[Toxicity Management and Efficacy Evaluation of BCMA-CART in the Treatment of Relapsed and Refractory Multiple Myeloma].

OBJECTIVE: To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM). METHODS: The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated. RESULTS: After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity. CONCLUSION: BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.

A Web of Science-based scientometric analysis about mammalian target of rapamycin signaling pathway in kidney disease from 1986 to 2020.

BACKGROUND: The mammalian target of rapamycin (mTOR) signaling pathway is vital for the regulation of cell metabolism, growth and proliferation in the kidney. This study aims to show current research focuses and predict future trends about mTOR pathway in kidney disease by the methods of scientometric analysis. METHODS: We referred to publications from the Web of ScienceTM Core Collection (WoSCC) Database. Carrot2, VOSviewer and CiteSpace programs were applied to evaluate the distribution and contribution of authors, institutes and countries/regions of extensive bibliographic metadata, show current research focuses and predict future trends in kidney disease's area. RESULTS: Until July 10, 2020, there are 2,585 manuscripts about mTOR signaling pathway in kidney disease in total and every manuscript is cited 27.39 times on average. The big name of course is the United States. Research hot spots include "diabetic nephropathy", "kidney transplantation", "autosomal dominant polycystic kidney disease", "tuberous sclerosis complex", "renal cell carcinoma" and "autophagy". Seven key clusters are detected, including "kidney transplantation", "autosomal dominant polycystic kidney disease", "renal transplantation", "renal cell carcinoma", "hamartin", "autophagy" and "tuberous sclerosis complex". CONCLUSIONS: Diabetic nephropathy, kidney transplantation, autosomal dominant polycystic kidney disease, tuberous sclerosis complex, renal cell carcinoma and autophagy are future research hot spots by utilizing scientometric analysis. In the future, it is necessary to research these fields.

[Treatment Selection of Elderly Acute Myeloid Leukemia Patients Guided by HCT-CI Score].

OBJECTIVE: To explore the feasibility of guiding the individalized treatment strategy for elderly AML patients by using hematopoietic cell transplantation-comorbidity index(HCT-CI) score. METHODS: The clinical and biological data of 165 elderly (260 years) AML patients in department of hematology of the first affiliated hospital of Wenzhou medical universtity from January 2000 to December 2014 were analyzed retrospectively. The AML patients were divided into 3 groups: score 0-1, 2-3 and ≥4 according to HCT-CI, then the patients in each group again were divided into standard chemotherapy group, low dose chemotherapy group and support therapy group accoriding to therapeutic regimens, and the efficacy of above mentioned 3 kinds of treatment and their effects on survival of ealderly AML patients were compared, the prognostic risk factors for patients were analyzed further. RESULTS: A total of 165 patients (100%) were followed-up, and the mean follow-up time was 309 days, median survival time was 210 days. The survival analysis showed that the patients in HCT-CI score 0-1 group and 2-3 group banefited from chemotherapy, while the survival analysis of the HCT-CI score ≥4 group showed that there were no significant differance in survival rate between support therapy and chemotherapy groups. The complete remission rate and early mortality of patients received low dose or standard dose chemotherapy in HCT-CI score 0-1, 2-3 and ≥4 groups were not significantly different. Univariate analysis and multivariante analysis of COX ratio risk model showed that the EOCG-PS≥2, WBC≥100×107/L at initial diagnosis and HCT-CI score ≥4 were the independent risk factor affecting the prognosis of elderly AML patients. The median survival time of patients received chemotherapy and support therapy was 840 and 150 d(P<0.01) in HCT-CI score 0-1 group respectively, 210 and 60 days (P<0.01) in HCT-CI score 2-3 group respectively, 130 and 90 days (P>0.05) in HCT-CI score ≥4 group, respectively. CONCLUSION: The HCT-CI score can be used as simple and feasible evaluation criteria to judge the selection of individualized treatment strategy for elderly AML patients.

Intestinal trefoil factor maybe useful in prophylaxis of acute graft-versus-host disease.

Graft-versus-host disease (GVHD) is a major complication of hematopoietic cell transplantation, GVHD pathophysiology can be divided into three phases, damage to the gastrointestinal (GI) tract in phase 1, principally by inflammatory cytokines, amplifies LPS release and leads to the "cytokine storm" characteristic of severe acute GVHD. It has been proved that disruption of phase 1 of the GVHD cascade is effective in prophylaxis of acute GVHD. Intestinal trefoil factor (ITF), a member of trefoil factor family (TFF) domain peptides, was proved to be very effective in prevention and healing of acute dextran sodium sulfate-induced colitis, and was also involved in protection against and recovery from intestinal mucositis induced by radiation and chemotherapy. So we hypothesise that ITF protects the intestinal tract mucosa from lesions and that it maybe useful in prophylaxis of acute GVHD. ITF can block GI tract damage in phase 1, preventing the amplification of the cascade. ITF may represent a novel strategy for the separation of GVHD and graft-versus-leukemia (GVL), and may serve as an effective adjunct to clinical regimens of GVHD prophylaxis.

[Construction of anti-cD20scFv/CD80/CD28/zeta recombinant gene modified T cell and research on its targeting cytotoxicity].

OBJECTIVE: To construct anti-CD20scFv/CD80/CD28/zeta recombinant gene modified T cells, test its effectiveness of eradicating CD20+ lymphoma cells and provide a probably new approach to tumor adoptive immunotherapy. METHODS: CD28-zeta cDNA were amplified from vector pBULLET and inserted into pLNCX vector that contained anti-CD20scFv/CD80 gene. The recombinant vectors were transduced into PA317 cells and high titer retroviruses were obtained to infect human peripheral blood T lymphocytes. Resistant T cells were obtained by G418 selection at one week. Then transduced T lymphocytes and lymphoma cell lines Daudi Raji were cocultured. The cytotoxicity and cytokine production of transduced T cells were determined by non-radio-activation cytotoxicity assay and ELISA respectively. RESULTS: The recombinant eukaryotic vector was constructed successfully as proved by enzyme digestion analysis and sequencing. These T cells were able to lyse CD20+ target cells and secrete high levels of IL-2 and IFN-gamma in vitro. CONCLUSION: Recombinant gene modified T cells can be constructed successfully. It can specially kill CD20 positive lymphoma cells in vitro.

[Apoptosis induced by hydroquinone in bone marrow mononuclear cells in vitro].

OBJECTIVE: To study the effect of hydroquinone on apoptosis of bone marrow mononuclear cells, and to evaluate the toxic effect of benzene on stem cells. METHODS: Cell morphology was observed by HT fluorescent stain method, and DNA fragments were analyzed by agarose gel electrophoresis. Anti-Annexin V FITC plus PI staining for apoptotic and necrotic rate was examined by flow cytometer. RESULTS: After adding different concentrations of hydroquinone to the cells for 6 h culture, the fluorescent intensity of nucleus increased, the color of nucleus became deep and inhomogeneous, and the chromatin was condensed and distributed around the neucleus. DNA ladder was detected in all samples. Cell apoptotic rate in different concentration of hydroquinone groups was significantly higher than that in blank control group (P < 0.05). With the increase of the concentration of hydroquinone, the apoptotic and necrotic rate also increased. The optimal concentration of hydroquinone was 50 micro mol/L. When it was >or= 75 micro mol/L, the necrotic rate increased significantly. Hydroquinone-induced apoptosis was associated with culture time at the concentration of 50 micro mol/L, and the peak apoptotic time was 10 h, then the apoptotic rate decreased and necrotic rate increased. CONCLUSION: Hydroquinone can induce apoptosis of bone marrow mononuclear cells in vitro with dose-effect and time-effect relationship.

Extraction and purification of biologically active intestinal trefoil factor from human meconium.

Intestinal trefoil factor (TFF3/ITF), a member of trefoil factor family (TFF) domain peptides, is normally expressed by goblet cells and secreted into the lumen of the intestinal tract, and plays an important role in the maintenance and repair of the intestinal mucosal barrier. Significant amounts of TFF3/ITF are present in the meconium of human infants. Here, we describe a relatively simple method for extraction and purification of natural human TFF3/ITF from meconium. The purification methods include acid treatment, ammonium sulfate precipitation, isoelectric precipitation, and iron exchange chromatography. A relatively large amount of natural TFF3/ITF can be purified from meconium of full-term infants and this purified, natural TFF3/ITF is biologically active in an ethanol-induced rat gastric mucosal injury model.