1.The protective effect of bone marrow mesenchymal stem cells by anoxic preconditioning on diabetic cardiomyopathy
Jiahui LI ; Nan ZHANG ; Wei QIAO ; Yong WANG ; Jianan WANG
Chinese Journal of Emergency Medicine 2011;20(10):1062-1066
Objective To explore the protective effect of bone marrow mesenchymal stem cells (MSC) on diabetic myocardium and anoxic pre-conditioning (AP).Methods Eight-week-- old male Sprague-Dawley rats were given with a single intraperitoneal injection of streptozotocin (STZ) (60 mg/kg)to induce diabetes mellitus (DM).Donor rats were 8-week-old male Sprague - Dawley rats.Before transplantation,MSC were incubated in CM-DiI at a concentration of 2 μg/mL for 20 min.AP-MSC were exposed to 3 hours of anoxia.At 4 months after STZ injection,diabetic rats were randomly given with an intramyocardial injection of one of the followings:150 μL of Dulbecco's modified Eagle's medium ( DMEM),5 ×106 MSC/150 μL,or 5 × 106 AP - MSC/150 μL (n =10 for each group).Three months after STZ injection and 2 weeks after transplantation,we evaluated the cardiac function by echocardiography,and also evaluated the cardiac conditions by alkaline phosphatase staining,western blot analysis for apoptosis related proteins and signal pathways.Results MSC,especially AP- MSC increased fractional shortening (FS) of diabetic heart (P <0.01 vs DMEM respectively).AP-MSC greatly increased the capillary density of diabetic myocardium (P <0.01 vs DMEM and MSC group respectively).AP-MSC are anti-apoptotic in the rat DCM model,possibly mediated through cardiac upregulation of Bcl-2/Bax ratio ( P < 0.05 ) and inhibiting the expression and activation of caspase - 3 ( P < 0.01 ).Conclusions Intramyocardial transplantation of APMSC has a protective effect on diabetic cardiomyopathy.
2.NEUROPROTECTIVE EFFECT OF c-fos ANTISENSE OLIGODEOXYNUCLEOTIDE UPON APOPTOSIS INDUCED BY SODIUM SELENITE IN CULTURED CORTICAL NEURONS: POSSIBLE CASCADE OF ACTIVATION OF RELATED GENES
Rong XIAO ; Yan DOU ; Jiahui ZHAO ; Rui WANG ; Xiuzhen YAN ; Jiantian QIAO
Chinese Journal of Neuroanatomy 2002;18(2):93-100
To investigate the role of immediate-early gene c-fos in sodium selenite-induced apoptosis and its position in a possible cascade of apoptogenic genes, we compared the time-courses of expression for 5 related genes, including c-fos, during the apop- tosis induced by sodium selenite with or without blockage of c-fos expression by adding c-fos antisense oligodeoxynucleotide ( ASO) in cultured cortical neurons. The results showed that: (1) in control experiments without c-fos ASO adding, 0. 5 μmol/ L sodium selenite-induced apoptosis as revealed by electrophoretic and flow cytometric examinations; at the same time, sodium selenite also induced down-regulation of bcl-2 mRNA expression and up-regulations of mRNAs related to bax, c-fos, p53, and acetylcholinesterase (AChE) genes; (2) in similar experimental conditions with c-fos ASO cotreatment, the sodium selenite-in- duced apoptosis was blocked with the up-regulation of p53 expression still emerging as before, while the changes in expressions of bcl-2, bax, AChE genes were reversed at the same time. The results suggest that c-fos ASO could play a protective role upon cortical neurons from suffering apoptosis induced by sodium selenite, and there might exist a cascade of gene expressions with p53 and c-fos genes being regulated upstream and then bcl-2, bax, and AChE genes being regulated downstream.
3.Efficient Derivation of Mesenchymal Stem Cells and Neural Precursor Cells From Human Embryonic Stem Cells Through Teratoma Formation
Qiao ZENG ; Shimin AN ; Qian PAN ; Kun XIA ; Jiahui XIA ; Zhuohua ZHANG ; Yi SUN ; Guoping FAN
Progress in Biochemistry and Biophysics 2008;35(12):1417-1424
Many somatic cell typos were obtained by in vitro differentiation or teratoma formation of human embryonic stem ceLls (hESCs). However, it is unclear whether specific cell types can be obtained from hESCs-derived teratoma. It was reported that many kinds of cells, including neural progetfitor/precursor cells (NPCs) and mesenchymal stem cells (MSCs) were isolated efficiently from the teratoma of hESCs through in vitro selection. The teratoma-derived NPCs and MSCs showed specific characteristics of molecular markers similar to the primary NPCs and MSCs. Moreover, these teratoma-induced NPCs and MSCs can be further induced to differentiate into neurons, astrocytes, or adipose and bone cells, reflecting their inherent multi-potencies. Given that teratoma normally contains a mixture of ectoderm, mesodenn, and endoderm lineage cells at different differentiation stage, it was suggested that hESCs-derived teratoma could be an alternative source to generate a variety of uncommitted progenitor cells or terminally differentiated somatic cells, which may be otherwise difficult to obtain through direct in vitro differentiation.
4.Clinical observation of postprandial blood pressure changes in the very elderly with nasal feeding
Wei QIAO ; Li CHEN ; Jiahui LI ; Lei CHEN ; Jing HUANG ; Zhigang ZHENG ; Xiaoping ZHANG
Chinese Journal of Geriatrics 2012;31(11):971-973
Objective To observe the changes of postprandial blood pressure and heart rate with two types of nasal feeding in the very elderly and explore the method for decreasing the postprandial hypotension (PPH).Methods Totally 49 patients (aged>80 years) were randomly divided into two groups of continuous versus intermittent nasal feeding.The clinical symptoms and changes in blood pressure and heart rate before and after meals were observed.Results The incidence of PPH was 100.0%(26 cases)in the group of intermittent nasal feeding,and 47.8% (11 cases) in the group of continuous nasal feeding (P<0.01).Postprandial blood pressure in the group of intermittent nasal feeding was decreased significantly as compared with the group of continuous nasal feeding (P <0.05); and the heart rate was accelerated in the group of intermittent nasal feeding compared with continuous nasal feeding (P<0.05).The incidence of serious cardio-cerebral ischemia was 7.7% (2cases)in the group of intermittent nasal feeding.The patients had no clinical symptoms in the group of continuous nasal feeding.Conclusions Continuous nasal feeding for the very elderly with gastrointestinal nutrition can reduce the extent of the falling blood pressure and the incidence of PPH,and avoide cardiocerebrovascular events.
5.Dilemmas and strategies for collaborative governance of medical preventive integration based on SFIC model
Bei LU ; Chenxiao YANG ; Jiahui QIAO ; Hongwei GUO ; Qiusha LI ; Jia SONG ; Wenqiang YIN
Chinese Journal of Hospital Administration 2023;39(8):626-630
Promoting medical preventive integration and improving its collaborative mechanism is an inevitable requirement for achieving the transformation of China′s medical and health care system from " disease centered" to " people′s health centered" and providing comprehensive and comprehensive health services for the people.This study established a research framework based on the SFIC model on the basis of clarifying the collaborative subjects of medical preventive integration, sorted out the dilemma of medical preventive integration collaborative governance in China from five aspects, including external environment, starting conditions, facilitative leadership, institutional design and collaborative process.In order to break the dilemma of medical preventive integration and promote collaborative governance among multiple subjects, the authors proposed such optimization strategies, including further improving relevant laws, regulations, and policy systems, filling resource gaps, attracting multiple entities to participate, providing reference for promoting China′s medical preventive integration work.
6.Key problems of medical and preventive integration at primary medical and health institutions in China
Bei LU ; Chenxiao YANG ; Jiahui QIAO ; Zixuan ZHAO ; Qiusha LI ; Hongwei GUO ; Wenqiang YIN
Chinese Journal of Hospital Administration 2023;39(11):810-815
Objective:To explore the problems of medical and preventive integration at primary healthcare institutions in China, for references for promoting the development of medical and preventive integration in China.Methods:This study searched for literatures covering the integration of medical and preventive at primary healthcare institutions on CNKI, Wanfang, and VIP databases(from the establishment of the database until March 1, 2023), and extracted text mentioning problems of the medical and preventive integration in primary healthcare institutions. The macro model of the health system was used for problem classification analysis, while the social network analysis method was used to measure the network density, point centrality, and intermediary centrality of the problem, and determine the key issues.Results:A total of 25 papers were included, and 28 problems of medical and preventive integration at primary medical and health institutions were extracted, including 6 problems at the external environment level, 15 problems at the structural level, 6 problems at the process level, and 1 problem at the result level. The results of social network analysis showed that the network density of these problems was 0.71. The point centrality and intermediary centrality of key problems were both high, including the lack of incentive mechanisms for medical and prevention integration (point centrality=69, intermediary centrality=21.44), fragmentation of health information systems(68, 15.70), insufficient awareness of medical and prevention integration among grassroots personnel(65, 17.47), shortage of talent at primary medical and health institutions(64, 11.69), weak service capabilities of primary medical institutions(50, 19.23), and insufficient information sharing(48, 15.80).Conclusions:A variety of problems were found in the integration of medical and preventive at primary medical and health institutions in China, which were closely interrelated. It was urgent to solve six key problems, including the lack of incentive mechanisms, talent shortage, and information system fragmentation, etc. It was suggested that primary medical and health institutions should further improve the incentive mechanism for medical and preventive integration, strengthen the construction of grassroots health talent teams, promote health information exchange and sharing, and enhance the awareness of medical and preventive integration.
7.The impact of digoxin on the long-term outcomes in patients with coronary artery disease and atrial fibrillation
Yan QIAO ; Yue WANG ; Chenxi JIANG ; Songnan LI ; Caihua SANG ; Ribo TANG ; Deyong LONG ; Jiahui WU ; Liu HE ; Xin DU ; Jianzeng DONG ; Changsheng MA
Chinese Journal of Internal Medicine 2021;60(9):797-805
Objective:To investigate the long-term safety of digoxin in patients with coronary artery disease (CAD) and atrial fibrillation (AF).Methods:This was a prospective study, in which 25 512 AF patients were enrolled from China Atrial Fibrillation Registry Study. After exclusion of patients receiving ablation therapy at the enrollment, 1 810 CAD patients [age: (71.5±9.3)years] with AF were included. The subjects were grouped into the digoxin group and non-digoxin group, and were followed up for a period of 80 months. Long-term outcomes were compared between the groups and an adjusted Cox regression analysis was applied to evaluate the risk of digoxin on the long-term outcomes. The primary endpoint was all-cause mortality.Results:The patients were followed up for a median period of 3.05 years. After multivariable adjustment, the Cox regression analysis showed that digoxin significantly increased the risk of all-cause mortality ( HR=1.28, 95% CI 1.01-1.61, P=0.038), cardiovascular mortality ( HR=1.48,95% CI 1.10-2.00, P=0.010), cardiovascular hospitalization ( HR=1.67,95% CI 1.35-2.07, P=0.008) and the composite endpoints ( HR=2.02,95% CI 1.71-2.38, P<0.001). In the subgroup of patients with heart failure (HF), digoxin was not associated with the risk of all-cause mortality, but was still associated with the increased risk of cardiovascular mortality ( HR=1.44,95% CI 1.05-1.98, P=0.025), cardiovascular hospitalization ( HR=1.44,95% CI 1.09-1.90, P=0.010) and the composite endpoints ( HR=1.37, 95% CI 1.01-1.70, P=0.004). However, in the subgroup of patients without HF, digoxin was only associated with all-cause mortality ( HR=2.56,95% CI 1.44-4.54, P=0.001). Conclusion:Digoxin significantly increased the risk of all-cause mortality in CAD patients with AF, especially in patients without HF.
8.Gefitinib inhibits glycolysis and induces programmed cell death in non-small cell lung cancer cells.
Qiao ZHOU ; Jiahui LI ; Jinlong PANG ; Fangtian FAN ; Shanshan LI ; Hao LIU
Journal of Southern Medical University 2020;40(6):884-892
OBJECTIVE:
To observe the cell death pattern induced by gefitinib in non-small cell lung cancer A549 and H1975 cells and explore the possible mechanism in light of glycolysis.
METHODS:
The inhibitory effects of gefitinib at 20, 30, or 40 μmol/L in A549 cells and at 20, 40, or 80 μmol/L in H1975 cells were examined using MTT assay. The changes of lactic acid level in the cells were determined with a lactic acid kit, and the expression levels of glycolysis-related proteins (PKM2 and HK2) and the proteins in PI3K-Akt-mTOR signaling pathway were detected using Western blotting. 2-NBDG was used for detecting glucose uptake capacity of the cells, and ATP kit was used to detect the intracellular ATP level. The mitochondrial membrane potential of the cells was examined with the JC-1 kit, and cell apoptosis was analyzed with Annexin V-FITC/PI double staining. The relative expression levels of the apoptotic proteins Bax and Bcl-2 and the autophagy marker protein LC3B were detected with Western blotting.
RESULTS:
MTT assay showed that gefitinib inhibited the proliferation of A549 and H1975 cells in a time- and dose-dependent manner ( < 0.05). The IC of gefitinib at 24, 48 and 72 h was 48.6, 28.6 and 19.7 μmol/L in A549 cells and was 321.6, 49.1 and 14.6 μmol/L in H1975 cells, respectively. Gefitinib significantly lowered intracellular lactic acid level of the cells ( < 0.05) and down-regulated the expressions of PKM2 and HK2 proteins ( < 0.05) and PI3K-Akt-mTOR signaling pathway-associated proteins ( < 0.05). Gefitinib obviously inhibited glucose uptake and ATP levels in both A549 and H1975 cells ( < 0.05). Treatment with gefitinib induced obviously enhanced apoptosis in the cells, resulting in apoptosis rates of (10.77± 1.0)%, (14.5±0.4)%, (17.4±0.2)% and (32.1±0.6)% at 0, 20, 30 and 40 μmol/L in A549 cells ( < 0.05) and of (10.5±0.6)%, (13.2± 0.92)%, (18.9±0.98)% and (35.1±1.4)% at 0, 20, 40 and 80 μmol/L in H1975 cells, respectively ( < 0.05). The protein expression of Bax increased and that of Bcl-2 decreased following gefitinib treatment in the cells ( < 0.05). Gefitinib significantly increased autophagy in A549 and H1975 cells as shown by increased LC3B expressions following the treatment ( < 0.05).
CONCLUSIONS
Gefitinib can inhibit the proliferation, induce apoptosis and increase autophagy in A549 and H1975 cells. Gefitinib induces apoptosis of the cells possibly by affecting glycolysis and PI3K-Akt-mTOR signaling pathway.
Apoptosis
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Carcinoma, Non-Small-Cell Lung
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Cell Line, Tumor
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Cell Proliferation
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Gefitinib
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Glycolysis
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Humans
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Lung Neoplasms
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Phosphatidylinositol 3-Kinases