基于TLR4/MyD88/NF-κB信号通路研究参苓白术散对IBS-D大鼠的干预机制

目的：基于TLR4/MyD88/NF-κB信号通路研究参苓白术散对腹泻型肠易激综合征（IBS-D）大鼠的干预机制。方法：将48只大鼠随机分为空白组、模型组、匹维溴铵组［20 mg/(kg·d）］、参苓白术散组［SLBZ组,1.44 g/（kg·d）］、TLR4抑制剂组［TAK-242组,1 mg/（kg·d）］、TLR4抑制剂+参苓白术散组（TAK-242+SLBZ组）,每组各8只。除空白组外,其余各组均采用4%乙酸构建IBS-D大鼠模型。造模成功后,各给药组给予相应的药物灌胃,连续7 d。观察大鼠一般情况,体质量及粪便Bristol评分,结肠组织病理学变化,血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）及白细胞介素-1β（IL-1β）水平,结肠组织闭锁小带蛋白-1（ZO-1）、紧密连接蛋白（Occludin）、Toll样受体4（TLR4）、髓样分化因子88（MyD88）、核转录因子-κB p65（NF-κB p65）蛋白表达水平。结果：成功造模38只。与空白组比较,模型组大鼠体质量下降,粪便Bristol评分升高,HE染色可见炎症细胞浸润,血清TNF-α、IL-6及IL-1β水平升高,结肠组织ZO-1与Occludin蛋白水平降低,TLR4、MyD88、NF-κB p65蛋白水平升高（P＜0.05）。与模型组比较,匹维溴铵组、SLBZ组、TAK-242组、TAK-242+SLBZ组大鼠体质量增加,粪便Bristol评分降低,HE染色炎症细胞浸润减少,血清IL-6、IL-1β及TNF-α水平均显著下降,ZO-1和Occludin蛋白表达水平升高,TLR4、MyD88和NF-κB p65蛋白表达水平下降（均P＜0.05）。与匹维溴铵组、SLBZ组、TAK-242组比较,TAK-242+SLBZ组大鼠结肠组织ZO-1与Occludin蛋白表达水平升高,TLR4、MyD88、NF-κB p65蛋白表达水平下降（均P＜0.05）。结论：参苓白术散可改善IBS-D大鼠腹泻症状,降低血清炎症因子水平,修复肠黏膜,其机制可能是通过调控TLR4 /MyD88 /NF-kB信号通路来达到减轻肠道炎症反应的目的。     

马钱子碱通过调控PI3K/Akt/mTOR通路对肺腺癌细胞的抑制作用研究

目的：探究马钱子碱对非小细胞肺癌的影响及其作用机制。方法：采用CCK-8法和划痕试验法研究马钱子碱抑制A549细胞的增殖、迁移能力,Western blot法检测各组细胞磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)通路相关的蛋白表达,ELISA法检测白细胞介素6（IL-6）、肿瘤坏死因子-α（TNF-α）的含量。结果：CCK-8试验结果显示,给药组对A549细胞增殖有明显抑制作用;划痕试验显示,与空白组比较,给药组细胞迁移率明显下降（P<0.01）;Western blot结果显示,给药干预后可显著下调p-Akt、p-mTOR的表达（P<0.001）,同时给药组的mTOR、Akt、PI3K蛋白表达下调（P<0.05）;ELISA试验结果显示,采用马钱子碱进行干预后,细胞上清IL-6和TNF-α含量均显著升高(P<0.01或P<0.001)。结论：马钱子碱可有效抑制非小细胞肺癌细胞的增殖、迁移,可能是通过抑制PI3K/Akt/mTOR通路而起作用,并通过调节TNF-α含量来达到抗肿瘤的作用。     

EGb761对视神经损伤后视神经节细胞自噬的影响

目的：观察银杏提取物EGb761对大鼠视神经损伤后视网膜神经节细胞自噬活性及自噬流的影响,并探讨其作用机制。方法：将48只SD大鼠随机分为EGb761组和对照组,分别给予EGb761（150mg/kg·d）和0.9%氯化钠注射液灌胃,均每天1次,直到处死。分别于损伤后第7天、第14天取材,采用免疫组化检测2组视网膜神经节细胞自噬相关蛋白LC3B、自噬标记蛋白p62及自噬基因Beclin-1及mTOR通路蛋白p-mTOR、p-S6表达水平,腺病毒GFP-mRFP-LC3荧光瞬时转染技术检测自噬流表达。结果：与对照组相比,EGb761组LC3B表达水平升高,p62、p-mTOR和p-S6蛋白表达水平均下降（均P<0.05）;2组Beclin-1差异无统计学意义（P＞0.05）;2组GFP和mRFP荧光点数比较,EGb761组的红点多于对照组,黄点少于对照组（均P<0.05）。结论：EGb761能够促进大鼠视神经损伤后视网膜神经节细胞自噬流,其机制可能与促进mTOR信号通路中的相关蛋白表达有关。     

肝宁方对NASH小鼠保护作用及大鼠肝星状细胞影响的实验研究

目的：探讨肝宁方对非酒精性脂肪性肝炎（NASH）小鼠的保护作用及其对活化后大鼠肝星状细胞（HSCs）的影响。方法：将24只小鼠随机分为正常组、模型组、肝宁方组,每组各8只。对模型组、肝宁方组采用高脂饮食联合四氯化碳豆油溶液皮下注射建立NASH小鼠模型,造模成功后正常组和模型组予0.9%氯化钠注射液灌胃,肝宁方组予肝宁方灌胃。干预3周。将大鼠HSCs分成正常组、模型组及肝宁方组,正常组予正常培养基培养,模型组及肝宁方组采用转化生长因子-β1（TGF-β1）活化,随后正常组和模型组用含正常大鼠血清培养基培养,肝宁方组加入含30%肝宁方含药血清培养基培养。培养24 h。观察肝组织病理学情况;血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、血清总胆固醇（CHOL）、三酰甘油（TG）水平;肝组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）表达,葡萄糖调节蛋白78（GRP78）及内质网核信号转导蛋白1α（IRE-1α）蛋白表达;肝细胞凋亡情况;HSCs的增殖情况。结果：肝宁方组和模型组小鼠相比,脂质空泡和出血减少,炎性细胞浸润减轻。小鼠血清AST、ALT、CHOL、TG水平,肝组织TNF-α、IL-6水平,GRP78、IRE-1α蛋白表达,肝细胞凋亡情况模型组与正常组比较,肝宁方组与模型组比较,差异均有统计学意义（P<0.01或P<0.05）。与模型组相比,肝宁方含药血清干预后HSCs增殖趋势明显减弱（P<0.01）。结论：肝宁方能够改善NASH小鼠肝脏病理学变化,保护肝脏、调节脂质代谢、抑制炎症反应、减轻肝细胞凋亡、抑制HSCs增殖,其机制可能与调控内质网应激有关。     

健脾消癌方对人结肠癌HCT116细胞AKT、mTOR表达的影响

目的：探讨健脾消癌方（JPXA）含药血清对人结肠癌HCT116细胞丝氨酸/苏氨酸蛋白激酶（AKT）、哺乳动物雷帕霉素靶蛋白（mTOR）表达以及对细胞增殖、细胞周期及凋亡的影响。方法：取不同浓度的JPXA含药血清作用于HCT116细胞,筛选JPXA含药血清处理HCT116细胞的半抑制浓度（IC50）,并将HCT116细胞分为实验组和对照组,予以相应处理后,采用CCK-8法检测细胞增殖能力,PI-FACS法检测细胞周期变化,Annexin V-APC 单染法流式细胞仪检测凋亡水平,并采用Rt-PCR检测AKT mRNA、mTOR mRNA水平,采用Western Blot检测AKT、p-AKT、mTOR及磷酸化哺乳动物雷帕霉素靶蛋白（p-mTOR）水平。结果：与对照组相比,实验组HCT116细胞增殖能力显著下降,能使细胞周期停留在G1期及S期,且细胞凋亡水平上升,差异均有统计学意义（P<0.05）。与对照组相比,实验组AKT mRNA、mTOR mRNA表达水平及AKT、p-AKT、mTOR、p-mTOR蛋白含量明显下降（P<0.05或P<0.01）。结论：JPXA能抑制AKT、mTOR表达,对结肠癌细胞的增殖、克隆能力有一定抑制作用,并可在一定程度上促进结肠癌细胞的凋亡。     

基于PI3K/Akt/mTOR通路探讨半夏泻心汤对PLGC大鼠黏膜微环境的影响

目的：对胃癌前病变（Precancerous Lesion of Gastric Cancer,PLGC）模型大鼠从整体、细胞及分子水平的指标进行观察,分析其胃黏膜微环境的特点,并初步探讨半夏泻心汤对其胃黏膜的作用机制。方法：清洁级雄性SD大鼠70只,随机分成3组：模型组50只,造模加中药干预组10只,空白组10只。采用改良MNNG+复合法制备PLGC大鼠模型,于造模中期第10周、造模结束期第20周,各组随机抽取5只大鼠,分别从整体水平、细胞水平及分子水平检测半夏泻心汤对其胃黏膜微环境的影响。结果：1）启动子PTEN,造模加中药干预组较模型组表达高,但仍低于空白组;2）调控器PI3K/Akt/mTOR信号通路,PI3K、Akt、mTOR的表达造模加中药干预组较模型组低,但仍高于空白组;3）效应子HIF-1α及其下游基因,造模加中药干预组较模型组表达低,但仍高于空白组;上述结果差异均有统计学意义（P<0.05）。结论：中药半夏泻心汤通过影响PLGC大鼠胃黏膜组织微环境变化的3个关键环节,即PI3K/Akt/mTOR信号通路中的启动子、调控器及效应子,从而影响并阻断PLGC的发生发展。     

桃红四物汤合七味白术散治疗糖尿病合并冠心病50例

目的：观察桃红四物汤合七味白术散治疗气阴两虚兼血瘀型糖尿病合并冠心病的临床疗效。方法：将100 例糖尿病合并冠心病患者随机分为治疗组和对照组,每组各50 例。对照组给予西医常规治疗,治疗组在对照组基础上加用桃红四物汤合七味白术散治疗。治疗12周后,观察2组的综合疗效,中医证候积分,实验室指标［空腹血糖（FBG）、糖化血红蛋白（HbA1c）、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C)、 C反应蛋白（CRP）、同型半胱氨酸（HCY）］,颈动脉内膜中层厚度（IMT）,颈部血管斑块大小以及安全性。结果：总有效率治疗组为94.0%（47/50）,对照组为72.0%（36/50）,2组比较,差异有统计学意义（P<0.05）。2组中医证候积分、TC、TG、LDL-C、CRP、HCY、IMT、斑块大小均较治疗前改善,且组间比较（除TC外）,差异均有统计学意义（P<0.05）。2组均未发生不良反应。结论：桃红四物汤合七味白术散治疗气阴两虚兼血瘀型糖尿病合并冠心病疗效显著,可减轻患者的临床症状,改善血管内皮功能,降低IMT水平,缩小颈部血管斑块,从而达到预防和减缓心血管事件发生的目的。     

补益营卫方对衰老表皮结构蛋白K17的影响

目的：观察补益营卫方对衰老表皮结构蛋白K17的基因和蛋白水平的影响。方法：将3个月龄小鼠（年轻组）与14个月龄小鼠（老年组）表皮细胞消化分离出来,然后进行传代培养,其中14个月龄小鼠（老年组）的表皮细胞分为2组,一组用常规方法培养细胞,另一组用含2.5%的补益营卫方培养基进行培养,采用荧光定量RT-PCR法和Western Blotting法分别检测细胞K17mRNA表达和细胞K17蛋白表达。结果：与年轻组比较,老年组的K17mRNA和蛋白表达水平均升高（P<0.05）;经药物干预后小鼠表皮细胞中K17mRNA和蛋白水平较老年组明显降低（P<0.05）。结论：补益营卫方可通过抑制衰老表皮结构蛋白K17的表达,起到延缓皮肤衰老作用。     

PCPA致大鼠NG2细胞的变化，NG2与GABA的共存关系及酸枣仁汤的干预作用研究

目的：探讨大鼠脑内五羟色胺（5-HT）含量下降后皮质部分NG2细胞的变化,NG2细胞与星形胶质细胞（Ast）、γ-氨基丁酸（GABA）的共存关系及酸枣仁汤的干预作用。方法：根据随机数字表法将雄性SD大鼠分为7 d正常组、7 d对照组、7 d对氯苯丙氨酸（PCPA）组、15 d正常组、15 d对照组、15 d PCPA组、酸枣仁汤（SZRD）组、PCPA+SZRD组,各组大鼠给予相应处理。取大脑皮质前额叶,采取免疫荧光双染法测定大鼠皮质NG2细胞、胶质纤维酸性蛋白（GFAP）、GABA的表达量及NG2/GFAP、NG2/GABA共存定位情况。结果：与7 d对照组比较,7 d PCPA组大鼠皮质NG2细胞、GFAP蛋白表达量增加（P<0.01）,GABA蛋白表达量下降（P<0.05）;与15 d PCPA组比较,PCPA+SZRD组大鼠皮质NG2细胞、GFAP蛋白表达量下降（P<0.01）,GABA表达量上升（P<0.05）;NG2细胞与GABA在同一区域表达较多,而与GFAP在同一区域表达较少。结论：5-HT系统的失调能激活皮质NG2细胞、Ast,抑制GABA的表达,NG2细胞可能与Ast、GABA共同影响大脑皮层兴奋性来调节睡眠,酸枣仁汤可能通过5-HT系统调控NG2细胞、Ast、GABA来参与皮层活动的神经调节。     

健脾益气方调控间隙连接蛋白43防治PD大鼠腹膜损伤的作用机制研究

目的：研究健脾益气方通过调控间隙连接蛋白（Cx）43干预腹膜透析大鼠腹膜间皮细胞转分化的作用机制。方法：将75只大鼠随机分为5组,即空白组、模型组、中药高剂量组、中药低剂量组、西药组,除空白组大鼠外,其余各组均采用5/6肾切除联合腹腔注射4.25％腹透液复制慢性肾衰竭腹膜纤维化大鼠模型。造模成功后,中药高、低剂量组给予健脾益气方,西药组给予阿托伐他汀钙,模型组给予0.9%氯化钠注射液,空白组不做任何处理。每天灌胃1次,连续4周。干预后光镜观察各组大鼠腹膜结构变化,测量腹膜致密层厚度;免疫组化法及蛋白质印迹法检测Cx43、蛋白激酶B/哺乳动物雷帕霉素靶蛋白（AKt/mTOR）通路和腹膜间皮细胞转分化（EMT）标志蛋白表达。结果：各组大鼠腹膜厚度及Cx43、pAKt、pmTOR、α平滑肌肌动蛋白（α-SMA）、E-钙黏附蛋白（E-cadherin）阳性面积比,空白组与模型组比较,中药高、低剂量组及西药组与模型组比较,中药高剂量组与西药组、中药低剂量组比较,差异均有统计学意义（P<0.05）。各组大鼠腹膜组织Cx43、pAKt、pmTOR、α-SMA、E-cadherin蛋白表达,空白组与模型组比较,中药高剂量组与西药组比较,差异均有统计学意义（P<0.05）。结论：健脾益气方可能通过调控Cx43表达,干预Akt/mTOR信号通路介导的腹膜间皮细胞EMT进程,从而发挥保护腹膜间皮细胞、防治腹膜损伤的作用。     

Tsunami generation,propagation, and run-up with a high-order Boussinesq model

In this work we extend a high-order Boussinesq-type (finite difference) model, capable of simulating waves out to wavenumber times depth kh < 25, to include a moving sea-bed, for the simulation of earthquake- and landslide-induced tsunamis. The extension is straight forward, requiring only an additional term within the kinematic bottom condition. As first test cases we simulate linear and nonlinear surface waves generated from both positive and negative impulsive bottom movements. The computed results compare well against earlier theoretical, numerical, and experimental values. Additionally, we show that the long-time (fully nonlinear) evolution of waves resulting from an upthrusted bottom can eventually result in true solitary waves, consistent with theoretical predictions. It is stressed, however, that the nonlinearity used far exceeds that typical of geophysical tsunamis in the open ocean. The Boussinesq-type model is then used to simulate numerous tsunami-type events generated from submerged landslides, in both one and two horizontal dimensions. The results again compare well against previous experiments and/or numerical simulations. The new extension compliments recently developed run-up capabilities within this approach, and as demonstrated, the model can therefore treat tsunami events from their initial generation, through their later propagation, and final run-up phases. The developed model is shown to maintain reasonable computational efficiency, and is therefore attractive for the simulation of such events, especially in cases where dispersion is important.     

Abundance and biomass of scyphomedusae, Aurelia aurita and Chrysaora melanaster, and Ctenophora, Bolinopsis mikado, with estimates of their feeding impact on zooplankton in Tokyo Bay, Japan

The abundance of a scyphomedusae, Aurelia aurita and Chrysaora melanaster, and a ctenophore, Bolinopsis mikado, in Tokyo Bay was investigated from 1995 to 1997. Aurelia aurita appeared throughout the year with a peak in abundance occurring from spring to summer. The average abundance and biomass during this period for the three successive years was 4.8, 43.8 and 3.2 ind. m⁻², and 1.02, 10.0 and 0.42 gC m⁻², respectively. The values in 1995 and 1997 were comparable with those previously reported for A. aurita abundance from 1990 to 1992. Values were very high in 1996, but the size composition of the bell diameter did not differ from other years, which suggested the absence of food limitation for A. aurita in 1996. C. melanaster was scarce over the survey period (<1.0 ind. m⁻²) while Bolinopsis mikado was more abundant during September to December, with maximum values of 172 ind. m⁻² and 0.33 gC m⁻² observed in December 1997. The weight-specific clearance rate for A. aurita on zooplankton (mainly copepods and their nauplii) was 0.16 ± 0.05 lgWW⁻¹ h⁻¹ (n = 13). Population clearance rate peaked from spring to summer, with average levels of 14.2%, 162% and 5.0% day⁻¹ obtained from spring to summer for respective years. Population clearance rates for B. mikado, calculated based on minimum carbon requirements, was 7.1% day⁻¹ in December 1997. Consequently, the trophic role of gelatinous zooplankton as predators in Tokyo Bay is important all the year round, considering the high impact of A. aurita from spring to summer and B. mikado from autumn to winter.     

The observation of tidal patterns, currents, and bathymetry with SLAR imagery of the sea

Work done until 1978 on the visualization of currents, bathymetry, internal waves, etc., in SLAR imagery of the sea is reported. It did not receive much attention until the SEASAT SAR imagery showed these effects on a global scale. Although we know, qualitatively, how these images come about we are yet far from knowing how to extract more quantitative data from them on depth, current speed, etc. Much research effort is still needed here and for this work a simple real-aperture SLAR can be a very useful tool.     

A current meter with intelligent data system, environmentalsensors, and data telemetry

To measure oceanographic parameters such as currents, temperature, conductivity, pressure, and suspended sediment concentrations, two film-recording current meters were upgraded with microprocessor-controlled data recorders and additional sensors. Two telemetry links relay data and allow the in situ operation of the remote instrument to be checked. In one configuration, the bottom-mounted current meter communicated by a 35-m-long wire to a small surface spar buoy, and then by a packet radio link to a nearby ship. In another development, the current meter relays data to a controller and buoyant data capsule on the bottom instrument package. The controller collects and processes the data from the current meter and periodically transfers these processed data to a data capsule and releases it. When released, the capsule rises to the surface and transmits its data to shore via the ARGOS satellite, while acting as a satellite tracked drifter     

防城港湾海域甲壳类群落结构及其与环境因子的关系

2016年5、8、11月和2017年2月对防城港湾海域开展渔业资源和环境调查,研究了河口湾甲壳类群落结构的空间和季节变化,并分析了甲壳类群落结构与主要环境因子的关系。结果表明:全年调查共捕获甲壳类60种,隶属于2目19科35属,暖水性种和暖温性种分别占60. 0%和40. 0%。春季有51种,夏季有34种,秋季有35种,冬季有26种,秋、冬季间种类相似性指数最高。周年优势种有亨氏仿对虾(Parapenaeopsis hungerfordi)、钝齿蟳(Charybdis hellerii)、日本囊对虾(Marsupenaeus japonicus)、刀额新对虾(Metapenaeus ensis)和近缘新对虾(Metapenaeus affinis)等5种,主要种有须赤虾(Metapenaeopsis barbata)、长毛明对虾(Fenneropenaeus penicillatus)、中型新对虾(Metapenaeus intermedius)、口虾蛄(Oratosquilla oratoria)、周氏新对虾(Metapenaeus joyneri)和远海梭子蟹(Portunus pelagicus)等6种。4个季度最大优势种分别为亨氏仿对虾(春季)、刀额新对虾(夏季)、近缘新对虾(秋季)、钝齿蟳(冬季)。全湾甲壳类年均密度和生物量分别为32 201尾/km2和212. 29 kg/km2,均呈现明显的季节变化和空间差异。甲壳类各站位种数变化范围为2～17种,种类多样性指数(H')在0. 200～3. 160之间,丰富度指数(d)在0. 200～2. 230之间,均匀度指数(J)在0. 160～0. 988之间;种数、H'、d和J表现出显著性空间差异,种数和J表现出显著性季节变化。聚类分析、相似性分析及相似性百分比分析表明该海域甲壳类群落存在一定程度的时空异质性。生物-环境分析表明影响该海域甲壳类群落结构的环境因子存在季节差异。     

Accumulation of sediment,organic matter and trace metals with space and time,in a creek along Mumbai coast,India

Two core sediment samples; one from inner part (ManI) and the other closer to the mouth (ManII); were collected from the intertidal regions of Manori, a tidally influenced creek near Mumbai, India. Both the cores were subjected to various geochemical analyses to determine parameters such as pH, sediment components, total organic carbon, total nitrogen, total phosphorus and selected metals viz., Fe, Mn, Cu, Pb, Co, Ni, Zn, Cr, Al, Ca and V. Analysis of ²¹⁰Pb activity was employed to assess the sediment deposition trend of the area. The data was further processed using factor and cluster analyses. The results indicate that the sediments from site ManI, had finer sediment composition, higher porosity, organic matter and metal contents but exhibited an erratic decline in ²¹⁰Pb activity downcore. Also ManI showed higher C:N ratio and enrichment factor values as compared to site ManII. The inner area (ManI) probably received a greater input of organic matter from the erosion of terrestrial matter as well as domestic and industrial discharge. Sediments from site ManII had typical marine organic matter composition (lower C:N ratio). The concentration of metals at this site was also low indicating the contents were getting diluted by freshwater and seawater mixing.     

Cadmium, copper, and zinc interactions with marine humus as a function of ligand structure

The interactions in seawater of cadmium, copper, and zinc with natural levels of marine humus (fulvic and humic acids) were studied using differential pulse anodic stripping voltammetry (DPASV). Interactions with Cu were also examined by ultraviolet spectrophotometry. The degree of interaction relates to the structure of the particular fulvic or humic acid tested. Marine fulvic and humic acids with different equivalent weights and varying degrees of aromaticity and heteroatom substitution were tested to assess the relative importance of these fundamental structural features in determining the degree of interaction. An index of heteroatom substitution, derived from proton magnetic resonance spectra of these materials, when combined with equivalent weights correlated with the nature and degree of metal interaction. Both marine fulvic and humic acids appreciably interacted with Zn. In contrast, the extent of interaction of fulvic acids with Cu appears to be related to their structure while humic acids appear to interact with Cu regardless of structure. Cadmium interacts only with mature, highly crosslinked humic acids.