腺样体肥大患者的认知功能改变

目的探讨腺样体肥大患者的认知功能改变,进一步指导临床。方法对70名10～19岁腺样体肥大患者采用《基本认知能力测验》（2.0版）进行认知功能检查。结果除无意义图形再认以外,基本认知能力总分及各分项分均为两个高年龄组低于10～12岁组。总分13～15岁组与10～12岁组差异有显著性（P=0.039）;汉字比较13～15、16～19岁组分别与10～12岁组的差异均有显著性（P值分别为0.007、0.001）;双字词再认16～19岁组与10～12岁组的差异有显著性（P=0.029）。两个高年龄组基本认知能力的印象评定均显著差于10～12岁组。除无意义图形再认外,总分及各分项分均为男性差于女性,其中总分及汉字比较、双字词再认男女差异均具有显著性（P分别为0.028、0.000、0.028）。结论腺样体肥大是认知功能损害的重要因素,认知速度、记忆能力的损害尤为显著;12岁是一重要的分界年龄;同等基线条件下男性的认知功能损害重于女性。建议早期手术治疗,对于男性相对放松手术指征,以减少对患者认知功能的损害。     

Expression of KiSS‐1 Gene and its Role in Invasion and Metastasis of Human Hepatocellular Carcinoma

KiSS‐1 has been identified as a putative metastasis‐suppressor gene in human melanomas and breast cancer cell lines. Although loss of KiSS‐1 expression has been associated with progression and poor prognosis of various cancers, the exact role of KiSS‐1 expression in HCC is not well‐defined. Our study investigated KiSS‐1 expression levels in HCC and its role in invasion and metastasis of human HCC. The expression levels of KiSS‐1 and MMP‐9 protein were determined by tissue microarray (TMA) serial sections, immunohistochemistry and semi‐quantitative image analysis. All clinical and histological data obtained were subjected to statistical analysis. The expression of KiSS‐1 protein in HCC and intrahepatic metastasis lesions was significantly lower (P < 0.01) when compared with non‐tumor liver tissue and normal liver tissue. Multivariate analysis revealed a significant inverse correlation between KiSS‐1 expression and ○1 TNM stage, (F = 7.113, P < 0.01) and ○2intrahepatic metastasis (t = 2.898, P < 0.01). Loss of KiSS‐1 in intrahepatic metastasis versus primary carcinomas was statistically significant (P<0.01). We also found a negative correlation between KiSS‐1 and MMP‐9 expression in HCC (r = ‐0.506, P < 0.01). We conclude that loss of KiSS‐1 during HCC metastasis, along with a concomitant upregulation of MMP‐9 suggests a possible mechanism for cell motility and invasion during HCC metastasis, with KiSS‐1 emerging as a possible therapeutic target during HCC metastasis. Anat Rec, 292:1128–1134, 2009. © 2009 Wiley‐Liss, Inc.     

Regulatory effects of IFN‐β on production of osteopontin and IL‐17 by CD4+ T Cells in MS

IFN‐β currently serves as one of the major treatments for MS. Its anti‐inflammatory mechanism has been reported as involving a shift in cytokine balance from Th1 to Th2 in the T‐cell response against elements of the myelin sheath. In addition to the Th1 and Th2 groups, two other important pro‐inflammatory cytokines, IL‐17 and osteopontin (OPN), are believed to play important roles in CNS inflammation in the pathogenesis of MS. In this study, we examined the potential effects of IFN‐β on the regulation of OPN and IL‐17 in MS patients. We found that IFN‐β used in vitro at 0.5–3 ng/mL significantly inhibited the production of OPN in primary T cells derived from PBMC. The inhibition of OPN was determined to occur at the CD4⁺ T‐cell level. In addition, IFN‐β inhibited the production of IL‐17 and IL‐21 in CD4⁺ T cells. It has been described that IFN‐β suppresses IL‐17 production through the inhibition of a monocytic cytokine, the intracellular translational isoform of OPN. Our further investigation demonstrated that IFN‐β also acted directly on the CD4⁺ T cells to regulate OPN and IL‐17 expression through the type I IFN receptor‐mediated activation of STAT1 and suppression of STAT3 activity. Administration of IFN‐β to EAE mice ameliorated the disease severity. Furthermore, spinal cord infiltration of OPN⁺ and IL‐17⁺ cells decreased in IFN‐β‐treated EAE mice along with decreases in serum levels of OPN and IL‐21. Importantly, decreased OPN production by IFN‐β treatment contributes to the reduced migratory activity of T cells. Taken together, the results from both in vitro and in vivo experiments indicate that IFN‐β treatment can down‐regulate the OPN and IL‐17 production in MS. This study provides new insights into the mechanism of action of IFN‐β in the treatment of MS.     

马氏钳蝎蝎毒分离组分Ⅲ体外抗癌活性的实验研究

蝎毒组分Ⅲ（ｓｃｏｒｐｉｏｎｖｅｎｏｍｃｏｍｐｏｏｃｎｔⅢ，ＳＶＥⅢ）是从马氏钳蝎粗毒分离纯化获得的有效成分之一。本文用ＳＶＣⅢ处理体外培养的人喉癌ＨＥｐ￣（－２）细胞系和人直肠腺癌Ｃ１１８４细胞系，研究其抗癌活性。结果表明，以丝裂霉素做为阳性对照，ＳＶＣⅢ（１．６～８．０μｇ／ｍｌ）对两种癌细胞呈毒性和杀伤作用（Ｐ＜０．０１）。当ＳＶＣⅢ浓度为４．８、６．４和８．０μｇ／ｍｌ时，ＨＥｐ￣（－２）细胞和Ｃ１１８４细胞的克隆形成率降低（Ｐ＜０．０１），具有剂量依赖性，半数抑制浓度分别为５．０１μｇ／ｍｌ和６．６μｇ／ｍｌ。较大剂量ＳＶＣⅢ处理癌细胞２４ｈ，生长抑制率呈明显增高，以后趋于坪式。ＳＶＣⅢ还使有丝分裂指数和多核率减少。分化程度较高的ＨＥｐ－２细胞对ＳＶＣⅢ更为敏感。提示ＳＶＣⅢ是存在于蝎毒中的天然、高效低毒的抗癌成分。     

T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface

The T cell immunoglobulin mucin (Tim) family of receptors regulates effector CD4(+) T cell functions and is implicated in autoimmune and allergic diseases. Tim-3 induces immunological tolerance, and engagement of the Tim-3 immunoglobulin variable (IgV) domain by galectin-9 is important for appropriate termination of T helper 1-immune responses. The 2 A crystal structure of the Tim-3 IgV domain demonstrated that four cysteines, which are invariant within the Tim family, form two noncanonical disulfide bonds, resulting in a surface not present in other immunoglobulin superfamily members. Biochemical and biophysical studies demonstrated that this unique structural feature mediates a previously unidentified galectin-9-independent binding process and suggested that this structural feature is conserved within the entire Tim family. The current work provided a graphic example of the relationship between sequence, structure, and function and suggested that the interplay between multiple Tim-3-binding activities contributes to the regulated assembly of signaling complexes required for effective Th1-mediated immunity.     

Grafting sulfobetaine monomer onto the segmented poly(ether-urethane) surface to improve hemocompatibility

Polyurethanes are widely used as blood-contacting biomaterials, due to their good biocompatibility and mechanical properties. Nevertheless, their blood compatibility is still not adequate for more demanding applications. Surface modification is an effective way to improve the hemocompatibility for biomaterials. The purpose of the present study was to synthesize a novel nonthrombogenic biomaterial by modifying the surface of polyurethane. Ozonization was used to introduce active peroxide groups onto the segmented poly(ether-urethane) (SPEU) film surface and graft polymerization of N,N'-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate (DMAPS), a sulfobetaine structure, onto the ozone-activated SPEU surface was conducted. The SPEU-g-PDMAPS film was characterized by ATR-FTIR, XPS, and contact angle measurements. ATR-FTIR and XPS confirmed the graft polymerization. The grafted film possessed a relatively hydrophilic surface, as revealed by contact angle measurement. The blood compatibility of the grafted films was evaluated by a platelet-rich plasma (PRP) adhesion study and scanning electron microscopy, using SPEU film as the reference. No platelet adhesion was observed for the grafted films incubated with PRP at 37 degrees C for 60 and 180 min. This new sulfobetaine structure grafted biomaterial might have potential for biomedical applications.     

Detection of parvovirus B19 capsid proteins in lymphocytic cells in synovial tissue of autoimmune chronic arthritis.

The pathogenic influence of viral agents in chronic inflammatory joint diseases like rheumatoid arthritis has been discussed for many years. More recently, DNA of several viruses, among them parvovirus B19 (B19), was traceable by PCR analysis in synovial fluid and synovial tissue. To investigate the potential role of parvovirus B19 in rheumatoid arthritis, we analyzed the expression of B19 VP1/VP2 proteins by immunohistochemistry in paraffin sections of 63 synovial specimens in rheumatoid arthritis (RA; n = 29), psoriatic arthritis (PSA; n = 6), nonspecific arthritis or synovitis (n = 26), and normal synovia (n = 2). Thereby we could demonstrate replicative virus infection in a variable number of cells in about 90% of rheumatoid specimens and in four of six (66%) cases of psoriatic arthritis, but only in 38% of cases with chronic reactive inflammation and one case of normal synovia. In virus-positive rheumatoid specimens, moreover, the average number of affected cells was significantly higher than in virus-expressing synovia of nonspecific reactive inflammation. These findings support the importance of B19-viral infection in the pathogenesis of chronic arthritis. B19-positive cells in the synovia could be ascribed to CD20- or CD3-positive B- or T-lymphocytes by double immunostaining. Based on these results, B19 infection of lymphocytic cells also seems possible.     

Altered resting‐state activity in seasonal affective disorder

At present, our knowledge about seasonal affective disorder (SAD) is based mainly up on clinical symptoms, epidemiology, behavioral characteristics and light therapy. Recently developed measures of resting‐state functional brain activity might provide neurobiological markers of brain disorders. Studying functional brain activity in SAD could enhance our understanding of its nature and possible treatment strategies. Functional network connectivity (measured using ICA‐dual regression), and amplitude of low‐frequency fluctuations (ALFF) were measured in 45 antidepressant‐free patients (39.78 ± 10.64, 30 ♀, 15 ♂) diagnosed with SAD and compared with age‐, gender‐ and ethnicity‐matched healthy controls (HCs) using resting‐state functional magnetic resonance imaging. After correcting for Type 1 error at high model orders (inter‐RSN correction), SAD patients showed significantly increased functional connectivity in 11 of the 47 identified RSNs. Increased functional connectivity involved RSNs such as visual, sensorimotor, and attentional networks. Moreover, our results revealed that SAD patients compared with HCs showed significant higher ALFF in the visual and right sensorimotor cortex. Abnormally altered functional activity detected in SAD supports previously reported attentional and psychomotor symptoms in patients suffering from SAD. Further studies, particularly under task conditions, are needed in order to specifically investigate cognitive deficits in SAD. Hum Brain Mapp 35:161–172, 2014. © 2012 Wiley Periodicals, Inc.     

磷酸钙骨水泥与外源性神经生长因子复合移植修复兔桡骨缺损★

背景：磷酸钙骨水泥仅具有传导成骨作用，缺乏成骨因子，因此单独应用还难以满足临床需要，而复合生长因子后有可能改善其性能，使其成为理想的骨替代材料。 目的：尝试将磷酸钙骨水泥和外源性神经生长因子复合，制备一种新型促进骨生长的人工骨材料，并观察其是否具有促进成骨的作用。 设计、时间及地点：随机对照动物体内观察，于2006-05/2007-05在中南大学湘雅三医院中心实验室完成。 材料：自制磷酸钙骨水泥，4 ℃下与神经生长因子复合制备磷酸钙骨水泥/神经生长因子复合人工骨。 方法：40只兔随机分成实验组和对照组2组，每组20只，制备右桡骨中段约1.5 cm的骨缺损模型，实验组桡骨断端间填入神经生长因子/磷酸钙骨水泥复合人工骨，对照组填入单纯磷酸钙骨水泥。 主要观察指标：术后2，3，4，8周4个时间点观察并取标本，应用X射线片、组织细胞形态学、扫描电镜及免疫组织化学染色等手段观察新骨形成的情况。 结果：实验组2周见到新骨长入，4周骨缺损修复基本完成，材料被部分吸收，剩余材料与新骨结合紧密；而对照组成骨量明显少于实验组，而且成骨速度缓慢，材料本身吸收降解现象不明显。 结论：磷酸钙骨水泥/神经生长因子复合物能促进骨组织生长，可作为一种新型人工骨材料修复骨缺损。     

Local synchronization and amplitude of the fluctuation of spontaneous brain activity in attention-deficit/hyperactivity disorder: a resting-state fMRI study

Regional homogeneity（ReHo）and the amplitude of low-frequency fluctuation（ALFF）are two approaches to depicting different regional characteristics of resting-state functional magnetic resonance imaging（RS-fMRI）data.Whether they can complementarily reveal brain regional functional abnormalities in attention-deficit/hyperactivity disorder（ADHD）remains unknown.In this study,we applied ReHo and ALFF to 23 medication-na ve boys diagnosed with ADHD and 25 age-matched healthy male controls using whole-brain voxel-wise analysis.Correlation analyses were conducted in the ADHD group to investigate the relationship between the regional spontaneous brain activity measured by the two approaches and the clinical symptoms of ADHD.We found that the ReHo method showed widely-distributed differences between the two groups in the fronto-cingulo-occipitocerebellar circuitry,while the ALFF method showed a difference only in the right occipital area.When a larger smoothing kernel and a more lenient threshold were used for ALFF,more overlapped regions were found between ALFF and ReHo,and ALFF even found some new regions with group differences.The ADHD symptom scores were correlated with the ReHo values in the right cerebellum,dorsal anterior cingulate cortex and left lingual gyrus in the ADHD group,while no correlation was detected between ALFF and ADHD symptoms.In conclusion,ReHo may be more sensitive to regional abnormalities,at least in boys with ADHD,than ALFF.And ALFF may be complementary to ReHo in measuring local spontaneous activity.Combination of the two may yield a more comprehensive pathophy-siological framework for ADHD.