To evaluate the safety and efficacy of modified CIK cells combined with PD-1 antibody in the treatment of refractory non-small cell lung cancer (NSCLC). Fifteen patients with refractory NSCLC who were treated in our hospital were recruited for this clinical study from January 2015 to December 2020. All patients had disease progression after completing routine treatment. Two of 12 patients achieved a partial remission, 6 had stable disease, and 4 had progressive disease. No serious side effects occurred. The percentage of T helper and NKT-like cells in patients increased significantly after immunotherapy (P < 0.05). In addition, the anti-tumor cytokines (IL-2 and INF-γ) increased significantly (P < 0.05). Although the anti-inflammatory cytokine, IL-10, did not change markedly after immunotherapy (P > 0.05), the Karnofsky Performance Scale was improved. Umbilical cord blood mononuclear cells can be induced into NKT-like cells. Induced NKT-like cells had powerful cytotoxicity against tumor cell lines in vitro when combined with PD1 antibody. Immunotherapy also had a significant therapeutic effect on refractory NSCLC with no serious side effects in vivo.

目的 附红细胞体(Eperythrozoon,EP)病是人兽共患性血液传染病,可以引发溶血、出血、血栓形成、流产等,其主要的致病机制不清,本研究应用源于猪的EP感染研究其致病机制.方法 收集EP感染养殖生猪27头和13例汉族饲养人员,对照组为无EP感染的同种猪26头和健康汉族人末梢血20份.ELISA和流式细胞检测猪和人感染EP后血清补体C3及其降解产物、补体调节蛋白CD55、CD59、补体膜攻击复合物(C5b-9)沉积及细胞因子在猪冠状动脉内皮中的表达.结果 EP感染后猪和人血清C3降解产物C3a升高有统计学意义(P＜0.05),猪红细胞CD55和CD59阴性比例显著增加具有显著的统计学意义(P＜0.01),红细胞膜和猪血管内皮沉积大量C5b-9,同时血管内膜中细胞因子产生增加具有统计学意义(P＜0.05).结论 EP感染诱发补体异常活化导致红细胞及血管内皮损伤,引发溶血、出血、血栓形成等.

To investigate the safety and efficacy of the islet-like cell (cell) induced from human umbilical cord mesenchymal stem cell (UCMSC) with different methods for the treatment of diabetic animal model. UCMSCs were induced to βcells with cytokines (CY) and neonatal bovine pancreatic mesenchymal cell exosomes (Ex) combined with CY (EX+CY). The insulin secretion of UCMSC and βcell was measured with ELISA when the cells were growing in different concentrations of glucose media for different times. UCMSCs (4×105) and the same number of cells prepared with two methods were transplanted to type I diabetic rat models. UCMSCs could be induced into islet βcells by CY or EX+CY in vitro. The insulin secretion of the prepared β cells growing in 25.0 mM glucose medium was over 5-fold of that in 6.0 mM glucose. The transplantation of the βcells to type I diabetic rat models could reduce the blood glucose and prolong the survival time. The β cells induced by EX+CY had much more significant effects on decreasing blood glucose and increasing survival time (p<0.01). The cells did not affect blood sugar level and had no serious side-effects in human health. UCMSC could be induced to islet βcells with either CY or EX+CY. The transplantation of the induced islet βcells could reduce blood glucose and prolong the survival time of diabetic animal models. Although the cells induced with EX+CY had more significant effects on diabetic rats, they did not affect blood glucose level and had no serious side-effects in human health.

Premature ovarian failure(POF)is a gynecological endocrine disease caused by ovarian dysfunction.Mesenchymal stem cells(MSCs)can effectively treat premature ovarian failure,and play a role in repairing ovarian structure and improving ovarian function.The specific mechanism can be a direct differentiation into granulosa cells or inhibition of their apoptosis through the homing effect of MSCs or differentiate into primordial germ cells.Benefit of MSCs can also be attributed to ovarian angiogenesis promotion,immune regulation,reduce oxidative stress re-sponse and paracrine,all potentially promote recovery of ovarian function,and thus improve the fertility of women of childbearing age.

ObjectiveTo retrospectively investigate the effect of combined treatment with human umbilical cord blood mononuclear cells (hUCB-MNCs) and human umbilical cord mesenchymal stem cells (hUC-MSCs) on liver function, inflammation grade, and immune function in patients with hepatitis B-related decompensated cirrhosis. Methods 11 patients with liver cirrhosis who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from November 2016 to June 2019 were enrolled in this clinical study and were given infusion of hUCB-MNCs (＞18×109/time) once in the first week and infusion of hUC-MSCs (1×106/kg) once a week in the second, third, and fourth weeks. Reexamination was performed at 4, 8, and 12 weeks after treatment to compare the changes in liver function, blood ammonia, blood coagulation factors, serum levels of cytokines, and lymphocyte subsets after treatment, and the changes in neurological and psychiatric symptoms were observed and recorded. A one-way repeated-measures analysis of variance was used for comparison of continuous data between groups. ResultsAfter the combined treatment with hUCB-MNCs and hUC-MSCs, all 11 patients achieved certain improvements in psychiatric and neurological symptoms after infusion, and liver function parameters and blood coagulation function basically returned to normal (all P＜0.05). At 12 weeks after the combined infusion of cells, blood ammonia level returned to the normal level (P＜0.05), and there were significant reductions in the levels of the inflammatory cytokines interleukin-6 and tumor necrosis factor (F=49497 and 37.071, both P＜0.05) and significant increases in the levels of the anti-inflammatory cytokines transforming growth factor-β and interleukin-10 (F=35.843 and 15.918, both P＜005). There were also significant reductions in the percentages of the cytotoxic cells CD3+CD8+ T and CD19+ B cells (F=52.242 and 89.097, both P＜0.05) and a significant increase in the regulatory T cells CD4+CD25+ (F=17.337, P＜0.05). ConclusionCombined treatment with hUCB-MNCs and hUC-MSCs for liver cirrhosis can optimize liver function, reduce the production of inflammatory cytokines, alleviate liver inflammation and liver cell destruction, and increase regulatory T cells, thereby affecting the body’s immune function.

神经干细胞的寿命是有限的,通过人脐带间充质干细胞诱导为神经干细胞,为临床代替受损的神经细胞治疗神经系统疾病提供理论资源,以寻找可以促进中枢神经系统损伤修复的理想细胞来源.这项技术通过对神经系统疾病发病机制的研究以及诱导型神经干细胞移植治疗机制的研究,为临床治疗提供新方向.本文将对来源于间充质干细胞的诱导型神经干细胞的应用前景做进一步阐述.

γδT细胞自发现以来,一度被研究学者忽视,甚至被认为是进化史上的”残留物”.随着研究的深入,人们发现γδT细胞数量虽少,但功能强大且全面,在免疫治疗方面更是突出,尤其在肿瘤免疫,感染免疫,自身免疫功能调节,修复损伤等方面的功能及临床治疗价值更是重要.近年来,肿瘤免疫治疗已经展现了独树一帜的运用价值和运用前景,以免疫靶向点治疗、“过继性免疫治疗”、肿瘤疫苗等为首的免疫治疗迅速进步并获得一定临床效果,是目前研究的一大热点,本文以“肿瘤免疫治疗”为立脚点,综述γδT细胞的免疫学特性,活化及抗肿瘤机制,以及在治疗肿瘤治疗方面的研究进展.

For decades, researchers have focused on building genetically and phenotypically stable neural stem cell lines designed to restore the irreversible loss of function of nerve tissue to meet clinical needs. Among them, stem cells that maintain their pluripotent state in adults have also become one of the research focuses. With the development of technologies such as induced pluripotent stem cells and direct differentiation of somatic cells into desired cell types, research methods based on the use of allogeneic neural stem cells derived from embryonic or fetal neural tissue have gradually become a thing of the past. This article will review the basic molecular mechanisms surrounding the maintenance of pluripotent states of stem cells and reprogrammed somatic cells, as well as experimental protocols for inducing neural stem cells.

在过去几十年里,以细胞因子为主的非特异性免疫治疗是晚期肾细胞癌(advanced renal-cell carcinoma,ARRC)的一线治疗标准,直到后来靶向药物的出现,使ARCC进入靶向药物治疗时代,但靶向药物的进一步应用及发展被其耐药和毒副作用所限制.而近年来,随着免疫检查点抑制剂(Immune checkpoint inhibitors,ICI)的研发和临床应用,肿瘤的ICI治疗逐渐成为研究热点,下面将围绕ICI治疗ARCC研究进展进行简单综述.

目的 探讨不同浓度二甲双胍(METF)对人脐带间充质干细胞(hUC-MSC)形态、增殖、表面标志及细胞周期的影响.方法 取健康足月新生儿脐带在体外分离出hUC-MSC进行传代培养,至第3代(流式细胞仪分析)对细胞进行鉴定,取第6代处于对数生长期的hUC-MSC(相对老化),将对照组与不同浓度METF(0.1,1,5,10,20 mmol/L)干预的细胞进行比较,观察不同浓度METF干预对细胞的形态、增殖率(MTT法分别于24、48、72 h检测)、及细胞表面标志和细胞周期的影响,采用One-Way ANOvA,及LSD-t检验进行统计学分析.结果 (1)METF为0.1 mmol/L、1 mmol/L,细胞形态无显著改变,当药物浓度为5～20 mmol/L时,随着药物浓度增加、培养时间延长,细胞形态改变越显著.(2)METF为0.1 mmol/L(24 h:101.28±0.98,24 h:104.06±1.76,24 h:101.51±0.67)促进hUC-MSC增殖,药物浓度为1～10 mmol/L在培养初期可增加间充质干细胞的增殖率,随着培养时间的延长,细胞的增殖逐渐被抑制.METF为20 mmol/L(24 h:86.64±0.66,48 h:58.38±2.52,72 h:17.75±1.35)抑制细胞增殖,抑制作用随着时间延长而增强(P<0.05).(3)当METF浓度为5,10,20 mmol/L时,随着药物浓度的增加,CD105的表达逐渐减弱(F=17.539,P<0.05).METF未对CD44、CD90产生影响.(4)METF为0.1 mmol/L时降低G0/G1期的比例(64.16±1.20,P<0.05),促进间充质干细胞的增殖,随着药物浓度的增加,细胞增殖逐渐被抑制.结论 METF浓度在0.1mmol/L促进hUC-MSC增殖,而在浓度5～20 mmol/L时抑制人脐带间充质干细胞的增殖及表面标志CD105的表达,不同浓度的METF均未对CD44、CD90的表达产生影响.

Objective To compare the clinical effects of oxaliplatin combined with fluorouracil (5-fluorouracil, capecitabine) in the treatment of colorectal cancer with liver metastases. Methods Retrospective analysis 94 patients with colorectal cancer liver metastases diagnosed by pathology from September 2009 to February 2017 in the Affiliated Hospital of Inner Mongolia Medical University were divided into two groups according to the first-line chemotherapy regimen. XELOX group 48 cases of oxaliplatin combined with Xeloda, 46 cases of FOLFOX group (oxaliplatin combined with 5-FU, calcium leucovorin). The clinical efficacy of the two groups of protocols was observed. Results/Conclusion The control rate, effective rate, and disease progression time of the XELOX regimen were similar to those of the FOLFOX regimen, and the difference was not statistically significant.

There are many small particles in the human circulation, such as platelet granule, extracellular vesicles (EVs), microparticles, DNA fragments, etc. In recent years, studies have found a small particle material different from the above substances, which is a nuclear-free structure. The diameter of the small particles is approximately 1-5 um, which has a thin two-layer membrane structure under electron microscope[1]. The small particles contains no DNA and is capable of self-amplification [1]. The DNA-free small particles (DFSPS) in the human circulation can also express surface markers such as octamer-binding transcription factor 4 (OCT4), sex determining region Y 2 (SOX2), and DEAD box polypeptide 4 (DDX4[2]). After observation, we found that the small particles is neither platelets nor extracellular vesicles. In addition, DNA-free small particles in the human circulation may be involved in the formation of stem cells, has function of repairing epithelial cell damage [3] and kidney regeneration [4].

目的:观察树突状细胞-细胞因子诱导杀伤细胞(DC-CIK)联合化疗、射频消融治疗结直肠癌术后肝转移疗效.方法:回顾性分析我院2012年8月至2015年8月收治的结直肠癌术后肝转移患者临床资料,全身化疗联合射频消融治疗者归入对照组,化疗、射频之外再联合DC-CIK治疗者归入观察组,比较两组患者肝转移灶切除率、治疗效果以及治疗前后T细胞亚群变化情况、生存率及生活质量.结果:治疗后观察组肝转移灶切除率24.66％高于对照组的10.67％,差异有统计学意义(P＜0.05).观察组客观控制率(ORR) 64.38％高于对照组的29.33％,差异有统计学意义(P＜0.05).治疗前T细胞亚群各指标组间比较差异无统计学意义(P＞0.05).治疗后观察组CD4+与CD4+/CD8+均高于对照组,差异有统计学意义(P＜0.05).治疗后CD8+组间比较差异无统计学意义(P＞0.05).治疗前两组肿瘤标志物水平组间比较差异无统计学意义(P＞0.05).治疗后观察组CEA及CA125水平较对照组低,差异有统计学意义(P＜0.05).观察组1年生存率、2年生存率及3年生存率均高于对照组,差异有统计学意义(P＜0.05).观察组情感功能、生理功能、社会生活与日常生活评分均高于对照组,差异有统计学意义(P＜0.05).结论:常规治疗基础上联合DC-CIK治疗可提高结直肠癌术后肝转移患者免疫功能及肝转移灶切除率,改善生存率及生活质量.

目的:评价脐带血来源单个核细胞(umbilical cord blood mononuclear cell,UCMC)诱导分化的免疫细胞对小细胞肺癌(small cell lung cancer,SCLC)患者免疫功能的影响.方法:选取2012年1月至2015年12月就诊于内蒙古医科大学附属医院的90例SCLC患者,采用分层随机方法分为对照组(45例,EP方案)和研究组(45例,EP方案+UCMC诱导分化的免疫细胞),研究组患者在化疗结束后3～5 d进行一个疗程的UCMC诱导分化的免疫细胞治疗[(1～3)×1010个细胞/疗程],每30 d为一个周期.治疗前及治疗结束后12周,采用流式细胞术检测患者外周血中T细胞亚群的变化及相关因子IFN-γ、IL-2、IL-10、TGF-β1的变化,评价患者生活质量和不良反应等.结果:研究组获得CR 15例、PR 25例、SD 5例,研究组T细胞亚群含量较对照组有明显增加(P＜0.01)、并且恢复正常范围的时间明显短于对照组(P＜0.05);80.9％的患者炎性细胞因子IFN-γ在血清中升至或高于正常范围,IL-10、TGF-β1较治疗前降低(P＜0.05);患者生活质量较对照组有显著提高.结论:UCMC诱导分化的免疫细胞可以促进SCLC患者化疗后免疫功能的恢复.

Dendritic cells (DCs) are the key to connecting innate and acquired immunity.In infections and allergic reactions,DCs,as full-time antigen-presenting cells,elicit a T-cell immune response and maintain the autoantigen immune tolerance.Mediated sarcoma immune responses are beneficial for the treatment of infectious diseases as well as cancers and the like,while the immune tolerance induced by DCs plays a role in the control of autoimmune diseases,allergies or inflammatory diseases.Studies have shown that a variety of plant components can regulate the phenotype and function of DCs and they are effective in the clinical use of immunotherapy.Therefore,the use of plant components which can regulate the immune function of DC will provide new ideas for developing effective and low-cost methods of cell therapy.This review summarizes the recent studies on the function of plant components in the regulation of DCs,the effects of plant components on the dendritic phenotypes and their regulatory roles in immune response and immnnosuppression.

近年来,恶性肿瘤已经严重危害人类健康,传统的肿瘤治疗方法包括手术、化学治疗、放射治疗、中医药治疗,但都有不同程度副作用,近年来兴起的生物免疫治疗有很好的前景.其中γδT细胞有待更进一步深入研究.目前已发现γδT细胞不仅在肿瘤疾病中可以发挥重要的作用,在感染性疾病、自身免疫性疾病等许多疾病中也可以发挥不可替代的作用.

Objective To study the changes in morphology , phenotypes and gene expression pro-files of dendritic cells (DCs) following treatment with Seabuckthorn flavones (SF).Methods DCs were treated with 200μg/ml of SF and then cultured for 7 days.Changes in the morphology of DCs were observed under light microscope .Flow cytometry was used to detect DC surface molecules .Total RNA was extracted to construct the library for digital gene expression profiling ( DGE ) .Differentially expressed genes were screened out and further analyzed by gene ontology ( GO) enrichment analysis and Kyoto encyclopedia of genes and genomes ( KEGG ) pathway enrichment analysis .Results Compared with control group , SF treatment significantly enhanced the expression of HLA-DR, CD80, CD83 and CD86 on DCs.A total of 355 differentially expressed genes were screened out by DGE , including 176 up-regulated genes and 179 down-regulated genes .GO enrichment was mainly involved in the regulation and development of the immune sys -tem and other biological processes .KEGG pathway analysis showed that the significantly enriched pathways were closely related to inflammation , the immune system, cancer and other diseases .Conclusion SF can promote the expression of DC co-stimulatory molecules and pro-mature molecules, and regulate the expres-sion of immunity-related genes such as CD11a, SLAMF6, LMCD1, TSC22D3 and IKZF3.

Objective:To study the effect of dendritic cell-cytokine induced killer cell (DC-CIK) immunotherapy combined with chemotherapy on advanced non-small cell lung cancer (NSCLC) and its influence on immune function.Methods:Sixty patients with stage Ⅲb～Ⅳ NSCLC treated in our hospital from January 2014 to December 2015,they were divided into combined group and chemotherapy group according to the random number table method,with 30 patients in each group.Combined group was treated with DC-CIK immunotherapy combined with chemotherapy (cisplatin+gemcitabine),1 month for a cycle,while the chemotherapy group was only treated with chemotherapy,1 month for a cycle.The short-term efficacy,progression-free survival (PFS),overall survival (OS),immune function,life quality,and adverse reactions were compared between the two groups.Results:DCR in combined group was significantly higher than chemotherapy group (P＜0.05).The median PFS of combined group was higher than chemotherapy group (P＜0.05).CD3+,CD3+CD4+ and natural killer (NK) cells in the peripheral blood of the combined group increased significantly after treatment (P＜0.05),and CD3+CD8+ cells significantly decreased after treatment (P＜0.05).CD3+,CD3+CD4+ and NK cells in combined group were significantly higher than chemotherapy group after treatment (P＜0.05),CD3+CD8+ cells were significantly lower than chemotherapy group after treatment (P＜0.05).The incidence of fatigue,pain,loss of appetite and sleep disorder in combined group were significantly lower than chemotherapy group (P＜0.05).The rate of leukopenia and thrombocytopenia in combined group were significantly lower than chemotherapy group (P＜0.05).Conclusion:DC-CIK combined with chemotherapy has obvious effect in the treatment of advanced NSCLC,which could improve the DCR,prolong PFS,improve immune function and improve life quality,reduce adverse reactions.

In recent years , bioimmunotherapies have been widely used in the clinical treatment of various malignant tumors,among which the tumor antigen loaded dendritic cells (DC) vaccine combined immunocompetent cells technology is the most mature and most widely used .DC are known to be the most potent antigen-presenting cells and play an important role in anti-tumor immunity.DC is closely related to the occurrence and development of tumor ,which greatly increases the survival rate of malignant tumor patients is greatly improved on the basis of combined traditional therapy .But the role of DC in the body and its characteristics are not entirely clear ,and further clarification of the role of DC in the tumor microenviron-ment,will provide reference for improving the effect of biological treatment .

Objectives . In order to enhance the immunity of cancer patients to prevent relapse or to prolong survival time, umbilical cord blood mononuclear cells (UCMCs) were transplanted to cancer patients. Patients and Methods . UCMCs were transfused to 63 immunocompromised gastrointestinal cancer patients with nonmyeloablative (NMA) conditioning regimen. Results . The clinical study showed that the number of both T and B cells increased much more rapidly after transfusion of UCMCs than that of the control group without transplantation (p<0.01). Proinflammation cytokines IFN γ and TNF α in serum increased to or above the normal range in 80.9% of patients at 12 weeks after UCMC transfusion. However, they recovered to the normal range in 21.7% of patients at the same time point in the control group only. In addition, the clinical investigation also showed that the transfusion of UCMC increased stable disease (SD) and reduced progressive disease (PD) significantly (p<0.01); however, it did not have significant effects on complete response (CR), partial response (PR), or mortality rates compared with the control group (p>0.05). Conclusions . UCMCs have powerful repairing effects on damaged cells and tissues and may reconstruct the impaired immunity. Transfusion of UCMCs could reconstruct the immunity of cancer patients with immunosuppression.