BACKGROUND: Some researches demonstrate that tea polyphenols (TP) has protective effects on neurotoxicity of hippocampal nerve cells induced byβ-amyloid peptide (Aβ), 6-hydroxydopamine (6-OHDA) and oxidative substances. In addition, clinical preliminary examination indicates that TP plays a certain preventive and therapeutic effects on the reduction of recognition function in high-risk population with Alzheimer disease (AD); however, its target and mechanism are still hot topics.OBJECTIVE: To observe the interfering effects of TP on cerebral nerve cell apoptosis induced by D-galactose and Aβ25～35 in mice.DESIGN: Randomized controlled animal study.SETTING: Department of Pharmacology, Pharmacological College of Jinan University.MATERIALS: The experiment was carried out in the Experimental Center of Jinan University from September 2004 to January 2005. A total of 90 healthy Kumning mice, aged 2 months, each gender in half, weighing 26-28 g, were provided by Guangdong Provincial Medical Laboratory Animal Center. Tea polyphenols was provided by Zhejiang Oriental Tea Science and Technology Corporation (batch number: 20040203); D-galactose by Shanghai Number 2 Reagent Plant (batch number: 20030708); Aβ25～35 by Sigma (batch number: 13/01/2004); vitamin E (Vit-E) by Shanghai Xinyi Pharmaceutical Factory (batch number: 20030708).METHODS: Experimental interference: Mice based on body mass were randomly divided into 6 groups: sham operation group (n =17), model group (n =16), vitamin E group (n =16), low-dose (n =13), moderate-dose (n =14) and high-dose (n =14) tea polyphenols groups. In above-mentioned animals, except those in the sham operation group, all were given 120 mg/(kg·d) D-galactose for 12 consecutive weeks, and Aβ25～35 (4 nmol) was slowly injected into the lateral cerebral ventricle. In sham operation group, the same volume of artificial cerebral spinal fluid (CSF) was internally injected into lateral ventricle. Drug treatment began at the first week. Mice in the sham operation group and model group were given distilled water, and the animals in other groups were given the above-mentioned drugs (100 mg/kg Vit-E, 100, 250 and 625 mg/kg TP), respectively. The volume of perfusion was 10 ml/kg, and the treatment lasted for 12 consecutive weeks. Experimental evaluation: After administration, LW-Ⅱ water maze was used to measure learning and memory condition; brain, liver tissues and serum were obtained to measure activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA); Fura-2/AM loading method was used to measure Ca2+ concentration in erythrocytes and neurons; flow cytometer was used to detect cerebral nerve cell apoptosis.MAIN OUTCOME MEASURES: Cl) Learning and memory ability; (2) SOD activity and MDA content in serum, liver and brain tissues; (3) Ca2+ concentration in erythrocytes and neurons;flow cytometer was used to cerebral nerve cell apoptosis.MAIN OUTCOME MEASURES：①Learning and memory ability;②SOD activity and MDA content in serum,liver and brain tissues；③Ca2+ concentration in erythrocytes and neurons；④cerebral nerve cell apoptosis．RESULTS：All 90 mice were involved in the final analysis．①At 12 weeks after administration,time to swim out of the water maze in the moderete-dose and high-dose TP groups and Vit-E group was shorter than that in the model group,and numbers of errors in passing the blind alleys in the water maze was reduced as compared with those in the model group,and there was significant difference(P＜0．05-0．01)．②SOD activities in the moderate-dose and high-dose TP groups were increased as compared with that in the model group,but MDA content in the high-dose TP group was decreased as compared with that in the model group．There was significant difference(P＜0．05-0．01)．③Ca2+ concentration in erythrocytes and neurons in the modemte-dose and high-dose TP groups and Vit-E group was lower than that in the model group,and there was significant difference(P＜0．05-0．01)．④The rates of brain neurons apoptosis in treatment groups with different doses of TP were 12．6％，18．6％,and 24．1％ respectively, exhibiting significant difference as compared with the mice in sham operation group(P＜0．05-0．01) CONCLUSION：TP can inhibit cerebral nerve cell apoptosis induced by D-galactose and Aβ25～35 and improve learning and memory ability in model mice．The effects may be related to its action of raising general anti-oxidative ability and improvement of intrecellular Ca overload induced by oxidative stress injury．

Objective To evaluate the value of MR spectroscopy (MRS) in the differential diagnosis between recurrence and radiation encephalopathy after radiotherapy for nasopharyngeal carcinoma (NPC). Methods Muhi-voxel proton MRS was performed on 50 patients with NPC, who were suspected of intracalvarium tumor recurrence or radiation encephalopathy after radiotherapy by conventional MRI,including 44 males and 6 females. Among the 50 patients, 26 cases were finally diagnosised as basicranial tumor recurrence and 24 cases as radiation encephalopathy by clinical and MRI follow-up. The following metabolites, such as Cho, NAA, Cr, lactate and lipid, were analyzed comparatively between basicranial tumor recurrence and radiation encephalopathy(RE), and between the lesions and the relative normal brain tissue. Wilcoxon's rank sum test was used to analyze the data. Results The median of Cho/Cr, Cho/NAA,LI/Cr in tumor recurrence group were 2. 22, 2. 13, and 1.77, respectively, and 1.40, 1.31, and 0. 57,respectively, in RE group. The difference of Cho/Cr, Cho/NAA, and LL/Cr between the two groups were statistically significant (P < 0. 01). Those in tumor recurrence group were higher than in RE group. The median of Cho, Cr, NAA in tumor recurrence group and in RE group were 3366. 00, 1023.00, 1930. 00 and 2469.50, 1864.50, 1734.00. There were no significant difference of Cho, Cr, and NAA between the two groups (P > 0. 05). In the 14 cases whose normal brain tissue were compared with the recurrent tumor tissue in tumor recurrence group, the median of Cr, NAA, LL, Cho/Cr, Cho/NAA, LL/Cr of recurrent tumor tissue and normal brain tissue were 1023.00, 1930.00, 2090.00, 3.76, 2. 13, 3.39 and 2370.00, 3012.00, 1680.00, 1.64, 1.17, 0.75,The difference of Cr, NAA, LL, Cho/Cr, Cho/NAA, LL/Cr between the normal tissue and recurrent tumor tissue were significant (P <0.05). LL, Cho/Cr, Cho/NAA, LL/Cr of recurrent tumors were higher than those of the normal brain tissue,while NAA and Cr of recurrent tumors were lower than those of the normal brain tissue. In the 12 cases whose normal brain tissue were compared with the RE tissue in RE group, the median of Cho, Cr, NAA, LL, Cho/Cr, IX,/Cr of RE tissue and normal brain tissue were 390.00, 217.50, 427.50, 39.00, 1.30, 0.40 and 680.00, 360.00, 610.00, 30.00, 1.54, 0. 09. The difference of above-mentioned parameters between RE tissue and normal tissue were significant. Cho, Cr, NAA, Cho/Cr of RE were lower than those of normal tissue (P <0. 05) ,while LL and LL/Cr of RE were higher than those of normal tissue (P < 0. 05). Conclusion The changes of the metabolites in recurrent lesions and RE lesions were different on MRS. Parameters such as Cho/Cr, Cho/NAA and LL/Cr, which were higher in recurrent lesions than those of RE, were valuable for the differential diagnosis between basicranial tumor recurrence and radiation encephalopathy after radiotherapy for NPC.

Animals ; Humans ; MicroRNAs ; physiology ; RNA, Small Interfering ; physiology ; RNA, Untranslated ; physiology

Objective: To explore the effect of moxibustion at Shenque (CV 8) on myocardial structure and function in exercise-induced fatigue rats. Methods: A 12-week treadmill running training was performed to create an exercise-induced fatigue rat model. Sixty eligible male specific-pathogen-free grade Sprague-Dawley rats were randomly divided into a blank group, a control group, a model group, a non-meridian non-acupoint group, a Zusanli (ST 36) group and a Shenque (CV 8) group, with 10 rats in each group. Rats in the blank group did not receive treadmill running training or moxibustion. Rats in the control group did not receive treadmill running training but received mild moxibustion at Shenque (CV 8). Rats in the model group received treadmill running training but no moxibustion. Rats in the non-meridian non-acupoint group, the Zusanli (ST 36) group and the Shenque (CV 8) group received moxibustion at the non-meridian non-acupoint points, Zusanli (ST 36) or Shenque (CV 8) immediately after each treadmill running training, 15 min each time, once a day for 5 consecutive days a week at a 2-day interval, 60 times of moxibustion in total. Left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), left ventricular diastolic volume (LVDv), left ventricular systolic volume (LVSv), ejection fraction (EF), stroke volume (SV), early diastolic peak flow velocity of mitral valve (E) and late diastolic peak flow velocity of mitral valve (A) of each group before and after the last treadmill running training were measured. Blood was collected 6 h after the last treadmill running training, and serum C-reactive protein (CRP), myoglobin (Mb), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI) and cardiac troponin T (cTnT) levels were detected. Finally, the heart was separated, the heart mass (HM) was measured, the cTnT level of the myocardial tissue was detected, the ultrastructural changes of the left ventricular myocardium were observed by transmission electron microscope, the left ventricular fraction shortening (LVFS), E/A and heart mass index (HMI) were calculated. Results: Compared with the same group before treatment, the rat cardiac LVEDd, LVESd, LVDv, LVSv, SV, E and A were significantly increased (all P<0.01), and the rat LVFS, E/A and EF were significantly decreased (all P<0.01) in the model group and the non-meridian non-acupoint group after treatment; the rat cardiac SV, LVDv, LVSv, E and A were all increased (all P<0.01), while E/A and EF were decreased (all P<0.01) in the Zusanli (ST 36) group after treatment; the rat cardiac LVDv, E and A were significantly increased (P<0.01 or P<0.05), and E/A was significantly decreased (P<0.01) in the Shenque (CV 8) group after treatment. After treatment, compared with the blank group, the rat cardiac LVEDd, LVESd, SV, LVDv, LVSv, E, A, the serum CRP, Mb, CK-MB, cTnI, cTnT and HMI, and the myocardial cTnT were increased (all P<0.01), and the LVFS, E/A and EF were all reduced (all P<0.01) in the model group; compared with the model group and the non-meridian non-acupoint group, rats in the Zusanli (ST 36) group and the Shenque (CV 8) group showed decreased LVEDd, LVESd, SV, LVDv, LVSv, E, A, serum CRP, Mb, CK-MB, cTnI, cTnT and HMI, and myocardial cTnT (P<0.01 or P<0.05), along with increased LVFS, E/A and EF (all P<0.01); compared with the Zusanli (ST 36) group, Mb and A of the Shenque (CV 8) group were decreased (both P<0.01), while both E/A and EF were increased (P<0.01, P<0.05). Transmission electron microscopy examination showed that myofibrils in the blank group and the control group were neatly arranged with clear light and dark bands; the model group and the non-meridian non-acupoint group showed different degrees of myofibril disintegration and breakage, increased and aggregated mitochondria of different sizes, and increased electron density. The myofibrils in the Shenque (CV 8) group and Zusanli (ST 36) group were arranged neatly with clear light and dark bands, and compensatory hyperplasia of mitochondria. Conclusion: Moxibustion at Shenque (CV 8) and Zusanli (ST 36) both can effectively improve the occurrence of myocardial remodeling in exercise-induced fatigue rats, and the effect of moxibustion at Shenque (CV 8) is better in improving cardiac function.

OBJECTIVE: To analyze the indications of the therapies for rheumatoid arthritis (RA) with neural network model analysis. METHODS: Three hundred and ninety-seven patients were included in the clinical trial from 9 clinical centers. They were randomly divided into Western medicine (WM) treated group, 194 cases; and traditional Chinese herbal medicine (CM) treated group, 203 cases. A complete physical examination and 18 common clinical manifestations were prepared before the randomization and after the treatment. The WM therapy included voltaren extended action tablet, methotrexate and sulfasalazine. The CM therapy included Glucosidorum Tripterygii Totorum Tablet and syndrome differentiation treatment. The American College of Rheumatology 20 (ACR20) was taken as efficacy evaluation. All data were analyzed on SAS 8.2 statistical package. The relationships between each variable and efficacy were analyzed, and the variables with P<0.2 were included for the data mining analysis with neural network model. All data were classified into training set (75%) and verification set (25%) for further verification on the data-mining model. RESULTS: Eighteen variables in CM and 24 variables in WM were included in the data-mining model. In CM, morning stiffness, swollen joint number, peripheral immunoglobulin M (IgM) level, tenderness joint number, tenderness, rheumatoid factor (RF), C-reactive protein (CRP) and joint pain were positively related to the efficacy, and disease duration and more urination at night negatively related to the efficacy. In WM, erythrocyte sedimentation rate (ESR), weak waist, white fur in tongue, joint pain, joint stiffness and swollen joint were positively related to the efficacy, and yellow fur in tongue, red tongue, white blood negatively related to the efficacy. In the analysis with the neural network model in the patients of verification set, the predictive response rates of 20% patients would be 100% and 90% in the treatment with CM and WM, respectively. CONCLUSION: Neural network model analysis, based on the full clinical trial data with collection of both traditional Chinese medicine and modern medicine diagnostic information, shows a good predictive role for the information in the efficacy in rheumatoid arthritis.

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

BACKGROUNDInflammation within vulnerable coronary plaques may cause unstable angina by promoting rupture and erosion. C-reactive protein (CRP) is the most reliable and accessible test method for clinical use for identifying coronary artery disease event. Matrix metalloproteinase 9 (MMP-9) is highly over-expressed in the vulnerable regions of a plaque. Our aim was to evaluate the plasma levels of MMP-9 and hsCRP in subjects with both unstable angina and coronary plaques, as well as in those with unstable angina without coronary plaques.

METHODSPatients with newly diagnosed unstable angina pectoris from clinical presentation and ECG, who were undergoing coronary angiography from April 2007 to April 2009, were included in this study. A total of 170 subjects were enrolled in the study. Before angiography, the baseline clinical data (mainly including conventional risk factors) was collected. These patients were divided into two groups, a non-plaque group (G1) which included 55 patients with no significant stenosis or less than 20% stenosis in at least one of the major coronary artery branches, and a plaque group (G2) which included 115 patients with at least one of the major coronary artery branches unstable angina pectoris with at least 50% stenosis of one major coronary artery. The patients presenting with calcified nodules of a major coronary artery were excluded from this study. We examined the serum levels of MMP-9 for all cases by multi-effect enzyme-linked immunosorbent assay.

RESULTSThere was a significant difference in the serum levels of MMP-9 between the two groups (P < 0.001). The percentage of patients with hypertension, diabetes and current smokers were significantly different between the two groups (P = 0.034, P = 0.031, and P = 0.044 respectively). The univariate Logistic regression analyses of risk factors showed that smoking was the main risk factor for angina in the non-plaque group with the OR being 1.95 (95%CI 1.02 - 3.75). Hypertension, diabetes mellitus were negatively related with the occurrence of angina in the non-plaque group with the ORs being 0.50, and 0.36, respectively (95%CI 0.26 - 0.96 and 0.14 - 0.94). The MMP-9 level was negatively related to the occurrence of angina in the non-plaque group with an OR of 0.59 (95%CI 0.47 - 0.81).

CONCLUSIONSThere is a significantly difference in MMP-9 levels between the plaque and non-plaque groups. Current smoking has a significant influence on unstable angina patients without documented plaques. The serum MMP-9 level may be a significant biomarker which can help differentiate patients with unstable angina with plaques from those with unstable angina but without plaques.

Aged ; Angina, Unstable ; blood ; metabolism ; physiopathology ; C-Reactive Protein ; metabolism ; Coronary Angiography ; Coronary Artery Disease ; blood ; metabolism ; physiopathology ; Coronary Vessels ; metabolism ; pathology ; Female ; Humans ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Multivariate Analysis ; Risk Factors ; Smoking ; adverse effects

Comparative pharmacokinetic (PK) analysis is often carried out throughout the entire period of drug development, the common approach for the assessment of pharmacokinetics between different treatments requires that the individual PK parameters, which employs estimation of 90% confidence intervals for the ratio of average parameters, such as AUC and Cmax, these 90% confidence intervals then need to be compared with the pre-specified equivalent interval, and last we determine whether the two treatments are equivalent. Unfortunately in many clinical circumstances, some or even all of the individuals can only be sparsely sampled, making the individual evaluation difficult by the conventional non-compartmental analysis. In such cases, nonlinear mixed effect model (NONMEM) could be applied to analyze the sparse data. In this article, we simulated a sparsely sampling design trial based on the dense sampling data from a truly comparative PK study. The sparse data were analyzed with NONMEM method, and the original dense data were analyzed with non-compartment analysis. Although the trial design and analysis methods are different, the 90% confidence intervals for the ratio of PK parameters based on 1000 Bootstrap are very similar, indicated that the analysis based on NONMEM is a reliable method to treat with the sparse data in the comparative pharmacokinetic study.
Area Under Curve ; Confidence Intervals ; Humans ; Nonlinear Dynamics ; Pharmacokinetics ; Sampling Studies

OBJECTIVETo investigate the time trends of cancer mortality among residents in Kaifeng county, Henan province.

METHODSData on cancer mortality from the vital registration system in Kaifeng county from 1988 to 2005 was analyzed. A total of 9543 death records (5974 males and 3567 females) due to malignant tumors were studied. A two-year-period age-specified standardized mortality rates were directly adjusted by the world standard population, and the annual percentage change (APC) of mortality were estimated by a linear logarithm regression.

RESULTSThe crude cancer death rate for male was 95.09/100,000 and its age-standardized death rate was 117.41/100,000. While, the crude cancer death rate for female was 59.13/100,000 and the age-standardized death rate was 57.15/100,000. There was a significant growth tread for lung cancer (APC: 6.54%), liver cancer (5.07%) in males and breast cancer (7.04%) in females in the groups aged over 18. On the contrary, the decreasing treads for esophageal cancer in both of sexes (-7.09%, -13.53%) were also observed in this study. Meanwhile, there was no other significant changes in the trend, either in the tumor sites or mortality, was observed.

CONCLUSIONIn the past two decades, there has been a significant increasing trend for cancer mortality in Kaifeng county, of Henan Province. Hence, it is necessary to enhance epidemiological survey to identify risk factors at the earlier stages.

China ; epidemiology ; Death Certificates ; Female ; Humans ; Male ; Mortality ; trends ; Neoplasms ; mortality ; Rural Population

OBJECTIVETo explore the neuroprotective effect of FK506 on acute spinal cord injury in dogs.

METHODSAcute spinal cord injury model was made with the Allen technique. Animals were randomly divided into 3 groups. Group A (n = 8) was the control group and received operation but no therapy, while group B and C (n = 8) received a single dose of FK506 (0.18 mg/kg and 0.3 mg/kg, respectively) administered with an arterial duct 2 h after spinal cord injury (SCI). Spine MRI, neurological function, histopathological examination of injured spinal cord and immunohistochemical examination of expression of NF(200) in neurons and GFAP in astrocytes were assessed at certain time after injury.

RESULTSNeurological function score of group C and B was better than that of group A (P < 0.05), with significance between group C and A, while no significance between group B and A statistically. The signal scope of spinal cord injury on MRI in group C was the smallest among all the groups, and the signal scope in group B was smaller than that in group A, which was directively associated with the neurological outcome. The expression of NF and GFAP was significantly higher in group C than in group A (P < 0.05), but without statistical significance between group B and A.

CONCLUSIONLocal administration of FK506 (0.3 mg/kg) possesses neuroprotective effect on acute spinal cord injury, which can improve neurological function recovery and attenuate secondary spinal cord injury. Local administration of FK506 possesses a dosage-effect relation.

Acute Disease ; Animals ; Disease Models, Animal ; Dogs ; Female ; Male ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Random Allocation ; Spinal Cord Injuries ; drug therapy ; Tacrolimus ; pharmacology ; therapeutic use