Clinical Efficacy of the MDS Patients Treated by Allo-HSCT / 中国实验血液学杂志

OBJECTIVE@#To analyze clinical effectiveness of myelodysplastic syndrome (MDS) patients treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to investigate new therapy strategy for the treatment of relapse after allo-HSCT.@*METHODS@#72 MDS patients treated by HSCT in our hospital from April 2013 to November 2019 were enrolled and analyzed retrospectively. The effect of allo-HSCT was summarized. The risk factors affecting the survival and relapse of the patients were investigated.@*RESULTS@#Among 72 patients, the median follow up was 37(12-111) months. 57 patients survived（79.2%），while 15 patients died（20.8%）. The 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were 76.6% and 62.3%, respectively. IPSS-R, TP53 mutation and chronic graft versus-host-disease (cGVHD) were the risk factors affecting the OS of the MDS patients after treated by allo-HSCT. IPSS-R, TP53 mutation and Ⅲ-Ⅳ° acute graft versus-host-disease (aGVHD) were the risk factors affecting the DFS of the MDS patients after treated by allo-HSCT. After transplanted, 19 patients (26.4%) emerged aGVHD, and 5 patients (6.9%) emerged Ⅲ-Ⅳ° aGVHD, 25 patients (34.7%) emerged cGVHD, while 4 patients (5.6%) emerged extensive cGVHD. 17 patients (23.3%) relapsed, and the 5-year cumulative incidence of relapse (CIR) rate was 27.5%. IPSS-R, TP53 mutation and cGVHD were the risk factors affecting the relapse of the patients. The median survival time after relapse was 9 months. There were 7 out of 17 relapsed patients survived without disease, while 10 patients died. The OS rate of patients treated with maintained hypomethylation agents(HMA) combined with G-CSF mobilized donor lymphocyte infusion (DLI) was significantly higher than the patients without HMA (80.0% vs 10.0%, P=0.002).@*CONCLUSION@#Allo-HSCT is an effective therapy for intermediate and high risk MDS patients. But relapse after HSCT is still a major problem that affecting the survival of the patients. Maintenance treatment of HMA combined with DLI may improve the long-time survival of MDS patients with relapsed after treated by allo-HSCT.

Clinical Analysis for Patients with AML Treated after Allo-HSCT / 中国实验血液学杂志

OBJECTIVE@#To analyze risk factors that affect survival and relapse of AML patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to investigate the therapy choices after AML relapse.@*METHODS@#Clinical data of 180 AML patients achieved complete remission (CR) before HSCT from January 2009 to December 2018 treated in our center were analyzed retrospectively. Risk factors for survival and relapse after allo-HSCT were analyzed by COX regression.@*RESULTS@#Among 180 AML patients, 134 survived (74.4%), 46 patients died (25.6%), and 40 patients relapsed (22.2%). The rate of overall survival (OS), event-free survival (EFS) and cumulative rate of relapse in 5-years was 74.3%、42.5% and 25.0%, respectively. High-risk, adverse cytogenetics, CR at HSCT and no cGvHD were independent risk factors that affect OS. CR at HSCT, high-risk were independent risk factors that affect EFS. High-risk, MRD after one course of induction therapy, adverse cytogenetics and no cGVHD were independent risk factors that affect relapse. The OS rate of relapse patients could be improved by the usage of hypomethylation agents combined with G-CSF mobilized donor lymphocyte infusion (DLI), and 2-year OS rate was 62.5%.@*CONCLUSION@#The survival rate of AML is greatly improved by allo-HSCT, but relapse is still one of the most important factors that influence survival of the AML patients. The maintenance therapy of hypomethylation agents combined with DLI may be a new effective treatment option for patients who relapse after HSCT.

Analysis of Decitabine Therapeutic Effeicacy for Patients with Relapsed MDS/AML and High-Risk AML Patients after HSCT / 中国实验血液学杂志

OBJECTIVE@#To investigate the therapeutic efficacy of using decitabine as maintenance therapy for patients with relapsed MDS/AML and as prophylactic therapy for patients with high-risk AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#Clinical data of 10 patients with MDS/AML from November 2016 to May 2018 were analyzed retrospectively. Among 10 patients there were 4 cases of AML, 2 cases of MDS, and 4 cases of AML transformed from MDS (t-AML). The 10 patients were devided into 2 groups: the relapsed group (n=8) and the prophylactic group (n=2). In relapsed group the decitabine was used as maintenance therapy after achieved complete remission (CR) with decitabine chemotherapy. In prophylactic group the decitabine was used as prophylactic therapy if the patients didn't appear the symptom of graft-versus- host-disease (GVHD) during 30 to 45 d after allo-HSCT. Eight patients received G-CSF-mobilized donor lymphocyte infusion (DLI). The dosage of decitabine for maintenance therapy and prophylactic therapy was 5 mg/m for 7 to 10 days every 4 to 6 weeks, as 1 cycle, amount to 3 to 7 cycles. The dosage was adjusted by the endurance of patients.@*RESULTS@#Until Nov 30, 2018, 7 out of 10 patients survived. The average survival time was 15.5±1.9 months. 1-year OS rate was 64.0%. Six patients appeared aGVHD, and four patients appeared cGVHD.@*CONCLUSION@#The usage of decitabine combined with DLI in patients with relapsed MDS/AML and high-risk AML after allo-HSCT can prolong lives of patients, reduce relapsed rate, and provide the probability for long time survival.

Pathological Features, Treatment Options and Prognosis Assessment of Patients with Bone Lymphoma in Real-World / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma.@*METHODS@#The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively.@*RESULTS@#The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43∶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31∶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 349 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods.@*CONCLUSION@#Bone lymphoma is usually concealed onset，an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.

Thrombophilia Caused by Beta2-Glycoprotein Ⅰ Deficiency: In Vitro Study of a Rare Mutation in APOH Gene / 华中科技大学学报（医学）（英德文版）

This study aimed to explore the mechanism of a novel mutation (p.Lys38Glu) in apolipoprotein H (APOH) gene causing hereditary beta2-glycoprotein Ⅰ (β2GPI) deficiency and thrombosis in a proband with thrombophilia.The plasma level of β2GPI was measured by ELISA and Western blotting,and anti-β2GPI antibody by ELISA.Lupus anticoagulant (LA) was assayed using the dilute Russell viper venom time.Deficiency of the major natural anticoagulants including protein C (PC),protein S (PS),antithrombin (AT) and thrombomodulin (TM) was excluded from the proband.A mutation analysis was performed by amplification and sequencing of the APOH gene.Wild type and mutant (c.112A＞G) APOH expression plasmids were constructed and transfected into HEK293T cells.The results showed that the thrombin generation capacity of the proband was higher than that of the other family members.Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband.The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation.It was concluded that the recurrent thrombosis of the proband is associated with the coexistence ofp.Lys38Glu mutation in APOH gene and LA in plasma.

Thrombophilia Caused by Beta2-Glycoprotein Ⅰ Deficiency: In Vitro Study of a Rare Mutation in APOH Gene / 华中科技大学学报（医学）（英德文版）

This study aimed to explore the mechanism of a novel mutation (p.Lys38Glu) in apolipoprotein H (APOH) gene causing hereditary beta2-glycoprotein Ⅰ (β2GPI) deficiency and thrombosis in a proband with thrombophilia.The plasma level of β2GPI was measured by ELISA and Western blotting,and anti-β2GPI antibody by ELISA.Lupus anticoagulant (LA) was assayed using the dilute Russell viper venom time.Deficiency of the major natural anticoagulants including protein C (PC),protein S (PS),antithrombin (AT) and thrombomodulin (TM) was excluded from the proband.A mutation analysis was performed by amplification and sequencing of the APOH gene.Wild type and mutant (c.112A＞G) APOH expression plasmids were constructed and transfected into HEK293T cells.The results showed that the thrombin generation capacity of the proband was higher than that of the other family members.Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband.The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation.It was concluded that the recurrent thrombosis of the proband is associated with the coexistence ofp.Lys38Glu mutation in APOH gene and LA in plasma.

Detecting HB-1 Expression Level in Bone Marrow of Acute Leukemia Patients by Real-Time Fluorescence Quantitative RT-PCR / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression level of HB-1 gene in patients with acute lymphoblastic leukemia (ALL) and the significance of HB-1 gene in monitoring of minimal residual disease (MRD).</p><p><b>METHODS</b>The method of real-time fluorescence quantitative RT-PCR (Taqman probe) was established to detect the expression levels of HB-1 gene; then the sensitivity, specificity and repeatability of this assay were evaluated and verified. The HB-1 gene expression levels in bone marrow of 183 cases of ALL, 70 cases of acute myeloid leukemias (AML), 52 cases of non-malignant hematologic diseases and 24 healthy hematopoietic stem cell donors were detected. The correlation of HB-1 level with diagnosis and relapse was analyzed by detecting bone marrow samples of 33 B-ALL.</p><p><b>RESULTS</b>The sensitivity of this assay reached the 10level. The coefficient of variation for inter-batch and inter-tube of HB-1 were 6.79% and 4.80%, respectively. It was found that HB-1 gene specifically expressed in acute B lymphoblastic leukemia. The median expression levels of HB-1 gene in newly diagnosed and relapsed B-ALL patients were statistically significantly higher than those in ALL in complete remission(CR), newly diagnosed T-ALL, newly diagnosed AML, non-malignant hematologic diseases, and healthy hematopoietic stem cell donors(33.0% vs 0.68%, 0.07%, 0.02%, 0.58% and 0, respectively) (P<0.01). No statistical differences were found between newly diagnosed T-ALL, newly diagnosed AML, non-malignant hematologic diseases and healthy donors (P>0.05). The expression level of HB-1 gene declined sharply when B-ALL patients reached complete remission (0-7.99%, with median level 0.68%), but increased when relapsed (7.69%, 8.08% and 484.0% in 3 relapsed samples), which was in accordance with results of flow cytometry.</p><p><b>CONCLUSION</b>HB-1 gene specifically expressed in acute B lymphoblastic leukemia cells. The established real-time fluorescence quantitative RT-PCR assay shows good sensitivity, specificity and repeatability, thus, can be used as a biological marker in the clinical detection, monitoring MRD and predicting of early relapse for B-ALL patients.</p>

Three-dimensional reconstruction of the nasomaxillary complex and upper airway following rapid maxillary expansion by cone-beam CT / 中国组织工程研究

BACKGROUND:Two-dimensional radiographs and plaster models are used to evaluate the changes in the maxillary bone and airway after rapid maxillary expansion,but the shortcomings like distortion,one-sidedness,and overlapping appear.Cone-beam CT can effectively solve the above problems and achieve the three-dimensional reconstruction and measurement of the maxillary bone and airway.OBJECTIVE:To investigate the morphological changes of nasomaxillary complex and upper airway in adolescent patients with malocclusion after rapid maxillary expansion by cone-beam CT and Dolphin software.METHODS:Thirty adolescent patients with malocclusion were enrolled to receive rapid maxillary expansion.All patients underwent cone-beam CT examination before and after treatment,and Dolphin software was used for image processing,three-dimensional reconstruction,fixed point and measurement,to evaluate the morphological changes of the nasomaxillary complex and upper airway.RESULTS AND CONCLUSION:After treatment,the nasal cavity and maxillary width was increased by (2.13±1.80) and (4.12±2.15) mm,respectively (P ＜ 0.05);the coronal diameter and area of the airway on the hard plate was increased by (3.30±2056) mm and (75.37±53.92) mm2,respectively (P ＜ 0.05),and all above indexes showed significant difference compared with baseline.While the sagittal diameter of the airway on the hard plate showed no significant changes.After treatment,the upper airway showed a significant increase in the area and volume at the nasopharynx,which was increase by (33.57±57.10) mm2 and (1 009.59±1 350.91) mm3,respectively (P ＜ 0.05).The upper airway showed no significant changes in the area and volume at the velopharynx and glossopharynx,as well as the height at each part.To conclude,in the growing patients with malocclusion after rapid maxillary expansion,the nasomaxillary complex and area and volume of upper airway at the nasopharynx showed a significant increase,but the airway at the velopharynx and glossopharynx reveal no significant changes.

Investigation on the difference of intolerance to food between southern and northern middle-aged Chinese and its association with eating habits / 中国应用生理学杂志

<p><b>OBJECTIVE</b>The aim of the present study was to investigate the difference of intolerance to food between southern and northern middle-aged Chinese, and furthermore analyze its association with eating habits in both study population.</p><p><b>METHODS</b>ELISA was applied to determine the serum concentrations of specific IgG of 14 food anaphylactogen in 1568 healthy subjects from totally 9 districts in both southern and northern China. Life style questionnaire was also applied to investigate the daily intake of six categorizes of food associated with food intolerance.</p><p><b>RESULTS</b>45.8% of all subjects were found to be intolerant to certain food. 62.3% of subjects from southern China and 40.4% of subjects from northern China were found to be intolerant to certain food, the difference between southern and northern Chinese was statistically significant. Top three foods intolerant by southern Chinese were crab, egg, and cold fish, while top three food intolerant by northern Chinese were egg, crab, and milk. The differences of intolerance to crab, cold fish, soy bean, rice, and tomato between southern and northern Chinese were statistically significant. Investigation on eating habits revealed that cereals and fish were the major food consumed by subjects in our study. There was no certain association between food intolerance and eating habits.</p><p><b>CONCLUSION</b>Considering that there are differences between southern and northern Chinese, southern and northern Chinese should pay attention to their daily food in order to avoid food allergy.</p>