土家医药半结构化数据的功效挖掘及可视化研究＊

目的 利用数据挖掘技术对半结构化数据的土家族医药进行品种规范和常用功效的可视化发现。方法 收集整理《中国民族药辞典》、《土家医方剂学》等土家族代表性医药文献，建立土家族医药原始数据库，包含药物拉丁学名、药用部位、性味、毒性、功效、主治疾病等。借助Visual FoxPro 9.0软件对土家族医药特性进行频次统计和品种规范，主要以法定标准收录；借助TCMISS (V2.5)、Cytoscape3.6.1、Gephi0.9.2等软件对土家药“药物-功效-主治”间的语义关系，进行功效挖掘和可视化展示。结果 筛选土家药共1453味，方剂共771首，其中土家药主要以“寒（凉）、平”性偏多，苦味药频次最高，其次是辛味药、甘味药；清热败毒、赶风除湿等功效出现频次最高；皮肤疮癣、妇科疾病等是关联程度较大的主治病症。结论 土家族医药的品种规范和“药性-药味-功效-主治”隐形关系可视化分析，可为完善土家药信息化研究奠定基础。     

高血压与中医体质相关性的荟萃分析＊

目的 通过Meta分析研究高血压与中医体质的相关性，为高血压防治提供依据。方法 通过检索国内文献库，纳入符合要求的高血压与中医体质相关性文献，提取原始文献资料并评价研究的质量；以RevMan 5.3软件进行异质性检验和Meta分析，并通过亚组分析探索异质性来源，以漏斗图评估发表偏倚。结果 共有10篇文献符合纳入标准，涉及高血压病人4 401例，对照组7 934例，全部为横断面研究。痰湿质（OR = 2.24，95%CI：1.77 - 2.83，P < 0.001）、阴虚质（OR = 1.28，95%CI：1.13 - 1.45，P < 0.001）、气虚质（OR = 1.21，95%CI：1.06 - 1.37，P = 0.005）、血瘀质（OR = 1.24，95%CI：1.06 - 1.46，P = 0.007）是高血压人群更易出现的体质类型；而平和质是对照组更易出现的体质类型（OR = 0.56，95%CI：0.51 - 0.61，P < 0.001）；阳虚质、气郁质、湿热质、特禀质在高血压人群和非高血压人群的分布无明显统计学差异。亚组分析显示是否明确纳入既往诊断的高血压和研究质量是异质性主要来源；目测漏斗图未发现明显发表性偏倚。结论 痰湿质、阴虚质、气虚质、血瘀质是高血压易感体质，平和质是保护体质，但由于纳入研究质量不佳，且存在设计缺陷，无法说明中医体质与高血压发生的因果关系，结论需谨慎对待。     

Safety and efficacy of allogeneic natural killer cell immunotherapy on human immunodeficiency virus type 1 immunological non-responders: a brief report

Background:Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART).Methods:From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People''s Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (10⁸ cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group.Results:From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/μL) in the NK + ART group and (144 to 176 cells/μL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (β = 54.59, P = 0.006) and CD8 level (β = 322.47, P = 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course.Conclusions:This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted.Registration info:www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).     

抑制EGFR信号通路对骨折愈合早期骨内、外膜来源干细胞增殖、分化能力影响的研究*

目的 探索抑制表皮生长因子受体（EGFR）信号通路对骨折愈合早期骨内、外膜来源SCs增殖、分化能力的影响。方法 将建立右股骨骨折模型成功的42只SD大鼠按随机数字表分为实验组与对照组，实验组给予Gefitinib 100 mg/（kg· d）（溶于0.5%甲基纤维素）灌胃，对照组给予等量0.5%甲基纤维素灌胃。术后1周提取右股骨骨内、外膜区域的SCs并进行体外培养。通过流式细胞术鉴定第3代干细胞表面标志物FITC-CD29、FITC-CD34、FITC-CD45、FITC-CD90; BrdU法检测各组干细胞增殖能力; 成骨诱导及成软骨诱导分化后行von Kossa染色及阿尔新蓝染色，检测干细胞的分化能力。结果 各组SCs表面标志物FITC-CD29、FITC-CD90呈高表达，FITC-CD34、FITC-CD45呈低表达; BrdU法检测发现实验组骨内、外膜SCs增殖能力较对照组显著降低（P<0.01）; 成骨诱导分化并染色后，实验组骨内、外膜SCs的矿化结节较对照组更多，成软骨诱导分化并染色后，实验组SCs的淡蓝色颗粒较对照组更多。结论 在骨折愈合早期，抑制EGFR信号通路能抑制骨内、外膜来源SCs的增殖，促进其成骨、成软骨的分化。     

The risk of systemic lupus erythematosus associated with Epstein–Barr virus infection: a systematic review and meta-analysis

Previous systematic reviews have found a higher sero-prevalence of EBV antibodies in SLE patients compared with controls. Because many studies have been published, there is a need to apply more precise systematic review methods. We examined the association between EBV and SLE patients by conducting a systematic review and meta-analysis of case–control studies that examined the prevalence of EBV antibodies and the DNA-positive rate. We searched the MEDLINE and EMBASE databases from 1966 to 2018 with no language restrictions. The Mantel–Haenszel odds ratios (OR) for EBV antibody sero-positivity were calculated, and meta-analyses were conducted. Quality assessment was performed using a modified version of the Newcastle–Ottawa scale, and 33 studies were included. Most studies found a higher sero-prevalence of VCA IgG and EA IgG in SLE patients compared with controls. Meta-analysis demonstrated a significantly higher OR for sero-positivity to VCA IgG and EA IgG for SLE cases (2.06 [95% confidence interval (CI) 1.30–3.26, p = 0.002] and 7.70, [95% CI 4.64–12.76, p < 0.001], respectively). The overall OR for the DNA-positive rate for SLE patients compared with controls was 3.86 (95% CI 1.52–9.83, p = 0.005). Other antibodies, i.e., VCA IgA/IgM, EBNA IgA, and EA IgA/IgM, also demonstrated a significant difference between SLE patients and controls. These findings support previous systematic reviews; however, publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly when selecting controls and analyses of laboratory conduct.

     

Human gingiva‐derived mesenchymal stem cells alleviate inflammatory bowel disease via IL‐10 signalling‐dependent modulation of immune cells

Current evidence indicates that inflammatory bowel disease (IBD) is caused primarily by impaired mucosal immunity, resulting in an imbalance between epithelial barrier function and tissue inflammation. Human gingiva‐derived mesenchymal stem cells (GMSCs) exhibit immunomodulatory and anti‐inflammatory effects in a variety of immunity‐ and inflammation‐associated diseases. However, the role of GMSCs in treating IBD has not been elucidated. Our study, therefore, examined the therapeutic effect and mechanism of GMSCs in a murine colitis model of IBD. Our results indicate that the infusion of GMSCs significantly prolonged survival and relieved symptoms. Phenotype analyses showed that the frequencies of NK1.1⁺ and CD11b⁺ cells, as well as CD4 T cells in the spleen, were suppressed in GMSC‐treated mice compared with the PBS‐ or fibroblast‐treated control groups. Additionally, GMSC treatment markedly increased the numbers of interleukin (IL)‐10⁺ regulatory T cells, reduced the secretion of pro‐inflammatory cytokines, and increased production of anti‐inflammatory cytokines. A mechanistic study revealed that anti‐IL‐10R antibody abolished the protective effect of GMSCs compared with mice treated with anti‐IgG antibody. Thus, our results indicate that GMSCs play a critical role in alleviating colitis by modulating inflammatory immune cells via IL‐10 signalling.