Efficacy of CLAE Chemotherapy Regimen Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy and safety of CLAE intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory acute leukemia (R/R AL).@*METHODS@#CLAE regimen [cladribine 5 mg/(m2·d), d 1-5; cytarabine 1.5 g/(m2·d), d 1-5; etoposide 100 mg/(m2·d), d 3-5] followed by allo-HSCT was used to treat 3 R/R AL patients. The patients received CLAE chemotherapy in relapsed or refractory status and underwent bone marrow puncture to judge myelodysplastic state. After an interval of 3 to 5 days, followed by preconditioning regimen for allo-HSCT [fludarabine 30 mg/(m2·d), d -7 to d -3; busulfan 0.8 mg/kg q6h, d -6 to d -3 or d -5 to d -2. If the bone marrow hyperplasia was not active and the blasts were less than 10%, busulfan should be used for 3 days. If the bone marrow hyperplasia was active and the blasts were more than 10%, busulfan should be used for 4 days]. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were used for graft-versus-host disease (GVHD) prevention. After transplantation, the status of minimal residual disease (MRD) and bone marrow chimerism were regularly monitored in all 3 patients, and demethylation drugs or dasatinib were used to prevent recurrence 3 months after transplantation.@*RESULTS@#2 patients with t(11;19) translocation and relapse/refractory acute myeloid leukemia recurred within 6 months after induction of remission, and received intensive chemotherapy with CLAE regimen followed by haploidentical allo-HSCT and unrelated donor allo-HSCT, respectively. The two patients both relapsed 6 months after transplantation, then achieved complete remission by donor lymphocyte infusion, interferon, interleukin-2 and other methods, and disease-free survival was 2 years after transplantation. The other patient was chronic myelogenous leukemia who developed acute lymphoblastic leukemia during oral administration of tyrosine kinase inhibitor, accompanied by T315I and E255K mutations in ABL1 kinase region and additional chromosomal abnormalities. After morphological remission by induction chemotherapy, central nervous system leukemia was complicated. Intensive chemotherapy with CLAE regimen followed by sibling allo-HSCT was performed in the positive state of MRD. The patient relapsed 3 months after transplantation, and achieved remission after chimeric antigen receptor T-cell (CAR-T) therapy, however, he died 5 months after transplantation because of severe cytokine release syndrome (CRS) and GVHD.@*CONCLUSION@#CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.

Effect of CXCR4 on the Treatment Response and Prognosis of Carfilzomib in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of CXCR4 on the treatment response and prognosis of Carfilzomib (CFZ) in multiple myeloma.@*METHODS@#Dataset GSE69078 based on microarray data from two CFZ-resistant MM cell lines and their corresponding parental cell lines (KMS11-KMS11/CFZ and KMS34-KMS34/CFZ) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Protein-protein interaction (PPI) network was established to identify the key genes involved in CFZ resistance acquisition. Finally, the prognostic roles of the CFZ risistance key genes in MM using MMRF-CoMMpass data study was verified.@*RESULTS@#44 up-regulated and 46 down-regulated DEGs were identified. Top 10 hub genes (CCND1, CXCR4, HGF, PECAM1, ID1, HEY1, TCF4, HIST1H4J, HIST1H2BD and HIST1H2BH) were identified via Protein-protein interaction (PPI) network analysis. The CoMMpass data showed that high CXCR4 expression showed correlation to relative higher relapse and progress rates and the overall survival was significant decreased in high CXCR4 patients (P=0.013).@*CONCLUSION@#CXCR4 perhaps plays a crucial role in CFZ acquired resistance, which might help identifying potential CFZ-sensitive patients before treatment and providing a new therapeutic target in CFZ-resistant MM.

Application of day checklist model combined with fault finding and error correction method in the teaching of new nurses in neurology department / 中华医学教育探索杂志

Objective:To analyze the application effect of day checklist model combined with fault finding and error correction method in the teaching of new nurses in neurology department.Methods:A total of 42 new neurology nurses accepted in the department of neurology from January 2019 to June 2020 were selected in the study and they were divided into control group and study group. The conventional group was given the conventional teaching method, while the study group was given the day checklist model combined with fault finding and error correction method, both of which were taught for 3 months. Assessment performance of theoretical knowledge and operational skills before and after teaching, critical thinking ability before and after teaching and satisfaction with the teaching after teaching in neurology nursing were compared between the two groups. SPSS 25.0 was used for t test and rank sum test. Results:After teaching, assessment performance of theoretical knowledge and operational skills, the 7 dimensions of critical thinking ability scores and the total scores were higher than those before teaching, and the study group did better than the control group ( P < 0.05). There were significant differences between the 2 groups of new nurses in the distribution of satisfaction with teaching ( P < 0.05), and the total satisfaction rate of the study group (100.00%) was higher than that of the control group (80.96%) ( P < 0.05). Conclusion:Using the method of day checklist model combined with fault finding and error correction method in the teaching of new nurses in the neurology department can improve their assessment results, enhance their critical thinking ability and improve the teaching satisfaction.

Efficacy of Micro-Transplantation Consolidation Therapy for Patients with Acute Myeloid Leukemia after Complete Remission / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of micro-transplantation in acute myeloid leukemia (AML).@*METHODS@#The clinical data of 13 adult AML patients who received micro-transplantation as consolidation therapy from July 2014 to October 2019 was retrospectively analyzed, and the adverse reactions and efficacy of micro-transplantation were followed up.@*RESULTS@#Eight patients received micro-transpantation were still in complete remission, 5 patients relapsed after micro-transplantation, 1 of them received umbilical cord blood micro-transplantation after remission by reinduction, and all of the 13 patients have survived till now. The median overall survival time was 13 months, and the median relapse-free survival time was 12 months. All 13 patients developed grade 2-4 hematological adverse reactions. The median recovery time of neutrophils and platesets was 13 (11-15) and 15 (13-17) days, respectively. None of the 13 patients developed acute or chronic graft versus host disease. Twelve patients suffered from different infections, however, there were no serious organ function injury complications happened.@*CONCLUSION@#The micro-transplomtation of HLA-incompatible stem cells derived from peripheral blood or umbilical and blood is an effective regimen for the consolidation therapy of AML, especially for the patients suffered from low and moderate risk of AML or the aged AML patients.

Clinical Analysis of 66 Patients with Essential Thrombocytopenia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics of essential thrombocytopenia (ET) patients with positive mutations including JAK2, CALR, MPL, or negative mutations.@*METHODS@#A total of 66 newly diagnosed ET cases from January 2016 to December 2018 in Department of Hematology, Huaian No.1 People's Hospital affiliated to Nanjing Medical University were analyzed. Statistical analysis data included the patient's sex, age, symptoms, thrombosis and embolism events, spleen omegaly, platelet count (Plt), leukocyte (WBC) count, hemoglobin (Hb), fibrinogen (FIB), thrombus elastic diagram (TEG), serum potassium, blood glucose (GLU), lactate dehydrogenase (LDH), JAK2, CALR and MPL mutations, treatment options, and efficacy.@*RESULTS@#All the patients were not MPL-positive, and divided in three groups: JAK2 mutation (46 cases, 69.7%), CALR mutation (9 cases, 13.6%) and gene negative mutation (11 cases, 16.7%) group. The average age of patients in the JAK2 mutation group was 63.2 years old, and significantly higher than that in the CALR mutation group (51.8 year) and gene negative group (50.2 year) (P＜0.05). Compared with the JAK2 mutation group and gene negative group, the CALR mutation group had lower WBC count (6.3×10/L vs 13.79×10/L) (P=0.003) (6.3×10/L vs 9.70×10/L) (P=0.009). Also the Hb level of patients in CALR mutation group was lower than the JAK2 mutation group (121.22 g/L vs 136.2 g/L) (P=0.036). However, there was higher tumor burden in the CALR mutation group, compared with the gene negative mutation group (300.11 U/L vs 227.4 U/L) (P=0. 033). There was no significant difference among the three groups, such as the Plt counts, serum potassium level, GLU level and FIB level (P＞0.05). In addition, thrombus and embolism appeared in 30.3% (20/66) cases. 18.2% (12/66) cases were complicated with hyperkalemia, which significantly correlated with Plt counts (r=0.518). TEG was performed in 34 patients, of which 41.2% (14/34) had abnormal TEG and 55.9% (19/34) were accompanied by Plt count ＞ 1 000 ×10/L, but there was no significant correlation between them (r=0.134). After routine clinical treatment, all the 66 cases achieved partial or complete hematological remission, but the disease usually repeated. Until now 4.5% (3/66) cases had been converted to myelofibrosis (MF) all with JAK2 mutation, but without advancing to acute myeloid leukemia.@*CONCLUSION@#ET patients with JAK2 mutation have higher incidence, moreover were in older age. However, the patients with CALR mutations display lower WBC count and Hb level, but higher tumor burden. In short, the multiple gene mutations of ET showed different clinical features closely relates with the prognosis, thus providing guidance for the clinical diagnosis and treatment.

Structures Characteristics and Bioactivity of Polysaccharide CALB-2 from Aurantii Fructus / 中国实验方剂学杂志

Objective:To isolate and purify a polysaccharide CALB-2 fraction from Aurantii Fructus，and analyze its basic chemical structure, morphological characteristics and bioactivity. Method:A refined CALB-2 was obtained from Aurantii Fructus by hot water extraction，then separated and purified by ion exchange resin，ion exchange agarose gel and propylene dextran gel to obtain homogeneous polysaccharide CALB-2. The molecular mass of CALB-2 was determined by high performance liquid chromatography （HPLC）. Monosaccharide composition analysis of CALB-2 was conducted by methylation analysis and Smith degradation. Structural analysis and morphological characterization were conducted by infrared scanning （IR） and scanning electron microscopy （SEM） analysis. Antioxidant activity of CALB-2 was studied by using H2O2-induced cardiomyocyte oxidative damage model. Result:CALB-2 was a homogeneous polysaccharide and the molecular weight of CALB-2 was estimated to be 3.57×107 Da，which was proved to be a kind of highly branched acidic polysaccharides in IR analysis, methylation analysis and Smith degradation, mainly present in form of 1→3，4 bonds. Through SEM observations，we indicated that the molecular morphology of CALB-2 was amorphous solid. The in vitro activity test showed that CALB-2 had obvious protective effects on injury of H9c2 myocardial cells induced by H2O2. Conclusion:CALB-2 is a kind of homogeneous polysaccharide extracted from Aurantii Fructus， with an anti-cardiomyocyte oxidative damage effect, laying a theoretical foundation for further study of Aurantii Fructus polysaccharides．

Significance of Targeted Sequencing Assay for Patients with Suspected Myeloid Malignancies / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical significance of the targeted next-generation sequencing assay for patients with suspected myeloid malignancies.@*METHODS@#A total of 39 hematopenia patients with suspected myeloid malignamies in Department of Hematology of The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from January 2018 to April 2019 were treated, 20 hot spot genes of myelodysplastic syndrome (MDS) were detected.@*RESULTS@#Regarding the diagnostic type, there were 7 cases of idiopathic cytopenia of undetermined significance (ICUS), 8 cases of clonal cytopenias of undetermined significance (CCUS) and 24 cases of myeloid myeloid malignancies which included 18 cases of MDS, 4 cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and 2 cases of acute myeloid leukemia. Positive mutation was detected in 70.8% (17/24) of myeloid malignancy patients , and 72.7% (16/22) in MDS and MDS/MPN patients. The main mutation types were ASXL1, TET2 and RUNX1. Compared with gene negative group, there were no significant differences in sex, age (＜60 years old or ≥60 years old), proportion of bone marrow blast cells (＜5% or≥5%) and cytogenetics (good, medium and poor) (P＞0.05). Furthermore, all 8 CCUS patients showed positive mutation, and the incidence of double or multiple mutation in CCUS group was significantly lower than that of the MDS and MDS/MPN group (37.5% vs 54.5%) (P=0.002). The mutation types between the two groups were similar, and there was no significant difference in variant allele frequency (P＞0.05).@*CONCLUSION@#Our results suggest that there are high rates of double or multiple mutations in myeloid malignancies, especially in patients with MDS and MDS/MPN. Targeted sequencing assay can improve the diagnosis of myeloid malignancies, and guide clinical treatment.

Therapeutic Response and Prognosis of Adult Acute Myeloid Leukemia with Chromosome Karyotype Abnormalities / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and prognosis of acute myeloid leukemia (AML) patients with chromosome karyotype abnormalities.@*METHODS@#The clinical features and treatment responses of 91 patients with AML were collected and analyzed retrospectively. The efficacy and survival rate of the AML patients with normal and abnormal chromosome karyotype were compared.@*RESULTS@#Chromosome translocations and monosomal karyotypes were the main heterogeneity of AML. There was no significant difference in complete remission rate and overall response rate between the normal and abnormal karyotype groups, but the recurrence rate was higher in abnormal karyotype group. There was no significant difference in response of AML patients received the standard "3+7 regimen" and pre-excitation chemotherapy in the treatment of normal and abnormal karyotype groups. The relapse free survival time (RFS) was longer in the normal karyotype group, but there was no significant difference in overall survival time (OS).@*CONCLUSION@#The abnormal karyotype of AML is an independent prognostic factor, monosomal karyotype shows a poor prognosis, and the recurrence rate in AML patients with monosomal karyotype is higher.

Intravitreal injection of Ranibizumab combined with laser photocoagulation for macular edema secondary to BRVO / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To observe the clinical efficacy of intravitreal injection of ranibizumab combined with retinal laser photocoagulation for macular edema secondary to branch retinal vein occlusion (BRVO). ·METHODS: A total of 47 cases (47 eyes) of patients diagnosed of macular edema secondary to BRVO by fundus examination, fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) were included who were admitted to our hospital from August 2013 to March 2016. All patients were divided into two groups randomly, 47 of them finished the follow up. observation group composed of 25 patients(25 eyes) who underwent ranibizumab injection and after 2wk they received retinal laser photocoagulation for blocking venous reflux area, and control group consisting of 22 cases (22 eyes) were given intravitreal injection of ranibizumab alone. The best corrected visual acuity (BCVA), intraocular pressure (IOP), central macular retinal thickness ( CMT ) and the incidence of complications of patients from two groups were compared at the first month after the treatment. ·RESULTS:Observation group and control group's BCVA and CMT were significantly different at 1mo after treatment compared with before treatment (P<0.01), but IOP were not different (P>0.05). The BCVA at 1mo after treatment were not different between the two groups (P>0.05),the CMT were significantly different (P<0.01). · CONCLUSION: The clinical effect of ranibizumab injection combined with laser photocoagulation for blocking venous reflux area has advantages when compared with ranibizumab injection alone in the treatment of branch retinal vein occlusion, and laser photocoagulation does not stimulate macula with higher security.

Analysis of influencing factors on the hardness of papillary thyroid carcinoma diagnosed by virtual touch tissue quantification technology / 中华医学超声杂志（电子版）

Objective To analyse the influencing factors diagnosed by the virtual touch tissue quantification (VTQ) technology on the hardness of papillary thyroid carcinoma (PTC).Methods From May 2011 to March 2014,a total of 266 PTCs in 266 patients confirmed by pathology were enrolled in Shanghai Tenth People's Hospital.The shear wave velocity (SWV) values of PTCs were measured by VTQ.PTCs were divided into 2 groups including SWV ≥ 2.87 rn/s and SWV ＜ 2.87 rn/s.The x2 test was used to compare the basic clinical data,ultrasound features and immunohistochemical results between 2 groups.The influencing factors of SWV values of PTCs were analyzed by forward stepwise Logistic regression analysis.Results Of the 266 PTCs,183 were SWV ≥ 2.87 m/s and 83 were SWV ＜ 2.87 m/s.The x2 test showed that the ultrasound features of PTCs such as single or multiple,with or without central lymph node metastasis,location,size,shape,with or without posterior acoustic attenuation,with or without calcification,with or without capsule invasion,whether close to the trachea between the 2 groups were significant different (x2=4.233,4.740,9.910,4.988,4.416,4.737,7.154,8.559,all P ＜ 0.05 or 0.01).Logistic regression analysis demonstrated that nodules were single or multiple,location,with or without posterior acoustic attenuation,with or without calcification,whether close to the trachea were influencing factors of SWV value of PTCs.The regression equation was defined as Y=-2.507 + 0.670X1 (nodules were single or multiple) + 0.800X3 (location of nodules) + 0.851X6 (with or without posterior acoustic attenuation) + 0.628X7 (with or without calcification) + 1.106X9 (whether close to the trachea).Conclusions Multiple nodules,central lymph node metastasis,located isthmus,nodules size ＞ 10 mm,irregular shape,posterior acoustic attenuation,calcification,capsule invasion,close to the trachea were correlated with the diagnosis of PTC by VTQ technology.The more characteristics of nodules appeared,such as multiple nodules,located isthmus,posterior acoustic attenuation,calcification,close to the trachea,the harder PTCs were.

Seroprevalence of Dirofilaria immitis in Cats from Liaoning Province, Northeastern China

The present study was performed to investigate the seroprevalence and risk factors for Dirofilaria immitis infection in cats from Liaoning province, northeastern China. From October 2014 to September 2016, sera of 651 cats, including 364 domestic cats and 287 feral cats (332 females and 319 males) were assessed. They were tested for the presence of D. immitis antigen using SNAP Heartworm RT test kit. In this population, the average prevalence was 4.5%. Age and rearing conditions (feral or domestic) were found to be associated with the prevalence of D. immitis. The prevalence was significantly higher in feral cats compared with domestic cats (8.4% vs 1.4%, P 0.05), but older cats (≥3 years old) showed a statistically higher prevalence compared with younger cats ( 0.05), all these results suggest that outdoor exposure time may be one of the most important factors for D. immitis prevalence in cats. Results reveal that D. immitis are prevalence in domestic and feral cats in northeastern China, which indicates that appropriate preventive measures should be taken to decrease the incidence of feline heartworm disease in Liaoning province, northeastern China.

Influence of Co-inhibiting mTORC2 and HSP90 on Proliferation Apoptosis of Multiple Myeloma Cells / 中国实验血液学杂志

<p><b>UNLABELLED</b>Objective：To explore the influence of co-inhibiting mTORC2 and HSP90 on the proliferation and apoptosis of multiple myeloma(MM) cell line U266.</p><p><b>METHODS</b>During culture, the human MM cell line U266 were treated with 20 nmol/L of rapamycin, 600 nmol/L 17-AAG, 20 nmol/L of rapamycin + 600 nmol/L 17-AGG and phosphate-buffered saline (PBS), then the growth inhibition rate, morphologic changes, apoptosis rate and the expression of caspase 3 and ATK protein in U266 cells were compared and analyzed.</p><p><b>RESULTS</b>The rapamycin and 17-AAG both could inhibit the growth of U266 cells, while the inhibitory effect of rapamycin in combination with 17-AAG on growth of U266 cells was significantly higher them that of rapamycin and 17-AAG alone and control (PBS); the apoptosis rate of U266 cells treated with rapamycin, 17-AAG and their combination was higher than that of control PBS groups, and the efficacy of 2 drug conbination was higher than that of control PBS group, and the efficacy of 2 drug combination was superior to single drug. The expression levels of caspase 3 and ATK in U266 cells treated with rapamycin, 17-AAG and their combination were higher and lower than those in control group respectively, and the efficacy of 2 drug combination was superior to signle drug. There were significant difference between them (P<0.05).</p><p><b>CONCLUSION</b>The co-inhibition of mTORC2 and HSP90 can suppress the proliferation and induce the apoptosis of MM cells.</p>

HSP90 Inhibitor 17-AAG Inhibits Multiple Myeloma Cell Proliferation by Down-regulating Wnt/β-Catenin Signaling Pathway / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of HSP90 inhibitory 17-AAG on proliferation of multiple myeloma cells and its main mechanism.</p><p><b>METHODS</b>The multiple myeloma cells U266 were treated with 17-AAG of different concentrations (200, 400, 600 and 800 nmol/L) for 24, 48, and 72 hours respectively, then the proliferation rate, expression levels of β-catenin and C-MYC protein, as well as cell cycle of U266 cells were treated with 17-AAG and were detected by MTT method, Western blot and flow cytometry, respectively.</p><p><b>RESULTS</b>The 17-AAG showed inhibitory effect on the proliferation of U266 cells in dose- and time-depetent manners (r = -0.518, P < 0.05 and r = -0.473, P < 0.05), while the culture medium without 17-AAG displayed no inhibitory effect on proliferation of U266 cells (P > 0.05). The result of culturing U266 cells for 72 hours by 17-AAG of different concentrations showed that the more high of 17-AAG concentration, the more low level of β-catenin and C-MYC proteins (P < 0.05); At same time of culture, the more high of 17-AAG concentration, the more high of cell ratio in G1 phase (P < 0.05), at same concentration of 17-AAG, the more long time of culture, the more high of cell ratio in G1 phase (P < 0.05).</p><p><b>CONCLUSION</b>The HSP90 inhibitory 17-AAG can inhibit the proliferation of multiple myeloma cells, the down-regulation of Wnt/β-catenin signaling pathway and inhibition of HSP90 expression may be the main mechnisms of 17-AAG effect.</p>

Structural characterization of coatomer in its cytosolic state

Studies on coat protein I (COPI) have contributed to a basic understanding of how coat proteins generate vesicles to initiate intracellular transport. The core component of the COPI complex is coatomer, which is a multimeric complex that needs to be recruited from the cytosol to membrane in order to function in membrane bending and cargo sorting. Previous structural studies on the clathrin adaptors have found that membrane recruitment induces a large conformational change in promoting their role in cargo sorting. Here, pursuing negative-stain electron microscopy coupled with single-particle analyses, and also performing CXMS (chemical cross-linking coupled with mass spectrometry) for validation, we have reconstructed the structure of coatomer in its soluble form. When compared to the previously elucidated structure of coatomer in its membrane-bound form we do not observe a large conformational change. Thus, the result uncovers a key difference between how COPI versus clathrin coats are regulated by membrane recruitment.

Effect of vitamin D on overload-induced hypertrophy of skeletal muscle and expression of vitamin D receptor in aged rats / 第二军医大学学报

Objective To establish an overload-induced hypertrophy model in aged rats by severing the distal tendon of gastrocnemius muscle, and to investigate the effect of vitamin D on overload-induced hypertrophy and the related mechanism. Methods A total of 20 male rats (24 months old) underwent tenotomy of the achilles tendon of the gastrocnemius muscle in the left hind limb; and a control sham operation was performed on the right hind limb. The rats were randomly divided into control group and experimental group. Experimental group received 1 000 IU/kg of vitamin D by intragastric administration, and the control group was given soybean oil. The animals were sacrificed one week later, the blood samples were collected, and the left, right hind musculus plantaris tissues were weighed and kept in liquid nitrogen. ELISA assay was used to examine serum 25(OH)D level and vitamin D receptor (VDR) in the skeletal muscle. Western blotting analysis was used to examine mTOR, rpS6 protein and their phosphorylation. Results The food intake and body mass were not significantly different between the two groups. Compared with the control side, vitamin D supplement significantly increased the muscle mass of the overload side in both groups (P<0. 05); and the mass of the overload side in the vitamin D supplement group was significantly higher than that in the control group (P<0. 05), while the mases were not significantly different for the sham sides in the two groups. The results of ELISA assay showed that vitamin D supplement significantly increased serum 25(OH)D levels in rats compared with the control group (P< 0. 05), and significantly promoted the expression of VDR in the overload side compared with the Sham side (P<0. 05), while there was no significant difference between the two sides in the control group. Western blotting analysis showed that p-rpS6/rpS6 and p-mTOR/mTOR ratios in the overload sides were higher than those in the Sham sides, but significant difference was only found for the vitamin D supplement group (P<0. 05). Conclusion Tenotomy of the achilles tendon of the gastrocnemius muscle can effectively promote the skeletal muscle hypertrophy in aging rats, and vitamin D supplement can further enhance overload-induced skeletal muscle hypertrophy, which might be related to VDR expression in skeletal muscle and protein synthesis protein mTOR and rpS6.

Expression of Btk and NFκB in acute myeloid leukemia cells and its significance / 中国实验血液学杂志

This study was purposed to investigate the expression of Btk and NFκB in acute myeloid leukemia (AML) cells and its significance. Bone marrow mononuclear cell specimens were taken from 14 AML patients who were in new diagnosis and complete remission respectively, the expressions of Btk and NFκB at mRNA and protein levels were detected by RT-PCR and Western blot, respectively. The results showed that Btk and NFκB expressed in all the samples at RNA and protein levels. At protein level, Btk and NFκB expressions were higher in the cells from newly diagnosed AML patients than that in the cells from patients in complete remission stage (P < 0.05). It is concluded that Btk and NFκB may play an important role in the development and progression of AML, they may be used as potential therapeutic targets of AML and used in predicting the prognosis.

Analysis of risk factors for relapse of 82 patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the risk factors for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the measures of prophylaxis and treatment.</p><p><b>METHODS</b>We summarized the clinical data of 82 patients with hematologic malignancies who were treated in our hospital from August 2003 to December 2008. Factors including age, sex, ABO blood group disparity of donor and recipient as well as the type of donor, status of disease, HLA-match, conditioning regimen, whether or not having developed acute GVHD and chronic GVHD, infusion number of CD34(+) cells, relationship between CMV infection and relapse post-transplantation were considered and analyzed.</p><p><b>RESULTS</b>Single factor analysis indicated that there were five independent risk factors related with the disease relapse (P < 0.05), including status of disease, time of diagnosis to transplantation, acute graft versus host disease (aGVHD), conditioning regimen, and chronic graft versus host disease (cGVHD). Simultaneously, the type of donor was a substantial factor (P < 0.01), determined by multi-factor Cox regression analysis. Cox regression analysis determined that disease status (OR = 2.58, 95%CI 1.26 - 5.01, P = 0.01), time from diagnosis to treatment (OR = 1.98, 95%CI 1.11 - 3.63, P = 0.025) and cGVHD (OR = 3.74, 95%CI 1.96 - 7.97, P < 0.001) were major factors for relapse of the patients who had undergone transplantation.</p><p><b>CONCLUSIONS</b>Relapse remains the primary cause of failure after allo-HSCT. Status of disease, time from diagnosis to treatment and not cGVHD are the major risk factors. Effective prevention and treatment of relapse after engraftment can improve the efficacy of HSCT.</p>

Risk factors for acute kidney injury in patients undergoing allogeneic hematopoietic stem cell transplantation / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Allogeneic hematopoietic cell transplantation (allo-HSCT) is a potent procedure for the treatment of hematologic diseases, yet it is associated with high risks of treatment-related complications. Except for transplant-related organ toxicities, renal insufficiencies which emerge earlier significantly limit patients' long survival. To analyze risk factors for acute kidney injury (AKI), we conducted a retrospective cohort study of 96 patients undergoing HSCT.</p><p><b>METHODS</b>During the first 100 days after allo-HSCT, all patients were evaluated for renal function by measuring serum creatinine clearance and glomerular filtration rate (GFR) with a classification below: Grade 0 (<25%, decline in creatinine clearance), Grade 1 (≥25% decline in creatinine clearance but <2-fold increase in serum creatinine), Grade 2 (≥2-fold rise in serum creatinine but no need for dialysis), and Grade 3 (≥2-fold rise in serum creatinine and need for dialysis). Cox regression model was used to calculate the hazard ratios (HRs) of demographic data, clinical variables, and risk factors for AKI.</p><p><b>RESULTS</b>Twenty-eight (29.2%) patients occurred Grades 1-3 renal dysfunction (Grade 1, 14 patients; Grade 2, 12 patients; Grade 3, 2 patients), and ratios of early kidney injury increased in high-risk malignancy group (HR = 2.945, 95% confidence interval (CI)=1.293-6.421), patients treated with myeloablative conditioning regimen (HR=2.463, 95% CI=1.757-4.320), and patients with acute GVHD (HR=3.553, 95% CI=1.809-6.978), sepsis (HR=3.215, 95% CI=1.189-6.333 ), or hepatic veno-occlusive disease (VOD) (HR=3.487, 95% CI=1.392-6.524). Whereas, HLA histocompatibility showed no striking increased risk for acute renal injury (HR=1.684, 95% CI=0.648-4.378). The survival rate was lower in patients with severe nephrotoxicity (21.4%) than in patients without nephrotoxicity (70.6%) (P=0.001).</p><p><b>CONCLUSIONS</b>Nephrotoxicity is the primary risk factor for AKI, severely impacting on survival. Sorts of risk factors mentioned will be useful for evaluation for kidney function of patients undergoing allo-HSCT.</p>

Analysis of risk factors for overall survival at 5 years in 96 patients after allogeneic hematopoietic cell transplantation / 中国实验血液学杂志

The aim of this study was to analyze the risk factors for overall survival at 5 years in 96 patients undergoing allogeneic hematopoietic stem cell transplantation by retrospective analysis. 11 clinical parameters including age, sex, disease status, HLA locus, donor type, donor-recipient blood type, conditioning regimen, aGVHD, HC, VOD and IP were selected for univariate analysis by using a Cox regression. Factors have statistic significance at the 0.1 level on univariate analysis were evaluated by multivariate analysis by a Coxs regression. The cumulative incidence of aGVHD and survival rate of patients were calculated by the method of Kaplan and Meier. The results showed that 95 patients achieved sustained donor engraftment except 1 patients. The median time of leukocyte engraftment (ANC > or = 0.5 x 10(9)/L) was 13 days. The aGVHD of I - IV grade was observed in 42 out of 96 patients (43.75%), in which 11 patients were with aGVHD of I grade (11.46%), 19 patients were with aGVHD of II grade (19.79%), 12 patients were with aGVHD of III - IV grade (12.50%). Out of 96 patients 10 relapsed and 38 dead, the overall survival at 5 years was 60.42%. The Cox regression analysis showed that aGVHD and disease status before transplant were main factors affecting long-term survival of patients, relative risks of which were 2.996 and 2.619 respectively. It is concluded that the main factors affecting long-term survival of patients are aGVHD and disease status. The key to improve the outcome of allo-HSCT is to reduce the incidence and severity of aGVHD, meanwhile to select the CR1 for allo-HSCT to treat the patients in advanced refractory and relapsed situation should be considered as important risk factors.

Influence of methylprednisolone on cell component of donor graft and on H-2 haploidentical hematopoietic stem cell transplantation in mice / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the influence of methylprednisolone (MP) on cellular component in donor graft and on H-2 haploidentical hematopoietic stem cell transplantation (HSCT) in mice.</p><p><b>METHODS</b>A murine model of H-2 haploidentical HSCT was established by using of c57BL/6J male mouse as donor and (c57BL/6J x LB/C) F1 female mouse as recipient. The donor mouse received peripheral-blood (PB) progenitor cells mobilization regimens consisted of recombinant human granulocyte colony-stimulating factor (rhGCSF) alone (control group) or combined with MP in dose of 2 mg/kg daily [small-dose (SD) group], 10 mg/kg daily [middle-dose (MD) group], and 50 mg/kg daily [large-dose (LD) group] respectively. Percentage of T cell subsets, DC1 (HLA-DR+CD11c+) and CD34+ cell in the grafts were detected by flow cytometry. Transplant rejection,severity of GVHD and survival time were observed.</p><p><b>RESULTS</b>The percentages of CD3+ T cell in donor grafts in the three groups were significantly lower than that in control group (P < 0.05). The percentage of CD3+ CD4+ T cells decreased more significantly than that of CD3+ CD8+ T cells, and CD4/CD8 ratios decreased significantly. The percentage of CD4+ CD25+ T cells increased significantly, the percentage of DC1( HLA-DR+CD11c+) decreased and the percentage of CD34+ cells increased in all the three groups than in control group. There were significant differences in the percentage of CD3+ T cells, CD3+ CD4+ T cells and CD34+ cells in donor grafts among SD group, MD group and LD group (P < 0.05). The engraftment rates in control, SD, MD and LD groups were 90%, 100%, 100% and 80% respectively. Severity of aGVHD in each study group decreased significantly compared with that in control group (P < 0.05). There were statistical differences among different dosage groups (P < 0.05). Survival time after transplantation in all study groups were significantly longer than that in control group (P < 0.05), and in MD group was significantly longer than in SD group and LD groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Addition of methylprednisolone to routine donor mice HSC mobilization regimen has a definite effect in alleviating aGVHD and prolonging survival time of mouse after H-2 haploidentical HSCT. With a suitable dosage addition of methylprednisolone to donor mice HSC mobilization regimen could avoid the increasing risk of graft rejection.</p>