Association of E-cadherin, matrix metalloproteinases, and tissue inhibitors of metalloproteinases with the progression and metastasis of hepatocellular carcinoma.

Molecular markers can provide additional information to traditional histomorphological evaluation for the assessment of tumor progression and predicting the likelihood of invasion and metastasis in various types of malignancies. We studied the association of E-cadherin, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinase with the progression and metastasis of hepatocellular carcinoma. Tissue microarray including six normal livers, 14 cirrhotic livers, 39 macroregenerative nodules, 16 dysplastic nodules, 22 grade I hepatocellular carcinomas, 43 grade II hepatocellular carcinomas, seven grade III hepatocellular carcinomas, and 10 metastatic hepatocellular carcinomas were stained immunohistochemically with antibodies against MMPs -1, -2, -3, -7, -9, tissue inhibitors of metalloproteinase-1, -2, -3, and E-cadherin. The intensities of staining were scored manually by two pathologists and verified by the Chromavision Automated Cellular Imaging System. Compared with normal liver, cirrhotic liver had significantly lower E-cadherin and tissue inhibitors of metalloproteinase-1 but higher MMP-1 and -7, which suggest a more favorable environment for tumor invasion and metastasis. Grade I and grade II hepatocellular carcinomas demonstrated high E-cadherin and decreased MMP-3 and -9, which may explain the rarity of extrahepatic metastasis in low-grade hepatocellular carcinomas despite the high circulatory volume of the liver. The histological progression from dysplastic nodule to well-differentiated hepatocellular carcinoma and to less differentiated tumors was associated with a gradual decrease in tissue expression of E-cadherin, tissue inhibitors of metalloproteinase-2 and -3. Metastatic hepatocellular carcinomas showed significantly lower level of tissue inhibitors of metalloproteinase-1, -2, -3 but higher level of MMP-7. These data suggest that tissue expression of E-cadherin, certain MMPs, and tissue inhibitors of metalloproteinases could be useful markers to predict the progression and metastasis of hepatocellular carcinoma.     

Downregulation of tonic GABA currents following epileptogenic stimulation of rat hippocampal cultures

Deficits in GABAergic inhibitory transmission are a hallmark of temporal lobe epilepsy and have been replicated in animal and tissue culture models of epilepsy. GABAergic inhibition comprises phasic and tonic inhibition that is mediated by synaptic and extrasynaptic GABA_A receptors, respectively. We have recently demonstrated that chronic stimulation with cyclothiazide (CTZ) or kainic acid (KA) induces robust epileptiform activity in hippocampal neurons both in vitro and in vivo . Here, we report a downregulation of tonic GABA inhibition after chronic epileptogenic stimulation of rat hippocampal cultures. Chronic pretreatment of hippocampal neurons with CTZ or KA resulted in a marked reduction in GABAergic inhibition, as shown by a significant decrease in whole-cell GABA currents and in the frequency of miniature inhibitory postsynaptic currents (mIPSCs). Interestingly, synaptically localized GABA_A receptors remained relatively stable, as evidenced by the unaltered amplitude of mIPSCs, as well as the unchanged punctate immunoreactivity of γ2 subunit-containing postsynaptic GABA_A receptors. In contrast, tonic GABA currents, assessed either by a GABA_A receptor antagonist bicuculline or a selective extrasynaptic GABA_A receptor agonist THIP, were significantly reduced following epileptogenic stimulation. These results reveal a novel form of neural plasticity, that epileptogenic stimulation can selectively downregulate extrasynaptic GABA_A receptors while leaving synaptic GABA_A receptors unchanged. Thus, in addition to synaptic alteration of GABAergic transmission, regulation of tonic inhibition may also play an important role during epileptogenesis.     

Synthesis and thermal properties of poly(enaminonitriles) containing flexible ether units

Poly(enaminonitriles) containing flexible alkyl ether units were prepared by reacting p-bis(1-chloro-2,2-dicyanovinyl)benzene with various α,ω-bis(4-aminophenoxy)alkanes in N-methyl-2-pyrrolidone (NMP). All the polymers are soluble in polar aprotic solvents such as N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMAc) and NMP as well as in common organic solvents such as tetrahydrofuran and acetone. High molecular weight polymers possessing inherent viscosities in the range of 0.82–1.20 dL/g were obtained and tough films were cast from a DMF solution. They showed a large exotherm around 340°C attributable to the chemical changes of the dicyanovinyl group. Thermogravimetric analyses exhibited a good thermal stability with a 10% weight loss around 450°C and 73–88% residual weight at 500°C under nitrogen.     

Kinetics of the polymerization of isoprene with isopropoxyneodymium dichloride/triethylaluminium binary lanthanide catalyst system

The kinetics of the polymerization of isoprene with the heterogeneous rare earth catalyst system isopropoxyneodymium dichloride/triethylaluminium (Nd(OPrⁱ)Cl₂-AlEt₃) was examined in a specially designed dilatometer. The rate of polymerization is expressed as R_p ≈ ?d[M]/dt = k[Nd]^1.40 [M]. The main kinetical parameters such as the concentration of active propagating chain, the efficiency of lanthanide catalyst used (ELCU), the absolute rate constant of propagation as well as the average life time of growing chains, were determined at 30°C, 40°C, 45°C and 50°C.     

七年制医学生消化内科临床见习带教体会

七年制医学生基础知识扎实、自学能力强,但临床分析和解决问题的实际工作能力欠缺,而临床见习是医学生理论联系实际的纽带和桥梁。因此,努力提高临床见习的带教效果,对于医学生理解、巩固所学基础知识,为临床实习奠定良好的实践基础至关重要。现结合我科多年带教七年制学生见习的具体情况,探讨如何提高七年制医学生临床见习的带教效果。1传统消化内科见习带教中的困难和缺陷消化内科理论课学时多、专业性强,学习内容多、概念抽象,使学生理解较困难。过去见习带教中大部分时间以教师讲课为主,学生多处于被动地位,部分学生出现厌烦、兴趣不浓…     

The NAD(P)H:quinone oxidoreductase I C609T polymorphism modifies the risk of Barrett esophagus and esophageal adenocarcinoma.

PURPOSE: The role of genetic susceptibility to esophageal adenocarcinoma and its precursor lesion Barrett esophagus has not been fully elucidated. This study investigated the effect of polymorphisms in the manganese superoxide dismutase (MnSOD) and NAD(P)H:quinone oxidoreductase 1 (NQO1) genes in modulating the risk of developing Barrett esophagus or esophageal adenocarcinoma. METHODS: A total of 584 patients (146 esophagitis, 200 Barrett esophagus, 144 esophageal adenocarcinoma, and 94 controls) were genotyped for the MnSOD C14T and NQO1 C609T polymorphisms using polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: The NQO1 TT genotype was less common in Barrett esophagus (2.0%) and esophageal adenocarcinoma (1.4%) patients, compared with both esophagitis patients (7.6%) and controls (5.4%). After adjustment for sex, age, body mass index, reflux symptoms, and smoking status, patients with the homozygous TT genotype had a 4.5-fold decreased risk of developing Barrett esophagus (odds ratio = 0.22, 95% confidence interval = 0.07-0.76, P = 0.01) and a 6.2-fold decreased risk of esophageal adenocarcinoma (odds ratio = 0.16, 95% confidence intervals = 0.03-0.94, P = 0.04) compared with individuals with the TC and CC genotypes. No significant differences between groups were observed for the MnSOD polymorphism (P = 0.289). CONCLUSIONS: Overall, the results of this study suggest that the NQO1 TT genotype may offer protection from reflux complications such as Barrett esophagus and esophageal adenocarcinoma.     

Diagnostic impact of core-needle biopsy on fine-needle aspiration of non-Hodgkin lymphoma

We retrospectively reviewed 74 fine-needle aspiration (FNA) cases of presumptive non-Hodgkin lymphoma (NHL). All the cases had cytology and core-needle biopsy and 53 cases had concurrent flow cytometric analysis. FNA (cytology and flow cytometry) and core-needle biopsy were evaluated independently. FNA was diagnostic of diffuse large B-cell lymphoma (DLBL) in 25% (13/53) of cases and small B-cell NHL in 15% (8/53) of cases, whereas core-needle biopsy was diagnostic of DLBL in 37% (27/74) of cases and small B-cell NHL in 8% (6/74) of cases. Subclassification of small B-cell NHL was reached in 3/6 cases by core-needle biopsy. Insufficient cases were observed in both FNA (47%; 25/53) and core-needle biopsy (28%; 21/74) groups. With the combination of FNA and core-needle biopsy, diagnostic cases of DLBL increased to 43% (32/74) and insufficient samples were reduced to 16% (12/74). There was no clear advantage in the diagnosis and classification of small B-cell NHL by adding core-needle biopsy to FNA (14%; 10/74). We conclude that core-needle biopsy is a useful adjunct to FNA in the diagnosis of DLBL and shall be encouraged. In small B-cell NHL, core-needle biopsy does not add to the diagnostic ability of FNA. Cases insufficient for diagnosis may be seen in both core-needle biopsy and FNA. A combined approach reduces the number of insufficient cases and is recommended in routine FNA practice.     

Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome

7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies.     

石灰水对埃及伊蚊不同发育阶段影响研究

目的通过石灰水对埃及伊蚊生活史幼期不同阶段生长发育影响的实验室研究,评价生石灰对防治埃及伊蚊的干预效果,为生石灰用于埃及伊蚊的防治提供实验数据。方法将一定数量的埃及伊蚊依据不同发育阶段(卵、Ⅰ~Ⅳ龄期蚊幼、蛹)分别饲养于石灰水中,观察蚊幼活动情况,记录不同时期相应孵化时间、孵化率和死亡率,同时将实验室过夜自来水(实验室脱氯水)饲养蚊虫作对照,分析比较不同饲养环境、不同发育阶段埃及伊蚊发育的变化差异。结果对照组埃及伊蚊卵的平均孵化时间为1.75 d,而试验组(1.3 g/L石灰水饲养)埃及伊蚊卵的平均孵化时间为3.84 d,是对照组的2.19倍,孵化时间的差异具有统计学意义(t=36.02,P<0.05)。试验组埃及伊蚊卵孵化率为59.3%,对照组为89.3%,两组之间孵化率的差异具有统计学意义(χ^(2)=35.38,P<0.05)。Ⅰ~Ⅳ龄试验组蚊幼死亡率分别为44.0%、92.0%、97.3%、98.7%,显著高于对照组蚊幼死亡率,两组之间死亡率的差异具有统计学意义(χ^(2)值为65.79~276.53,P<0.05)。试验组蛹的死亡率为98.7%,显著高于对照组的死亡率,两组之间死亡率的差异具有统计学意义(χ^(2)=280.35,P<0.05)。对照组埃及伊蚊卵、蚊幼和蛹的死亡率分别为10.7%、2.3%和2.0%,三组之间死亡率的差异具有统计学意义(χ^(2)=25.09,P<0.05)。对照组埃及伊蚊卵的死亡率明显高于蚊幼和蛹。试验组埃及伊蚊卵、蚊幼和蛹的死亡率分别为40.7%、83.0%和98.7%,三组之间死亡率差异具有统计学意义(χ^(2)=170.88,P<0.05)。结论石灰水对埃及伊蚊不同发育阶段均具有明显抑制作用,对蛹的杀灭作用最大,其次是蚊幼和卵。随着埃及伊蚊幼虫年龄的增长,石灰水对其抑制效果逐渐增强。但生石灰对埃及伊蚊成蚊的防治效果有待进一步的现场验证。     

LT受体拮抗剂对大鼠肺纤维化LTB_4及血F_n的影响

45只大鼠随机分为 3组 ,对照组、模型组、治疗组各 15只。治疗组气管内单次灌注博莱霉素 (5 mg)后每日以安可来 (ACL,10 mg/ kg)灌胃 ;模型组气管内灌注同治疗组 ,灌胃以生理盐水代替。 3组动物在气管内灌注后分别于第 7、14、2 8d随机处死 5只 ,取左肺下叶 1g匀浆测 L TB4,心腔血测纤维联结蛋白 (Fn)。模型组和治疗组在气管内灌注后白三烯 B4(L TB4)迅速上升 ,第 7d达高峰 ,第 2 8d模型组 L TB4仍较高 ,治疗组 L TB4明显下降 ;Fn浓度模型组在第 7d明显升高 ,治疗组及对照组较低。结论 :在鼠实验性肺间质化过程中 L TB4明显增高 ,白三烯对肺间质纤维化的发生发展起一定作用