Efficacy and Safety of the Induction Therapy with Different Doses of Anthracyclines for Patients with Newly Diagnosed Acute Promyelocytic Leukemia / 中国实验血液学杂志

@#]Objective:To investigate the efficacy and safety of induction regimens containing arsenite, allo-transretinoic acid (ATRA) and anthracyclines of different doses as induction chemotherapy for acute promyelocytic leukemia (APL).@*METHODS@#The clinical data of 129 consecutive hospitalized newly diagnosed APL patients from January 2011 to December 2017 were collected and retrospectively analyzed. Sixty-six patients received arsenite, ATRA and anthracyclines of low doses (low dose group), while other 63 patients received arsenite, ATRA and anthracyclines of standard doses (standard dose group), the efficacy and safety were compared and analyzed in 2 groups.@*RESULTS@#There were no statistically significant differences in terms of age, sex, routine blood indexes,LDH level, bone marrow promyelocyte count,prognostic stratification between patients in two groups (P>0.05). During the treatment, WBC count peak and its time point were not significantly different between two groups (P>0.05). Both induction regimens showed good efficacy, the PML-RARα gene conversion rate from positive into negative, the 2-year overall survival rate and disease-free survival rate in the low-dose group were similar to those in the standard dose group(P＞0.05). The recovery time of neutrophils and platelets in the low-dose group was 0 d and 11 d, respectively, which were statistically  significantly shorter than those in the standard dose group (3 d,15 d) (both P=0.000). The median value of platelet and erythrocyte transfusion in the low-dose group was 6.9 U and 4.2 U, respectively, which were statistically significantly lower than that in the standard dose group (8.4 U,6.8 U) (P=0.037，0.000). And the inpatient time in the low and the standard dose groups were 30.98 and 30.71 days, respectively (P=0.770).@*CONCLUSION@#For newly diagnosed patients with APL, the efficacy was similar between induction therapy containing arsenite,ATRA and low dose anthracyclines and the induction therapy containing arsenite, ATRA and standard dose anthracyclines, however, the former appears even safer.

Clinical study of temperature contrast injection procedure in prevention of bone cement leakage during vertebroplasty / 中国骨伤

OBJECTIVE@#To observe the effect of temperature contrast injection procedure on prevention and reduction of bone cement leakage in vertebroplasty (PVP).@*METHODS@#The clinical data of 42 patients(48 vertebral bodies) with osteoporotic vertebral compression fractures(OVCFs) treated from July 2014 to July 2018 were retrospectively analyzed. There were 19 males and 23 females, aged from 62 to 80 years old with an average of 72 years. The vertebral fracture segment was T₈-L₅, including 30 lumbar vertebrae and 18 thoracic vertebrae. The course of the disease ranged from 3 d to 2 months. Twenty cases (20 vertebral bodies) were treated by single vertebroplasty (group A) and 22 cases (28 vertebral bodies) were treated by temperature contrast injection procedure(group B). The operative time, amount of bone cement injection, VAS score at 3 days after surgery, leakage rate and refracture rate were compared between two groups.@*RESULTS@#The operative time, amount of bone cement injection and VAS score at 3 days after surgery in group B were (40.05±7.78) min, (3.93±0.19) ml, (3.55±0.74) points, respectively, and in group A were(38.90±6.81) min, (4.03±0.24) ml, (4.05±1.00) points, there was no significant difference between two groups(>0.05). The leakage rate in group B was lower than that in group A (9.1% vs 40.0%, 0.05).@*CONCLUSIONS@#Temperature contrast injection procedure is an effective method to reduce the bone cement leakage in vertebroplasty.

3D finite element modeling and analysis of the whole cervical spine based on Simpleware / 医用生物力学

Objective To build a 3D finite element model of the whole cervical spine by using Simpleware software, as well as validate and analyze the model, so as to provide a reliable model for exploring the mechanism of cervical spine injury. Methods The 3D entity model of the whole cervical spine C1-7 was established based on CT tomography images, medical image processing software Simpleware, reverse engineering software Geomagic, which was imported to Hypermesh for meshing, adding ligaments and introducing facet joint contact relation, etc., thus to establish the finite element model of the whole cervical spine C1-7. Biomechanical properties of the cervical spine under flexion, extension, lateral bending and torsion were simulated by ANSYS. Results The established model was proved to be accurate and reliable, and its range of motion (ROM) under flexion, extension, lateral bending and axial rotation was similar to in vitro experiment and finite element analysis results in related literatures. The stress of intervertebral disc was concentrated on the compression side of the vertebral body, and the cervical spine C4/5 was more prone to have a stress concentration. Conclusions The finite element model of the whole cervical spine C1-7 can effectively simulate the biomechanical characteristics of the cervical vertebra, which establishes a good foundation for the follow-up studies on whiplash injury of the cervical spine.

Inhibitory effect of Akt inhibitor deguelin on the growth of PC-3 prostate cancer cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the inhibitory effect of Akt inhibitor deguelin on PC-3 human prostate cancer cell lines and its possible mechanism.</p><p><b>METHODS</b>PC-3 human prostate cancer cells were cultured in deguelin at the concentrations of 10, 100, 500 and 1 000 nmol/L for 24, 48 and 72 hours, respectively. Then the inhibitory effect of deguelin on the proliferation of the PC-3 cells was determined by MTT assay and that on the cell cycle was detected by flow cytometry. The expression levels of MDM2 and GSK3beta mRNA were measured by RT-PCR and those of MDM2 and GSK3beta proteins by Western blot.</p><p><b>RESULTS</b>At 24, 48 and 72 hours, the inhibition rates of deguelin on the proliferation of the PC-3 prostate cancer cells were (91.10 +/- 3.75), (86.39 +/- 1.16) and (79.51 +/- 2.63)% at 10 nmol/L, (82.46 +/- 3.65), (76.84 +/- 0.97) and (69.69 +/- 2.30) % at 100 nmol/L, (81.46 +/- 0.41), (75.56 +/- 1.12) and (54.07 +/- 3.21)% at 500 nmol/L, and (66.77 +/- 2.82), (58.22 +/- 0.35) and (39.34 +/- 2.40)% at 1000 nmol/L, all with statistically significant differences from the control group (P < 0.01). Deguelin at 10, 100, 500 and 1 000 nmol/L increased the cell cycles blocked in the G0/G1 phase ([62.4 +/- 2.2], [63.6 +/- 1.1 ], [65.0 +/- 0.3] and [66.5 +/- 1.9]%, P < 0.01) and reduced the percentage of the S-phase cells ([14.7 +/- 2.4], [11.1 +/- 5.2], [5.8 +/- 1.1] and [7.0 +/- 0.6]%, P < 0.01). RT-PCR and Western blot showed markedly up-regulated expressions of GSK3 P3 a3beta down-regulated expressions of MDM2 mRNA and proteins in the PC-3 cells treated with deguelin.</p><p><b>CONCLUSION</b>Akt inhibitor deguelin can inhibit the proliferation of PC-3 human prostate cancer cells by affecting the down-stream signal molecules GSK3P3 and betaDM2 in the Akt pathway.</p>

Clinical study of umbilical cord-derived mesenchymal stem cells for treatment of nineteen patients with steroid-resistant severe acute graft-versus-host disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of umbilical cord-derived mesenchymal stem cells (MSCs) infusion in patients with steroid-resistant severe acute graft-versus-host disease (aGVHD).</p><p><b>METHODS</b>A total of 19 patients with steroid-resistant severe aGVHD received MSCs infusion treatment. The treatment response, transplantation-related mortality, events associated with infusion and relapse rate were analyzed.</p><p><b>RESULTS</b>Two patients with grade II, 5 patients with grade III and 12 patients with grade IV aGVHD received a total of 58 infusions of MSCs. The mean total dose of MSCs was 2.13 (range 0.60 - 7.20)×10(6) cells per kg bodyweight. Seven patients received one infusion, 2 patients received two infusions, and 10 patients received three or more infusions. Eleven patients had a complete response and 4 had a partial response and 4 had no response. No patients had side-effects during or immediately after infusions, and no MSCs related tumorigenesis was detected to date. Eleven patients survived and 8 died, 4 for aGVHD, 1 for infection and 2 for aGVHD with concomitant infection and 1 for underlying leukemia relapse. The cell viability of freshly prepared MSCs is 93% (92% - 95%) by trypan blue staining. The cell viability of programmatically frozen and thawed MSCs is 72% (70% - 74%).</p><p><b>CONCLUSION</b>Infusion of umbilical cord-derived MSCs expanded in vitro is an effective therapy for patients with steroid-resistant severe aGVHD without negative impact on relapse. Freshly prepared MSCs are superior to frozen and thawed cells in terms of cell viability.</p>

Clinical significance of TNF-alpha, IL-1beta and IFN-gamma levels at early phase after allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

The objective of this study was to investigate the alterations of cytokines TNF-alpha, IL-1beta and IFN-gamma at early phase after allogeneic hematopoietic stem cell transplantation and in the course of preconditioning, and to explore the relation of these cytokines with transplant-related complications. Alterations of TNF-alpha, IL-1beta, and IFN-gamma levels in serum were detected by ELISA in 95 patients received allogeneic hematopoietic stem cell transplantation (among them 43 cases with GVHD, 5 cases with thrombosis, 31 cases with infection) and 20 in healthy adults. Alterations of the three cytokines were analyzed during the preconditioning and the early phase after transplantation. The results showed that the TNF-alpha levels in aGVHD patients underwent allo-HSCT were already higher than that in normal controls before preconditioning (p<0.01), other patients did not show significant change during this course. TNF-alpha level in all patients were higher than that at day 4 of preconditioning, then decreased at end of preconditioning (p<0.05). TNF-alpha level increased at occurrence of aGVHD, thrombosis and infection, which is most significant in patients with aGVHD, and less significant in patients with infection as compared with patients with thrombosis (p<0.05). TNF-alpha level began to increase at 2 weeks before aGVHD and thrombosis developed in patients, while TNF-alpha levels did not change in patients with infection at the same time. IL-1beta levels did not change during preconditioning, but increased at time of aGVHD, thrombosis and infection in patients, in which IL-1beta levels in patients with thrombosis increased obviously, and more obviously in patients with aGVHD than that in patients with infection (p<0.01). IL-1beta levels in patients with aGVHD began to increase at 1 week before aGHVD developed, but IL-1beta levels in patients with thrombosis began to increase at two weeks before complication developed. IFN-gamma levels did not change in all patients during the process of transplantation. It is concluded that the alterations of cytokine levels exist during the course of allo-HSCT, which reflects the vascular damage following preconditioning and occurrence of some transplant associated complications. Levels of TNF-alpha and IL-1beta are closely related to aGVHD or thrombotic complications. Monitoring changes of TNF-alpha and IL-1beta levels contributes to early discovery of aGVHD and thrombotic complications.

Acute T cells lymphoblastic leukemia with a t(1;19)(q23;p13) and E2A-PBX1 in an adult: one case report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To report a case of T cell acute lymphoblastic leukemia (ALL) with t(1;19)(q23;pl3) and E2A-PBX1 fusion gene, which is a characteristic translocation of childhood B cell ALL (B-ALL).</p><p><b>METHODS</b>The chromosome, karyotype, immunophenotype and mRNA for fusion gene of the leukemic cells were examined by cytogenetic analysis, flow cytometry (FCM) and reverse transcriptase PCR (RT-PCR), respectively.</p><p><b>RESULTS</b>The cytogenetic karyotype of the patient was 47, XY, 9p+, 15p+, 17q-, der(19), t(1;19)(q23;pl3)\[5\]/46, XY\[15\], and E2A-PBX1 was positive. The leukemic cells expressed T cell markers. The patient was induced with hyper CVAD regimen (cyclophosphamide, vincristine, adriamycin, and dexamethasone), and achieved complete remission with normal cytogenetic karyotype 46 XY\[10\], and negative E2A-PBX1.</p><p><b>CONCLUSION</b>t(1;19)E2A-PBX1(+) can be implicated in adult T-ALL, besides childhood B-ALL.</p>

Clinical significance of plasminogen activator inhibitor-1 (PAI-1) in the early development of HSCT-associated thrombotic complications / 中华血液学杂志

<p><b>OBJECTIVE</b>To illustrate the early alteration of plasminogen activator inhibitor-1 (PAI-1) in the recipients of hematopoietic stem cell transplantation (HSCT) and explore its clinical significance in transplantation-associated thrombotic complications.</p><p><b>METHODS</b>Ninety-five patients undergoing HSCT were enrolled in this study. PAI-1 level and other hemostatic parameters were measured by enzyme linked immunosorbent assay (ELISA) in platelet poor plasma samples from patients on conditioning therapy and then weekly until four weeks after HSCT.</p><p><b>RESULTS</b>Significant increase in PAI-1 was detected after conditioning treatment, followed by a diminution in the very week on transplantation (week 0), then increased with in time after transplantation. According to the occurrence of transplant-associated complications, patients were classified into four groups: thrombus group \[veno-occlusive disease (VOD) (n = 5), thrombotic microangiopathy (TMA) n = 1\], aGVHD group (n = 29), infection group (n = 19) and non-complication group (n = 41). One of 30 patients (3.3%) was diagnosed as thrombus in the auto-HSCT group, while five of 65 patients (7.7%) did in the allo-HSCT group. PAI-1 level of thrombotic patients was significantly increased compared with non-thrombotic subjects, and the patients without thrombotic complications have higher PAI-1 level in the allo-HSCT group than in auto-HSCT group. All the patients with complications presented with significantly increased PAI-1 compared with those with no complications (P < 0.05). The six patients with thrombotic complications showed extremely elevated PAI-1 \[(62.8 +/- 7.5) microg/L\] compared with that of aGVHD patients \[(45.1 +/- 9.1) microg/L\] or infection patients \[(50.0 +/- 11.2) microg/L\] post-HSCT (P < 0.05).</p><p><b>CONCLUSION</b>The increase in plasma PAI-1 may be a specific mark for transplantation-associated thrombotic complications. Increased PAI-1 reflects the development of thrombotic complications. Extreme elevation of PAI-1 contributes to the early diagonsis of VOD and TMA after HSCT.</p>

Surgical treatment and pathological findings of hematological malignancies patients complicated with lung diseases / 中华血液学杂志

<p><b>OBJECTIVE</b>To determine the pulmonary pathological changes in hematological malignancy patients with pulmonary complications.</p><p><b>METHODS</b>17 hematological malignancy patients underwent surgical treatment were evaluated retrospectively. The pathological changes of all the surgical specimens were examined postoperatively by standard hematoxylin and eosin (HE) staining.</p><p><b>RESULTS</b>Pathological examination confirmed: aspergillus infection in 9 patients, sub-acute inflammation (fibrosis and hematoma formation) in 3, and each in 1 of pulmonary infarction with granulomatous tissue in the periphery; granulomatous inflammation with calcified tubercle; alveolar dilation and hemorrhage, interstitial fibrosis and focal vasculitis; intercostal neurilemmoma; and moderate-differentiated adenocarcinoma accompanied by intrapulmonary metastasis. And several operative complications (1 case of fungal implantation, 3 pleural effusion and adhesions and 2 pulmonary hematoma) were occurred. The coincidence rate of pre- and post-operative diagnosis was 9/14 (64.3%). After surgery, 8 patients were received hematopoietic stem cell transplantation (HSCT, allo-gene or autologous), with 7 succeeded. On effective secondary antifungal prophylaxis, 4 of 5 patients of aspergillosis succeeded in transplantation with free from mycotic relapse, one patient died from fungal relapse.</p><p><b>CONCLUSION</b>Hematological malignancies with persistent and/or resistant pulmonary infection, hemoptysis, or unexplained lung diseases, should be treated in time by surgery operation to effectively eliminate residual disease and obtain a definitive diagnosis, so as to create a prerequisite condition for the following treatments. Moreover, the secondary antifungal prophylaxis can provide active roles for patients scheduled for chemotherapy and/or HSCT.</p>

Expression of neuropeptide substance P during wound healing of deep partial thickness scalding in diabetic rats / 上海第二医科大学学报

Objective To study the expression and change of neuropeptide substance P (SP) during the wound healing of deep partial thickness scalding in diabetic rats. Methods Eighty-four Wistar rats were randomly divided into diabetes mellitus group (n=42) and control group (n=42). Diabetic rat models were established by intraperitoneal injection of streptozotocin (STZ) in diabetes mellitus group, and those in control group were intraperitoneally injected with aseptic citrate buffer solution. Deep partial thickness scalding with diameter of 2 cm on the back were prepared in all the rats. The pre-scalding and post-scalding wound specimens of different time points were obtained, and the percentages of wound closure were calculated. The wound specimens were also obtained for immunohistological staining to compare the areas with positive staining of SP, and ELISA was employed to detect the expression of SP in the wound tissues. Results The percentage of wound closure was significantly lower in diabetes mellitus group than that in control group from 7 days post-scalding (P< 0.01). The areas with positive staining of SP in diabetes mellitus group were much smaller than those in control group at different time points, which was most significant on the seventh day post-scalding[(1 350.93±99.28) μm2 vs(1 715.86± 103.41) μm2](P < 0.01). The expression of SP in the wound tissues was significantly lower in diabetes mellitus group than that in control group at different time points, which was most significant on the seventh day post-scalding[(114.04±9.96) vs(143.39±8.94)](P<0.01). Conclusion The significantly lower expression of SP in wound site may be one of the causes of delayed wound healing in diabetic rats.

Function of matrix metalloprotenase-2 by RNA interference / 中国实验血液学杂志

The study was aimed to reveal the effects of matrix metalloproteinase-2 (MMP-2) on cell proliferation, migration, invasion, angiogenesis and cell cycle. The small interfering RNA (siRNA) of MMP-2 transfected into endothelial cells EAhy926, the transformation efficiency at protein and gene levels was evaluated by using flow cytometry and RT-PCR respectively. MTT method was used to detect the proliferation ability of EAhy926. The migration and invasion abilities of EAhy926 induced by two kinds of factors, type IV collagen (COL IV) and fibronectin (Fn) were assayed with Rose Bengal dying method. The changes of angiogenesis were determined by three-dimension culture. The changes of cell cycle and related gene expression were assayed by using flow cytometry and RT-PCR respectively. The results indicated that the proliferation ability of EAhy926 had no obvious difference between interference or not. The migration ability of EAhy926 induced by two kinds of factors, type IV collagen (COL IV) and fibronectin (Fn) was inhibited after interfered by siRNA for 48 hours, and was stronger inhibition to COL IV than Fn (Fn control: 0.581+/-0.012 vs 0.261+/-0.002; COL IV control: 0.467+/-0.009 vs 0.110+/-0.010, p<0.01). The invasion test had the similar result as migration test. (Fn vs control: 0.365+/-0.012 vs 0.101+/-0.002; COL IV vs control: 0.317+/-0.009 vs 0.102+/-0.010, p<0.01). The angiogenesis ability of endothelial cells dropped to 58.9% of control after interference with siRNA for 48 hours. In the cell cycle experiments, after RNAi for 48 hours and 72 hours, the cell ratio of G1 rose from [(65.9+/-2.53)%; (63.2+/-1.89)%] to [(83.9+/-2.53)%, (89.2+/-1.24)%]% (p<0.01); the cell ratio of S and G2 dropped from [(32.7+/-1.91)%, (37.1+/-2.65)%] to [(18.1+/-1.49)%, (10.2+/-0.85)%] (p<0.01). The results analyzed by semi-quantitative RT-PCR showed that the expression levels of Rb, cyclin D1 PCNA genes dropped to 35%, 51% and 22% of normal control respectively. It is concluded that the expression of MMP-2 does not distinctly correlate with the proliferation of endothelial cells, but plays a very important role in affecting endothelial cell migration, invasion and angiogenesis, and participates in regulating cell cycle through Rb, cyclinD1 and PCNA.

Construction of lentivirus vector containing human ?-catenin-EGFP and its expression in human hair follicle stem cells / 上海第二医科大学学报

Objective To construct the lentivirus carrying human ?-catenin-EGFP(enhanced green fluorescent protein)and observe its expression in human follicle stem cells.Methods The ?-catenin gene sequence was amplified by RT-PCR from extraction of total RNA of human vascular endothelial cells.TA cloning technique was utilized to acquire gene subcloned pUCm-T-?-catenin.After transformation reaction,candidate clone was further analyzed by PCR and gene sequencing.Then the plasmid was transfected into FT293 cells.After identification by Western blotting,the plasmid was transfected into FT293 cells again for packaging.Infection titer was monitored by green EGFP expression.The expression of ?-catenin-lentivirus in human follicle stem cells were observed under inverted fluorescence microscope.Results The ?-catenin gene was cloned into the lentivirus successfully.The high expression of green fluorescence protein in FT293 cell line was found under fluorescent microscope.Viral titer checked by real-time PCR was about 2.0?108 TU/mL.When the multiplicity of infection(MOI)was 10,the infection efficiency of ?-catenin-lentivirus in human follicle stem cells was nearly 80% after infection 48 h around.After 3 weeks of continuous observation,we found the infection efficiency still keeping in the range of 80%-90%.Conclusion The lentivirus expression vector for ?-catenin was successfully constructed.It can steadily infect human follicle stem cells and the infection efficiency is considerable high.

Effects of ferulic acid on E-selectin expression in activated endothelial cell and leukocyte-endothelial cell adhesion / 药学学报

<p><b>AIM</b>To study the effects of ferulic acid (FA) on E-selectin expression in human umbilical vein endothelial cells (HUVECs) activated by lipopolysaccharide and leukocyte-endothelial cell adhesion.</p><p><b>METHODS</b>The effects of FA on E-selectin and E-selectin mRNA expression were determined by flow cytometry and reverse transcription polymerase chain reaction. The effect of FA on HL60-HUVEC adhesion was evaluated with the method of staining the cells by Rose Bengal.</p><p><b>RESULTS</b>The expression of E-selectin and E-selectin mRNA were down regulated by FA (0.62 and 0.41 mmol x L(-1), respectively). HL60 cells adhered to activated HUVECs were also reduced by FA (0.62 and 0.41 mmol x L(-1), respectively).</p><p><b>CONCLUSION</b>FA can inhibit the expression of E-selectin and E-selectin mRNA and HL60-HUVEC adhesion. This may contribute to its protective effect against ischemia-reperfusion injury.</p>

Inhibition of angiogenesis properties by SZ-21 / 中国实验血液学杂志

The aim of this study is to screen out the monoclonal antibody reactive to a kind of endothelial cell line (ECV304) from SZ-1, -2, -21, -22, -51, -65, -262 and explore its function of anti-angiogenesis. The inhibitory effects of monoclonal antibody reactive to ECV304 and human lung carcinom cells (A549) adhesion and migration to extracellular matrix proteins (i.e, fibronectin and collagen IV) were studied by ELISA, the inhibition of angiogenesis in vivo was analyzed by chick chorioallantoic membrane (CAM) assays, the percentage of apoptotic cells in A549 cells was assayed by flow cytometric Annexin-V-FITC/PI dual labeling technique. The results showed that SZ-21 exhibited inhibitory effects on human umbilical vein endothelial cell line (ECV304) and pulmonary cancer cell line (A549) adhesion and migration to extracellular matrix proteins (i.e, fibronectin and collagen IV). In addition, it disrupted ongoing angiogenesis on the chick chorioallantoic membrane (CAM) model. SZ-21 also induced apoptosis of the A549 cells. In conclusion, SZ-21 inhibits angiogenesis in vivo and in vitro by blocking integrin beta(3) and inducing apoptosis. SZ-21 recognized the sequence beta(3) 28 - 35 which is far away from the RGD ligation site on GPIIIa. Integrin may interact the extracellular matrix via recognition sites other than RGD sequence.