沙门氏菌gyrA基因的变异对氟喹诺酮类药物敏感性的影响

目的分析125株萘啶酮酸耐药性沙门氏菌gyrA基因QRDR区变异情况及其对氟喹诺酮类药物敏感性的影响。方法用常规血清学方法鉴定沙门氏菌分离株血清型,通过微量稀释法测定其对萘啶酮酸和3种氟喹诺酮的敏感性,用PCR方法扩增沙门氏菌gyrA基因QRDR的序列并进行序列分析。结果这些分离株涉及18个血清型,最常见的血清型为德尔卑沙门氏菌和肠炎沙门氏菌,它们的分离率分别为22.4%(28/125)和19.2%(24/125)。沙门氏菌分离株对萘啶酮酸的耐药率为39/125。3种氟喹诺酮药物对萘啶酮酸耐药性沙门氏菌的最小抑菌浓度明显比萘啶酮酸敏感株高。萘啶酮酸耐药性沙门氏菌gyrA基因QRDR的序列分析表明,所有萘啶酮酸耐药性沙门氏菌gyrA基因的83或87位点发生了突变,83位点发生点突变的菌株对萘啶酮酸的MIC范围大于或等于1024μg/ml,而87位点突变的菌株的MIC范围为32～512μg/ml。结论沙门氏菌分离株gyrA基因发生点突变的位点与萘啶酮酸耐药水平高低存在关联,且导致对三种氟喹诺酮类药物的敏感性下降。     

Inhibiting MT2‐TFE3‐dependent autophagy enhances melatonin‐induced apoptosis in tongue squamous cell carcinoma

Autophagy modulation is a potential therapeutic strategy for tongue squamous cell carcinoma (TSCC). Melatonin possesses significant anticarcinogenic activity. However, whether melatonin induces autophagy and its roles in cell death in TSCC are unclear. Herein, we show that melatonin induced significant apoptosis in the TSCC cell line Cal27. Apart from the induction of apoptosis, we demonstrated that melatonin‐induced autophagic flux in Cal27 cells as evidenced by the formation of GFP‐LC3 puncta, and the upregulation of LC3‐II and downregulation of SQSTM1/P62. Moreover, pharmacological or genetic blockage of autophagy enhanced melatonin‐induced apoptosis, indicating a cytoprotective role of autophagy in melatonin‐treated Cal27 cells. Mechanistically, melatonin induced TFE3^(Ser321) dephosphorylation, subsequently activated TFE3 nuclear translocation, and increased TFE3 reporter activity, which contributed to the expression of autophagy‐related genes and lysosomal biogenesis. Luzindole, a melatonin membrane receptor blocker, or MT2‐siRNA partially blocked the ability of melatonin to promote mTORC1/TFE3 signaling. Furthermore, we verified in a xenograft mouse model that melatonin with hydroxychloroquine or TFE3‐siRNA exerted a synergistic antitumor effect by inhibiting autophagy. Importantly, TFE3 expression positively correlated with TSCC development and poor prognosis in patients. Collectively, we demonstrated that the melatonin‐induced increase in TFE3‐dependent autophagy is mediated through the melatonin membrane receptor in TSCC. These data also suggest that blocking melatonin membrane receptor‐TFE3‐dependent autophagy to enhance the activity of melatonin warrants further attention as a treatment strategy for TSCC.     

老年性痴呆与健康老人的脑电图、脑电地形图比较

目的比较老年性痴呆患者（AD）与健康老人的脑电图（EEG）和脑电地形图（BEAM）特点。方法对35例AD患者和32例健康老人的EEG和BEAM检查结果进行比较。结果AD患者组EEG、BEAM的异常率分别为77．14％和80．95％。明显高于健康老人组的27．77％和33．33％,差异有统计学意义（P〈0．01）;AD患者中α节律慢化、泛化、低至中波幅,θ波弥漫性活动,δ波活动增多比例均明显高于健康老人组（P〈0．05）;AD患者随病情加重EEG、BEAM的中度异常率明显升高（P〈0．05）。结论EEG、BEAM检查可以作为AD常规临床检查和评价指标之一,有助于对病情严重程度及进展的判断。     

Phase II study of megestrol acetate in the treatment of hepatocellular carcinoma

This is a report of a phase II study of megestrol acetate (160mg/day, orally) in the treatment of hepatocellular carcinoma (HCC). Forty-six patients with advanced HCC were studied and tumour response, changes in appetite, bodyweight, a feeling of well-being, survival and toxicity were evaluated. Thirty-two patients were able to be evaluated for response; there were no complete responders or partial responders. Twelve patients (38%) had stable disease and seven of these patients had a minor response with a median size reduction in the tumour of 18%. Twenty patients (62%) had progressive disease. Five of 24 (21%) patients had a median reduction in α-fetoprotein levels of 59ng/mL. The overall median survival was 4 months (range 1 week to 27 months). Twenty of 32 (62%) patients had an increased appetite and feeling of well-being. Fourteen of 22 (64%) patients had a median lean bodyweight gain of 5 kg (range 1–14 kg). Toxicities were minimal. Tests for glucocorticoid receptors were performed in 10 patients. Four of five patients who were positive for glucocorticoid receptors in the tumour had a stable disease and all five patients who were negative for glucocorticoid receptors had progressive disease. Megestrol acetate had no significant effect on the tumour in HCC patients. However, megestrol acetate is useful in the palliative management of HCC patients, with improvements in appetite, bodyweight and a feeling of well-being with minimal side effects. Some patients had stable disease, a minor reduction of tumour size and a prolonged survival after megestrol acetate treatment and this response may be related to the presence of glucocorticoid receptors in the HCC tumour.     

超声在肺周围型病变良恶性判定中的诊断价值

目的 探讨超声在肺周围型病变良恶性判定中的诊断价值.方法 对467例肺周边型病变患者行二维及彩色多普勒超声检查,观察病灶形态、内部回声及血流信号.超声引导下穿刺后送病理检查,并对良性病变术后随访2年.结果 楔形病灶和/或病灶内支气管征(肺低回声病变内见散在等号样强回声)对诊断肺周围型病变良恶性有显著价值(P﹤0.001).内含支气管征的楔形病灶诊断为良性病灶的敏感性为85.71%,特异性为85.95%,准确性为81.99%;内部血流信号对判定病灶良恶性差异无统计学意义(P=0.083).结论 超声对肺周围型病变良恶性判断有一定临床应用价值.     

肝纤维化血清学诊断的研究

肝纤维化是多种慢性肝病的共同病理过程,可导致肝硬化及相关并发症的发生,而肝纤维化具有可逆性。因此,肝纤维化诊断对慢性肝病的防治及预后评估具有重要意义。肝活检一直是诊断肝纤维化的金标准,但有其局限性,近来研究发现血清学指标与肝纤维化之间有良好的相关性,且简便易行,有望替代肝活检,本文就血清学检查在肝纤维化诊断中的研究作一概述。     

京杭运河丹阳段钉螺消长与扩散趋势观察

目的 了解长江洲滩钉螺通过京杭运河丹阳段向内陆扩散情况,为制订控制策略提供依据。方法采用常规调查方法,纵向观察20年来运河水系钉螺分布及动态消长情况。结果丹阳市钉螺主要分布于运河水系,占全市总有螺面积的99％以上;钉螺扩散呈“上游-中游-下游”顺序扩散,上游段复现早,下游段复现迟;1987-1996年钉螺以河道分布为主,1997-2006年内陆灌渠钉螺分布快速增加。结论洲滩钉螺通过京杭运河丹阳段向下游扩散,并通过电灌站向内陆灌区扩散。应加强通江河道钉螺监测,实施防螺工程结合灭螺措施控制钉螺扩散,防止血吸虫病再流行。     

RGD肽修饰的纯钛种植材料表面成骨细胞黏附增殖能力

目的:评价精氨酸-甘氨酸-天冬氨酸(RGD)肽修饰纯钛表面对细胞早期黏附增殖影响. 方法:利用分子自组装技术氨基化纯钛表面,化学接枝GYRGDS肽,计算不同时点材料表面黏附细胞数;不同浓度RGD肽液预处理接种前细胞,计算材料表面细胞黏附率;MTT法和扫描电镜分别检测材料表面细胞的增殖、生长.结果:RGD肽修饰的纯钛表面细胞早期黏附率、增殖活性和生长情况在各时点均优于未修饰组,高浓度肽液预处理对RGD肽修饰组表面细胞有较强黏附抑制作用.结论:采用分子自组装技术可将活性RGD肽稳定的化学接枝于纯钛表面,修饰后材料的细胞早期黏附增殖等生物学行为有明显改善.     

黏附肽改性纯钛表面成骨细胞的早期黏附能力研究

目的 对纯钛表面钝化态氧化膜进行生物化学活化改性,探讨生物化学改性对钛表面成骨细胞黏附的影响.方法 24个纯钛试件打磨抛光后均分为4组,每组6个;纯钛组不处理,碱-热处理组行碱-热处理,溶胶涂层组行碱-热处理+溶胶涂层处理,黏附肽组行碱-热处理+溶胶涂层+黏附精氨酸-甘氨酸-天冬氨酸-丝氨酸肽(Glycine-Tyrosine-Arginine-Glycine-Asparticacid-Serine,GYRGDS)处理.使用X射线光电子能谱(X-ray photoelectron spectroscopy,XPS)、傅里叶变换红外光谱计(Fourier transform infrared spectrometer,FTIR)分析各组钛表面化学元素及功能基团组成;在各组钛试件表面接种成骨细胞,经2.05 Pa流体剪切力作用30 min、1 h、2 h,计算细胞残留率.结果 碱-热处理组钛表面富含大量活性羟基,溶胶涂层组钛表面富含大量羟氧基团.黏附肽组钛表面经XPS及FTIR分析检测到酰胺峰,显示GYRGDS肽成功固定于钛表面.流体剪切力作用30 min、1 h和2 h后黏附肽组钛表面的成骨细胞残留率(分别为93.0%、54.4%、34.4%)均高于相应时间点其他组.结论 GYRGDS肽修饰后的钛表面成骨细胞黏附稳定性均优于非GYRGDS肽修饰组.     

A Prospective,Randomized Comparison of Modified Pulmonary Vein Isolation Versus Conventional Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation

Modified Pulmonary Vein Isolation in AF Ablation. Introduction: Pulmonary vein isolation (PVI) is the primary ablation therapy in patients with atrial fibrillation (AF). We hypothesized that high dominant frequency (DF) sites (AF nests during sinus rhythm [SR]) adjacent to the PV ostia are associated with the atrial substrate that maintains AF, and PVI incorporating the high‐frequency AF nests may have a higher efficacy. Methods and Results: In a prospective and randomized comparison, 126 symptomatic paroxysmal AF patients that underwent PVI were enrolled. We compared the efficacy of a modified PVI (ablation line: 1.0–1.5 cm from the PV ostium with encircling the AF nests [spectral analysis with DF >70 Hz during SR, Group II]) versus the anatomy‐guided conventional PVI (Group I). In Group II, the DF value along the PV ostium was lower than 70 Hz after the PVI. The primary endpoint was the freedom from symptomatic atrial arrhythmias after a single procedure. We also followed the autonomic function by a time‐domain analysis of the heart rate variability. In both groups, AF nests were observed and electric isolation was successfully obtained in all patients. With a mean duration of 16 ± 6.1 months of follow‐up, Group II had a higher single procedure efficacy without drugs (78.7% vs 66.1%, log‐rank test: P = 0.02), and fewer repeat procedures (6.6% vs 23%; P = 0.04), as compared to Group I. Conclusion: PVI incorporating the high frequency AF nests adjacent to the PV ostia had a better single procedure efficacy. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1155–1162, November 2012)