Kaji-ichigoside F1 (KF1), a natural oleanane-type triterpenoid saponin, is the main active constituent from Rosa roxburghii. In the southwest regions of China, particularly in Guizhou Province, this plant was used as a Miao ethnic medicine to prevent and treat dyspepsia, dysentery, hypoimmunity, and neurasthenia. In the present study, the neuroprotective effect of KF1 was evaluated against N-methyl-D-aspartate (NMDA)-induced neurotoxicity in vivo and in vitro. An NMDA-induced PC12 cell neurotoxicity assay showed that KF1 effectively improved cellular viability, inhibited the release of lactate dehydrogenase (LDH), and reduced cell apoptosis. Furthermore, KF1-treated NMDA-induced excitotoxicity mice displayed a remarkable capacity for improving spatial learning memory in the Y-maze and Morris water maze tests. In addition, KF1 increased the levels of the neurotransmitters 5-hydroxytryptamine, dopamine, and monoamine oxidase and reduced the calcium ion concentration in the hippocampus of mice. Hematoxylin and eosin and Nissl staining indicated that KF1 effectively reduced the impairment of neurons. Furthermore, Western blot assays showed that KF1 decreased NMDAR1 expression. In contrast, the NMDAR2B (NR2B), glutamate receptor (AMPA), TrkB, protein kinase B (AKT), mammalian target of rapamycin (mTOR), PSD95, and synapsin 1 were upregulated in NMDA-induced PC12 cells and an animal model. These results suggest that KF1 has a remarkable protective effect against NMDA-induced neurotoxicity, which is directly related to the regulation of the NMDA receptor and the activation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and BDNF/AKT/mTOR signaling pathways.

目的:通过网络药理学和分子对接技术探讨芪归药对调控肿瘤免疫微环境(tumor immune microenviroment,TIME)的机制和物质基础.方法:通过TCMSP数据库筛选黄芪、当归的有效活性成分及相关靶点蛋白,将经GeneCards数据库挖掘的TIME相关靶标与药物靶点蛋白交集;运用Cytoscape 3.7.1软件构建活性成分-靶点-疾病网络图,运用STRING数据库构建交集靶点的PPI网络并拓扑分析核心靶点,运用David数据库进行KEGG通路和GO功能富集分析;利用Auto Dock Vina软件将主要活性成分、阳性对照药与核心靶蛋白进行分子对接、PyMol 2.3软件绘制对接模式图.结果:筛选出芪归药对的有效活性成分18个,靶点蛋白100个,芪归药对与TIME的交集靶点79个,分析得到78条KEGG富集通路、304条GO功能富集条目,涉及microRNA、PI3K/Akt、TNF、MAPK、HIF-1等通路及炎症、增殖凋亡、缺氧等生物过程;活性成分槲皮素、山柰酚、β-谷甾醇与IL-6、VEGF、EGFR、CAPS3、MAPK8等潜在核心靶点蛋白均存在较强的分子对接关系.结论:初步揭示了芪归药对可通过多成分、多途径和多靶点协同调节TIME的作用机制,为临床筛选调节TIME药物提供可靠理论依据.

Hypertension is a major health problem common in the elderly people. Green tea is a popular beverage recommended in folk medicine for lowering blood pressure. However, the molecular mechanisms involved in the antihypertensive effects of green tea are not fully understood. Therefore, the aim of this study was to investigate the antihypertensive effects of green tea on high-salt diet-induced hypertension in old male rats. Forty old male rats were divided into five groups: control, hypertensive, and hypertensive-green tea (2, 4, and 6 g/kg). Heart rate (HR) and systolic blood pressure (SBP) were measured. Cardiac and renal histology were also performed. Lipid profile, NO, angiotensin II (Ang II), and aldosterone were determined, and the expression of eNOS, ATIR and ATIIR, aldosterone receptor, and Atp1a1 were measured. Green tea could significantly decrease HR and SBP, lipid profiles, renin-angiotensin II-aldosterone system activity, and Ang II signaling in kidney tissue of hypertensive rats (p < .01). It also increased Atp1a1, Nrf2, and eNOS expression along with antioxidant enzymes activity and NO concentration (p < .05) and decreased NF-ĸB and iNOS expression and IL-1β levels in the heart, kidneys, and aorta of rats with hypertension. It can be concluded that green tea can improve salt-induced blood pressure by modulating the function of the renin-angiotensin-aldosterone system, enhancing the synthesis of nitric oxide in the endothelium, increasing antioxidant activity and suppressing inflammation in the heart and kidney, improving the expression of the sodium-potassium pump, and reduction in serum lipids and glucose in aged male rats. PRACTICAL APPLICATIONS: The results of this study showed that green tea could improve hypertension in elderly rats by modulating (1) the expression of the sodium-potassium pump in the heart, kidney, and aortic tissues, (2) the activity of the renin-angiotensin II-aldosterone system in kidney, (3) enhancing antioxidant and anti-inflammatory activities in the heart, aorta, and kidneys, (4) enhancing the synthesis of nitric oxide in the endothelium, and (5) lowering lipid profile. The results of these studies show that the consumption of green tea and its products can be a good candidate for the prevention of cardiovascular diseases such as hypertension in the elderly. In addition, attention to its bioactive compounds can be considered by researchers as an independent therapeutic strategy or adjunctive therapy for the treatment of hypertension.

Triptolide is a natural active compound that has significant neuroprotective properties and shows promising effects in the treatment of Alzheimer's disease (AD). Recent studies have shown that autophagy occurs in AD. In this study, we determined whether autophagy regulated by triptolide ameliorates neuronal death caused by amyloid-Beta1-42 (Aβ1-42). We examined the effects of triptolide on cell viability, autophagy, apoptosis, and the protein kinase B/mammalian target of the rapamysin/70 kDa ribosomal protein S6 kinase (Akt/mTOR/p70S6K) signaling pathway in PC12 cells. The results indicated that triptolide treatment exhibited a cytoprotective effect against cell injury induced by Aβ1-42. Triptolide also reduced apoptosis and enhanced cell survival by decreasing autophagosome accumulation and inducing autophagic degradation. Furthermore, our results also showed that activating the Akt/mTOR/p70S6K mechanism was one reason for the protection of triptolide. Triptolide treatment protected against Aβ1-42-induced cytotoxicity by decreasing autophagosome accumulation, and inducing autophagic degradation in PC12 cells. These findings also suggest that the reduction of autophagosome accumulation observed in triptolide-treated cells was Akt/mTOR/p70S6K pathway dependent. Overall, triptolide exhibits a neuron protective effect and this study provides new insight into AD prevention and treatment.

目的 探讨"芪归药对"干预NF-κB通路调控骨髓造血干细胞(HSCs)辐射旁效应损伤的机制.方法 模拟辐射旁效应HSCs与BMSCs的共培养模型.共培养细胞被随机分为4组:模型组(MX)、"芪归药对"载药血清组(QG)、SN50组(SN50)、药物联用组(LY).各实验组共培养48h后,镜下观察旁细胞集落数,荧光探针DAFFM-DA、DCFH-DA检测旁细胞的NO、ROS水平,流式细胞仪检测旁细胞凋亡率;realtime RT-PCR检测旁细胞的NF-κB通路及凋亡相关基因mRNA水平.结果 与MX组相比,QG组旁细胞HSCs集落增多(P＜0.05),凋亡率降低(P＜0.05),ROS与NO水平下降(P＜0.05),在基因转录水平,NF-κB、COX2、iNOS及Bax表达呈下调趋势,Bcl-2表达上调,Caspase-3表达下调(P＜0.05);SN50组旁细胞HSCs集落增多(P＜0.05),凋亡率、ROS水平呈下降趋势,在基因转录水平,NF-κB、COX2、iNOS、Bax表达均呈下调趋势,Bcl-2表达上调(P＜0.05);LY组旁细胞HSCs集落增多(P＜0.05),凋亡率降低(P＜0.05),ROS、NO的水平下降(P＜0.05),在基因转录水平,NF-κB、iNOS表达下调(P＜0.05),COX2、Bax、Caspase-3表达均呈下降趋势.与SN50组相比,QG组凋亡率降低(P＜0.05),ROS、NO的水平下降(P＜0.05);LY组旁细胞HSCs集落增多(P＜0.05),凋亡率呈下降趋势,ROS、NO的水平下降(P＜0.05),在基因转录水平,NF-κB、COX2、iNOS、Bax、Caspase-3表达均呈下降趋势.结论 "芪归药对"载药血清可能通过抑制NF-κB通路,使旁细胞HSCs内ROS和NO水平下降,促进HSCs增殖、抑制其凋亡,降低了HSCs辐射旁效应损伤程度.

据统计在全球范围内,白血病死亡率处于恶性肿瘤前十位,急性髓系白血病( acute myelocytic leukemia, AML)成人发病率最高,儿童位居第二,占儿童白血病死亡率50％以上.髓系原始细胞常恶性增殖,具有克隆进化、遗传异质性的特征[1].癌细胞浸润骨髓、外周血后,患者产生一系列贫血、出血、感染和骨痛等急性症状.目前AML临床治疗手段有造血干细胞移植,化疗,放疗,免疫治疗,靶向药物治疗等,化疗是首选方法,但随着治疗进程的不断推进,治疗耐药性已成为临床治疗难、治疗失败的首因.因此,介导白血病细胞耐药的机制研究已成为临床关注的热点,耐药过程中涉及多种信号通路,本文将对AML耐药相关信号通路的研究进展加以综述,以期为临床的靶向用药的研究提供新的方向和思路.

目的 系统评估老年脑卒中患者下肢深静脉血栓(DVT)形成的危险因素.方法 全面检索从建库至2021年3月关于老年脑卒中患者下肢深静脉血栓形成危险因素的病例对照研究.采用Stata 12.0进行meta分析.结果 共纳入23篇文献,病例组1965例,对照组8985例.Meta分析结果显示,卧床(OR=4.65,95％CI:2.97～7.26)、合并高血压(OR=3.94,95％CI:2.97～5.23)、股静脉穿刺(OR=27.55,95％CI:16.14～47.03)、肺部感染(OR=2.34,95％CI:1.70～3.23)、高龄(OR=2.08,95％CI:1.46～2.96)、D-2聚体升高(OR=2.17,95％CI:1.77～2.67)、C-反应蛋白升高(OR=4.18,95％CI:2.98～5.86)、血浆纤维蛋白原升高(OR=1.12,95％CI:1.03～1.22)、同型半胱氨酸升高(OR=1.47,95％CI:1.16～1.85)、BI评分低(OR=2.71,95％CI:1.59～ 4.6)、GCS评分低(OR=2.32,95％CI:1.41～3.81)、Wells评分高(OR=4.62,95％CI(2.77～7.71)、无康复治疗(OR=1.90,95％CI:1.39～2.61)、无抗凝治疗(OR=1.77,95％CI:1.28～ 2.45)、吸烟史(OR=1.41,95％CI:1.11～1.80)、心力衰竭(OR=1.43,95％CI:1.10～1.87)、糖尿病(OR=1.36,95％CI:1.06～1.74)是老年脑卒中患者下肢DVT发病的危险因素.结论 老年脑卒中患者下肢深静脉血栓的预防应从保持良好的饮食和生活习惯、血清生化指标的持续监控、早期康复和抗凝治疗、其他合并疾病的及时治疗等方面提供及时有效的措施.

目的 基于自噬-NF-κB通路探讨阿魏酸钠对白血病化疗耐药株增敏的机制.方法 复制白血病化疗耐药细胞模型,Western blot法观察L1210、L1210/DDP细胞自噬-NF-κB通路的基础表达水平,将L1210/DDP随机分为control组(L1210/DDP)、model组(L1210/DDP+ 8μg/ml DDP)、SF组(model组+0.5mmol/L SF)、3-MA组(model组+10μmol/L 3-MA)、SN50组(model组+2μmol/L SN50)、SF+3-MA组(model组+0.5mmol/L SF+ 10μmol/L 3-MA)及SF+SN50组(model组+0.5mmol/L SF+ 2μmol/L SN50)7组.据实验分组进行药物干预48h,行指标检测.cck-8法检测实验各组细胞活力,流式细胞仪检测实验各组细胞凋亡率、细胞周期的变化;Western blot检测实验各组细胞自噬-NF-κB通路关键节点蛋白表达变化.结果 与L1210细胞相比,L1210/DDP细胞自噬与NF-κB通路异常激活(P＜0.05);与model组相比,各给药组细胞活力降低、G0/G1期细胞百分比减少(P＜0.05)、S期细胞百分比增加(P＜0.05)、凋亡率增加(P＜0.05),且SF与抑制剂联用效果更佳,LC3BⅡ/Ⅰ表达减少(P＜0.05)、p-p65/p65比值降低、bcl-2/bax表达减少(P＜0.05);与SF组相比,SF与抑制剂联用组Beclin1、LC3BⅡ/I蛋白减少(P＜0.05),bcl-2/bax比值降低(P＜0.05).结论 SF通过抑制耐药株自噬-NF-κB通路,增加耐药株对DDP的敏感性,具有抑制癌细胞增殖,促进癌细胞凋亡的功效.

放化疗是目前临床治疗恶性肿瘤的主要手段,而骨髓抑制是其主要的毒副作用,直接影响患者在放化疗期间的疗效、预后及转归。防治骨髓抑制是恶性肿瘤放化疗成功的关键。以中医的观点来看,放化疗作为一种毒邪,侵犯机体,伏而不发或伏而小发,积久成"伏毒",进而影响脏腑,甚至髓络的生理功能,导致肿瘤患者发生骨髓抑制。从"伏毒"与骨髓抑制相关性进行探讨分析,并结合脾肾两脏与生血的关系,认为"伏毒"能从多个方面对骨髓抑制的发病及治疗产生影响。

本文对近年来关于熊胆粉的相关报道进行总结,对其化学成分进行了详细的论述,特别对其保肝、抗癌作用机制进行总结阐述,为更进一步研究熊胆粉保肝、抗癌作用提供参考,并对今后开发利用熊胆粉新药进行了展望.

[目的]基于冰山模型构建护士综合素质测评指标体系,为临床护士综合素质测评提供可视化工具.[方法]在冰山模型的基础上,通过查阅国内外文献、小组讨论和运用德尔菲法对16名专家进行2轮专家函询,建立了系统、全面的护士综合素质测评体系.[结果]最终确定了护士综合素质测评指标体系,包括3项一级指标,8项二级指标和31项三级指标.两轮专家有效应答率均为100％,第2轮函询专家权威系数为0.8875,二级、三级指标的Kendall W系数分别为0.492和0.387(P<0.05).[结论]基于冰山模型的护士综合素质测评指标体系科学、客观、内容全面,可用于对临床护士综合素质的测评,并对其他医院护理团队建设有借鉴价值.

肌源性干细胞(muscle-derived stem cells,MDSCs)作为骨骼肌来源的成体干细胞,在造血微环境的诱导下可以向造血分化.就其来源而言,MDSCs属于"水谷之精"范畴,造血能力与"脾主运化"有关;就其造血微环境而言,与中医"肾藏精"关系密切.从来源和造血微环境两方面,基于"脾主运化""肾藏精"探讨MDSCs造血分化能力.

肌源性干细胞(muscle-derived stem cells,MDSCs)是从骨骼肌组织中获取的具有自我更新能力和多项分化潜能的成体干细胞.在无诱导因素作用下可定向分化为骨骼肌细胞,而在体内外特定微环境的诱导下,能向造血方向分化,具有明显的造血分化潜能.MDSCs具有取材容易,利于体外培养,移植后免疫原性低等特点,有望成为恶性血液病移植治疗的新种子细胞.但MDSCs造血分化的机制尚未明确,而本课题组长期致力于MDSCs的研究.因此本文将从近年来对MDSCs的研究进展、MDSCs造血分化相关机制的研究、存在的问题以及应用前景进行综述.

近年来,我国医学研究生教育飞速发展,但在"量"的迅猛扩张的同时,"质"的提升却不是很显著,凸显了医学研究生教育创新教育的必要性.本文以学生视角分析了医学研究生教育现状的透视及弊端,提出了构建医学研究生创新教育保障体系的建议,助推基于医学研究生创新教育的健康发展.

心力衰竭(HF)是导致各类心脏疾病患者死亡的内科常见重症之一,5年病死率较高.心力衰竭发病因素及机制复杂,近年来有研究认为其与代谢组学密切相关,即机体内三羧酸循环(TCA cycle)、糖代谢、氨基酸代谢、脂代谢等能量代谢紊乱情况可能与心力衰竭的发生及发展具有一定相关性.本文就心力衰竭、心力衰竭的代谢组学及代谢组学在心力衰竭治疗中的作用作一综述,以期为临床治疗提供参考.

目的 系统评价中医药治疗恶性肿瘤化疗后骨髓抑制的临床疗效.方法 计算机检索PubMed、The Cochrane Library、EMbase、CNKI、WanFang Data数据库,查找关于中医药治疗恶性肿瘤化疗后骨髓抑制的随机对照试验(RCT),检索时限均从建库至2018年12月.由两位研究者按事先设计好的纳入与排除标准筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan5.3和R3.5.1软件进行Meta分析.结果 共纳入20个RCT,1703例患者.Meta分析结果显示:与单纯化疗组相比,中药联合化疗组能更有效的治疗恶性肿瘤化疗后骨髓抑制,降低白细胞、血小板及血红蛋白下降发生率[RR =0.63,95％ CI(0.52,0.77),P ＜0.00001;RR =0.44,95％ CI(0.32,0.62),P ＜0.00001;RR =0.48,95％ CI(0.35,0.67),P＜0.0001];提高化疗后白细胞、血小板、血红蛋白计数水平[MD=1.55,95％ CI(1.07,2.03),P＜0.00001;MD=52.79,95％ CI(33.91,71.67),P＜0.00001;MD=17.36,95％ CI(9.45,25.26),P＜0.001;MD=1.17,95％ CI(0.77,1.57),P＜0.00001];改善患者生活质量[RR=1.71,95％ CI(1.27,2.30),P=0.0005],且差异具有统计学意义.结论 中药联合化疗与单纯化疗相比,能更有效的治疗恶性肿瘤化疗后骨髓抑制.但受纳入研究质量限制,上述结论尚待更多高质量RCT予以验证.

OBJECTIVETo investigate the mechanism of hematopoietic reconstruction in mice treated with Danggui Buxue Decoction (DBD) combined with the muscle-derived stem cell transplantation (MDSCT).METHODSFemale Kunming mice were randomly divided into the 6 groups: irradiation model, the bone marrow transplantation, the MDSC transplantation, the DBD 1 (4.5 g/kg), 2 (13.5 g/kg), and 3 (22.5 g/kg) + MDSC transplantation. After a week of oral administration of normal saline or different doses of DBD, The mice were exposied to 8 Gy 137Cs γ ray and were followed by bone marrow or MDSC transplantation. The expression levels of Notch1, Jagged1 and Hes1 in bone marrow, thymus and spleen were measured at 3 and 8 weeks after irradiation and transplantation.RESULTSIn the bone marrow, 3 weeks after above-mentioned treatment, the expression of Notch1 mRNA increased obviously and the expression of Jagged1, Hes1 mRNA decreased obviously in each intervention group, compared with the irradiation model group. 8th week after treatment, the expression of Notch1 mRNA decreased obviously in each intervention group, the Jagged1 mRNA expression decreased obviously except the bone marrow group, and Hes1 mRNA expression increased (P＜0.05) in each intervention group. 3 weeks after treatment, compared with the irradiation model group, the expression of Notch1 mRNA in the thymocytes increased only in DBD1+MDSC group, Jagged1, Hes1 mRNA was increased in the MDSC transplantation group and the DBD1、2+MDSC group. 8th week after treatment, the expression of Notch1, Jagged1 mRNA expression decreased in each intervention group, the expression of Hes1 mRNA increased obviously in the MDSC transplantation group and the DBD1、2+MDSC group (P＜0.05). In the spleen, 3 weeks after treatment, the expression of Notch1, Jagged1 mRNA in the spleen of each intervention group decreased obviously, compared with the irradiation model group. The expression of Jagged1, Hes1 mRNA in each intervention group were increased obviously 8th week after treatment (P＜0.05).CONCLUSIONMDSC transplantation after pretreatment of DBD can improve the hematopoietic reconstitution in mice with lethal dose radiation damage. Notch1、Jagged1 and Hes1 play different roles in this process, but the concrete mechanism needs to be further studied.

为探讨中医院校医学相关专业《组织学》课程相对稳定的形成性评价考核模式,自2016-2018年在天津中医药大学护理专业和药学专业的组织学教学实践中,就形成性评价的具体考核手段和方法进行了尝试,从期末成绩与形成性评价的相关性等方面对形成性评价考核方法进行了评价,结果提示所采用的形成性评价考核方法能够客观、合理、有效地反映学生的学习过程.

目的 基于p62-NRF2通路探讨黄芪甲苷(AST)对白血病耐药细胞株化疗敏感性的影响机制.方法 复制白血病细胞模型,cck-8法测L1210、L1210/DDP细胞株对DDP的敏感性;将L1210/DDP细胞随机分成5组,即L1210组、L1210/DPP组、给药1组(L1210/DDP+ 8μg/ml DDP)、给药2组(L1210/DDP+ 8μg/ml DDP+ 100μg/ml AST)、给药3组(L1210/DDP+ 8μg/ml DDP+ 70μg/ml verapamil组),评价AST对L1210/DDP耐药性的逆转作用;流式细胞仪检测各组细胞周期、凋亡率变化,DCFH-DA荧光探针检测各组细胞内ROS变化;real time RT-PCR检测p62-NRF2通路各节点基因的表达变化.结果 L1210/DDP细胞对DDP的敏感性明显弱于L1210细胞,相对耐药指数为2.56;100μg/ml AST作用24h后,相对逆转倍数为13.67,70μg/ml verapamil的相对逆转倍数为20.46;与L1210组相比,含L1210/DDP各组内ROS水平低(P＜0.05);与L1210/DDP组相比,给药2、3组肿瘤细胞G1期阻滞,S期缩短,细胞增殖受到抑制(P＜0.05);给药各组细胞p62、NRF2基因mRNA表达下调,除给药1组外,细胞HO-1基因mRNA表达均下调,而各给药组细胞cyclinD、Caspase3 mRNA表达均上调,但无统计学意义.结论 AST具有增强L1210/DDP细胞株对DDP敏感性,逆转L1210/DDP细胞株耐药的功效,其机制可能通过调控p62-NRF2通路及其靶基因的表达有关.

脂代谢紊乱是前列腺癌(PCa)的一个标志性特征.固醇调节元件结合蛋白(SREBPs)是调节细胞脂类代谢的重要转录因子,能够调控脂肪酸和胆固醇合成关键基因的表达.研究表明SREBPs可能是作为治疗前列腺癌的潜在靶点.总结了SREBPs在前列腺癌发生发展中的作用机制,以及靶向SREBPs治疗前列腺癌的研究进展.