巨大淋巴结增生症的影像学诊断

目的:研究巨大淋巴结增生症(Castleman Disease)的CT和MR影像表现特点,以提高对本病的认识,提高诊断准确率。方法:收集我院自1995年1月~2012年10月间,经手术病理证实的19例巨大淋巴结增生症,患者均接受CT或MRI平扫及增强扫描检查。其中,男7例,女12例,年龄19~62岁,平均43.4岁。结果:19个病例中14例病灶位于胸部(胸腔或纵隔),2例位于颈部,3例位于腹膜后区,局限型16例,弥漫型3例。CT检查采用CT动态增强扫描技术,局限型病灶在动脉期可见明显强化,强化程度近似主动脉,弥漫型病灶在动脉期表现为中等程度强化,两者在延迟期均表现为持续强化。MR扫描:4例表现为T1WI低信号,1例为中等信号,T2WI均呈高信号,动态增强扫描病灶的强化方式与CT基本一致。结论:颈部、胸部或腹膜后区的富血供病变,在CT及MRI增强扫描动脉期表现明显强化,延迟期持续强化,应高度怀疑巨大淋巴结增生症的可能性。     

Selective killing of Kaposi's sarcoma-associated herpesvirus lytically infected cells with a recombinant immunotoxin targeting the viral gpK8.1A envelope glycoprotein

Kaposi sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) is etiologically associated with three neoplastic syndromes: Kaposi sarcoma and the uncommon HIV-associated B-cell lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman disease. The incidence of the latter B-cell pathology has been increasing in spite of antiretroviral therapy; its association with lytic virus replication has prompted interest in therapeutic strategies aimed at this phase of the virus life cycle. We designed and expressed a recombinant immunotoxin (2014-PE38) targeting the gpK8.1A viral glycoprotein expressed on the surface of the virion and infected cells. We show that this immunotoxin selectively kills KSHV-infected cells in dose-dependent fashion, resulting in major reductions of infectious virus release. The immunotoxin and ganciclovir, an inhibitor of viral DNA replication, showed marked reciprocal potentiation of antiviral activities. These results suggest that the immunotoxin, alone or in combination, may represent a new approach to treat diseases associated with KSHV lytic replication.     

Focus: Personalized Medicine: Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in “omics” technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN’s collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.     

Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice

While there have been enormous strides in the understanding of Huntington's disease (HD) pathogenesis, treatment to slow or prevent disease progression remains elusive. We previously reported that dietary creatine supplementation significantly improves the clinical and neuropathological phenotype in transgenic HD mice lines starting at weaning, before clinical symptoms appear. We now report that creatine administration started after onset of clinical symptoms significantly extends survival in the R6/2 transgenic mouse model of HD. Creatine treatment started at 6, 8, and 10 weeks of age, analogous to early, middle, and late stages of human HD, significantly extended survival at both the 6- and 8-week starting points. Significantly improved motor performance was present in both the 6- and 8-week treatment paradigms, while reduced body weight loss was only observed in creatine-supplemented R6/2 mice started at 6 weeks. Neuropathological sequelae of gross brain and neuronal atrophy and huntingtin aggregates were delayed in creatine-treated R6/2 mice started at 6 weeks. We show significantly reduced brain levels of both creatine and ATP in R6/2 mice, consistent with a bioenergetic defect. Oral creatine supplementation significantly increased brain concentrations of creatine and ATP to wild-type control levels, exerting a neuroprotective effect. These findings have important therapeutic implications, suggesting that creatine therapy initiated after diagnosis may provide significant clinical benefits to HD patients.     

Serous fluid cytology of multicentric Castleman’s disease and other lymphoproliferative disorders associated with Kaposi sarcoma‐associated herpes virus: a review with case reports

C. Lobo, S. Amin, A. Ramsay, T. Diss and G. Kocjan Serous fluid cytology of multicentric Castleman’s disease and other lymphoproliferative disorders associated with Kaposi sarcoma‐associated herpes virus: a review with case reports Objective: The aim of this study is to describe and review the cytological features of Kaposi sarcoma‐associated herpes virus (KSHV) related entities, such as multicentric Castleman’s disease (MCD), plasmablastic‐lymphoma (PBL) and primary effusion lymphoma (PEL), which all may present as body cavity effusions. Serous fluid cytology of MCD and PBL has not, to our knowledge, thus far been described. Although different in nature, MCD, PBL and PEL are characterized by similar morphological features. Materials and methods: Body cavity effusions from four different patients with previously known or unknown KSHV‐related lymphoproliferations have been examined by routine cytology, immunocytochemistry (IC) and polymerase chain reaction (PCR). Results: MCD, PBL and PEL are all characterized by increased cellularity, comprising mainly lymphoid and plasmacytoid cells with variable proportions of immunoblasts. Immunocytochemistry and PCR results show the MCD to be CD138 and KSHV positive, CD30 negative, IgM, IgH and lambda restricted but IgH polyclonal. PBL was CD138 positive, kappa restricted, weakly positive with VS38 and over 80% positive with MIB 1. PEL was CD45, EMA, CD138, KSHV, p53 and CD3 positive, CD20, EBV, CD30, CD2, CD4, ALK1, epithelial and mesothelial markers negative, and PCR monoclonal B‐cell expanded (Ig‐kappa bands). Conclusion: Cytological examination of effusions in KSHV‐related lymphoproliferative disorders may show similar morphological features but clonality studies and immunocytochemistry are very helpful in distinguishing between these rare benign and malignant lymphoproliferative diseases.     

局部进展期胃癌术前动静脉结合化疗的疗效观察

目的:局部进展期胃癌,即使没有出现远处转移或腹膜种植,预后也极不理想.我们对局部进展期胃癌患者进行术前mECF方案的动静脉结合化疗,以评价其治疗疗效.方法:选取自2009年1月至2011年6月间我院局部进展期胃癌Ⅱ-ⅢC期患者38例,均由影像学确定淋巴结高度可疑转移或浸润、包绕主要血管结构,且没有发现远处转移或腹膜种植,进行2个周期的术前动静脉结合化疗后,行手术治疗.记录化疗毒性反应、临床、病理缓解率、手术并发症发生率和病死率以及1年无病生存率.结果:化疗毒性反应低,3级反应不超过10％,仅有1例出现4级反应,表现为腹泻、恶心和呕吐.38例患者中临床CR有6例,占15.8％,PR17例,占44.7％,NC13例(34.2％),PD2例(5.3％),RR为60.5％(23/38).全部患者均施行了手术,37例患者进行了根治性手术,R0切除率为97％.病理缓解率为5例完全缓解(13.2％),21例部分缓解(55.3％),8例轻微缓解(21.1％),4例未缓解(10.5％).手术并发症发生率为7.9％,无治疗相关死亡发生.1年无病生存率为81.6％.结论:局部进展期胃癌患者术前进行mECF方案的动静脉化疗毒性反应低,疗效理想,之后行手术完整切除后临床效果突出,是理想的治疗方法.     

Structure-activity relationships for a class of selective inhibitors of the major cysteine protease from Trypanosoma cruzi

Chagas' disease is a parasitic infection widely distributed throughout Latin America, with devastating consequences in terms of human morbidity and mortality. Cruzain, the major cysteine protease from Trypanosoma cruzi, is an attractive target for antitrypanosomal chemotherapy. In the present work, classical two-dimensional quantitative structure-activity relationships (2D QSAR) and hologram QSAR (HQSAR) studies were performed on a training set of 45 thiosemicarbazone and semicarbazone derivatives as inhibitors of T. cruzi cruzain. Significant statistical models (HQSAR, q² = 0.75 and r² = 0.96; classical QSAR, q² = 0.72 and r² = 0.83) were obtained, indicating their consistency for untested compounds. The models were then used to evaluate an external test set containing 10 compounds which were not included in the training set, and the predicted values were in good agreement with the experimental results (HQSAR, = 0.95; classical QSAR, = 0.91), indicating the existence of complementary between the two ligand-based drug design techniques.     

窦房结优势起搏点兴奋向心房传导方式的探讨

本文采用同步双标测法,研究了窦房结(SN)优势起搏点兴奋向心房传导的规律。在14只麻醉狗心脏界沟部缝上一装有32个电极的电极板,标测优势起搏点(P点),最早起始负电位点(N点),心房激动过程图及最早激动点(O点)。在用异丙肾上腺索、心得安或刺激迷走神经使P点移位后,我们研究了P点位置与P—O、P—N的关系。在计60次实验中:(1)P—O、P—N多数并不重叠(分别为46次和40次);(2)随着P点从SN头部向尾部移位,O(N)点在P点头侧的出现率下降,在P点尾侧的出现率上升;(3)出现两个O点者23次,出现两个N点者11次,但P点始终只有一个。 本文提出了SN兴奋在SN内优先向头、尾两端扩布,再传向心房肌的窦房传导模式。并对心房激动多中心起源、界沟部兴奋超速传导等现象及Boiaeau的“心房综合起搏”假说进行了讨论。     

Plant growth regulators and virus infection: A critical review

Virus infection can severely inhibit plant growth and distort development. This article reviews changes in plant growth regulator metabolism caused by infection. In general, virus infection decreases auxin and gibberellin concentrations and increases abscisic acid concentration. Ethylene production is stimulated in necrotic or chlorotic reactions to infection, but not where the virus spreads systemically without necrosis. While these broad trends are true for most host-virus combinations studied, several situations are recorded where the virus had other effects on growth substance concentration. Cytokinin changes do not show any common pattern: both increases and decreases after infection have been reported.The extent to which virus-induced changes in growth substance concentration could be responsible for observed alterations in host growth and development is discussed. While changes in abscisic acid, gibberellin and ethylene production seem potentially important, the experimental evidence does not provide conclusive proof for control of growth by these changes.The numerous investigations of effects of exogenous regulators on virus multiplication and pathogenesis are reviewed. Different regulators, or the same regulator applied at different times or concentrations, had very diverse effects, and in some cases did significantly alter virus multiplication and pathogenesis. However, such studies seem to have yielded disappointingly little understanding of the biochemistry of the host-virus interaction, and the possible involvement of growth substances in this.Possible uses of plant growth regulators in chemotherapy of virus disease, and their possible involvement in natural or induced resistance mechanisms are discussed.     

Lymphoid disorders associated with HHV-8/KSHV infection: facts and contentions

Following the demonstration in 1994, that Kaposi's sarcoma (KS) was associated with a novel virus (KSHV or HHV-8) belonging to the lymphotropic herpes family, this virus was also found in certain lymphoid neoplasias of immunodeficient (HIV⁺) and immune competent hosts. The association of HHV-8/KSHV infection is now well established with primary effusion lymphoma (PEL) or body cavity based lymphoma (BCBL) and multicentric Castleman's disease (MCD) of the plasma cell type. A possible pathogenic role of HHV-8/KSHV in other lymphoid tumours including primary central nervous system lymphoma (PCNSL) and multiple myeloma (MM) as well as some atypical lymphoproliferations and sarcoidosis has also been suggested, but this is at present a controversial matter, or not confirmed. SeveralHHV-8/KSHV genes, including potential oncogenes, genes homologous to various cellular genes and growth factors have been incriminated in the pathogenesis of KS and PEL/BCBL, but a common pathogenic mechanism for the clearly diverse proliferations represented by PEL, MCD and KS is at present not evident.     

静脉联合腹腔热灌注化疗对老年复发卵巢癌的临床效果

目的:对比分析静脉联合腹腔热灌注化疗与全身静脉化疗治疗老年复发卵巢癌的临床效果。方法:以2010年1月至2010年12月我院收治的80例老年复发卵巢癌患者为研究对象,行随机数字表法均分为观察组和对照组。观察组(n=40)行静脉联合腹腔热灌注化疗对照组(n=40)仅行全身静脉化疗。持续四个周期后统计疗效、不良反应,治疗前后CD3~+、CD4~+、CD4~+/CD8~+;持续随访,统计1年生存率、2年生存率、3年生存率、平均生存时间。结果觌察组总有效率(75.0%vs 52.5%)显著高于对照组;不良反应发生率(22.5%vs 80.0%)明显低于对照组;CD3~+、CD4~+、CD4~+/CD8~+均显著高于对照组;1年生存率(72.5%vs 55.0%)、2年生存率(27.5%vs 7.5%)均显著高于对照组;平均生存时间(16.8±2.1)月vs(13.8±1.8)月显著长于对照组。结论:静脉联合腹腔热灌注化疗治疗老年复发卵巢癌疗效显著,值得推广。     

放化疗与介入性动脉化疗治疗局部晚期宫颈癌的临床研究

目的:比较分析放化疗与介入性动脉化疗治疗局部晚期动脉宫颈癌的临床效果。方法:选择我院局部晚期宫颈癌患者97例,依据治疗方法分为常规组(行传统放化疗)55例和介入组(行介入性动脉化疗)42例。观察治疗后肿瘤大小、近期疗效、根治性手术率、术后并发症,对生活质量指数进行评分,评价两种方法的临床效果。结果:治疗后,两组患者近期疗效比较差异无统计学意义(P0.05);介入组肿瘤直径明显小于常规组,而根治性手术率明显高于常规组,差异均具有统计学意义(P0.05);介入组患者日常生活、健康、总体情况以及总的评分均明显高于常规组,差异具有统计学意义(P0.05),同时介入组并发症较少。结论:放化疗与介入性动脉化疗治疗局部晚期动脉宫颈癌近期临床疗效均较好,但介入性动脉化疗具有较高的根治性手术率以及生活质量,且并发症少。     

光化学疗法治疗神经性皮炎60例临床疗效观察

采用光化学疗法,外涂0.2%8-MOP半小时后以光化肤康灯(主峰波长365 nm,终端输出功率25.4 W连续可调,幅照度:930μW/cm2)照射,治疗神经性皮炎60例,平均治疗间期1月,治愈率51.67%,显效率23.33%,有效率21.67%,无效率3.33%。未发现明显毒副作用。结果显示光化学疗法对神经性皮炎有很好的疗效。     

动脉介入新辅助化疗对宫颈癌细胞增殖及凋亡的影响

目的:探讨动脉介入新辅助化疗对宫颈癌细胞增殖及凋亡的影响,为中晚期宫颈癌的临床治疗提供依据。方法:选择2012年8月-2015年5月在我院确诊为中晚期宫颈癌并行动脉介入化疗的患者60例作为研究对象。分别在入院时和动脉介入化疗后收集患者肿瘤组织标本,应用免疫组化法检测肿瘤细胞增殖指数(LI),TUNEL法检测肿瘤细胞凋亡指数(AI)。结果:经动脉介入化疗后,宫颈癌细胞的增殖指数显著降低,而凋亡指数显著提高,与化疗前比较,差异具有统计学意义(P0.05)。宫颈癌细胞增殖指数LI随临床分期的增加而升高,而凋亡指数AI随临床分期的增加而降低,差异具有统计学意义(P0.05);介入化疗后,同一临床分期宫颈癌细胞的增殖指数LI均低于化疗前,而凋亡指数AI则高于化疗前,差异具有统计学意义(P0.05)。结论:动脉介入新辅助化疗能够抑制中晚期宫颈癌细胞的增殖,并促进其凋亡,为患者创造手术切除的机会。