1.Molecular mechanisms of cardiac aging
Journal of Geriatric Cardiology 2010;07(3):184-188
Age-associated changes in cardiovascular structure/ function are implicated in the markedly increased risk for cardiovascular disease in older persons. Aging not only prolongs exposure to several other cardiovascular risks, but also leads to intrinsic cardiac changes, which reduces cardiac functional reserve, predisposes the heart to stress and contributes to increased cardiovascular mortality in the elderly. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans, including left ventricular hypertrophy, fibrosis and diastolic dysfunction. Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations, increased mitochondrial biogenesis, as well as decreased cardiac SERCA2 protein. All of these age-related changes are significantly attenuated in mice overexpressing catalase targeted to mitochondria (mCAT). These findings demonstrate the critical role of mitochondrial reactive oxygen species (ROS) in cardiac aging and support the potential application of mitochondrial antioxidants to cardiac aging and age-related cardiovascular diseases.
2.Neuronal tracing and immunohistochemistry of BDNF gene transfected olfactory ensheathing cells transplant in spinal cord injury
Tianjun GAO ; Shaojun LIU ; Shuxun HOU
Medical Journal of Chinese People's Liberation Army 2001;0(11):-
Objective To evaluation of the result of transplantation of BDNF gene transfected olfactory ensheathing cells (OECs) to repair spinal cord injury (SCI). Methods The rat with SCI were divided into non-OECs, OECs and transfected OECs groups. The evidences of anatomical regeneration across the transection site were demonstrated by both neuronal tracing and immunohistochemical methods. Results 12w after implantation the retrograde labeling study with flurogold showed abundant labeled neurons in the superior part of CNS. There were a lot of labeled neurons in the intermediate zone and dorsal column of lower thoracic spinal cord rostral to the transection site. Labeled neurons were also observed in the upper thoracic and cervical spinal cord, reticular nucleus and raphe nucleus of oblongata, as well as reticular nucleus and parabrachial nucleus of pons. The anterograde labeling of PHA-L showed that regenerated fibers of upper neurons overcame glial scar and regrew into the distal part of spinal cord through the grafts. Some labeled fibers extended long enough to the caudal gray matter of the transected site. Conclusion The implantation of OECs transfected by BDNF gene may benefit the survival and regeneration of the injured axons, and accelerate the repair of the injured spinal cord in a more efficient way than that with OECs alone.
3.Effects of high glucose on the expression of angiotensin-converting enzyme/angiotensin converting enzyme 2 in human proximal tubular cells
Hancheng GUO ; Xue MENG ; Tianjun GUAN ; Qing GAO
Chinese Journal of Endocrinology and Metabolism 2011;27(8):680-682
HK-2 cells cultured in vitro were divided into three groups: normal glucose group ( NG ), high glucose group( HG), and mannitol group(MG). The expression of angiotensin-converting enzyme( ACE ) and ACE2 mRNA in HK-2 cells was detected. The concentration of angiotensin Ⅱ ( Ang Ⅱ ) in the culture medium was detected. The mRNA and protein expression of ACE and ACE2 existed in normal cultured HK-2 ( NG group ). In comparison with NG group, the mRNA and protein expressions of ACE in HG group increased significantly ( P<0. 01 ), and the expression of ACE2 mRNA decreased significantly( P<0. 01 ). The level of Ang Ⅱ in HG group was significantly higher than in NG group( P<0. 05 ). The result show that high glucose may induce ACE expression and inhibit ACE2 expression, then promote synthesis of Ang Ⅱ in proximal tubular cells.
4.Comparative study of cerebrospinal fluid flow in the cerebral aqueduct between empty sella syndrome and normal volunteer
Weidong HU ; Li XIANG ; Tianjun GAO ; Hongguang ZHANG ; Xiurong WANG
Chinese Journal of Postgraduates of Medicine 2011;34(1):9-12
Objective To compar the cerebrospinal fluid (CSF) flow between empty sella syndrome (ESS) and normal volunteer in the cerebral aqueduct with MRI in phase contrast cine mode. Methods Thirty-eight ESS patients (ESS group) and 38 normal volunteers (control group ) were involved in this study.The aqueduct CSF flow image was positioned perpendicularly to the midbrain aqueduct at the middle sagittal T1WI or T2WI image. The waveforms were analyzed for the flow direction, flow rate, flow volume rate and cardiac cycle. Results The CSF flow of the aqueduct in control group and ESS group had two directions which was downward flow during the systolic period and upward flow during the diastolic period of the cardiac cycle. The.systolic period downward peak flow rate, diastolic period upward peak flow rate, mean downward flow rate, mean upward flow rate and mean flow rate were (5.231 ± 0.262), (4.902 ± 0.281 ),(3.083 ± 0.191 ), (3.032 ± 0.151 ), (3.151 ± 0.162) cm/s in control group, and (6.244 ± 0.356), (6.091 ±0.430), (3.916 ± 0.196), (3.812 ± 0.273 ), (3.690 ± 0.291 ) cm/s in ESS group respectively,and there was no significant difference between the two groups ( P > 0.05 ). The systolic period downward peak flow volume rate, diastolic period upward peak flow volume rate, mean downward flow volume rate,mean upward flow volume rate and mean flow volume rate were (0.050 ± 0.003 ), (0.050 ± 0.004), (0.030± 0.002), (0.031 ±0.002), (0.030 ± 0.003 ), ( 0.004 ± 0.001 )ml/s in control group, and (0.058 ± 0.003 ), (0.063 ± 0.005),(0.039 ±0.002), (0.038 ±0.003), (0.038 ±0.003), (0.004 ±0.001) ml/s in ESS group respectively,and there was no significant difference between the two groups(P > 0.05 ). The correspond cardiac cycle of systolic period downward peak flow rate, correspond cardiac cycle of diastolic period upward peak flow rate, mean cardiac cycle were (40.890 ± 37.096), (501.026 ± 19.374), (719.511 ± 14.946) ms in control group,and (35.921 ±6.218), (531.553 ± 16.764), (770.700 ±21.579) ms in ESS group,and there was no significant difference between the two groups (P > 0.05 ). Conclusion Part of CSF flows into the area of saddle in ESS patients, but it has no effect on CSF indexes in area of cerebral aqueduct.
5.In vitro experimental study of novel porphyrin-typed photosensitizer photodynamically treating hepatic carcinoma
Jinxing CHEN ; Ge HONG ; Lijing GAO ; Tianjun LIU
International Journal of Biomedical Engineering 2014;37(5):283-286,294,封3
Objective To study the photodynamic therapy (PDT) mediated by a novel porphyrin-typed photosensitizer on human hepatic carcinoma HepG2 cell and the mechanisms.Methods Experiments were derided into four groups:control group,PDT group,photosensitizer group and photosensitizer+PDT group.The photostability of novel photosensitizer upon repetitive illumination was evaluated by bleaching method,and cell survival rate was determined by MTT assay.Cellular uptake of novel photosensitizer was measured with luminescence spectrometer,and cellular localization ofphotosensitizer was observed by laser scanning confocal microscopy (LSCM).Furthermore,apoptotic cell was detected with Hoechst 333342 staining.Results Novel photosensitizer was stable after repetitive light irradiation,and PDT or photosensitizer alone showed no dark cytotoxicity toward HepG2 cell (P>0.05),but intense killing was observed in photosensitizer+PDT group (P<0.05).The IC50 is 1.21 μmol/L.Cellular uptake of novel photosensitizer was concentration-dependent and the highest uptake is at concentration of 12.5 μmol/L.Novel photosensitizer localizes in lysosomes of HepG2 cell,and the death mode of HepG2 cell was mainly apoptosis.Conclusions Novel photosensitizer exerts profound cytotoxic effects on HepG2 cell mainly through the initiation of secondary cell apoptosis by lysosome destruction.
6.A prospective study on indwelling suture in preventing re-adhesion of fallopian tube after interventional recanalization
Tianjun GAO ; Duanying GUO ; Meili XU ; Hongguang ZHANG ; Zhiyong XU ; Lilan LIU ; Yi FAN ; Mingwu LOU
Chinese Journal of Radiology 2015;(9):675-678
Objective To explore the clinical efficacy of indwelling suture in preventing re-adhesion of fallopian tube after fallopian tube recanalization(FTR). Methods Screen 93 patients with fallopian tube obstruction and FTR indications of prospective, the patients without other interference factors of infertility, they were randomized with random sampling into two groups (treatment group 50 and control group 43)and treated by FTR,then the treatment group with indwelling sutures in fallopian tube for 3 days, the control group were infused lipiodol into the tube and with a intrauterine cavity perfusion in 3 days. The two groups received followed up examination at 2,6 months after operation ( a treatment was repeated with the case of re-obstruction) . Follow-up for 12 months to appraise the pregnancy rate and the influence of pregnancy competence of tube with indwelling suture(6 months after operation, to collect and compare the pregnancy rate and ectopic pregnancy rate of patent tube in two groups). Results The tubal patency rate were 89.8%(53/59),89.5%(51/57)of treatment group at 2,6 months after operation and the control group were75.9%(44/58),75.0%(39/52), there was a significant difference between the two groups(2 m:χ2=4.027, P<0.05;6 m:χ2=3.958,P<0.05). One year after operation,the pregnancy rate of treatment group was 43.2%(16/37) , the control group was 20.6%(7/34) ,there was a significant difference(χ2=4.152,P<0.05). Six
months after operation, the pregnancy rate and ectopic pregnancy rate of patent tube in treatment group were 21.6%(11/51),2/11, the control group were15.4%(6/39),1/6, there was no significant difference between them(pregnancy rate:χ2=0.552,P>0.05). Conclusions The indwelling suture of fallopian tube can prevent re-adhesion better after FTR, then improve the long-term recanalization rate and the pregnancy rate. There is no change on the pregnancy competence of fallopian tube.
7.Angiographic diagnosis and therapeutic embolization of Dieulafoy disease
Tianjun GAO ; Donghai WU ; Hongguang ZHANG ; Zhiyong XU ; Lilan LIU ; Yi FAN ; Mingwu LOU
Chinese Journal of Radiology 2015;(2):130-132
Objective To evaluate the clinical efficacy of interventional techniques in the diagnosis and therapy of Dieulafoy disease. Methods A retrospective study was performed, including 17 patients with massive upper gastrointestinal hemorrhage (patients without peptic ulcer and portal hypertension or diagnosed with Dieulafoy disease by endoscopic examination). All patients had both DSA and interventional embolization treatment, and were followed for 12 months to appraise the clinical effectiveness. Results Sixteen patients were diagnosed as Dieulafoy disease by using DSA. Fifteen of the 16 patients were treated with embolization successfully withoutserious complications. One patient received subtotal gastrectomy because of upper gastrointestinal hemorrhage recurrence. Nine patients with irregular upper abdominal pain and burning sensation had complete remission after symptomatic management. Fifteen patients who had embolization showed no serious complications during the follow-up period of 12 months, there was no hematemesis and melena for the 15 cases with successful embolization. Conclusion The angiography and embolization are safe and efficacious in the diagnosis and therapy of Dieulafoy disease.
8.Efficacy and safety of colistimethate sodium in critical patients: anin vitro study by using of Monte Carlo simulation
Aijun PAN ; Qing MEI ; Tianjun YANG ; Xiaolan GAO ; Huaiwei LU ; Ying YE ; Jiabin LI ; Bao LIU
Chinese Critical Care Medicine 2017;29(5):385-389
Objective To evaluate the efficacy and safety of colistimethate sodium (CMS) for the treatment of critical patients infected by pan-drug resistantAcinetobacter baumannii (PDR-AB) or pan-drug resistant Pseudomonas aeruginosa (PDR-PA).Methods 321 isolates of PDR-AB and 204 isolates of PDR-PA from critical patients admitted to 35 intensive care units (ICUs) of grade two or above were collected from the Anhui Antimicrobial Resistance Investigation Net (AHARIN) program from September 2012 to September 2015, while the minimal inhibitory concentrations (MIC) of colistin were determined by the E-test. A series of Monte Carlo simulations was performed for CMS regimens (1 MU q8h, 2 MU q8h, and 3 MU q8h, and MU meant a million of unit), and the probability of achieving a 24-hour area under the drug concentration time curve (AUC24)/MIC ratio > 60 and risk of nephrotoxicity for each dosing regimen was calculated. Each simulation was run over three CLCr ranges: < 60, ≥ 60-90, ≥ 90-120 mL/min. The probability of target attainment (PTA)for the AUC24/MIC ratio was calculated using the partial MIC value, while the cumulative fraction of response (CFR) was determined by integrating each PTA with the MIC distributions, the value greater than or equal to 90% or more than 80% was set as the optimal dosing regimen or suboptimal dosing regimen respectively. The probability of average 24-hour serum concentrations up to 4 mg/L for three dosage regimens was used to predict the risks of nephrotoxicity.Results All 321 isolates of PDR-AB and 204 isolates of PDR-PA were susceptible to colistin, the MIC50/90 against PDR-AB were 0.5mg/L and 1.0 mg/L, and those against PDR-PA were 0.5 mg/L and 1.5 mg/L, respectively. When recommended dose (1 MU q8h) was used for patients with CLCr of < 60 mL/min, high CFR value (89.78% for PDR-AB, 81.06% for PDR-PA) were obtained, but with a high risks of nephrotoxicity (> 32.51%). Moreover, low value of PTA (< 66.56%) was yielded for isolates with MIC of ≥ 1 mg/L. Recommended dose also yielded a low CFR value (56.97%-69.31% for PDR-AB, 44.76%-56.94% for PDR-PA) in patients with CLCr of ≥ 60-120 mL/min. When dose was increased to 2 MU q8h, CFR (77.45%-92.87%) and the risks of nephrotoxicity (< 0.15%) was optimal for patients with CLCr ≥ 60-120 mL/min, but low value of PTA (< 75.36%) was also yielded for isolates with MIC of ≥ 1 mg/L. The most aggressive dose of 3 MU q8h provided high CFR (> 89.24%) even in patients with CLCr ≥ 90-120 mL/min, and PTA was < 76.20% only for isolates with MIC of ≥ 1.5 mg/L, but this dosing scheme was associated with unacceptable risks of nephrotoxicity (> 33.68%).Conclusion Measurement of MIC, individualized CMS therapy and therapeutic drug-level monitoring should be considered to achieve the optimal drug exposure and ensure the safety of CMS.
9.The Correlation between MR Perfusion Imaging and Pathology in Rabbit VX2 Liver Cancer before and after TACE
Yi FAN ; Jinghua LIU ; Tianjun GAO ; Bing LIANG ; Zhehui LIU ; Yong LI ; Mingwu LOU
Chinese Journal of Clinical Oncology 2009;36(23):1365-1366,1369
Objective: To study the correlation between MR perfusion imaging and pathology after transcatheter arterial chemoembolization (TACE) using VX2 liver cancer model and to provide a theoretical basis to evaluate the curative effect of TACE. Methods; Fifteen New Zealand white rabbits (weight: 2.5-3.0kg) were randomly divided into three groups, with 5 in each group (group 1, pre-TACE; group2, 3 days after TACE; group 3,1 week after TACE). The rabbit VX2 hepatic carcinoma models were presented in all rabbits. All of the three groups received TACE at three weeks after the tumor was implanted. The MR perfusion imaging was performed before chemoembolization, at 3 days and 1 week after chemoembolization respectively for group 1, 2 and 3. Each animal was then sacrificed for pathology observation after MR examination. Results: The lesions assessed before TACE were hyperintense compared with the surrounding liver parenchyma on DWI images. The volume of neoplastic cells became large. Nucleus was hypertrophic with different size and shape. Phase of nucleous mitosis showed in many cells and necrosis was hardly seen. No obvious difference was found between the peripheral area and the core area. At 3 days after TACE, the heterogeneous hypo-intense was observed on DWI images. Many nuclear fragmentation and caryolysis appeared on pathology. Neoplasm necrosis was seen. At 1 week after TACE, the heterogeneous hypo-intense areas became larger. Light microscopy showed incomplete necrosis. There were increased karyopycnosis and nuclear fragmentation. Conclusion: MR perfusion imaging of VX2 liver cancer corresponds well with pathology and can reflect the outcome of liver cancer after TACE.