Distinct Rab7-related Endosomal-Autophagic-Lysosomal Dysregulation Observed in Cortex and Hippocampus in APPswe/PSEN1dE9 Mouse Model of Alzheimer's Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Amyloid-β deposition and accumulation of autophagic vacuoles are pathologic features of Alzheimer's disease (AD). Dysregulation of the endosomal-autophagic-lysosomal (EAL) pathway, which impairs amyloid precursor protein processing, is one of the earliest changes in AD. However, the precise role of EAL pathway in neurodegeneration remains unclear. This study aimed to investigate the role of EAL pathway in AD and further study the mechanism of EAL dysfunction.</p><p><b>METHODS</b>We used 3-, 7-, and 12-month-old APPswe/PSEN1dE9 (APP/PS1) mice to model different stages of AD with age- and gender-matched wild-type littermates as controls (4-7 mice per group) and detected the changes of EAL markers, endosomal organizers Rab5 and Rab7, autophagosome marker LC3B, and lysosomal proteins Lamp1/2 in cortex and hippocampus by immunohistochemistry and Western blotting analysis. To further explore the mechanism of EAL dysregulation in AD, components of the class III phosphatidylinositol 3-kinase (PI3KC3) complex, activators of Rab7 (Beclin1 and UVRAG), and the negative regulator of Rab7 (Rubicon) were also measured in this two brain regions.</p><p><b>RESULTS</b>In 7-month-old APP/PS1 brain that amyloid beta initiated to accumulate intracellularly, EAL pathway, and related PI3KC3 members, UVRAG and Beclin1 were upregulated both in cortex and hippocampus (all P < 0.05). By the age of 12 months old, when abundant amyloid plaques formed, EAL markers, UVRAG, and Beclin1 were also upregulated in the cortex (all P < 0.05). However, Rab7 was decreased significantly (P = 0.0447), accompanied by a reduction of its activating PI3KC complex component Beclin1 (P = 0.0215) and enhancement of its inhibiting component Rubicon (P = 0.0055) in the hippocampus.</p><p><b>CONCLUSIONS</b>Our study implies that EAL pathway, represented as Rab7 and its PI3KC3 regulators' expressions, showed temporal and spatial variation in brains at different stages of AD. It provides new insights into the role of EAL pathway in pathogenesis and indicates potential therapeutic targets in neurodegenerative diseases.</p>

A study on the clinical value of oxidative stress related index in chronic kidney disease diagnosis / 预防医学

Objective To evaluate the clinical value of oxidative stress related indicators in chronic kidney disease (CKD)diagnosis.Methods A total of 220 CKD patients in different stages and 100 healthy persons were enrolled.The serum levels of Creatinine (Cr), uric acid (UA),γ-glutamyl transpeptidase (GGT) and homocysteine (HCY) were measured.CKD patients were divided into 5 stages according to the calculated estimated glomerular filtration rate (eGFR).CKD patients in stage 1, 2 were incorporated as group CDKⅠand incorporating CKD patients in stage 3, 4, 5 patients were incorporated as group CDKⅡ.T test was used to compare the difference of UA, GGT, HCY levels between healthy people and CKD patients.Receiver operating characteristic (ROC) curve was used to evaluate the clinical value of each index in CKD diagnosis.Z test was used to compare the difference of the area under curve (AUC) of UA, GGT, HCY and combined detection.Results The mean levels of serum UA, GGT, HCY between CKD patients and healthy person were statistically significant (P<0.05).In healthy persons and CKD patients study, the AUC of UA, GGT, HCY and combined detection were 0.823, 0.585, 0.850 and 0.924, respectively.The AUC of combined detection was significantly higher than single detection (P<0.05).In group CDKⅠ andⅡ study, the AUC of UA, GGT, HCY and combined detection were 0.719, 0.485, 0.828 and 0.834, respectively.The AUC of combined detection was not significantly higher than HCY detection (P>0.05).Conclusion Combined detection of oxidative stress related index has high application value in CKD early diagnosis.

S100A4 siRNA inhibits human pancreatic cancer cell invasion in vitro / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Pancreatic cancer is one of the most deadly cancers, which is characterized by its high metastatic potential. S100A4 is a major prometastatic protein involved in tumor invasion and metastasis which precise role in pancreatic cancer has not been fully investigated. We knocked down the S100A4 gene in the Bxpc-3 pancreatic cancer cell line via RNA interference to study the changes in cell behavior.</p><p><b>METHODS</b>Real-time polymerase chain reaction and western blotting were used to detect mRNA and protein expression levels of S100A4, matrix metalloproteinase (MMP)-2, E-cadherin and thrombospondin (TSP)-1. Transwell chambers were used to detect the migration and invasion abilities; a cell adhesion assay was used to detect adhesion ability; colony forming efficiency was used to detect cell proliferation; flow cytometry was used to detect apoptosis.</p><p><b>RESULTS</b>S100A4 mRNA expression was reduced to 17% after transfection with S100A4-siRNA, and protein expression had a similar trend. mRNA and protein expression of MMP-2 was reduced and that of E-cadherin and TSP-1 was elevated, indicating that S100A4 affects their expression. S100A4-silenced cells exhibited a marked decrease in migration and invasiveness and increased adhesion, whereas overall proliferation and apoptosis were not overtly altered.</p><p><b>CONCLUSION</b>S100A4 and its downstream factors play important roles in pancreatic cancer invasion, and silencing A100A4 can significantly contain the invasiveness of pancreatic cancer.</p>

Clinical application of double balloon endoscopy in the elderly / 中华老年医学杂志

Objective To investigate the diagnostic value of double balloon endoscopy (DBE) in the elderly. Methods Clinical manifestations and endoscopic findings of 42 elderly patients (aged 60-80 years) and 73 young and middle-aged patients (aged 12-59 years) with small bowel lesions were obtained and compared. Factors influencing the diagnostic outcome of DBE in patients with small bowel bleeding were identified,and the optimal check time after the latest bleeding was determined.Results The procedures of 85.7％ (36/42) in the elderly and 79.5％(58/73) in young and middle aged were completed (P＞0.05).There was no significant difference in the procedure time between the two age groups.No severe complications were observed in the elderly group.The overall positive rate by double balloon enteroscopy examination were 71.4 ％ (30/42) and 63.0 ％ (46/73),respectively in the two groups (P＞ 0.05). Ulcer and tumor lesions were the most common findings,and diverticula and angiodysplasia were the second common findings. Longer duration of bleeding and higher number of bleeding episodes were found in the elderly with positive DBE findings than those with negative findings. Positive diagnostic rate was significantly higher when DBE was performed within 7 days than that after 7 days (90％ vs. 40％). Conclusions DBE is a safe,reliable diagnostic modality,especially in the elderly patients with small bowel bleeding in which ulcer and tumor lesions are the most common identifications.DBE is of greater benefit in patients with more bleeding episodes over a long period,and should be performed within 7 days after the last bleeding.

Effect of imatinib at different concentrations on rat C6 glioma cell apoptosis and cell cycle / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of imatinib on rat C6 glioma cell apoptosis and cell cycle.</p><p><b>METHODS</b>MTT assay was used to determine the OD value of C6 glioma cells following treatment with imatinib at different concentrations (0.156, 10 and 15 micromo/L) for 24, 48 and 72 h. The cell apoptosis was assayed by Hochest/PI staining and the cell cycle changes were analyzed by flow cytometry.</p><p><b>RESULTS</b>Imatinib treatment resulted in increased number of apoptotic cells in a time- and dose-dependent manner. A 72-h treatment of the cells with imatinib at 10 and 15 micromo/L caused increased cell percentage in G(0)/G(1) phase to (68.53-/+0.83)% and (70.41-/+0.62)%, (P<0.01), decreased the percentage of G(2) phase cells to (14.48-/+0.12)% and (13.84-/+2.86)% (P<0.01), and decreased the percentage of S phase cells to (16.98-/+0.72)% and (15.78-/+2.28)%, respectively (P<0.01).</p><p><b>CONCLUSION</b>Imatinib can induce apoptosis and affect the distribution of the cell cycle of C6 cells in vitro.</p>

Value of carcinoembryonec antigen in biochemotherapy response monitoring in patients with Her-2-positive advanced breast cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the value of serum carcinoembryonec antigen (CEA) in monitoring the response to biochemotherapy by Herceptin plus taxol (TAX) in patients with Her-2-positive advanced breast cancer.</p><p><b>METHODS</b>The changes in serum CEA level were investigated retrospectively after two cycles of biochemotherapy in 83 patients with Her-2-positive advanced breast cancer. The correlations between the changes and radiological objective response were analyzed.</p><p><b>RESULTS</b>After two cycles of biochemotherapy, the clinical benefit rate (CBR) was 81.9%. In the 60 patients with lowered CEA level, the CBR was 85.0% (51/60), with a non-response rate of 15.0% (9/60); in contrast, the CBR was only 34.8% in 23 patients with elevated CEA, with a non-response rate of 65.2%, showing significant difference between the two groups (P<0.05).</p><p><b>CONCLUSION</b>Serum CEA level can be used to monitor the therapeutic effect of biochemotherapy in patients with Her-2-positive advanced breast cancer.</p>

The role of S100A4 in cancer cells and its potential application in the search for new treatment targets / 军事医学科学院院刊

S100A4, a member of S100 superfamily of Ca~(2+)-binding proteins, is a polypeptide containing 101 amino acids. S100A4, which is overexpressed in most tumor cells, plays pivotal roles in growth, invasion and migration of tumor by regulating cell cycle progression, differentiation, apoptosis, invasion and metastasis of cells. This article reviews S100A4′s structure, function and potential application as the new target in the therapy of tumors.

Mechanism of photodynamic therapy against human esophageal carcinoma xenografts in nude mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of photodynamic therapy (PDT) in nude mice bearing human esophageal cancer cell line Eca-109 xenografts.</p><p><b>METHODS</b>A nude mouse model bearing human esophageal carcinoma was established by subcutaneous transplantation of Eca-109 cells. The mice were then randomized into 4 groups, namely hematoporphyrin derivative (HpD)-PDT group (given HpD and laser irradiation), exclusive laser irradiation group, exclusive HpD group and blank control group. In HpD-PDT group, the mice were exposed to irradiation at the light energy density of 120 Jsol;cm(2) delivered via a DIOMED 630 PDT system 24 h after intraperitoneal HpD injection, and the mice in exclusive laser irradiation group received only laser irradiation. Three days later, all the nude mice were sacrificed for determination of malondialdehyde (MDA) production, immunohistochemistry for caspase-3 protein and HE staining of the tumor tissue.</p><p><b>RESULTS</b>The MDA level was significantly higher in HpD-PDT group than in the other 3 groups (P<0.01), and comparable between the latter 3 groups. Expression of caspase-3 protein was similar between HpD-PDT group and the blank control group (P>0.05). Under light microscope, HE staining visualized massive tissue necrosis in HpD-PDT group with homogeneous red staining.</p><p><b>CONCLUSION</b>In human esophageal carcinoma xenografts in nude mice, HpD-PDT generates singlet oxygen to result in direct tumor cell damage and cause MDA production. Caspase-3 may not be activated in the apoptotic pathway, suggesting that this pathway may not be caspase-3-dependent.</p>

Investigation epidemiology and sub-clinical infection of hepatitis E in voluntary blood donors in south Zhejiang / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the southern region of Zhejiang hepatitis E virus (HEV) infection.</p><p><b>METHODS</b>A cluster sampling strategy was used to sample all blood donors from February to October in 2008 in Wenzhou blood center. Their blood was tested for IgG and IgM antibody against HEV. Reverse transcriptase-polymerase chain reaction(RT-PCR) and sequencing were applied to detect its genotype and sequence homology in HEV IgM-positive specimen.</p><p><b>RESULTS</b>The prevalence of anti-HEV IgG in 3044 cases of blood donors was 33.28%. IgG increased with age. There are certain increase in positive rates between the 20-year-old group and over 40 years of age group from 21.16% to 50.36%. The positive rate of IgM was 0.92%. The ratio of infection among different age group was the highest in the age range from 31 to 40 years and up to 1.90%. IgG and IgM through their negative and positive analysis of samples found in their group with donors age, sex and blood type does not significantly related to each other. Nucleic acids were found in three cases through PCR amplification in all 28 cases of HEV IgM positive samples. The total positive rate was one-thousandth, of which two cases for gene 4, 1 cases of infection for gene 1.</p><p><b>CONCLUSION</b>The results indicate that there was a certain percentage of HEV virus in voluntary blood donors in south Zhejiang.</p>

Inhibitory effect of soman on stress induced hyperthermia in rats and the influence of central and peripheral cholinergic antagonists / 中国应用生理学杂志

<p><b>AIM</b>To determine the effect of soman on stress induced hyperthermia and the influence of central and peripheral cholinergic antagonists.</p><p><b>METHODS</b>Effects of subcutaneous injection of soman, scopolamine, methylscopolamine and pyridostigmine on stress-induced hyperthermia were observed in rats by radio telemetry in an open-field environment. Plasma cholinesterase (ChE) activity was measured by a spectrophotometry.</p><p><b>RESULTS</b>(1) Core temperature of the control group increased by 0.96 degrees C when exposed to open-field, whereas core temperature only increased by 0.55 degrees C in soman treated animals. Scopolamine, a central cholinergic antagonist, nearly abolished inhibitory effects of soman on core temperature when exposed to open-field. Methylscopolamine, a peripheral cholinergic antagonist, coadministered with soman reduced significantly the hyperthermic response to open-field exposure compared with rats dosed with soman. (2) Pyridostigmine, a peripheral anti-ChE agent that caused a 52% decrease in plasma ChE activity led to a significant enhancement of the hyperthermic response to open-field exposure. Methyl scopolamine nearly abolished the effects of pyridostigmine on stress-induced hyperthermia response.</p><p><b>CONCLUSION</b>Inhibitory effect of soman on the open field hyperthermia suggested that soman treatment hampered the ability of the rat to develop a normal hyperthermic response when placed in the open-field environment. Its inhibitory effects were mediated primarily through a central muscarinic pathway. In addition, peripheral cholinergic nerve was involved in the control of stress hyperthermic response.</p>

Design of a medical equipment purchasing system / 中国医疗器械杂志

This paper introduces the network data dynamic exchange technology applied to the design of the medical equipment purchase system according to the process of the medical equipment purchasing. The new system adopts B/S structure based on .net technology, to realize the medical equipment purchasing information's dynamic management of network purchase application and verification, suppliers qualification examination and the contact file inquiry etc.

Main factors affecting the effect of photodynamic therapy against human esophageal cancer cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the tumor cell-killing effect of photodynamic therapy against human esophageal cancer cells in vitro and identify the main factors affecting the effect.</p><p><b>METHODS</b>Human esophageal cancer Eca-109 cells were incubated for 24 h in vitro with hematoporphyrin derivative (HpD) and Photofrin at different concentrations prior to exposure to a light energy density of 15 J/cm(2) delivered from a DIOMED 630 PDT system. The cell killing effect was also evaluated for different HpD concentrations combined with 3 light energy densities (10, 30, and 50 J/cm(2)), respectively. The cell survival rate was measured using MTT assay, and fluorescence spectrometry was used to detect the intracellular photosensitizer fluorescence of the tumor cells after incubation with HpD for 4 h.</p><p><b>RESULTS</b>The cell survival rate after incubation with the two photosensitizers at different concentrations were significantly different, and under the 3 different light energy densities, incubation of the cells with different HpD concentrations also resulted in significantly different cell survival rates (P<0.05). At the 4 low photosensitizer concentrations and with different light energy densities, the cell survival rates were similar (P>0.05), but the 4 higher photosensitizer concentrations resulted in significant difference in the cells survival (P<0.05). Correlation analysis showed that the intracellular photosensitizer concentration was positively correlated to the photosensitizer concentrations in cell incubation (r=0.997).</p><p><b>CONCLUSION</b>When the light source remains constant, the light energy density, the kinds of photosensitizers and their concentrations are the main factors affecting the Eca-109 cell-killing effect of PDT.</p>

Study on genotyping of Mycobacterium leprae and families with multi-cases / 中华流行病学杂志

<p><b>OBJECTIVE</b>Multiple locus variable number-tandem repeat (VNTR) analysis (MLVA) had been proposed as a means of strain typing for tracking of source and studying the transmission chain of pathogens. However, empirical data for a defined population from scale and duration were lacking for studying the transmission chain of leprosy.</p><p><b>METHODS</b>MLVA on 7 VNTR loci was applied to the strain typing on prevalent Mycobacterium leprae isolates collected from Qiubei county, Yunnan province during 2002-2006 in the study on the relationship between geographic distribution and genotypes of M. leprae. The strain typing, combined with conventional epidemiological investigation was performed to trace the transmission chain.</p><p><b>RESULTS</b>(1) Phylogenetic analyses through application of PAUP 4.0, The M. leprae were grouped into A, B, C, D and E strains according to the allelic range 9, 11-13, 15-26 and > 26 on the GTA9 locus. The strains with 9 copies on GTA9 locus, was named A. (2) Genotypes of strains from the five multi-case families located at North and North-West parts were similar and belonged to A strains. VNTR patterns of intra-family were identical or similar but not identical inter-family. (3) Not only A cluster appeared higher proportion in total isolates but also distributes cluster, indicating ongoing transmission from recent findings.</p><p><b>CONCLUSION</b>VNTR strain typing was suitable to trace the short chain of transmission in both small area and intra-families. Multi-case families might constitute epidemic foci and source of M. leprae in villages, causing the predominant strain or cluster which tends to be those identified in multi-case families and resulted in the spreading of leprosy. A long-term study was underway to reveal whether A strain was predominant strain and to observe the evolution of M. leprae in this spatially and temporally defined endemic population.</p>

Development and application of network system in radiotherapy / 中华放射肿瘤学杂志

Objective To develop a network system for radiotherapy.Methods Delphi 6.0 lan- guage was used to program the system based on PACS through the model of client-server machine and local network.Data of different facilities were transferred among each other through Dicom 3.0 and Dicom RT pro- tocol.Results The main function of this system was a management software for radiotherapy,a PACS sys- tem,a TPS system and a therapeutic machine system.Conclusion The network system operates steadily with data safe and reliable,and is an important part of the information construction in the department of radio- therapy

Transabdominal ultrasonography in the diagnosis of achalasia Transabdominal ultrasonography in the diagnosis of achalasia / 第二军医大学学报

Objective: To assess the clinical application of transabdominal ultrasonography for the diagnosis of achalasia. Methods: The subjects were divided into 3 groups, with 8 patients suffered from achalasia as patient group, 10 normal individuals and 8 patients with cardiac carcinoma as controls. All subjects received water provocative test to study the lower esophagus and cardia. Sonographic findings were compared between the 3 groups. After treatment by administration of drugs, pneumatic balloon dilation, or intrasphincteric injection of botulinum toxin, the 8 patients were re-examined by TAUS for longitudinal comparison. Results: (1)The normal subjects had no dilation of cardia and lower esophagus before drinking water, but their cardias opened rapidly with the drinking action. (2)All the patients of achalasia were found to have dilation of lower esophagus before taking water. During 10 min continuous TAUS scanning, 5 of 8 demonstrated absence of relaxation of cardias and absence of water from the esophagus into the stomach. The other 3 showed slight and intermittent relaxation of cardias with water flow into the stomach. Thirty minutes after water provocative test, all the 8 patients had water retardation within the lower esophagus. (3)The patients of cardiac carcinoma had an ultrasound feature of cardiac ring enlargement and thickening of cardiac wall without dilation of lower esophagus before water provocative test. Water passed the cardia more slowly. Conclusion: TAUS is a readily accepted examination. It can quickly give reliable diagnostic clues to achalasia. TAUS can also be used for making assessment of therapeutic effect on achalasia.

Transabdominal ultrasonography in the diagnosis of achalasia Transabdominal ultrasonography in the diagnosis of achalasia / 第二军医大学学报

Objective: To assess the clinical application of transabdominal ultrasonography for the diagnosis of achalasia. Methods: The subjects were divided into 3 groups, with 8 patients suffered from achalasia as patient group, 10 normal individuals and 8 patients with cardiac carcinoma as controls. All subjects received water provocative test to study the lower esophagus and cardia. Sonographic findings were compared between the 3 groups. After treatment by administration of drugs, pneumatic balloon dilation, or intrasphincteric injection of botulinum toxin, the 8 patients were re-examined by TAUS for longitudinal comparison. Results: (1)The normal subjects had no dilation of cardia and lower esophagus before drinking water, but their cardias opened rapidly with the drinking action. (2)All the patients of achalasia were found to have dilation of lower esophagus before taking water. During 10 min continuous TAUS scanning, 5 of 8 demonstrated absence of relaxation of cardias and absence of water from the esophagus into the stomach. The other 3 showed slight and intermittent relaxation of cardias with water flow into the stomach. Thirty minutes after water provocative test, all the 8 patients had water retardation within the lower esophagus. (3)The patients of cardiac carcinoma had an ultrasound feature of cardiac ring enlargement and thickening of cardiac wall without dilation of lower esophagus before water provocative test. Water passed the cardia more slowly. Conclusion: TAUS is a readily accepted examination. It can quickly give reliable diagnostic clues to achalasia. TAUS can also be used for making assessment of therapeutic effect on achalasia.

The analysis of epidemiological and clinical characteristics of 112 cases patients with adult-measles / 中华传染病杂志

Objective To analyze the clinical data of 112 patients with adult-measles in the Af- filiated Shanghai Sixth People's Hospital and Third People's Hospital of Shanghai Jiaotong University from January to June in 2005,and to evaluate the epidemiologieal and clinical characteristics of adult- measles.Methods To retrospectively analyze the clinical data of 112 patients with adult-measles. Results Totally,112 measles patients were involved in this study,with male 63 and female 49 re- spectively.The gender rate was 1.3:1,average age about 32 years and the proportion of non-resi- dents was 40.18%.The peak of the incidence of disease emerged in April and May,and the positive rate of measle virus IgM antibody in serum was 96.43%.There were 97 patients(86.61%)who had the fever that beyond 39℃and 36 patients(32.14%)who had measle caused viral hepatitis.Conclu- sions There is a trend that the ages of patients that suffered from measle were postponed and the in cidences of disease are increased year by year,which maybe related to the nonstandard inoculation of measle vaccine,or the decrease of IgM antibody levels and so on.Meanwhile,serious toxemie symp- toms and liver damage can be observed.