Mucocutaneous ulcer positive for Epstein–Barr virus,misdiagnosed as a small bowel adenocarcinoma:A case report

BACKGROUND Epstein–Barr virus(EBV)-positive mucocutaneous ulcers(MCUs)are an uncommon disorder characterized by ulcerative lesions in the skin,oral cavity or gastrointestinal tract in patients with iatrogenic or aging-induced immunosuppression.The nonspecific lesions are difficult to differentiate from small bowel adenocarcinomas.We present the case of a 69-year-old woman who was initially misdiagnosed with a small bowel adenocarcinoma but was later surgically diagnosed with and treated for EBV-MCU.Through this case,we aim to emphasize the importance of accurately distinguishing between the two conditions.CASE SUMMARY The patient presented with an incidental finding of a small bowel tumor during computed tomography(CT)examination performed for hematuria.The CT scan showed irregular thickening of the distal ileum,which was suggestive of a malignant small bowel tumor.An exploratory laparotomy revealed an 8-cm mass in the distal ileum;thus,a segment of the small intestine,including the mass,was resected.Histopathological analysis revealed an ulceroinfiltrative mass-like lesion with luminal narrowing,marked inflammatory cell infiltration,and large atypical lymphoid cells(positive for EBV-encoded small RNA).A final diagnosis of an EBV-MCU was established.The postoperative course was uneventful,and the patient was discharged on postoperative day 7.The patient remained recurrencefree until 12 mo after surgery.CONCLUSION This case highlights the diagnostic challenges for EBV-MCUs and emphasizes the importance of comprehensive evaluation and accurate histopathological analysis.

Epstein-Barr病毒RPMS1基因的克隆及其编码区序列分析

目的:克隆Epstein-Barr(EB)病毒的RPMS1基因,并分析其编码区序列的变异情况。方法:从7例高发区鼻咽癌组织中分别提取总RNA,以RT-PCR扩增出RPMS1基因编码序列,克隆入pGEM-T载体,构建重组质粒pGEM-T/RPMS1,重组质粒经PCR、BamHⅠ和HindⅢ双酶切鉴定,并进行序列测序。结果:成功克隆了高发区鼻咽癌的RPMS1基因,该基因编码序列第151nt发生G→A替换,导致相应第51位氨基酸由天冬氨酸变为天冬酰氨。该变异位于DNA第Ⅴ外显子的155849nt,变异频率为6/7。结论:高发区鼻咽癌EB病毒RPMS1基因的编码序列存在变异;RPMS1基因可能参与高发区鼻咽癌的发生。

Fe-6.5%Si高硅钢铁芯与Epstein Square标准单片铁损检测结果对比及数据差异分析

作为一种具有优异高频铁磁性能的合金,Fe-6.5%Si(质量分数)高硅钢在高频工况条件下降损效果明显,对电气行业应用器件高频化、小型化、节能等具有十分重要的意义。通过与取向硅钢测量B-P数据对比,验证了高硅钢高频超低损特性,且轧制高硅钢与日本CVD法生产高硅钢存在基本相同的铁损值。采用国标Epstein Square法对0.30mm高硅钢薄板进行单片测试,并对由0.30mm高硅钢薄板首次装配成的电感器进行铁损测试,对比测试结果表明,元件测试与单片测试数据基本吻合,高磁感应强度条件下,元件测试结果略低于单片测试,分析原因为:线圈引起励磁压降;元件叠片间出现短路,电流增大,损耗增加;气隙板厚度过大。

Epstein-Barr病毒相关噬血细胞综合征的研究进展

Epstein-Barr病毒相关噬血细胞综合征(EBV-HLH)的病情进展快,病死率高。高细胞因子血症是其发病的重要机制,临床表现多样。诊断需符合HLH诊断标准并存在EBV感染的证据。治疗首选依托泊苷、糖皮质激素、环孢素A联合应用。如化疗效果不佳,可行造血干细胞移植。现就该病的最新研究进展进行综述。

基于习惯形成的Epstein-Zin效用函数模型与股权溢价之谜——来自中国A股市场的证据

美国资本市场历史数据显示股票收益远远高于债券收益,不能用基于消费的资产定价模型解释,Mehra and Prescott提出了所谓的股权溢价之谜,而Campbell and Cochrane的习惯形成模型在用HJ方差界检验股权溢价之谜时受到局限。对Epstein and Zin(1991)的广义期望效用模型进行修正,使用随机贴现因子的HJ方差界来检验中国股票市场是否存在股权溢价之谜,并比较CRRA模型、Epstein and Zin的模型及修正模型的定价能力。实证分析发现:(1)修正后的模型要求消费者的相对风险厌恶系数为2左右就可以解释中国的高股权溢价现象,而且中国股票市场不存在股权溢价之谜,也不存在无风险利率之谜;(2)同CRRA模型、Epstein and Zin的模型相比,修正后的模型具有更强的定价能力。

肠道B细胞淋巴瘤Epstein-Barr病毒感染与癌基因

目的 :研究肠道非霍奇金淋巴瘤B细胞型的Epstein Barr(EB)病毒感染、p5 3、p2 1ras基因表达及其相关性。方法 :应用单克隆抗体、免疫组化方法对瘤细胞进行免疫表型研究 ,CD2 0、CD45RA、CD79a鉴定瘤细胞的B细胞分化 ,CD45RO、CD3除外瘤细胞T细胞分化。同时用免疫组化方法 ,检测瘤细胞 p5 3基因表达、p2 1ras基因表达。EB病毒寡核苷酸探针 (EBER)原位杂交 ,观察瘤细胞EB病毒感染情况。结果 :34例肠道B细胞淋巴瘤好发部位为回肠和结肠 ,以单发瘤结节多见 ,常伴有表面溃疡形成。 34例中 ,弥漫性大B细胞淋巴瘤 9例 (2 6 .5 % ) ,19例为惰性的边缘区B细胞淋巴瘤黏膜相关淋巴组织型 (MZL MALT型 ) (5 5 .9% ) ,6例为MZL MALT型伴高度恶性转化(17.6 % )。EBV EBER原位杂交检测 ,全部病例为阴性。p5 3蛋白表达共有 2 3例 ,占全部病例的 6 7.6 % (其中高度恶性占 47.8% ) ;16例有 p2 1ras的表达 ,为 47.1% (其中高度恶性占 43.8% )。有 15例同时检出 p5 3蛋白和p2 1ras的表达 ,占病例数的 44 .1%。结论 :34例肠道B细胞淋巴瘤以惰性为多见 ,但恶性转化明显。EBV的研究提示肠道B细胞淋巴瘤有别于T细胞淋巴瘤 ,与EBV感染无关。p5 3蛋白的表达高于 p2 1ras,p5 3和 p2 1ras的共同表达检出率较高 ,提示癌基因 p5

5-Aza-CdR联合EBNA1-DC疫苗诱导的淋巴细胞对鼻咽癌C666-1细胞的杀伤作用

目的:探讨EB病毒核抗原1(EBNA1)mRNA修饰的DC(EBNA1-DC)诱导的淋巴细胞联合甲基化抑制剂5-Aza-CdR对鼻咽癌C666-1细胞的杀伤作用。方法:以构建的EBNA1-pCDNA3.1质粒为模板,体外转录获得EBNA1 mRNA,通过脂质体转染至健康人外周血来源DC,构建EBNA1-DC疫苗。流式细胞术检测转染后DC表型及5-Aza-CdR处理后的C666-1细胞凋亡情况。实时无标记动态细胞分析技术检测EBNA1-DC疫苗诱导的淋巴细胞联合5-Aza-CdR的特异性抗肿瘤活性。结果:转染EBNA1 mRNA后EBNA1-DC表面EBNA1阳性率为(59.3±5.85)%,HLA-DR的表达与未转染DC相比显著升高[(84.9±5.5)%vs(68.0±5.8)%,P=0.026],CD80的表达也显著升高([88.2±3.9)%vs(61.1±4.4)%,P=0.015]。低剂量5-Aza-CdR处理后的C666-1细胞凋亡情况与未处理的细胞相比无显著差异。经低浓度5-Aza-CdR预处理的C666-1细胞中IRF7基因表达与未处理的细胞相比显著升高(P=0.0001)。与空载的DC相比,EBNA1-DC诱导的淋巴细胞对EBV阳性表达的C666-1细胞具有更强的特异性杀伤活性(P=0.049);经低浓度5-Aza-CdR预处理的C666-1细胞对EBNA1-DC诱导的特异性免疫杀伤更敏感(P=0.019)。结论:5-Aza-CdR与EBNA1-DC疫苗联合可显著增强对C666-1细胞的特异性免疫杀伤,本研究为开拓以mRNA为基础的DC疫苗及其在临床综合治疗中的应用转化提供前期研究基础。

Prognostic value of plasma Epstein-Barr virus DNA level during posttreatment follow-up in the patients with nasopharyngeal carcinoma having undergone intensity-modulated radiotherapy

Background: The value of Epstein-Barr virus(EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma(NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment followup in the patients with NPC who have undergone intensity-modulated radiotherapy.Methods: The medical records of 385 NPC patients treated with intensity-modulated radiotherapy between November 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within3 months after treatment, and then every 3-12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed.Results: Of the 385 patients, 267(69.4%) had detectable pretreatment plasma EBV DNA(> 0 copy/mL) and 93(24.2%) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months(range 9.3-73.8 months).Detectable EBV DNA during posttreatment follow-up was found in 14.4%(17/118) and 28.5%(76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8%(40/313) of patients who remained disease-free,56.4%(22/39) of patients with locoregional recurrence alone, and 93.9%(31/33) of patients with distant metastasis as the first recurrence event(P < 0.001); 6.5%(19/292) of patients with undetectable EBV DNA and 57.0%(53/93) of patient with detectable EBV DNA during posttreatment follow-up experienced tumor recurrence. Compared with other cut-off values, the cut-off value of 0 copy/mL for EBV DNA during posttreatment follow-up had the highest area under the ROC curve(AUC) value(0.804,95% confidence interval 0.741-0.868) for predicting tumor recurrence(sensitivity, specificity, and accuracy: 73.6%, 87.2%, and 84.7%, respectively).Conclusion: Plasma EBV DNA level during posttreatment follow-up is a good marker for predicting distant metastasis but not locoregional recurrence in the patients with NPC irrespective of the pretreatment EBV DNA levels.

Prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum Epstein-Barr virus DNA copy number in predicting distant metastasis in patients with N1 nasopharyngeal carcinoma

Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node(GTVnd) and pretreatment serum copy number of Epstein-Barr virus(EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic(ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results: The 5-year distant metastasis-free survival(DMFS) rates for patients with GTVnd > 18.9 vs.≤ 18.9 mL were82.2% vs. 93.2%(P < 0.001), and for patients with EBV DNA copy number > 4000 vs. < 4000 copies/mL were 83.5% vs.93.9%(P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-,moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1,87.4, and 73.8%, respectively(P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification(hazard ratio [HR],4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.

Epstein Barr virus-positive mucocutaneous ulcer of thecolon associated Hodgkin lymphoma in Crohn＇s disease

Epstein Barr virus （EBV） positive mucocutaneous ulcers（EBVMCU） form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosuppression, affecting the oropharyngeal mucosa,skin and gastrointestinal tract （GIT）. Case reports andseries to date suggest a benign natural history respondingto conservative management, particularly in the GIT. Wereport an unusual case of EBVMCU in the colon, arisingin the setting of immunosuppression in the treatment ofCrohn＇s disease, with progression to Hodgkin lymphoma18 mo after cessation of infliximab. The patient presentedwith multiple areas of segmental colonic ulceration,histologically showing a polymorphous infiltrate withEBV positive Reed-Sternberg-like cells. A diagnosisof EBVMCU was made. The ulcers failed to regressupon cessation of infliximab and methotrexate for 18mo. Following commencement of prednisolone for herCrohn＇s disease, the patient developed widespreadHodgkin lymphoma which ultimately presented as alife-threatening lower GIT bleed requiring emergencycolectomy. This is the first report of progression ofEBVMCU to Hodgkin lymphoma, in the setting of ongoingiatrogenic immunosuppression and inflammatory boweldisease.

Recombinant Vaccinia Virus is an Effective and Non-perturbing Vector for Human Dendritic Cells Transfected with Epstein-Barr Virus Latent Membrane Protein 2A

ObjectiveTo study the effects of dendritic cells (DC) transfected with recombinant vaccinia virus encoding Epstein Barr virus (EBV) latent membrane protein 2A(LMP2A) gene,and to provide evidence for further investigation on the therapeutic vaccines against EBV associated malignancies. MethodsMature DC were transfected with EBV LMP2A recombinant vaccinia virus (rVV LMP2A). Before and after the transfection,the expression of surface antigens on mature DC including CD1a,CD83,CD40,CD80,HLA DR was measured by fluorescence activated cell sorter (FACS) and the function of DC to stimulate allogeneic T cells proliferation was measured by mixed leukocyte reactions (MLR). ResultsLMP2A protein was highly expressed (66.1 %) in DC after the transfection of rVV LMP2A. No significant changes in the primary surface antigens expression and in the MLR were detected during the transfection. Transfected DC still had strong potential in stimulating the proliferation of allogeneic T cells. ConclusionRecombinant vaccinia virus was an effective and non perturbing vector to mediate the transfection of LMP2A into DC. The functions of mature DC were not affected significantly by the transfection of Vac LMP2A. This study could provide evidence for the further immunotherapy of EBV associated malignancies,e.g. nasopharyngeal carcinoma (NPC).

STUDIES ON THE RELATIONSHIP BETWEEN EPSTEIN BARR VIRUS (EBV) AND PATHOGENESIS OF MULTIPLE MYELOMA

In order to explore the relationship between Epstein Barr virus (EBV) and pathogenesis of multiple myeloma (MM), the presence of EBV DNA in mononuclear cells of bone marrow (BMMC) and peripheral blood (PBMC) taken from 23 multiple myeloma patients who were neither posttransplanted nor HIV positive were examined by polymerase chain reaction (PCR). Meanwhile the presence of EBV EBERs in bioptic bone marrow's specimens of 4 MM patients were examined by in situ hybridization (ISH). Acute leukemia, aplastic anemia and malnourished anemia patients were taken as control. It showed EBV DNA detective rate in BMMC (69 6%) and in PBMC (39 1%) of MM patients were higher significantly than control groups (P<0 05). The positive signals of EBERs were located in BMMC and the EBV positive samples detected by ISH were consistent with those by PCR. The results indicate that EBV is closely correlated to pathogenesis of MM.

Epstein Barr Virus—The Cause of Multiple Sclerosis

Although many studies have found a kind of a relationship between an Epstein-Barr Virus (EBV) and the development of Multiple Sclerosis (MS), a fundamental aspect of this relationship remains uncertain. What is the cause of Multiple Sclerosis (MS)? In this study, we re-analysed the data as published by Wandinger et al. and were able to establish a new insight: without an Epstein-Barr Virus (EBV) infection no development of Multiple Sclerosis (MS). Furthermore, we determined a highly significant causal relationship between Epstein-Barr Virus (EBV) and multiple sclerosis. Altogether, Epstein-Barr Virus (EBV) is the cause of multiple sclerosis (p-value 0.0004251570).

SERO-EPIDEMIOLOGICAL STUDIES OF EPSTEIN-BARR VIRUS(EBV) INFECTION BY TESTING ANTIBODIES AGAINST EBV SPECIFIC DNASE(EDAb) AS A METHOD FOR EARLY DETECTION OF NASOPHARYNGEAL CARCINOMA(NPC)

In 1987, a mass survey of EDAb was carried out in Sihui county of Gunagdong Province (the highest incidence area of NPC in China) and the city of Guangzhou using the methods previously established by our lab. In order to study the correlation between EDAb level and NPC, the titre of DEAb and their distribution in sera from 430 patients with NPC and 5030 normal persons were detected. It was found that the AER (level of EDAb was represented by the anti enzyme rate) of NPC patients gave a negative skew distribution and the Md=65.3% while the natural population (30 59 years old) gave a serious positive skew distribution and the Md is 7.9%. According to the pattern of EDAb distribution curve of 430 NPC patients and 2060 natural population. AER≥30% was defined as a cut off point between EDAb positive and negative. Using this value we got a rate of 90.7% (390/430) positive diagnosis in NPC patients, while in natural population the positive rate was 3.3% (68/2060), and in the IgA/VCA positive (1:5) normal person the positive rate was 6.0% (41/681). As to the other tumors including head and neck tumors the positive rate was 3.4% (7/204), similar to the natural population. After a period of 62 months of follow up surveillance, 15 of 224 EDAb positive normal persons found in the mass survey were diagnosed as NPC by histopathological examination. While in 4806 EDAb negative normal person only one case NPC patient was found in this period. 60% of these patients were diag nosed in their early stage of NPC. From these patients it was found that EDAb could appear in the sera of the patients as early as 62 months before NPC was definitely diagnosed. 2 of these patients were shown IgA/VCA negative and EDAb positive in mass survey. This suggested that in some of the precancerous patients EDAb could appear earlier than IgA/VCA. The signifi cance of the sera EDAb positivity of normal person was discussed.

THE DETECTION OF CD56 AND EPSTEIN-BARR VIRUS IN T-CELL LYMPHOMAS

Objective: To study the relationship between EBV infection and the expression of CD56 in T cell lymphomas (TCLs). Methods: 46 cases of TCLs and 15 cases of reactive hyperplasia of lymphonodes (RHs) were detected CD56 by immunohistochemistry and EBERs by in situ hybridization. Results: 8 cases of 46 TCLs (17.4%) showed CD56 positive. On sites, CD56 positive rate of nasopharyngeal TCLs was highest (5/17, 29.4%), and on subtypes, that of DLs was highest (6/16, 37.5%). Additionally, 4 RHs were also CD56 positive. Of 46 TCLs, 24 showed expression of EBERs. There were only 4 TCLs expressing both CD56 and EBERs. Conclusion: The expression of CD56 was not especially for TCLs that EBV infected. EBV infection was not related with CD56 positive TCLs. The findings also suggested the expression of CD56 in TCLs be possibly related to original sites and subtypes of TCLs.

CK5/6-positive,P63-positive lymphoepithelioma-like hepatocellular carcinoma:A case report and literature review

BACKGROUND Lymphoepithelioma-like carcinoma(LELC),a rare and unique variant of liver cancer,can be divided into lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like intrahepatic cholangiocarcinoma.Dense lymphocytic infiltration is its characteristic pathological feature.In recent years,the number of reported cases of this type has increased each year.Studies have shown that lymphoepithelioma-like cholangiocarcinoma occurs more frequently in Asian women;LELC is associated with Epstein–Barr virus infection of liver cells of epithelial origin.Existing research shows that the prognosis of this tumour is good.CASE SUMMARY A 38-year-old female patient was hospitalized after 3 mo of abdominal pain and nausea.She had been infected with hepatitis B virus more than 10 years prior.The patient was hospitalized on January 21,2022.Magnetic resonance imaging showed a 36 mm×28 mm mass under the envelope of the left inner lobe of the liver.No metastasis of lymph nodes or other organs was observed.After left hemihepatectomy,biopsy and immunohistochemistry yielded a final diagnosis of lymphoepithelial hepatocellular carcinoma.After 12 mo of outpatient follow-up and chemotherapy,no tumour metastases were found on the latest computed tomography examination.CONCLUSION Herein,the patient was treated surgically and then followed up as an outpatient for 12 mo.This case will further expand our overall knowledge of the diagnosis and treatment of this rare tumor.

THE INTRACELLULAR FORM OF EPSTEIN-BARR VIRUS GENOME IN NASOPHARYNGEAL CARCINOMA

This work was supported by the National Natural Science Foundation of China (No. 39370766). Object: To study the existent form of EBV genome in nasopharyngeal carcinoma (NPC) biopsies, in a trans planted NPC tumor SUNT 1 and its corresponding epithelial cell line SUNE 1. Methods: By using polymerase chain reaction (PCR) amplification of Epstein Barr virus (EBV) BamHI W fragment, EBV DNA was detected in 20/20 biopsy specimens of poorly differentiated, as well as in a nude mouse xenografted NPC tumor (SUNT 1, from passage 1 to 34) and in the corresponding epithelial cell line (SUNE 1, from passage 1 to 62). The intracellular form of EBV genome was studied by analyzing the terminal structure using a LMP2A probe and an “ in situ lysing gel” technique. Results: A single EBV fused terminal DNA fragment was detected in 19 biopsy specimens, two hybridized bands were seen in one specimen. These results indicate that an episomal form of EBV genome is predominantly present in most NPC biopsy specimens, but insertion of the genome into the host chromosome could not be excluded. Conclusion: The finding suggests that EBV infection precedes clonal amplification of transformed cells, or in a rare case, that a single EBV infected clone is predominant in the development of NPC. Linear form of EBV DNA was detected in the 20th passage of SUNE 1; this may imply the in vitro activation of the productive cycle of EBV.

Tibet in Transition as Seen by Israel Epstein

ICAME upon Israel Epstein’s book Tibet Transformed in early 2014, the only one of his works without a Chinese edition. It mentioned Xizang Minzu University, where I work, several times, which drew me closer to it. I therefore thought of translating the book into Chinese, so that more Chinese readers can learn of the tremendous changes in Tibet since the democratic reform (in 1959) and share the Tibetan people’s joy of a free, happy life under the leadership of the Communist Party of China (CPC).

A Case Report of Pediatric Epstein Barr Virus (EBV) Related Cholestasis from Al-Adan Hospital, Kuwait

Infectious mononucleosis is an acute illness due to Epstein Barr virus infection, which occurs commonly in young adults. Liver involvement in acute EBV infection occurs in up to 95% of patients between the 6th and 15th day of illness and is usually mild [1]. Here we report on a 7-year-old girl treated by Gastroenterology, Hepatology, and Nutrition Unit of Al-Adan Hospital pediatric Department, presented with prolonged fever, lymphadenopathy, generalized edema, hyperbilurubi- nemia and elevated liver enzymes secondary to EBV infection. This case represents a rare presentation of common viral infection in pediatric population.