海桐皮汤熏洗治疗膝骨性关节炎：与扶他林乳剂的比较

背景：膝骨性关节炎是由于风寒湿邪痹阻关节、经络所致,而海桐皮汤具有使气血通畅,经络舒展,肿胀消退之功效。 目的：观察海桐皮汤熏洗治疗膝骨性关节炎的临床疗效。 方法：将符合纳入标准的110例膝骨性关节炎患者按就诊先后顺序随机分为熏洗组与对照组,其中熏洗组55例,对照组55例。根据设计好的症状体征评分标准,计算治疗前患者的症状体征积分;分别予以海桐皮汤熏洗及扶他林乳剂外用治疗,1个月后比较治疗前后患者的临床症状、体征、疼痛积分的变化及两治疗组在不良反应、失访率和复发率等的差异。 结果与结论：两种药物在改善患者症状体征方面均具有良好疗效,海桐皮汤熏洗疗效[(控显率57.45%,总有效率95.74%)]优于外用扶他林乳剂[(控显率37.0%,总有效率78.3%)]。两组治疗后疼痛积分较治疗前减少(P <0.01或0.05);熏洗组明显优于对照组(P < 0.01)。熏洗组有3例患者出现皮疹、红斑等过敏现象,对照组中2例患者也出现上述过敏现象,均在休息一两天后缓解,两组不良反应差异无显著性意义;熏洗组复发率低于对照组。结果证实,海桐皮汤熏洗对治疗早、中期膝骨性关节炎疗效确切,疗效优于外用扶他林乳剂,且复发率低于对照组。     

Epigenetic inactivation and tumor suppressor activity of HAI‐2/SPINT2 in gastric cancer

Hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI‐2/SPINT2) encodes Kunitz‐type protease inhibitor that regulates HGF activity. Inspection of the human HAI‐2/SPINT2 locus uncovered a large and dense CpG island within the 5′ region of this gene. Analysis of cultured human gastric tumor lines indicated that HAI‐2/SPINT2 expression is either undetectable or in low abundance in several lines; however, enhanced gene expression was measured in cells cultured on the DNA demethylating agent 5‐aza‐2′‐deoxycytidine. Bisulfite DNA sequencing confirmed the densely methylated HAI‐2/SPINT2 promoter region. Forced expression of HAI‐2/SPINT2 induced cell apoptosis, suppressed anchorage independent growth in vitro and tumor growth in vivo. We investigated HAI‐2/SPINT2 aberrant methylation in patients with gastric cancer. The HAI‐2/SPINT2 methylation was found preferentially in cancerous tissues (30 of 40, 75%) compared with nontumor tissues (no methylation was detected), indicating that this aberrant characteristic is common in gastric malignancies. In conclusion, epigenetic inactivation of HAI‐2/SPINT2 is a common event contributing to gastric carcinogenesis and may be a potential biomarker for gastric cancer.     

Report of the fourth meeting on ‘Influenza vaccines that induce broad spectrum and long-lasting immune responses’, World Health Organization and Wellcome Trust,London, United Kingdom, 9–10 November 2009

Current influenza vaccines are limited by the need for annual immunisation, frequent antigenic updating to match the evolution of circulating influenza virus strains, and reduced efficacy in elderly persons. On 9–10 November 2009, the Initiative for Vaccine Research of the World Health Organization convened jointly with the Wellcome Trust in London, United Kingdom, the fourth meeting on ‘Influenza vaccines that induce broad spectrum and long-lasting immune responses’. Presentations were made by representatives from industry, academia, governmental and non-governmental organisations. The objectives of the meeting were to update the progress of research in the field of influenza vaccine strategies able to generate cross protection against divergent influenza virus strains. Improvements in existing strategies including live attenuated influenza vaccines and adjuvantation of inactivated vaccines were summarised. Developments in novel antigen production methods, new routes of vaccine delivery and administration, and vaccine approaches based on conserved virus antigens were explored. In addition, correlates of immune protection and regulatory issues for the evaluation and approval of future novel vaccine strategies were discussed.     

Apparent diffusion coefficient measurements with diffusion-weighted magnetic resonance imaging for evaluation of hepatic fibrosis

PURPOSE: To evaluate the use of apparent diffusion coefficient (ADC) measurements based on diffusion-weighted MRI (DWI) to assess stage of liver disease. MATERIALS AND METHODS: A total of 31 patients who underwent both a liver biopsy and DWI and 132 patients who only underwent DWI were enrolled. Biopsy specimens were scored for fibrosis and necroinflammation according to the Knodell histology activity index (HAI). The 31 patients consisted of 21 patients with chronic hepatitis and 10 with cirrhosis (Child-Pugh stage A in nine and stage B in one), and the 132 patients consisted of 56 patients with cirrhosis (Child-Pugh stage A in 41, stage B in 10, and stage C in five), 42 with chronic hepatitis, and 34 with normal liver function. The ADCs in the liver parenchyma were measured using DWI with relatively low b factors (b = 0.01 and 128.01 seconds/mm(2)) and were compared among the HAI scores and among patients with cirrhosis, chronic hepatitis, and normal liver function. RESULTS: The ADCs decreased as the fibrosis score in the HAI increased, and the correlation was statistically significant (P < 0.0001). No relationship between the ADCs and the necroinflammation scores in the HAI was found. The ADCs decreased as the stage of liver disease progressed or as the Child-Pugh stage progressed, and these relationships were statistically significant (P < 0.0001). CONCLUSION: ADC measurements are potentially useful for the evaluation of fibrosis staging in the liver.     

Deregulated matriptase activity in oral squamous cell carcinoma promotes the infiltration of cancer‐associated fibroblasts by paracrine activation of protease‐activated receptor 2

Cancer‐associated fibroblasts (CAFs) are known to contribute to cancer progression. We have reported that cell surface expression of hepatocyte growth factor activator inhibitor 1 (HAI‐1) is decreased in invasive oral squamous cell carcinoma (OSCC) cells. This study examined if HAI‐1‐insufficiency contributes to CAF recruitment in OSCC. Serum‐free conditioned medium (SFCM) from a human OSCC line (SAS) stimulated the migration of 3 human fibroblast cell lines, NB1RGB, MRC5 and KD. SFCM from HAI‐1‐knockdown SAS showed an additive effect on the migration of NB1RGB and MRC5, but not KD. SAS SFCM induced protease‐activated receptor‐2 (PAR‐2) expression in NB1RGB and MRC5, but not in KD, and a PAR‐2 antagonist blocked the stimulatory effect of HAI‐1 knockdown on migration of the PAR‐2 expressing cell lines. Moreover, HAI‐1‐deficient SFCM showed additive stimulatory effects on the migration of wild‐type but not PAR‐2‐deficient mouse fibroblasts. Therefore, the enhanced migration induced by HAI‐1‐insufficiency was mediated by PAR‐2 activation in fibroblasts. This activation resulted from the deregulation of the activity of matriptase, a PAR‐2 agonist protease. HAI‐1 may thus prevent CAF recruitment to OSCC by controlling matriptase activity. When HAI‐1 expression is reduced on OSCC, matriptase may contribute to CAF accumulation by paracrine activation of fibroblast PAR‐2. Immunohistochemical analysis of resected OSCC revealed increased PAR2‐positive CAFs in 35% (33/95) of the cases studied. The increased PAR‐2 positive CAFs tended to correlate with infiltrative histology of the invasion front and shorter disease‐free survival of the patients.     

Oral administration of an adenovirus vector encoding both an avian influenza A hemagglutinin and a TLR3 ligand induces antigen specific granzyme B and IFN-γ T cell responses in humans

Purpose

To test the safety and immunogenicity of an orally delivered avian influenza vaccine. The vaccine has a non-replicating adenovirus type 5 vector backbone which expresses hemagglutinin from avian influenza and a TLR3 ligand as an adjuvant.

Methods

Forty-two subjects were randomized into 3 groups dosed with either 1 × 10¹⁰, 1 × 10⁹, or 1 × 10⁸ IU of the vaccine administered in capsules. Twelve subjects were vaccinated with identical capsules containing placebo. A portion of the 1 × 10⁹ dose group were immunized a second time 4 weeks after the first immunization. The safety of the vaccine was assessed by measuring the frequency and severity of adverse events in placebo versus vaccine treated subjects. IFN-γ and granzyme B ELISpot assays were used to assess immunogenicity.

Results

The vaccine had a positive safety profile with no treatment emergent adverse events reported above grade 1, and with an adverse event frequency in the treated groups no greater than placebo. Antigen specific cytotoxic and IFN-γ responses were induced in a dose dependent manner and cytotoxic responses were boosted after a second vaccination.

Conclusion

This first in man clinical trial demonstrates that an orally delivered adenovirus vectored vaccine can induce immune responses to antigen with a favorable safety profile. Clinical Trial Registration number: NCT01335347.     

HAI‐2 is epigenetically downregulated in human hepatocellular carcinoma,and its Kunitz domain type 1 is critical for anti‐invasive functions

Pharmacological demethylation‐based gene expression profile analysis is a useful tool to identify epigenetically silenced tumour suppressor genes. HGF activator inhibitor 2 (HAI‐2), a serine protease inhibitor, has been identified as one of the candidate tumour suppressor genes in human hepatocellular carcinoma (HCC) with this technique. In this study, we aimed to characterise the epigenetic status and tumour suppressive function of HAI‐2 in HCC. We validated that HAI‐2 expression was either absent or low in most of the HCC cell lines tested, and 5‐Aza‐2′‐deoxycytidine treatment significantly restored its expression in 9 (75%) of these 12 cell lines. HAI‐2 was found to be frequently underexpressed in human HCCs (p < 0.001). With bisulphite DNA sequencing and methylation‐specific PCR, we found that the promoter of the HAI‐2 gene was frequently hypermethylated in both HCC cell lines and human HCCs. Ectopic expression of HAI‐2 significantly inhibited cell migration and invasiveness of HCC cells in vitro and suppressed tumourigenicity in vivo. In addition, we also provided the first evidence that HAI‐2 mediated its tumour suppressor function via the Kunitz domain 1 (KD‐1), as KD‐1 but not KD‐2 inactivating mutant abolished its anti‐tumour invasiveness in vitro. Our findings suggest that HAI‐2 is a candidate tumour suppressor gene that is frequently hypermethylated and underexpressed in human HCCs, and the KD‐1 domain of HAI‐2 is the key region responsible for its anti‐invasive function. © 2008 Wiley‐Liss, Inc.     

消化外科老年患者发生医院感染的调查分析和护理对策

目的调查分析我院消化外科老年患者发生医院感染的情况,以提出相应的措施来降低和控制医院感染发生率。方法采用回顾性调查方法对我院消化外科2006年1-3月出院的90例老年患者发生的医院感染情况进行分析。结果90例老年患者中19例发生医院感染,医院感染发生率为21．11％;患者的年龄越大、住院时间越长,医院感染率越高。老年患者发生医院感染的高发部位为呼吸道,其次为泌尿道;胰腺疾病患者的医院感染发生率最高;引起感染的病原体中以金黄色葡萄球菌居首位（20．69％）。结论必须加强综合性医院消化外科老年住院患者院内感染的管理,尤其是控制呼吸系统感染,加强胰腺疾病的术后护理,严格无菌技术,规范抗生素使用,减少侵入性操作,以促进消化外科老年患者的身体康复。     

Evaluation of correlates of protection against influenza A(H3N2) and A(H1N1)pdm09 infection: Applications to the hospitalized patient population

Background

Influenza vaccines are important for prevention of influenza-associated hospitalization. However, the effectiveness of influenza vaccines can vary by year and influenza type and subtype and mechanisms underlying this variation are incompletely understood. Assessments of serologic correlates of protection can support interpretation of influenza vaccine effectiveness in hospitalized populations.