1.Iron overload inhibits osteogenesis and promotes adipogenesis in human bone marrow mesenchymal stem cells by producing reactive oxygen
Yanjiu HAN ; Guohui LIU ; Yong LIU
Chinese Journal of Tissue Engineering Research 2016;20(14):2007-2014
BACKGROUND:Iron overload as a new etiological factor participate in the pathogenesis of senile osteoporosis, but its mechanism remains unclear. But the mechanism of iron overload cause senile osteoporosis pathogenesis remains unclear. Osteogenic/adipogenic differentiation homeostasis of bone marrow mesenchymal stem cel s (BMSCs) plays an important role in the maintenance of normal human bone mass, and its imbalance can lead to senile osteoporosis. Iron effects on the osteogenic/adipogenic differentiation of BMSCs remain unclear. Therefore, we clarify the role of iron overload in the pathogenesis of senile osteoporosis by studying the effect of iron overload on BMSCs osteogenic/adipogenic differentiation. OBJECTIVE:To explore the effect of iron overload on the osteogenesis and adipogenesis of human BMSCs (hBMSCs) in vitro and to explicit the role of iron overload in the pathogenesis of senile osteoporosis. METHODS:hBMSCs were isolated by using density gradient centrifugation method. Isolated cel s were treated with normal saline as normal control group, treated with 10, 20, 30μmol/L ferrous citrate to mimic iron overload conditions, or treated with 30μmol/L ferrous citrate fol owed by 0.5 mmol/L N-acetylcysteine as an antioxidant. RESULTS AND CONCLUSION:Iron overload did not remarkably inhibit the proliferation of hBMSCs, but it could promote the generation of reactive oxygen in hBMSCs. After treatment with ferrous citrate, the expression of c-Maf and Runx2 decreased, and the expression of peroxisome proliferator-activated receptorγincreased;moreover, formation of calcium nodules decreased, but lipid droplets were produced. N-acetylcysteine could inhibit the production of reactive oxygen and increase the expression of c-Maf induced by iron overload. These findings indicate that iron overload inhibits osteogenesis and promotes adipogenesis in hBMSCs through the generation of reactive oxygen. Meanwhile, c-Maf plays an essential role in the iron-overload induced differetiation imbalance.
2.Investigation on Perioperative Renal Aquaporin 2 Expression in Experimental Obstructive Jaundice
Yong WANG ; Jilong HAN ; Jingang LIU
Chinese Journal of Bases and Clinics in General Surgery 2003;0(05):-
Objective To investigate the changes of renal medulla aquaporin 2 expression and morphological changes of epithelia of collecting tube after bile duct recanalizaiton operation.Methods Thirty rats were divided into two groups randomly.Common bile duct ligation was performed on 20 experimental rats with silicon tubes 2 mm in extre-diameter,and sham operation on the other 10 rats.Seven days later,bile duct recanalizaiton was performed on obstructive jaundice group and sham operation on contrast group.Experimental rats were divided into two subgroups randomly.Half of them were killed immediately and the others would be killed 24 hours later.Serum of each rat was collected to detect hepatic function and renal function.Renal medulla was fixed for microscopic examination and was kept in the-80 ℃ refrigerator for aquaporin 2 expression measurement by Western blot technique.ResultsAll of the animals accomplished the experiment smoothly.Golden ascites were found in the rats of obstructive jaundice group.Twenty-four hours after recanalization,serum bilirubin levels decreased 〔(45.95?8.39)?mol/L〕,P
3.Experimental investigates on changes of expression of Aquaporin2 (AQP2) in renal of rats with obstructive jaundice
Jilong HAN ; Yong WANG ; Jingang LIU
Chinese Journal of Immunology 2015;(2):261-264
Objective:To investigate the change of expression of AQP 2 in renal of obstructive jaundice rats , and the relationship between AQP 2 and the changing of Cr and BUN.Methods: Legated the common bile duct of rats to form the obstructive jaundice group.Scarified the rats on the 3th,5th,7th,10th,14th day,took blood samples and the kidney of the rats.Test direct bilirubin BUN and Cr in serum,the renal histopathological changes were observed by optical microscopy .The expression of AQP2 in renal of rats was tested by using radio immunological method.Results: Light microscopic examination of kidney showed that swelling epithelium arranged irregularly in 3rd day ,bleb in the 5th day.The expression of AQP2 in renal of rats with obstructive jaundice were greatly less than sham operation.Mesenchyma inflammatory cells infiltrate in 7th day.Local epithelial necrosis and lots of inflammatory cells infiltrate in the mesenchyma in 10th day and 14th day.The expression of AQP2 in renal collective tubule was decreased on the 5th day compared with sham operation ,and the decrease was more as time gone by.The renal function injury can be confirmed though the renal collective tubule change.Cr and BUN in serum began to increase on the 10th day and 14th day.Conclusion: Decrease of AQP2 is earlier than the increase of Cr and BUN ,and it can be the early sign of renal function injury.
4.Drug Analysis and Literature Review of One Patient with Heart Failure and Gouty Attack
Jingyi ZHU ; Yong HAN ; Yihui LIU
China Pharmacist 2017;20(5):880-882
Objective: To investigate the principles of rational drug use for the patients suffering from heart failure complicated with diuretic-induced gouty arthritis.Methods: The clinical pharmacist participated in the diagnosis, treatment and drug adjustment of one patient suffering from heart failure complicated with furosemide-induced gouty arthritis.Taking the disease symptoms and potential gouty-inducing drugs into full consideration, clinical pharmacist suggested the withdrawal of related-drugs and the adjustment of treatment plan.Results: Considering the characteristics of the patient, clinical pharmacist adjusted the rational drug treatment.After the adoption of the suggestions, the gouty symptoms were relieved, heart failure was controlled and the condition was improved.Conclusion: Loop diuretics can easily trigger an acute attack of gout, especially for the patients with heart failure and gout history.Clinical pharmacist can make full use of professional advantages to optimize the treatment plan in order to reduce adverse reactions and promote the rational drug use by participating in clinical practice.
5.Therapeutic effect and safety of atorvastatin sequential treatment on patients with acute coronary syn- drome undergoing PCI
Ying LIU ; Yong YANG ; Huiliang LIU ; Wei HAN
Chinese Journal of cardiovascular Rehabilitation Medicine 2015;24(2):175-179
Objective:To observe therapeutic effect and safety of six‐month atrovastatin sequential treatment on pa‐tients with acute coronary syndrome (ACS) undergoing PCI .Methods :A total of 280 ACS patients were consecu‐tively enrolled ,randomly and equally divided into sequential treatment group (received atorvastatin 80mg 2d before PCI operation ,then 40mg/d after operation ,20mg/d a month later ) and routine treatment group (no taking atorv‐astatin before PCI operation ,then 20mg/d after operation and as a maintenance dose ) .Both groups were observed for six months ,therapeutic effect and safety were compared between two groups .Results:Compared with before PCI ,there were significant rise in levels of creatine kinase isoenzyme (CK‐MB) and cardiac troponin I (cTnI) after PCI 18h~24h in two groups ,and those of sequential treatment group were significantly lower than those in routine treatment group [CK‐MB:(2.72 ± 0.52) μg/L vs .(6.04 ± 0.51) μg/L ,cTnI : (0.28 ± 0.13) μg/L vs .(0.42 ± 0.16) μg/L , P < 0.01 both ];Compared with routine treatment group , the high sensitive C reactive protein (hsCRP) level significantly reduced in sequential treatment group after PCI 2d ,and continued until post‐operation six months [ (2.34 ± 0.51) mg/L vs .(1.49 ± 0.78) mg/L ,P=0.001];the blood lipids levels (except level of high density lipoprotein cholesterol significantly rose ) in sequential treatment group were significant lower than those of routine treatment group , P<0.01 all;there were no significant difference in percentage of transaminase level high‐er than normal three times and incidence rates of major adverse cardiovascular events (MACE) between two groups , P>0.05 all .Conclusion:Preoperative 80mg atrovastatin combined postoperative 40mg atrovastatin treatment can significantly reduce inflammatory reaction ,improve blood lipids ;compared with routine dose ,it doesn't significant‐ly increase adverse drug reactions ,so it's safe and effective .
6.Prognostic factors of low-and undifferentiated gastric cancer with negative metastasis of lymph nodes
Nan JIANG ; Jingyu DENG ; Yong LIU ; Honggen LIU ; Han LIANG
Chinese Journal of Digestive Surgery 2014;13(8):629-632
Objective To investigate the prognostic factors of low-and undifferentiated gastric cancer with negative metastasis of lymph nodes.Methods The clinicopathological data of 270 patients with low-and undifferentiated gastric cancer and negative metastasis of lymph nodes who were admitted to the Tianjin Cancer Hospital from January 2002 to December 2007 were retrospectively analyzed.All the patients received radical gastrectomy.One hundred and sixty-one patients had the number of lymph nodes dissected under 15,53 patients had 15-20 lymph nodes dissected,33 had 21-30 lymph nodes dissected and 23 patients with the number of lymph nodes dissected more than 30.Patients were followed up via out-patient examination,phone call and mail till October 2013.The prognosis analysis was done by COX step-wise regression.The survival curve was drawn by KaplanMeier method,and the survival was analyzed using the Log-rank test.Results All the patients were followed up for a median time of 63 months (range,2-103 months).The median survival time was 63 months (range,2-103 months),and the 1-,3-,5-year overall survival rates were 93.0%,69.5% and 58.5%,respectively.The median survival time of the 161 patients with the number of lymph nodes dissected under 15 was 58 months (range,2-103 months),and the 1-,3-,5-year survival rates were 91.4%,59.3% and 48.8%,respectively.The median survival time of the 53 patients with the number of lymph nodes dissected between 15 and 20 was 68 months (range,4-95 months),and the 1-,3-,5-year survival rates were 94.3%,84.9% and 71.7%,respectively.The median survival time of the 33 patients with the number of lymph nodes dissected between 21 and 30 was 68 months (range,34-94 months),and the 1-,3-,5-year survival rates were 100.0%,97.0% and 87.9%,respectively.The median survival time of the 23 patients with the number of lymph nodes dissected more than 30 was 60 months (range,2-84 months),and the 1-,3-,5-year survival rates were 87.5%,62.5% and 54.2%,respectively.There was significant difference in the prognosis between the 4 groups (x2 =25.077,P < 0.05).There was significant difference in the prognosis between patients who had 21-30 lymph nodes resected and those had 15-20 lymph nodes resected (x2=3.924,P <0.05).Significant difference was also observed in the prognosis between patients who had 15-20 lymph nodes resected and those had more than 30 lymph nodes resected (x2=4.454,P < 0.05),while no significant difference was observed in the prognosis between patients who had lymph nodes resected more than 30 and those had lymph nodes resected less than 15 (x2=0.450,P >0.05).The results of univariate analysis showed that gender,age,location and diameter of the tumor,serosal invasion,Borrmann classification,range of gastric resection and the number of lymph nodes dissected were factors influencing the prognosis of patients with low-and undifferentiated gastric cancer and with negative metastasis of lymph nodes (x2 =4.143,12.607,23.665,11.549,26.350,8.059,5.222,25.077,P <0.05).The results of multivariate analysis showed that the tumor diameter longer than 5 cm and serosal invasion were the independent factors influencing the prognosis of patients with low-and undifferentiated gastric cancer and with negative metastasis of lymph nodes (HR =1.842,3.084,95% confidence interval:1.286-2.638,1.956-4.861,P < 0.05).Lymph nodes dissected for 21-30 was the protective factor of prognosis (HR =1.533,95% confidence interval:1.229-2.248,P < 0.05).Conclusions Lymph nodes dissected for 21-30 during radical gastrectomy may improve the long-term survival of patients.The tumor diameter longer than 5 cm,serosal invasion and the number of lymph nodes dissected (less than 15,15-20 and more than 30) were the independent factors influencing the prognosis of patients with low-and undifferentiated gastric cancer and with negative metastasis of lymph nodes.
7.Role of heme oxygenase-1 in inflammatory responses in septic rats
Li XU ; Xiaoliang WANG ; Liu HAN ; Yong ZHANG ; Hongguang BAO
Chinese Journal of Anesthesiology 2012;32(4):494-496
Objective To evaluate the role of heme oxygenase-1 ( HO- 1 ) in inflanmatory responses in septic rats.Methods Seventy-two male Wistar rats,aged 10-14 weeks,weighing 250-300 g,were used in this study.The animals were anesthetized with intraperitoneal 2% pentobarbital sodium 50 mg/kg.Sepsis was induced by cecal ligation and puncture (CLP).The animals were randomly divided into 4 groups ( n =18 each):control group (C group),CLP group,HO-1 inducer cobalt protoporphyrin Ⅸ (CoPPⅨ) group (Co group) and HO-1 inhibitor zinc protoporphyrin Ⅸ (ZnPPⅨ) group (Zn group).Six rats in each group were randomly chosen at 6,12 and 24 h after operation to collect blood samples,and then the animals were sacrificed to obtain lung tissues at 24 h after operation.The serum levels of TNF-α,IL-6 and high mobility group box 1 (HMGB1) were determined by ELISA.The expression of HMGB1 mRNA in lung tissues was detected by RT-PCR.Another 40 Wistar rats with the same conditions were grouped according to the method mentioned above and the survival curve was drawn.Results Compared with group C,the serum levels of TNF-α,IL-6 and HMGB1 were significantly increased,the expression of HMGB1 mRNA in lung tissues was up-regulated,and the survival rate was significantly decreased in CLP,Co and Zn groups ( P <0.05).Compared with group CLP,the serum levels of TNF-α,IL-6 and HMGB1 were significantly decreased,the expression of HMGB1 mRNA in lung tissues was down-regulated,and the survival rate was significantly increased in group Co ( P < 0.05),while no significant change was found in the parameters mentioned above in group Zn ( P > 0.05).Conclusion Inducing the expression of HO-1 is helpful in reducing inflammatory responses in septic rats.
8.Dynamic observation on bone mineral density of unsexed rabbits with QCT
Yong HAN ; Guizhi WANG ; Guang ZHANG ; Jing SUN ; Jingxin LIU
Journal of Jilin University(Medicine Edition) 1999;25(3):221-222
Objective: The purpose of this tudy was to dynamicly observe the weight and the bone mineral density (BMD) of the unsexed rabbits with a few self-made standardized phantoms. Methods:The eighteen healthy adult female rabbits were measured for their weight and BMD in preunsexed and postunsexed 5 months, 10 months with quantitative CT(QCT). Results:There were 61.1% of rabbits whose weight and BMD decreased after 5 months of the postunsexed and 100% of rabbits whose weight and BMD decreased after 10 months of the operation. Conclusion:QCT can be used to dynamicly observe curative effect of drugs in various periods as well,and it is a good method to study osteoporosis.
9.The preliminary study of using MR spectrum to predict the cellular differentiation of prostate cancer
Yang ZHAO ; Yong XU ; Yue HAN ; Zhihong ZHANG ; Ranhu LIU
Chinese Journal of Radiology 2011;45(10):951-954
ObjectiveTo investigate the feasibility of using the ratio of (Cho + Cr)/Cit derived by MRS to predict the differentiation grades of prostatic cancer and Gleason grading.Methods Five postoperative prostate specimens were spitted and layered according to the region of interest of MRS inspections.The correlation between the CC/C values of each region of interest in each layer and the Gleason scores of the corresponding pathological sections was analyzed.The optimum diagnostic cutoff value was determined by conducting the hypothesis test of the area below the ROC curve of the well and moderately differentiated groups and poorly differentiated ones on the basis of CC/C values with a Spearman test.Results A total of 90 regions with valid pathologic diagnosis were obtained,70 cancer-affected and 20 cancer-free.In MRS,a CC/C value above 0.86 was used as a criterion for defining a cancer-affected region As a result,65 cancer-affected regions and 25 cancer-free regions were identified,among which pathologic diagnosis confirmed 59 and 14,respectively.Spearman′s rank correlation analysis revealed that the CC/C values of the prostatic carcinoma had significant positive correlation with Gleason scores ( r =0.746,P =0.000).For the well and moderately differentiated groups,the hypothesis test about the cutoff value,which was obtained by calculating the area below the ROC curve,was of no statistical significance.For the poorly differentiated groups,the optimum cutoff value was defined as 0.948,and the sensitivity and specificity were 81.4% and 75.0%,respectively.It was also observed that the Gleason scores of the poorly differentiated endemic regions had positive correlation with the CC/C values ( r =0.605,P =0.000 ),suggesting that CC/C value was associated with the differentiation grade of the poorly differentiated prostatic cancer.When CC/C value was above 0.948,the poorly differentiated prostatic cancer was typically detected and Gleason score was often above 7.Conclusions CC/C values has positive correlation with Gleason scores.MRS may be used to predict the differentiation of prostate cancer.
10.Applications of global left ventricular myocardial strain in detection of anthracycline-induced cardiotoxicity in breast cancer survivors with postoperative chemotherapy
Yong HAN ; Yun DONG ; Yi LIU ; Lianghua XIA ; Ming CHEN
Chinese Journal of Ultrasonography 2014;23(2):104-108
Objective To assess the clinical significance of three-dimensional speckle tracking imaging (3D-STI) in the evaluation of left ventricular myocardial function in breast cancer survivors with postoperative anthracycline-based chemotherapy.Methods A total of 51 breast cancer survivors with postoperative anthracycline-based chemotherapy were recruited and 31 female healthy volunteers as the controls.Conventional echocardiography and 3D-STI derived parameters [including global longitudinal strain (GLS) and global area strain (GAS)] were measured before and at 3 and 6 anthracycline-based chemotherapeutic cycles.The receiver operating characteristics (ROC) curve was constructed to determine optimal sensitivity and specificity of 3ID-STI derived parameters for the prediction of future cardiotoxicity.Results In comparison with the controls and baseline cases,GLS and GAS deteriorated significantly (P < 0.05 for both).No statistical difference in GCS and conventional parameters showed before and after the initiation of chemotherapy (P <0.05,respectively).The ROC curves showed that GAS as the best 3D-STI predictor of patients who develop cardiotoxicity during the follow-up.The area under ROC(AUC) of GAS was 0.894,and its optimal cut-off value was-28.4%,with a specificity of 88.0% and a sensitivity of 82.9%.AUC of GLS was 0.802,and its optimal cut-off value was-14.3%,with a specificity of 62.0% and a sensitivity of 85.4%.Conclusions Early decreases in GAS and GLS based on 3D-STI may allow the prediction of subsequent cardiotoxic development accurately in breast cancer survivors with postoperative anthracycline-based chemotherapy.