1.Study on Tanshinone ⅡA Inhibiting the Proliferation and Migration Induced by Homocysteine of VSMCs and Its Mechanism
China Pharmacy 2016;27(22):3072-3076
OBJECTIVE:To study tanshinone ⅡA inhibiting the proliferation and migration induced by homocysteine(Hcy)of rat aortic vascular smooth muscle cells(VSMCs)and its signal pathway. METHODS:VSMCs were selected for the following ex-periments. In order to validate TanshinoneⅡA inhibiting the proliferation and migration induced by Hcy of VSMCs,VSMCs were di-vided into control group,Hcy group(1 000μmol/L),TanshinoneⅡA low-dose,medium-dose and high-dose groups(5,10,20 μg/L). In mechanism study test,VSMCs were divided into control group,TanshinoneⅡA group(20 μg/L),rapamycin group(20 nmol/L), MHY1485 group(10μmol/L),TanshinoneⅡA+rapamycin group(TanshinoneⅡA,20 μg/L+rapamycin,20 nmol/L),TanshinoneⅡA+MHY1485 group (TanshinoneⅡA,20 μg/L+MHY1485,10 μmol/L). In validation test of P70S6K and p-P70S6K pathway expres-sion,rapamycin and MHY1485 were used for inhibitory test and activation test,respectively. The proliferation of VSMCs was de-termined by ELIASA,and Transwell chambers and wound healing test were employed to test the migratory ability of VSMCs. West-ern blotting were used to investigate the expressions of P21,P27,MMP-2,MMP-9,P70S6K and p-P70S6K in VSMCs. RE-SULTS:In validation test,compared with control group,24,48 h absorbance,migration area,the number of VSMCs penetration and the expression of MMP-2,MMP-9 and p-P70S6K increased significantly,while the expression of P21 and P27 decreased sig-nificantly(P<0.01). Compared with Hcy group,48 h absorbance of TanshinoneⅡA low-dose group,24,48 h absorbance and the expression of MMP-2 of TanshinoneⅡA medium-dose and high-dose groups,migration area,the number of VSMCs penetration, the expression of MMP-9 and p-P70S6K in low-dose,medium-dose and high-dose groups all decreased significantly;the expres-sion of P21 and P27 increased significantly in TanshinoneⅡA medium-dose and high-dose groups(P<0.01);there was no statisti-rapamycin group,while 24,48 h absorbance increased significantly in MHY1485 group(P<0.01). Compared with TanshinoneⅡA group,24,48 h absorbance decreased significantly in TanshinoneⅡA+rapamycin group,while 12,24,48 h absorbance,migration area and the number of VSMCs penetration increased significantly in TanshinoneⅡA+MHY1485 group (P<0.01). In inhibitory test,compared with control group,the expression of p-P70S6K decreased significantly in TanshinoneⅡA group (P<0.01);com-pared with TanshinoneⅡA group,the expression of p-P70S6K decreased significantly in rapamycin group and TanshinoneⅡA+rapa-mycin group(P<0.01);in activation test,the expression of p-P70S6K decreased significantly in TanshinoneⅡA group(P<0.01), compared with TanshinoneⅡA group,the expression of p-P70S6K increased significantly in MHY1485,TanshinoneⅡA+MHY1485 group (P<0.01). CONCLUSIONS:TanshinoneⅡA can inhibit the proliferation and migration of VSMCs by suppressing mTOR/P70S6K signal pathway.
2.Expression of matrix metalloproteinase-9 and tension protein homologous gene(PTEN)in gingival carcinoma and its clinical significance
Zhifang DONG ; Jun JING ; Yixuan JING
Chinese Journal of Biochemical Pharmaceutics 2017;37(7):37-39
Objective To investigate the expression and clinical significance of matrix metalloproteinase(MMP-9)and tension protein homologous gene in gingival cancer tissue.Methods 50 cases in Guyuan people's hospital from June 2013to December 2016 were selected to study the expression of matrix metalloproteinase(MMP-9)and tension protein homologous gene in gingival cancer tissue.Results The positive rate of PTEN in gingival cancer group was 54.00%, the positive rate of PTEN was 94.00% in normal tissue, normal control group positive rate of PTEN was significantly higher than that of gingival cancer group(P<0.05);the positive rate of MMP-9 in gingival cancer group was 76.00%, the positive rate of control group was 20.00%, gingival cancer group was significantly higher than the normal control group(P<0.05).The expression of MMP-9 and PTEN in in gingival cancer tissue was unrealted with gender, age, and tissue differentiation, and associated with lymph node metastasis and tissue infiltration(P<0.05).Conclusion PTEN expression is low in gingival cancer tissue low, MMP-9 expression is high in gingival cancer tissues.PTEN and MMP-9 are closely related to the incidence and development of gingival cancer.Therefore, MMP-9 positivity is a risk factor for gingival cancer, while PTEN positivity is a protective factor for gingival cancer.
3.Protective effect of Xinyi capsule pretreatment on myocardial ischemia reperfusion injury in rabbits
Yuexin ZHU ; Kai MA ; Yong CAO ; Xiangyu LI ; Yixuan ZHOU ; Lei ZHOU ; Mei DONG ; Li LI
International Journal of Traditional Chinese Medicine 2015;(1):56-60
Objective To investigate the protective effect of Xinyi capsule pretreatment on myocardial ischemia reperfusion injury in rabbits and its possible mechanism. Methods Ninety-four rabbits were randomly divided into 6 groups: model group (n=16), tirofiban group (n=16), high-, medium- and low-dose Xinyi capsule groups (4.0, 2.0, 1.0 g/kg;n=16 in each group), and sham operation group (n=14). Five days after intragastric administration with drug, myocardial ischemia reperfusion was induced by ligation of the proximal left circumflex artery. The electrocardiogram (ECG) was continuously recorded. The serum levels of myeloperoxidase (MPO), lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were measured. Myocardial histopathological damage was evaluated. Results The changes of J-point amplitude on ECG in high-, medium-and low-dose Xinyi capsule groups (0.064 ± 0.049 mV, 0.069 ± 0.061 mV, 0.079 ± 0.060 mV) were significantly lower than that in the model group (0.158 ± 0.105 mV, P<0.01 or P<0.05), the serum levels of LDH (399.7 ± 202.3 U/L, 369.6 ± 229.0 U/L, 435.5 ± 152.4 U/L), CK-MB (900.8 ± 231.2 U/L, 1 268.3 ± 899.8 U/L, 1 386.7 ± 621.6 U/L), MPO (69.81 ± 5.51 U/L, 85.44 ± 10.31 U/L, 81.33 ± 16.87 U/L) were significantly lower than those in the model group (LDH:817.1 ± 401.9 U/L, CK-MB:2 071.3 ± 693.5 U/L, MPO:149.9 ± 20.11 U/L;P<0.01 or P<0.05). Histopathological examination showed that myocardial damage in high-, medium- and low-dose Xinyi capsule groups reduced compared with the model group. Conclusions Xinyi capsule pretreatment can protect against myocardial ischemia reperfusion injury in rabbits, and its mechanism may be related to inflammation inhibition.
4.Study on purification technic of total saponins in Panacis Japonici Rhizoma with macroporous resin
Jing WANG ; Yixin DONG ; Liying HE ; Yasen SUBINUER ; Yixuan SUN ; Ping YU ; Haiyan ZOU
International Journal of Traditional Chinese Medicine 2021;43(6):570-574
Objective:Select a suitable macroporous resin for the purification technic of total saponins from Panacis Japonici Rhizoma and determine the parameter of purification technic. Methods:Made the content of total saponins as the index, used static adsorption test and combined the adsorption kinetic parameters to select the type of macroporous resin. By using dynamic adsorption experiment to investigate the technical parameters of the purified macroporous resin extracted from Panacis Japonici Rhizoma. Then the preparation technic of the total saponins of Panacis Japonici Rhizoma was determined. Results:The D101 macroporous resin could absorpt and desorpt total saponins of Panacis Japonici Rhizoma effectively. The optimal purification parameters were as follow: the loading mass concentration was 0.1 g/ml (based on crude drug), and the loading volume was 100 ml (which means the loading volume of resin per ml was equivalent to 3.3 grams of crude drug). During the elution process, distilled water (3 BV) and 20% ethanol (3 BV) were used to remove impurity, and then 70% ethanol elution (6 BV) was used to enrich the total saponins. The flow rate of loading and elution was 0.5 ml/min. The transfer rate of total saponins could reache 85.6%. Conclusion:The D101 macroporous resin can effectively enrich and purify the total saponins of Panacis Japonici Rhizoma, which provides the scientific basis for the development and utilization of Panacis Japonici Rhizoma.
5.Three cases of orthotopic cardiac transplantation for congenital dextrocardia
Nianguo DONG ; Jinping LIU ; Guohua WANG ; Yixuan WANG ; Jie CAI ; Jing ZHANG ; Yongfeng SUN
Chinese Journal of Organ Transplantation 2019;40(2):111-115
Objective To summarize the surgical strategies of orthotopic cardiac transplantation for congenital dextrocardia .Methods Three patients with congenital dextrocardia suffered from endstage heart failure and underwent orthotopic cardiac transplantation from March 2014 to September 2017 .They were aged 10 ,29 ,13 years respectively .Donor hearts were from brain death donors and procured with extra length on inferior vena cava , aorta and pulmonary artery tissues . After cardiectomy , left atrial-atrial anastomosis was performed initially between donor ' s left-upper pulmonary vein orifices and recipient's left-lower pulmonary vein orifices .Apex was orientated at a 90 degrees' clockwise to right . Then aorta ,inferior and superior vena cava and last pulmonary artery were anastomosed continuously . The prosthetic conduits were also used owing to a lack of tissue . Results All operations were successful . The cold ischemic time was (130-375 ) (251 .00 ± 122 .53) min ,cardiopulmonary bypass time (127-212 )(179 .67 ± 55 .72 ) min and aortic clamp time (38-105 ) (65 .33 ± 35 .166) min . Two patients had stable hemodynamics and recovered well after HTx .During a follow-up period of 1 .5-3 .5 years , echocardiography showed excellent cardiac functions without blood flow obstruction . Chest radiology showed well-placed donor heart in right mediastinum .One left-sided patient with total cavopulmonary connection before HTx died at 59 days after HTx because of pneumonia and multiple organ failure .Conclusions Heart transplantation is curative for patients with congenital dextrocardia and surgical strategies are the key factor of successful treatment .
6.Predictive value of prognostic nutritional index for recipients of heart transplantation
Yang ZHAO ; Yixuan WANG ; Nianguo DONG
Chinese Journal of Organ Transplantation 2023;44(11):668-674
Objective:To explore the predictive value of prognostic nutritional index(PNI)for recipients of heart transplantation.Methods:From January 2015 to December 2020, the relevant clinical data were reviewed retrospectively for 438 post-heart transplantation recipients at Union Hospital of Tongji Medical College of Huazhong University of Science and Technology.The optimal cut-off value of PNI was determined by receiver operating characteristic(ROC)curve.The inter-group differences of clinicopathologic characteristics were compared.Overall survival(OS)was calculated by Kaplan-Meier survival curve and compared by Log-rank test between two groups.The risk factors affecting OS were examined by univariate and multivariate Cox regression.Results:The optimal cut-off value of PNI was 49.3.They were assigned into two groups of low PNI(PNI≤49.3, 284 cases)and high PNI(PNI>49.3, 154 cases). As compared with high PNI group, low PNI group was significantly correlated with lower BMI, hemoglobin, neutrophil count, albumin, low-density lipoprotein, triglyceride, recipient/donor BMI ratio and recipient age and total bilirubin(all P<0.05). Cox regression multivariate analyses indicated that recipient age, waiting time, preoperative use of intra-aortic ballon pump(IABP)and lower PNI score were risk factors(all P<0.05). Kaplan-Meier survival curve revealed that OS was better in high PNI group than that in low PNI group( χ2=15.122, P<0.01). The area under the ROC curve of PNI for predicting OS was 0.603. Conclusions:PNI score upon admission is correlated positively with postoperative survival of heart transplantation patients.PNI has some predictive value for OS.When PNI score upon admission≤49.3, postoperative survival rate is relatively worse with a shorter postoperative survival.
7.Macrophage-to-myofibroblast transition promotes pulmonary fibrosis occurred in LPS-induced acute lung injury of mouse models
Dong ZHAO ; Shiqian ZHA ; Yixuan WANG ; Zhou PAN ; Wenzhen YU ; Ke HU
Basic & Clinical Medicine 2024;44(3):281-287
Objective To explore the impact of macrophage-to-myofibroblast transition(MMT)on pulmonary fibro-sis induced by acute lung injury by LPS.Methods Totally 21 male mice were randomly classified into 7 groups:control group,model group(LPS-PF)at different time points and intervention group of clodronate-liposomes(CL-LIP)treatement at different time points(n=3).Pulmonary fibrosis was identified by HE and Masson staining microscopy.The immuno-fluorescence technology was used for the evaluation of numbers of macrophage-to-myofi-broblast transition cells(MMT cell which co-expressed CD68 and α-SMA).Bone marrow-derived macrophages(BMDMs)were randomly classified into two group:control(Ctrl)group and TGF-β1-treated group induced by transforming growthfactor-β1.α-SMA,FN and Col1 were detected by RT-qPCR.The expression of α-SMA,Smad3 and p-Smad3 protein was evaluated by Western blot.Results At day 7,the Ashcroft score of lung tissue in LPS-PF mouse model was significantly increased when compared with the Ctrl group(P<0.01);While the score signifi-cantly declined when the model was pretreated with CL-LIP(P<0.05).As detected by immuno-fluorescence stai-ning,in CL-LIP group the number of CD68-positive cells co-labeled with α-SMA was obviously less then that of LPS-PF group of the corresponding time point(P<0.01).When the BMDMs were stimulated by TGF-β1 at 24 h,48 h and 96 h respectively,a higher expression of α-SMA,FN,Col1,were found in TGF-β1-treated group than that in Ctrl group at the corresponding time point(P<0.01).The expression of Smad3,p-Smad3 significantly higher in LPS-PF group(at both day 7 and day 10)and TGF-β1-treated group(at both 48 h and 96 h)as compared to cor-responding control group(P<0.01).Conclusions MMT promotes pulmonary fibrosis induced by ALI via LPS.Smad3 is proved to be involved in the MMT process.
8.Hazards of game addiction to health in adolescents
Xiaolian DONG ; Yizhou JIANG ; Yixuan ZHANG ; Weibo ZHANG ; Na WANG
Shanghai Journal of Preventive Medicine 2022;34(5):504-508
Gaming addiction, as a main manifestation of internet addiction, is characterized by a pattern of persistent or recurrent gaming behaviors. Gaming behaviors are common among adolescents and can result in marked distress or significant impairment in personal, family, social or other important areas of functioning. Recent research on health hazards of gaming addiction is relatively scattered. This article reviews the harm of adolescent game addiction to physical and mental health.
9.Noninvasive prenatal screening for twin pregnancy: an analysis of 2057 cases.
Yixuan YIN ; Hui ZHU ; Yeqing QIAN ; Jinglei JIN ; Jin MEI ; Minyue DONG
Journal of Zhejiang University. Medical sciences 2019;48(4):403-408
OBJECTIVE:
To analyze the results of noninvasive prenatal screening (NIPS) for fetal chromosome aneuploidy in twin pregnancy.
METHODS:
A total of 2057 women with twin-pregnancy between 12-26 weeks were recruited from Women's Hospital, Zhejiang University School of Medicine, Hangzhou Municipal Women's Hospital and Jiaxing Maternal and Child Health Hospital during February 2015 to August 2018. The cell-free DNA was extracted from the peripheral blood sample for DNA library, and non-invasive prenatal testing (NIPT) was performed by high-throughput sequencing technique. The fetal karyotype analysis or neonatal karyotype analysis was performed in pregnant women with fetal chromosome aneuploidy, and all subjects were followed up. The efficiency of NIPS testing for twin aneuploidy was calculated.
RESULTS:
NIPS revealed chromosome abnormalities in 11 out of 2057 twin pregnant women, 9 cases were confirmed chromosome abnormalities, 2 cases were normal and no false negative cases. In this screening, the detection rate, sensitivity, specificity, positive predictive value, false positive rate of NIPS were 100.00%, 100.00%, 99.90%, 81.82%, 0.10%. Those were 100.00%, 100.00%, 99.95%, 87.50% and 0.05% for trisomy 21, 100.00%, 100.00%, 100.00%, 100.00%, 0.00% for trisomy18, and the specificity and false positive rate for trisomy13 were 99.95% and 0.05%, respectively.
CONCLUSIONS
NIPS can detect fetal chromosomal aneuploidy rapidly and accurately in twin pregnancies,and it is of value in clinical application.
Aneuploidy
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Female
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Humans
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Noninvasive Prenatal Testing
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standards
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Pregnancy
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Pregnancy, Twin
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Prenatal Diagnosis
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methods
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Reproducibility of Results
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Trisomy
10.Combination therapy using microwave ablation and d-mannose-chelated iron oxide nanoparticles inhibits hepatocellular carcinoma progression.
Rui CUI ; Luo WANG ; Dongyun ZHANG ; Kun ZHANG ; Jianping DOU ; Linan DONG ; Yixuan ZHANG ; Jiapeng WU ; Longfei TAN ; Jie YU ; Ping LIANG
Acta Pharmaceutica Sinica B 2022;12(9):3475-3485
Despite being a common therapy for hepatocellular carcinoma (HCC), insufficient thermal ablation can leave behind tumor residues that can cause recurrence. This is believed to augment M2 inflammatory macrophages that usually play a pro-tumorigenic role. To address this problem, we designed d-mannose-chelated iron oxide nanoparticles (man-IONPs) to polarize M2-like macrophages into the antitumor M1 phenotype. In vitro and in vivo experiments demonstrated that man-IONPs specifically targeted M2-like macrophages and accumulated in peri-ablation zones after macrophage infiltration was augmented under insufficient microwave ablation (MWA). The nanoparticles simultaneously induced polarization of pro-tumorigenic M2 macrophages into antitumor M1 phenotypes, enabling the transformation of the immunosuppressive microenvironment into an immunoactivating one. Post-MWA macrophage polarization exerted robust inhibitory effects on HCC progression in a well-established orthotopic liver cancer mouse model. Thus, combining thermal ablation with man-IONPs can salvage residual tumors after insufficient MWA. These results have strong potential for clinical translation.