川陈皮素对糖尿病肾病大鼠AMPK和eNOS表达的影响研究

【摘要】目的 观察川陈皮素对糖尿病肾病大鼠的治疗作用，并从腺苷酸蛋白活化激酶（AMPK）和内皮型一氧化氮酶（eNOS）途径探讨其作用机理。方法 采用高脂高糖饲料喂养+链脲佐菌素（STZ）腹腔注射复制2型糖尿病肾脏损害大鼠模型，模型构建成功后，将其随机分为正常组、模型组、贝那普利干预组以及川陈皮素低、中和高剂量治疗组（n=20）。实验中密切监测大鼠一般情况，治疗期结束后收集尿液检测24h蛋白尿，收集血液检测肾功能指标、抗氧化指标，收集肾脏观察肾脏病理学，同时检测肾脏组织中AMPK及eNOS蛋白和mRNA的表达结果。结果 正常组肾小球正常，无明显病理特征；模型组出现肾小球增大，系膜和肾间质纤维组织增生；贝那普利组和川陈皮素三个剂量组相较于模型组明显减轻。与正常组相比，模型组24h尿蛋白定量、UREA、CREA和MDA明显升高(P＜005)；SOD和GSH明显降低(P＜005)，与模型组相比，贝那普利和川陈皮素三个剂量组24h尿蛋白定量、UREA、CREA和MDA明显降低(P＜005)，SOD和GSH明显升高(P＜005)。与正常组相比，模型组p AMPK、AMPK和eNOS蛋白和mRNA表达均明显降低(P＜005)；与模型组相比，贝那普利组和川陈皮素低、中和高剂量组AMPK和eNOS蛋白和mRNA表达明显升高(P＜005)。结论 川陈皮素可保护肾功能，提高血清和肾脏抗氧化指标，同时增加AMPK和eNOS蛋白和mRNA表达，最终保护糖尿病肾脏损害。     

基于PERK/eIF2α/ATF4/CHOP 信号通路探讨银杏内酯B 治疗代谢性脂肪性肝病的作用

目的：通过动物实验验证银杏内酯B (GB)治疗代谢性脂肪性肝病（MAFLD）的作用是否与调控PERK/eIF2α/ATF4/CHOP信号通路,抑制内质网应激,减少肝细胞凋亡及炎症反应相关。方法：72只雄性SD大鼠随机分为正常组,模型组,辛伐他汀组,GB低、中、高剂量（GB-L、GB-M、GB-H）组（n=12）,高脂高糖饲料喂养12周构建MAFLD模型（正常组除外）。治疗8周后,收集血清和肝组织。生化试剂盒检测血脂和肝脂[总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）]及肝功能[天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）];酶联免疫吸附法（ELISA）法检测血清和肝脏中的炎性因子[白细胞介素-6 (IL-6)、白细胞介素-1 (IL-1)、肿瘤坏死因子-α (TNF-α)]水平;HE染色、油红O染色观察肝组织病理学;Western blot法检测肝脏组织中GRP78、PERK、p-eIF2α、ATF4、CHOP、Bcl-2和Bax的蛋白表达。结果：肝脏组织病理学显示,与正常组相比,模型组大鼠肝脏脂肪变性显著,与模型组...     

A Physiologically Inspired Model for Solving the Cocktail Party Problem

At a cocktail party, we can broadly monitor the entire acoustic scene to detect important cues (e.g., our names being called, or the fire alarm going off), or selectively listen to a target sound source (e.g., a conversation partner). It has recently been observed that individual neurons in the avian field L (analog to the mammalian auditory cortex) can display broad spatial tuning to single targets and selective tuning to a target embedded in spatially distributed sound mixtures. Here, we describe a model inspired by these experimental observations and apply it to process mixtures of human speech sentences. This processing is realized in the neural spiking domain. It converts binaural acoustic inputs into cortical spike trains using a multi-stage model composed of a cochlear filter-bank, a midbrain spatial-localization network, and a cortical network. The output spike trains of the cortical network are then converted back into an acoustic waveform, using a stimulus reconstruction technique. The intelligibility of the reconstructed output is quantified using an objective measure of speech intelligibility. We apply the algorithm to single and multi-talker speech to demonstrate that the physiologically inspired algorithm is able to achieve intelligible reconstruction of an “attended” target sentence embedded in two other non-attended masker sentences. The algorithm is also robust to masker level and displays performance trends comparable to humans. The ideas from this work may help improve the performance of hearing assistive devices (e.g., hearing aids and cochlear implants), speech-recognition technology, and computational algorithms for processing natural scenes cluttered with spatially distributed acoustic objects.

     

Reproducibility of Serologic Assays for Influenza Virus A (H5N1)

Hemagglutination-inhibition (HI) and neutralization are used to evaluate vaccines against influenza virus A (H5N1); however, poor standardization leads to interlaboratory variation of results. A candidate antibody standard (07/150) was prepared from pooled plasma of persons given clade 1 A/Vietnam/1194/2004 vaccine. To test human and sheep antiserum, 15 laboratories used HI and neutralization and reassortant A/Vietnam/1194/2004, A/turkey/Turkey/1/2005 (clade 2.2), and A/Anhui/1/2005 (clade 2.3.4) viruses. Interlaboratory variation was observed for both assays, but when titers were expressed relative to 07/150, overall percentage geometric coefficient of variation for A/Vietnam/1194/2004 was reduced from 125% to 61% for HI and from 183% to 81% for neutralization. Lack of reduced variability to clade 2 antigens suggested the need for clade-specific standards. Sheep antiserum as a standard did not reliably reduce variability. The World Health Organization has established 07/150 as an international standard for antibody to clade 1 subtype H5 and has an assigned potency of 1,000 IU/ampoule.     

喜炎平注射液与氟罗沙星配伍的稳定性研究

目的考察中药制剂喜炎平注射液与氟罗沙星注射卉c配伍的稳定性。方法采用反相高效液相色谱法测定喜炎平注射液在5％的葡萄糖注射液中与氟罗沙星注射剂配伍后6h内穿心莲内酯磺化物的含量,观察配伍后6h内溶液的外观及pH值及不溶性微粒数的变化情况。结果在室温务件下,喜炎平注射液在5％葡萄糖注射液与氟罗沙星注射剂配伍6h内外观无明显变化,不溶性微粒在安全范围内有所增加;但喜炎平注射液主要成分穿心莲内酯磺化物的含量下降,氟罗沙星的含量几乎没变,配伍溶液pH值随时间降低。结论在室温条件下,喜炎平注射液在5％葡萄糖注射液中与氟罗沙星不可以配伍使用。     

干黄茶乳剂对慢性牙周炎患者龈沟液中TNF-α、IL-6和IL-10水平的影响及疗效观察

目的:观察干黄茶乳剂对慢性牙周炎患者龈沟液中TNF-α、IL-6和IL-10水平的影响及其疗效。方法:慢性牙周炎患者82例随机分为治疗组(41例)和对照组(41例)。2组患者均给予龈上洁治、龈下刮治和根面平整等常规牙周基础治疗。治疗组给予干黄茶乳剂注满牙周袋内,对照组给予等量复方碘甘油液。1次/周,连续6周治疗。观察2组患者治疗前后龈沟液中TNF-α、IL-6和IL-10水平变化,比较临床有效率。结果:治疗结束后,2组患者龈沟液中TNF-α、IL-6水平均明显下降,IL-10水平明显升高(P0.05或P0.01),且治疗组下降或升高幅度较对照组更显著(P0.05)。治疗组临床总有效率为95.12%,明显优于对照组75.61%(P0.05)。结论:干黄茶乳剂局部治疗慢性牙周炎的效果良好,能够降低龈沟液中TNF-α、IL-6水平,提高IL-10水平,从而有效控制牙周组织炎性反应损伤,改善局部炎性反应状况。     

Color postprocessing of conventional CT images: preliminary results in assessment of nondisplaced proximal femoral fractures

Purpose

The purpose of this study was to demonstrate the diagnostic performance and effect on reader confidence of a custom computed tomography (CT) color postprocessing algorithm for assessment of nondisplaced proximal femoral fractures.

Materials and methods

Four radiologists, including two PGY-3 radiology residents and two emergency radiologists, independently interpreted 30 CT examinations of the hip and/or pelvis performed for trauma, consisting of a total of 15 cases positive for nondisplaced hip fracture and 15 age and sex-matched controls. Images were reviewed first with conventional CT images and after at least 8 weeks, all images were reviewed again with the addition of coronal color postprocessed images. Sensitivity and specificity were compared with McNemar’s test, and diagnostic confidence was compared with paired t tests.

Results

There was no significant difference in diagnostic performance between conventional and postprocessed images, although there was nominally increased sensitivity and decreased specificity with the postprocessed images: for all readers, the sensitivity and specificity for conventional images was 88.3 and 95.0%, compared to 93.3% (p?=?0.25) and 88.3% (p?=?0.14) for postprocessed images. Three of four readers (including both attending radiologists) reported an increase in confidence with postprocessed images for cases negative for fracture (10-point confidence scale of 7.25 for conventional images, compared to 8.2 for postprocessed images for all readers, p?=?0.0053). There was no difference in diagnostic confidence for cases positive for fracture.

Conclusions

A custom color CT postprocessing algorithm did not demonstrate a significant difference in diagnostic performance for assessment of nondisplaced proximal femoral fractures within the limitations of a relatively small sample size; however, postprocessing increases confidence of experienced readers in cases negative for fracture.

     

Inactivation of Beclin‐1‐dependent autophagy promotes ursolic acid‐induced apoptosis in hypertrophic scar fibroblasts

A hypertrophic scar (HS) is caused by abnormal proliferation of dermal fibroblasts. Thus, promoting hypertrophic scar fibroblast (HSFB) apoptosis is an effective strategy for HS therapy. Ursolic acid (UA) has been widely used as an inducer of apoptosis in diverse cancers. However, whether UA plays an inhibitory role in HS formation is still unknown. In our study, UA was used to treat HSFBs and the cell viability, apoptosis, and collagen synthesis were determined by a Cell Counting Kit 8 assay, flow cytometry, and an H³‐proline incorporation assay, respectively. Autophagy activity was detected by LC3 immunoblotting and electron microscopy, and siRNAs targeting Beclin‐1 were used to inhibit autophagy. Western blotting was performed to investigate the molecular changes in HSFBs after various treatments. We found that UA inhibited collagen synthesis and induced cell apoptosis in HSFBs, evidenced by the deregulated expression of Bim, Bcl‐2 and Cyto C. Furthermore, we demonstrated that UA induced autophagy and inactivation of autophagy promoted UA‐induced apoptosis and collagen synthesis inhibition in HSFBs. Molecular investigation indicated that UA‐induced autophagy through upregulation of Beclin‐1 and knockdown of Beclin‐1 prevent UA‐induced autophagy. Overexpression of Bcl‐2 prevents UA‐induced autophagy, Beclin‐1 upregulation, apoptosis and collagen synthesis inhibition in HSFBs. Collectively, our study demonstrated that UA is a novel agent for inhibiting HS formation by promoting apoptosis, especially in combination with an autophagy inhibitor. Our results provide strong evidence of the application of UA in clinical HS treatment.     

低分子肝素与银杏达莫注射液联合应用改善急性心源性脑栓塞患者神经功能缺损的临床观察

目的：探讨低分子肝素与银杏达莫注射液联合用于改善急性心源性脑栓塞患者神经功能缺损的临床效果。方法：选取2013年1月—2014年12月牡丹江医学院红旗医院收治的40例急性心源性脑栓塞患者,以随机数字表法分为观察组和对照组各20例。对照组患者采用基础治疗联合低分子肝素治疗,观察组患者在基础治疗的基础上给予低分子肝素联合银杏达莫治疗,对比2组患者治疗前后神经功能缺损评分和临床疗效。结果：观察组患者治疗3 d、1周、2周的神经功能缺损评分分别为（18．80±6．13）、（17．34±6．17）、（15．89±5．57）分,均明显低于对照组的（20．99±7．12）、（20．87±7．42）、（18．38±7．20）分,差异均有统计学意义（P＜0．05）;观察组患者的总有效率为95．00％（19／20）,明显高于对照组的75．00％（15／20）,差异有统计学意义（P＜0．05）。结论：采用低分子肝素联合银杏达莫治疗急性心源性脑栓塞,能明显改善患者的神经功能缺损情况,值得在临床上推广。     

Intracranial extramedullary hematopoiesis following bilateral chronic subdural hematoma in a patient with idiopathic myelofibrosis

This is a case of remarkable intracranial extramedullary hematopoiesis (EMH) in a 63-year-old male patient with a history of idiopathic myelofibrosis. Intracranial EMH was suspected following cranial computed tomography and magnetic resonance imaging and was found in the same sites as the bilateral subdural hematomas. The patient subsequently received whole brain irradiation (30 Gy). The lesion was controlled for one and a half years. After the patient died from bacterial infection, intracranial EMH was confirmed in autopsy and histological diagnoses.