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The incidence of hematologic malignancies is increasing, and although new drugs and treatments have made great progress, relapse and drug resistance are still urgent problems to be solved. Exosomes are tiny membrane vesicles secreted in cells that carry lipid bilayer membrane structures including mRNA, microRNA and proteins. It carries and transmits important signaling molecules, forming an entirely new intercellular information transfer system that exhibits a wide range of biological properties and functions in organisms. Tumor cell exosomes are confirmed to contribute to cancer cell proliferation, angiogenesis, invasiveness, distant metastasis and drug resistance. Multiple studies have shown that exosomes from some malignant hematological tumor cells are closely related to tumor resistance. This review summarizes the research progress of exosomes in the mechanism of drug resistance of hematologic malignancies, in order to provide a theoretical basis for the clinical treatment of hematologic malignancies.
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Objective To determine the effect of rapamycin(Rapa) on JAK2, ABCA3, and the immune checkpoint PD-1/PD-L1 in exosomes derived from JAK2 V617F positive HEL cells. Methods Human erythroleukemia HEL cells (JAK2 V617F mutation-positive) were cultured in vitro, and rapamycin was added at concentrations of 10, 50, and 100 nmol/L. The control group was established and cell proliferation inhibition rate was detected by CCK-8. Based on the inhibition rate of cell proliferation, cells intervened with 10 and 50 nmol/L Rapa were selected. Exosomes were extracted using a kit and identified by Western blot and flow cytometry. JAK2, ABCA3, and PD-1/PD-L1 mRNA changes in exosomes were detected by fluorescent quantitative PCR. The expression of exosome PD-1/PD-L1 protein was determined by flow cytometry. Results The exosomes extracted with the exosome kit all expressed characteristic CD9, CD63, and CD81 proteins, which were consistent with the general characteristics of exosomes. JAK2 mRNA can be detected in exosomes from HEL cells; Rapa reduced exosome production by HEL cells, and dose-dependently decreased gene expression of JAK2, ABCA3, and PD-L1 in exosomes. In addition, Rapa inhibited exosomal PD-L1 protein expression and had no significant effect on PD-1 protein expression. Conclusion HEL cells may transmit JAK2 mutant gene signals via exosomes. Rapa can reduce the production of exosomes and inhibits JAK2 mutated signals delivered by exosomes and suppresses PD-L1 protein expression.
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Objective:To evaluate the clinical effect of surgical treatment of scapular body complicated fractures with reverse Judet operation approach.Methods:A retrospective review was made on 36 patients with scapular body complicated fractures from Jan. 2013 to Jan. 2019. All the fractures were type Ⅳ according to Miller ME classification. There were 29 males and 7 females, at mean age of 46 years(ranged from 20 to 63 years). High energy traffic injury occurred in 13 patients, high fall injury in 8 patients, heavy pound in 3 patients.CT scan and 3D reconstruction were performed before operation, to expose the scapula with reverse Judet approach and do the internal fixation operation with reconstruction plate. Instructed the patients in functional exercises and clinic effects. All patients were followed up after operation. Twenty patients with scapular body complicated fractures from Jan. 2013 to Jan. 2019 treated by classic Judet approach operation were control analysised, compared the operation time, blood less, Incision healing and the shoulder function score after 1 year postoperation.Results:One-stage incision healing were achieved in all 36 patients, no infection and necrosis occurred in the muscle and skin flaps, all patients were followed up for 1 to 6 years(mean 3.8 years). According to Hardegger evaluation standard, 28 cases were excellent, 8 cases were good, the excellent and good rate was 100%. Opteration time and blood loss were less than those in classic Judet group, the differences were significant( P<0.001). Conclusion:For the surgical treatment of complicated fractures, reverse Judet approach that muscle flap and skin flap separated is feasible, the operation is simple, which can obviously shorten the operation time and blood loss, sufficient exposure is good for the reduction and stable fixation of fractures in the operation, early functional exercise can be proformed after operation, reverse Judet approach is a safe and efficient choice for the surgical treatment of scapular body complicated fractures.
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Objective@#To investigate the regulation of JAK2 tyrosine kinase inhibitor ruxolitinib on extracellular matrix metalloproteinase (MMP in JAK2V617F positive myeloproliferative neoplasms (MPN) cells.@*Methods@#①Forty cases of newly diagnosed JAK2V617F positive MPN patients and 15 healthy volunteers as control in Baoding No.1 Hospital between January 2012 and December 2015 were enrolled in this study. JAK2V617F/JAK2 ratio was detected by real-time-PCR; the expression levels of phosphorylation protein tyrosine kinase 2 (p-JAK2) , MMP-2 and MMP-9 in pathological tissues of bone marrow were detected by immunohistochemistry. The bone marrow cells of JAK2V617F positive MPN patients were treated with ruxolitinib, then the migration ability and MMP-2, MMP-9 gene and protein expression levels were detected. ②The human erythroleukemia cell line HEL cells were treated with different concentrations of ruxolitinib (0, 50, 100, 250, 500, 1 000 nmol/L) . The cell viability was detected by CCK-8 test; cell migration ability was tested by transwell chambers. The mRNA expression levels of JAK2, MMP-2 and MMP-9 were detected by real-time-PCR. The protein expression levels of p-JAK2, MMP-2 and MMP-9 were detected by Western blot.@*Results@#①The expression levels of p-JAK2, MMP-2 and MMP-9 in the newly diagnosed group were significantly higher than control group respectively [ (78.56±24.55) % vs (41.59±17.29) %, P<0.05; (48.25±18.74) % vs (22.79±13.89) %, P<0.05; (53.29±19.28) % vs (15.56±14.96) %, P<0.05]. Spearman correlation analysis showed the positive correlation of MMP-2 and MMP-9 protein expression levels with JAK2V617F mutation (r=0.526, P=0.001; r=0.543, P=0.001) . ②The proliferation of HEL cells was inhibited by different concentrations of ruxolitinib in time and dose dependent manner. ③Cell migration test showed the number of cells leaked to the low chamber in MPN patients bone marrow cells and HEL cells treated with 5 nmol/L of ruxolitinib group were significantly lower than that without ruxolitinib treatment after 24 h [ (154.7±27.5) vs (320.3±67.3) , t=13.47, P<0.05; (70.7±10.5) vs (135.3±16.7) , t=13.89, P<0.05]. The mRNA and protein expression levels of JAK2, MMP-2 and MMP-9 decreased with the increased concentration of ruxolitinib.@*Conclusion@#Ruxolitinib inhibits MPN cell migration and expression of MMP-2 and MMP-9 via JAK2 signal pathway.
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AIM:To investigate the effect of AG 490 on the expression of VEGF and HIF-1α, and the capacity of invasion in human erythroleukemia (HEL) cells.METHODS:The HEL cells were treated with AG490 at different con-centrations .The cell viability was detected by CCK-8 assay.The apoptosis was detected by Hoechst staining .The apoptosis and the cell cycle were analyzed by flow cytometry .The capacity of migration was evaluated by Transwell assay .The mRNA expression level of JAK2 was measured by RT-PCR.The protein levels of p-JAK2, VEGF and HIF-1αwere determined by Western blot.RESULTS:The HEL cell viabilities were 88%, 75%, 48%, 10%and 0.12%after treated with AG490 at 20, 40, 60, 80 and 100 μmol/L for 48 h, respectively.The results of Hoechst staining showed that brilliant blue cells in 80 μmol/L AG490 group was significantly increased compared with control group for 48 h.The apoptosis rate of 80μmol/L AG490 group was significantly increased compared with control group at 48 h after AG490 treatment.The number of membrane-permeating HEL cells in 20μmol/L AG490 group at 24 h after AG490 treatment was significantly lower than that in control group (P<0.05).The mRNA level of JAK2 decreased in a concentration-dependent manner after the HEL cells were treated with different concentrations of AG 490 for 48 h.The protein levels of p-JAK2, VEGF and HIF-1αwere lower in AG490 treatment groups than those in control group (P<0.05).CONCLUSION: AG490 inhibits the expression of VEGF and HIF-1αin HEL cells by inhibiting JAK2 pathway.
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Objective To investigate the application of intravascular ultrasonography in guiding the performance of interventional management for coronary true bifurcation lesions. Methods A total of 62 patients with coronary true bifurcation lesions, who were admitted to authors’ hospital during the period from April 2010 to Jan. 2014 to receive double stenting treatment, were included in this study. The patients were randomly divided into intravascular ultrasonography group (IVUS group, n=32) and coronary angiography group(CA group, n=30). The minimal lumen diameter(MLD), the minimal lumen area(MLA), the reference lumen diameter (RLD), the length of the lesion and the diameter and length of the implanted stent were determined, and the results were compared between the two groups. During the follow-up period lasting for 12 months after percutaneous coronary intervention, the incidence of in - stent thrombus, target lesion revascularization (TLR) and major adverse cardiac events were recorded. Results The MLD values of the main artery and branches in IVUS group were higher than those in CA group, but the difference was not significant (P>0.05). The MLA, RLD, the diameter and length of the implanted stent in IVUS group were significantly larger than those in CA group (P0.05). Conclusion Intravascular ultrasound- guided double stent implantation for coronary true bifurcation lesions can help optimize the performance of stenting and improve the long-term outcome of percutaneous coronary intervention.
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BACKGROUND:Studies have shown that arthroscopic al-inside technology for meniscus repair has achieved good outcomes, and arthroscopic suture combined with sodium hyaluronate has an important role in the cartilage repair. OBJECTIVE:To observe the therapeutic effect of arthroscopic al-inside suture repair combined with sodium hyaluronate injection in the repair of discoid meniscus tears. METHODS:Twenty-two patients with discoid meniscus injury were subjected to arthroscopic al-inside suture repair combined with sodium hyaluronate injection. Al cases were confirmed to have attached edge relaxation or longitudinal crack in operation. After repair, effective rehabilitation training was done. RESULTS AND CONCLUSION:The operations for the 22 cases were al successful and there was no complication. Al patients were fol owed up for over 18 months. According to Ikenchi’s method (Lysholm knee score criterion), 11 cases were rated excel ent, 8 were rated good, and 3 were rated fair, with an excel ent/good rate of 86.36%. It is demonstrated that the al-inside suture repair under the guide of arthroscopy in discoid meniscus cases can remain the most appropriate anatomical structure of the meniscus that can play an effective function, and has the advantage of minimal invasion. Arthroscopic al-inside suture repair combined with intra-articular injection of sodium hyaluronate and standard rehabilitation training result in a lower complication rate and effectively promotes the meniscus repair.
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Objective To evaluate the efficiency and toxicities of Gemcitabine combined with S -1 cap-sule in the treatment of advanced esophageal cancer .Methods Twenty-nine patients with advanced esophageal cancer were treated with S-1 capsule 80 mg/m2 ,twice daily for 14 days and Gemcitabine (1 000 mg/m2 ) was in-travenously administrated on day 1 and 8.The chemotherapy was repeated every 21 days.After two consecutive treatment circles ,the short term efficacy ,adverse effects and follow -up condition were evaluated .Results One case showed complete remission (CR),11cases showed partial remission (PR),9 cases showed stable disease (SD),8 cases showed progressive disease(PD).The responsive rate(CR+PR)was 41.4%;the illness control rate(CR+PR+SD)was 72.4%.The major adverse events were myelosuppression ranging from grade Ⅰto Ⅲ, hand-foot syndrome,disgusting and the damage of liver function .Some patients displayed the damage of liver function.The median time to progress ( mTTP) was 6.9 months.The median 1-year survival rate was 64.3%. Conclusion The combination of Gemcitabine and S -1 capsule is an effective and well -tolerated method for the patients with advanced esophageal cancer .
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Objective To explore the microanatomy technique of the endoscopy-assisted extreme lateral supracerebellar infratentorial keyhole approach and clinical significance.Methods The extreme lateral supracerebellar infratentorial keyhole approach was imitated in 10 vascular perfusion adult cadaveric heads fixed in formalin,the dorsolateral mesencephalon region was dissected and observed by microscopy and neuroendoscopy from December 2012 to March 2013.Results The extreme lateral supracerebellar infratentorial keyhole approach could be fully exposed the ambient cisterns,the posteromedial tentorial incisura,the dorsolateral mesencephalon region,the trochlear nerve,the root of the trigeminal nerve,the superior cerebellar artery,the posterior cerebral artery and other important anatomical structures.The temporal lobe and parahippocampal gyrus could be exposed when the tentorial was incised.The application of neuroendoscopy could clearly reveal the trigeminal nerve and surrounding structures.Conclusion The extreme lateral supracerebellar infratentorial keyhole approach is suitable for the surgical resection in dorsolateral mesencephalon region.The application of neuroendoscopy can make up for the lack of the trigeminal nerve observed under microscopy and expand the operative field.
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BACKGROUND:Numerous studies have shown that air wave pressure therapy plays an important role in prevention of deep venous thrombosis of lower limb after a major operation on the hip. OBJECTIVE:To explore the efficacy of air wave pressure therapy on deep vein thrombosis of the lower extremity in patients with total knee arthroplasty. METHODS:A total of 80 patients with total knee arthroplasty were randomly divided into experimental group and control group. Patients in the control group were treated only with conventional method to help the patient massage the lower extremity by the nurse and combined with active functional exercise;patients in the experimental group were treated with air wave pressure therapy at 2 days postoperatively, and were also treated with conventional method to help the patient massage the lower extremity by the nurse and combined with active functional exercise. Swel ing index, coagulation index and the number of patients with deep venous thrombosis of the lower extremity were recorded in both groups. RESULTS AND CONCLUSION:At 2 weeks after treatment, swel ing index, coagulation index and the number of patients with deep venous thrombosis of the lower extremity were significantly reduced in the experimental group, and its effects were significantly better than those in the control group (P<0.05). Early use of air wave pressure therapy after total knee arthroplasty can al eviate limb swel ing effectively and have obvious advantages in improving coagulation index and blood coagulation condition and in preventing deep vein thrombosis of the lower extremity after total knee arthroplasty.
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Objective To investigate expression and regulatory mechanism of phosphatase and tensin hemology deleted on chromosome ten gene (PTEN) and cyclooxygenase-2 (COX-2) in human myeloid leukemia cells.Methods Thirty patients was collected from the First Hospital of Baoding and Second Affiliated Hospital of Hebei Medical University,including 10 chroni myeloid leukemiac (CML)patients in chronic phase (CML-CP),10 CML patients in blast crises (CML-BC) and 10 normal controls.The recombinated adenovirus containing green fluorescent protein (GFP) and PTEN ( Ad-PTEN-GFP) or empty vector (Ad-GFP) was transfected into human CML K562 cells.The growth of K562 cells and cell adhesion ability was observed by 3-[4,5-dimethyl-2-thiazolyl]-2,5-dip (MTF) assay; PTEN and COX-2 messenger ribonucleic acid (mRNA) levels were detected by real-time fluorescent relative-quantification reverse transcriptional PCR (FQ-PCR).PTEN and p-Akt protein levels were detected by western blot,and COX-2 protein were measured with cytochemical staining.ResultsThe mRNA expression levels of PTEN in CML-BC patients (0.022 ±0.021 ) were lower than CML-CP patients (1.134 ± 1.124) and normal control ( 1.059 ±0.595).The mRNA expression levels of COX-2 in CML-BC patients (0.761 ±0.418) were higher than CML-CP (0.211 ± 0.158) and normal control (0.165 ± 0.152).The growth of K562 cells was suppressed markedly,and the maximum growth inhibition rate was 38.67％ ± 4.30％ after transfected with PTEN gene,which was higher than Ad-GFP group (5.34％ ±0.31％,t =13.39,P ＜0.01 ).COX-2 mRNA expression levels in Ad-PTEN-GFP(0.013 ± 0.001 )were significantly lower than Ad-GFP group (0.199 ±0.018) and untransfected group (0.217 ± 0.021,F =499.45,P ＜ 0.01 ),and p-Akt as well as COX-2protein were also down-regulated after K562 cells transfected ( MOI =200) with wild type PTEN in three days.ConclusionPTEN may inhibit proliferation and adhesion ability of leukemia cell in myeloid leukemia via down-regulating COX-2 expression.
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[Objective] To investigate the anti-proliferative and apoptosis effect induced by Honokiol (HNK) on human myeloid leukemia cell line U937 cells in vitro.[Methods] After treated with different concentration of HNK,Hoechst33342 fluorescent staining was used to detect cell apoptosis;the growth inhibition ration of U937 cells and PBMCs were analyzed by MTT assay;the apoptosis ration was detected by flow cytometry;mitochondrial membrane potential was explored by rhodamine 123 stain;Caspase3/7 protein activity kit was used to test the Caspase3/7 activity;the Caspase-3 and Caspase-7 mRNA levels were detected by real-time fluorescent relative-quantification reverse transcriptional PCR (FQ-PCR).[Results] Honokiol could significantly inhibit the proliferation of U937 cells in terms of the indexes of IC50/U937 11.8 μg/mL and IC50/PBMCs 40.3 μg/mL,and the anti-proliferative effect was in a time and concentration dependent manner;Flow cytometry analysis manifested that Honokiol could induce U937cells apoptosis by Annexin V/PI double Annexin V/PI fluorescein stain;Honokiol significantly inhibited the mitochondrial membrane potential of U937 cells and enhanced the ability of Caspase3/7 and the mRNA expression levels,but not the PBMCs.[Conclusion] HNK can inhibit U937 cells proliferation and induce cells apoptosis via activating Caspase 3/7.
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High mobility group A1 belongs to the family of high mobility group. It is widespread in human,and involved in the physiological and pathological situations. It is overexpressed in many human cancers including haematological malignancies as the oncogene.