临床诊疗
目的 观察蒜氨酸对血管性痴呆(VD)脑损伤的作用,并探讨其可能的作用机制。方法 采用随机数字表法将40只大鼠分为假手术组、模型组、蒜氨酸低、中、高剂量组,每组大鼠为8只。模型组和蒜氨酸组采用双侧颈总动脉结扎建立VD大鼠模型。造模7 d后蒜氨酸组分别给予蒜氨酸10、20、30 mg/kg灌胃治疗,假手术组和模型组给予等量生理盐水灌胃治疗,每组均为1次/d,共4周。采用Morris水迷宫实验检测大鼠学习记忆能力,ELISA法检测大鼠海马超氧化物歧化酶(SOD)活性,蛋白免疫印迹法(Western blotting)检测大鼠海马iNOS、IL-1β及TNF-α蛋白的表达。结果 与假手术组相比,模型组大鼠逃避潜伏期延长,找到平台次数减少,SOD活性降低,iNOS、IL-1β及TNF-α蛋白表达量增加,差异均有统计学意义(P<0.05);与模型组相比,蒜氨酸各剂量组大鼠潜伏期缩短,找到平台次数增多,SOD活性增高,iNOS、IL-1β及TNF-α蛋白表达量减少,差异均有统计学意义(P<0.05)。结论 蒜氨酸能改善血管性痴呆大鼠的学习记忆能力,其机制可能与其抗氧化应激,抑制相关炎症因子的释放有关。
论著
目的 利用GEPIA数据库,包括TCGA数据库和GTEX数据库,探讨二氢丹参酮I通过氧化应激治疗胃癌的潜在靶点。方法 在数据库中检索二氢丹参酮I在胃癌中潜在靶点的文献,利用GEPIA数据库工具分析二氢丹参酮I在胃癌中的潜在作用机制,分析潜在靶基因与表达关键抗氧化应激蛋白基因的相关性;二氢丹参酮I对胃癌潜在靶基因表达水平的分析;二氢丹参酮I对胃癌潜在靶基因的预后分析。结果 二氢丹参酮I对潜在靶基因的主要靶向基因(蛋白)为缺氧诱导因子-1(hif-1)和瓜氨酸组蛋白h3(cith3),其基因分别为HIF1 A和NOS2;GEPIA数据库显示HIF1 A与CAT(P=e-04,r=0.18)、GPX1(P=0.033,r=0.11)或NFE2L2呈正相关。(P=0,r=0.41),而NOS2与SOD1仅呈正相关(P=0.21,r=0.18),与其它三个基因均无相关性;HIF1 A和NOS2在胃癌组织中的表达水平高于正常胃旁组织;HIF1 A的高表达降低了胃癌患者的总生存率。结论 二氢丹参酮I可通过活性氧介导的氧化应激诱导AGS细胞凋亡,抑制HIF1 A和NOS2的表达,从而抑制AGS细胞的抗氧化应激,提高胃癌患者的总生存率。
Objective In this study, GEPIA database, including TCGA database and GTEx database, were used to explore the potential targets of dihydrotanshinone I on gastric cancer through oxidative stress. Methods Literatures on potential targets of dihydrotanshinone I in gastric cancer were searched in the database;GEPIA database tool was used to analyze the potential mechanism of dihydrotanshinone I on gastric cancer;taking analysis of the correlation between potential target genes and genes expressing key antioxidant stress proteins;We had analysis of expression level of dihydrotanshinone I on potential target genes in gastric cancer patients;and prognostic analysis of dihydrotanshinone I on potential target genes in gastric cancer patients. Results The main targeting genes(proteins) of dihydrotanshinone I on potential target genes were hypoxia inducible factor-1(hif-1) and citrulline histone H3(CITH3), whose genes were HIF1 A and NOS2, respectively;GEPIA database showed that there was a positive correlation between HIF1 A and CAT(P=2e-04, R=0.18), GPX1(P=0.033, R=0.11), or NFE2L2(P=0, R=0.41), while NOS2 only had a positive correlation with SOD1(P=0.21, R=0.18), and no correlation with other three genes. The expression levels of HIF1 A and NOS2 in gastric cancer tissues were higher than those in normal adjacent gastric tissues. The overall survival rate of patients with gastric cancer decreased with the high expression of HIF1 A. Conclusion Dihydrotanshinone I may induce apoptosis of AGS cells through reactive oxygen species mediated oxidative stress, and inhibit the expression of HIF1 A and NOS2, thus inhibit their antioxidative stress, which may improve the overall survival rate of gastric cancer patients.
论著
目的 探讨骨髓间充质干细胞源性微泡(BMSC-MV)修复大鼠早发性卵巢功能不全的自噬机制。方法 大鼠骨髓分离培养骨髓间充质干细胞;超速离心法从骨髓间充质干细胞培养液中分离微泡;腹腔注射顺铂溶液制备早发性卵巢功能不全(POI)模型,制备后3 d尾静脉取血ELISA检测血清雌二醇(E2)及卵泡刺激素(FSH);尾静脉注射BMSC-MV移植治疗POI大鼠模型,移植后28 d尾静脉取血ELISA检测E2、FSH及抗苗勒管激素(AMH),同时取卵巢组织检测自噬相关蛋白LC3及P62。结果 模型对照组及微泡移植组在模型制备后3 d的E2 含量低于正常对照组,FSH 含量高于正常对照组(P<0.001);微泡移植组在移植后28 d的E2、AMH含量高于模型对照组(P<0.001),FSH含量低于模型对照组(P<0.001);微泡移植组的LC3较模型对照组表达升高,而P62表达降低(P<0.001)。结论 BMSC-MV介导自噬修复大鼠早发性卵巢功能不全。
Objective To investigate the autophagy mechanism of bone marrow mesenchymal stem cell-derived microvesicle (BMSC-MV) in repairing premature ovarian dysfunction in rats. Methods The whole bone marrow adherence method was used to isolate,culture and identify BMSCs of SD rats. Microvesicles were isolated from bone marrow mesenchymal stem cell by ultracentrifugation. Premature ovarian insufficiency (POI) model was prepared by intraperitoneal injection of cisplatin solution,and serum estradiol (E2) and follicular stimulating hormone (FSH) were detected by ELISA from tail vein 3 days after preparation. Rat model of POI was treated with BMSC-MV transplantation by tail vein. Blood from tail vein was collected 28 days after transplantation to detect E2,FSH and AMH by ELISA. Meanwhile,ovarian tissues were collected to detect autophagy-related proteins LC3 and P62. Results The E2 content of the model control group and the microvesicle transplantation group was lower than that of the normal control group,and the FSH content was higher than that of the normal control group (P<0.001). The content of E2 and AMH in the microvesicle transplantation group at 28 days after transplantation was higher than that in the model control group (P<0.001),and the content of FSH was lower than that in the model control group (P<0.001). Compared with the model control group,LC3 expression in the microvesicle transplantation group was increased,while P62 expression was decreased (P<0.001). Conclusion BMSC -MV mediate autophagy to repair premature ovarian insufficiency in rats.
论著
目的 运用网络药理学方法预测生白术活性成分、作用靶点及生物学意义,探讨其防治便秘的作用机制,并结合导师临床应用取得的疗效进行进一步的验证。方法 借助TCMSP在线数据库查找白术的药效成份并选择其生物利用度(OB)>30%且类药性(DL)>0.18的化合物,并查询每种成分所对应的靶标。通过Gene Cards、OMIM共2个疾病相关靶点的数据库检索便秘相关靶点信息。将二者靶基因相映射获得交集靶点。借助 cytoscape 3.7.1 软件对查询结果进行可视化。所得到的基因通过相互作用数据库(STRING)进行相互作用蛋白查询并构建蛋白质相互作用(PPI)网络。使用R语言对关键靶点行GO和KEGG富集分析,以构建“成分-靶点-信号通路”的网络。结果 共得到白术人源靶蛋白7个,便秘相关的人源基因2 859个。发现其主要通过干预PGR、CHRM3、CHRM1、ACHE、CHRM2五个基因并参与胆碱能突触、钙信号通路、肌动蛋白细胞骨架的调控、神经活性配体-受体相互作用、cAMP信号通路、PI3K-AKT信号通路共6条信号通路以达到防治便秘的效果。结论 应用网络药理学方法分析预测得到重用生白术防治便秘的潜在药效成分、作用靶点及其信号通路,为临床应用提供了理论依据。
Objective To predict the active ingredients, targets and biological significance of Atractylodes macrocephala by network pharmacology, to explore the mechanism of its prevention and treatment of constipation, and to further verify its efficacy in combination with the clinical application of tutors. Methods The constituents of Atractylodes macrocephala were searched by TCMSP database and the compounds with bioavailability (OB) > 30% and drug-like property (DL) > 0.18 were screened, and the corresponding targets of each constituent were queried. Constipation-related target information was retrieved from two disease-related target databases of GeneCards and OMIM, mapping the two target genes to obtain intersecting targets, by visualization of query results with cytoscape 3.7.1. The resulting genes were queried by the interaction database (STRING) and the protein interaction (PPI) network was constructed. GO and KEGG enrichment analysis of key targets was carried out by R language in order to construct the network of “component-target-signal pathway”. Results Seven human target proteins and 2 859 constipation related human genes were obtained from Atractylodes macrocephala. It was found that the effect of prevention and treatment of constipation was mainly achieved by interfering with five genes of PGR, CHRM3, CHRM1, ACHE and CHRM2 and participating in six signaling pathways: cholinergic synapse, calcium signaling pathway, regulation of actin cytoskeleton, neuroactive ligand-receptor interaction, cAMP signaling pathway and PI3K-AKT signaling pathway. Conclusion The potential pharmacodynamic components, targets and signaling pathways of reuse Rhizoma atractylodis macrocephalae in the prevention and treatment of constipation can be predicted by network pharmacological method, which provides a theoretical basis for clinical application.
临床诊疗
目的 探究血清外泌体对小鼠烫伤伤口愈合的促进作用及机制。方法 选取我院60只NIH小鼠作为研究对象,对其血清中的外泌体进行提取和分离,建立起皮肤烫伤模型。采用血清外泌体进行治疗,评估治疗的效果,观察皮肤组织的病理变化,检测小鼠成纤维细胞增殖和表皮HaCat细胞迁移使用血清外泌体受到的影响。结果 空白对照组和血清外泌体小鼠烫伤创口愈合时间比较,差异有统计学意义(P<0.05);血清外泌体作用24 h后,不同剂量OD值差异有统计学意义(P<0.05);10 μL Exo组和PBS组内部不同时间点OD值差异均有统计学意义(P<0.05);外泌体组和PBS组24 h的HaCat细胞迁移率相比较,差异有统计学意义(P<0.05)。结论 血清外泌体可以促进小鼠烫伤伤口的愈合,对成纤维细胞的增殖和表皮HaCat细胞的迁移作用也比较显著,可能成为临床治疗烫伤的新手段。
综述
瘦素(leptin)是由控制各种生理过程的脂肪组织合成和分泌的一类激素,通过作用于靶细胞膜上的瘦素受体并经信号传导在各器官和系统中发挥一系列生物学效应。肾脏是高血压常见的靶器官之一。相关研究表明,瘦素在高血压肾损害中发挥作用,其机制可能与氧化应激及其炎症反应有关。本文以瘦素对高血压肾损害及其相关机制作一综述,并探讨瘦素对高血压肾损害发病机制研究进展。
Leptin which is a kind of synthesis and secretion of hormone that participates in various physiological processes is the role of the leptin receptor on the target cell membrane and the signal transduction through a series of biological effects in different organs and systems. Kidney is one of the common target organs of hypertension, and related research shows that leptin plays a role in hypertensive kidney damage, whose mechanism may be related to oxidative stress and its inflammatory reaction. The paper reviewed leptin on renal damage in hypertension and its related mechanisms, to explore the leptin on renal pathogenesis of hypertension research progress.
综述
青蒿素类药物作为抗疟特效药,其特殊分子骨架和过氧基在抗疟中起着关键作用。通过损伤虫体的器膜、诱导蛋白变性、抑制ATP 蛋白6(Pf ATP6)活性等方式杀灭疟原虫。恶性疟原虫基因序列的突变和长期不规范用药均会使其产生耐药性。本文依据文献报道,对世界关于青蒿素类药物抗疟机制、耐药性的产生原因作一综述。
Artemisinin is an effective anti-malaria drug, It's special molecular framework and peroxy group play a key role in antimalarial. Plasmodium falciparum was killed by the inducing cytoplasmic organelledamage protein denaturation, inhibiting ATP6 activity. Mutations in the genetic sequence of plasmodium falciparum and long-time using drugs without rule will develop drug resistance. This article is based on the literature, do a review of the world's causes for the resistance of artemisinin to antimalarial mechanisms.
论著
目的 探讨拔岗晋级结合激励机制在护士岗位管理的实践和体会。方法 在护士岗位管理中运用拔岗晋级结合激励机制,收集实施岗位管理前后1年护士满意度、患者满意度、护士职业获益感、护士职业投入、离职率资料,进行统计学分析。结果 实施后护士满意度、患者满意度、护士职业获益感、护士职业投入较实施前提高(P<0.05),离职率下降(P<0.05),差异有统计学意义。结论 建立在拔岗晋级及激励机制上的护士岗位管理能提高护士满意度,降低护士离职率,稳定护士队伍,能够提高护士职业获益感、护士职业投入,从而提高护士工作的主观能动性和工作积极性,为高质量护理服务和优质护理服务长效机制的建立奠定了基础,促进优质护理服务的可持续发展,提高护理管理效能。
Objective To explore the application and experience of job promotion combing with excitation mechanism in nurses position management. Methods We used job promotion combing with excitation mechanism in nurses position management to compare the satisfaction rate, perceived career benefit, work engagement and separation rate of nurses. Results After the application, the satisfaction rate, perceived career benefit and work engagement of nurses were increased, while separation rate of nurses was decreased(P<0.05), the difference has statistical significance. Conclusion The application may increase the satisfaction rate, perceived career benefit and work engagement of nurses, and decrease the separation rate of nurses, elevate the subjective initiative and work enthusiasm. Nursing quality is improved continuously. The management efficacy is promoted.
论著
目的 探讨黏附因子E-钙粘蛋白(E-cadherin)和Toll样受体9(TLR9)在系统性红斑狼疮(SLE)发病机制中的作用。方法 随机选取SLE患者41例,健康对照组18例,采用酶联免疫吸附试验(ELISA)法检测血清中sE-cadherin的表达,采用流式细胞技术(FCM)检测外周血单核细胞上TLR9的表达。分析 sE-cadherin,TLR9与系统性红斑狼疮患者病情的活动性。结果 SLE组血清中sE-cadherin的表达水平高于正常组(P=0.00),差异有统计学意义;SLE活动组血清中sE-cadherin表达水平高于稳定组(P=0.06),但差异无统计学意义;SLE组TLR9表达高于健康组(P=0.00),活动组高于稳定期组(P=0.00),差异均有统计学意义;SLE患者TLR9表达与SLEDI呈正相关(r=0.727,P=0.00),差异有统计学意义。结论 血清中sE-cadherin和外周血单核细胞内TLR9均参与了SLE患者病情发展的过程,并且二者在SLE发病机制中可能具有协调作用。
Objective To explore the effect of adhesion molecule E-cadherin and Toll-like receptor-9(TLR9) in the pathogenesis of systemic lupus erythematosus(SLE). Methods 41 patients with SLE and 18 healthy controls were selected randomly.Expression of TLR9 in peripheral blood mononuclear cells determined by FCM. SE-cadherin levels were measured in the serum by ELISA analysis. The correlation between sE-cadherin、TLR9 and the patient's condition of SLE was analyzed. Results Compared with healthy subjects,the expression of sE-cadherin in serum was higher among SLE patients(P=0.00),there was statistically significant between two groups;activity group was higher than inactivity group and healthy controls(P=0.06),but there was no statistically significant between activity group and inactivity group. Compared with healthy subjects,the expression of TLR9 in peripherql blood mononuclear cells was higher among SLE patients(P=0.00);activity group was higher than inactivity group(P=0.00),there was all statistically significant between two groups.The positive correlation was observed between TLR9 expression levels and clinical measure of the SLEDAI(r=0.727,P=0.00),there was statistically significant between two groups. Conclusion SE-cadherin and TLR9 may play an important role in SLE,and may interact with each other which needed further study.
论著
目的 探讨胆碱能受体激动剂尼古丁对子痫前期大鼠的治疗作用及机制。方法 将30只妊娠SD大鼠分为对照组(n =10)、子痫前期组(n =10)和尼古丁治疗组(n =10)。子痫前期组中,大鼠妊娠第14天注射内毒素(l.0 μg/kg);对照组给予等量生理盐水2 mL,研究组妊娠第14 天开始皮下注射尼古丁1 mg/(kg·d)至妊娠第19天。检测各组干预前后收缩压、24小时蛋白、妊娠结局和大鼠外周血IL-6,TNF-α,IFN-γ和IL-1β的表达水平。结果 和对照组相比,大鼠动脉收缩压妊娠第14天注射LPS后升高,治疗组中在尼古丁注射后,妊娠第16天、第18天较子痫前期组血压下降(14.99±0.48 vs 16.61±0.55 kPa,15.01±0.60 vs 17.04±0.49 kPa,P<0.05);大鼠24 h蛋白尿在子痫前期组中妊娠第17、19天升高(P<0.05),尼古丁治疗组尿蛋白较子痫前期组降低(P <0.05)。妊娠第20天,子痫前期组胎儿重量和对照组相比下降(P <0.05),尼古丁治疗组较子痫前期模型组胎儿重量增加(P <0.05)。各组间存活胎儿数、胎盘重量差异无统计学意义(P >0.05)。子痫前期组炎性因子IL-6,TNF-α,IFN-γ和IL-1β 较对照组升高,差异有统计学意义;尼古丁治疗组IL-6,TNF-α,IFN-γ 和IL-1β 降低(P <0.05)。结论 胆碱能受体激动剂尼古丁通过降低炎性反应来改善子痫前期大鼠的妊娠结局。
Objective To examine the effects and mechanism of cholinergic receptor agonist nicotine on preeclampsia rats. Methods 30 pregnant SD rats were divided into control group(n=10),preeclampsia group(n=10) and nicotine treatment group(n=10).In preeclampsia group,rats were injected LPS(l.0 μg/kg) on the day 14th of gestation,the control rats were injected 2 mL of physical saline on the day 14th of gestation,the rats in nicotine treatment group were injected nicotine 1mg/(kg·d) from the day 14th to the day 19th of gestation. The systolic blood pressure,24 hour urine protein,pregnancy outcome and serum levels of IL-6,TNF-α,IFN-γ and IL-1β were compared between each groups. Results Compared to control group,the systolic blood pressure rose after LPS injection on the day 14th of gestation,the systolic blood pressure in nicotine treatment group decreased on the day 16th and the day 18th of gestation compared to preeclampsia group(14.99±0.48 vs 16.61±0.55 kPa,15.01±0.60 vs 17.04±0.49 kPa,P<0.05).The 24 hour urine in preeclampsia group rose on day 17 and day 19 of gestation(P <0.05),which decreased in nicotine group(P <0.05). The fetal weight were higher in nicotine treatment group compared to the preeclampsia group,there were no statisitical difference in viable fetal number and placental weight among groups. The serum levels of IL-6,TNF-α,IFN-γ IL-1β were higher in preeclampsia group compared to the control group,while nicotine decreased the levels of IL-6,TNF-α,IFN-γ IL-1β(P <0.05). Conclusion Nicotine improved pregnancy outcome of LPS induced preeclampsia rats by decreasing inflammatory levels.