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Objective:To investigate the changes of various cytokines and coagulation function in B cell acute lymphoblastic leukemia(ALL) patients with different CRS scores during CD19-CAR-T cell immunotherapy.Methods:87 patients with B-ALL hospitalized in the First Affiliated Hospital of Soochow University and 30 normal controls were enrolled into this study from July 2018 to October 2020. The age of the patients was 32(20, 56) years old and 36(41.4%) were female. All these coagulation indicators, prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, fibrinogen (Fg) were analyzed by automatic blood coagulation in B-ALL patients before and after treated with CAR-T cell. The ratio of CD19-CAR-T cells and the expression of IL-6, IL-10, IFN-γ, TFN-α, IL-2, IL-4, and IL-17A were analyzed using flow cytometry. The patients′ clinical parameters were detected, and the CRS classification of severity was made according to the standard of consensus.Results:Patients with CRS>3 had prolonged PT and APTT, increased D-dimer, and decreased fibrinogen ( P<0.05). The levels of cytokines of IFN-γ, IL-6, and IL-10 were significantly higher in patients with CRS>3 than that in controls ( P<0.05).The D-dimer level is positively correlated with IL-10. Conclusion:Patients with severe CRS grading have significant coagulation dysfunction in CD19-CAR-T cell immunotherapy. Cytokines IFN-γ, IL-6, and IL-10 may affect coagulation function and CRS grading during CD19-CAR-T cell immunotherapy.
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Objective:Based on the degradation of skeletal muscle protein MuRF mediated by pFoxO1 when insulin resistance occurs, this paper explores the content change of skeletal muscle protein and the effect of Jianpi Qinghua formula when insulin resistance occurs.Methods:C57 mice were fed with high-fat food and made as the model of obesity accompanied by insulin resistance. Then they were divided into model group, Jianpi Qinghua formula group and metformin group according to random number table method with 10 mice in each group. Jianpi Qinghua formula group was orally administered with water decoction 20.961 g/kg, and the metformin group was orally administered with metformin suspension 18.498 g/kg, once a day for 12 consecutive weeks. Intraperitoneal Glucose Tolerance Tests (IPGTT) was used after the model was established and intervened respectively. The relative protein content of pFoxO1, FoxO1, MuRF, MyoD and myosin were detected by Western blot method, and the localization of MyoD and myosin was detected by immuno-histochemistry.Results:Compared with the model group, the blood glucose of IPGTT at 0 min, 60 min and 120 min of both Jianpi Qinghua formula group and Metformin group decreased ( P<0.05). Compared with model group, the ratio of pFoxO1/FoxO1 protein expression level (0.27±0.07, 0.24±0.14 vs. 0.05±0.03) of both Jianpi Qinghua formula group and Metformin group increased ( P<0.05), and the relative expression of MuRF protein (1.22±0.42, 1.15±0.32 vs. 3.21±0.35) of both Jianpi Qinghua formula group and Metformin group decreased ( P<0.05). The relative protein expression of MyoD (1.42±0.45 vs. 0.40±0.11) and myosin (0.80±0.11 vs. 0.51±0.08) relative protein expression of Jianpi Qinghua formula group was significantly higher than that of model group ( P<0.05). Immunohistochemical staining showed that MyoD (5.06±1.72 vs.2.28±0.83) and myosin (60.28±7.47 vs. 39.77±3.34) of Jianpi Qinghua formula group significantly increased compared with model group ( P<0.05). Conclusion:Jianpi Qinghua formula could effectively increase the content of skeletal muscle protein, enhancing the phosphorylation of FoxO1 in skeletal muscle and the inhibition of MuRF degradation pathway.
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Objective:To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the cognition of patients with mild cognitive impairment (MCI).Methods:The PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, and VIP databases were searched for randomized controlled trials of rTMS treating MCI patients before March 2019. After screening the literature, extracting the data and two independent reviewers evaluating the quality of the included studies, the meta-analysis was conducted using version 5.3 of the RevMan software.Results:Nine studies covering 368 patients were included. The pooled results showed that compared with sham stimulation, rTMS treatment could effectively improve the cognitive ability (assessed using the Montreal instrument), episodic memory, verbal fluency and the amplitude of MCI patients′ P300 signals. P300 latency was also reduced. However, there was no significant difference, on average, in memory quotient or P300 latency between patients given rTMS plus donepezil hydrochloride and those given donepezil hydrochloride alone. Compared with the control groups, the rTMS treatment groups displayed slightly more frequent adverse reactions, mainly mild dizziness and scalp pain which disappeared within 1-2 hours without obvious residual effects.Conclusions:TMS treatment can effectively improve cognitive and memory function.
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Objective To evaluate the value of dynamic contrast-enhanced MRI (DCE-MRI)in diagnosing benign and malignant solitary pulmonary nodule (SPN)with Meta-analysis.Methods The databases including PubMed,EBSCO,Cochrane Library,Ovid, CBM,VIP,Wan Fang Database and CNKI were searched to select the literatures about the diagnosis of SPN with DCE-MRI.Inclusion criteria were established,according to the validity criteria for diagnostic research published by the Cochrane Methods Group on Screening and Diagnostic Tests .Methodological quality was assessed by using the quality assessment of diagnostic studies (QUADAS-2)instrument.Meta-analysis was performed by Stata 12.0 and Meta-Disc 1.4.According to the results of heterogeneity of the included articles,proper effect model was selected to calculate the pooled sensitivity,specificity,positive likelihood ration,negative likelihood ration,and diagnostic odds ratio.Summary receiver operating characteristic (SROC)curve was drawed and the area under the curve (AUC)was calculated.Results A total of 17 studies involving 1255 lesions were included.The results of Meta-analysis showed the pooled sensitivity,specificity,positive likelihood ration,negative likelihood ration,and diagnostic odds ratio were 0.95,0.81,4.9,0.06 and 85,respectively.The AUC of SROC was 0.97.Conclusion DCE-MRI has relatively high sensitivity and specificity in the differential diagnosis of benign and malignant SPN.
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Objective To evaluate the value of dynamic contrast-enhanced MRI (DCE-MRI)in diagnosing benign and malignant solitary pulmonary nodule (SPN)with Meta-analysis.Methods The databases including PubMed,EBSCO,Cochrane Library,Ovid, CBM,VIP,Wan Fang Database and CNKI were searched to select the literatures about the diagnosis of SPN with DCE-MRI.Inclusion criteria were established,according to the validity criteria for diagnostic research published by the Cochrane Methods Group on Screening and Diagnostic Tests .Methodological quality was assessed by using the quality assessment of diagnostic studies (QUADAS-2)instrument.Meta-analysis was performed by Stata 12.0 and Meta-Disc 1.4.According to the results of heterogeneity of the included articles,proper effect model was selected to calculate the pooled sensitivity,specificity,positive likelihood ration,negative likelihood ration,and diagnostic odds ratio.Summary receiver operating characteristic (SROC)curve was drawed and the area under the curve (AUC)was calculated.Results A total of 17 studies involving 1255 lesions were included.The results of Meta-analysis showed the pooled sensitivity,specificity,positive likelihood ration,negative likelihood ration,and diagnostic odds ratio were 0.95,0.81,4.9,0.06 and 85,respectively.The AUC of SROC was 0.97.Conclusion DCE-MRI has relatively high sensitivity and specificity in the differential diagnosis of benign and malignant SPN.