Risk Assessment before Conducting Clinical Trials of Medical Devices / 中国医学伦理学

Due to the rapid development of new medical devices and the national policy adjustment of medical device review and approval, the difficulty of clinical trial institution and ethics committee in the risk assessment of medical device clinical trials has greatly increased. By sorting out the legal norms, standards and safety evaluation materials of medical devices, this paper systematically summarized and suggested the existing risks in clinical trials of medical devices from seven aspects, including the collection and utilization of biological sample, site environment safety, information security, product production and inspection, use of device, clinical trial design, and technical capabilities, with a view to providing a reference basis for the sponsors, clinical trial institutions, and ethics committees to scientifically establish a risk assessment system for medical devices before clinical trials, thereby reducing potential risks of compliance and safety during the clinical trial process.

Focus of Ethical Review on the Research of New Generation Artificial Intelligence Independent Software Based on Deep Learning Algorithm / 中国医学伦理学

By sorting out the research of new generation of artificial intelligence (AI) independent software reviewed by medical ethic committee of a grade A tertiary hospital in Beijing from January 2017 to November 2021, this paper analyzed and summarized the common problems involved in multiple dimensions, such as the integrity of the protocol design, protection of the rights and interests of the subjects, the data using and storing, and proposed that ethic committee should pay special attention to the protocol integrity, data security, risk assessment, track review, and other aspects different from conventional clinical research, thus providing a idea for ethical review of new generation AI independent software research.

Regulation of Dracocephalum Moldavica total flavonoids on foaming and inflammatory response of RAW264. 7 maerophages / 中国药理学通报

Aim To investigate the effeets of Dracocephalum Moldavica total flavonoids (TFDM) on the foaming lipoprotein (ox-LDL), and to further elucidate the mechanism of anti-atherosclerosis (AS) of TFDM. Methods RAW264. 7 maerophages were cultured in vitro and induced to become foam cells by ox-LDL stimulation, and inflammation of mouse monocyte macrophage leukemia cells (RAW264. 7) induced by oxi-dized low density TFDM(25, 50, 100 mg • L"

Observation of liver indexes in patients with relapsed/refractory multiple myeloma treated with CAR-T-cells based on BCMA / 中华血液学杂志

Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.

Effect of Hemoglobin on Efficacy of CAR-T Therapy in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM).@*METHODS@#From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, β2-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed.@*RESULTS@#Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy.@*CONCLUSION@#The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.

Novel CD19-KIRS2/Dap12-BB CAR-T Treatment for 3 Patients with Relapsed and Refractory B-Cell Tumors / 中国实验血液学杂志

OBJECTIVE@#To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM).@*METHODS@#Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed.@*RESULTS@#After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively.@*CONCLUSION@#The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.

Influence of the Ratio of Peripheral Hemoglobin-to-Red Cell Distribution width on the Prognosis of Patients with Diffuse Large B-cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the influence of peripheral hemoglobin (Hb)-to-red cell distribution width (RDW) ratio (HRR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#Data of 265 patients with diffuse large B-cell lymphoma (DLBCL) at the Affiliated Hospital of Xuzhou Medical University from January 2014 to December 2019 were retrospectively analyzed. 132 healthy people in the same period were used as normal control group. The best cut-off points of HRR was determined by receiver operating characteristics (ROC) curve; the chi-square test was used to analyze the correlation of clinical characteristics with HRR; the Kaplan-Meier method was used to compare the overall survival (OS) and progression-free survival (PFS) of HRR patients in different groups; the Cox proportional risk model was used for univariate and multivariate analysis.@*RESULTS@#The best cut-off value of HRR was 0.936, which was divided into low HRR group and high HRR group. The low HRR group had a higher ECOG score, higher incidence of advanced Ann Arbor stage, higher NCCN-IPI score, and elevated LDH level. K-M survival analysis showed that OS (P<0.001) and PFS (P<0.001) in the low HRR group were significantly shorter than that in the higher HRR group. The multivariate analysis revealed that HRR was an independent predictor of OS（HR＝0.379，95％CI：0.237-0.605，P<0.001） and PFS （HR＝0.384，95％CI：0.241－0.614，P<0.001） in DLBCL patients.@*CONCLUSION@#Low HRR（<0.936） in patients with DLBCL indicates a poor prognosis, which is an independent prognosis risk factor.

Preparation and characterization of Ad-ERα-36-Fc-GFP / 生物工程学报

ERα-36 is a novel subtype of estrogen receptor α which promotes tumor cell proliferation, invasion and drug resistance, and it serves as a therapeutic target. However, only small-molecule compounds targeting ERα-36 are under development as anticancer drugs at present. Gene therapy approach targeting ERα-36 can be explored using recombinant adenovirus armed with decoy receptor. The recombinant shuttle plasmid pDC316-Ig κ-ERα-36-Fc-GFP was constructed via genetic engineering to express an Ig κ-signaling peptide-leading secretory recombinant fusion protein ERα-36-Fc. The recombinant adenovirus Ad-ERα-36-Fc-GFP was subsequently packaged, characterized and amplified using AdMaxTM adenovirus packaging system. The expression of fusion protein and functional outcome of Ad-ERα-36-Fc-GFP transduction were further analyzed with triple-negative breast cancer MDA-MB-231 cells. Results showed that the recombinant adenovirus Ad-ERα-36-Fc-GFP was successfully generated. The virus effectively infected MDA-MB-231 cells which resulted in expression and secretion of the recombinant fusion protein ERα-36-Fc, leading to significant inhibition of EGFR/ERK signaling pathway. Preparation of the recombinant adenovirus Ad-ERα-36-Fc-GFP provides a basis for further investigation on cancer gene therapy targeting ERα-36.

Mid- and long-term outcomes and prognostic factors of drug-coated balloon angioplasty for treatment of femoropopliteal long lesions / 中华外科杂志

Objective: To examine the effective and safe outcomes of drug-coated balloon (DCB) angioplasty for the treatment of femoropopliteal long lesions in mid-term and long-term follow-up. Methods: The clinical data of 114 patients with symptomatic (Rutherford 2 to 6) femoropopliteal long lesions who underwent angioplasty with DCB between June 2016 and May 2021 at Department of Vascular Surgery,Beijing Tsinghua Changgung Hospital were retrospectively analyzed. A total of 75 males and 39 females were enrolled, aged (71.9±8.4)years (range: 49 to 89 years). Among 138 lesions in 114 patients, there were 111 de nove lesions (80.4%, 111/138). Total occlusions were recanalized in 116 limbs (84.1%, 116/138). The lesion length was (280.9±78.7)mm (range: 150 to 520 mm). DCB angioplasty combined with debulking devices was used in 59 lesions (42.8%, 59/138).The bail-out stent implantation was performed in 27 limbs (19.6%, 27/138). The Kaplan-Meier method was used to evaluate cumulative primary patency rate, freedom from the clinically driven target lesion revascularization (CD-TLR) rate and accumulate survival rate. Univariate and multivariate analyses with Cox proportional hazards models were performed to determine the significant prognostic factors for primary patency. Results: DCB angioplasty was completed in 114 patients. The technical success rate was 98.2%(112/114). The mean follow-up time was 18 months (range: 3 to 54 months).The results showed that primary patency rates at 12, 24 and 36 months postoperatively were 87.5%, 75.2% and 55.1%, respectively. Freedom from CD-TLR rate at 12, 24 and 36 months postoperatively were 92.4%, 81.8% and 68.7%, respectively. Accumulate survival rate at 12, 24 and 36 months postoperatively were 96.2%, 94.0% and 80.2%. Multivariate Cox's regression analyses showed that chronic limb-threatening ischemia(CLTI) (HR=2.629, 95%CI:1.519 to 4.547, P<0.01) and hyperlipidemia (HR=2.228, 95%CI: 1.004 to 4.948, P=0.026) were independent prognosis factors for primary patency in DCB treatment of femoropopliteal long lesions. Conclusions: DCB provided favorable outcomes for the treatment of femoropopliteal long lesions. CLTI and hyperlipidemia are independent prognosis factors for restenosis after DCB angioplasty.

Correlation between peripheral blood hypersensitive C-reactive protein and cognitive function in patients with depression / 中国基层医药

Objective:To correlate peripheral blood hypersensitive C-reactive protein (hs-CRP) with cognitive function in patients with depression.Methods:Seventy-five patients with depression who received treatment in the Second People's Hospital of Lishui from January 2019 to May 2020 were included in the depression group. An additional 50 healthy controls were included in the control group. The MATRICS Consensus Cognitive Battery (MCCB) was used to evaluate participates' cognitive function. Serum hs-CRP level was determined using enzyme-linked immunosorbent assay.Results:Speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores in the depression group were significantly lower than those in the control group ( t = 10.774, 2.774, 9.840, 5.064, 7.915, all P < 0.01). Serum hs-CRP level in the depression group was significantly higher than that in the control group [(13.05 ± 2.94) mL vs. (1.13 ± 0.18) mL, t = 28.595, P < 0.01]. Speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores in patients with moderate and severe depression were significantly lower than those in patients with mild depression. Serum hs-CRP level in patients with moderate and severe depression was (10.41 ± 2.21) mg/L and (25.71 ± 4.04) mg/L, respectively, which was significantly higher than that in patients with mild depression [(3.03 ± 0.49) mg/L, t = 3.015, 3.370; 3.903, 3.441; 3.541, 3.604; 4.503, 4.661; 4.001, 3.980; 4.035, 3.669, all P < 0.01]. Speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores in patients with severe depression were significantly lower than those in patients with moderate depression ( t = 8.331, 5.227, 10.031, 6.003, 9.416, all P < 0.01). Serum hs-CRP level in patients with severe depression was significantly higher than that in patients with moderate depression [(25.71 ± 4.04) mg/L vs. (10.41 ± 2.21) mg/L, t = 11.005, P < 0.01]. Pearson correlation analysis showed that serum hs-CRP level in patients with depression was remarkably negatively correlated with speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores (all P < 0.01). Conclusion:Serum hs-CRP level in patients with depression is greatly increased, can reflect the severity of depression and is related to cognitive function.

Analysis of Related Early Warning Indexes of Cytokine Release Syndrome in Multiple Myeloma Patients after CAR-T Treatment / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationship between the levels of ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH) and interleukin-6 (IL-6) in peripheral serum and cytokine release syndrome (CRS) in patients with relapse and/or refractory multiple myeloma (R/R MM) after receiving chimeric antigen receptor T cells (CAR-T) immunotherapy.@*METHODS@#Twenty-eight patients with R/R MM were treated with 1×10@*RESULTS@#Among the 28 patients, 27 cases (96.4%) developed CRS, 24 cases (85.7%) in 1-2 grade CRS and 3 cases (10.7%) in 3-5 grade. The severity grade of CRS of 27 patients was positively correlated with the peak values of ferritin, CRP, LDH, and IL-6 in peripheral blood (r@*CONCLUSION@#After receiving CAR-T cellular immunotherapy, the incidence of CRS in patients with R/R MM is higher, but most of them are in grade 1 or 2. The severity of CRS is positively correlated with the levels of ferritin, CRP, LDH and IL-6 in peripheral blood.

Construction, expression and purification of a mammalian secretory recombinant fusion protein rPC / 生物工程学报

Drugs targeting immune checkpoint are used for cancer treatment, but resistance to single drug may occur. Combination therapy blocking multiple checkpoints simultaneously can improve clinical outcome. Therefore, we designed a recombinant protein rPC to block multiple targets, which consists of extracellular domains of programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). The coding sequence was inserted into expression vector and stably transfected into HEK293 cells. The culture supernatant was collected and rPC was affinity-purified. Real-time quantitative PCR was used to evaluate the expression levels of ligands for PD-1 and CTLA-4 in several human cancer cell lines. The binding of rPC with cancer cells was examined by immunofluorescence cell staining, the influence of rPC on cancer cell growth was assayed by CCK-8. The results showed that rPC could be expressed and secreted by stably transfected HEK293 cells, the purified rPC could bind to lung cancer NCI-H226 cells which have high levels of ligands for PD-1 and CTLA-4, no direct impact on cancer cell growth could be observed by rPC treatment. The recombinant protein rPC can be functionally assayed further for developing novel immunotherapeutic drugs for cancer.

Th17 Cell Subset levels in Peripheral Blood of Patients with Aplastic Anemia and Their Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To study the level and clinical value of Th17 cell subset in the peripheral blood of the patients with aplastic anemia (AA).@*METHODS@#Eighty-five patients with aplastic anemia in our hospital from May 2017 to February 2018 were selected. Among them, 51 patients with poor curative effect were enrolled in group A. and the 34 patients with good curative effect were enrolled in group B, the 35 healthy persons were selected as controls. The levels of serum IL-17, IL-6, IL-4 and IFN-β were analyzed by ELISA; the levels of peripheral blood Th17 cell subset were analyzed by flow cytometry; the expression levels of RORγt and STAT3 mRNA in lymphocytes were analyzed by RT-PCR; the expression levels of RORγt and STAT3 protein in lymphocytes were analyzed by Western blot.@*RESULTS@#There was no significant difference in sex, age, WBC count and complications between group A and group B (P＞0.05). Non-severe aplastic anemia (NSAA) in group B accounted for 23 cases, and the NSAA ratio (23/34) was significantly higher than that in group A (20/51) (P＜0.05). The Hb level (86.25±7.9 g/L) and Plt count (54.7 ± 6.3×10/L) in group B were significantly higher than those in group A (P＜0.05). ELISA showed that the levels of IL-17 and IL-6 in group A were significantly higher than those in control group (P＜0.05); the levels of IL-17 and IL-6 in group B were significantly lower than those in group A (P＜0.05); the levels of IL-4 and IFN-β in group A were significantly lower than those in control group (P＜0.05); the levels of IL-4 and IFN-βin group B were significantly higher than those in group A (P＜0.05). Flow cytometry showed that the proportion of Th17 cells in peripheral blood of group A was higher than that of group B (P＜0.05). RT-PCR showed that the levels of RORγt and STAT3 mRNA in group A were significantly higher than those in control group (P＜0.05), and the mRNA levels of RORγt and STAT3 in group B were significantly lower than those in group A (P＜0.05). Western blot showed that the protein levels of RORγt and STAT3 in group A were significantly higher than those in control group (P＜0.05), and the protein levels of RORγt and STAT3 in group B were significantly lower than those in group A (P＜0.05).@*CONCLUSION@#The Th17 cells in peripheral blood of AA patients increase, and the inflammatory reaction in the patients are enhanced. It may be related with the rise of RORγt and STAT3 gene expression, which provides a research direction for clinical treatment of AA.

Clinical observation of amitriptyline combined with Xiaoyao Powder in the treatment of postpartum depression / 中国基层医药

Objective@#To investigate the clinical effect of amitriptyline combined with Xiaoyao Powder in the treatment of postpartum depression.@*Methods@#From January 2018 to February 2018, 128 patients with postpartum depression in the Second People's Hospital of Lishui were selected.The patients were randomly divided into observation group and control group according to the digital table, with 64 cases in each group.The observation group was treated with Chinese and western medicine (amitriptyline combined with Xiaoyao Powder), and the control group was treated with amitriptyline alone.The self-rating anxiety scale (SAS), self-rating depression scale (SDS) score, and the concise health survey scale (SF-36) score before and after treatment were compared between the two groups.@*Results@#The SDS scores of the two groups were decreased after treatment (t=4.564, 3.656, P=0.012, 0.027), and the SDS score of the observation group was lower than that of the control group, the difference was statistically significant (P=0.035). The SDS scores had no statistically significant difference between the two groups before treatment (P=0.961). The SAS scores in the two groups were decreased after treatment (t=4.352, 3.432, P=0.015, 0.029). The SAS score of the observation group was lower than that of the control group, and the difference was statistically significant (t=3.021, P=0.038). After treatment, the scores of SF-36 in the observation group were significantly increased (all P<0.05), and the comparison of various indicators: emotional function (t=2.951, P=0.048), vitality (t=3.012, P=0.042), mental health (t=3.131, P=0.043), social function (t=2.967, P=0.048), physical pain (3.320, P=0.039), physiological function (t=3.467, P=0.038), physiological function (t=3.986, P=0.035), overall health (t=4.045, P=0.021), which had statistically significant differences compared with the control group.@*Conclusion@#Amitriptyline combined with Xiaoyao Powder in the treatment of postpartum depression can significantly improve the quality of life and improve the anxiety and depressive symptoms of patients, which is better than amitriptyline alone.

Effect of group cognitive behavior intervention on self-rated health of middle school students with e-motional disorder / 中华行为医学与脑科学杂志

Objective To explore the effect of group cognitive behavior intervention on self-rated health of middle school students with emotional disorders. Methods From January 2018 to June 2018,79 middle school students with emotional disorders were randomly divided into intervention group ( 41 cases) and control group (38 cases) according to the single or double number of medical records. The control group only received drug treatment,while the intervention group received group cognitive behavior intervention on the basis of drug treatment. All the students in the two groups completed the self-rated health measurement scale before intervention (T0),after intervention (T1) and 8 weeks after intervention (T2). Results (1) There were no significant differences in total health score and dimension score between the two groups before intervention (both P<0. 05). (2)The repeated measurement variance analysis showed that there was a signif-icant group × time interaction effect on total health score and dimensions(P>0. 05). (3) The group effect of physical health was not significant (P>0. 05). The group effect of total mental health, social health and health score at T1 and T2 time points were significant (all P>0. 05). (4)Compared with before intervention, mental health ((123. 34±9. 33),( 122. 63± 9. 11)),social health ((102. 89 ± 7. 28),( 101. 89± 7. 73)) and total health score ((370. 34±17. 99),(367. 63±17. 89)) of intervention group at T1 and T2 increased ( all P<0. 05),while that of control group increased only at T1 (all P<0. 05). Conclusion Group cognitive behavioral intervention has no obvious effect on physical health of middle school students with emotional dis-orders. And group cognitive behavioral intervention can effectively improve their mental health,social health and overall health level,and the long-term effect is better.

Clinical observation of amitriptyline combined with Xiaoyao Powder in the treatment of postpartum depression / 中国基层医药

To investigate the clinical effect of amitriptyline combined with Xiaoyao Powder in the treatment of postpartum depression.Methods From January 2018 to February 2018,128 patients with postpartum depression in the Second People＇s Hospital of Lishui were selected.The patients were randomly divided into observation group and control group according to the digital table ,with 64 cases in each group.The observation group was treated with Chinese and western medicine (amitriptyline combined with Xiaoyao Powder ),and the control group was treated with amitriptyline alone.The self-rating anxiety scale ( SAS),self-rating depression scale (SDS) score,and the concise health survey scale ( SF -36) score before and after treatment were compared between the two groups. Results The SDS scores of the two groups were decreased after treatment (t＝4.564,3.656,P＝0.012,0.027), and the SDS score of the observation group was lower than that of the control group ,the difference was statistically significant (P＝0.035).The SDS scores had no statistically significant difference between the two groups before treatment (P＝0.961).The SAS scores in the two groups were decreased after treatment ( t＝4.352,3.432,P＝0.015,0.029).The SAS score of the observation group was lower than that of the control group ,and the difference was statistically significant (t＝3.021,P＝0.038).After treatment,the scores of SF -36 in the observation group were significantly increased (all P＜0.05),and the comparison of various indicators :emotional function (t＝2.951, P＝0.048),vitality (t＝3.012,P＝0.042),mental health (t＝3.131,P＝0.043),social function (t＝2.967,P＝0.048),physical pain (3.320,P＝0.039),physiological function ( t＝3.467,P＝0.038),physiological function (t＝3.986, P ＝0.035), overall health ( t ＝4.045, P ＝0.021 ), which had statistically significant differences compared with the control group.Conclusion Amitriptyline combined with Xiaoyao Powder in the treatment of postpartum depression can significantly improve the quality of life and improve the anxiety and depressive symptoms of patients,which is better than amitriptyline alone.

Survey and Establishment of the Hematological Parameter Reference Intervals for Adult in Xuzhou Area of China / 中国实验血液学杂志

OBJECTIVE@#To establish the reference intervals of the hematological parameters in normal adult people of Xuzhou erea.@*METHODS@#The red blood cells (RBC), platelets, white blood cells (WBC) and related parameters were detected by hematoanalyzers in 82514 healthy people including 41257 males and 41257 females in the Medical Center of the Affiliated Hospital of Xuzhou Medical University.@*RESULTS@#The range of RBC count: (4.33-5.51) ×10/L in male and（3.82-4.85）×10/L in female, the range of Hb level: (132-172) g/L in male and（107-145）g/L in female, the range of HCT: 40 %-50 % in male and 34 %-44 % in female, the range of platelet count: (113-268) ×10/L in male and (126-289) ×10/L in female, the range of WBC count: (4.00-9.40) ×10/L in male and （3.54-9.30）×10/L in female, the range of NEUT count: (1.91-5.76) ×10/L in male and（1.67-5.30）×10/L in female, the range of MONO count: (0.18-0.58) ×10/L in male and（0.16-0.52）×10/L in female, the range of LYM is（1.3-3.4）×10/L in male and（1.2-3.1）×10/L in female, etc.Conclusion: There is significant difference in the blood cell parameters between Xuzhou and other areas. Among them, the lower limit of Hb reference interval for adult women in Xuzhou area is obviously lower, and the upper and lower limits of adult Plt reference interval are significantly lower than other areas in China and abroad. The upper and lower limits of the WBC reference interval are close to the domestic areas, but lower than that in some foreign regions. Through this survey, the reference intervals of different hematologic parameters of healthy people in Xuzhou area primarily has been established, Some of the indexes, such as RBC, Hb, HCT, and Plt have significant sex differences. The reference intervals for them have been estublisted respectively.

Clinical Efficacy of Humanized Anti-CD19 Chimeric Antigen Receptor T Cells in the Treatment of Acute B Lymphocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To study the safety and effectiveness of humanized CD19-targeted CAR-T cells (hCART19s) for treatment of patients with refractory/relapsed (R/R) B-ALL.@*METHODS@#The analyzed patients were 15 children and adults with relapsed/refractory B-ALL who not received treatment with murine CD19 CAR-T cells. The patients received a single dose (1×10/kg) of autologous hCART19 infusion after lymphodepletion chemotherapy based on cyclophosphamide and fludarabine.@*RESULTS@#Among the 15 patients, 13/14 (92.9%) evaluable patients achieved complete remission (CR) or CR with incomplete recovery of blood cells (CRi) on day 30 after hCART19s infusion. At day 180 after the infusion, the overall survival rate was 73.3%, and the leukemia-free survival rate was 69.2%. The cumulative incidence of relapse was 24.5% and non-relapse mortality rate was 7.7%. During treatment,12/15 patients (80%) developed cytokine release syndrome (CRS) of grade 1-2, and 3 patients (20.0%) developed CRS of grade 3-5. Only one patient (6.7%) suffered from the reversible neurotoxicity.@*CONCLUSION@#hCART19s can effectively treat refractory/relapsed (R/R) adult and children with B-ALL, and the incidence of treatment-related CRS and neurotoxicity is low.

Curative Efficacy of Rituximab for ITP Patients with Different Sensitivity to Hormone / 中国实验血液学杂志

OBJECTIVE@#To investigatc the curative efficacy of low dose rituximab for glucocorticoid ineffective on dependent ITP patients and its relation with sensitivity to glucocorticoid so as to provide reference basis for rational use of drugs in clinical treatmant.@*METHODS@#Seventy-ninth ITP patients enrolled in this study included the glucocorticoid-ineffective patients (19 cases) and glucocorticoid-dependent patients (60 cases). All ITP patients were treated with regimen consisted of high dose dexamethasone plus low dose rituximab (dexal-methasone 40 mg/d for 4 days per os, ritaximab 100 mg by intravenous infusion at D7, 14, 21 and 28 respectively). The patients after treatment were followed-up for 12 month, and the relation of patients sensitivity to glucocorticoid with therapentic response of rituximab was analyzed. The changes of Treg cell ratio and BAFF, IL-2 and sCD40L levels before and after treatment were detected by flow cytometry and ELISA respectively.@*RESULTS@#The overall response rate (ORR) of patients treated with above- mentioned regemen at 1, 3, 6 and 12 months after treatment was 79.7% (63/79), 69.6% (55/79), 63.3% (50/79) and 60.8% (48/79) respectivcly, out of which the ORR of glucocorticoid ineffective and glucocorticoid-dependent ITP patients treated with above-mentioned regimen at 1, 3, 6 and 12 months after treatment was 47.4% (9/19) vs 90.0% (54/60), 36.8% (7/19) vs 80.0% (48/60), 21.1% (4/19) vs 76.7% (46/60), 21.1% (4/19) vs 73.3% (44/60), and the difference between 2 groups was statistically significant. The detection of T reg cell showed that the T reg cell ratio in glucocorticoid- ineffective and dependent patients at 1, 3, 6 and 12 months after treatment was (1.70±0.43)% vs (3.47±0.72)%, (1.66±0.33)% vs (4.29±0.91)%, (1.71±0.37)% vs (4.44±0.97)%, (3.36±0.54)% vs (4.29±1.04)%, respectively. The detection of cytokines showed that the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-dependent patients at 1 month after treatment significanlly decreased (P＜0.05), the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-ineffective patients although decreased at 1 mouth after treatment, but there was no statistical difference as compared with glucocosticoid-depenment patients.@*CONCLUSION@#The treatment of glucocorticoid-dependent ITP patients with rituximab is more effective. The regulatory effect of rituximab on the T-reg cells, BAFF, IL-2 and sCD40L may be one of its mechanisms.

Construction and in vitro verification of a new humanized anti-CD19 CAR-T cells with high affinity / 中华血液学杂志

Objective: To construct humanized anti-CD19 chimeric antigen receptor T cells and investigate its ability to kill leukemia cells in vitro and in vivo. Methods: Humanized anti-human CD19 antibody with a high affinity was obtained based on mouse anti-human CD19 antibody (FMC63). Humanized CD19 CAR-T cells (hCART19) were constructed through transfection of lentivirus carrying a CAR sequence of humanized anti-CD19 scFv into human peripheral CD3(+) T cells. The ability of hCART19 to kill leukemia cells and secrete cytokines was detected by LDH release assay and ELISA. The in vivo tumor-killing effect of hCART19 was evaluated in a leukemia mouse model. Results: Several different humanized CD19 single-chain antibodies which were constructed by IMGT database were expressed in the eukaryotic expression vector and purified followed by acquiring humanized CD19 antibody (Clone H3L2) with similar binding ability to FMC63. Humanized CD19 CAR lentivirus vector was constructed and transfected into T cells to obtain hCART19 cells. The LDH release experiment confirmed that the killing rate of target cells was increased gradually along with the increased E/T ratio. When the ratio of E/T was 10∶1, the killing rate of target cells by hCART19 reached a maximum. When Raji cells were used as target cells, the hCART19 cells group had a significantly higher kill rate [(87.56±1.99)%] than the untransduced T cells group [(19.31±1.16)%] and the control virus transduced T cells group [(21.35±1.19)%](P<0.001). ELISA analysis showed that the secretion of IL-2 [ (10.56±0.88) pg/ml] and IFN-γ [ (199.02±12.66) pg/ml] in the hCART19 cells group were significantly higher than those in the untransduced T cells group [IL-2: (3.55±0.26) pg/ml; IFN-γ: (37.63±0.85) pg/ml] and the control virus transduced T cells group [IL-2: (2.92±0.32) pg/ml; IFN-γ: (52.07±3.33) pg/ml](P<0.001). The above experiments also showed similar results when CHO-K1-CD19 cells were used as target cells. Moreover, in a human leukemia xenograft animal model, the results showed that mice in the untransduced T cells group and the control virus transduced T cells group all died within 20 to 30 days, and the hCART19 cell group survived >40 days, which was more than the survival time of the other two groups of mice. The difference was statistically significant (χ(2)=11.73, P=0.008). Conclusion: Humanized CD19 CAR-T cells with anti-leukemic activity have been successfully constructed, which will lay a foundation for clinical studies in the future.