Genetic regulation of microvascular proliferation under high altitude hypoxia / 中华地方病学杂志

Hypoxia is a typical characteristic of the high altitude environment. Chronic hypoxia arises due to the excessive production of erythrocytes, which increases the blood viscosity causing blood flow retardation to exacerbate hypoxic-ischemic injury and eventually angiogenesis. The "blood rich face" of people who have lived in high altitude for a long time is a typical representative of microvascular proliferation. In recent years, the mechanism of microvascular proliferation under high altitude hypoxia has become a hot topic at home and abroad. Therefore, the pathways and genes of microvascular proliferation under high altitude hypoxia are reviewed in this paper.

Research progress on the novel glutaminase inhibitor and its antitumor activity / 中国肿瘤临床

Tumor cells use several metabolic pathways to support bioenergetic and biosynthetic demands of proliferation. In addition to glucose, glutamine is an important source of precursor substances and energy for cancer cell growth. Glutaminase (GSL) activity is associated with Ras, c-Myc, and other oncogenes, as well as Rho GTP enzyme. Many preclinical studies have confirmed that glutamin-ase inhibitors not only exhibit anti-tumor activity, but can also remarkably enhance the sensitivity of resistant cancer cells to targeted drugs. At present, the novel GSL inhibitor CB-839 has entered phase I clinical trials and is expected to become a new drug for cancer treatment. This paper reviews the research progress on this novel glutaminase inhibitor and its antitumor activity.

Research Progress on Role of Gene Mutations in Prognostic Evaluation of Patients with Myelodysplastic Syndrome after Stem-Cell Transplantation--Review / 中国实验血液学杂志

Abstract　　Myelodysplastic syndromes (MDS) represent a clonal hematopoietic stem cell disorder characterized by morphologic features of dyspoiesis, high risk of transformation from MDS into AML. Allogeneic hematopoietic stem-cell transplantation is the only curative therapy for MDS, but the failure rate of transplantation is still high, which attribute to relapsed disease and transplant-related complications. Recently, the spectrum of gene abnormalities in MDS has been revealed by next generation genomic sequencing techniques. It was found that more than 80% MDS patients have at least one gene mutation. Mutated genes in MDS are powerfully associated with clinical phenotype and prognosis. In this review , the recent advancements regarding recurrent gene mutations in MDS are briefly summarized, and the  prognostic values of gene mutations are discussed in MDS or after allogeneic hematopoietic stem-cell transplantation,so as to set up a predicting model and to guide the treatment.

Echocardiographic Measurements Results in Healthy Han, Tibetan and Yugur Adults / 中国循环杂志

Objectives:The aim of this study was to compare the potential differences on echocardiographic cardiac chambers size and systolic function among the healthy Han, Tibetan and Yugur adults. Methods:A total of 1 820 healthy volunteers aged 20 to 80 years were screened at Qinghai province and Gansu province, including 887 Han (456 men), 506 Tibetan (262 men) and 427 Yugur (187 men) Chinese adults. Standard two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and left ventricular ejection fraction (LVEF). The impacts of nationality, age and gender on all echocardiographic results were analyzed. Results:The values of left ventricular end-diastolic volume was higher in Yugur male adults than in Han and Tibetan male adults ([96.29±21.60]ml vs [93.64±18.30] ml vs [91.16±16.77] ml, P＜0.05).The differences remained after adjusting body surface area ([54.16±11.14]ml/m2 vs [53.92±10.20] ml/m2 vs [52.76±8.94] ml/m2, P＜0.05). There was no significant difference in LVEF among three nationalities (P＞0.05). The values of cardiac chambers dimensions were significantly higher in men than in women (P＜0.05). The anteroposterior dimension of the left atrium increased with age in both genders (P＜0.05). Conclusions:Our results show that the left ventricular end-diastolic volume is related to nationality and some parameters vary with gender and age. Not only the differences in age, gender, body size, but also ethnic differences should be considered when defining the normal values of echocardiographic examination.

Effect of ERK1/2 Signaling Pathway Inhibitor PD98059 on the Expression of Ras, BRaf, MEK, ERK1/2 in Marrow Nucleated Red Blood Cells of CMS Patients / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of ERK1 / 2 signaling pathway inhibitor PD98059 on Ras, Raf, MEK, ERK1, ERK2 expression in order to explore a new way for basic research and clinical treatment of the chronic mountain sickness(CMS).</p><p><b>METHODS</b>Sixteen CMS patients were selected, the bone marrow was collected for isolation of monomuclear cells (MNC), the cells were sorted by using CD71 and CD235a antibody magnetic beads, then positive cells were diveded into 5 groups: blank control, DMSO and PD98059 5, 10 and 20 µmol/L, and were cultured in hypoxid condition for 72 hours. The Ras-GTP levels in supernatant was detected by ELISA, the RT-PCR was used to determine the expression of BRaf, MEK, ERK1, ERK2 mRNA in nucleated red blood cells, and the Western blot method was used to detect expression of BRaf, MEK, ERK1, ERK2 protein.</p><p><b>RESULTS</b>PD98059 had no effect on the level of Ras-GTP in each groups. Compared with the blank control group, the expression levels of BRaf, MEK mRNA in DMSO group were not statistically significant (P values were 0.826, 0.298). Compared with the PD98059 20 mol/L group, the expression level of ERK1/2 mRNA was statistically significant (P=0.001, 0.002). Compared with the blank control group, expression levels of p-BRaf, p-MEK protein in DMSO group were not statistically significant (P=0.370, 0.351). Compared with the PD98059 20 mol/L group, the difference of p-ERK1/2 protein level in other 4 groups were statistically significant (P values were <0.001, 0.007).</p><p><b>CONCLUSION</b>PD98059 can up-regulate the expressions of ERK1/2 miRNA and p-ERK1/2 protein in bone marrow nucleated red blood cells, the Ras / Raf / MEK / ERK 1/2 pathway is the main signal transduction pathway in regulating bone marrow nucleated red blood cells, suggesting that Ras/Raf /MEK /ERK 1/2 pathway may be involved in the pathogenesis of chronic mountain sickness process.</p>

Meta-analysis of efficacies of dasatinib and imatinib for patients with chronic myeloid leukemia-chronic phase / 白血病·淋巴瘤

Objective To compare the efficiencies of imatinib and dasatinib in patients with chronic myeloid leukemia-chronic phase (CML-CP).Methods The databases were retrieved,including Cochrane Library,OVID,Embase,PubMed,China National Knowledge Infrastructure (CNKI),WanFang database and VIP database,besides,references of articles were further to search.The quality of randomized controlled trials (RCTs) was assessed by the Cochrane collaboration' s risk tool.Meta-analysis was performed by RevMan 5.1 software.Results A total of 5 articles involved 2 031 patients with CML-CP were included.Meta-analysis showed that the rate of complete cytogenetic response (CCyR) at the 12th month in dasatinib group was higher than that in imatinib group [83.6 ％ (478/572) vs 70.6 ％ (406/575),OR =2.11,95 ％ CI 1.59-2.80,P＜ 0.05],and the rate of major molecular response (MMR) at the 12th month in dasatinib group was higher than that in imatinib group [49.3 ％ (296/600) vs 30.6 ％ (185/605),OR =2.22,95 ％ CI 1.75-2.82,P ＜ 0.05].Conclusion Dasatinib can improve CCyR and MMR rate at the 12th month in CML-CP patients.

Effect of PD98059 on Proliferation and Apoptosis of CD71(+),CD235a(+) Nucleated Erythrocytes in the Patients with High Altitude Polycythemia / 中国实验血液学杂志

<p><b>UNLABELLED</b>Objective： To study the effect of PD98059, a specific inhibitor of Ras/Raf/MEK/ERK signaling pathway, on the proliferation and apoptisis of bone marrow CD71(+), CD235a(+) nucleated erythrocytes in patients with high altitude polycythemia (HAPC) and the pathogenesis of HAPC.</p><p><b>METHODS</b>The CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients and controls (patients with simple obsolete stracture) were sorted by using the immunemagnetic beads, then were added with 5, 10, 20 µmol/L of PD98059 and DMSO (as control) and were cultured for 72 h under hypoxia. The cell apoptosis was detected by flow cytometry with Annexin V and PI double staining, the cell proliferation was detected by CCK8 method, at same time the erythroid colong-formation ability of bone marrow mononuclear cells (BMMNC) treated with 5, 10, 20 µmol/L of PD98059 and DMSO was observed.</p><p><b>RESULTS</b>With the increase of PD98059 concentration, the apoptosis rate of bone marrow CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients was enhanced (r=0.807,P<0.01), while the proliferation rate of CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients dereased (r=0.502,P<0.01). The erythroid colong-formation ability of BMMNC in HAPC patients decreased with the increase of PD98059 concentration (r=0.504,P<0.01). There were statistic differences among different groups at 7 and 14 d.</p><p><b>CONCLUSION</b>The MEK specific inhibitor PD98059 can inhibit the proliferation and promote the apoptosis of CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients, then inhibit the excessive accumulation of erythrocytes.</p>

Clinical application of Voriconazole treatment in invasive fungal infection for malignant hematology patients: a meta analysis / 实用医学杂志

Objective To estimate the efficacy and safety of Voriconazole as antifungal prophylaxis of invasive fungal infection ( IFI) for malignant hematology patients. Methods The randomized controlled trials of Voriconazole treatment in invasive fungal infection for malignant hematology patients (ended in September 2014) were searched from Cochrane library, Medline, Embase, Pubmed, CBM, CNKI, Blood database. The meta analysis were performed by RevMan5.0. Results Ten literatures reported in 1 773 cases, in which there was significantly difference in effective rate between Voriconazole and other antifungal agents such as Amphotericin-B, Itraconazole, Micafungin and Fluconazole(P < 0.000 01); Four literatures indicated that there was significantly difference in adverse event rate between Voriconazole and amphotericin-B (P < 0.00 001); no significantly difference in adverse event rate between Voriconazole and amphotericin-B(P = 0.57); no significantly difference in adverse event rate between Voriconazole and Micafungin (P = 0.69); no significantly difference in adverse event rate between Voriconazole and Fluconazole (P = 0.70); Subgroup analysis indicated that adverse event rate between Voriconazole and Itraconazole is P=0.001, P = 0.17 respectively. Conclusion Voriconazole showed relative high efficient and low toxicity characteristics in treatment of malignant hematology accompanied by invasive fungal infection. But with its widely clinical application, the clinical value of Voriconazole needs to be further tested.

Analysis of clinical characteristics and prognostic factors of 253 lymphoma cases in Qinghai / 白血病·淋巴瘤

Objective To analyze the clinical features and prognostic factors of lymphoma.Methods The clinical data,pathologic data and survival state of 253 patients with lymphoma in Qinghai were retrospectively studied.The survival differences of patients with different clinical characteristics and laboratory tests were analyzed using Kaplan-Meier method.The prognostic factors of lymphoma were analyzed by Cox proportional hazards regression model.Results Among all of 253 cases of lymphoma,males were in the majority (male∶female =1.56∶1).The median age of patients was 48 years old.There were two peaks of about 40 years old and 60 years old in age of onset.The nodal lymphoma (56.13 ％) was more commonly than the extranodal lymphoma (43.87 ％).The more common extranodal lymphomas were found in the nasopharynx and gastrointestinal tract.Among all cases,40 cases (15.81％) were confirmed to be Hodgkin lymphoma (HL),of which,the commonest subtype was nodular sclerosis (72.5 ％).While 213 of 253 cases (84.19 ％) belonged to non-Hodgkin lymphoma (NHL),of which,B-cell lymphoma was 148 cases (69.48 ％).Overall,three subtypes including diffuse large B-cell lymphoma (39.91％),follicular lymphoma (12.21％) and peripheral T-cell lymphoma (9.39 ％) were the commonest subtypes among all cases.Univariate analysis showed that the clinical stage,B symptoms,Hb concentration,serum LDH level,international prognostic score (IPI) and treatment programs were related to the prognosis of NHL (P ＜ 0.05).However,the Cox regression multivariate analysis showed that only the clinical stage,IPI and treatment programs,not B symptoms,Hb concentration and serum LDH level,were closely related to the prognosis of NHL (P ＜ 0.05).Conclusions In Qinghai area,there are two peaks of about 40 and 60 years old in the age of onset of lymphoma.The nodal lymphoma is more than extranodal lymphoma.B-cell lymphoma is more common.IPI could be as an independent prognostic factor and might be used to estimate the prognosis of NHL.

Studies on apoptosis and caspase-8 and caspase-9 expressions of bone marrow cells in chronic mountain sickness / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the expressions of caspase-8 and caspase-9 mRNA, and explore the changes of apoptosis of bone marrow hematopoietic cells in patients with chronic mountain sickness (CMS).</p><p><b>METHODS</b>Of 18 CMS patients and 16 controls were enrolled in this study. The apoptotic index (AI) of bone marrow mononuclear cells (BMMNC) was measured by TUNEL technique, the levels of caspase-8 and caspase-9 mRNA in BMMNC of CMS patients and controls were determined by RT-PCR. Results (1)The AI of BMMNC in patients with CMS (8.51 ± 3.35)% was lower than that in controls (16.00 ± 4.28)% (P < 0.01); (2) The values of caspase-8 and caspase-9 mRNA were (0.28 ± 0.07) and (0.23 ± 0.08) respectively, in CMS patients, which were significantly lower than those of (0.45 ± 0.09) and (0.41 ± 0.09) respectively, in the controls (both P < 0.01); (3) Hemoglobin (Hb) value was negatively correlated with levels of caspase-8 and caspase-9 mRNA (r values were -0.52 and -0.61 respectively, both P < 0.05) in CMS patients. There was a negative correlation between AI and Hb (r value was -0.89, P < 0.01) in CMS patients. However, the significant relationship was not found between AI and level of caspase-8 or caspase-9 mRNA (P > 0.05).</p><p><b>CONCLUSIONS</b>The results showed a decrease apoptosis of BMMNCs and reduced levels of caspase-8 and caspase-9 mRNA in CMS patients, the latter might be involved in the change of BMMNCs apoptosis.</p>

Two-end intimal flap suturing method in establishing stanford B type aortic dissection model in canine / 第二军医大学学报

Objective: To search for a satisfactory method for establishing Stanford B type aortic dissection model in canine. Methods: Totally 12 adult dogs were used in the present study. The proximal descending aorta was clamped partially and laterally after a left thoracotomy; half circumference of the aorta, including the media and adventitia,was cut open transversely, with the intima kept intact. The aortic wall was then separated inferiorly, laterally and superiorly at a special dissecting space with a unique dissecting device. Then the intima at the same site was also cut open transversely and the two ends of the distal intimal flap were sutured to the adjacent aorta to allow blood entry. The distal adventitia and media were sutured to the proximal aorta to close the incision. Follow-up was carried out with pigtail catheter guided digital subtraction angiography (DSA) using omnipaque (16-18 ml/s) via either of the common iliac arteries and color Doppler ultrasound. Results: Formation and distal extension of aortic dissections were observed immediately after the procedure and were further confirmed by intra-operative color Doppler ultrasound, DSA, and post-operative biopsy at different time points. Conclusion: The present two-end intimal flap suturing method can be used for establishing Stanford B type aortic dissection model in canine; the model is similar to human Stanford B type aortic dissection.