Calmodulin,as an important signaling regulatory protein,widely exists in eukaryotic cells and participates in a variety of physiological activities.Alzheimer's disease (AD) is a typical neurodegenerative diseasemostly affecting the old people.Senile plaques (SP) caused by amyloid protein deposition and neurofibrillary tangles (NTF) caused by over-phosphorylation of Tau protein in the brain are the two major neuropathological hallmarks of AD.Neuronal apoptosis induced by dysregulation of calcium homeostasis also plays a significant role during this pathological process.Recent studies have found that calcium and its downstream receptor,calmodulin,are closely associated with the pathogenesis and progress of Alzheimer's disease.This article reviews the current development and the latest research progress on the effects of calmodulin on β-amyloid protein generation and deposition,neurofibrillary tangle formation,synaptic plasticity in AD around the world,comprehensively discusses the role of calmodulin in the pathogenesis of Alzheimer's disease.

Objective To determine the factors contributing to the development of deep vein thrombosis (DVT) in the lower extremity in patients after hip or knee arthroplasty and hip fracture internal fixation.Methods One hundred and forty-seven consecutive patients receiving hip or knee arthroplasty and hip fracture internal fixation from 2004 to 2005 were included in this study. Their age ranged from 33 to 92 years. Duplex color ultrasonic inspection was performed on veins of the bilateral lower extremities before operation and 2 weeks after operation for detection of DVT. The patients were divided into a DVT group and a DVT-free group based on the development of DVT after operation. Detailed perioperative clinical information about the patients, surgery and anesthesia was collected.Results Lower extremity DVT was found in 42.2% of the patients after operation, while the incidence of proximal DVT was 2.7%. Compared with the DVT-free group, the usage rate and dosage of ephedrine increased significantly, the duration of anesthesia was significantly longer, and the white blood cell count (WBC) on the 1st postoperative day and the highest WBC count were significantly higher in the DVT group(P＜0.05). Logistic regression analysis indicated that the above factors were closely related to DVT.Conclusion Duration of anesthesia ＞ 3 h, ephedrine administration and a marked increase in WBC count after operation are the risk factors for DVT in the lower extremities in patients after hip or knee arthroplasty and hip fracture internal fixation.

Objective To assess the effect of a noninvasive equipment (the human biological stimulation feedback instrument) for the screening of metabolic syndrome (MS). Methods The samples were selected from the International Health Care Center of the Second Affiliated Hospital of Zhejiang University College of Medicine. From January to December 2012, according to the inclusion criteria, a total of 5674 consecutive participants (3 437 men, 2 237 women) without medical history of diabetes mellitus underwent general health screening in this hospital, which included questionnaire investigation, all MS components and the risk assessment of the human biological stimulation feedback instrument. MS was defined according to 2004 the Chinese Diabetes Society (CDS) criteria. Results The 5 674 subjects were divided into three groups in accordance with the human biological stimulation feedback instrument risk score: the normal group, metabolic abnormalities low risk group, metabolic abnormalities high risk group. The detection rate of MS corresponding to the three groups was 8.73% (251/2 876), 29.32% (612/2 087), 32.77% (233/711), respectively (trend χ2=372.14,P<0.001). With the increase of risk score, the detection rate of MS increased. A total of 1 096 (male 879, female 217) were diagnosed MS by CDS criteria. The area under the curve (AUC) of the test was 0.674 (95%CI 0.658-0.691, P<0.000 1)for predicting MS. The corresponding cutoff value was 25.00%, the sensitivity, specificity, positive predictive value and negative predictive value of diagnosis of MS was 77.80%, 56.00%, 30.20%and 91.30%, respectively;409 subjects who had no history of MS and diabetes mellitus follow up for two years, the AUC of the test was 0.719 (95%CI 0.644-0.794)for predicting MS. The corresponding cutoff value was 25.00%, too. And the sensitivity and specificity of diagnosis of MS was 78.00%and 59.80%, respectively. The detection rate of MS was positively correlated with the risk score. Conclusion We found that the human biological stimulation feedback instrument is a potential screening approach for early predicting MS in health checkup with simple and noninvasive procedure and high negative predictive value, although its diagnostic efficiency is not so good. And it might have a warning effect on the progress of MS.

BACKGROUND:Poly(D,L-lactide-co-glycolide)(PLGA)may produce lactic acid and glycolic acid when PLGA degrades,thus leading to the acid accumulation and inducing the inflammatory reaction locally.OBJECTIVE:To investigate the effect of lysine,histidine and arginine on regulating the acid accumulation of PLGA copolymer during the degradation.DESIGN:Repeated measurement and experiment.TIME AND SETTING:The experiments were performed in the College of Bioengineering.Chongqing University from July 2006 to August 2007.MATERIALS:PILGA(80:20)was produced by Sigma(USA);Lysine,histidine and arginine(purlty>99%)were purchased from Sigma(USA);Chitosan(deacetylation degree:85%)was purchased from Chengdu Kelong Chemical Reagent Factory;Algin(viscosity:1.05-1.15)was purchased from Tianiin Damao Chemical Reagent Factory.METHODS:Lysine,histidine and arginine were added into PLGA with the proportion of 5%(w/v)and 10%(w/v)respectively.The resultant film sample was put into a bottle with tri-distilled-water for 2-month degradation at 37℃.The pH value of degradation solution was detected by pH meter;Each film sample was taken out and lyophilized 12 hours to get its dry weight and calculate mass loss ratio.Each variety of the solution was sampled three specimens,the average pH value,average initial weight and average finial weight of these three specimens were taken as the indices at each sampling time point,respectively.Accordingly,the regulation effect of basic amino acid was comparexl with that of algin,chitosan and NaHCO3.MAIN OUTCOME MEASURES:The changes of pH value of degradation solution;the mass loss ratio of the composite.RESULTS:Each basic additive could relieve the acid accumulation,among them,NaHCO3 was the strongest,while algin and chitosan showed a lowest capacity,basic amino acid was moderate;The suitable regulation effect could be achieved at a level of 5%lysine.CONCLUSION:Basic amino acid can effectively regulate the acid accumulation after PLGA degrades,and the optimal concentration of lysine is 5%.

OBJECTIVETo understanding the molecular mechanisms in invasion and metastasis of the ovarian carcinoma, we investigate a novel candidate metastasis-associated gene (MTA1) and nm23H1 mRNA expression and mutation in ovarian carcinoma.

METHODSTwenty primary ovarian carcinoma specimens, 20 corresponding lymph nodes and 8 normal ovarian was examined for mRNA expression and mutation of MTA1 and nm23H1 genes by reverse-transcription polymerase chain reaction (RT-PCR) and RT-PCR-SSCP analysis. The level of the expression was determined by the relative optic density (ROD) of the PCR products.

RESULTSThe frequency of MAT1 overexpression was 100% (7/7) in primary ovarian carcinoma with metastasis but only 38.5% (5/13) in those without metastasis (P=0.0103). Overexpression of MAT1 was observed in 87.5% (6/7) of lymph nodes with metastasis but only 23% (3/13) of lymph nodes without metastasis (P=0.0118). In contrast with MAT1, low expression of nm23H1 mRNA was seen in 7 of 7 ovarian carcinoma with metastasis but only in 4 of 13 (30%) of those without metastasis (P=0.0043). Low nm23H1 expression was also seen in 7 of 7 lymph nodes with metastasis but only in 5 of 13 (38.5%) nonmetastatic lymph nodes (P=0.0102). The ROD ratio of MAT1 to nm23H1 increased with the development of metastasis. No mutation of MAT1 and nm23H1 genes was found by SSCP analysis.

CONCLUSIONThe mRNA expression of MTA1 and nm23H1 is positively and negatively correlated with lymph node metastasis, respectively. Expression abnormalities but not mutation of the two genes are frequent events related to lymph node metastasis of ovarian cancer.

Female ; Histone Deacetylases ; Humans ; Lymphatic Metastasis ; genetics ; Monomeric GTP-Binding Proteins ; biosynthesis ; genetics ; Mutation ; NM23 Nucleoside Diphosphate Kinases ; Neoplasm Invasiveness ; Neoplasm Proteins ; biosynthesis ; genetics ; Nucleoside-Diphosphate Kinase ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; RNA, Messenger ; genetics ; Repressor Proteins ; Transcription Factors ; biosynthesis ; genetics

Objective To identify the genotype of the APP/tau/PS1 triple transgenic Alzheimer's disease (AD) mice,and investigate the pathological changes of tau protein in the pathogenic process.Methods Using specific primers of PS1,APP,tau gene,the genotypes of the triple transgenic AD mice were identified.Expression of tau protein in hippocampal tissue of mouse model aged 2,4,8 month was detected by immunohistochemistry.The expression of tau and its hyperphosphorylation in different sites in the hippocampal tissue and different month old mice was detected by Western blotting.Results PCR amplification fragment of 960 bp,530 bp and 400 bp of transgenic mouse genome were the expected size of APP,PS1,tau,respectively.Expression of tau in hippocampal CA3 region was increased obviously in the 8 month old mice.Compared with the normal wild-type mice,the expressions of tau and phosphorylation of pS262,pS404 and pS202 were increased significantly in hippocampus tissue of the transgenic mice (P＜0.01).Expression of tau were significantly higher in 8-and 12-monthsold mice than in 2 months-old mice (P ＜ 0.01).Phosphorylation level of pS404 and Ps202 was significantly increased since 2-months-old in transgenic mouse compared to the wild type mouse (P＜0.01),and in 8-monthold mice,there was also a significant increase as compared to that in 2 month-old mice (P＜0.01).As to the phosphorylation level of pSs262,the significant increase did not appear until 12 months old in transgenic mouse as compared to the wild type mouse (P＜0.01).Conclusions The triple transgenic mice can stably express the APP/tau/PS1 gene.The transgenic animals can be a useful model with the pathological features of tau of AD.The phosphorylation level of tau in different site increases in different time,which will provide useful research reference in Alzheimer's disease pathology and medication research.

The intestinal microbiota refers to the microbial group that exists in the intestine, and its composition disorder may affect human health. Many studies have found that intestinal microbiota and their metabolites may be closely related to the pathologies of Alzheimer′s disease (AD) through the gut-brain axis. This article will review the roles and possible mechanisms of lipopolysaccharide, functional bacterial amyloid proteins and bile acids, which are common metabolites of intestinal microbiota, in the pathogenesis of AD, and provide valuable information for exploring the pathogenesis of AD.

At present, the treatment methods of lymphoma mainly include the combined chemotherapy, hematopoietic stem cell transplantation, immunotherapy and new targeted therapies, but the treatment-related drug resistance, recurrence, extranodal and central nervous system infiltration, and leukemia transformation are still intractable problems that need to be solved in clinical practice. Studies have shown that cytokines are expressed to varying degrees in patients with lymphoma, which are significantly related to the progression of lymphoma, poor prognosis, chemotherapy response, and drug resistance. It has been confirmed that interleukin 6 (IL-6) and IL-10 are highly expressed in all types of lymphoma, and IL-10 is highly expressed in the cerebrospinal fluid of central nervous system lymphoma, all of which indicate a poor prognosis. This article reviews the role of cytokines in the development, treatment and prognosis of lymphoma.

Objective To explore the behavior characteristics ofamyloid precursor protein / tau protein / presenilin-1 (APP/Tau/PS1) transgenic mice in different months of age and study the progress of inflammation and the changes of autophagy level in brain of these APP/Tau/PS1 Alzheimer's disease(AD) mice.Methods Four-month-old wild-type (WT) mice (B6:129SF2/J) and Tau/APP/PS1 transgenic mice at 2,4,6,8 and 12 months old (n=8) were chosen in our study.Morris water maze was used to detect the spatial learning and memory abilities ofAPP/Tau/PS1 AD mice.After the paraffin section,immunohistochemical fluorescence technology was used to detect the expression and distribution of glial fibrillary acidic protein (GFAP) in the brain of mice in the above 6 groups.The expression changes of GFAP,CD45 (inflammation marker) and LC3 (autophagy marker) in the hippocampal tissues of 6 groups were detected by Western blotting.Results In the morris water maze test,the escape latency increased obviously following the increasing of months:the latency of 6 months old mice was significantly prolonged as compared with that of 2 months old mice (P＜0.05),which was further significantly increased in 12-month-old mice (P＜0.05).In the exploring experiment,with the increasing of months,the times of crossing the original table in mice showed a trend of decline,time ofresidencing in the original platform quadrant was significantly reduced.As compared with that in the WT mice,the GFAP expression in the hippocampus of 8 and 12 months old AD mice was significantly increased (P＜0.05); meanwhile,the GFAP expression in 8-month-old mice was also significantly higher than that in 2 months old AD mice (P＜0.05).The CD45 expression in 6 months old AD mice was obviously increased as compared with that of WT mice (P＜0.05).As to the level of LC3-Ⅱ/Lc-Ⅰ,there was a significant increase in 2 months old AD mice as compared with WT mice (P＜0.05),which was further increased in 4 months old AD mice (P＜0.05),but decreased in 6 and 8 months old AD mice.Conclusion With the gradually loss of the leaming and memory abilities,inflammatory reaction is significantly increased,and the autophagy level increases at first,and then,decreases in the brain ofAPP/Tau/PS1 AD mice.