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目的比较全酸蚀和自酸蚀黏结系统对牙颈部楔状缺损形成的黏结界面超微结构的影响。方法2006年9月至2007年1月在大连医科大学附属第一医院口腔科选用6颗新鲜拔除的无龋人上颌前磨牙在颊侧颈部制备3mm×3mm×2mm人造楔状缺损。使用全酸蚀单瓶系统(single bond,SB),自酸蚀一步黏结系统(adper prompl-pop,AP)处理牙面,以罗丹明B异硫氰酸盐(rhodamine B isothiocyanate)为荧光素,使用激光扫描共聚焦显微镜(CLSM)观察比较黏结界面的微观结构。结果在全酸蚀和自酸蚀黏结剂形成的黏结界面上,两种黏结剂均有良好的渗透,没有发生黏结材料与黏结界面分离的情况。SB产生的树脂突较长、混合层较厚,均大于黏结剂AP。结论SB与AP作用同类型的牙本质上,AP比SB形成的混合层薄,树脂突短。     

A framework to select clinically relevant cancer cell lines for investigation by establishing their molecular similarity with primary human cancers

Experimental work on human cancer cell lines often does not translate to the clinic. We posit that this is because some cells undergo changes in vitro that no longer make them representative of human tumors. Here, we describe a novel alignment method named Spearman's rank correlation classification method (SRCCM) that measures similarity between cancer cell lines and human tumors via gene expression profiles, for the purpose of selecting lines that are biologically relevant. To show utility, we used SRCCM to assess similarity of 36 bladder cancer lines with 10 epithelial human tumor types (N = 1,630 samples) and with bladder tumors of different stages and grades (N = 144 samples). Although 34 of 36 lines aligned to bladder tumors rather than other histologies, only 16 of 28 had SRCCM assigned grades identical to that of their original source tumors. To evaluate the clinical relevance of this approach, we show that gene expression profiles of aligned cell lines stratify survival in an independent cohort of 87 bladder patients (HR = 3.41, log-rank P = 0.0077) whereas unaligned cell lines using original tumor grades did not. We repeated this process on 22 colorectal cell lines and found that gene expression profiles of 17 lines aligning to colorectal tumors and selected based on their similarity with 55 human tumors stratified survival in an independent cohort of 177 colorectal cancer patients (HR = 2.35, log-rank P = 0.0019). By selecting cell lines that reflect human tumors, our technique promises to improve the clinical translation of laboratory investigations in cancer.     

Hydrogen sulfide in the rostral ventrolateral medulla inhibits sympathetic vasomotor tone through ATP-sensitive K+ channels

Hydrogen sulfide (H(2)S) acts as an endogenous gaseous transmitter in the central nervous system and plays important roles in regulating cardiovascular function. The rostral ventrolateral medulla (RVLM) is a putative critical central region in the control of sympathetic vasomotor tone and plays an important role in the baroreflex by integrating the inputs from a variety of visceral and somatic stimuli. In this study, we tested the hypothesis that H(2)S decreases sympathetic vasomotor tone through ATP-sensitive potassium channels (K(ATP)) in the RVLM. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) of anesthetized rats were recorded. Bilateral microinjections of sodium hydrosulfide (NaHS; 4, 8, and 16 mM, 50 nl), an H(2)S donor, into the RVLM decreased ABP, HR, and RSNA in a dose-dependent manner. Preinjection of glibenclamide (40 μM, 50 nl), a K(ATP) channel blocker, abolished the sympathoinhibitory effects of NaHS (8 mM, 50 nl). Preinjection of a nitric-oxide synthase inhibitor, N(ω)-nitro-l-arginine methyl ester (200 μM, 50 nl) partially inhibited the sympathoinhibitory effects of NaHS. Prior microinjection of 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-[trifluoromethyl]phenyl)pyridine-3-carboxylic acid methyl ester (Bay K8644) (1 μM, 50 nl), an agonist of Ca(2+) channels, did not alter the effects of NaHS. Infusion of hydroxylamine (30 mM, 50 nl), a cystathionine β-synthase inhibitor, increased ABP, HR, and RSNA. Taken together, these findings suggest that exogenous H(2)S in the RVLM inhibits sympathetic vasomotor tone by opening K(ATP) channels. Nitric-oxide signaling may partially be involved in the sympathoinhibitory effect of H(2)S in the RVLM.     

Rheumatologic and neurological events in an elderly patient with tricho-rhino-phalangeal syndrome type I

Sparse scalp hair, a peculiar shape of the nose, and cone-shaped epiphyses of the phalanges are the hallmarks of the tricho-rhino-phalangeal syndromes (TRPS). Short stature, hip dysplasia, and malformations of inner organs including mitral valve prolpase have also often been described for these conditions. Here, we described a 64-year-old woman with molecularly proved TRPS I and several atypical late-onset rheumatologic and neurological symptoms.     

Noncyclam tetraamines inhibit CXC chemokine receptor type 4 and target glioma-initiating cells

The three stereoisomers of the noncyclam compound 1 (1(R,R), 1(S,S), and the meso form 1(S,R)) and their corresponding tetrahydrochlorides 11 were prepared from (S)- and (R)-2-methylpiperidine. We have evaluated their inhibitory activity on the CXC chemokine receptor type 4 (CXCR4), toxicity properties, and assessment of their effect on glioma initiating cells (GICs) in comparison with the prototype compound AMD3100. The IC(50) values determined on human recombinant (CHO) cells showed very similar inhibitory activities albeit a lower K(B) for AMD3100, with the 1(R,R) isomer being second in potency. All the compounds showed low cardiac toxicity but, contrary to AMD3100, gave maximum nonlethal doses of around 2.0 mg/kg. The CXCR4 inhibitors had an effect on the state of differentiation of GICs, decreasing the percentage of CD44+ cells in glioblastoma multiform neurospheres in vitro. Moreover, these CXCR4 inhibitors blocked the capacity of cells to initiate orthotopic tumors in immunocompromised mice.     

Sulfur mustard and respiratory diseases

Victims exposed to sulfur mustard (HD) in World War I and Iran-Iraq war, and those suffered occupational or accidental exposure have endured discomfort in the respiratory system at early stages after exposure, and marked general physical deterioration at late stages due to pulmonary fibrosis, bronchiolitis obliterans or lung cancer. At molecule levels, significant changes of cytokines and chemokines in bronchoalveolar lavage and serum, and of selectins (in particular sE-selectin) and soluble Fas ligand in the serum have been reported in recent studies of patients exposed to HD in Iran-Iraq war, suggesting that these molecules may be associated with the pathophysiological development of pulmonary diseases. Experimental studies in rodents have revealed that reactive oxygen and nitrogen species, their product peroxynitrite (ONOO(-)), nitric oxide synthase, glutathione, poly (adenosine diphosphate-ribose) polymerase, activating protein-1 signaling pathway are promising drug targets for preventing HD-induced toxicity, whereas N-acetyl cysteine, tocopherols, melatonin, aprotinin and many other molecules have been proved to be effective in prevention of HD-induced damage to the respiratory system in different animal models. In this paper, we will systemically review clinical and pathophysiological changes of respiratory system in victims exposed to HD in the last century, update clinicians and researchers on the mechanism of HD-induced acute and chronic lung damages, and on the relevant drug targets for future development of antidotes for HD. Further research directions will also be proposed.     

Increased serum levels of S100B are related to the severity of cardiac dysfunction, renal insufficiency and major cardiac events in patients with chronic heart failure

Objective

To investigate the correlations between S100B and the severity of cardiac dysfunction, renal insufficiency (RI) and prognosis in chronic heart failure (CHF).

Method

Serum levels of S100B, TNF-α, high sensitivity CRP and NT-proBNP were determined in CHF patients with (n = 96) and without RI (n = 146). Patients with RI only (n = 62) and control subjects (n = 64) served for comparison. Patients were followed up for one year.

Results

S100B levels were higher in CHF patients with a further elevation in those with RI (P < 0.01). Serum S100B levels correlated with left ventricular ejection fraction, left ventricular end-diastolic volume and NT-proBNP in CHF patients, and eGFR in patients with RI (all P < 0.05). Increased S100B levels were associated with major cardiac events (MCE), and were independently associated with the presence of CHF (all P < 0.05).

Conclusion

Increased serum S100B levels were associated with the severity of cardiac dysfunction, RI and an adverse prognosis in CHF patients. It represents an independent risk factor for CHF.