Heavy ion and X-ray irradiation alter the cytoskeleton and cytomechanics of cortical neurons

Heavy ion beams with high linear energy transfer exhibit more beneifcial physical and biological performance than conventional X-rays, thus improving the potential of this type of radiotherapy in the treatment of cancer. However, these two radiotherapy modalities both cause inevitable brain injury. The objective of this study was to evaluate the effects of heavy ion and X-ray irra-diation on the cytoskeleton and cytomechanical properties of rat cortical neurons, as well as to determine the potential mechanism of neuronal injury after irradiation. Cortical neurons from 30 new-born mice were irradiated with heavy ion beams at a single dose of 2 Gy and X-rays at a single dose of 4 Gy;subsequent evaluation of their effects were carried out at 24 hours after irradiation. An immunolfuorescence assay showed that after irradiation with both the heavy ion beam and X-rays, the number of primary neurons was signiifcantly decreased, and there was ev-idence of apoptosis. Radiation-induced neuronal injury was more apparent after X-irradiation. Under atomic force microscopy, the neuronal membrane appeared rough and neuronal rigidity had increased. These cell changes were more apparent following exposure to X-rays. Our ifnd-ings indicated that damage caused by heavy ion and X-ray irradiation resulted in the structural distortion and rearrangement of the cytoskeleton, and affected the cytomechanical properties of the cortical neurons. Moreover, this radiation injury to normal neurons was much severer after irradiation with X-rays than after heavy ion beam irradiation.     

Acupuncture and moxibustion reduces neuronal edema in Alzheimer’s disease rats

To examine the possible correlation of aberrant Wnt signaling and pathological changes in Alzheimer's disease, we established a rat model of Alzheimer's disease and measured axin and β-catenin expression in the hippocampus. Rats were pretreated with moxibustion or electroacu-puncture, or both, at Baihui(GV20) and Shenshu(BL23). Axin expression was lower, β-catenin expression was greater, and neuronal cytoplasmic edema was visibly prevented in the rats that had received the pretreatments. Our results suggest that the mechanism underlying the neuro-protective effect of acupuncture and moxibustion in Alzheimer's disease is associated with axin and β-catenin expression in the Wnt signal transduction pathway.     

Eholecystokinin octapeptide antagonizes apoptosis in human retinal pigment epithelial cells

Although cholecystokinin octapeptide-8 is important for neurological function, its neuroprotective properties remain unclear. We speculated that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against oxidative injury. In this study, retinal pigment epithelial cells were treated with peroxynitrite to induce oxidative stress. Peroxynitrite triggered apoptosis in these cells, and increased the expression of Fas-associated death domain, Bax, caspase-8 and Bcl-2. These changes were suppressed by treatment with cholecystokinin octapeptide-8. These results suggest that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against apoptosis induced by peroxynitrite.     

Effects of diazepam on glutamatergic synaptic transmission in the hippocampal CA1 area of rats with traumatic brain injury

The activity of the Schaffer collaterals of hippocampal CA3 neurons and hippocampal CA1 neurons has been shown to increase after fluid percussion injury. Diazepam can inhibit the hyperexcitability of rat hippocampal neurons after injury, but the mechanism by which it affects excitatory synaptic transmission remains poorly understood. Our results showed that diazepam treatment significantly increased the slope of input-output curves in rat neurons after fluid percussion injury. Diazepam significantly decreased the numbers of spikes evoked by super stimuli in the presence of 15 μmol/L bicuculline, indicating the existence of inhibitory pathways in the injured rat hippocampus. Diazepam effectively increased the paired-pulse facilitation ratio in the hippocampal CA1 region following fluid percussion injury, reduced miniature excitatory postsynaptic potentials, decreased action-potential-dependent glutamine release, and reversed spontaneous glutamine release. These data suggest that diazepam could decrease the fluid percussion injury-induced enhancement of excitatory synaptic transmission in the rat hippocampal CA1 area.     

莫西沙星与肺结核痰转化率相关性的Meta分析

目的系统评价抗结核药莫西沙星与肺结核痰转化率（SCR）的相关性。方法检索中国知网（CNKI）、维普中文科技期刊全文数据库和万方数据库等中文数据库以及美国国立图书馆（PubMed）、荷兰医学文摘（EMBASE）和Cochrane图书馆等英文数据库,运用Meta分析方法综合评价莫西沙星与肺结核SCR的相关性。文献资料使用RevMan4．2软件进行Meta分析。结果共纳入7篇研究,包含治疗组503例和对照组527例。7项研究的合并分析结果显示,莫西沙星与肺结核SCR存在相关性（OR=1．37,95％CI：1．04-1．81）。结论莫西沙星提高了肺结核患者的SCR,可能是当前短疗程治疗药物敏感性肺结核的一种选择。     

经腹腔途径腹膜前补片置入术和无张力疝修补术治疗嵌顿性腹股沟疝的对照分析

目的探讨经腹腔途径腹膜前补片置入术（TAPP）治疗嵌顿性腹股沟疝的安全性、有效性及优势。方法将124例成年嵌顿性腹股沟疝患者按随机配对法分为两组,观察组56例,采用腹腔镜下复位＋TAPP治疗;对照组68例,采用切开复位＋无张力疝修补术治疗。记录两组手术时间、住院时间、下床活动时间、住院费用、复发率及并发症情况,并进行统计学分析。结果观察组所有病例均在腹腔镜下完成手术,无中转开放手术。观察组手术时间、住院时间、下床活动时间均短于对照组[（37．52±7．78）min比（44．23±11．32）min、（4．53±O．89）d比（6．85±2．03）d、（9．30±2．65）h比（12．63±3．97）h],差异有统计学意义（P〈0．05）。观察组住院费用多于对照组[（9324±599）元比（7203±507）元],差异有统计学意义（P〈0．05）。两组并发症发生率比较差异无统计学意义（P〉O．05）。术后随访1年,观察组无复发,对照组有1例复发,两组复发率比较差异无统计学意义（P〉0．05）。结论TAPP治疗嵌顿性腹股沟疝微创、恢复快,是安全有效的,住院费用略高,复发率与无张力疝修补术相当。     

炎性乳腺癌新辅助化疗疗效和影响因素分析

目的探讨炎性乳腺癌（IBC）的分子生物学特点与新辅助化疗疗效的关系及影响化疗疗效的相关因素。方法收集2005年1月至2013年6月收治的103例术前化疗的IBC患者临床资料,应用免疫组织化学方法检测乳腺癌组织的雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）及E钙黏蛋白（E—cadherin）的表达,评价IBC新辅助化疗的疗效。结果103例IBC患者ER阴性48例,PR阴性51例,HER．2阳性45例,E．cadherin阳性66例。总体化疗有效率为72．8％（75／103）,联合紫杉类为主化疗方案的患者（紫杉组,62例）化疗有效率显著高于蒽环类为主化疗方案的患者（蒽环组,41例）[80．6％（50／62）比61．0％（25／41）],差异有统计学意义（P〈0．05）;ER阴性、PR阴性、E—cadherin阴性的患者化疗有效率均显著高于其对应的ER阳性、PR阳性、E—cadherin阳性的患者[83．3％（40／48）比63．6％（35／55）、82．4％（42／51）比63．5％（33／52）、83.8％（31／37）比66．7％（44／66）],差异有统计学意义（P〈0．05）;紫杉组E—cadherin阳性表达的患者化疗有效率显著高于蒽环组[77．5％（31／40）比50．0％（13／26）],差异有统计学意义（P〈0．05）;HER-2的表达与炎性乳腺癌患者的化疗疗效无相关性（P〉0．05）。结论ER、PR及E—cadherin阴性的患者对IBC患者化疗敏感,E．cadherin的阳性表达可能是影响IBC患者化疗耐药的重要因素,选择含紫杉类药物联合化疗方案有助于提高E．cadherin阳性IBC患者的化疗疗效。     

固相萃取-HPLC法同时测定盐酸帕洛诺司琼注射液中6种杂质

目的：固相萃取—高效液相色谱法同时测定盐酸帕洛诺司琼注射液中差向异构体、对映异构体、氮氧杂质等6种杂质的含量。方法：样品经1 mol·L-1氢氧化钠溶液调节pH,经Agilent Bond Elut C8固相萃取柱（200 mg,3 mL）去除大部分基质干扰,实现净化与富集,再用乙醇洗脱得到富集物。采用USP40盐酸帕洛诺司琼原料药已知杂质测定方法,以Astec CHIROBIOTIC?誖V（250 mm × 4.6 mm,5 μm）为色谱柱对其进行分离检测。结果：6种杂质在0.2~4.3 μg·mL-1范围内线性良好,相关系数r≥0.999 5,方法的检测限为0.056~0.065 μg·mL-1,低、中、高3个浓度的加样回收率为90.60%~105.7%。结论：本方法可用于同时检测盐酸帕洛诺司琼注射液中的6种杂质。     

MicroRNA-328 as a regulator of cardiac hypertrophy

Cardiac hypertrophy is a primary predictor of progressive heart disease that often results in heart failure. Growing evidence has demonstrated that microRNAs (miRNAs) play a critical role in regulating cardiac hypertrophy. This study was designed to evaluate the effect of miR-328 on cardiac hypertrophy and the potential molecular mechanisms. We found that transgenic overexpression of miR-328 in the heart induced cardiac hypertrophy in mice, which was accompanied by reduced SERCA2a level increased intracellular calcium concentration and calcineurin protein level, and enhanced NFATc3 nuclear translocation. However, normalization of miR-328 level by its antisense chemically modified with locked nucleic acid (LNA-antimiR-328) reversed the changes. Forced expression of miR-328 resulted in cardiomyocyte hypertrophy in cultured neonatal rat ventricular cells, which was accompanied by downregulation of SERCA2a expression and activation of the calcineurin/NFATc3 signaling pathway. These changes were abolished by LNA-antimiR-328. We validated the SERCA2a as a direct target for miR-328. MiR-328 expression was upregulated in cardiomyocyte treated with isoproterenol (ISO) to induce hypertrophy; while knockdown of miR-328 attenuated the hypertrophic responses. The level of miR-328 was significantly elevated in a mouse model of hypertrophy by thoracic aortic banding (TAC). Consistently, SERCA2a was downregulated, whereas calcineurin were upregulated, and NFATc3 nuclear translocation was enhanced. In contrast, hypertrophy in these mice was significantly alleviated when treated with miR-328 antisense. MiR-328 promotes cardiac hypertrophy by targeting SERCA2a. Our study therefore uncovered a novel molecular mechanism for cardiac hypertrophy and indicated miR-328 as a potential therapeutic target for this cardiac condition.