Targeted Metabolic Reprogramming to Improve the Efficacy of Oncolytic Virus Therapy

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Detection of type-specific antibodies to HSV-1 and HSV-2: comparative analysis of a chemiluminescence immunoassay with a conventional ELISA

Type-specific serologic tests for human herpes simplex virus (HSV) are critically important for sexually transmitted disease evaluation. We compared the LIAISON® HSV-1 and HSV-2 Type Specific assays relative to an established commercial ELISA. The overall agreement of the chemiluminescence immunoassay versus the ELISA assay was 99.6% (HSV-1) and 100% (HSV-2). The LIAISON® methodology has several advantages.     

HMGB1——血液恶性肿瘤治疗的潜在靶点

HMGB1是一种广泛的DNA结合蛋白,参与维持基因稳定、调节DNA转录和修复。在损伤、感染、化疗等因素作用下,HMGB1还可作为DAMP与RAGE、TLR、CXCL12等PRR受体结合,通过活化CDC42、MyD88／TRAF6、NF—KB、MAPK和抗细胞凋亡蛋白c—IAP等多种途径,介导炎症反应、血管生成及肿瘤细胞生长转移等,促进肿瘤发生发展,参与T细胞依赖的免疫应答,发挥免疫效应。有研究表明,在血液系统恶性疾病治疗过程中HMGB1可过表达,促进恶性细胞增殖,进而降低疗效;HMGB1与Beclinl、ERK、JNK等蛋白相互作用促进血液恶性肿瘤细胞自噬（外源性HMGB1则直接诱导自噬）,参与化疗、放疗抵抗。因此,通过抑制HMGB1表达,促进肿瘤细胞凋亡及增加血液病细胞对化疗药物的敏感性,是治疗血液恶性肿瘤的新策略。本文就HMGB1的基本特征和HMGB1与肿瘤的研究进展进行综述。     

HSV-1重组蛋白GST-G1为抗原的IgM捕获法ELISA的研究

目的研究单纯疱疹病毒1型(HSV-1)近期感染的IgM酶免疫诊断技术。方法用捕获法ELISA(G-ELISA)和HerpeSelect ELISA(H-ELISA)平行检测1296份孕妇血清HSV-1-IgM。结果 G-ELISA检出阳性血清12份,H-ELISA检出阳性血清11份。G-ELISA多捡出的1份阳性,并经其他试验证实为真阳性。乳胶凝集试验诊断为类风湿因子(RF)阳性的6份血清,经H-ELISA检出阳性血清2份,但经G-ELISA试剂盒检测全为阴性。结论在检测孕妇HSV-1-IgM方面,G-ELISA比H-ELISA可能敏感性更强,特异性更高。G-ELISA是诊断HSV-1近期感染的有效方法。     

SDF-1/CXCR4与血液系统恶性肿瘤的关系研究进展

基质细胞衍生因子（SDF—1）及其受体CXCR4相互作用转导特定信号，在许多生理和病理过程中都发挥了重要的效应，CXCR4在多种血液系统肿瘤中高表达，与疾病的预后、耐药、复发密切相关。用SDF-1抗体或CXCR4抗体能有效的抑制肿瘤细胞的生长，为治疗血液系统肿瘤开辟了新途径。本文就SDF—I／CXCR4在血液系统肿瘤中的表达，及其与预后、耐药、复发和治疗关系的研究进展作一综述，     

血液恶性肿瘤及造血干细胞移植患者侵袭性真菌感染的早期抗原诊断实验研究

本研究评价血清1,3-β-D葡聚糖(G)和半乳甘露聚糖(GM)联合检测用于血液恶性肿瘤及造血干细胞移植患者侵袭性真菌病(IFD)早期诊断的敏感度及特异度,确定GM阳性值、探讨G/GM测定前后诊断级别的变化及GM水平与疗效的关系。用双抗体夹心酶联免疫吸附分析(ELISA)测定患者血清G和GM值。结果表明:按照实验中测定的界值,G/GM联合检测的敏感度100%,特异度65.7%,阳性预测值67.6%,阴性预测值为100%;G/GM检测后临床诊断IFD由1例上升至24例,有12例非感染者上升为拟诊IFD;治疗前GM水平维持在较高水平,抗真菌治疗有效患者的GM值呈下降趋势,无效死亡患者GM值呈上升趋势。结论:G及GM实验联合检测提高了IFD诊断的敏感度,降低了假阴性的发生,具有早期诊断价值,动态监测G/GM值的变化可作为评价疗效的指标。     

免疫功能检测对评估细胞因子诱导的自体杀伤细胞治疗老年血液肿瘤疗效的研究

本研究探讨细胞因子诱导的自体杀伤(cytokine induced killer,CIK)细胞输注对造血系统恶性肿瘤老年患者免疫功能的影响及其与疗效的关系。采集20例造血系统恶性肿瘤老年患者外周血单个核细胞,在体外经重组干扰素-γ(IFN-γ)、白介素-2(IL-2)、抗CD3单克隆抗体诱导成CIK细胞,回输细胞数为(2-3)×109个,回输后第1-10天应用IL-2 100万单位/天,皮下注射。28天为1个疗程,共完成了136个周期的自体CIK细胞输注。观察治疗前后细胞免疫功能变化,结合肿瘤相关生物学指标、缓解情况、生活质量及生存期的变化进行疗效分析。结果表明,14例接受8个疗程的CIK细胞输注,6例接受4个疗程的输注,回输后所有患者未出现不良反应。CIK细胞治疗后外周血CD3+、CD3+CD8+、CD3+CD56+细胞比例明显升高(p0.05),β2微球蛋白、LDH水平显著下降(p0.05)。所有患者症状改善、生活质量显著提高(p0.01)。11例达完全缓解,7例达部分缓解,2例疾病稳定。结论:自体CIK细胞输注可提高造血系统恶性肿瘤老年患者的细胞免疫功能且安全有效。     

甲型H1N1流感病毒性肺炎的胸部X线和CT表现

目的总结甲型H1N1流感病毒性肺炎患者的胸部X线和CT表现特征。方法回顾分析2009年3月-11月3例经临床表现及病原学检查证实的甲型H1N1流感病毒性肺炎的胸部X线、CT表现。结果肺部病灶多呈散在小片状高密度影,边缘模糊,邻近胸膜;病变最常累及肺基底段;病灶多有少量胸腔积液;病灶有扩散迅速,合理用药后消失较快的特点;病灶吸收落后于临床表现。结论甲型H1N1流感病毒性肺炎的X线、CT表现具有一定的特点,总结并掌握这些特点,有利于早期诊断。其确诊有赖于实验室检查和流行病学调查。     

Advanced hepatocellular carcinoma treated by radiofrequency ablation combined with oncolytic virus and anti-PD-1 antibody therapy: a case report and literature review

The development of an effective therapy for advanced hepatocellular carcinoma (HCC) represents an important global concern. In recent years, the combination of multiple treatment methods with immunotherapy has achieved great progress in patients with advanced HCC. Patient survival has been significantly prolonged, but cases of complete response (CR) remain rare. Here, we report two cases in which CR was achieved by radiofrequency ablation combined with an oncolytic virus (recombinant human adenovirus type 5) and anti-programmed cell death protein 1 antibody. Additionally, a literature review is presented to describe similar advancements in this field and explore viable methods for the treatment of advanced HCC.     

Recent developments with immunotherapy for hepatocellular carcinoma

Introduction: Immunotherapy is on the way to become the new standard of care for advanced hepatocellular carcinoma (HCC) worldwide. With higher rates of objective responses, and overall less side effects compared to tyrosine-kinase inhibitors (TKIs) immunotherapeutics will probably replace sorafenib from standard first-line treatment.

Areas covered: This review covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC focusing on immunotherapy.

Expert opinion: In unselected patients with advanced HCC immunotherapeutics, namely the programmed cell death-1 (PD-1) antibodies, nivolumab and pembrolizumab have shown promising efficacy in therapy-naïve, as well as pre-treated patients with advanced HCC. However, only 10–20 percent of treated patients show an objective and durable response to the indicated therapeutics. Therefore, combination therapies including different immunotherapeutics, e.g. PD-1/programmed cell death 1 ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies, or combinations of immunotherapeutics and small molecules, or bifunctional antibodies will be needed to improve response rates.

Abbreviations: HCC: hepatocellular carcinoma; TKI: tyrosine-kinase inhibitors; PD-1: programmed death receptor-1; PD-L1: programmed cell death 1 ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated Protein 4; CAR-T: chimeric T cell receptors; TACE: transarterial chemoembolization; SIRT: selective internal radiation therapy; SBRT: stereotactic body radiation therapy; VEGF: vascular endothelial growth factor; MEK: mitogen-activated protein kinase kinase; NK cell: natural killer cell; TGFβ: transforming growth factor-β; OV: Oncolytic viruses; PFU: plaque-forming unit     

首发重症及危重症甲型H1N1流感6例

甲型H1N1流感患者的胸部影像学改变出现早、分布广、变化快,认识其特征及动态变化,密切结合临床表现及实验室检查对早期确诊和有效治疗有积极的指导作用.本文对我院2009年收治首批确诊的6例散发重症及危重症甲型H1N1流感患者的临床、实验室、影像学表现进行回顾性分析.     

Dolutegravir for the treatment of adult patients with HIV-1 infection

Dolutegravir, is a second generation integrase inhibitor that had recently received United States Food and Drug Administration and European Commission approval for the treatment of adult patients with HIV-1 infection. Dolutegravir provides distinct advantages compared with first generation integrase inhibitors. Unlike raltegravir, dolutegravir can be given once daily for patients who are antiretroviral treatment naïve. Once-a-day dolutegravir dosing also does not require a pharmacokinetic booster like elvitegravir which minimizes the drug-drug interaction potential of dolutegravir. In Phase III clinical trials, dolutegravir-containing regimens have demonstrated either non-inferiority or superiority to current first line agents such as raltegravir, darunavir/ritonavir, and efavirenz containing regimens. Moreover, dolutegravir may be effective for patients with a history of raltegravir and/or elvitegravir resistance. Dolutegravir will likely play a major role in the management of patients with HIV-1 infection, and will be aided when coformulation with abacavir/lamivudine as a single pill, once-daily regimen is available.     

慢性乙型肝炎肝组织ICAM-1、HBsAg、HBcAg的表达及分析

目的探讨ICAM-1、HBsAg、HBcAg在慢性乙型肝炎肝组织中的表达及其在发病机制中的意义.方法免疫组化SABC法检测慢性乙型肝炎肝组织中ICAM-1、HBsAg、HBcAg的表达.结果在慢性乙肝中,随着炎症活动度的增高,ICAM-1表达增强,HBcAg表达减弱,HBsAg表达由胞浆显色为主逐渐转为胞膜显色为主.结论肝细胞ICAM-1、HBcAg的表达在慢性乙肝的炎症反应中起重要作用.肝细胞中HBsAg的表达在一定程度上反映了病毒的复制活动.     

靶向序列捕获联合高通量测序鉴定成人型多囊肾PKD1基因新突变

目的 探讨一个成人型多囊肾蛋白激酶D1(PKD1)基因新剪切位点突变及临床表型.方法 收集一个成人型多囊肾病家系临床资料,对家系内成员采用靶向序列捕获对PKD1基因行高通量测序,并结合文献加以分析.结果 该家系中先证者存在成人型多囊肾PKD1基因的c.12138+1G>A(IVS44)突变,而在家系内父亲因多囊肾引发尿...     

维持性血液透析患者继发性甲状旁腺功能亢进的治疗观察

目的研究低钙透析联合1，25（0H）2D3及碳酸钙治疗维持性血液透析患者继发性甲状旁腺功能亢进的有效性和安全性。方法选择山东省千佛山医院肾脏病血液净化中心23例血液透析患者，校正血钙≥8．00mg／dl，iPTH〉300pg／ml，分为Ⅰ组[iPTH（300-600）pg／ml]和Ⅱ组（iPTH600-1000pg／ml），起始量分别给予1，25（OH）2D32～3μg／w和4～6μag／w，分2～3次较大剂量间断口服治疗，配合碳酸钙日服降磷，并联合低钙透析（透析液钙浓度为1．25mmol／L），总观察期20周。监测治疗前后患者血钙、磷、钙磷乘积、iPTH、碱性磷酸酶（hKP）等指标及药物用量变化情况。结果为期20周的治疗显著降低血液透析患者血磷、钙磷乘积、iPTH水平，血钙水平在治疗过程中保持稳定。不良反应较小且均可耐受。结论合理调整活性维生素D用量，配合碳酸钙及低钙透析可有效控制血液透析患者继发性甲状旁腺功能亢进，并且在治疗的早期疗效更显著，安全性良好。