Correlation between Serum miR-34a Level and Thrombocytopenia after Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the relationship between serum miR-34a level and thrombocytopenia after chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#A total of 69 eligible DLBCL patients who received chemotherapy in our hospital from January 2018 to January 2020 were prospectively included as the research subjects, all patients received R-CHOP 21 regimen (rituximab + cyclophosphamide + adriamycin + vincristine + prednisone) for chemotherapy, 3 weeks was 1 cycle, and 2 cycles of chemotherapy were used. The patients were divided into a reduction group and a non reduction group according to whether there was thrombocytopenia after chemotherapy, the general data and laboratory indexes of the two groups were investigated and compared, the relationship between serum miR-34a before chemotherapy and thrombocytopenia after chemotherapy in patients was analyzed.@*RESULTS@#Among the 69 DLBCL patients, 36 patients developed thrombocytopenia after 2 cycles of R-CHOP 21 regimen for chemotherapy, the incidence was 52.17%; the level of serum IL-11 and the relative expression of miR-34a mRNA in the reduction group were significantly lower than the non reduction group (P<0.05), compared other data between groups, there was no statistical significant difference (P>0.05); after Logistic regression analysis, the results showed that the level of serum IL-11 and the relative expression of miR-34a mRNA were related to thrombocytopenia after chemotherapy in DLBCL patients, low expression of each index may be a risk factor of thrombocytopenia after chemotherapy in DLBCL patients (OR>1, P<0.05); ROC curve was drawn, and the results showed that the AUC of serum IL-11 level and miR-34a mRNA relative expression before chemotherapy alone and in combination predicted the risk of thrombocytopenia after chemotherapy in DLBCL patients were all >0.80, and the predictive value was ideal, when the cut-off value of serum IL-11 level before chemotherapy was 42.094 pg/ml, and the cut-off value of miR-34a mRNA relative expression was 3.894, the combined prediction value was the best.@*CONCLUSION@#The relative expression of miR-34a mRNA is associated with thrombocytopenia after chemotherapy in DLBCL patients, which may be a risk factor for thrombocytopenia in patients after chemotherapy, has certain value in predicting the risk of thrombocytopenia of patients after chemotherapy.

Study on choroidal neovascularization genetically engineered mice model / 国际眼科杂志(Guoji Yanke Zazhi)

@#With the maturity of genetic engineering technology, a variety of genetic engineering mouse models for the development of key factors and processes of choroidal neovascularization(CNV)have been adapted to meet the needs of different research points in the CNV process. For example, VEGF164 RPE65 transgene, Tet/VMD2/VEGF, <i>etc.</i> which are key factors in the process of CNV. ApoE overexpression rats are an important model of spontaneous CNV formation in AMD-like lesions; Ccl2/Cx3cr1-deficient mice associated with changes in retinal pigment epithelial(RPE); choroidal neovascularization and retinal neovascularization can be seen in SOD1-/-aging, Vldlr-/-directed mutation, <i>etc</i>; retinal neovascularization secondary to choroidal neovascularization can be found in Cp-/-Heph-/Y knockout mice, <i>etc</i>. The main advantages of the CNV genetic engineering mouse model are rapid induction and short time of occurrence; strong correlation with CNV pathophysiology, which can compare various biological components of CNV and facilitate the study of its mechanism; closely relating to human CNV, and providing research methods for human CNV treatment evaluation. However, there are also limitations, such as low induction rate, low percentage and small area of CNV; frenquent occurrence of retinal angiomatous hyperplasia,which interferences CNV research. Researchers might select the appropriate model according to his own needs and modify the corresponding experimental parameters as needed.

Mechanism of HIF-1α-PDK1 signaling system involved in glucose metabolism and drug resistance in acute monocytic leukemia / 上海交通大学学报（医学版）

Objective • To investigate the mechanism of HIF-1α-PDK1 signaling system mediated glucose metabolism and drug resistance in acute monocytic leukemia cells. Methods • The expression of pyruvate dehydrogenase kinase 1 (PDK1) mRNA in U937, U937/DNR and acute monocytic leukemia cells was detected by quantitative polymerase chain reaction (qPCR). siRNA HIF-1α plasmid was constructed and transferred to U937 and U937/ DNR cells for 24 h by gene silencing. Cell proliferation inhibition was examined by MTT assay. The level of PDK1 mRNA was detected by qPCR, and the expression of PDK1 and multi-drug resistance gene 1 (MDR1) proteins was detected by Western blotting. Cell membrane potential was measured by flow cytometry using JC-1. Lactic acid level in the culture fluid was determined by blood gas analyzer. Dichloroacetate (DCA) and daunorubicin (DNR) were added to treat U937/DNR and acute monocytic leukemia cells for 24 h, MTT was used to calculate cell proliferation inhibition and Western blotting was used to estimate the expression of PDK1 and MDR1 proteins. Results • PDK1 mRNA was highly expressed in U937, U937/DNR and acute monocytic leukemia cells. Silencing hypoxia-inducible factor-1α (HIF-1α) significantly inhibited the proliferation activity, PDK1 and MDR1 expression and lactic acid production in U937 and U937/DNR cells. DCA could reverse the resistance to DNR in U937/DNR and relapsed acute monocytic leukemia cells. Conclusion • HIF-1α-PDK1 signaling system may regulate glucose metabolism and participate in the drug resistance of acute monocytic leukemia.

Effects of benzalkonium bromide and citalopram on the thickness of corneal epithelium and full-thickness of the cornea in mice / 眼科新进展

Objective To explore the effects of benzalkonium bromide and citalopram on the corneal epithelium and corneal thickness of mice using optical coherence tomography angiography (OCTA).Methods Together 60 mice were randomly divided into 5 groups (group A,B,C,D and E;n =12),with group A left untreated,group B receiving PBS eye drops,group C given benzalkonium bromide eye drops,group D undergoing intraperitoneal administration of citalopram suspension,and group E treated with combination of benzalkonium bromide eye drops and citalopram suspension.After 2 weeks,OCTA was applied for corneal subarea,followed by measurement of the thickness of corneal epithelium and full-thickness of the cornea of all mice,and then the mean values were calculated.Results The thickness of corneal epithelium and fullthickness of the cornea was (66 ±7) μm and (141 ± 11) μm in the group A,(66 ± 8) μm and (140 ± 12) μm in the group B and D,(73 ± 10) μm and (141 ± 14) μm in the group C,(76 ± 12) μm and (141 ± 15) μm in the E group,respectively.And there was no significant difference in the thickness of corneal epithelium and full-thickness of the cornea before treatment and 2 weeks after treatment in the group A,B and D (all P ＞ 0.05),but both variables were markedly thickened in group C and E 2 weeks after treatment,and the difference was statistically significant (all P ＜0.05).Moreover,the increased levels on the both variables in the group E was higher than those in the group C 2 weeks after treatment,and the difference was statistically significant (both P ＜ 0.05).The average thickness of corneal epithelium and full-thickness of the cornea in the group C and E were significantly thickened after treatment,and the difference was statistically significant (all P ＜ 0.05).The average values of both variables in the group C and E were obviously larger than those in the group A,and the difference was statistically significant (all P ＜ 0.05).Conclusion Citalopram alone has no significant effects on the corneal thickness by OCTA,whereas both the thickness of corneal epithelium and fullthickness of the cornea tend to thicken by benzalkonium bromide treatment,which has a synergistic effect on corneal thickening with citalopram.

The role of miR-301b in the regulation of adipocyte differentiation / 天津医药

Objective To examine the effect of miR-301b in the regulating the differentiation of mesenchymal stem cells into adipocytes.Methods Murine ST2 stromal cells were isolated,cultured and induced with adipogenic agents.The expression of miR-301b was detected by qRT-PCR in adipogenic differentiation group and control group.Stromal ST2 cells were transfected with miR-301b mimics followed by adipogenic treatment.qRT-PCR and Western blotting were conducted to detect the changes of adipocyte specific genes and protein expression levels in the miR-301b mimics transfection group and negative control(NC)transfection group. Results qRT-PCR showed that the expression of miR-301b was decreased after adipogenic treatment in ST2 cells.The relative expression level of miR-301b was less in the adipogenic differentiation group (0.219 ± 0.021) than that of the control group (1.000 ± 0.425, P<0.05). The relative expressions of peroxisome proliferator activated receptor γ(PPARγ),CCAAT/enhancer-binding protein α(C/EBPα)and adipocyte fatty acid binding proteins(aP2)were lower in the miR-301b mimics transfecting group than those in the NC transfecting group(P<0.05).The protein levels of the marker gene aP2 and transcription factors PPARγ and C/EBPα decreased in miR-310b mimics transfecting group compared with those of the NC transfecting group (P<0.05). Conclusion miR-301b can reduce adipocyte differentiation.

Comprehensive evaluation of Rebif® based on Guideline for Comprehensive Evaluation of Medicine in China / 中国药学杂志

OBJECTIVE: Based on Guideline for Comprehensive Evaluation of Medicine in China, to make a comprehensive evaluation of Recombinant Human Interferon beta 1a, Rebif®. METHODS: Induction, summary and analyses were used, mainly according to National Pharmacopeias, diagnosis and treatment guidelines, drug instruction, clinical study literatures and official data related with Rebif, based on the nine sections of the Guideline including safety, efficiency, compliance, pharmaco economics and so on. RESULTS AND CONCLUSION: The evaluation of Rebif is objective and comprehensive. The Guideline for Comprehensive Evaluation of Medicine in China is a relatively complete pharmaceutical review system.

Meta-analysis on elemene injection combined with cisplatin chemotherapeutics in treatment of non-small cell lung cancer / 中国中药杂志

To research databases of Cochrane library, Web of Science, PubMed, FMJS, CBM, VIP, CNKI and Wanfang Data Konwledge Service Platform by computers as at July 5, 2012, which was supplemented with other search results. The findings were included into randomized controlled trials (RCTs) of elemene injection combined with cisplatin chemotherapeuties in treating small cell lung cancer (NSCLC). Data was separately collected by two researchers for literature quality evaluation, and a Meta analysis was made with RevMan 5. 2 software, in order to assess the efficacy and safety of elemene injection combined with cisplatin chemotherapeutics in treating NSCLC. Totally 11 RCTs or 844 cases were included. Meta analysis results suggested that compared with cisplatin chemotherapy alone, the combination of elemene injection and cisplatin chemotherapeutics showed a higher clinical benefit rate ( OR = 2. 03, 95% CI:1.43-2. 88, P <0. 000 1) and a better quality of life (OR = 3.23, 95% CI:2. 20-4. 74, P <0. 000 01). Besides,the combination could also reduce leucopenia (OR =0. 50, 95% CI:0. 33-0. 76, P <0. 001) , and thrombocytopenia (OR =0. 38, 95% CI:0. 16-0. 85, P <0. 02), increase CD4 (MD = 3.32, 95% C1:2. 94-3.70, P <0. 000 01), and CD4/CD8 (MD = 0. 36, 95% CI:0. 28-0. 44, P < 0. 000 01) , and relieve gastrointestinal reactions such as nausea and vomiting (OR = 0. 37, 95% CI: 0. 19-0. 71, P = 0. 003). The analysis indicates that elemene can enhance the chemotherapeutic effect on NSCLC, improve the quality of life, and reduce adverse effect of platinum-contained chemotherapeutics, thereby being worth promoting in clinic.

Causes of death analysis in 133 congestive heart failure patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the causes of death in patients with heart failure.</p><p><b>METHODS</b>A total of 133 heart failure patients died during hospitalization in our hospital between January 2005 and December 2008 were enrolled in this study. Patients were divided to two groups: sudden death (group A, n = 73, 54.9%), chronic end-stage pump failure (group B, n = 55, 41.4%). The remaining 5 cases died of other causes were excluded from the final analysis. Clinical data (medical history, blood pressure, clinical manifestation, NYHA cardiac function class, left ventricular diameter of diastole, left ventricular ejection fraction, ventricular arrhythmias, drug therapy) of group A and B were analyzed.</p><p><b>RESULTS</b>There were no significant differences in terms of medical history (including hypertension and diabetes), blood pressure, heart rate and the incidence of ventricular arrhythmia between the two groups. In group A, the NYHA functional class was mostly II or III grade, and LVEF value was significantly higher than that of group B. The incidence of angina pectoris was significantly higher in group A compared to group B. beta-blocker and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use was also significantly higher in group A than in group B, however, the treatment dose was significantly lower and therapy duration was significantly shorter in group A than in group B. There were significantly less patients received statins and anti-platelet aggregation drugs in group A compared to group B.</p><p><b>CONCLUSION</b>In our patient cohort, sudden cardiac death often occurred in heart failure patients with NYHA cardiac function II to III grade, angina pectoris, probably due to the unstable coronary plaque and less statins and anti-platelet drug use in these patients.</p>

Effect of Tangyikang in improving the function of pancreatic islet beta cells in patients with latent autoimmune diabetes mellitus in adults / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect and mechanism of Tangyikang (TYK) for improving pancreatic islet beta cell function in patients with latent autoimmune diabetes mellitus in adults (LADA).</p><p><b>METHODS</b>Seventy-four LADA patients were randomly assigned to two groups. The 37 patients in the treatment group were treated with TYK decoction (one dose consisted of red ginseng 10 g, milkvetch root 30 g, lilyturf root 15 g, wild weed 10 g, coptis root 15 g, cape-jasmine fruit 10 g, giant knotweed rhizome 10 g, safflower 10 g and moutan bark 10 g) combined with insulin therapy, and the 37 in the control group treated with insulin therapy alone, and the course for all was 3 months. Changes of glycosylated hemoglobin, index of pancreatic islet beta-cell function (delta CP(2h)/delta BS(2h)), serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were observed before and after treatment.</p><p><b>RESULTS</b>All the above-mentioned indexes were improved after treatment in both groups, the post-treatment data showed significant difference between groups in delta CP(2h)/delta BS(2h), (0.258 +/- 0.106 vs 0.168 +/- 0.054, higher in the treatment group, t = 4.626, P < 0.01), but with insignificant difference in glycosylated hemoglobin (t = 0.441, P = 0.660). Besides, the dosage of insulin used in the treatment group was less than that in the control group (t = -4.169, P < 0.01); covariance analysis showed, through excluding impact of different dosages insulin used, IL- 4 level was higher (F = 24.217, P < 0.01) and IFN-gamma level was lower (F = 14.198, P < 0.01) in the treatment group than those in the control group.</p><p><b>CONCLUSIONS</b>TYK could improve the function of islet beta-cell, its possible mechanism is related with the regulation on cell immunity and the correction of T-lymphocyte subsets (Th1/Th2 ratio) imbalance.</p>

Association between mRNA level of Pde4d and Alox5ap and hypertensive stroke as well as hypertension in rats / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate whether mRNA levels of Pde4d and Alox5ap were associated with hypertensive stroke and hypertension in stroke-prone renovascular hypertensive rats (RHRSP) which could simulate human being's hypertensive cerebral stroke.</p><p><b>METHODS</b>Five groups were established: normotensive group, gradient hypertensive groups I, II and III(with contractive pressure of 140-159 mmHg, 160-179 mmHg and 180-199 mmHg respectively) and spontaneous stroke group. RNA from leukocytes in peripheral blood of each rat underwent real time PCR after reversed.</p><p><b>RESULTS</b>The mRNA levels of Pde4d and Alox5ap of spontaneous stroke group were statistically higher than that of the other groups. Expression of Pde4d of hypertensive group I was a bit higher than that of normotensive group and hypertensive groups II and III; as for Alox5ap, there was no statistical difference between normotensive group and all gradient hypertensive groups.</p><p><b>CONCLUSION</b>Animal experiments come to conclusions that over-expression of Pde4d and Alox5ap are associated with hypertensive stroke but not with hypertension. Therefore, the two genes confer the risk of hypertensive stroke independent of traditional risk factors. It is speculated that over-expression of Pde4d and Alox5ap can motivate onset of hypertensive cerebral stroke by participating in inflammation of arterial walls.</p>

Arsenic trioxide induced leukemic cell apoptosis relative to NF-kappaB activation / 中国实验血液学杂志

To investigate the relationship of As(2)O(3)-induced leukemic cell apoptosis with NF-kappaB activation and expression of VEGF, MMP9, apoptosis of K562-n cells induced by As(2)O(3) was analyzed by Annexin V, the dynamic changes of NF-kappaB, MMP9 and VEGF expressions were detected by immunohistochemistry. The results showed that activity of NF-kappaB could be increased, accompanied by higher level of expression of MMP9 and VEGF when apoptosis of K562-n cells was induced by As(2)O(3). Dexamethasome not only increased significantly the apoptotic rate, but also suppressed the activation of NF-kappaB of K562-n cells induced by As(2)O(3). Furthermore, there was a positive correlation between the expression of MMP9, VEGF and the activity of NF-kappaB. It is concluded that As(2)O(3) can induce apoptosis, in the meanwhile, activate NF-kappaB and up-regulate expression of MMP9 and VEGF in K562-n cell line. The mechanism of apoptosis of K562-n cells enhanced by dexamethasome may be related to suppression of the activation of NF-kappaB and expression of MMP9 and VEGF.

Establishment of a mouse model for detecting multi-drug resistant minimal residual leukemia cells expressing green fluorescent protein / 中国实验血液学杂志

This study aimed to investigate the pathophysiology and therapy of multi-drug resistant model of minimal residual leukemia in mice. The multi-drug resistant model of minimal residual leukemia was established by using P388/VCR-G cell line expressing enhanced green fluorescent protein (EGFP) and DBA mice. The results showed that P388/VCR-G were inoculated in the abdominal cavities of DBA mice, the incidence of leukemia was 100%. Any of these mice with leukemia could not obtain remission spontaneously. The model of leukemia was sensitive to cyclophosphamide (Cy) and the time of survival was related to the dose of Cy received. The logarithm of cells inoculated in mice correlated regressionally with the dose of Cy. So this model was ideal for research on minimal residual leukemia. The distribution of residual leukemia cells in complete remission was not uniform in different organs including liver, spleen, thymus and bone marrow. Minimal residual leukemia cells could be found by fluorescent microscopy in freezing tissue slice. It is concluded that the multi-drug resistant model of minimal residual leukemia expressing EGFP can be established by using P388/VCR-G cell line and DBA mice. The minimal residual leukemia cells can be observed by fluorescence microscopy in complete remission stage.

Effects of dexamethasone on arsenic trioxide induced apoptosis, NF-kappaB activation and gene expression in lymphoma cell line / 中华血液学杂志

<p><b>OBJECTIVES</b>To study the effect of dexamethasone (Dex) on the apoptosis and NF-kappaB activation in Raji cells as well as expression of MMP9 and VEGF induced by As2O3, and to observe the effect of inhibited activity of NF-kappaB by Dex on apoptosis.</p><p><b>METHODS</b>Cell apoptosis was analysed by Annexin V. Fluctuation of NF-kappaB, MMP9 and VEGF was detected by semi-quantitative immunohistochemistry.</p><p><b>RESULTS</b>The apoptosis and activation of NF-kappaB of Raji cells could be induced by As2O3. The percentage of apoptosis was (39.2 +/- 1.3)%. Dex significantly increased (77.5%) the apoptosis induced by As2O3 (P < 0.05). Dex suppressed the activation of NF-kappaB induced by As2O3 (a suppression rate of 28.0%, P < 0.05). There was a positive correlation between the changes of MMP9, VEGF and NF-kappaB.</p><p><b>CONCLUSIONS</b>As2O3 could induce apoptosis, activate NF-kappaB and up-regulate expression of MMP9 and VEGF of Raji cells. The mechanism of enhanced apoptosis by Dex may be related to suppressing activation of NF-kappaB and down-regulating expression of MMP9 and VEGF.</p>