目的:探讨含培美曲塞(PEM)联合方案治疗原发性中枢神经系统淋巴瘤(PCNSL)的有效性和安全性.方法:收集16例中枢神经系统淋巴瘤患者的资料,其中7例已接受一线方案化疗后复发,9例为初治患者.化疗方案为PEM 600 mg/m2静脉滴注,第1天;联合伊达比星(IDA)和地塞米松(DXM),或福莫司汀(FTM)和DXM,或替莫唑胺(TMZ)和DXM.结果:7例复发难治患者均完成至少2个周期的化疗,部分缓解(PR)3例,稳定(SD)3例,病情进展(PD)1例(该例死亡).9例初治患者均完成至少4个周期的化疗,完全缓解1例,PR4例,SD3例,PD1例.主要不良反应为骨髓抑制,无因严重不良反应导致停药者,患者耐受性好.结论:含PEM联合方案对于PC-NSL具有较好安全性和临床治疗活性.

Objective: To study the expressions of telomerase reverse transcriptase (hTERT), vascular endothelial growth factor (VEGF), Ret and P53, and their relationship to various pathological factors in different pathological types of thyroid carcinoma (TC) patients. Method: Paraffin-embedded pathological specimens of thyroid carcinoma (174) and 40 normal hypothyroid tissue specimens preserved in the Pathology Department from July 2012 to June 2017, were used in the study. The expressions of hTERT, VEGF, Ret and P53 were assayed using immunohistochemical staining in order to analyze their association with pathological types, ages, tumor diameters, lymphatic metastasis and TNM tumor stage of the TC patients. Results: The expressions of hTERT, VEGF, Ret and P53 were 79.89, 78.16, 70.69 and 81.03%, respectively, and significantly higher than the corresponding expressions in normal hypothyroid tissue (p<0.05). The positive expressions of hTERT and VEGF were associated with tumor diameter, while VEGF and Ret expressions were related to lymphatic metastasis; hTERT, VEGF, Ret and P53 expressions were associated with TNM tumor stage (p<0.05). However, there was no association between the expressions of hTERT, VEGF, Ret and P53, and age and tumor pathology (p>0.05). Conclusion: The increased positive expressions of hTERT, VEGF, Ret and P53 in thyroid carcinoma are of clinical significance, and can aid in early diagnosis of thyroid carcinoma.

目的 晚期乳腺癌患者一般体质较弱,既往治疗失败后,对化疗耐受性差、效果不明显,因此寻找疗效好、不良反应轻的新药尤为重要.本研究对阿帕替尼治疗晚期乳腺癌疗效及安全性进行分析.方法 回顾性分析2016-09-06-2018-03-10郑州大学第一附属医院收治的47例既往化疗失败或复发转移后使用阿帕替尼的晚期乳腺癌患者临床资料,分析阿帕替尼单药(17例)和联合化疗(30例)患者的无进展生存期(progression free survival,PFS)、客观有效率和疾病控制率.结果 Kaplan-Meier法分析结果显示,47例晚期乳腺癌患者的中位PFS为113 d(95.54～130.46).17例阿帕替尼单药组患者中位PFS为90 d,30例阿帕替尼联合化疗组患者中位PFS为113 d,差异无统计学意义,P=0.672.治疗后部分缓解(partial response,PR)6例,疾病稳定(stable disease,SD)31例,疾病进展(progressive disease,PD)10例,客观有效率(objective response rate,ORR)为12.77％,疾病控制率(disease control rate,DCR)为78.72％,两组ORR(P=1.000)和DCR(P=0.512)差异均无统计学意义.多因素Cox回归结果显示,雌激素受体(estrogen receptor,ER)阳性表达(HR=0.429,95 ％％CI:0.204～0.905,P=0.026)、治疗期间出现高血压(HR=0.452,95％CI:0.232～0.881,P=0.020)是影响阿帕替尼治疗晚期乳腺癌PFS的预后保护性因素;既往化疗次数≥4次(HR=2.197,95％CI:1.163～4.418,P=0.015)是其预后危险性因素.不良反应大多数为轻中度(1～2级),经处理可以好转或耐受.结论 阿帕替尼治疗晚期乳腺癌有一定疗效,不良反应可控,耐受性好,但尚需扩大样本进一步验证.

目的探讨程序性细胞死亡蛋白-1（programmed cell death protein 1，PD-1）、程序性细胞死亡蛋白-2配体（programmed death-ligand 2，PD-L2）及程序性细胞死亡蛋白-1配体（programmed death-ligand 1，PD-L1）在EB病毒（Epstein-Barr virus，EBV）阳性T/NK淋巴组织增殖性疾病[Epstein-Barr virus-positive T/natural killer（NK）-cell lymphoproliferative disease，EBV（+）-T/NKLPD]中的表达及临床意义。 方法收集2013年1月至2017年12月郑州大学第一附属医院17例EBV（+）-T/NK-LPD患者的病理石蜡包埋组织，其中男性12例，女性5例，年龄为10~82岁，平均年龄29岁，Ⅰ级4例，Ⅱ级7例，Ⅲ级3例，种痘水疱病样淋巴组织增殖性疾病3例。采用免疫组织化学SP法检测PD-1、PD-L1和PD-L2在人EBV（+）-T/NK-LPD组织中的表达，并采用Fisher确切概率法、Spearman秩相关，分析其与临床病理学参数、病理分级及患者预后之间的关系。 结果在17例组织标本中，PD-1表达阳性12例，PD-L1表达阳性6例，PD-L2表达阳性5例。PD-1、PD-L2的表达与预后无显著相关性（P>0.05），PD-L1的表达与预后呈正相关（P 0.05）。PD-1及PDL2的表达与病理分级之间无显著相关性（r=0.141，r=-0.149，均P>0.05），而PD-L1的表达与病理分级之间呈负相关（r=-0.563），PD-L1的表达与病理分级之间的相关关系具有统计学意义（P 结论PD-1、PD-L1和PD-L2在EBV（+）-T/NK-LPD病理组织中异常表达，虽然PD-1的表达与预后、病理分级之间无显著相关性，但在EBV（+）T/NK-LPD中显著高表达，PD-1/PD-Ls信号通路可能成为EBV（+）-T/NK-LPD免疫治疗的潜在新靶点。

Background Extranodal NK/T-cell lymphoma, nasal type (ENKL) is a distinct clinicopathological entity and EBV-associated disease that is highly aggressive. Many patients had failed to respond to conventional chemotherapy or relapsed after treatment. Multi-drug resistance is a major cause that leads to these desperate failures. However, the specific mechanism of drug resistance is still unclear. Methods In the previous study, we firstly developed a doxorubicin-resistant ENKL cell line known as SNK-6/ADM, and then a small quantity of side population (SP) cells were derived from SNK-6/ADM and named SNK-6/ADM-SP. In order to explore the biological characteristics and mechanism of drug-resistance of these cells, SNK-6, SNK-6/ADM and SNK-6/ADM-SP cells were utilized to evaluate potentially differences of chemotherapy resistance index (RI), morphology, proliferation, cell cycles, expression of ATP-binding cassette (ABC) transporters (ABCG1, ABCG2 and ABCC4) and surface markers, cytokine sensitivity, and situation of EBV infection. Results We identified SNK-6/ADM-SP is a specific multidrug resistant cell population with a higher level of RI than SNK-6/ADM. Relevant evaluations showed that SNK-6/ADM-SP presented a series of conserved biological behaviors including relatively poor proliferation ability, high expression of ABCG2, weak sensitivity to IL-15 which could stimulate normal ENKL cells’ proliferation and differentiation, and EBV inhibition with low level of EBV-DNA replication and EBV-antigen expression. Conclusions This discovered cellular heterogeneity of ENKL could provide a new perspective to better understand the mechanisms of drug resistance and overcome elusive response to chemotherapy of ENKL.

目的:分析非上呼吸消化道来源的结外NK/T细胞淋巴瘤(non-upper aerodigestive tract extranodal NK/T-cell lymphoma,NU?AT-ENKTCL)的不良预后因素.方法:回顾性分析郑州大学第一附属医院2011年1月至2015年12月收治的20例NUAT-NKTCL患者临床资料,采用Kaplan-Meier法进行生存分析,应用Log-Rank法检验对EBER表达、年龄、性别、乳酸脱氢酶(lactic dehydro?genase,LDH)水平和治疗前外周血EBV-DNA拷贝数等进行单因素分析.结果:20例患者中,男女比为13:7.中位年龄为39(12～66)岁,其中≥60岁3例(15％),<60岁17例(85％).Ann Arbor分期:Ⅰ、Ⅱ期8例(40％),Ⅲ、Ⅳ期12例(60％).LDH水平升高12例(60％).治疗前外周血EBV-DNA拷贝数增加11例(55％).病变组织中EBER(+)13例(65％).患者截至随访时间死亡4例,生存16例,中位总生存期(median overall survival,mOS)为15.4个月,中位无进展生存期(median progression free survival,mPFS)为8个月.完全缓解(complete response,CR)11例(55％),部分缓解(partial response,PR)5例(25％),客观缓解率(objec?tive response rate,ORR)为80％.单因素分析显示年龄与预后呈显著相关性.结论:EBER的表达并不影响NUAT-ENKTCL患者的预后,年龄≥60岁患者预后较差.

To investigate the presence of integrated Epstein-Barr virus (EBV) DNA in the NK/T cell lymphoma (NKTCL) ge-nome and analyze the integration information in the genome of NKTCL cell lines. Methods: PCR and in situ hybridization were used to detect EBV infection in five EBV (+) NK/T samples and four EBV (-) NK/T samples provided by the biobanks of the First Affiliated Hospi-tal of Zhengzhou University. Whole-genome DNA of the samples was sequenced and subjected to bioinformatics analysis. Whole-ge-nome sequence alignment was used to identify the EBV integration sequence. BLAST analysis was used to compare EBV fasta files of the samples and EBV fasta library. CREST software was used to extract softclip reads, filter all paired reads, and enumerate their distri-bution on chromosomes. The integrated genomics viewer (IGV) was used to compare the distribution of reads in partial regions of chromosome. PCR was used to amplify the high-frequency integration region of the EBV DNA. The amplified fragments were sanger se-quenced. Results: EBV DNA and EBER expression were detected in five EBV (+) NK/T samples but not in the four EBV (-) NK/T samples. Sequencing depth, coverage depth, proportion of coverage, and proportion of alignment all met the requirements for subsequent re-search. Sequence alignment revealed that the captured sequences were viral sequences. Filtered reads were most numerous in EBV (+) NKTCL cell line SNK, YTS, and EBV (+) nasal NKTCL tissue. The reads were non-randomly enriched in chromosome 2. EBV DNA inte-gration in the 400 bp region of chr2:30234084-30234483 caused insertion or deletion in the chr2p23.1 site. Conclusions: EBV DNA is highly integrated in the chr2p23.1 site of EBV (+) NKTCL cells and may affect the expression of related genes.

This study aimed to analyze the clinical characteristics and prognostic factors of patients, divided into over 40-year-old group or not, with precursor T-cell lymphoblastic lymphoma (Pre-T-LBL). Based on the retrospective analysis of the clinical data of 59 patients with Pre-T-LBL during the period from December 2010 to December 2015, albumin level, anemia, pleural or pericardial effusion, protocol, therapy response, mediastinal mass, lactate dehydrogenase (LDH), and international prognostic index (IPI) or age-adjusted international prognostic index (aaIPI) were summarized. For patients aged <40 years, factors correlating with poor progression-free survival (PFS) were pleural or pericardial effusion, regimen, albumin level and therapy response. Pleural or pericardial effusion, aaIPI score, regimen, LDH increased, albumin level, therapy response and mediastinal mass were all related with poor overall survival (OS). In the patients aged ≥40 years, only anemia associated with PFS. However, anemia, involvement of bone marrow and therapeutic response were all related with poor OS. In conclusion, the patients with Pre-T-LBL are characterized by a low incidence and bad prognosis. Different prognostic factors can be discovered for patients over 40-year-old with Pre-T-LBL comparing to the youngers. New prognostic evaluation factors should be explored for patients ≥40 years old.