BACKGROUND: D-galactose-induced aging animal model is similar tohuman natural aging. Whether the expression of protein phosphatase-1(PP-1) in the brain of D-galactose-induced aging mice is related to cerebralaging process or not should be researched further. OBJECTIVE: To investigate the effect of the APP17 peptide and theliquid extract ofjiunao yizhi capsule on regulating the expression of PP-1 inhippocampal neurons of the aging mice induced by the D-galactose (D-gal). DESIGN: A random controlled study. SETTING: Department of Pathology, College of Basic Medical Sciences, Capital University of Medical Sciences and Beijing Research Laboratory forBrain Aging, Xuanwu Hospital of Capital University of Medical Sciences. MATERIALS: The study was completed between July 2003 and July2004 in the Experimental Center of Capital University of Medical Sciences. Forty male Kunming mice (SPF grade) with a body mass fron 28 g to 32 gwere purchased from Chinese Academy of Medical Sciences Institute ofMaterial Medical.METHODS: Kunming mice were randomly divided into 5 groups: control group, D-gal group, APP17 peptide treatment group, low dose herb treatment group, and high dose herb treatment group with 8 mice in each group. In Dgal group, APP17 peptide treatment group, low dose herb treatment group and high dose herb treatment group, galactose was injected subcutaneously (50 nmg/kg). Meanwhile, 0.1 mL normal saline containing 0.35 μg of APP17 peptide was injected subcutaneously into the mice in APP17 peptide treatment group, once a day for 3 months; liquid extract of jiunao yizhi capsule (provided by Beijing Chaoyangmen Hospital and Shanxi Quwo Traditional Medical Institute; the main component: dangshen, baizhu, guijia and chuanshanjia, etc.) was perfused by stomach (0.3 g/kg and 1.0 g/kg respectively) in low dose herb treatment group and high dose herb treatment group, once a day. And equivalent normal saline was injected and perfused in the two control groups. After 3 months of survival, the mice were killed and their brains were cut into sections. The immunohistochemical staining of these sections was then performed with PP-1 antibody.MAIN OUTCOME MEASURES: The results of immunohistochemical staining analysis of PP-1.RESULTS: Forty mice entered the final analysis without any loss. PP-1 positive cells in the hippocampus were poorly stained in the D-gal mice. In contrast, PP-1 positive neurons were widely distributed in the hippocampus of those normal mice, the APP17 peptide-treated D-gal mice and the high liquid extract of raw herb-treated D-gal mice. These cells were darkly stained in cytoplasm. The unexpected result was that in the low liquid extract of raw herb-treated D-gal mice the number of PP-1 positive neurons did not increase to normal.CONCLUSION: The results demonstrated that the expression of PP-1 decreased in the hippocampus of D-gal mice. The APP17 and low dose liquid extract of raw herbs can regulate the distribution of PP-1 in the brain of D-gal mice and make them recover to normal situation.

BACKGROUND: In brain insulin does its work through the insulin receptor substrate (IRS). Amyloid beta protein precursor 17 (APP17) peptide has the neurotrophic function, which may improve diabetic encephalopathy resulted from insulin deficiency by affecting insulin receptor substrate.OBJECTIVE: The mouse diabetic model was produced to observe the effect of APP17 peptide on the distribution of IRS-1 in brain tissues.DESIGN: Randomized control animal experiment.SETTING: Staff Room of Pathology, College of Basic Medical Sciences,Capital University of Medical Sciences; Beijing Research Laboratory for Brain Aging of Xuanwu Hospital.MATERIALS: The experiment was performed in Staff Room of Pathology,College of Basic Medical Sciences, Capital University of Medical Sciences and Beijing Research Laboratory for Brain Aging of Xuanwu Hospital from September to October 2003. Totally 18 male kunming mice were employed,and randomly assigned into control group, diabetic group and APP17 peptide treatment group with 6 mice in each group.METHODS: ①The mice were subjected to intraperitoneal injection of streptozotocin (STZ, Sigma) by 200 mg/kg, and 3 days later, the tail blood was sampled to examine non-fasting blood glucose, and the blood glucose over 15 mmol/L was set as the criteria for successful diabetic model establishment. ②In APP17 + diabetes mellitus group, the mice received subcutaneous injection of 0.35 μg APP17 peptide once daily for 2 weeks. The mice in the normal control group were not interfered. ③Then brain was removed and crystat sections were prepared. Immunohistochemical staining was done for IRS-1 at four weeks after giving streptozotocin.MAIN OUTCOME MEASURES: Pattern and distribution of IRS-1 positive cells of mice in each group.RESULTS: Totally 18 mice were involved in the result analysis. ①In the brains of diabetic mice the IRS-1 immunohistochemical positive cells distributed at cortex, hippocampus, thalamus, hypothalamus and so on, while the positive cells distributed only at cortex and hippocampus in the normal control group and APP17 peptide treatment group, lightly stained. ②Numbers of immunohistochemical positive cells of IRS-1 of cerebral hippocampus in the diabetic group, normal control group and APP17 peptide treatment group were (28.7±1.5), (9.2±1.5), (10.1±1.4) piece per 10 power object lens, and that in the diabetic group was higher than that in the other two groups (P ＜ 0. 001 ). CONCLUSION: Neurons in many regions of brains of diabetic mice have plenty of IRS-1 positive cells. APP17 peptide can make part and quantity of IRS-1 positive cells normality so as to ameliorate the degeneration of hippocampal neurons of diabetic mice.

Objective To investigate the relationships of pulmonary arterial pressure (PAP) with serum protein S100B, cytokines and plasma procalcitonin (PCT) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods A prospective controlled study was conducted, 160 subjects admitted in the Critical Care Medicine and Respiratory Disease Departments in the Affiliated Hospital of Shanxi Medical University/Changzhi Municipal People's Hospital from January 2012 to August 2013 were enrolled in the study, including 80 patients with AECOPD (AECOPD group) and 80 COPD under stable condition (SCOPD group). Meanwhile 100 healthy people having passed physical examinations were chosen as healthy control group. The levels of blood routine and plasma PCT were examined, PAP was evaluated by modified Simpson, sequation with echocardiography, serum S100B was measured by radioimmunoassay, and enzyme linked immunosorbent assay (ELISA) was used to measure interleukins (IL-18, IL-1β) and tumor necrosis factor-α(TNF-α). The linear correlation analysis was carried out for the various indicators. Results The gender and age in different groups were matched. Compared with the healthy control group, the levels of white blood cell count (WBC), ratio of neutrophil granulocyte (PMN), PAP, PCT and S100B, IL-18, IL-1β, and TNF-αwere significantly higher in SCOPD and AECOPD groups [WBC (×109/L):0.84±0.22, 1.94±0.64 vs. 0.73±0.12, PMN: 0.70±0.09, 0.85±0.08 vs. 0.54±0.05, PAP (mmHg, 1 mmHg = 0.133 kPa): 39±5, 47±8 vs. 24±5, PCT (μg/L): 0.41±0.08, 6.35±2.14 vs. 0.11±0.01, S100B (μg/L): 0.081±0.017, 0.101±0.028 vs. 0.041±0.011, IL-18 (ng/L): 162±19, 181±27 vs. 112±19, IL-1β(ng/L): 55±12, 75±14 vs. 34±10, TNF-α(ng/L):67±17, 89±18 vs. 35±17, all P<0.05], and the increase in level of indexes was more significant in AECOPD group than that in the SCOPD group (all P < 0.01). Serum S100B was significantly positively correlated with PCT, IL-18, PMN and PAP (r value was 0.36, 0.41, 0.39, 0.35, all P<0.05), and plasma PCT was also significantly positively correlated with PMN and PAP (r value was 0.41, 0.37, both P<0.05). Conclusion The level of serum S100B might have positive obvious correlation to the changes of plasma PCT, cytokines and PAP.

ObjectiveTo observe the influence of medical exercise on rehabilitation of patients suffering from chronic obstructive pulmonary disease (COPD).Methods26 COPD patients who were organized in the form of training class practised medical exercise for three months. Respiratory function, exercise capacity and psychological health level were assessed respectively before and after exercise.ResultsValues of forced vital capacity(FVC), forced expiratory volume in one second (FEV1), FVC% , FEV1/ FVC and 6-minute walking distance (6MD) were significantly higher after medical exercise than before(P<0.01). Anxiety and depression scores also notably dropped after medical exercise than before(P<0.01).Conclusions Medical exercise can remarkably improve respiratory and moving capacity and decrease anxiety and depression of patients suffering from chronic obstructive pulmonary disease.

Objective To investigate the expression of vitronectin (VN) in placental basal plate and its relationship with the pathogenesis of severe preeclampsia.Methods From March 2010 to December 2011,17 patients with early-onset severe preeclampsia who delivered in the Second Hospital of Jilin University were recruited as the early-onset severe preeclampsia group; and 16 women were recruited as the late-onset severe preeclampsia group.Meanwhile,15 healthy pregnant women who delivered before 34 weeks were defined as the early control group (termination of pregnancy was carried out because of fetal heart malformations),and 15 healthy pregnant women delivered after 34 weeks were defined as the late control group.Imnunohistochemistry and semi-quantitative reverse transcription (RT)-PCR were used to investigate the expression of VN protein and mRNA in the placental infarct center and its surrounding tissue of placental basal plate.The levels of serum prothrombin time (PT),part thromboplastin time (APTT) and fibrinogen (FIb) were detected and the international normalized ratio (INR) was calculated.The correlation of abnormal coagulation markers and VN expression levels in the early-onset severe preeclampsia group and the early control group was studied.Results (l) VN protein was detected in all placental basal plate of the four groups.It was highly expressed in the necrotic tissue of placental infarct center and weakly expressed in the tissue far from the infarcted area.(2) The mean levels of VN protein expression in placental basal plate of the early-onset severe preeclampsia group,the late-onset severe preeclampsia group,the late control group and the early control group were 0.152 ± 0.019,0.113 ± 0.023,0.095 ± 0.014 and 0.055 ± 0.010,respectively.And the differences between the groups were statistically significant (P ＜ 0.01).The VN protein expression in placental infarct center,infarct edge,peri-infarct tissue and tissue far from the infarcted area gradually reduced,and the differences were statistically significant (P ＜ 0.01).Compared with the same areas of each group,the differences were not statistically significant (P ＞ 0.05).(3) VN mRNA were detectable in infarct center,infarct edge,per-infarct tissue and tissue far from the infarcted area of placental basal plate.In the early-onset severe preeclampsia group and the early control group,it was statistically higher in infarct center than in tissue far from the infarcted area (P ＜ 0.05).(4) PT of the early-onset severe preeclampsia group was (9.45 ± 0.63) s,significantly shorter than that of the early control group [(9.88 ± 0.17) s,P ＜ 0.05].While there was no statistically significant difference in APTT,FIB and INR among the four groups (P ＞ 0.05).(5) In the early-onset severe preeclampsia group,VN expression level and PT were significantly negative correlated (r =-0.612,P ＜0.05) ; while in the early control group there was no correlation (r =0.489,P ＞ 0.05).Conclusion VN was highly expressed in placental basal plate of the early-onset severe preeclampsia group,which caused the imbalance of coagulation and fibrinolysis system and the pathogenesis of severe preeclampsia.

Objective To investigate the value of X-ray and MRI in judging degree of the deltoid ligament injury after lateral malleolus fracture.Methods The data of X-ray and MRI of 41 patients with acute lateral malleolus fracture,excluding patients combined with medial malleolus fracture,were retrospectively analyzed.The medial clear space (MCS) was measured according to the mortise X-rays.The degree of injury of the superficial deltoid ligament and deep deltoid ligament was graded according to MRIs obtained from PACS (picture archiving and communication system) system.Moreover,the correlation between the width of the MCS and the degree of the deltoid ligament injury were statistically analyzed.The classification results of all patients according to the Lauge-Hansen classification based on X-rays and MRIs were recorded,respectively.Results A positive correlation was found between the width of the MCS and the degree of the deltoid ligament injury,and the optimal critical value of MCS was 7.85 mm for diagnosing complete rupture of the total deltoid ligament or the single rupture of the deep deltoid ligament,while 6.48mm for the complete rupture of the superficial deltoid ligament.Based on the MRIs,the accuracy of the results of Lauge-Hansen classification was 58.5％,and the accuracy for predicting the rupture of the deltoid ligament was 82.9％,however the degree of the deltoid ligament injury cannot be distinguished very well.Conclusion The deltoid ligament injury is common in acute lateral malleolus fracture,even though there is no medial malleolus fracture.The X-ray is still the prefenred choice for the evaluation of the ankle fracture; however the MRI is helpful in judging the degree of the deltoid ligament injury.

The biotransformation, CYP reaction phenotyping, the impact of CYP inhibitors and enzyme kinetics of 3-cyanomethyl-4-methyl-DCK (CMDCK), a new anti-HIV preclinical candidate belonging to DCK analogs, were investigated in human intestinal microsomes and recombinant cytochrome P450 (CYP) enzymes. CMDCK (4 micromol L(-1)) was incubated with a panel of rCYP enzymes (CYP1A2, 2C9, 2C19, 2D6 and 3A4) in vitro. The remaining parent drug in incubates was quantitatively analyzed by a LC-MS method. CYP3A4 was identified as the principal CYP isoenzyme responsible for its metabolism in intestinal microsomes. The major metabolic pathway of CMDCK was oxidation and a number of oxidative metabolites were screened with LC-MS. The Km, Vmax, CLint and T1/2 of CMDCK obtained from human intestinal microsome were 45.6 micromol L(-1), 0.33 micromol L(-1) min(-1), 12.1 mL min(-1) kg(-1) and 25.7 min, respectively. Intestinal clearance of CMDCK was estimated from in vitro data to be 3.3 mL min(-1) kg(-1), and was almost equal to the intestinal blood flow rate (4.6 mL min(-1) kg(-1)). The selective CYP3A4 inhibitors, ketoconazole, troleandomycin and ritonavir demonstrated significant inhibitory effects on CMDCK intestinal metabolism, which suggested that co-administration of CMDCK with potent CYP3A inhibitors, such as ritonavir, might decrease its intestinal metabolic clearance and subsequently improve its bioavailability in body.

Objective To investigate the prevalence of hyperuricemia in health check-up population of Beijing suburb.Methods Total 1 336 rural residents in Nankou Township of Beijing received health check-up from July to Aug 2014,including 686 subjects aged 20-59 years (young/middle-aged group) and 650 subjects aged 60-96 years (elderly group).The blood pressure and body mass index (BMI) were measured;serum uric acid (SUA),fasting blood glucose (FBG) and blood lipids (TG,TC,HDL-C,LDL-C) were determined.The SUA levels ＞ 420 μmol/L for male and ＞ 360 μmol/L for female were defined as hyperuricemia.Results The four quartiles of SUA levels were 27.00-254.59 μmol/L (Q1),254.60-302.35 μmol/L (Q2),302.36-359.78 μmol/L(Q3) and 359.79-702.0 μmol/L (Q4).The prevalence of hyperuricemia was significantly higher in young/middle-aged group than that in elderly group [20.41％ (140/686) vs.13.85％ (90/650),x2 =10.08,P =0.001 5],the systolic blood pressure [SBP,(126.8±15.7) vs.(116.7±12.0)mmHg(1 mmHg=0.133 kPa),t=2.76,P=0.008],FBG [(7.40±4.10) vs.(6.11 ±2.03)mmol/L,t=2.12,P=0.036],TC [(5.52±1.10) vs.(5.23±1.00)mmol/L,t =2.04,P =0.045],LDL-C [(3.5 ±0.7) vs.(2.4 ±0.9)mmol/L,t =2.21,P =0.029]in young/middle-aged group were significantly higher than those in elderly group.BMI,FBG were significantly higher in Q4 than those in other quartiles [BMI:(26.44 ± 3.88) vs.(24.19 ± 3.37),(25.49±3.42) and (25.61 ±3.49)kg/m2,t =2.78,P=0.008;FBG:(8.19 ±1.52) vs.(6.34±1.34),(6.09 ± 1.51) and (6.40 ± 1.98) mmol/L,t =2.80,P =0.007].The triglyceride (TG) levels in group Q3 and Q4 [(1.85 ± 0.90) and (1.92 ± 0.44) mmol/L] were higher than those in Q1 and Q2 [(1.37 ±0.76) and (1.70 ±0.84) mmol/L,t =2.1,P =0.035].Only 9.57％ subjects (22/230)with hyperuricemia was not combined with metabolic disorder;subjects combined with one and two metabolic disorders accounted for 20.87％ (48/230) and 69.57％ (160/230),respectively.Conclusion Screening for hyperuricemia is important for comprehensiye treatment and management of hyperuricemia in rural residents,especially in the young and middle-aged population.

Objective To explore the change of monocyte chemotactic factor-1 protein(MCP-1)and matrix metalloproteinase-9( MMP-9)of patients with coronary artery disease( CAD)following percutaneous coronary interventional( PCI). Methods Fifty patients underwent PCI procedures for CAD compromising a single coronary artery were selected as PCI group and 30 healthy individuals with normal findings by coronary angiography were selected as the control group. Plasma MCP-1 and MMP-9 were measured in all the subjects. Results The plasma MCP-1 level of patients with CAD after PCI was(19. 87 ± 5. 31)ng/ L,higher than that before operation((15. 71 ± 5. 23)ng/ L,t = 3. 95,P < 0. 01). Whereas in the control group,the MCP-1 level after coronary angiography was(13. 78 ± 5. 58)ng/ L,which was as same as that before operation (12. 42 ± 5. 39 ng/ L,P = 0. 34). Plasma MMP-9 level in the CAD patients after PCI procedures was(22. 69 ± 5. 97)mg/ L,higher than that before operation((19. 52 ± 5. 72)mg/ L,t = 2. 71,P < 0. 01). There was no significant difference in term of plasma MMP-9 level in control group befor and after operation((17. 53 ± 5. 51) mg/ L vs.(16. 69 ± 5. 42)mg/ L,P = 0. 55). Conclusion Plasma MCP-1 and MMP-9 increase in CAD patients following PCI procedures. But their roles in the vascular restenosis following the procedures need further investigation.

Objective To investigate the clinical and biochemical metabolic features of 12 patients with systemic primary carnitine deficiency(CDSP) and to identify the SLC22A5 gene mutation types of the disease. Method The clinical and biochemical data were collected by retrospective analysis. DNA direct sequencing and multiplex ligation dependent probe amplification(MLPA)were applied for SLC22A5 gene analysis. Result Among 12 patients with CDSP, 3 cases had evident infection factors, 6 cases with convulsions, 5 cases manifested liver hypertrophy, 8 cases with hyperammonemia, and 9 cases showed myocardial damage. All CDSP patients were detected biallelic pathogenic mutation in SLC22A5 gene by direct sequencing. The gene types include IVS2+1G>T, c.3G>T(p.Met1Ile), c.760C>T(p.Arg254X), c.1400C>G(p.Ser467Cys), c.844dupc(p.Arg282fs), c.338G>A(p.Cys113Tyr), c.51C>G(p.Phe17Leu), c.659A>T(p.Glu220Val), and c.1365dupC(p.Thr456fs). c.659A>T(p.Glu220Val) and c.1365dupC(p.Thr456fs)are novel mutations. One female patient was maternal CDSP, her child had abnormal newborn screening. The allele frequency of c.760C>T(p.Arg254X) and c.1400C>G(p.Ser467Cys) were 37.5%(9/24)and 29.2%(7/24)respectively. The MLPA test results of all patients were negative. Conclusion The clinical manifestations are complex and various in patients with CDSP. Point and small InDel(insertions/deletions)mutation constitute the major alteration in SLC22A5 gene. c.1400C>G(p.Ser467Cys) might be another prevalence mutation type in Chinese CDSP patient.