Atorvastatin Pretreatment Ameliorates Mesenchymal Stem Cell Migration through miR-146a/CXCR4 Signaling

BACKGROUND@#We previously found that atorvastatin (ATV) enhanced mesenchymal stem cells (MSCs) migration, by a yet unknown mechanism. CXC chemokine receptor 4 (CXCR4) is critical to cell migration and regulated by microRNA-146a (miR-146a). Therefore, this study aimed to assess whether ATV ameliorates MSCs migration through miR-146a/CXCR4 signaling. @*METHODS@#Expression of CXCR4 was evaluated by flow cytometry. Expression of miR-146a was examined by reverse transcription-quantitative polymerase chain reaction. A transwell system was used to assess the migration ability of MSCs. Recruitment of systematically delivered MSCs to the infarcted heart was evaluated in Sprague–Dawley rats with acute myocardial infarction (AMI). Mimics of miR-146a were used in vitro, and miR-146a overexpression lentivirus was used in vivo, to assess the role of miR-146a in the migration ability of MSCs. @*RESULTS@#The results showed that ATV pretreatment in vitro upregulated CXCR4 and induced MSCs migration. In addition, flow cytometry demonstrated that miR-146a mimics suppressed CXCR4, and ATV pretreatment no longer ameliorated MSCs migration because of decreased CXCR4. In the AMI model, miR-146a-overexpressing MSCs increased infarct size and fibrosis. @*CONCLUSION@#The miR-146a/CXCR4 signaling pathway contributes to MSCs migration and homing induced by ATV pretreatment. miR-146a may be a novel therapeutic target for stimulating MSCs migration to the ischemic tissue for improved repair.

Atorvastatin Pretreatment Ameliorates Mesenchymal Stem Cell Migration through miR-146a/CXCR4 Signaling

BACKGROUND@#We previously found that atorvastatin (ATV) enhanced mesenchymal stem cells (MSCs) migration, by a yet unknown mechanism. CXC chemokine receptor 4 (CXCR4) is critical to cell migration and regulated by microRNA-146a (miR-146a). Therefore, this study aimed to assess whether ATV ameliorates MSCs migration through miR-146a/CXCR4 signaling. @*METHODS@#Expression of CXCR4 was evaluated by flow cytometry. Expression of miR-146a was examined by reverse transcription-quantitative polymerase chain reaction. A transwell system was used to assess the migration ability of MSCs. Recruitment of systematically delivered MSCs to the infarcted heart was evaluated in Sprague–Dawley rats with acute myocardial infarction (AMI). Mimics of miR-146a were used in vitro, and miR-146a overexpression lentivirus was used in vivo, to assess the role of miR-146a in the migration ability of MSCs. @*RESULTS@#The results showed that ATV pretreatment in vitro upregulated CXCR4 and induced MSCs migration. In addition, flow cytometry demonstrated that miR-146a mimics suppressed CXCR4, and ATV pretreatment no longer ameliorated MSCs migration because of decreased CXCR4. In the AMI model, miR-146a-overexpressing MSCs increased infarct size and fibrosis. @*CONCLUSION@#The miR-146a/CXCR4 signaling pathway contributes to MSCs migration and homing induced by ATV pretreatment. miR-146a may be a novel therapeutic target for stimulating MSCs migration to the ischemic tissue for improved repair.

Establishment of A Mixed Chimeric Mouse Model of Allogeneic Bone Marrow Transplantation and Its Influencing Factors / 中国实验血液学杂志

OBJECTIVE@#To establish a mouse mixed chimerism (MC) model of nonmyeloablative allogeneic bone marrow transplantation(allo-BMT) and explore its affecting factors.@*METHODS@#The MC model was established by nonmyeloablative allo-BMT followed by high-dose post-transplant cyclophosphamide (PTCY). 123 mice in the experiments was retrospectively analyzed, and the factors related with the chimerism were explored with the univariate and multivariate logistic regression analysis. A multivariate linear regression was performed by R project to obtain a mathematical model for predicting the chimeric level with relevant affecting factors.@*RESULTS@#The model presented mixed chimerism on day 14 after transplantation, and was characterized by a donor lymphocyte infusion (DLI) which significantly promoted donor engraftment on day 15, but transfplantation of PBS in control group was failed. Among 123 mice, 47 (38.21%) mice were MC, while 76 (61.79%) mice were non-MC in 123 mice, respectively; univariate analysis showed that the baseline body weight of mice (P=0.001, 17.84±1.19 g vs 18.50±0.94 g), total body irradiation(TBI，P=0.048) and the using of cyclophosphamide (P=0.16) were affected the chimeric state of mice, while the number of infusing cells and the time of detection showed no significant effects. Multivariate regression analysis showed that under certain conditions, the body weight of mice on day 0 was an independent factor affecting chimeric levels (OR=0.493, 95% CI 0.307-0.791, P=0.003). Through R project multiple linear regression, the math model was achieved, which was chimerism=6.09-12×weight(g)+80.03×TBI(Gy)-4.4×cell-counts (× 10@*CONCLUSION@#The experiment presents a method for establishing a mixed chimeric mice model after non-myeloablative bone marrow transplantation and constructs a mathematical model with relevant factors affected chimerism status.

Evaluation of the Sensitivity and Specificity of the New Clinical Diagnostic and Classification Criteria for Kashin-Beck Disease, an Endemic Osteoarthritis, in China / 生物医学与环境科学（英文）

This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease (KBD) using six clinical markers: flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling. The survey included baseline characteristics and clinical diagnoses, and the sensitivity and specificity of the new criteria was evaluated. We identified 3,459 KBD patients, of which 69 had early stage KBD, 1,952 had stage I, 1,132 had stage II, and 306 had stage III. A screening test classified enlarged finger joints as stage I KBD, with a sensitivity and specificity of 0.978 and 0.045, respectively. Shortened fingers were classified as stage II KBD, with a sensitivity and specificity of 0.969 and 0.844, respectively, and dwarfism was classified as stage III KBD with a sensitivity and specificity of 0.951 and 0.992, respectively. Serial screening test revealed that the new clinical classification of KBD classified stages I, II, and III KBD with sensitivities of 0.949, 0.945, and 0.925 and specificities of 0.967, 0.970, and 0.993, respectively. The screening tests revealed that enlarged finger joints, shortened fingers, and dwarfism were appropriate markers for the clinical diagnosis and classification of KBD with high sensitivity and specificity.

Comparison of T-2 Toxin and HT-2 Toxin Distributed in the Skeletal System with That in Other Tissues of Rats by Acute Toxicity Test / 生物医学与环境科学（英文）

Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone, knee joints, and costal cartilage) were significantly higher than those in the heart, liver, and kidneys (P < 0.05). The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone and costal cartilage) were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.

Effects of DNMT3A gene mutations on prognosis of patients with acute myeloid leukemia: a meta-analysis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the effects of DNMT3A gene mutation on prognosis of patients with acute myeloid leukemia (AML) by a meta-analysis.</p><p><b>METHODS</b>Methods of Cochrane systematic review was followed by 7 databases,including PubMed, Embase, Ovid, CNKI, CBM, WanFang Data and VIP, were searched for peer-reviewed articles related to DNMT3A gene mutations and prognosis of patients with AML.Then manual retrieval was applied into literature references. After the evaluation of quality and extract of clinical trialliterature data, Stata 11.0 was employed to perform meta-analysis.</p><p><b>RESULTS</b>Seven randomized controlled trials involving 1493 cases were included in the meta-analysis. The prognosis of patients with DNMT3A mutations and without DNMT3A mutations was compared. There was no statistically significant difference in complete remission(CR) rate (OR=1.034, 95%CI: 0.596~1.796, P=0.905 between two groups, but the overall survival (OS（HR=1.990, 95%CI: 1.463~2.510, P=0.000 and disease free survival (DFS) (HR= 2.840, 95%CI: 1.063~4.613, P=0.002) of patients without DNMT3A mutations were longer than those with DNMT3A mutation.</p><p><b>CONCLUSION</b>DNMT3A gene mutation is an independent risk factor of poor prognosis of patients with acute myeloid leukemia.</p>

Changing Grains for the Prevention and Treatment of Kashin-Beck Disease in Children: a Meta-analysis / 生物医学与环境科学（英文）

To evaluate the efficacy of changing grains on the prevention and treatment of Kashin-Beck Disease (KBD) in children, community-based trials were acquired from seven electronic databases (up to July 2014). As a result, the methodological quality of the six trials that have been included into our analysis was low. The pooled ORs favoring the prevention and treatment effects of changing grains were 0.15 (95% CI: 0.03-0.70) and 2.13 (95% CI: 1.44-3.16) respectively by meta-analysis. Subgroup analysis demonstrated the pooled OR favoring treatment effect of exchanging grains rather than drying grains both compared with endemic grains. The results showed that changing grains had obvious effects on the prevention and treatment of KBD in children. However, the evidences were limited by the potential biases and confounders. Large and well-designed trials are still needed.

WT1 gene expression difference in leukemia and non-leukemia and its clinical significance / 中国实验血液学杂志

This study was aimed to investigate the expression level of Wilms' tumor 1( WT1) gene in hematologic neoplasm (leukemia, multiple myeloma and lymphoma) patients and its clinical significance. Real-time quantitative polymerase chain reaction (RQ-PCR) was used to detect the copy number of WT1 gene and reference gene (ALB) in bone marrow cells of 228 patients with hematologic neoplasm in our hospital. The gene expression level was determined by using the ratio of the copy number of WT1 gene and reference gene. The results showed that the WT1 expression level between male and female patients was not statistically significantly different (P > 0.05). All the patients were divided into 3 groups: the group aged under 19, the group aged between 19-50, and the group aged over 50; the WT1 expression level among the three groups were not statistically significantly different (P > 0.05) . The above-mentioned patients were redivided into the groups aged under 45 and over 45, the difference between them was not statistically significant (P > 0.05). The difference of WT1 expression level between newly diagnosed patients and treated patients with hematologic neoplasm was statistically significant (P < 0.01), but no statistically significant difference of WT1 expression was found (P > 0.05) at each stage within 3 years after treatment, however, among them the difference between newly diagnosed leukemia patients and treated leukemia patients was very statistically significant (P < 0.01), while the difference between newly diagnosed and treated non-leukemia patients was not statistically significant (P > 0.05). The expression difference of WT1 between leukemia and non-leukemia patients was very statistically significant (P < 0.01), the difference between the newly diagnosed leukemia and non-leukemia patients also was very statistically significant (P < 0.01). The difference of WT1 expression between treated leukemia and non-leukemia patients was not statistically significant (P > 0.05). It is concluded that the WT1 expression level in leukemia patients can be a reliable marker to evaluate the prognosis of newly diagnosed leukemia and the curative effect for minimal residual disease. No WT1 expression difference has been found before and after treatment among the patients with non-leukemia, such as multiple myeloma and lymphoma, therefore, which should be furtherly explored.

Metabolic syndrome and coronary artery calcification: a community-based natural population study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Little is known about the influence of metabolic syndrome (MetS) on coronary artery calcification (CAC) in China. In this article, we aimed to explore the distribution of CAC in populations with and without MetS, and estimate the influence of MetS and its components on CAC in a community-based population of Beijing.</p><p><b>METHODS</b>A total of 1647 local residents of Beijing, age 40-77 years, were recruited for a cardiovascular risk factors survey and were determined fasting plasma glucose (FPG), blood lipids, and 64 multi-detector computed tomography (64-MDCT) coronary artery calcium score (CACS) measurement (Agatston scoring). The distribution of CAC was described, and the influence of MetS components on CAC was evaluated.</p><p><b>RESULTS</b>In this population, the prevalence and extent of CAC increased with increasing age and both were higher in MetS subjects compared to nonMetS subjects (all P < 0.05), with the exception of those older than 65 years old. The risk of CAC increased with increasing numbers of MetS components, and the odds ratios for predicting positive CAC in subjects with 1, 2, 3, and = 4 MetS components were 1.60, 1.84, 2.12, and 3.12, respectively (all P < 0.05). Elevated blood pressure, elevated FPG, elevated triglycerides, and overweight increased the risk of CAC, yielding odds ratios of 2.64, 1.67, 1.32, and 1.37, respectively (all P < 0.05).</p><p><b>CONCLUSIONS</b>In the Beijing community-based population, MetS increases the risk of CAC. The risk of CAC increases with increasing numbers of MetS components. Not only the number, but also the variety of risk factors for MetS is correlated with the risk of CAC. Elevated blood pressure, hyperglycemia, hypertriglyceridemia and overweight increase the risk of CAC.</p>

Relation between uric acid and coronary artery calcification:a community-based cross-sectional survey among Beijing natural population / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the influence of uric acid on coronary artery calcification in the natural population in Beijing.</p><p><b>METHODS</b>From April to July 2012, 903 subjects from the natural population(aged 37-76 years for men, aged 42-76 years for women)in Xishan community, Beijing, were selected to accept a survey on the risk factors of cardiovascular. Blood tests and CT coronary artery calcium scans were carried out.</p><p><b>RESULTS</b>At the 1 Quartile(1 Q), 2 to 3 Quartile(2-3 Q)and 4 Quartile(4 Q)of uric acid levels, the prevalence rates of coronary artery calcium were 37.2% , 45.5% , 60.6% (P<0.001) and the coronary artery calcium scores were (109.7±333.1)AU, (133.9±356.9)AU, (200.8±459.4) AU (P < 0.001)respectively. Data from the univariate logistic regression analysis showed that with the increase of uric acid, the prevalence rates of coronary artery calcium also increased(OR2-3Q = 1.41, 95% CI:1.02-1.95, P = 0.040; OR4Q = 2.60, 95% CI:1.78-3.80, P < 0.001). However, the relationship between uric acid and coronary artery calcium disappeared when using the multivariate logistic regression analysis(OR2-3Q = 0.92, 95% CI: 0.60-1.43, P = 0.713;OR4Q = 1.38, 95% CI:0.80-2.39, P = 0.247).</p><p><b>CONCLUSION</b>Uric acid did not seem to be an independent risk factor for coronary artery calcium, although the prevalence and extent of coronary artery calcium increased along with the increasing trend of uric acid.</p>

Coronary atherosclerosis lesion features in coronary artery disease patients complicating with metabolic syndrome / 中华心血管病杂志

<p><b>PURPOSE</b>To compare coronary plaque burden, composition, distribution and the degree of coronary artery stenosis in invasive coronary angiography (ICA) diagnosed coronary artery disease (CAD) patients with or without metabolic syndrome (MetS).</p><p><b>METHODS</b>From January 2008 to June 2011, consecutive patients underwent both coronary computed tomography angiography (CCTA) and ICA within three months were enrolled. Patients with history of previous percutaneous coronary interventions (PCI) and coronary artery bypass grafting (CABG) were excluded. Plaque characteristics and maximal luminal diameter stenosis were analyzed on a 16-segment basis as suggested by the American Heart Association classification.</p><p><b>RESULTS</b>The study population consisted of 872 patients [age (60.2 ± 10.0) years, 72.70% males] including 377 patients with MetS and 495 patients without MetS. The median coronary artery calcium score (CACS) was higher in MetS patients than in non-MetS patients [102 (10, 410) vs. 58 (0, 274) , P < 0.01]. Percentage of patients with no coronary artery calcium was significantly lower in MetS group than in non-MetS group [19.63% (74/377) vs. 30.71% (152/495) , P < 0.01], while percentage of patients with severe coronary calcium (CACS ≥ 1000) were significantly higher in MetS than non-MetS group [8.22% (31/377) vs. 4.65% (23/495) , P = 0.03]. The proportion of patients with 1-vessel disease was lower [23.61% (89/377) vs. 36.77% (182/495), P < 0.01], 2-vessel [29.71% (112/377) vs. 22.83% (113/495), P < 0.05] and 3-vessel disease [35.54% (134/377) vs. 24.44% (121/495) , P < 0.01] were higher in MetS group than in non-MetS group. Calcified plaque of LM and the middle and distal coronary artery were significantly higher in MetS group than in non-MetS group (all P < 0.05) .</p><p><b>CONCLUSIONS</b>CAD patients with MetS are associated with severer coronary artery calcium deposition and higher percentage of calcified plaque in the middle and distal coronary arteries and severer obstructive coronary vessels.</p>

Correlation between Chlamydia pneumoniae infection and chronic obstructive pulmonary disease / 中华流行病学杂志

Objective To investigate the correlation between Chlamydia pneumonia (Cpn)infection and chronic obstructive pulmonary disease (COPD).Methods 82 patients with acute exacerbation COPD (AE-COPD) or stabilized COPD patients at outpatient visits,in the People' s Hospital of Jiangyin city from Aug.2010 to May 2012,together with 46 cases having stationary phase COPD and 38 healthy volunteers as control group,were involved in this study.Patients were bled 2 ml,on the next day of hospitalization while patients at emergency room were bled 2 ml immediately,but bled again on the 15th day.Serum was separated through cryopreservation and the Cpn antibodies (IgG,IgM and IgA antibodies) were detected,under micro-immunofluorescence.Results In terms of IgG in the three groups,the positive rates did not show significant differences (P＞0.05) but the GMT of the IgG in the AE-COPD group was significantly higher (P＜0.01) than that in the control group.IgA positive rate among the three groups; AE-COPD appeared the highest.There was no significant difference between the AE-COPD group and stationary phase COPD group (P＞0.05),however,there were significant differences between the AE-COPD group,the stationary phase COPD group and the control group (P＜0.01).In terms of GMT of IgA in the three groups,there was significant difference between the AE-COPD group and stationary phase COPD group (P＞0.05),but with significant difference between the AE-COPD group and the control group (P＞0.01).There was significant difference between stationary phase COPD group and the control group (P＞0.05).When comparing both the rates of acute infection and chronic infection on the AE-COPD groups with the control group,there appeared significant differences (P＜0.05,P＜0.01).When comparing the acute and chronic infection between the stationary phase COPD group and the control group,the rate of acute infection did not show significant difference (P＞0.05) while the chronic infection rate appear to have had significant difference (P＜0.01).Conclusion Cpn infection seemed to be closely related to the development of COPD.

Clinic diagnosis and treatment of patients with Cantrell syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the diagnostic feature, treatment and prognosis of patients with Cantrell syndrome.</p><p><b>METHODS</b>Clinical manifestation, diagnosis, operation and follow-up data of 5 patients with Cantrell syndrome were summarized in this retrospective analysis.</p><p><b>RESULTS</b>The age of the 5 patients was 7 days-76 years, definite diagnosis was made in 3 cases and 2 cases presented feature of incomplete Cantrell syndrome. Three patients with full Cantrell syndrome were correctly diagnosed before operation and confirmed by operation. One patient with incomplete Cantrell syndrome (two-vessel stenosis) received bypass surgery. Another asymptomatic patient with incomplete Cantrell syndrome (apical diverticulum of the left ventricle) does not need operation and is under observation. During follow-up, 1 patient died at 60 months after operation and the remaining 4 patients are alive and well.</p><p><b>CONCLUSIONS</b>With the development of modern imaging technology, it becomes easy to make correct diagnose Cantrell syndrome before operation. Prognosis is fine post timely operation and related intervention.</p>