Objective To explore the role of tissue inhibitor of metalloproteinase-1(TIMP-1) during renal senescence by using human TIMP-1 transgenic mice.Methods Renal histological changes of wild type mice and transgenic mice at the age of 3,12,24 months were observed by periodic acid-schiff(PAS)staining of paraffin sections.The numbers of F4/80 positive cells were detected by immunofluoreseence.The protein expressions of TIMP-1,TIMP-2,matrix metalloproteinase(MMP)-9,MMP-2,intercellular adhesion molecule-1(ICAM-1),transforming growth factor?1(TGF-?1),collagenⅢand collagenⅣwere detected by Western blot.The activities of gelatinases and TIMP-1 were examined by gelatin zymography and reverse zymography respectively.Results Focal renal fibrosis was found in two genotypes with aging.At the age of 24 months,compared with wild type,in kidneys of transgenic type,the expressions and activities of gelatinases were dowregulated (MMP-2:2.08?0.20 vs.3.39?0.43;MMP-9:4.02?0.82 vs.6.72?1.40,all P＜0.05);the expressions of collagenⅢ,collagenⅣ,ICAM-1,and TGF-?1 were upragulated(0.72+0.11 vs.0.57?0.09;0.84?0.13 vs.0.6?0.11,0.72?0.12 vs.0.53?0.07; 0.69?0.12 vs.0.45?0.09,all P＜0.05),and the numbers of F4/80 positive cells were increased (18.8?4.4 vs.12.7?3.6,P＜0.05)with the upregulated expression and activity of TIMP-1(1.10?0.18 vs.0.62?0.09;50.75?7.25 vs.20.64?3.50,P＜0.05).Conclusions TIMP-1 could promote age-related renal fibrosis through enhancing inflammation reaction by ICAM-1 upregulation.

OBJECTIVETo explore the pathological basis of diffusion-weighted imaging (DWI) findings in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE).

METHODSDWI was performed in 15 patients with HCC treated by TACE within 24 - 48 hours before II-phase operation. The DWI findings of the liver lesions were analyzed and correlated with pathological findings including macroscopic observation, HE staining and immunohistochemical staining for bFGF.

RESULTS(1) The viable tumor area showed mostly hypersignal intensity (12/15), whereas coagulative necrotic lesions showed hyposignal (8/15) or isosignal intensity (6/15). The ADC values of zones of viable tumor and necrosis in tumor were (1.42 +/- 0.16) x 10(-3) mm(2)/s and (1.58 +/- 0.18) x 10(-3) mm(2)/s, respectively. There was a significant difference of ADC values between the two zones (t = 2.618, P < 0.05). (2) There was a significant difference in ADC values of viable tumor between well and poorly differentiated tumors (t = -2.646, P < 0.05). The distinction of ADC values of the whole tumor was significant among tumors with different degree of necrosis (chi(2) = 7.236, P < 0.05). (3) A negative correlation was observed between bFGF protein expression index and ADC values of viable parts of the tumors in the study group (r = -0.552, P = 0.033).

CONCLUSIONDWI shows certain characteristic features of the HCC after TACE, and can be used to distinguish viable and necrotic tumor tissues in HCC after TACE.

Adolescent ; Adult ; Carcinoma, Hepatocellular ; metabolism ; pathology ; therapy ; Chemoembolization, Therapeutic ; Cisplatin ; administration & dosage ; Diffusion Magnetic Resonance Imaging ; methods ; Female ; Fibroblast Growth Factor 2 ; metabolism ; Fluorouracil ; administration & dosage ; Humans ; Iodized Oil ; therapeutic use ; Liver Neoplasms ; metabolism ; pathology ; therapy ; Male ; Middle Aged ; Mitomycin ; administration & dosage ; Young Adult

OBJECTIVETo evaluate the value of human fatty acid binding protein (h-FABP) in predicting myocardial ischemia and injury in the perioperative period of cardiac surgery, we observed the dynamic changes of h-FABP in perioperative period of patients underwent coronary artery bypass grafting and ventricular septal defects repairing surgery, and evaluated the relationship of h-FABP and ischemia modified albumin (IMA), CK-MB, cTnI.

METHODSPatients underwent coronary artery bypass grafting (n=30) and ventricular septal defect repairing (n=30) surgery between February 2008 and December 2008 were included in this study. Venous blood sample was obtained at preoperative, aortic clamping, aortic unclamping of 10 min, 2 h, 6 h, 12 h, 24 h for the measurements of h-FABP, IMA, cTnI and CK-MB.

RESULTSh-FABP and IMA changed in the same way at various examined time points, h-FABP changes also paralleled cTnI and CK-MB changes, h-FABP peaked early during myocardial ischemia and injury and returned to baseline level at 2 h post myocardial ischemia and injury. Linear correlation analysis showed that the peak value of h-FABP was positively correlated with IMA, CK-MB and cTnI in both CABG group (r = 0.948, 0.964 and 0.961, P < 0.05) and in the VSD group (r = 0.986, 0.978 and 0.957).

CONCLUSIONSh-FABP is an early diagnostic parameter reflecting perioperative myocardial ischemia and injury in cardiac surgery. Quantitative h-FABP monitoring could predict the severity of myocardial ischemia and injury early during cardiac surgery.

Aged ; Albumins ; analysis ; Biomarkers ; blood ; Creatine Kinase, MB Form ; blood ; Fatty Acid-Binding Proteins ; blood ; Humans ; Middle Aged ; Myocardial Ischemia ; diagnosis ; surgery ; Myocardium ; metabolism ; Perioperative Period ; Predictive Value of Tests ; Thoracic Surgery ; Troponin I ; blood

BACKGROUNDThe autosomal dominant form of retinitis pigmentosa (ADRP) can be caused by mutations in 14 genes and further loci remains to be identified. This study was intended to identify mutations in a Chinese pedigree with ADRP.

METHODSA large Chinese family with retinitis pigmentosa was collected. The genetic analysis of the family suggested an autosomal dominant pattern. Microsatellite (STR) markers tightly linked to genes known to be responsible for ADRP were selected for linkage analysis. Exons along with adjacent splice junctions of PRPF31 were amplified by polymerase chain reaction (PCR) and screened by direct sequencing.

RESULTSThe caused gene of ADRP was mapped to 19q13.4 between markers D19S572 and D19S877, with a maximum LOD score of 3.01 at marker D19S418 (recombination fraction = 0).

CONCLUSIONThe affected gene linked to the 19q13.4 in a Chinese family with ADRP, which is different from other mutations at the same loci in other Chinese families.

Asian Continental Ancestry Group ; genetics ; Chromosome Mapping ; DNA Mutational Analysis ; Exons ; genetics ; Eye Proteins ; genetics ; Female ; Genotype ; Humans ; Male ; Microsatellite Repeats ; genetics ; Pedigree ; Polymerase Chain Reaction ; Retinitis Pigmentosa ; genetics

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Logistic Models ; Lung Diseases, Interstitial ; diagnostic imaging ; Male ; Radiography, Thoracic ; methods ; Tomography, X-Ray Computed ; methods

OBJECTIVETo evaluate the outcome of endovascular stent graft placement in patients with acute thoracic aortic syndromes.

METHODSEmergency stent-graft implantations were performed in 57 patients with acute thoracic aortic syndromes from May 2001 to December 2005 (45 Stanford B aortic dissections, 9 acute penetrating aortic ulcers or pseudoaneurysms. 3 traumatic thoracic aneurysms). The clinical data, efficacy and follow-up results were analyzed.

RESULTSProcedures were successful in all patients. Type I endoleaks were evidenced in 5 patients and ascending aortic dissection occurred in 1 patient during operation, 5 patients with acute penetrating aortic ulcer complicating with coronary artery disease received successful PCI immediately post endovascular stent graft placement. Adynamia in extremities occurred in 1 patient and recovered two days later post anisodamine and mcnicol treatments. Left vertebral artery ischemia was found in 1 patient due to coated subclavian artery by stent-graft and the patient recovered spontaneously after two days lethargy without special treatment. The mean ICU time after surgery was 3.5 days (1 - 8 days) and the mean hospitalization time was 10 days. The mean follow-up time was 25.30 +/- 13.1 months (1 - 47 months). Two patients died within 30 days after operation, 1 patient died of rupture of the ascending aortic dissection (7 days post operation), 1 patient died of acute renal failure at the 2nd day post operation. One patient died of empsyxis 3 months after procedure, 1 patient died at the 4th month post procedure for unknown reason, 1 patient received second stent-graft implantation because of a newly formed endoleak at the proximal end of the stent-graft, 5 patients received second stent-graft implantation because of newly formed leaks at the remote end of the stent-graft. No paraplegia or stent migration or stenosis was observed during the follow up period. Total mortality during hospitalization and follow-up was 7.0%.

CONCLUSIONPatients with acute thoracic aortic syndrome could be effectively and safely treated by coated stent-graft endovascular placement.

Acute Disease ; Adult ; Aged ; Aged, 80 and over ; Aneurysm, Dissecting ; surgery ; Aneurysm, False ; surgery ; Aorta, Thoracic ; Aortic Aneurysm, Thoracic ; surgery ; Blood Vessel Prosthesis Implantation ; methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Stents ; Syndrome

OBJECTIVEDiscussing the natural history and the influencing factors of HIV infection among former commercial blood and plasma donors engaged in unsafe blood donation practices in China.

METHODSUsing ambispective cohort study, with data obtained from ten counties (districts) from six provinces in the National AIDS Control Demonstration Area. HIV/AIDS cases were found and confirmed prior to July 24, 2006 being former commercial blood. Plasma donors were selected and data regarding infection, incidence, death, and influencing factors was collected. Analysis was performed using SPSS 12.0 statistical analysis software.

RESULTS(1) In 7551 cases of HIV infection, there were 6533 typical progressors (86.52%, 4757 cases of AIDS), 108 rapid progressors (1.43%), 910 long-term non-progressors (12.05%) with 4865 cases progressed to AIDS (64.43%). The median incubation period for HIV progression to AIDS was nine years (95% CI:8.96-9.04). (2) According to data, from a total of 1157 AIDS cases without ARV therapy (23.78% of total AIDS cases), there were 283 confirmed AIDS-related deaths, of which the median survival time was 6 months (95% CI:4-7) and the two and three year fatality rates were 95% and 99%, respectively. (3) The duration of HIV incubation period was irrespective to gender and age at the time of HIV infection (P > 0.05). Length of survival for untreated AIDS showed correlation to gender (P < 0.05) but no correlation with culture, marital status or age at the time of diagnosis of AIDS (P > 0.05).

CONCLUSIONCompared with the UNAIDS theory regarding slow disease progressors among adults, our study showed a longer AIDS incubation period and shorter outlook for untreated survival, but a similar incubation period for other routes of HIV infection.

Acquired Immunodeficiency Syndrome ; epidemiology ; mortality ; Adolescent ; Adult ; Aged ; Blood Donors ; statistics & numerical data ; China ; Female ; HIV Infections ; epidemiology ; mortality ; Humans ; Infectious Disease Incubation Period ; Male ; Middle Aged ; Young Adult

Objective:To investigate the protective effect of Yiqi Huoxue recipe on rats with cerebral ischemia injury by using oxidative stress injury as an entry point. Method:SD rats were randomly divided into model group, sham operation group, nimodipine group (20 mg·kg^-1), Yiqi Huoxue recipe high, medium and low dose group (2.916,1.458,0.729 g·kg^-1). After 14 days of stomach, acute cerebral ischemic injury model was established by ligation of bilateral common carotid arteries. Ultrasound of synapse was observed by transmission electron microscopy. Total superoxide dismutase (T-SOD) and dialdehyde (MDA), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), horizontal adenine nucleoside triphosphate (ATP) levels were detected by biochemical method. Western blot and Real-time PCR was used to determine the expression of heme oxygenase-1(HO-1) and nuclear factor E₂-related factor 2 (Nrf2) protein and mRNA in the ischemic cortex of rats. Result:Transmission electron microscopy showed that Yiqi Huoxue recipe had a significant improvement on the degree of cerebral ischemic injury. Compared with sham operation group, MDA levels in the brain homogenate of model group increased significantly, T-SOD and GSH-Px levels were significantly decreased (P<0.01). The activity of LDH, Na⁺-K⁺-ATP ase, Ca²⁺-Mg²⁺-ATP ase and ATP was significantly decreased (P<0.05,P<0.01). The levels of HO-1 and Nrf2 protein and the expression of HO-1 and Nrf2 mRNA in brain tissue were significantly decreased (P<0.01). Compared with model group, the medium and high dose group of Yiqi Huoxue recipe significantly decreased MDA content in brain tissue and increased the levels of T-SOD and GSH-Px(P<0.05,P<0.01). Yiqi Huoxue recipe high dose group can significantly increase LDH, Na⁺-K⁺-ATP ase, Ca²⁺-Mg²⁺-ATP ase and total ATP activity(P<0.05,P<0.01). The contents of HO-1 and Nrf2 protein in the brain of rats with middle and high-dose Yiqihuoxue recipe group were significantly increased(P<0.05,P<0.01). The expressions of HO-1 and Nrf2 mRNA in high-dose Yiqi Huoxue recipe group were significantly increased(P<0.05,P<0.01). Conclusion:Yiqi Huoxue recipe may protect against cerebral ischemic injury by inhibiting oxidative stress through Nrf2/HO-1 signaling pathway.

OBJECTIVE: To establish an efficient protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into functional midbrain dopaminergic progenitor cells (DAPs) in vitro. METHODS: hiPSCs were induced to differentiate into DAPs in two developmental stages. In the first stage (the first 13 days), hiPSCs were induced into intermediate cells morphologically similar to primitive neuroepithelial cells (NECs) in neural induction medium containing a combination of small molecule compounds. In the second stage, the intermediate cells were further induced in neural differentiation medium until day 28 to obtain DAPs. After CM-DiI staining, the induced DAPs were stereotactically transplanted into the right medial forebrain bundle (MFB) of rat models of Parkinson's disease (PD). Eight weeks after transplantation, the motor behaviors of PD rats was evaluated. Immunofluorescence assay of brain sections of the rats was performed at 2 weeks after transplantation to observe the survival, migration and differentiation of the transplanted cells in the host brain microenvironment. RESULTS: hiPSCs passaged stably on Matrigel showed a normal diploid karyotype, expressed the pluripotency markers OCT4, SOX2, and Nanog, and were positive for alkaline phosphatase. The primitive neuroepithelial cells obtained on day 13 formed dense cell colonies in the form of neural rosettes and expressed the neuroepithelial markers (SOX2, Nestin, and PAX6, 91.3%-92.8%). The DAPs on day 28 highly expressed the specific markers (TH, FOXA2, LMX1A and NURR1, 93.3-96.7%). In rat models of PD, the hiPSCs-DAPs survived and differentiated into TH⁺, FOXA2⁺ and Tuj1⁺ neurons at 2 weeks after transplantation. Eight weeks after transplantation, the motor function of PD rats was significantly improved as shown by water maze test (P < 0.0001) and apomorphine-induced rotation test (P < 0.0001) compared with rats receiving vehicle injection. CONCLUSION HiPSCs can be effectively induced to differentiate into DAPs capable of differentiating into functional neurons both in vivo and in vitro. In rat models of PD, the transplanted hiPSCs-DAPs can survive for more than 8 weeks in the MFB and differentiate into multiple functional neurocytes to ameliorate neurological deficits of the rats, suggesting the potential value of hiPSCs-DAPs transplantation for treatment of neurological diseases.
Humans ; Rats ; Animals ; Induced Pluripotent Stem Cells ; Cell Differentiation/physiology* ; Neurons ; Parkinson Disease ; Mesencephalon ; Cells, Cultured

This study aimed to propose an operational definition of late-onset hypogonadism (LOH) that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China. A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured and free testosterone (cFT) was calculated. The Aging Males' Symptoms (AMS) scale was used to evaluate the LOH symptoms. Finally, 5078 men were included in this analysis. The TT levels did not decrease with age (P = 0.59), and had no relationship with AMS symptoms (P = 0.87 for AMS total score, P = 0.74 for ≥ 3 sexual symptoms). The cFT levels decreased significantly with age (P < 0.01) and showed a negative association with the presence of ≥ 3 sexual symptoms (P = 0.03). The overall estimated prevalence of LOH was 7.8% (395/5078) if a cFT level <210 pmol l