Effect of Rheb1 in the Development of Mouse Megakaryocyte-Erythroid Progenitor Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of Rheb1 in the development of mouse megakaryocyte-erythroid progenitor cells and its related mechanism.@*METHODS@#Rheb1 was specifically knocked-out in the hematopoietic system of Vav1-Cre;Rheb1fl/fl mice(Rheb1Δ/Δ mice). Flow cytometry was used to detect the percentage of red blood cells in peripheral blood and erythroid cells in bone marrow in Vav1-Cre;Rheb1fl/fl mice and control mice. The CFC assay was used to detect the differentiation ability of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Real-time fluorescence quantification PCR was used to detect the relative expression of PU.1,GATA-1,GATA-2,CEBPα and CEBPβ of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Rapamycin was added to the culture medium, and it was used to detect the changes in cloning ability of megakaryocyte-erythroid progenitor cells from wild-type mice in vitro.@*RESULTS@#After Rheb1 was knocked out, the development and stress response ability of megakaryocyte-erythroid progenitor cells in mice were weaken and the differentiation ability of megakaryocyte-erythroid progenitor cells in vitro was weaken. Moreover, the expression of GATA-1 of megakaryocyte-erythroid progenitor cells was decreased. Further, rapamycin could inhibit the differentiative capacity of megakaryocyte-erythroid progenitor cells in vitro.@*CONCLUSION@#Rheb1 can regulate the development of megakaryocyte-erythroid progenitor cells probably through the mTOR signaling pathway in mice.

Analysis of risk factors for perinatal hysterectomy / 中国实用妇科与产科杂志

OBJECTIVE: To analyze the risk factors for peripartum hysterectomy.METHODS: Retrospectively analyze the clinical data of 36 cases of peripartum hysterectomy in Shijiazhuang Obstetrics and Gynecology Hospital from January2012 to December 2018. The impact factors for peripartum hysterectomy were divided into clinical characteristics and obstetric treatment capacity. The annual rates of peripartum hysterectomy were compared and the risk factors for peripartum hysterectomy were analyzed by multi-factor Logistic regression analysisRESULTS: The indications of 36 cases of peripartum hysterectomy were intractable postpartum hemorrhage. The causes of hysterectomy included placenta implantation,amniotic fluid embolism,uterine atony and secondary infection. The annual rate of peripartum hysterectomy decreased gradually due to the promotion of obstetric treatment capacity. The peripartum hysterectomy rate in 2018 decreased significantly（P<0.001,P<0.001,P=0.004,P=0.009）compared with that of 2012,2013,2014 and 2015. Multifactor Logistic regression analysis showed that cesearen-section scar was a risk factor for peripartum hysterectomy（OR=1.403,P=0.018）.CONCLUSION: The severity of disease results in peripartum hysterectomy. The reduction of the peripartum hysterectomy rate lies in the promotion of obstetric treatment capacity,including improving maternal health care,reducing obstetric complications and improving the timely and effective treatment of patients with postpartum hemorrhage.

Research Progress in New Dosage Forms of Anti-tumor Drugs for Pulmonary Administration / 中国药师

Lung cancer is one of the most common malignancies. Anti-tumor drugs with intravenous administration have systemic adverse effects as well as limited efficacy. Drugs can concentrate in lungs after pulmonary administration,which limits the distribution in the other organs and reduces the side effects of anti-tumor drugs. The paper focused on the recent progress in the studies on new dos-age forms of anti-tumor drugs for pulmonary administration for the therapy of lung cancer,so as to provide reference for the development of anti-tumor drugs for pulmonary administration.

Impact of smoking on young acute coronary syndrome patients evaluated by optical coherence tomography / 中国介入心脏病学杂志

Objective To explore the impact of smoking on coronary plaque characteristics on optical coherence tomography(OCT) in young patients with acute coronary disease(ACS).Methods We assessed the atherosclerotic plaque characteristics and vulnerability by OCT and coronary angiography in 60 ACS patients aged 45 years or younger in Beijing Anzhen Hospital, from June 2014 to June 2017. The patients were divided into the smoking group(n=33) and the non-smoking group(n=27) to compare the plaque characteristics and vulnerability.Results Smoking patients showed a less extent of fibrosis(48.55％vs. 77.8％,P=0.032)and microchannels(18.2％vs. 44.4％,P=0.033), and a greater extent of plaque rupture (24.2％vs. 3.7％,P=0.033) compared with non-smoking patients. In multivariate analysis, smoking was the only independent predictors of plaque rupture(OR 8.320, 95％CI 0.969-71.435,P=0.027) and less fibrosis (OR 0.269, 95％CI 0.086-0.837,P=0.020). Conclusions Patients who are smokers have less extensive fibrosis and a greater extent of plaque rupture, showing more extensive vulnerable plaque phenotype. Therefore, smoking is one of the major risk factors of advanced cardiovascular events in young patients.

Role of Rheb in Human Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the role of Rheb (mTOR activator) in AML development by measuring Rheb expression in bone marrow of adult AML patients and in AML cell line HL-60.</p><p><b>METHODS</b>Real-time PCR assay was used to measure the Rheb mRNA expression in 27 AML patients and 29 ITP patients as control. The relationship between Rheb mRNA expression and age, AML subtype, fusion gene, splenomegaly, hepatomegaly and survival of AML patients was analyzed and compared. In addition, HL-60 cell line over-expressing Rheb was established, and the HL-60 cells and HL-60 cells with overexpression of Rheb were treated with Ara-C of different concentrations, the proliferation level was detected by CCK-8 method, and the IC50 was calculated.</p><p><b>RESULTS</b>The mRNA level of Rheb in AML patients was similar to that in ITP patients (control). Interestingly, higher expression of Rheb was associated with better survival and was sensitive to Ara-C treatment. However, the expression level of Rheb was not associated with age, AML subtype, fusion gene, and hepatomegaly of patients. Lower expression level of Rheb was associated with splenomegaly. In vitro analysis of HL-60 line indicated that overexpression of Rheb could increased the cell sensitivity to Ara-C treatment (IC50=0.54 µmol/L) and caused HL-60 cell apoptosis.</p><p><b>CONCLUSION</b>The lower Rheb expression is a poor prognostic indicator for AML patients, which is associated with AML splenomegaly, the patients and HL-60 cells with low expression of Rheb are insensitive to Ara-C treatment.</p>

Effect of TEB-415, a Derivative of Imatinib, on Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the growth inhibitory effect of Imatinib derivative TEB-415 on various multiple myeloma (MM) cell lines, such as U226, H929, RPMI8226, MM1R and MM1S.</p><p><b>METHODS</b>TEB-415, a derivative of Imatinib was synthesized by modifying the chemical structure of Imatinib. MM cell lines (U226, H929, RPMI8226, MM1R and MM1S) were treated with TEB-415, Imatini and Bortezomib of various concentrations. Cells were grown for 72 hours and the growth rate was measured by CCK-8 method, cell morphology was observed and the IC50 was calculated.</p><p><b>RESULTS</b>TEB-415 could inhibit H929 and RPMI8226 growth significantly. When the concentration of TEB-415 was <0.1 nmol/L, >50% H929 cells died. The IC50 of Imatinib was 0.123 mol/L while the IC50 of Bortezomib was 0.03 nmol/L. In RPMI8226 cell line, when the concentration of TEB-415 was 11.9 mol/L, more than 50% of cells died. In contrast, when RPMI8266 were treated with Imatinib of the concentration of 12.8 mol/L, cells grew normally.</p><p><b>CONCLUSION</b>In comparison to Imatinib, TEB-415, a derivative of Imatinib, can kill H929 MM cells much effectively, its effecacy is only inferior to Bortezomib. RPMI8226, an MM cell line is insensitive to Imatinib, but still sensitive to TEB-415 and its growth can be inhibited by TEB-415.</p>

Applications of Microscopic Imaging and Analysis Technology in Studies of Neutrophil Movement and Phagocytosis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze and evaluate the application of spinning disk confocal microscopy and imaging analysis software in movement and phagocytosis of neutrophils.</p><p><b>METHODS</b>Neutrophils were isolated from bone marrow by centrifugation on discontinuous Percoll gradient, and then were stained with PE Gr-1 antibody and mixed with FITC-labeled Zymosan A bioparticles. Multichannel time-lapse videos were captured by using the spinning disk confocal microscopy. The result was analyzed by using volocity and ImageJ software, the parameters associated with movement and phagocytosis of neutrophils were analyzed, including morphological changes, cell tracking, pseudopod dynamics, binding and phagocytosis index.</p><p><b>RESULTS</b>Most neutrophils would be polarized in response to Zymosan particles during a short time. Binding and phagocytosis process occured in forty minutes.</p><p><b>CONCLUSION</b>A method of precisely quantifying the movement and phagocytosis of neutrophils using microscopic imaging and imaging analysis technique has been set up successfully. Using this method, biological activity and function of neutrophils can be evaluated visually and rapidly. The physiologically rapid response to Zymosan particles can be applied to the neutrophils function research in the future.</p>

The rheology properties of common hydrophilic gel excipients / 药学学报

To investigate theological properties of common hydrophilic gel excipients such as Carbopol based on viscosity, the viscosity was determined by rotation method and falling-ball method. Linear regression was made between ln(eta) and concentration, the slope of which was used to explore the relation between viscosity and concentration of different excipients. The viscosity flow active energy (E(eta)) was calculated according to Arrhenius equation and was used to investigate the relation between viscosity and temperature of different excipients. The results showed that viscosities measured by two methods were consistent. Concentration of guargum (GG) and hydroxypropylmethyl cellulose (HPMC) solution had a great influence on the viscosity, k > 5; while concentration of polyvinylpyrrolidone-K30 (PVP-K30) and polyethylene glycol 6000 (PEG6000) exerted a less effect on viscosity, k < 0.2; viscosity flow active energy of different excipients were close, which ranged from 30 to 40 kJ x mol(-1). Therefore, theological properties study could provide the basis for application of excipients and establish a foundation for the research of relation between excipients structure, property and function.

Effects of Rheb overexpression in HL-60 and K562 leukemia cell lines / 中国实验血液学杂志

mTOR (mammalian target of rapamycin) is the center for cellular activities. It controls many cell activities via inhibiting apoptosis and promoting cell growth. Rheb can activate mTOR signaling pathway and participate in genesis and development of multiple cancers. This study was purposed to explore the underlying role of Rheb in human myeloid leukemia by using the myeloid leukemia cell lines. Two myeloid leukemia cell lines HL-60 and K562 overexpressing Rheb were established with retrovirus containing Rheb. The mRNA and protein expressions of Rheb were determined by Real-Time PCR and Western blot respectively. Cell proliferation rate was examined by CCK-8 assay and apoptosis rate was analyzed using Annexin V and 7-AAD double-staining. The results showed that Rheb was overexpressed in both HL-60 and K562 cell lines. The Rheb overexpression cell lines were successfully established. It is found that overexpression of Rheb could promote cell growth. Furthermore, the overexpression of Rheb could accelerate cells entering into G2/M phase (P < 0.01), while did not affect the apoptosis. It is concluded that Rheb overexpression promotes myeloid leukemia cell proliferation through accelerating cell cycle progression.