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The development of premature coronary artery disease (PCAD) is dependent on both genetic predisposition and traditional risk factors. Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies. Genome-wide association studies (GWASs) have identified a considerable number of common genetic variants that are associated with PCAD. Most of these genetic variants are attributable to lipid and blood pressure-related single-nucleotide polymorphisms (SNPs). The genetic variants that predispose individuals to developing PCAD may depend on race and ethnicity. Some characteristic genetic variants have been identified in Chinese populations. Although translating this genetic knowledge into clinical applications is still challenging, these genetic variants can be used for CAD phenotype identification, genetic prediction and therapy. In this article we will provide a comprehensive review of genetic variants detected by GWASs that are predicted to contribute to the development of PCAD. We will highlight recent findings regarding CAD-related genetic variants in Chinese populations and discuss the potential clinical utility of genetic variants for preventing and managing PCAD.

To improve the hydrophobicity and biological activity of corn starch, starch ferulate was prepared by Novozym 435 lipase catalyzed transesterification of ultrasonic pretreated corn starch and ethyl ferulate. The ferulic acylation of starch was confirmed by UV and Fourier transform infrared spectroscopy (FT-IR). Starch ferulate was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimeter (DSC). In addition, the hygroscopicity and free radical scavenging ability of esterified starch (ES) were evaluated. In the results, the maximum degree of substitution (DS) of ES was 0.0728 under the optimal ultrasonic pretreatment conditions, which was much higher than that of 0.0142 without ultrasonic pretreatment. The XRD and DSC analysis showed that ferulic acylation destroyed the crystalline structure of corn starch to a certain extent. Moreover, ferulic acylation can improve the hydrophobicity and free radical scavenging ability of starch. In conclusion, ES obtained with ultrasonic pretreatment followed by enzyme catalysis can improve physical and chemical properties of starch. Ultrasonic provides an effective method for synthesizing high-quality modified starch and lays a theoretical foundation for expanding the application of corn starch.

To screen the differential expression of diffuse large B-cell lymphoma (DLBCL) autophagy-related gene (ARG), explore the mechanism of differential expression of autophagy gene (DEARG) in the occurrence and development of DLBCL and establish a prognostic model.Using the NCICCR database containing clinical information and gene expression profile data of 481 patients with DLBCL and the HADb database containing 232 ARGs, the differential expression of ARG in DLBCL was determined by R language, the relationship between ARG and the occurrence and development of DLBCL was analyzed by GO and KEGG, the polygene prognostic model was established by Cox regression algorithm, the survival curve was drawn by Kaplan-Meier method, and the reliability of the prognostic model was evaluated by ROC curve.A total of 122 DEARGs were extracted from lymph node samples of 481 patients with DLBCL and 5 normal lymph nodes, including 4 up-regulated genes and 118 down-regulated genes. GO enrichment mainly focused on ontological annotations such as mitochondrial autophagy, autophagy regulation, and cell response to external stimuli. KEGG enrichment was mainly concentrated in cell senescence, NOD-like receptor signal pathway, PI3K-Akt signal pathway, and PD-1/PD-L1 signal pathway. Survival analysis was performed on 230 samples with complete clinical information. Univariate Cox analysis showed that 20 ARGs were significantly correlated with overall survival of DLBCL patients. Nine prognostic ARGs (HIF1A, CAPN1, ITPR1, PRKCQ, TRAIL, HDAC1, TSC2, NRG3, and MAPK3) were screened by multivariate Cox regression to establish DLBCL ARG prognostic model. Kaplan-Meier survival curve analysis showed that there was significant difference in survival rate between high risk group and low risk group (P0.001). Multivariate Cox regression analysis showed that international prognostic index and risk value were independent prognostic indicators of DLBCL patients (P0.05), the area under ROC curve was 0.762 and 0.747, respectively.DLBCL ARG prognostic model can be used to predict the prognosis of patients, but it still needs to be confirmed by a large sample of clinical studies.弥漫大B细胞淋巴瘤预后相关差异表达自噬基因筛选及模型的建立.筛选弥漫大B细胞淋巴瘤（DLBCL）自噬相关基因（ARG）的差异表达，探讨差异表达自噬基因 （DEARG）在DLBCL发生发展中的作用机制并建立预后模型。.利用包含481例DLBCL患者临床信息及基因表达谱数据的NCICCR数据库与包含232个ARG的HADb数据库，通过R语言确定DLBCL中ARG的差异表达，GO和KEGG分析ARG与DLBCL发生发展的关系，Cox回归算法建立多基因预后模型，Kaplan-Meier方法绘制生存曲线，ROC曲线评价预后模型的可靠性。.从481例DLBCL患者淋巴结样本及5例正常淋巴结样本中共提取DEARG 122个，其中上调基因4个，下调基因118个。GO富集主要集中在线粒体自噬、自噬调节、细胞对外部刺激的反应等本体学注释。KEGG富集主要集中在细胞衰老、NOD样受体信号通路、PI3K-Akt信号通路、PD-1/PD-L1信号通路等。对230个临床信息完整的样本进行生存分析，单因素Cox分析发现20个ARG与DLBCL患者整体生存明显相关，多因素Cox回归筛选出9个预后相关ARG（HIF1A、CAPN1、ITPR1、PRKCQ、TRAIL、HDAC1、TSC2、NRG3和MAPK3）建立DLBCL ARG预后模型。Kaplan-Meier生存曲线分析显示，高、低风险组患者的生存率比较具有显著差异（P0.001）。多因素Cox回归分析结果表明，国际预后指数和风险值是DLBCL患者的独立预后指标（P0.05），ROC曲线下面积分别为0.762和0.747。.DLBCL ARG预后模型可用于预测患者的预后，但仍需大样本的临床研究加以证实。.

This article summarizes the background, specific conditions, main measures, steps and effects of the implementation of Mass Drug Administration (MDA) to control the local P. vivax malaria epidemic in Anhui Province in central China. Distributing medicines to the designated population quickly controlled the local epidemic of P. vivax. Implementing MDA to control P. vivax ensured the correct selection of medicines, clarification of the targeted population for receipt of medicines, and assurance of a high rate of compliance through government support and health education. These results provide a reference for countries and regions experiencing similar events and planning to implement MDA in malaria control.

Most acute promyelocytic leukemia cases are characterized by the PML-RARa fusion oncogene and low white cell counts in peripheral blood.Based on the frequent overexpression of miR-125-family miRNAs in acute promyelocytic leukemia, we examined the consequence of this phenomenon by using an inducible mouse model overexpressing human miR-125b.MiR-125b expression significantly accelerates PML-RARa-induced leukemogenesis, with the resultant induced leukemia being partially dependent on continued miR-125b overexpression. Interestingly, miR-125b expression led to low peripheral white cell counts to bone marrow blast percentage ratio, confirming the clinical observation in acute promyelocytic leukemia patients.This study suggests that dysregulated miR-125b expression is actively involved in disease progression and pathophysiology of acute promyelocytic leukemia, indicating that targeting miR-125b may represent a new therapeutic option for acute promyelocytic leukemia.

To evaluate the efficacy and safety of CHOP regimen based on doxorubicin hydrochloride liposome in the initial treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL).Thirty-one patients with DLBCL treated from January 1, 2012 to December 31, 2019 were analyzed retrospectively, their median age was 83 (71-95) years old, and all of them were in Ⅲ-Ⅳ stage, including 17 cases who had international prognostic index (IPI) ≥ 3. The patients were treated with R-CHOP and CHOP regimens based on doxorubicin hydrochloride liposome. The efficacy and safety were evaluated during and after treatment.A total of 219 chemotherapy cycles and 7 median cycles were performed in 31 patients. The overall response (OR) rate and complete remission (CR) rate was 80.7% (25/31) and 61.3% (19/31), respectively, as well as 2 cases (6.5%) stable, 4 cases (12.9%) progressive. The main toxicities were as follows: the incidence of grade Ⅲ -Ⅳ neutropenia was 29% (9/31); two patients (6.5%) developed degree Ⅰ-Ⅱ cardiac events, which were characterized by new degree Ⅰ atrioventricular block; there were no cardiac events requiring emergency treatment and discontinuation of chemotherapy. The 1-year, 2-year and 3-year overall survival rate was 83.9%, 77.4% and 61.3%, respectively. The 1-year, 2-year and 3-year progression-free survival rate was 77.4%, 64.5% and 61.3%, respectively.The chemotherapy regimen based on doxorubicin hydrochloride liposome has better efficacy and higher cardiac safety for elderly patients with DLBCL.以盐酸多柔比星脂质体为基础的CHOP联合方案治疗初治高龄弥漫大B细胞淋巴瘤患者的回顾性研究.评价以盐酸多柔比星脂质体为基础的CHOP联合方案治疗初治高龄弥漫大B细胞淋巴瘤（DLBCL）患者的有效性和安全性.回顾性分析2012年1月1日至2019年12月31日本中心血液科收治的初治DLBCL患者31例，中位年龄为83（71-95）岁，均为Ⅲ-Ⅳ期患者，国际预后指数≥3分患者为17例。治疗方案采用以盐酸多柔比星脂质体为主的R-CHOP及CHOP方案。在治疗过程中和治疗后对其疗效和安全性进行评价.31例患者共进行219个化疗周期，中位周期7个，总缓解率和完全缓解率分别为80.7%（25/31）和61.3%（19/31），疾病稳定2例（6.5%），疾病进展4例（12.9%）。主要毒副反应为：Ⅲ-Ⅳ级中性粒细胞减少症发生率为29%（9/31）；2例（6.5%）患者出现Ⅰ-Ⅱ度心脏事件，表现为新发的Ⅰ度房室传导阻滞；未出现需要紧急治疗和中止化疗的心脏事件。1、2、3年的总生存率分别为83.9%、77.4%和61.3%，无进展生存率分别为77.4%、64.5%和61.3.对于高龄DLBCL患者，以盐酸多柔比星脂质体为主的化疗方案疗效较好，患者心脏安全性较高.

Decitabine is used to treat myelodysplastic syndrome (MDS). This meta-analysis evaluated the efficacy and safety of different dosing regimens of decitabine in treating intermediate and/or high-risk MDS. Medline, Cochrane, EMBASE, and Google Scholar databases were searched up to October 23, 2015. Randomized controlled trials, prospective, cohort, and case series studies were included. Fifteen studies were included with a total of 1378 patients. The decitabine 100 mg/m2/course dosing regimen had a greater overall response rate than the 60–75 mg/m2/course (51 vs. 25%; P = 0.003). It also had higher complete response rate compared with the 135 mg/m2/course regimen (24.2 vs.13.7%; P = 0.016). The three dosing regimens were similar with respect to bone marrow complete response and partial response and hematologic improvement (P values > 0.05). Decitabine 135 mg/m2/course regimen had similar hematologic improvement as best supportive care (P = 0.066). The incidence of neutropenia, thrombocytopenia, infections, and anemia was similar across treatment groups (range, 31 to 38%; P values ≥ 0.899). The 100 mg/m2/course decitabine regimen showed benefit with respect to overall response rate compared with the 60–75 mg/m2/course regimen, as well as greater improvement in complete response rate compared with the 135 mg/m2/course regimen. All three dosing regimens had similar frequency of adverse events.

To screen genes associated with poor prognosis of hepatocellular carcinoma (HCC) and to explore the clinical significance of these genes.The proper expression profile data of HCC was obtained from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) were identified by differential expression analysis. The DAVID and String database were used for function enrichment analysis and to construct the protein-protein interaction (PPI) network respectively. The Cancer Genome Atlas (TCGA) database and the Cox Proportional Hazard Model were used for prognosis analysis of the DEGs.A eligible human HCC data set (GSE84402) met the requirements. A total of 1141 differentially expressed genes were identified, including 720 up-regulated and 421 down-regulated genes. The results of function enrichment analysis and PPI network performed that CDK1、CDC6、CCNA2、CHEK1、CENPE 、PIK3R1、RACGAP1、BIRC5、KIF11 and CYP2B6 were prognosis key genes. And the prognosis analysis showed that the expressions of CDC6、PIK3R1、KIF11 and RACGAP1 were increased, and the expression of CENPE was decreased, which was closely related to prognosis of HCC.CDC6、CENPE、PIK3R1、KIF11 and RACGAP1 may be closely related to poor prognosis of HCC, and can be used as molecular biomarkers for future research of HCC prognosis.

To investigate the prognosis-related miRNA histological features and clinical significance of lung adenocarcinoma.Using The Cancer Genome Atlas (TCGA) data, the miRNA expression profile data of human lung adenocarcinoma were searched for differential analysis, and the prognosis-related miRNAs were screened by Cox risk regression model. The targeted miRNAs were predicted by mirwalk analysis platform, KEGG functional enrichment analysis, and finally, predict the function of prognosis-related miRNAs.A total of 46 differential miRNAs in lung adenocarcinoma were screened, including 19 up-regulated and 27 down-regulated. Six prognostic-related miRNAs were screened by Cox survival analysis, namely hsa-mir-21, hsa-mir-142, hsa-mir-200a high expression, hsa-mir-101, hsa-let-7c, hsa-mir-378e low expression, hsa-mir-21 and hsa-mir-378e were associated with poor prognosis in patients with lung adenocarcinoma, and the survival time was shortened significantly (Hsa-mir-21 and hsa-mir-378e are associated with poor prognosis of lung adenocarcinoma, and may be used as a molecular marker for prognosis of lung adenocarcinoma after further clinical verification.

To analyze the molecular markers associated with occurrence, development and poor prognosis of acute myeloid leukemia (AML) by using the data of GEO and TCGA database, as well as multiomics analysis.The transcriptome data meeting requirements were down-loaded from GEO database, the differentially expressed genes were screened by using the R language limma package, and the GO function enrichment analysis and KEGG pathway analysis were performed for differentially expressed genes, at the same time, the protein interaction network was contracted by using STRING database and cytoscape software to screen out the hub gene, then the prognosis analysis was carried out for hub gene by combination with the clinical information affected in TCGA database.620 differentially expressed genes were screened out, among which 162 differentially expressed genes were up-regulated, and 458 differentially expressed genes were down-regulated. Based on the results of GO functional enrichment, the KEGG pathway enrichment and protein interaction network, CXCL4, CXCR4, CXCR1, CXCR2, CCL5 and JUN were selected as hub genes. The survival analysis showed that the high expression of CXCL4, CXCR1, and CCL5 was a risk factor for poor prognosis of patiants.CXCL4, CXCR1 and CCL5 can be used as biomarkers for the occurrence and development of AML, which relateds with the unfavorable prognosis and can provide a basis for further study.急性髓系白血病患者预后不良相关基因的多组学分析.利用GEO数据库和 TCGA数据库的数据，通过多组学分析方法分析与急性髓系白血病（acute myeloid leukemia，AML）发生、发展及不良预后相关的分子标志物。.从GEO数据库下载符合要求的转录组数据，运用R语言Limma程序包进行差异表达基因的筛选，并对差异表达基因进行GO功能富集分析和 KEGG 通路富集分析，同时使用STRING数据库数据，利用Cytoscape软件构建蛋白质相互作用网络，筛选出hub gene，结合TCGA 数据库附带的临床信息对hub gene进行预后分析。.共筛选出620个差异基因，上调的差异表达基因162个，下调的差异表达基因458个。综合GO功能富集、KEGG 通路富集分析及蛋白相互作用网络结果，筛选出CXCL4、CXCR4、CXCR1、CXCR2、CCL5、JUN为hub gene。生存分析显示，CXCL4、CXCR1、CCL5高表达是患者预后不良的危险因素。.CXCL4、CXCR1、CCL5可以作为AML发生、发展的相关生物标志物，且与不良预后相关，这可以为进一步研究提供依据。.

Amifostine is a cytoprotective drug that was initially used to control and treat nuclear radiation injury and is currently used to provide organ protection in cancer patients receiving chemotherapy. Clinical studies have also found that amifostine has some efficacy in the treatment of cytopenia caused by conditions such as myelodysplastic syndrome and immune thrombocytopenia, both of which involve megakaryocyte maturation defects. We hypothesized that amifostine induced the differentiation of megakaryocytes and investigated this by exposing the human Dami megakaryocyte leukemia cell line to amifostine (1 mmol/L). After 12 days of amifostine exposure, optical microscopy showed that the proportion of Dami cells with diameters >20 μm had increased to 24.63%. Transmission electron microscopy identified the development of a platelet demarcation membrane system, while flow cytometry detected increased CD41a expression and decreased CD33 expression on the Dami cell surface. Ploidy analysis found that the number of polyploid cells with >4N DNA content increased to 27.96%. We did not detect any elevation in the mRNA or protein levels of megakaryocytic differentiation‐associated transcription factors GATA‐binding factor 1 (GATA‐1) and nuclear factor, erythroid 2 (NF‐E2), but nuclear import assay revealed an increased nuclear translocation of these proteins. These findings indicate that amifostine induced the differentiation of Dami cells into mature megakaryocytes via a mechanism involving increased nuclear translocation of the transcription factors, NF‐E2 and GATA‐1.

Objective This study was performed to examine the treatment regimen used for an elderly patient with diffuse large B-cell lymphoma (DLBCL) complicated with renal dysfunction. Case report An 85-year-old man presented with nasal and sinus disorders in May 2018. He was also found to have renal insufficiency caused by long-term consumption of compound aminopyrine phenacetin tablets. Physical examination revealed irritation of the nasal mucous membrane on the right side and dark red nasal passages with a smooth surface. The right side of the neck contained several small peanut-sized lymph nodes. A biopsy of the right nasal neoplasm revealed germinal center type DLBCL. The mini–rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone regimen (mini-R-CHOP) was administered as the main chemotherapy regimen. Additionally, the use of thrombopoietin prevented further deterioration in renal function. This individualized treatment program helped the patient to achieve complete remission. The creatinine level decreased and was well maintained. Conclusion The mini-R-CHOP and rituximab cross-use regimen was found to be safe in an elderly patient with chronic renal insufficiency. Thrombopoietin exerted a protective effect on renal function.

Regulatory T (Treg) cells are crucial players in the prevention of autoimmunity. Mechanistic target of rapamycin (mTOR) signalling negatively controls the development and function of Treg cells. The aim of the present study was to evaluate the effects of rapamycin, under the generic name sirolimus, on CD4+CD25+FoxP3+ Treg cells in rheumatoid arthritis (RA) patients with low disease activity or in DAS28 remission.Fifty-five RA patients and 60 healthy controls were enrolled in this study. All patients had previously received conventional disease-modifying anti-rheumatic drugs (DMARDs) and were considered to have a low DAS28 score (≤3.2). Peripheral blood samples and clinical information were obtained at baseline and following 6 and 12 weeks of sirolimus treatment, or after 12 weeks of conventional treatment. Peripheral blood samples were also obtained from the healthy controls. The circulating levels of lymphocyte subpopulations were assessed by flow cytometry.Thirty-five patients received sirolimus and 20 patients continued treatment with conventional DMARDs. The absolute counts and proportions of CD4+CD25+FoxP3+ Treg cells were significantly lower in all RA patients with DAS28 ≤ 3.2 as compared with those in healthy controls. By contrast, the difference in circulating Th17 cell numbers was not significant. Sirolimus administration resulted in elevations in circulating Treg cell numbers and significant reductions in the Th17/Treg cell ratio, whereas the circulating level of Treg cells and the Th17/Treg cell ratio in patients under conventional treatment both showed a tendency of reduction. Furthermore, a greater proportion of patients under sirolimus treatment achieved DAS28-based remission at 12 weeks.Sirolimus can favourably expand Treg cells in RA patients with DAS28 ≤3.2, consequently restoring a healthy balance of Th17/Treg cells, which might improve the likelihood of long-term and sustained clinical remission and reduce the probability of disease flare-ups in RA.

// Qian Mei 1,2,* , Meixia Chen 1,2,* , Xuechun Lu 1,2,* , Xiang Li 1,2 , Feng Duan 3 , Maoqiang Wang 3 , Guangbin Luo 1,4,* and Weidong Han 1,2 , * 1 Department of Molecular Biology, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China 2 Department of Bio-therapeutic, School of Life Sciences, Chinese PLA General Hospital, Beijing, P. R. China 3 Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, P. R. China 4 Department of Genetics and Genome Sciences, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA * These authors have contributed equally to this work Correspondence to: Weidong Han, email: // Guangbin Luo, email: // Keywords : decitabine, lower dose, advanced hepatocellular carcinoma, hepatotoxicity, phase I/II Received : September 19, 2014 Accepted : March 04, 2015 Published : March 29, 2015 Abstract Purpose: We conducted this phase I/II clinical trial to determine the safety and efficacy of lower-dose decitabine based therapy in pretreated patients with advanced HCC. Experimental Design: Patients with advanced HCC were eligible. The administered dose of decitabine was 6 mg/m 2 /d intravenously on days 1 to 5 of a 28-day cycle. Additional therapies were given based on their disease progression status. The endpoint was to ensure the safety, hepatotoxicity, clinical responses, progression-free survival (PFS) and pharmacodynamics assay of lower-dose decitabine. Results: Fifteen patients were enrolled. The favorable adverse events and liver function profiles were observed. The most beneficial responses were 1 complete response (CR), 6 stable disease (SD) and 8 progressive disease (PD). MRI liver scans post-treatment indicated a unique and specific characteristic. The immunohistochemistry result from the liver biopsy exhibited noteworthy CTL responses. Median PFS was 4 months (95% CI 1.7, 7), comparing favorably with existing therapeutic options. Expression decrement of DNMT1 and global DNA hypomethylation were observed in PBMCs after lower-dose decitabine treatment. Conclusion: The lower-dose decitabine based treatment resulted in beneficial clinical response and favorable toxicity profiles in patients with advanced HCC. The prospective evaluations of decitabine administration schemes and tumor tissue-based pharmacodynamics effect are warranted in future trials.

Based on evidence that low-dose interleukin-2 (IL-2) increases CD4+CD25+FOXP3+ Treg (CD4Treg) cells in patients with graft-versus-host disease, induction of autoimmune tolerance has been proposed as a treatment.1 However, evidence-based guidelines for the management of primary Sjogren’s syndrome (pSS) are lacking.2 Using a modified method of flow cytometry, we aimed to revaluate the exact levels of Th17 and CD4Treg cells in the peripheral blood (PB) of patients with pSS and explore the effects of short-term and low-dose IL-2.3 4 A total of 190 patients with pSS (169, treated with immunosuppressants; 21, new-onset (sampled as treated or new pSS patients below)) consented at enrolment to donate PB samples for comprehensive immunophenotyping (see online supplementary table S1 and figure S1). In the study, BD Trucount tubes were used to determine the absolute counts of total CD4+ T cells in the PB, and then, the absolute number of CD4+ T subsets, such as CD4Treg cells, were calculated. Detailed methods and statistical analysis is in online version (see online supplementary text). ### Supplementary file 11 [annrheumdis-2018-213036-SP11.docx] Among the CD4+ T subsets in the PB of the healthy control …

We compared the safety and efficacy of haploidentical stem cell transplantation (haplo-SCT) to matched donor SCT (matched-SCT) in treating hematological malignancies. The Medline, Cochrane, EMBASE, and Google Scholar databases were searched through 21 June 2017 using the search term "(hematological disease) AND matched AND (haploidentical OR haplo-identical OR haplo identical OR haplo transplantation OR haplo transplant OR haplo-SCT OR haplo-HSCT OR haplo-HCT)." Twenty-five studies enrolling 11,359 patients (haplo-SCT: 2677; matched-SCT: 8682) were included. The primary outcomes were acute and chronic graft-versus-host disease (GVHD), non-relapse mortality, and 1-year cumulative incidence of relapse. Haplo-SCT was associated with similar risks as matched-SCT for all primary endpoints. Subgroup analysis of patients who received a matched-SCT from a related donor revealed that patients who received haplo-SCT had a lower risk of acute GVHD. Among patients who received reduced-intensity conditioning (RIC), those who received haplo-SCT had a higher risk of acute grade II-IV GVHD and non-relapse mortality than did patients who received a matched-SCT from a related or unrelated donor. Haplo-SCT should continue to be considered as a safe and effective transplant option when a matched donor is unavailable, but it may not be suitable for patients who receive RIC.

PURPOSE Our purpose was to investigate the relationship between intake of excess free fructose beverages and allergy among children and adolescents. METHODS We analyzed data of 860 children (aged 6 to 12 years) and 1,142 adolescents (aged 13 to 19 years) from the National Health and Nutrition Examination Survey 2005-2006. Logistic regression analyses were performed to determine the associations between consumption of excess free fructose beverages and allergic symptoms or allergic sensitization. RESULTS The pattern of findings was not entirely consistent, but some analyses supported the hypothesis of an association between intake of excess free fructose beverages and allergy. After controlling for the potential confounders, children who consumed nondiet fruit drinks at least 5 times per week had a nearly 2.5-fold greater odds of allergic sensitization than did those who consumed such drinks only 1 to 3 times per month (OR = 2.446; 95% CI, 1.583-3.780). Adolescents who consumed excess free fructose beverages at least 5 times per week or 1 to 4 times per week had about fivefold greater odds of presence of allergic symptoms than did those who seldom consumed these beverages (OR = 5.164; 95% CI, 1.866-14.297 and OR = 4.112; 95% CI, 1.857-9.107, respectively). Adolescents who consumed apple juice at least 5 times per week had a twofold greater odds of presence of allergic sensitization than did the seldom consumers (OR = 2.215; 95% CI, 1.178-4.164). CONCLUSIONS These findings provide some support for the hypothesis of a link between intake of excess free fructose beverages and allergic symptoms or allergic sensitization in children and adolescents.

Ruili Yu,1 Bo Yang,2 Xiaohua Chi,3 Lili Cai,4 Cui Liu,5 Lei Yang,6 Xueyan Wang,1 Peifeng He,7 Xuechun Lu2 1Department of Allergy, Beijing Shijitan Hospital, Affiliated to Capital Medical University, 2Department of Geriatric Hematology, Chinese PLA General Hospital, 3Department of Pharmacy, Chinese PLA Rocket Force General Hospital, 4Department of Geriatric Laboratory Medicine, 5Department of Geriatric Ultrasound, 6Medical Department, Nanlou Clinic, Chinese PLA General Hospital, Beijing, 7School of Medical Information Management, Shanxi Medical University, Taiyuan, People’s Republic of China Abstract: This study was designed to evaluate the efficacy and safety of cytokine-induced killer (CIK) cell-based immunotherapy as an adjuvant therapy for hepatocellular carcinoma (HCC). Published studies were identified by searching Medline, Cochrane, EMBASE, and Google Scholar databases with the keywords: cytokine-induced killer cell, hepatocellular carcinoma, and immunotherapy. The outcomes of interest were overall survival, progression-free survival, and disease-free survival. Eight randomized controlled trials (RCTs), six prospective studies, and three retrospective studies were included. The overall analysis revealed that patients in the CIK cell-treatment group had a higher survival rate (pooled hazard ratio (HR) =0.594, 95% confidence interval [CI] =0.501–0.703, P

Purpose Elderly acute myelocytic leukemia (AML) patients have limited treatment options because they poorly tolerate standard-dose chemotherapy. The present article describes our experience with ultra-low-dose decitabine combined with infusion of autologous cytokine-induced killer (CIK) cells for 2 elderly patients with myelodysplastic syndrome–transformed AML. Methods Decitabine (10 mg) was given on days 1 to 5, and CIK cells on day 14 with 2 to 8 × 10 9 cells per infusion. Findings The therapeutic regimen resulted in marked hematologic recovery and was associated with better than expected survival in both cases. Implications Our experience suggests that the combination therapy is safe and effective for elderly patients with myelodysplastic syndrome–transformed AML.

Background aims Currently available treatment methods for advanced plasmacytoma include surgery, chemotherapy, radiotherapy, immunomodulatory agents, hematopoietic stem cell transplantation and donor lymphocyte infusion. We report a case of advanced refractory multiple solitary plasmacytomas in a 68-year-old Asian man with multiple bone lesions, in whom autologous cytokine-induced killer (CIK) cells were administered in an effort to eliminate residual tumor lesions. Methods CIK cells were infused monthly for 21 courses. Results The patient has survived 63 months since the first hospital visit without disease progression for 40 months. Conclusions This case represents the first report of autologous CIK cell immunotherapy used successfully to suppress multiple solitary plasmacytomas and resolve bone lesions.

Objective: To examine the efficacy and adverse events of recombinant human thrombopoietin (rhTPO) in the treatment of infection-associated thrombocytopenia in senile patients. Methods: The current study is a retrospective analysis of the patients receiving rhTPO for infection-associated thrombocytopenia in our hospital. Results: Forty-nine cases were included in the analysis as rhTPO group. The absolute platelet count after treatment, increase in platelet count, and the overall response rate were considerably higher in the rhTPO group than that in the control group. Improvement in bleeding score was higher in the rhTPO treatment group than that in the control group (2.1 ± 5.4 vs 0.4 ± 1.7). Bleeding event was stopped in 68.2% of the patients after rhTPO treatment and in 35% of the patients in the control group ( P = .032). A stratified analysis indicated that the therapeutic efficacy is much better in patients without organ failure. Conclusion: Recombinant human TPO is effective in alleviating infection-associated thrombocytopenia and hemorrhage in senile patients, particularly if given prior to the emergence of organ failure.

The incidence of acute myelogenous leukemia (AML) in patients over 80 years old is >20 times greater than that observed in younger patients. Previously, no standard treatment protocol for elderly patients with AML existed, however the development of hypomethylating agents, including decitabine, has brought about promising results in AML. In the present study, we report on the usage of a lower than routine dosage of decitabine in patients over 80 years old with AML. Since January 2010, 5 patients diagnosed with AML over the age of 80 years old received treatment with decitabine in our hospital. Decitabine was administered at a dose of 10–15 mg/m2 and repeated every other day for a total of 5 days. This cycle was repeated for ∼6 weeks. The 5 patients received a total of 19 cycles of treatment with decitabine. No patient achieved complete or partial remission. An antileukemic effect was observed in 25% of courses (3/12). An increase in platelet count of >20×109/l was observed in 26.3% (5/19) of cycles compared with previous treatment. An increase in hemoglobin concentration of >20 g/l was observed in 36.8% (7/19) of cycles in comparison to previous treatment, four of which achieved normal hemoglobin levels. One patient became red blood cell transfusion-independent. The median survival time was 19.8±4.8 months. Survival time from decitabine administration to mortality was 13.2±5.1 months. The main side-effect was bone marrow suppression with grade III–IV thrombocytopenia, grade III–IV leukocytopenia, grade III–IV neutropenia and anemia accounting for 94.7% (18/19), 47.4% (9/19), 89.5% (17/19) and 21.1% (4/19), respectively. Severe infection or bleeding was not observed and no patient stopped treatment due to adverse effects. In conclusion, extremely low-dose decitabine may be used safely in elderly patients and achieved longer survival times than reported previously in AML patients aged 80 and above. It is suggested that complete remission may not be the primary objective, while improvement of quality of life may be a better choice in AML patients over 80 years old. The cases observed in our study were limited, so more cases are required for further study.

Objective. To evaluate the efficacy of autologous cytokine-induced killer (CIK) cells in patients with renal cell carcinoma (RCC).Methods. 20 patients diagnosed with TNM stage I or II RCC were randomly divided into two groups, a CIK cell treatment group and a control group. The endpoint was progression-free survival (PFS) evaluated by Kaplan-Meier analyses.Results. CD3+, CD3+/CD8+, CD3+/CD4+, and CD3+/CD56+levels increased after CIK cell culture (P<0.01). The median PFS in CIK cell treatment group was significantly longer than that in control group (PFS, 32.2 months versus 21.6 months; log-rank,P=0.032), all patients were alive during the course of followup, and there are no statistically significant differences between two groups in OS (log-rank,P=0.214). Grade III or greater adverse events were not observed.Conclusions. CIK cells treatment could prolong survival in patients with RCC after radical nephrectomy and showed acceptable curative effect with potential enhancement of cellular immune function. This trial is registered with Clinicaltrials.govNCT01799083.

To analyze the clinical course of a very elderly patient with advanced diffuse large B cell lymphoma (DLBCL), so as to explore the incidence, prognosis and treatment of DLBCL and to analyse the prognostic and therapeutic significance of molecular subtype.The clinical history, auxiliary examinations, clinical diagnostic standards, therapeutic methods, biopsy and autopsy of this patient were retrospectively analyzed; the incidence, current treatment status, molecular biological features, and prognostic and therapeutic significance of molecular subtype were studied.After admission, this patient was diagnosed as non-GCB DLBCL, NOS, stage IV B and in the high risk group (IPI = 5, ECOG = 2). She achieved a decent partial response after many times of imunochemotherapy, but his disease status soon progressed. The liver occupying biopsy revealed non-GCB, while the spleen tumor pathology revealed GCB; pathological typing of these two methods was completely opposite. Autopsy pathological diagnosis showed that the death causes included extensive tumor metastasis, dyscrasia and respiratory circle failure.Incidence of aged patients with DLBCL is high, and the disease is aggressive; the treatment is low responsive and difficult, and new therapeutic methods are needed. Gene expression profile (GEP) can provide molecular subtype and potential pathogenic mechanism, which can promote the development of new targeted therapy and individualized treatment.

Amifostine (AMF), 2-(3-Aminopropyl) aminoethyl phosphorothioate is a broad-spectrum cytoprotective agent used to treat nuclear radiation and chemical weapon injuries. Recently, amifostine has been shown to have a profound biological influence on tumor cells. In order to examine the effects and mechanisms underlying the effects of amifostine on human acute megakaryocytic leukemia, we evaluated the efficacy of amifostine against Dami cells and observed a cell cycle arrest in G2/M phase. Amifostine treatment also induced cell apoptosis of Dami cells which corresponds to formal studies. Through whole-genome microarray and bioinformatics analyses, we found that amifostine affected the gene expression of CCND1, BCL2 and CASP3 which revealed the mechanism amifostine acted on Dami cells. Thus, CCND1-BCL2 Gene Network is predicted to be a direct target of amifostine treating human acute megakaryocytic leukemia, which may provide a novel potential target for the therapy of several subtypes of human AML. This article is protected by copyright. All rights reserved.

Background Although angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are equally important in the treatment of hypertension, there is less evidence whether they have equal cardiovascular and cerebrovascular protective effects, especially in elder hypertensive patients. This study aims to clarify this unresolved issue. Methods This cross-sectional study included clinical data on 933 aged male patients with hypertension who received either an ARB or ACEI for more than two months between January 2007 and May 2011. The primary outcome was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary endpoints were unstable angina, new atrial fibrillation, and transient ischemic attack. Results The median follow-up time was 24 months. Age, drug types, cerebral infarction history, renal dysfunction history were the independent predictors of the primary endpoint. The risk of an occurrence of a primary endpoint event was higher in the ARB group than the ACEI group [P = 0.037, hazard ratios (HR): 2.124, 95% confidence interval (95% CI): 1.048–4.306]. The Kaplan-Meier method also suggests that the rate of primary endpoint occurrence was higher in the ARB group than the ACEI group (P = 0.04). In regard to the secondary endpoints, there were no significant differences between the two treatment arms (P = 0.137, HR: 1.454，95% CI: 0.888–2.380). Patient age and coronary heart disease history were independent predictors of the secondary endpoint. Conclusion ACEI were more effective than ARB in reducing cardiovascular and cerebrovascular morbidity and mortality in aged patients with hypertension. J Geriatr Cardiol 2012; 9: 252−257. doi: 10.3724/SP.J.1263.2011.12031

Acute tumor lysis syndrome (ATLS) is a recognized complication of the treatment of malignant lymphomas and is associated with significant morbidity and mortality. However, there have been few reports of the occurrence of ATLS in patients treated with rituximab. This study reports 2 patients with high-grade diffuse large B-cell non-Hodgkin's lymphoma who presented high tumor load, were sensitive to treatment and had multiple risk factors for ATLS. Both patients developed ATLS after treatment with rituximab and, despite aggressive supportive therapy, died of multiple organ failure. These cases illustrate that ATLS can occur after treatment with rituximab and that a high index of suspicion is necessary for the prompt diagnosis of ATLS.

To evaluate the effectiveness and safety of autologous cytokine-induced killer (CIK) cells in elderly patients with diffuse large B-cell lymphoma. Peripheral blood mononuclear cells (PBMC) were isolated from nine elderly patients with diffuse large B-cell lymphoma. PBMCs were augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. Autologous CIK cells (range 5 × 10(9)-1 × 10(10)) were then infused back to individual patients; infusion was repeated every 4 weeks for 32 weeks (eight cycles). Patients were assessed for changes in lymphocyte subgroup, tumor-related biological parameters, imaging characteristics, the condition of remission, quality of life (QOL), and survival. Prior to CIK infusion, two patients were in complete remission and seven patients were in partial remission. After autologous CIK cell transfusions, the proportion of CD3+, CD3+CD8+, and CD3+CD56+ cells were significantly increased compared with baseline (P < 0.05); whereas serum levels of β2-microglobulin and LDH were significantly decreased (P < 0.05). The lymphoma symptoms were reduced and QOL was improved (P < 0.05) in all patients. All patients achieved complete remission at study endpoint. No adverse reactions were reported. Autologous CIK cell immunotherapy is safe and efficacious for the treatment of elderly patients with diffuse large B-cell lymphoma.

Background: We retrospectively evaluated the efficacy and safety of individualized liposomal doxorubicin-based treatment in elderly patients with non-Hodgkin’s lymphoma and poor general health. Patients and Methods: 22 patients (median age 83.5 years) were treated with liposomal doxorubicin combined with CHOP-based chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) or other individualized doxorubicin-based treatments including liposomal doxorubicin combined with rituximab. Efficacy and adverse reactions were measured. Results: Patients received a total of 80 courses of chemotherapy (mean dose 143.6 mg/patient liposomal doxorubicin). The numbers of patients achieving complete remission, uncertain complete remission, partial remission, stable disease, or progressive disease were 10 (45.5%), 4 (18.2%), 4 (18.2%), 1 (4.5%), and 3 (13.6%), respectively. The most frequently reported adverse reaction was bone marrow suppression. No serious infections were reported. 3 (13.6%) patients showed skin changes. None experienced congestive heart failure or acute myocardial infarction. There were no chemotherapyrelated deaths. Overall survival rates at 1, 3, and 5 years were 81.8, 59.1, and 40.9%, and progression-free survival rates were 83.3, 66.7, and 54.5%. Conclusions: Individualized liposomal doxorubicin-based chemotherapy is effective and safe for elderly patients with non-Hodgkin’s lymphoma.

Dear Editor, The myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell diseases that are characterized by cytopenia, dysplasia in one or more of the major myeloid cell lines, and a tendency to transform into acute myeloid leukemia (AML). Approximately, one third of MDS patients will undergo transformation into AML, which is resistant to treatment and ultimately fatal. We describe here a case of MDS in an 85-year-old male patient with transformation AML from MDS who was successfully treated with ultralow dose decitabine, amifostine, and infusion of autologous cytokineinduced killer (CIK) cells (dubbed the DAC regimen). The patient was admitted on March 11, 2010 due to pancytopenia. Past history was unremarkable except hypertension and COPD. His routine blood chemistries were as follows: white blood cell count, 2.9×10/L (neutrophils, 40 %; lymphocytes, 50 %; monocytes, 4.5 %); platelets, 67×10/L; and hemoglobin, 98 g/L. Bone marrow (BM) aspirate revealed 5.2 % blasts and trilineage dysplasia (Fig. 1a). Cytogenetic analysis demonstrated 46, XY[13]/t(7;11)(q35;q14)[10]/ del(4)(p10),t(7;11)(q35;q14)[2]/subdiploid(44)[2]. He was diagnosed with MDS-RAEB-I, IPSS intermediate-2 risk. The patient was given amifostine and erythropoietin, but hemoglobin progressively declined and he became transfusion dependent. BM aspirate on December 17, 2011 revealed 20.2 % blasts and flow cytometry demonstrated transformation AML-M4 (FAB classification) (Fig. 1b). One week later, the patient was started on the DAC regimen. Decitabine (10 mg; Chia-Tai Tianqing Pharmacy Co., Jiangsu, China) was given on d1, 3, 5, 7, and 9. Autologous CIK cells were prepared as previously described [1]. Briefly, on d0, 54 mL venous blood was collected from the median cubital vein of the patient, and peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque density–gradient centrifugation. PBMCs were then washed and cultured in the presence of anti-human CD3 monoclonal antibody, recombinant human interferon-γ, and recombinant human interleukin-2 for 14 days. On d14, 2–6×10 cells were infused. Amifostine (0.4 g) was given on d14–18 and d21–25. The patient received a total of three courses of the regimen. The main side effects included Bo Yang, Hai-tao Wang, Li-li Cai, Yu Zhao, Xiao-hua Chi, Hong-li Zhu, Hai-hong Ran, Yang Yang, Rui-li Yu, Song-wei Li and Xue-chun Lu contributed equally to this work.

Adoptive immune cell transfer such as cytokine-induced killer (CIK) cells has become an important adjuvant approach in patients with tumours.The aim of this study was to analyse the adverse events (AEs) that occur during the transfusion of autologous CIK cells and to identify the risk factors associated with these AEs.Cell infusion-associated AEs were evaluated according to National Cancer Institute Common Terminology Criteria. Analysis was performed from a single-centre data on 893 malignant tumour patients who received a total of 4088 transfusions from March 2008 to October 2013.A total of 215/4088 (5.26%) transfusion cases from 893 patients presented with AEs (Grade 1 - 4); 204/215 (94.88%) were Grade 1 - 2, and 156/215 (72.56%) occurred within 24 h. The most common AEs were fever (0.88%), chills (0.56%) and fatigue (0.49%). The rare but severe AEs included anaphylactoid purpura, tumour lysis syndrome, anaphylactic shock, arthralgia. No transfusion-associated death was noticed. The mainly relative risk factors for AEs included transfer cycles and clinical stages.This study is a large-sample AEs research, to our knowledge, relative to immune cell transfusion from a single centre data analysis, revealing that autologous CIK cell therapy represents a fairly safe and well-tolerated treatment modality for malignant tumour patients, even rare severe, but not lethal AEs were observed in few patients.

The advances of treatment improved the prognosis of the patients with acute leukemia (AL) in the last decade, but the lack of general biomarker for predicting relapse in AL, which is one of the most important factors influencing the survival and prognosis. DNA methylation of ID4 gene promoter occurred frequently in patients with AL and was found to be highly related to the tumor progression. Based on the previous work of the setup of methylation-specific quantitative PCR system for ID4 gene, this study was designed to investigate the relation between the quantitative indicator of methylation density, percentage of methylation reference(PMR) value, and different disease status of AL. PMR of ID4 was detected by MS-PCR in bone marrow (BM) samples of 17 healthy persons and 54 AL patients in the status of newly diagnosis, complete remission and disease relapse. The results showed that at different disease status, PMR value in newly diagnosed group was significantly lower than that in complete remission group (P = 0.031). Among serial samples, PMR value remained very low at the status of patients with continuous complete remission (1.5‰), and increased along with the accumulation of tumor cells at relapse. In 1 relapse case, the abnormal rise of PMR value occurred prior to morphological relapse. PMR value seemed to be related to body tumor cell load. It is concluded that the quantitative indicator of methylation density and PMR value may reflect the change of tumor cell load in acute leukemia patients. Dynamic monitoring of PMR maybe predict leukemia relapse.

DNA methylation of ID4 gene promoter occurred frequently in patients with acute leukemia and was found to be highly related to the tumor progression. Due to lack of the appropriate methylation detection methods, the relation between the quantification of ID4 methylation and the states of acute leukemia is still unclear. This study purposed to set up a methylation-specific quantitative PCR system for ID4 and investigate the specificity and sensitivity of this methylation detection. The plasmids combined with target gene as well as with internal reference were constructed, and the standard curves were set up by using above mentioned plasmids. The specificity of this detection system in cell lines was verified through techniques of MSP and quantitative MSP. The sensitivity of this detection system was verified by mixing methylation-positive and negative cell lines in varying proportions and through amplification of qualitative MSP. The results showed that the standard curves were establish successfully. The results of quantitative MS-PCR in cell lines were consistent with those of MS-PCR, and as low as 1: 10(-5) of ID4 methylation positive cells could be detected by the new methylation detection assay. In newly diagnosed acute leukemia patients, the positive rate of quantitative MSP was higher. It is concluded that a complete quantitative MSP system for ID4 methylation detection has been established and this quantitative MSP method has good specificity and high sensitivity.

Imatinib has been recognized as the frontline therapy drug in chronic myeloid leukemia (CML), however, only limited patients could achieve complete molecular remission (CMR). Recent clinical and basic proofs indicated an improved treatment outcome by the combination of interferon and Imatinib. This study was purposed to evaluated systematically the efficacy and safety of interferon plus Imatinib in patients with CML. Data from relative clinical trials were from clinical trial of gov and Cochrane Collaboration. A comprehensive literature search was performed from data bases such as pubMed and EM. The results indicated that 7 clinical trials and 12 research papers met the criteria enrolled in study, included 697 cases in total. The combination group had higher complete cytogenetic remission (CCgR) rate than imatinib alone at 6 months (58% vs 42%; P = 0.0001) and 12 months (74% vs 68%; P = 0.004). The major molecular remission (MMR) rate was also higher in the combination group at 6 months (58% vs 34%; P = 0.0001) and 12 months (66% vs 47%; P0.0001). Furthermore, compared with single drug, the combination group had superior CMR rate at 6 months (13% vs 2%; P = 0.0002) and 12 months (14% vs 5%; P = 0.0009). The major adverse effects of combination therapy were rash, asthenia, edema and musculoskeletal events, and combination therapy was more prone to inducing neutropenia, thrombocytopenia and mild anemia. It is concluded that compared with Imatinib alone, the combination of interferon and Imatinib has better clinical efficacy in treating CML with earlier cytogenetic and molecular remission. It is also a safe therapy in spite of slightly weaker tolerance than single drug therapy.

This study was purposed to evaluate the effectiveness and safety of autologous cytokine induced killer (CIK) cells combined with chemotherapy in treatment of elderly patients with acute myeloid leukemia. Peripheral blood mononuclear cells (PBMNC) were isolated from 5 elderly patients with acute myeloid leukemia, and then augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. The autologous CIK cells thus obtained were infused back to individual patients, 28 days as one cycle. The changes in cellular immune function, incidence of infection, independence of hematoglobin or blood transfusion, and progression of disease were observed and assessed before and after therapy. The results showed that the 46 cycles of CIK cell infusion were performed for 5 patients, no adverse reaction was observed in these patients. The percentages of CD3(+), CD3(+)CD8(+) and CD3(+)CD56(+) increased significantly (P0.05), The therapy of CIK could significantly reduce the incidence of infection (P0.05) and shorten the time of high fever in AML patients (P0.05). CIK also could reduce the volume of erythrocyte infusion to maintenance hematoglobin level (P0.05). We found that although CIK could not change the outcome of AML, the combination of CIK and chemotherapy could control patients' condition and prolong their survival during the development and end stage of AML. It is concluded that autologous CIK cells combined with chemotherapy is safe and efficacious for the elderly patients with acute myeloid leukemia.

The purpose of this study was to explore the clinicopathological features, therapy and prognostic factors of elderly patients with non-Hodgkin's lymphoma (NHL). The clinical data including general clinical characteristics, pathological features, chemotherapy selection and treatment response of 30 patients with NHL in our hospital from January 2003 to December 2012 were analyzed retrospectively. The survival was analyzed by using Kaplan-Meier methods, and the prognosis was evaluated by COX regression multivariate analysis model. The clinical parameters selected include age, Ann Arbor stage, international prognostic index (IPI), B symptom and lactate dehydrogenase (LDH) levels. The results showed that all the patients suffered from underlying disease, and the cardiovascular disease (hypertension, coronary heart disease, arrhythmia) is the most common, and minority (8/30) combined with secondary tumor, the 63% (19/30) cases had B symptoms at diagnosis. only 2 cases were diagnosed as T-cell lymphoma; the 93% (28/30) cases combined with B-cell lymphoma, 57% (17/28) of them combined with diffuse large B-cell lymphoma. Ann-Arbor stage ≤ IIwas 37% (11/30);10(37%) patient's IPI score was ≤ 2, and 67% (20/30) was scored 3-5; 13(43%) patient's serum LDH level was abnormal. Modified R-CHOP chemotherapy was given individually on the basis of clinical features. The patients achieved complete remission, partial remission, stable disease, or progressive disease accounted for 14 (46.7%), 13 (43.3%), 1 (3.3%), and 2 (6.7%), respectively; the total reaction rate was 90% after 4 cycles of chemotherapy; the overall survival (OS) rate at 1 and 2 years was 73.3% and 43.3%, and progression-free survival (PFS)rate at 0.5 and 1 years was 62.2% and 54.9%; multivariate analysis by COX regression showed that B symptoms and Ann-Arbor stage were independent factors (P = 0.014, 0.039; RR = 6.678, 4.939, respectively) affecting the OS of elderly NHL, and IPI score affected PFS independently. It is concluded that elderly patients with NHL usually are of late stage at newly diagnosis and have suffered from underlaying diseases. Besides strengthening supportive treatment, modified R-CHOP chemotherapy should be given individually according to different prognosis. B symptoms and Ann-Arbor stageII are indicators for poor prognosis of elderly NHL.

This study was aimed to investigate the effect of all-trans retinoic acid (ATRA) combined with SBA-Na on the biologic activities of human leukemia K562 and Kasumi-1 cell lines and their mechanism. The ATRA solution of 10(-6) mol/L (W1), 10(-4) mol/L (W2) and the SBA-Na solution of 100 µg/ ml (Z1) and 200 µg/ml (Z2) were prepared respectively. The K562 and Kasumi-1 cells were treated with W1, W2, Z1, Z2, W1 + Z1 and W2 + Z2 respectively, at same time, the blank control was set up. The cell morphology and growth in different treated groups were observed under light microscope. The CCK-8 method was used to detect the proliferation ability of cells, the cell growth curves were drawn, the inhibitory rate of cells was calculated. The flow cytometry with PI single staining and PI/Annexin V double stainings was used to detect the change of cell cycle and apoptosis of 2 cell lines treated with different drugs. The RQ-PCR was used to detect the change of Cyclin A mRNA expression in K562 cells. The results showed both ATRA and SBA-Na displayed inhibitory effect on cell proliferation, and the combination of these two drugs had stronger effect. As compared with the control group, the cell cycle distribution were changed obviously, and the apoptosis increased more significantly in treated groups, especially in group of ATRA combined with SBA-Na. The Cyclin A mRNA expression was up-regulated in Z1 group, while Cyclin A mRNA expression was down-regulated in other groups. It is concluded that both ATRA and SBA-Na can inhibit the proliferation of K562 and Kasumi-1 cell lines and promote their apoptosis. This effect may be stronger when both drugs combined. For K562 cells, the inhibitory effect may be accomplished through down-regulation of Cyclin A mRNA.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder of hematopoiesis due to the inactivation of PIG-A gene. However, the presence of mutant PIG-A gene in a group of hematopoietic cells is not enough for the development of PNH, immunologic injury and apoptotic effects are considered to play an important role in clonal expansion. Knowledge of the molecular mechanisms leading to PNH has substantially increased in the past decades, which remarkably advances the diagnostic modalities and treatment approaches of patients with PNH. Though great progress has been made because of targeted therapy method, the challenges are still ahead. In this review the advances of studies on mechanism, laboratorial diagnosis and therapeutic protocols of PNH are summarized.

This study was aimed to evaluate the effectiveness and safety of low methylation drug decitabine combined with autologous cytokine induced killer cells (CIK) to treat the elderly patients with acute myeloid leukemia (AML). Two AML patients aged over 80 years old were diagnosed and treated in our department from 2006 to 2012; both company with MDS history, and one case was M4-type, another case was M6-type according to FAB classification. The changes in lymphocyte subsets, hematologic response, transfusion frequency, leukemic gene expression, obtaining CR or PR, quality of life and survival time of the patients with different treatment regimen (decitabine alone; CIK alone; decitabine combined with CIK) were systematically observed. The results showed that therapy of decitabine combined with CIK cells could reduce bone marrow suppression extent, decrease the frequency and volume of blood transfusion, and prolong the duration of partial remission, compared with the single use of CIK cell infusion and single use of decitabine treatment. Meanwhile, the kinds of expressed genes associated with leukemia decreased and the survival time was prolonged obviously. The patients' life quality significantly improved. It is concluded that decitabine combined with CIK for treatment of elderly patients with AML is safe and effective.

The aim of this study was to observe the curative effects and safety of autologous cytokine induced killer (CIK) cells in treatment of aged patients with orbital diffuse large B cell lymphoma after rituximab therapy. The patient was given rituximab three times with low dose COP chemotherapy one time when he was diagnosed with orbital diffuse large B cell lymphoma. Two months later, the patient began to receive five cycles CIK cells infusion. One course of therapy was defined as follows: about (2-3)×10(9) of CIK cells (survival rate95%) was transfused twice and then rhIL-2 (1 MU daily) was subcutaneously administered for 10 consecutive days. Efficacy and adverse effect was observed during or after CIK cells infusion. The results showed that the peripheral blood mononuclear cells of the patient could be cultured and expanded into CIK cells. The majority of CIK cells was positive for CD3 and CD8 after culture. The CD3(+)CD56(+) cells markedly increased after culture. After two cycles of CIK cell infusion, the orbital lymphoma and possible involvement of the kidney disappeared. The patient obtained complete remission after five cycles of CIK cells infusion. The side effects of CIK cell treatment were minor. It is concluded that CIK cell infusion may prevent recurrence, prolong progression-free survival and improve quality of life after rituximab (alone or with chemotherapy) for aged patients with orbital diffuse large B-cell lymphoma.

Objective Increased platelet activity predicts adverse cardiovascular events. The objective was to assess the effects of long-chain omega-3 polyunsaturated fatty acid ( n -3 PUFA)-supplementation on platelet aggregation. Methods and results We conducted a meta-analysis of randomized controlled trials identified using PubMed, Embase and the Cochrane Library. Fifteen studies were included. In comparison to placebo using the random-effect model, n -3 PUFA-supplementation significantly reduced adenosine diphosphate-induced platelet aggregation (standard mean difference [SMD] = −1.23 with 95% confidence interval [CI] −2.24 to −0.23, p = 0.02) and platelet aggregation units, determined using the VerifyNow ® rapid platelet-function assay system (SMD = −6.78 with 95% CI −12.58 to −0.98, p = 0.02). There was a trend toward decreased collagen-induced (SMD = −0.70 with 95% CI −0.72 to 0.33, p = 0.18) and arachidonic acid-induced platelet aggregation (SMD = −0.43 with 95% CI −2.26 to 1.40, p = 0.64) compared with controls; however, statistical significance was not reached. Conclusions Our meta-analysis demonstrates that n -3 PUFA-supplementation is associated with a significant reduction in platelet aggregation when the participants were at poor health status, but not in healthy persons. High-risk patients with cardiovascular disease and even diabetics may potentially benefit from n -3 PUFAs therapy. However, n -3 PUFAs may not be effective in primary prevention. Larger trials need to be carried out to confirm the present findings.

Autologous cytokine-induced killer (CIK) cell transfusion may prevent tumor relapse in acute myeloid leukemia (AML). This study investigated whether CIK cells from recurrent or refractory AML patients with high peripheral leukemia cell burdens could be expanded to a clinically usable number, and it further evaluated the antitumor potentials in vitro and in vivo. The numbers and phenotypes of CIK cells expanded from nine AML patients and 10 healthy donors were compared. Cytotoxicity (against K562 and U937 cell lines) and cytokine secretion (interleukin-2, interferon-γ, tumor necrosis factor-α and vascular endothelial growth factor) were tested for AML-derived and healthy donor-derived CIK cells and fresh peripheral blood mononuclear cells from healthy donors. Importantly, we assessed the therapeutic effects of autologous CIK cell infusions in two patients with AML. The proportions of CD3 + and CD3 + CD56 + CIK cells from patients with AML were similar to those from healthy donors, and the number of CD3 + CD56 + cells in AML-derived CIK cells was expanded approximately 1,020-fold. Phenotype analyses with flow cytometry showed that the leukemic cells were gradually eliminated during the process of CIK cell preparation to an almost undetectable level. Although the cytotoxic effect of AML-derived CIK cells was equivalent to that of healthy donors, AML-derived CIK cells had a significantly higher cytokine-secreting capacity. In clinical treatment, the leukemia burden in the peripheral blood of one patient was dramatically decreased after four transfusions within 4 months. CIK cells can be efficiently expanded in vitro from patients with recurrent or refractory AML and may be used for reduction of leukemic blasts in vivo.

The function of immune system degenerates in an aging-dependent manner and this results in immunosenescence. Human immune system includes two parts: genetic/innate immunity and adaptive immunity. The former is involved in monocytes, nature killer cells, and dendritic cells, the later is involved in acquired B and T lymphocytes. During the aging of immunity system, the both parts of immunity are damaged to some degree. Generally, innate immunity seems well-retained and the acquired immunity is degenerative seriously with aging. Immunocyte senescence is closely related to the elderly decreased ability to control infectious disease, cancer and to their generally poor response to vaccination. This review summarized the research progress on immunosenescence characteristics in aged phase.

This study was purposed to characterize the effect of carboxylic acid metabolite (SR26334) of clopidogrel bisulfate deprived of antiplatelet efficacy on the spectrum of gene expression in the cultured human umbilical vein endothelial cell (HUVEC) line (EA.hy926), and to explore the potential molecule mechanism of SR26334 impact on HUVEC. By using a Affymetrix HU133 plus 2.0 oligonucleotide microarray, the alteration of gene expression spectrum induced by SR26334 in HUVEC was detected, the real-time PCR was used to confirm the results of selected differentially expressing genes. The results indicated that total 235 including 176 up-regulated and 59 down-regulated genes were obtained with change more than 1.5-fold after SR26334 (10 µmol/L) acted on HUVEC for 48 h. SR26334 affected the expression levels of genes involved regulation of transcription, transcription, positive regulation of transcription from RNA polymerase II promoter, cell cycle, cell division, protein amino acid dephosphorylation in HUVEC. It is concluded that carboxylic acid metabolite SR26334 of clopidogrel bisulfate modulates function of endothelial cells through different pathway at gene level.

This study was purposed to evaluate the safety and curative effect of autologous cytokine induced killer cells (CIK) combined with low-dose IL-2 regimen containing immune enhancement of thymic peptide on elderly patients with B-cell chronic lymphocytic leukemia (B-CLL). Thymic peptide α1 was subcutaneously given as the immunoenhancement agent at a dose of 1.6 mg/d, 14 days as one cycle. Peripheral blood mononuclear cells (PBMNC) from 5 patients with B-CLL were isolated once a week to induce ex vivo CIK cells through culture in the context of interferon (IFN)-γ, interleukin (IL)-2 and anti-CD3 monoclonal antibody. The PBMNC were separated from patients before and after 14 days as one cycle of thymic peptide α1 administration. Parameters of amplification ability, effector cells quantity, lymphocyte subgroups percentage and antitumor cytotoxicity were compared before and after thymic peptide administration. The 5 patients were treated with CIK cells combined with low-dose IL-2 regimen immediately after injection of thymic peptide α1. The CIK cells plus low-dose IL-2 regimen containing thymic peptide enhancement was defined as: thymic peptide α1 1.6 mg/d was subcutaneously administered once every other day; (4 - 6) ×10(9) of CIK cells were transfused followed by IL-2 subcutaneous administration of 1 mU/d on days 1-10, 28 days as one cycle. Clinical evaluation parameters including cellular immunity function, CLL related biomarkers, disease state and infectious frequency and degree were investigated before and after CIK cells infusion puls IL-2. The results showed that the amount of amplified CIK cells, the percentage and amplification times of effector cells and antitumor cytotoxicity more significantly increased after thymic peptide α1 treatment than before its use (P0.05). The total 46 cycles of CIK cells infusion plus IL-2 were completed in the 5 CLL patients. No adverse reaction was observed. After treatment of CIK cells plus IL-2, the general conditions of 5 CLL patients were to different extent improved. Simultaneously, percentages of CD3(+), CD3(+)CD8(+), and CD3(+)CD56(+) cells in peripheral blood remarked by raised (P0.05), the serum level of β2 microglobulin was significantly declined (P0.05), and the frequency and degree of infection was also decreased (P0.05). Following CIK cells plus IL-2 therapy, the transformation of disease state from partial remission (PR) to complete remission was seen in 3 patients, from stable disease (SD) to PR in 1 patient, and from progress of disease to SD in 1 patient. It is concluded that the regimen of autologous CIK cells combined with low-dose IL-2 containing immune enhancement of thymic peptide is safety and effective for the treatment of elderly patients with B-CLL.

Angiogenesis occurs commonly in various physiological and pathological processes. Improving blood supply through promoting angiogenesis is a novel approach for treating ischemic diseases. Angiotensin II type 1 receptor blockers (ARBs) dominate the management of hypertension, but evidence of their role in angiogenesis is contradictory. Here we explored the angiogenic effects of ARBs through characterizing gene expression of the human umbilical vein endothelial cell line EA.hy926 exposed to irbesartan.The human umbilical vein endothelial cell line EA.hy926 was grown for 72 hours after treatment with different concentrations of irbesartan. The cell proliferative capacity was assessed by CCK8 assay at 24, 48 and 72 hours. Gene expression levels in EA.hy926 cells responding to irbesartan were measured under optimal proliferation conditions by microarray analysis using Affymetrix U133 plus 2.0. The differential expression of genes involved in angiogenesis was identified through cluster analysis of the resulting microarray data. Quantitative RT-PCR and Western blotting analyses were used to validate differential gene expression related to the angiogenesis process.In the 10(-4), 10(-5), 10(-6) mol/L treatment groups, cell proliferation studies revealed significantly increased proliferation in EA.hy926 cells after 24 hours of irbesartan treatment. However, after 48 and 72 hours of treatment with different concentrations of irbesartan, there was no significant difference in cell proliferation observed in any treatment group. We selected the group stimulated with irbersartan at a concentration of 10(-6) mol/L for microarray experiments. Statistical analysis of the microarray data resulted in the identification of 56 gene transcripts whose expression patterns were significantly correlated, negatively or positively, with irbesartan treatment. Cluster analysis showed that these genes were involved in angiogenesis, extracellular stimulus, binding reactions and skeletal system morphogenesis. Of these 56 genes we identified seven genes (VEGF, KDR, PTGS2, PLXND1, ROBO4, LMO2, and COL5A1) involved in the angiogenesis process. qRT-PCR analysis of these genes confirmed the microarray results. Protein expression of three VEGF pathway genes (VEGF, KDR, and PTGS2) was further confirmed by Western blotting.Our study showed that irbesartan may induce angiogenic effects in vascular endothelial cells. It suggested that the mechanism of angiogenic effects of ARBs might be attributed to the signaling cascade from angiotensin receptors in the VEGF pathway. It also provided evidence indicating that ARBs could be used as a novel therapeutic approach to treat chronic ischemic heart disease as well as anti-hypertensive agents.

To compare the effects of clopidogrel with or without combined with CYP3A4-metabolized statin in treating coronary artery disease (CAD) among the elderly patients.The study cohort was defined as all patients were over 60 years of age and hospitalized for CAD who were prescribed clopidogrel between January 2000 and February 2011. A total of 1021 patients were enrolled, with 178 of them prescribed clopidogrel and 843 patients were administrated clopidogrel combined with statins (CYP3A4-metabolized statins 636 and non CYP3A4-metabolized statins 207). The primary endpoint was all cause of death and the second endpoint were non-fatal myocardial infarction (MI), but hospitalized for unstable angina, stroke, transient ischemic attack, or repeated revascularization (PCI or coronary artery bypass graft).Among the clopidogrel group and the clopidogrel plus statins group, the incidence density of death was 6.86/1000 and 3.18/1000 respectively, with crude RR as 2.15 (95%CI: 1.39-3.33) and statistically significant (χ2=3.53, P0.01). The incidence density of composite thromboembolic events did not show statistical significance (P0.05). The two groups were 1:1 matched, after propensity score matching, clopidogrel coadministrated with statins group showed significant decrease in all cause of death, with RR as 0.42 (95%CI: 0.19-0.93), χ2=7.23, P0.01. No significant difference was observed in deaths or composite thromboembolic events between statins via different cytochrome P450 pathways.Clopidogrel with statin could reduce the mortality of elderly CAD patients compared with clopidogrel without statin. The result did not show statistical significance between CYP3A4-metabolized statins or non CYP3A4-metabolized statins regarding the mortality or composite endpoint events.

This study was purposed to investigate the effect of clopidogrel on gene expression profile of cultured human umbilical vein endothelial cell (HUVEC) line (EA.hy926), and explore its potential molecule mechanism. A Affymetrix U133 plus 2.0 oligonucleotide microarray was applied to detect the alteration of gene expression profile induced by clopidogrel in HUVEC. Real time RT-PCR was used to verify the result of selected differentially expressing genes. The results showed that total 508 genes (including 139 up-regulated and 369 down-regulated genes) were obtained with differential expression more than 1.5-fold after clopidogrel (10 µmol/L) acted on HUVEC for 48 h. Clopidogrel affected the expression levels of genes involved protein binding, transcription factor activity, zinc ion binding, regulation of DNA-dependent transcription, transcription, RNA splicing and so on. It is concluded that the clopidogrel modulate function of endothelial cells by regulating sets of genes through different pathway.

To evaluate the effect of irbesartan on the proliferation, apoptosis, and VEGF mRNA expression of human umbilical vein cell line EA.hy926 in vitro.The human umbilical vein cell line EA.hyY926 were treated with various concentrations of irbesartan for 24 h. The cell proliferation after the treatment was detected by CCK8 assay, flow cytometry and FITC Annexin V/PI kit were used to detect changes in the cell apoptosis. RT-PCR was used to evaluate the expression of VEGF mRNA.There were no changes in cell shape with various concentration of irbesartan. CCK-8 assay showed a greater rate of the cell proliferation in irbesartan group than that in control group with a dose-independent manner after 24 h treatment. After incubation with irbesartan, cell proliferation rate was significant (P0.05). FCM analysis showed no significantly changes in the cell apoptosis. Irbesartan increased the proliferation of EA.hy926 cells. At concentration of 1 x 10(-4), 1 x 10(-5), 1 x 10(-6) mol/L, VEGF mRNA expression enhanced either (P0.05).Irbesartan could promote the proliferation and up-regulated VEGFmRNA expression in EA.hy926 cell line. This result suggested that in addition to antihypertensive effect, angiotensin receptor antagonist might be a novel therapeutic approach to chronic ischemic heart disease as heart failure.