Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis.@*METHODS@#A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared.@*RESULTS@#The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively.@*CONCLUSION@#Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

Hematological Neoplasms Secondary to Malignant Solid Tumors with Radiotherapy and Chemotherapy: a Clinical and Prognostic Analysis / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics, treatment and prognosis of therapy-related hematological neoplasms patients secondary to malignant solid tumors.@*METHODS@#The clinical features, treatment and prognosis of 36 hematological neoplasms patients secondary to malignant solid tumors with radiotherapy and chemotherapy in the Second Hospital of Shanxi Medical University were retrospectively analyzed.@*RESULTS@#The 36 patients with therapy-related hematological neoplasms had a median age of 60 (47-81) years, 14 were male and 22 were female. Among them, 22 cases were acute myeloid leukemia, 5 cases were acute lymphoblastic leukemia, 4 cases were multiple myeloma, 3 cases were myelodysplastic syndrome, and 2 cases were non-hodgkin's lymphoma. The median latency of malignant tumor to hematological neoplasm was 42.5 (12-120) months. The median survival time of therapy-related hematological neoplasms was 10.5 (1-83) months, and the 3-year overall survival (OS) rate was 24.3%. The therapy-related acute myeloid leukemia patients had a very poor prognosis, with a median survival of 7 (1-83) months and a 3-year OS rate of 21.4%.@*CONCLUSION@#The prognosis of therapy-related hematological neoplasms secondary to malignant solid tumors with radiotherapy and chemotherapy is poor, and individualized treatment should be implemented according to the clinical situation of patients.

Clinical Features of Infection in Newly Diagnosed Patients with Myelodysplastic Syndrome and Its Correlation with Curative Effect / 中国实验血液学杂志

OBJECTIVE@#To explore the characteristics of infection in patients with myelodysplastic syndromes (MDS), risk factors of serious infection, and their correlation with curative effect.@*METHODS@#The clinical data of 92 newly diagnosed MDS patients with nosocomial infection from January 2016 to June 2020 in our hospital were retrospectively analyzed.@*RESULTS@#A total of 306 courses of treatment were completed in 92 newly diagnosed MDS patients. The infection rate was the highest in the first course of treatment (84.8%, 78/92), and then decreased gradually. The top three infection sites were lung, upper respiratory tract, and gastrointestinal tract. A total of 90 strains of pathogenic bacteria were detected, of which 33.4% (30/90) were gram-negative bacilli, 23.3% (21/90) were gram-positive cocci, 23.3% (21/90) were fungi, and 20.0% (18/90) were viruses. The serious infection rate among 92 patients with MDS was 22.8% (21/92). Multivariate analysis showed that neutrophil deficiency>7 days (OR=10.875, 95%CI: 2.747-43.051, P=0.001) was an independent risk factor for serious infection in MDS patients. Compared with non-severe infection group, the total effective rate of severe infection group was lower (90.9% vs 63.6%, χ2=4.393, P<0.05).@*CONCLUSION@#The infection rate of MDS patients is high in the first course of treatment, and the most common infection site is the lung. Gram-negative bacteria is the most common pathogen. MDS patients with neutrophil deficiency>7 days have a high risk of serious infection and poor efficacy.

Epidemiological characteristics of COVID-19 cases in Xianyang, Shaanxi / 上海预防医学

Objective To analyze the epidemiological characteristics of COVID-19 cases reported in Xianyang City from January to February 2020. Methods We retrospectively studied 17 COVID-19 patients diagnosed in Xianyang Central Hospital. The patients were characterized clinically and epidemiologically. Results The 17 patients included 10 male and 7 female, with an average age of(39.59±17.31)years. The median interval of time between onset and diagnosis was four days(1-10 days), whereas the median duration of COVID-19 was 16 days(3-23 days). Of the patients, six were mild, 10 were pneumonia, and one was severe. A total of 15 patients had fever as the onset, accompanied by fatigue, sore throat, sputum, vomit, muscle soreness; the other two patients were asymptomatic. There were no complications documented in all the patients. Patients had low levels of white blood cells and lymphocytes. Chest CT scan showed diverse diffuse ground-glass shadow. Eleven patients had travel history in Wuhan before the onset, four patients had contact with people who had travel history or residence history in Wuhan, and the other two patients did not report epidemiological exposure history. In addition, four of the 17 patients were clustered cases. Conclusion General population is susceptible to COVID-19. The majority of the confirmed cases have epidemiological exposure history. Routine examination, including white blood cell, lymphocyte count and CT scan may facilitate early diagnosis.

Clinical Efficacy of Modified BU/CY as Conditioning Regimen Combined with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Young Acute Myeloid Leukemia Patients with Low or Intermediate Risk / 中国实验血液学杂志

OBJECTIVE@#To investigate the safety and efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) using modified BU/CY conditioning regimen for young AML patients of low and middle risk in the first complete remission (CR1).@*METHODS@#Ten young AML patients of low and middle risk who did not want to accept allogeneic hematopoietic stem cell transplantation（allo-HSCT）and underwent auto-PBHSCT in CR1 during May 2013 to December 2016 were retrospectively analyzed. From 3 months after auto-PBHSCT, the maintenance therapy with interleukin-2 (IL-2) or IL-2 combined with histamine dihydrochloride was performed for these patients in the next 18 months. The side effects of the conditioning regimen, hematopoietic recovery time, transplant-related mortality (TRM) within 100 days and 1 year after auto-PBHSCT, relapse rate, leukemia-free survival (LFS) rate at 2 years and 3 years, overall survival (OS) were evaluated at 3 years and 4 years.@*RESULTS@#Gastrointestinal side effects were the major non-hematologic toxicity reaction, among which, 7 cases relatively mild and 3 cases displayed moderate, just one case suffered from severe reaction. In 4 cases, the mild liver damage occurred, but no hemorrhagic cystitis occurred. All the patients experienced different kinds of infection, including 5 cases of bloodstream infection, 2 cases of gastrointestinal infection, 3 cases of crissum infection and 2 cases of oral infection. The myeloablative effect occurred in all ten patients. The median times for absolute neutrophil count (ANC)0.5×10/L at 10 to 19 days, median was 13 days after auto-PBHSCT. The patients achieved platelet count >20×10/L at 10 to 72 days; median was 32 days after auto-PBHSCT. The TRM within 100 days and 1 year after transplantation was 0. The relapse occurred in 2 cases at 6 and 14 months after auto-PBHSCT raspectively. The median follow-up time was 48.1 months, and the median survival time was 54.7 months after transplantation. The 2-year and 3-year LFS were 100% (10 cases) and 80% (8 cases), respectively. The 3-year and 4-year OS were 80% (8 cases) and 70% (7 cases), respectively.@*CONCLUSION@#Modified BU/CY as conditioning regimen for auto-PBHSCT can achieve the myeloablative effect without raising TRM and obtain good LFS and OS. As for young AML patients without high risk, it is a valuable therapeutic option, especially for those lacking the chance of allo-HSCT.

On the basis of three-dimensional finite element technique to construct a mandible model of the miniature pig and study its biomechanics / 解放军医学杂志

Objective The finite element model of the mandible of the miniature pig was constructed to explore the strain and stress changes of the mandible during loading, which laid the foundation for the analysis of the biomechanical properties of the subsequently developed mandibular external fixation holder. Methods We randomly selected a healthy Bama miniature pig, weighing 20kg, and made a CT scan to its head for obtaining the DICOM data. The DICOM data were imported into the software Mimics17.0 for 3D image reconstruction, and output the STL format. Then we imported the STL format into Geomagic Studio software to make data preprocessing, and got general curved surface file in IGES format. Then we imported the IGES format into ICEM software to carry on the grid, output the UNS grid file, then we imported it into the Workbench software for setting material attributes and definition of boundary conditions, and data post-processing. Applying this model, we simulated the occlusal force and loaded 9.8-392 N vertically downward on the left mandibular first molar, then calculating the strain and stress changes of the mandible and testing the stability of the model. Results Using medical digital image and three-dimensional finite element analysis software, we had successfully established an ideal mandibular model of miniature pig. When loading on the mandible, the results showed that there was no continuous interruption and the data generated were reasonable. Conclusions The three-dimensional finite element model of the mandible of the miniature pig can effectively simulate the strain and stress changes of the mandible, and provide a simulation mechanical analysis for the reasonable design of the external fixationholder .

Effect of tuina exercise on simple obesity in college students / 针灸推拿医学（英文版）

Objective:To observe the effect of tuina exercise on simple obesity in college students.Methods:Fifty-seven college students with simple obesity were divided into two groups according to the stratified randomization method.Twenty-eight in the tuina exercise group were trained in tuina exercise;while 29 in the auricular acupoint sticking group were treated with acuricular acupoint sticking.The tuina exercise group was trained once every other day,and 10 times made one course.The auricular acupoint sticking was replaced once every 4 d,and 5 times made one course.After 2-course treatment,the total therapeutic effect,weight,body mass index (BMI),waist and hip circumferences,serum total cholesterol (TC),triglyceride (TG),high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed.Results:The total therapeutic effect was 86.2％ in the auricular acupoint sticking group and 85.7％ in the tuina exercise group.There was no significant difference between the two groups (P＞0.05).After treatment,the weight,BMI,waist and hip circumferences were decreased and the differences were statistically significant (all P＜0.05).The waist and hip circumferences in the tuina exercise group were lower than those in the auricular acupoint sticking group,showing statistically significant differences (all P＜0.05).After treatment,there were no significant intra-group differences in TC,TG,HDL-C and LDL-C in the two groups (all P＞0.05),and the between-group differences were not significant (all P＞0.05).Conclusion:Tuina exercise has reliable effect in treating obesity.It can produce more significant improvements in waist and hip circumferences than auricular acupoint sticking.But no obvious effect is shown in blood lipid indicators.

Expression of CD25 in acute B cell lymphoblastic leukemia and its clinical significance / 中国实验血液学杂志

This study was purposed to investigate the relation of CD25 with the acute B cell lymphoblastic leukemia (B-ALL) and its clinical significance. A totol of 88 newly diagnosed B-ALL patients were enrolled in this study. The immunophenotype of leukemic myeloblasts were detected by flow cytometry, including interleukin 2 receptor α chain (CD25), β chain (CD122), γ chain (CD132), CD19, CD20, CD10, CD34, CDIgM, CD79a, CD22 and CDTDT. The expression of BCR/ABL fusion gene was detected by qualitative PCR. The expression of IL2RA (CD25 gene) was detected by real-time qualitative RT-PCR. The results showed that there was no significant statistical difference in WBC count, Hb level, PLT count, marrow blast rate, peripheral blast rate, hepato-lienal infiltration, lymph node infiltration, levels of CD10, CD20, CD22, CD34, CD79a, CDTDT, CDIgM expression between B-ALL patients with CD25(+) and B-ALL patients with CD25(-), while the CD19 expression level in B-ALL patients with CD25(+) was higher than that in B-ALL patients with CD25(-). Out of 88 B-ALL patients, 21 patients showed BCR/ABL(+)(21/88) and their CD25(+) expression level was 66.7% (14/21); 67 patients showed BCR/ABL(-) and their CD25(+) expression level was 4.5% (3/67), there was statistical difference between these two groups (P < 0.05), but the expression level of IL2RA mRNA was not statistical different between CD25(+) and CD25(-) groups (P > 0.05). Among 21 BCR/ABL(+) B-ALL patients the remission rate and relapsed rate were not statistical different between CD25(+) an CD25(-) groups.In BCR/ABL(+) B-ALL patients 8 patients relapsed, the relapsed rate was 38.1% (8/21). In BCR/ABL(-) B-ALL patients 9 patients relapsed, the relapse rate was 13.4% (9/67), there was statistical difference between BCR/ABL(+) and BCR/ABL(-) two groups (P < 0.05). In BCR/ABL(+) group the RFS (relapse free survival) was 21 months, in BCR/ABL(+) CD25(+) patients the RFS was 15 months, while in BCR/ABL(+) CD25(-) patients the RFS was 21 months, in BCR/ABL(-) CD25(-) patients, the RFS was 24 months. It is concluded that the CD25 expresses at high level in B-ALL patients with BCR/ABL(+), which may serve as a predictive marker for the presence of BCR/ABL fusion gene, and relates with relapse, CD25(+) may serve as a adjuvant indicator for poor prognosis.

Expressions of Th17 cells and interleukin 17 in patients with primary immune thrombocytopenia and their clinical significance / 中国实验血液学杂志

The aim of this study was to detect the rate of T-helper (Th)17 cells and interleukin (IL)-17 level in peripheral blood of patients with primary immune thrombocytopenia (ITP) and to explore their clinical significance. The proportion of Th17 cells from 48 patients with ITP and 28 healthy controls was detected by flow cytometry, and the IL-17 level was evaluated by enzyme-linked immunosorbent assay (ELISA). The results showed that the percentage of Th17 cells in ITP group was (1.40 ± 1.35)%, which was significantly higher than that in healthy control group (P < 0.05), but in the glucocorticoid hormone-treated group it was significantly lower than that in treated group without glucocorticoid hormone(P < 0.05). The level of IL-17 expressed by Th17 cells in ITP patients was (19.624 ± 5.187) pg/ml, which was higher than that in the healthy control group (P < 0.05), it was lower in the glucocorticoid hormone treated group than that in treated group without glucocorticoid hormone, but there was no statistically significant difference between the glucocorticoid treated and treated group without glucocorticoid hormone (P > 0.05). It is concluded that the Th17 cells may involve in the pathogenesis of ITP, and the glucocorticoid hormone probably plays a therapeutic role through inhibiting Th17 cells.

1059 g/c gene polymorphism of C-reactive protein in patients with deep vein thrombosis / 中国实验血液学杂志

This study was aimed to investigate the distribution of 1059 G/C gene polymorphism of C-reactive protein(CRP) in deep vein thrombus (DVT) and its clinical significance. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to screen 1059 G/C polymorphism in exon 2 of C-reactive protein gene in 61 cases of DVT and 60 healthy controls. The frequency of mutation was calculated. The results showed that there was no statistical difference of 1059 G/C genotype and mutation frequency of allele between deep vein thrombosis group and control group (p > 0.05). It is concluded that the 1059 G/C gene polymorphism of CRP displays certain difference in races and areas, and whether 1059 G/C gene polymorphism of CRP is a dangerous factor for deep vein thrombosis, which needs to be deeply explored.

Effects of decitabine on biological behavior of U266 cells / 中国实验血液学杂志

This study was aimed to explore the effects of decitabine on the biological behaviour of U266 cells in vitro so as to provide a new thinking and experiment basis, as well as new evidences for the pathogenesis of multiple myeloma. MTT and colony formation assays were used to evaluate the impact of decitabine on the ability of proliferation of U266 cells; flow cytometry was used to analyze the cell distribution in cell cycle; transwell chamber and matrigel assays were used to observe the ability of migration and invasion. The results indicated that decitabine could significantly suppress the proliferation of U266 cells in time-and dose-dependent manners. The flow cytometric analysis demonstrated that the cells in G(0)-G(1) phase significantly increased while the cells in S and G(2)/M phase decreased. The migration and matrigel invading tests showed that the number of cells moving into under chamber of transwell decreased after U266 cells treated with decitabine. It is concluded that decitabine may act as an effective drug for MM by inhibiting the proliferation, migration and invasion ability, and the specific mechanism needs to be deeply explored.

Effect of antisense KLF4 gene on the expression of vWF and PAI-1 in endothelium cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of antisense KLF4 (Krüppel-like factor 4) gene on the expression of vWF and PAI-1 in endothelial cells.</p><p><b>METHODS</b>Human umbilical vein endothelial cells (HUVEC) were isolated from umbilical vein and cultured in endothelial cell medium. The recombinant adenoviral plasmid carrying the antisense KLF4 gene was constructed by homologous recombination. KLF4, PAI-1 and vWF mRNAs and proteins expression were detected by real time-PCR, Western blot, and confocal laser microscopy.</p><p><b>RESULTS</b>Recombinant adenoviral plasmid carrying the antisense KLF4 gene (Ad-KLF4AS) was constructed successfully. Compared with the control Ad-GFP infection group, Ad-KLF4AS at a 200 MOI can down-regulate the expression of KLF4 gene in HUVEC (from 0.59 ± 0.01 to 0.44 ± 0.06) (P < 0.05), and increase vWF mRNA (from 1.04 ± 0.03 to 1.17 ± 0.05) and protein expression (P < 0.05). PAI-1 mRNA and protein of Ad-KLF4AS infection group was higher than that of Ad-GFP infection group. PAI-1 mRNA between the two groups had no significant difference (P > 0.05).</p><p><b>CONCLUSIONS</b>Down-regulation of KLF4 leads to increase in expression of vWF and PAI-1 in endothelial cells. KLF4 might play an important role in regulation of endothelial coagulant function.</p>

Construction and identification of recombinant adenoviral vector for antisense klf4 gene / 中国实验血液学杂志

This study was aimed to construct a recombinant adenovirus vector for antisense klf4 gene through AdEasy system. Human klf4 cDNA was reversely inserted into the multiple cloning sites (MCS)of the pShuttle-CMV by using the backbone plasmid AdEasy-l, the antisense klf4 gene was constructed through homologous recombination in E.coli BJ5183, then the adenoviruses were packaged and amplified in the HEK 293 ce1ls. The adenovirus vector for antisense klf4 gene confirmed by PCR, restriction analysis and DNA sequencing. After being transfected with the adenoviruses at 200 MOI for 48 hours, total RNA and protein were extracted from human umbilical vein endothelial cells (HUVEC). Klf4 mRNA and KLF4 protein expression levels were evaluated by Real-time PCR and Western-blot. The results showed that the recombinant adenovirus vector for antisense klf4 gene was successfully constructed, recombinant adenovirus could suppress the expression of klf4 mRNA and KLF4 protein in HUVECs. It is concluded that the adenovirus vector for antisense klf4 gene has been constructed successfully, which provides the material basis for further studying the biologic function and potential application of klf4.

Correlation of inflammatory marker and coagulation factors with deep vein thrombosis / 中国实验血液学杂志

This study was purposed to investigate the correlation of deep vein thrombosis (DVT) with C-reactive protein (CRP), fibrinogen (Fg), coagulation factor VIII (FVIII:C), coagulation factor IX (FIX:C) and to explore the effect of inflammation and coagulation as well as their interaction in DVT and its mechanism. 59 patients with DVT undergoing selective venous ultrasonography and 26 healthy individuals as controls were enrolled in this study. The plasma level of CRP was detected by immunoturbidimetry, FVIII:C, FIX:C levels were determined by a one-stage assay and fibrinogen level was measured by full-automatic biochemical apparatus. The results showed that the mean levels of plasma CRP, Fg, FVIII:C and FIX:C were significantly higher in deep vein thrombosis group than that in controls [CRP (2.67 +/- 0.91) vs (0.14 +/- 0.08) mg/dl; Fg (4.73 +/- 1.36) vs (2.79 +/- 0.66)g/L; FVIII:C (126.71 +/- 28.10) vs (81.35 +/- 20.77)%; FIX:C (81.01 +/- 23.60) vs (70.71 +/- 11.3)%] (p < 0.01), and the level of plasma CRP was strongly correlated with Fg, FVIII:C and FIX:C (r(s) = 0.432, 0.571 and 0.544, p < 0.01). It is concluded that the DVT and inflammation are closely related, increased level of plasma CRP may be a predictor of DVT. Increased plasma levels of Fg, FVIII:C and FIX:C all are important risk factors to DVT. Interaction between inflammation and coagulation promote the incidence of DVT, which may be one of DVT pathogenesis.

Effect of inflammatory cytokines on the expression of Krupple-like factor 4 in endothelium / 中国实验血液学杂志

The aim of this study was to investigate the expression of Krupple-like factor 4 (KLF-4) in human umbilical vein endothelial cells (HUVEC) under stimulating of cytokines IL-1beta and TNF-alpha. The HUVEC were isolated, cultured and exposed to IL-1beta, TNF-alpha for 2 and 4 hours, the expression level of KLF-4 mRNA was detected by real-time PCR, the expression level of KLF-4 protein was measured by Western blot, the location of KLF-4 in HUVEC was determined by confocal laser microscopy. The results showed that the KLF-4 mRNA lowly expressed in normal HUVEC, but highly expressed in HUVEC after stimulation with IL-1beta and TNF-alpha; furthermore the expressions of KLF-4 mRNA and protein were enhanced along with prolonging of time. Confocal laser microscopy showed that the expression of KLF-4 was enhanced in nucleus and plasma of HUVEC after stimulating with IL-1beta. It is concluded that the expression of KLF-4 increases under IL-1beta and TNF-alpha stimulation which may participate in regulation of endothelial activity.