nursing and nursing education in Japan

In this editorial we discuss the challenges and issues in nursing and nurse education in Japan. These include a rapid growth in the number of universities offering nursing programs without sufficient time for preparation of faculty; issues in the traditional ways of teaching in classrooms; the appearance of nursing shortages in a country with the highest rate of longevity in the world; and the position of nursing faculty in a society that is largely male dominated.     

Similarities and differences in clients treated and in medications prescribed by APRNs and psychiatrists in a CMHC

This study is part of a larger study comparing prescribing practices of psychiatrists and advanced practice psychiatric nurses (APRNs) using the following three groups of patients: patients treated by psychiatrists, those treated by APRNs, and those treated by both APRNs and psychiatrists at different times in 1 year. Demographics for 5507 patients were examined. A subsample of APRNs and psychiatrists prescribed similar total numbers of medications. Psychiatrists prescribed more types of antidepressant medications other than the SSRI antidepressants, and they prescribed more than twice the number of benzodiazepines. APRNs prescribed more SSRIs and spent more time with clients during medication visits.