Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies

Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+T cell function in esophageal squamous cell carcinoma

Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.

Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+T Cell-Related Immune Genes

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment efficacy.CD8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing technology.By leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to immunotherapy.Methods Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC databases.In the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T cells.Subsequently,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic model.The accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)curves.Furthermore,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic responses.Additionally,we investigated the potential underlying biological pathways that contribute to divergent treatment responses.Results We successfully developed a model capable of predicting the prognosis of patients with TNBC.The areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,respectively.Employing this risk model,we stratified the samples into high-and low-risk groups.Through KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine pathways.Furthermore,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores,indicating that our model effectively predicted the response of patients to immune-based treatments.Conclusion Our study demonstrates the potential of CXCL13,GBP2,and GZMB as prognostic indicators of clinical outcomes and immunotherapy responses in patients with TNBC.These findings provide valuable insights and novel avenues for developing immunotherapeutic approaches targeting TNBC.

Revolutionizing tumor immunotherapy:unleashing the power of progenitor exhausted T cells

In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8^(+) T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.

Identification of prognostic molecular subtypes and model based on CD8+ T cells for lung adenocarcinoma

Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.

Effect of substrate temperature and oxygen plasma treatment on the properties of magnetron-sputtered CdS for solar cell applications

Cadmium sulfide(CdS)is an n-type semiconductor with excellent electrical conductivity that is widely used as an electron transport material(ETM)in solar cells.At present,numerous methods for preparing CdS thin films have emerged,among which magnetron sputtering(MS)is one of the most commonly used vacuum techniques.For this type of technique,the substrate temperature is one of the key deposition parameters that affects the interfacial properties between the target film and substrate,determining the specific growth habits of the films.Herein,the effect of substrate temperature on the microstructure and electrical properties of magnetron-sputtered CdS(MS-CdS)films was studied and applied for the first time in hydrothermally deposited antimony selenosulfide(Sb_(2)(S,Se)_(3))solar cells.Adjusting the substrate temperature not only results in the design of the flat and dense film with enhanced crystallinity but also leads to the formation of an energy level arrangement with a Sb_(2)(S,Se)_(3)layer that is more favorable for electron transfer.In addition,we developed an oxygen plasma treatment for CdS,reducing the parasitic absorption of the device and resulting in an increase in the short-circuit current density of the solar cell.This study demonstrates the feasibility of MS-CdS in the fabrication of hydrothermal Sb_(2)(S,Se)_(3)solar cells and provides interface optimization strategies to improve device performance.

The Mechanisms of CD8+ T Cells Exhaustion in the Tumor Microenvironment and Immune Therapy

In the tumor immune microenvironment, CD8+ T cells differentiate towards functional failure. The exhaustion of CD8+ T cells (Tex) showed varying degrees of effect dysfunction, loss of proliferation ability, and sustained high expression of a variety of inhibitory receptors, with metabolic and epigenetic changes. Tex cells are heterogeneous, including several subsets with different characteristics at different stages of differentiation. Immune checkpoint inhibitors (ICIs) can restore the effect or function of Tex cells, indicating that this T cell subset plays a key role in tumor immunotherapy. The understanding of the mechanism of CD8+ T cell exhaustion will be helpful to the implementation of tumor immunotherapy. This article reviews the production, differentiation and functional characteristics of Tex cells and their relationship with tumor immunotherapy.

Repetitive administration of cultured human CD34+cells improve adenine-induced kidney injury in mice

BACKGROUND There is no established treatment to impede the progression or restore kidney function in human chronic kidney disease(CKD).AIM To examine the efficacy of cultured human CD34+cells with enhanced proliferating potential in kidney injury in mice.METHODS Human umbilical cord blood(UCB)-derived CD34+cells were incubated for one week in vasculogenic conditioning medium.Vasculogenic culture significantly increased the number of CD34+cells and their ability to form endothelial progenitor cell colony-forming units.Adenineinduced tubulointerstitial injury of the kidney was induced in immunodeficient non-obese diabetic/severe combined immunodeficiency mice,and cultured human UCB-CD34+cells were administered at a dose of 1×106/mouse on days 7,14,and 21 after the start of adenine diet.RESULTS Repetitive administration of cultured UCB-CD34+cells significantly improved the time-course of kidney dysfunction in the cell therapy group compared with that in the control group.Both interstitial fibrosis and tubular damage were significantly reduced in the cell therapy group compared with those in the control group(P<0.01).Microvasculature integrity was significantly preserved(P<0.01)and macrophage infiltration into kidney tissue was dramatically decreased in the cell therapy group compared with those in the control group(P<0.001).CONCLUSION Early intervention using human cultured CD34+cells significantly improved the progression of tubulointerstitial kidney injury.Repetitive administration of cultured human UCB-CD34+cells significantly improved tubulointerstitial damage in adenine-induced kidney injury in mice via vasculoprotective and anti-inflammatory effects.

CD19 CAR-T细胞治疗难治/复发急性B淋巴细胞白血病儿童及青少年患者的疗效及安全性

目的探讨CD19嵌合抗原受体T细胞(CAR-T)治疗对于儿童及青少年难治/复发急性B淋巴细胞白血病(B-ALL)的疗效及安全性。方法回顾性分析2017年6月至2021年3月接受CD19 CAR-T治疗的<25岁难治/复发B-ALL患者的临床资料,评估该疗法的疗效及安全性。结果共纳入64例难治/复发B-ALL患者,男35例、女29例,中位年龄8.5(1.0~17.0)岁。CD 19 CAR-T回输后1个月进行短期疗效评估,64例患者均获得完全缓解(CR)/完全缓解兼部分血细胞计数缓解(CRi),其中有62例患者达骨髓微小残留病灶(MRD)阴性。细胞因子释放综合征(CRS)及免疫效应细胞相关神经毒性综合征(ICANS)发生率分别为78.1%及23.4%。共22例患者复发,中位复发时间10.1个月,4年总生存(OS)率为(66.0±6.0)%,4年无白血病生存(LFS)率为(63.0±6.0)%。长期随访结果显示桥接异基因造血干细胞移植(allo-HSCT)患者的LFS和OS率均优于未桥接移植患者(4年LFS率:81.8%±6.2%对24.0%±9.8%,4年OS率:81.4%±5.9%对44.4%±11.2%;均P<0.01)。结论CD 19 CAR-T可有效治疗难治/复发B-ALL,输注后桥接allo-HSCT能进一步改善患者的长期生存情况。

非小细胞肺癌不同胸腔积液严重程度及预后患者lncRNA MEG3表达及其与Th17/CD4^(+)T细胞的关系

目的:研究非小细胞肺癌(NSCLC)不同胸腔积液严重程度及预后患者lncRNA MEG3表达及其与Th17/CD4^(+)T细胞的关系。方法:选取2020年1月至2022年12月福建医科大学附属泉州第一医院收治的104例NSCLC恶性胸腔积液患者作为研究对象,根据胸腔积液量分为3组:少量胸腔积液组(35例)、中量胸腔积液组(42例)、大量胸腔积液组(27例)。根据患者疾病实际发展转归分为预后良好组(29例未出现复发和转移)和预后不良组(75例出现复发和转移)。另选取同期于福建医科大学附属泉州第一医院治疗的60例肺炎良性胸腔积液患者作为对照组。实时荧光定量PCR检测两组胸腔积液中MEG3表达。收集受试者外周静脉血,流式细胞术检测外周血Th17细胞、CD4^(+)T细胞比例,并计算Th17/CD4^(+)T。对比各组患者lncRNA MEG3及外周血Th17、CD4^(+)T细胞水平。Logistic回归分析NSCLC胸腔积液及预后的影响因素。结果:NSCLC组胸腔积液lncRNA MEG3表达及CD4^(+)T细胞百分比低于对照组,Th17细胞百分比、Th17/CD4^(+)T高于对照组(P<0.05)。大量胸腔积液组lncRNA MEG3表达及CD4^(+)T细胞百分比低于少量胸腔积液组、中量胸腔积液组,中量胸腔积液组lncRNA MEG3表达及CD4^(+)T细胞百分比低于少量胸腔积液组,大量胸腔积液组Th17细胞百分比、Th17/CD4^(+)T高于少量胸腔积液组、中量胸腔积液组,中量胸腔积液组Th17细胞百分比、Th17/CD4^(+)T高于少量胸腔积液组(P<0.05)。预后不良组lncRNA MEG3表达及CD4^(+)T百分比低于预后良好组,而Th17细胞百分比、Th17/CD4^(+)T高于预后良好组(P<0.05)。Logistic回归分析结果显示,lncRNA MEG3为NSCLC胸腔积液的保护因素,Th17/CD4^(+)T为危险因素(P<0.05);lncRNA MEG3为NSCLC预后的保护因素,Th17/CD4^(+)T为危险因素(P<0.05)。结论:NSCLC不同胸腔积液严重程度及预后患者lncRNA MEG3表达及Th17/CD4^(+)T不同,且lncRNA MEG3为NSCLC胸腔积液及预后的保护因素,Th17/CD4^(+)T为危险因素,可作为胸腔积液严重程度及预后诊断的有效生物标志物。

外周血CD4^(+)PD-1^(+)Tcells及CD4^(+)T淋巴细胞ATP含量与复发性卵巢癌疗效的相关性分析

目的 探讨外周血CD4^(+)程序性细胞死亡受体-1(PD-1)^(+)T cells及CD4^(+)T淋巴细胞三磷酸腺苷(ATP)含量与复发性卵巢癌疗效的相关性。方法 选取30例复发性卵巢癌患者为复发组,30例未复发卵巢癌患者为非复发组;另选取30名同期体检健康者作为对照组。评估外周血CD4^(+)PD-1^(+)T cells及CD4^(+)T淋巴细胞ATP含量与复发性卵巢癌疗效的相关性。结果 复发组和非复发组的CD4^(+)PD-1^(+)T cells较对照组明显升高(P<0.05)。复发组和非复发组的CD4^(+)T淋巴细胞ATP含量较对照组明显降低(P<0.05)。复发组治疗后CD4^(+)PD-1^(+)Tcells显著低于治疗前(P<0.05),治疗后CD4^(+)T淋巴细胞ATP含量显著高于治疗前(P<0.05)。CD4^(+)PD-1^(+)T cells与复发性卵巢癌疗效成负相关(r=-0.393,P=0.039),CD4^(+)T淋巴细胞ATP含量与复发性卵巢癌疗效成正相关(r=0.449,P=0.031)。结论 复发性卵巢癌患者外周血CD4^(+)PD-1^(+)T cells及CD4^(+)T淋巴细胞ATP含量与疗效密切相关。

Pt-Pd-Ni体系相图与热力学研究进展

铂基催化剂具有活性高、选择性好、电化学稳定性佳等优点,在工业催化和燃料电池领域具有非常重要的地位。然而,由于成本较高、可用性较低限制了其实际发展。因此,有必要优化铂基催化剂的利用率,设计低成本和高稳定性的铂基催化剂。本研究首先介绍了在燃料电池催化剂领域具有应用前景的Pt-Pd-Ni系合金电催化剂的发展和研究现状,然后详细介绍了Pt-Pd-Ni体系的三个二元系相图与热力学评估数据和研究进展,并对Pt-Pd-Ni三元系的一些实验研究进展和今后的研究工作提出展望,对不同相结构对催化性能的影响进行了分析和讨论。通过Pt-Pd-Ni系相图和相结构等的研究将为燃料电池用新型贵金属合金催化材料的设计及工业应用奠定理论和实验基础。

儿童CD19 CAR-T细胞治疗相关B细胞再生障碍的临床意义和对策

急性B系淋巴细胞白血病(B-ALL)患儿在CD 19 CAR-T细胞治疗后普遍发生B细胞再生障碍(BCA),BCA持续的时间长短对患者的免疫状态及预后会产生影响。对BCA的充分认识有助于临床医师科学、规范、合理地选择治疗策略,减少CAR-T治疗后白血病患儿的感染机会,提高生活质量,改善预后。

多孔状Ni-NiO/CdS催化剂的制备及其光催化性能研究

该文以Ni泡沫为Ni源,经不完全氧化得到Ni-NiO,然后通过一锅法水浴合成了一种多孔结构的Ni-NiO/CdS光催化剂.利用SEM、XRD、XPS和BET等表征手段对光催化剂的微观形貌和结构以及表面成分和组成进行了全方位表征,并以光诱导裂解水制氢气的实验对催化剂的光催化活性进行评价.研究了Ni-NiO与CdS的比例和不同硫源对Ni-NiO/CdS光催化剂催化性能的影响.实验结果表明:Ni-NiO/CdS的光催化析氢速率高达19 947.9μmol·h^(-1)·g^(-1),是纯CdS的近8倍,量子效率高达32.6%.这是由于CdS和NiO形成p-n异质结和Ni~0/Ni^(2+)电子对的存在,明显提高载流子分离效率,从而提高了其光催化活性.

Donor-derived CD 19 CAR-T Cells versus Chemotherapy Plus Donor Lymphocyte Infusion for Treatment of Recurrent CD 19-positive B-ALL after Allogeneic Hematopoietic Stem Cell Transplantation

Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.

红辉沸石两步水热制备高品质X型分子筛及其高效吸附Cd^(2+)、Ni^(2+)性能研究

本研究以红辉沸石为原料,经两步水热法制备高品质的X型分子筛,探究了n(H_(2)O/SiO_(2))、n(Na_(2)O/SiO_(2))、n(Al_(2)O_(3)/SiO_(2))、陈化时间、晶化温度、晶化时间等因素对红辉沸石转化为X型分子筛的影响,以及考察了X型分子筛对Cd^(2+)、Ni^(2+)的吸附性能。研究表明,X型分子筛的最优转化条件为:n(H_(2)O/SiO_(2))=55、n(Na_(2)O/SiO_(2))=1.1、n(Al_(2)O_(3)/SiO_(2))=0.33、陈化时间48 h、晶化温度82℃、晶化时间4 h。红辉沸石溶解后解聚为低聚态Si物种且在体系中保留参与分子筛的生长,使得所合成的X型分子筛相对结晶度达100%、n(Si/Al)值为1.14,并缩短了晶化时间和降低了晶化温度,其中所合成的X型分子筛对Cd^(2+)和Ni^(2+)的吸附容量分别达到173.553 mg/g和75.897 mg/g。因此,本研究将为天然矿物快速转化为高品质的X型分子筛设计与制备提供理论基础和技术支持。

Study on the effect and mechanism of the dysfunction of CD4^+ T cells in the disease process of chronic cardiac failure

Objective: To study the effect and mechanism of the dysfunction of CD4+ T cells in the disease process of chronic cardiac failure (CHF).Methods:According to different group technologies, 100 CHF patients were divided into the following groups: ischemia group and non-ischemia group, heart function Ⅰ-Ⅱ group and heart function Ⅲ-Ⅳ group, event group and non-event group, and 50 healthy volunteers were included in the control group. Realtime PCR was used to detect transcription factors T-bet and GATA-3 of Th1 and Th2; flow cytometry was applied to determine the ratio of Th17 and Treg cells; ELISA was employed to test cytokines IFN-γ, IL-4, IL-17 and IL-10 of peripheral blood Th1, Th2, Th17 and Treg cells, respectively; ultrasonic cardiogram was used to exploit to LVEF and LVEDd; and electrochemilu minescene immunoassay was used to examine plasma BNP. The differences of all indexes of all groups were analyzed and the correlation between CD4 T cells and clinical indexes was analyzed by Pearson correlation analysis. Results: As compared to the control group, the transcription factors T-bet and GATA-3 of Th1 and Th2, the ratio of cytokines Th17 and IFN-γ, cytokines IL-17, T-bet/GATA-3, IFN-γ/IL-4, Th17 cells/Treg cells, IL-17/IL-10 of the ischemia group and non-ischemia group, heart functionⅠ-Ⅱgroup and heart function Ⅲ-Ⅳ group, event group and non-event group were all increased significantly, while their transcription factor GATA-3 of Th2, cytokines IL4, Treg cells ratio, cytokines IL10 were decreased obviously. The differences showed statistical significance (P < 0.05). The increase or decrease of the partial CD4+ T cells of the ischemia group, heart function Ⅲ-Ⅳ group and event group was more distinctly. The results of Pearson correlation analysis showed that IFN-γ and IL-17 were significantly positively correlated with LVEDd and BNP, IL-4 and IL-10 were also significantly positively correlated with LVEF, but correlated negatively with BNP, and IL-17 was negatively correlative with LVEF. Conclusions: There was a correlation between CHF and the dysfunction of CD4+ T cells showing immune activation phenomenons of deviations from the Th1/Th2 balance towards Th1 and from the Th17/Treg balance towards Th17, which was also related to the types, severity and prognosis of the disease.

Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation

Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.

CD133^+ gallbladder carcinoma cells exhibit self-renewal ability and tumorigenicity

AIM： To identify cancer stern cells （CSCs） in human gallbladder carcinomas （GBCs）. METHODS： Primary GBC cells were cultured under serum-free conditions to produce floating spheres. The stem-cell properties of the sphere-forming cells, including self-renewal, differentiation potential, chemoresistance and tumorigenicity, were determined in vitro or in vivo. Cell surface expression of CD133 was investigated in primary tumors and in spheroid cells using flow cytometry. The sphere-colony-formation ability and tumorigenicity of CD133＋ cells were assayed.floating spheroids were generated from primary GBC cells, and these sphere-forming cells could generate new progeny spheroids in serum-free media. Spheroid cells were differentiated under serum-containing conditions with downregulation of the stem cell markers Oct-4, Nanog, and nestin （P 〈 0.05）. The differentiated cells showed lower spheroid-colony-formation ability than the original spheroid cells （P 〈 0.05）. Spheroid ceils were more resistant to chemotherapeutic reagents than the congenetic adherent cells （P 〈 0.05）. Flow cytometry showed enriched CD133＋ population in sphereforming cells （P 〈 0.05）. CD133＋ cells possessed high colony-formation ability than the CD133 population （P 〈 0.01）. CD133＋ cells injected into nude mice revealed higher tumorigenicity than their antigen-negative counterparts （P 〈 0.05）. CONCLUSION： CD133 may be a cell surface marker for CSCs in GBC.