Combination of CRISPR/Cas9 System and CAR-T Cell Therapy:A New Era for Refractory and Relapsed Hematological Malignancies

Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple myeloma.However,treatment-related toxicities such as cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)have become significant hurdles to CAR-T treatment.Multiple strategies were established to alter the CAR structure on the genomic level to improve efficacy and reduce toxicities.Recently,the innovative gene-editing technology-clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease9(Cas9)system,which particularly exhibits preponderance in knock-in and knockout at specific sites,is widely utilized to manufacture CAR-T products.The application of CRISPR/Cas9 to CAR-T cell therapy has shown promising clinical results with minimal toxicity.In this review,we summarized the past achievements of CRISPR/Cas9 in CAR-T therapy and focused on the potential CAR-T targets.

Effects of low molecular heparin combined with ursodeoxycholic acid on liver function, immunologic function and pregnancy outcome in patients with intrahepatic cholestasis of pregnancy

Objective: To investigate the effects of low molecular heparin (LMWH) combined with ursodeoxycholic acid (UDCA) on liver function, immunologic function and pregnancy outcome in patients with intrahepatic cholestasis of pregnancy (ICP). Methods: A total of 110 patients with ICP were randomly divided into the observation group (n=55) and the control group (n=55). Patients in the control group received conventional therapy, while patients in the observation group were treated with LMWH hypodermic injection and UDCA orally on the basis of the treatment plan of the control group. Before and after treatment, the levels of serum total bile acid (TBA), glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP) and immunoglobulin (IgG, IgA, IgM) between the two groups were compared. The changes of T lymphocyte subsets of peripheral blood in the two groups were analyzed, and the pregnancy outcomes of the two groups were observed. Results: After treatment, the serum levels of TBA, ALT, AST, TBIL, DBIL and ALP in the two groups were significantly lower than those before treatment, and the change of each index in the observation group was more obvious than that in the control group. The serum levels of IgG, IgA and IgM in the observation group after treatment were significantly higher than those before treatment and those in the control group after treatment. However, the percentage of CD4+T cells and the ratio of CD4+/CD8+ in the observation group after treatment were significantly lower than those before treatment and those in the control group after treatment. Conclusions: LMWH combined with UDCA could effectively reduce serum bile acid level, improve liver function and regulate immune balance in patients with ICP, and improve outcomes of maternal and fetal.

Detection of vitamin D in patients with gestational diabetes mellitus and its effects on insulin resistance, adipokines and TNF-α

Objective:To detect vitamin D levels in patients with gestational diabetes mellitus and the influence and clinical effect of Vitamin D supplement on insulin resistance, fatty factors and TNF-α.Methods:A total of 100 patients with GDM from September 2014 to May 2015 in our hospital were selected as object of observation (GDM Group). 52 cases patients with Vitamin D deficiency were randomly divided into two groups. At the same time, 50 cases of healthy pregnant women were selected as normal group. Biochemical indexes of observation group and normal group were detected. Biosynthetic Human Insulin Injection were given to the patients in the control group. The patients in the observation group were supplemented with vitamin D drops on the basis of the treatment of control group. The level of insulin resistance, adipokines and TNF-α were detected in the 2 groups.Results:FBG, PBG, FINS, TG, Visfatin, TNF-α and HOMA-IR in GDM group were higher compared with that in normal group. 25(OH)D3 and APN in GDM group decreased significantly compared with that in normal group. The comparison of TC, HDL-C and LDL-C in the two groups were not statistically significant. PBG, FINS, HOMA-IR, Visfatin and TNF-α in both groups after treatment significantly decreased compared with that before treatment. PBG, Visfatin and TNF-α in treatment group after treatment decreased more significantly than that in control group. FINS, HOMA-IR in treatment group after treatment increased more significantly than that in control group. The decrease of FBG was not obvious and there was no significant difference between the two groups after treatment. APN and 25(OH)D3 in both groups after treatment significantly increased compared with that before treatment. And they in treatment group after treatment increased more significantly than that in control group. In the correlation analysis, 25(OH) D3in serum was positively correlated to the the level of APN. Also, it was negatively correlated to HOMA-IR, Visfatin and TNF-α.Conclusion:Vitamin D levels in patients with gestational diabetes mellitus decreased more significantly compared with that in healthy pregnant women. And the patients with vitamin D deficiency have higher risk to get GDM. Vitamin D can treat GDM by regulating the degree of insulin resistance and the level of adipokines. And it has clinical value in the treatment of GDM.