AIM To optimize the extraction process for Jigen Standard Decoction,and to establish its quality standard.METHODS With soaking time,water addition and first decoction time as influencing factors,comprehensive score for 3,6'-disinapoyl sucrose content and yield rate as an evaluation index,the extraction process was optimized by response surface method on the basis of single factor test.The content and transfer rate of 3,6'-dimustayl sucrose were determined,after which HPLC characteristic chromatograms were established,cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed.RESULTS The optimal conditions were determined to be 60 min for soaking time,(12+11)times for water addition,and(47+20)min for decoction time,the comprehensive score was 97.98.Fifteen batches of standard decoctions demonstrated the average yield rate and transfer rate of 14.182％and 20.468％,respectively,whose characteristic chromatograms existed six common peaks with the similarities of more than 0.9(except for S4,S8).Various batches of standard decoctions were clustered into two types,three principal components displayed the acumulative variance contribution rate of 91.4％,peaks 2,6 were quality markers.CONCLUSION This precise,stable and reproducible method can be used for the preparation and quality control of Jigen Standard Decoction.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To explore the changes of Ⅻ antithrombin (FⅫa-AT), thrombospondin-1 (TSP-1), and lupus anticoagulant (LA) ratio in the peripheral blood factor of patients with systemic lupus erythematosus (SLE) and the clinical value of combined diagnosis of thrombotic events. METHODS: A total of 133 SLE patients treated in Xingtai People's Hospital were selected and divided into simple SLE group (105 cases) and SLE complicated with thrombosis group (28 cases) according to whether thrombotic events occurred, and 102 cases of healthy people in the same period were selected as control. The clinical data of the 3 groups, the level of peripheral blood FⅫa-AT, TSP-1, and LA ratio were compared, the relationship between each peripheral blood index and SLE disease activity index (SLEDAI) score were analyzed. The influencing factors of thrombotic events in SLE patients were analyzed, and the value of each peripheral blood index in the diagnosis of SLE complicated with thrombotic events were evaluated. RESULTS: The proportion of the patients with age ≥60 year, hypertension, and smoking history in SLE complicated with thrombosis group was higher than those in simple SLE group and control group (P＜0.05). The SLEDAI score, peripheral blood FⅫa-AT, TSP-1, LA ratio levels of the patients in SLE complicated with thrombosis group were significantly higher than those in simple SLE group and control group, and the simple SLE group was significantly higher than the control group (P＜0.05). FⅫa-AT, TSP-1, LA ratio in peripheral blood of SLE patients were positively correlated with SLEDAI score (r=0.663, 0.578 and 0.625). Age, blood pressure, smoking history, peripheral blood FⅫa-AT, TSP-1, LA ratio were the important influencing factors of thrombotic events in SLE patients (P＜0.05). The AUC diagnosed by the FⅫa-AT, TSP-1, and LA ratio in peripheral blood was 0.881, the 95% CI was 0.813-0.931, the sensitivity was 82.14%, and the specificity was 91.43%, which was superior to each index alone (P＜0.05). CONCLUSION Peripheral blood FⅫa-AT, TSP-1, LA ratio level changes in SLE patients are significantly related to disease activity, and the combined diagnosis of thrombotic events is more reliable.
Humans ; Lupus Erythematosus, Systemic/complications* ; Risk Factors ; Thrombosis/etiology* ; Thrombospondin 1

OBJECTIVE: To evaluate the prognostic value of GELTAMO-IPI for patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 238 newly diagnosed DLBCL patients treated in Shanxi Cancer Hospital from September 2011 to March 2016 were collected retrospectively, the risk stratification and prognostic evaluation of the patients were analyzed according to GELTAMO-IPI. Progression-free survival (PFS) and overall survival (OS) of the patients were analyzed by the Kaplan-Meier method, COX regression analysis was used to compare the risk of death and progress in each risk group. Harrell's C statistics was used to compare the prognostic stratification ability of each model. RESULTS: The 3-year OS rate statistics showed that both IPI and GELTAMO-IPI could distinguish low risk group and Low-intermediate risk group, but the prognosis stratification ability of IPI was better (IPI: HR=5.085, P<0.05; GELTAMO-IPI; HR=4.639, P>0.05). GELTAMO-IPI could distinguish High-intermediate risk group from high risk group (GELTAMO-IPI: HR=2.966, P<0.05; 3 years OS rate was 34.5%), but the ability of IPI to identify high risk groups was weak (3 years OS>50%). The results of Harrell's C statistics showed the C-index of IPI and GELTAMO-IPI was 0.687 and 0.721 (P<0.001); the C-index of the predicted PFS was 0.672 and 0.700 (P<0.001). It was suggested that the prognostic stratification ability of GELTAM0-IPI be superior to that of IPI, R-IPI, NCCN-IPI. CONCLUSION GELTAMO-IPI can make a clear distinction between DLBCL patients with different prognosis, especially for high-risk patients, and the prognostic stratification ability of GELTAMO-IPI is significantly better than that of IPI.
Antineoplastic Combined Chemotherapy Protocols ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prognosis ; Retrospective Studies ; Risk Factors

Sickle cell disease (SCD) is a single gene genetic disease, which seriously threatens the life span and quality of patients. On the basis of the pathogenesis of SCD and the alternative therapy based on fetal hemoglobin F (HbF), the research progress of transcription factors involved in the regulation of HbF gene expression, such as BCL11A, ZBTB7A, KLF-1, c-MYB and SOX6, as well as the application of CRISPR / Cas9, TALEN, zinc finger nuclease and other gene editing technologies in this field has been made, providing a solid theoretical basis for the exploration of new treatment schemes for β- like hemoglobin diseases, such as sickle cell disease and β- thalassemia.
Anemia, Sickle Cell/therapy* ; Cell Line, Tumor ; DNA-Binding Proteins ; Fetal Hemoglobin/genetics* ; Genetic Therapy ; Humans ; Repressor Proteins/genetics* ; Transcription Factors

OBJECTIVE: To explore the kinetics of infiltrated T cell in murine acute graft-versus-host disease (aGVHD) target organs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its relationship with tissue pathological damage and aGVHD progress. METHODS: Male C57BL/6 (H-2K RESULTS: Compared with BMT group, the number of infiltrated T cells in aGVHD target organs including liver, lung and gut increased since day 7 in BMT+T group (P<0.05). On day 14, 28, 40 and 47 after transplantation, more infiltrated CD3 CONCLUSION Pathological damage of aGVHD target organs is induced by CD3
Animals ; Bone Marrow Transplantation ; Graft vs Host Disease ; Kinetics ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes ; Transplantation, Homologous

OBJECTIVE: To study the single nucleotide polymorphisms (SNPs) in promoter region of the Jk gene and its allele frequency as well as distribution characteristics in the Chinese Han nationality population. METHODS: 127 blood samples containing 8 Jk(a-b-) and 119 samples (as control) taken randomly from voluntary blood donors of Chinese Han nationality persons in Shenzhen Blood Center were collected. The Kidd phenotypes were identified by using the serologic test and urea hemolysis test; the Jk promoter, exon 1-11 region and respective flanking area were amplified and sequenced, then the sequence information was analyzed. RESULTS: 8 Jk(a-b-) samples all carried JkB/JkB allele which belongs to 2 kind of Jk genotypes commonly observed in Chinese Han nationality population. 6 IVS5-1g>a and 2 896G>A were found in 8 Jk(a-b-) samples. Besides, all Jk(a-b-) samples were homozygous for JkB/JkB allele. Three SNPs-110(rs900974), -160(rs1484877) and -258(rs1484878) in promoter region of the Jk gene were found and sequenceds calculation of allele and genotype frequencies showed that the result accorded with Hardy-Weinberg equilibrium, indicating that the population in this study possesses representative characteristics of the Chinese Han nationality population. CONCLUSION The polymorphism of the Jk gene occurs in promoter region. This study calculates the allele frequencies of three SNPs-110(rs900974), -160(rs1484877) and -258(rs1484878) in promoter region of the Jk gene, and shows their distribution characteristics in distinct Kidd phenotypes. These findings provide the basic foundation for further population genetics research.

OBJECTIVE: To investigate the proliferation, differentiation potential and autophagic mechanism HL-60 cells via ULK1 protein targeted by Haishengsu extracted from Tegillarca granosa. METHODS: The HL-60 cells were divided into five groups: Haishengsu of 10,100,1000 mg/L-treated group, all-trans retinoic acid (ATRA) 5 μmol/L-treated group and control group. The cell proliferation rates were detected by MTT after culture 12,24,48 h and 72 h. The expression of differentiation and maturation markers CD11b and CD15 were detected by flow cytometry, and the expression of autophagy molecules ULK1 and LC-3 proteins were measured by Western blot. RESULTS: After cultured for 48 and 72 h the cell proliferation rates of HL-60 in Haishengsu 100 and 1000 mg/L groups were significantly lower than those of ATRA 5 μmol/L group and Haishengsu 10 mg/L group and control group (P<0.05). After 72 h, the levels of CD11b, CD15, ULK1 and LC-3 expression of HL-60 cell in Haishengsu 100 and 1000 mg/L groups were higher than those in ATRA 5 μmol/L group, Haishengsu 10 mg/L group and control group (P<0.05). While the HL-60 cells in Haishengsu 10, 100 and 1000 mg/L group were treated with ULK1 protein inhibitor and after cultured for 72 h, the proliferation rate of HL-60 cell increased, levels of CD11b and CD15 expression decreased at the same time, and the levels of ULK1 and LC-3 proteins in HL-60 cells also decreased (P<0.05). CONCLUSION Haishengsu, which extracted from Tegillarca granosa, can induce HL-60 cell proliferation and differentiation by targeting ULK1 protein in a concentration and time dependent manner, its effective mochanism may be mediating autophagic activity, promoting cell differentiation and maturation.

OBJECTIVE: To analyze the clinical efficacy and safety of rituximab therapy for patients with Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL), and to explore the factors influencing the clinical efficacy. METHODS: According to therapeutic regimen, 66 patients with EBV-positive DLBCL were divided into two groups: CHOP group (32 cases) and R-CHOP group (CHOP+ rituximab, 34 cases). The clinical efficacy and the incidence of complication were compared between two groups. The clinical risk factors for the clinical efficacy in patients with EBV-positive DLBCL were confirmed by multivariate Logistic analysis. RESULTS: Compared with CHOP group, the complete remission rate, partial remission rate and the overall effective rate in R-CHOP group all were high (P＜0.05), moreover the disease progression rate in R-CHOP group were low (P＜0.05). The occurrences rate of myelotoxicity, hepatic injury and gastrointestinal reaction were not statistically significantly different between two groups (P＞0.05). Multivariate Logistic analysis showed that the Ann Arbor staging, IPI risk score and Ki-67 positive rate were independent risk factors for the clinical efficacy in patients with EBV-positive DLBCL (OR=2.689, P=0.038; OR=3.232, P=0.025; OR=2.919, P=0.023). CONCLUSION The clinical efficacy and safety of the therapy with rituximab on the patients with EBV-positive DLBCL are better. The poor Ann Arbor stage, high IPI risk score and the Ki-67 positive rate are factors affecting the clinical efficacy for the patients with EBV-positive DLBCL.
Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Herpesvirus 4, Human ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Prednisone ; therapeutic use ; Rituximab ; therapeutic use ; Treatment Outcome ; Vincristine ; therapeutic use

OBJECTIVE: To explore the role of bone marrow niche in the chemotherapy resistance of patient with acute myeloid leukemia (AML), and to investigate the effects of the MSCs on the apoptosis of HL-60 cell and its underlying mechanisms. METHODS: MSCs were derived from the bone marrow of newly diagnosed AML patients (AML-MSCs) and health donors(MSCs) were co-cultured with HL-60 cells respectively. The apoptosis of HL-60 cells in the presence/absence of MSCs and/or Daunorubicin were determined by flow cytometry with Annexin V/PI double staining. In addition, the morphological features of HL-60 cells were observed by Wright-Giemsa staining, and the ratio of blasts and differentiated cells were counted. Furthermore, the expressions of apoptosis-related factors including Caspase-3, Caspase-8,Caspase-9 and Survivin were detected by Western blot. RESULTS: The flow cytometry showed that there was no significant change in apoptosis of HL-60 cells co-cultured with MSC derived from healthy donors or AML patients. After adding Daunorubicin into different cultural systems, the apoptotic rates of HL-60, HL-60 co-cultured with normal MSCs and HL-60 co-cultured with AML-MSCs were (49.57±7.44)%, (30.72±4.05)% and (22.99±4.08)%, respectively, which showed that normal MSCs and AML-MSCs could remarkably supress Daunorubicin-induced HL-60 apoptosis, however, there was no statistically significant difference of apoptosis between HL-60 co-cultured with normal MSCs and HL-60 co-cultured with AML-MSCs. Wright-Giemsa staining showed that most of the HL-60 cells co-cultured with AML-MSCs were primitive, and cell differentiation was unusual. In AML-MSCs co-cultured group, the cell apoptosis and differentiation caused by DNR was significant decreased, and most of HL-60 cells were initial. Western blot showed that the cleavage activity of Caspase-3 of HL-60 in AML-MSCs and normal MSCs co-cultured group was decreased, compared with HL-60 in single cultured group, moreover, the decrease was significantly in AML-MSC group. Additionally, the expression of survivin in AML-MSCs and normal MSCs co-cultured group was increased, compared with that in single cultured group, and increase was significant in AML-MSCs group. CONCLUSION MSCs can suppress Daunorubicin-induced HL-60 apoptosis via inhibiting Caspase-3 and maintaining survivin level.
Apoptosis ; Bone Marrow Cells ; Caspase 3 ; Cell Proliferation ; Daunorubicin ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; Mesenchymal Stem Cells ; Survivin