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.
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。
目的 探讨血必净注射液对SAP大鼠TLR4信号通路介导肠黏膜屏障功能障碍的影响。方法 24只SD大鼠随机分成空白组(n=8)、对照组(n=8)和治疗组(n=8)。对照组和治疗组用4.5%牛磺胆酸钠溶液胆胰管逆行注射制备SAP模型,空白组采用等量生理盐水逆行注射。治疗组在造模3 h后经鼠尾静脉注射血必净注射液(3 mL/kg)。三组大鼠造模后观察24 h,然后处死取胰腺和小肠组织送病理检查,采用荧光RT-PCR技术检测TLR4和NF-κB表达水平,采用ELSIA法检测血清TNF-α、IL-6、淀粉酶(AMS)及二胺氧化酶(DAO)水平,比较三组大鼠各项指标。结果 对照组和治疗组小肠组织TLR4和NF-κB表达以及血清TNF-α、IL-6、AMS及DAO水平均高于空白组(P>0.05),治疗组小肠组织TLR4和NF-κB表达以及血清TNF-α、IL-6、AMS及DAO水平低于对照组(P＜0.05)。结论 血必净注射液通过干预SAP大鼠TLR4信号通路,降低小肠组织TLR4和NF-κB的表达,减轻小肠组织的炎症反应,对肠黏膜屏障具有一定的保护作用。
Objective To investigate the effect on intestinal mucosal barrier dysfunction (IBF) of Xuebijing injection mediated by Toll-like receptor 4 (TLR4) signal pathway in rats of severe acute pancreatitis (SAP). Methods 24 Sprague Dawley (SD) rats were randomly divided into Sham group (n=8), control group (n=8) and treatment group (n=8). The SAP model was established by retrograde injection of 4.5% sodium taurocholate into the biliopancreatic duct in control group and treatment group, while control group was injected with the same amount of saline. In treatment group, Xuebijing injection (3 mL/kg) was injected via tail vein after 3h of modeling. All rats were monitored and sacrificed after 24 hours of modeling. Samples of pancreas and intestine were collected for pathologic determination. A fluorescent RT-PCR was used to determine the expression of TLR4 and NF-κB of small intestine. The serum levels of TNF-α, IL-6, amylase (AMS) and diamine oxidase (DAO) were measured by using ELISA. All parameters of three groups were compared. Results The expression of TLR4 and NF-κB of small intestine in control group and treatment group were higher than it in control group (P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO (P<0.05). The expression of TLR4 and NF-κB of small intestine in treatment group were lower than it in control group (P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO (P<0.05). Conclusion Xuebijing injection may not only reduce the expression of TLR4 and NF-κB of small intestine, but also alleviate the inflammation reaction of small intestine by interfering with TLR4 signal pathway, which may have a protective effect on intestinal mucosal barrier in SAP rats.
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.
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.
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.
目的 通过高通量测序法对多重耐药大肠埃希菌HX43进行耐药分子机制的研究。方法 用Illumina Miseq平台对HX43进行高通量测序,用Edena、RAST、ResFinder、MLST和BLAST等生物信息学工具或数据库进行数据分析,获得耐药基因相关序列数据。结果 HX43对多种临床常用抗生素均不敏感,仅对碳氢霉烯类药物敏感。对高通量测序数据的分析研究发现,该菌存在多种耐药基因,包括β-内酰胺类耐药基因3个(blaCMY-42、blaCTX-M-14和blaOXA-30),氨基糖苷类耐药基因5个(aac(3)-IIa、aadA5、 strA、 strB和aac(6′)-Ib-cr),喹诺酮类耐药基因1个(aac(6′)-Ib-cr),磺胺及甲氧苄啶类耐药基因3个(sul1、sul2和dfrA17),四环素耐药基因1个(tet(B)),氯霉素耐药基因2个(catB3和cmlA1),大环内酯类耐药基因2个(erm(B)和mph(A))。对包含blaCMY-42的contigs进行分析,发现该基因与ISEcp1插入序列、blc和sugE等基因相关联。质粒分型发现HX43携带5种不相容群的质粒。多位点序列分型(MLST)分析发现HX43属于ST3835,为国内外较少见的序列型。结论 高通量测序技术可准确获得临床菌株抗生素耐药的相关基因信息,为临床抗菌治疗提供重要的实验室数据支持。
Objective To investigate the molecular resistance mechanism of Escherichia coli HX43 by high-throughput sequencing. Methods HX43 was sequenced by the Illumina Miseq platform, and sequencing data were analyzed by the Edena, RAST, ResFinder, MLST and BLAST softwares and databases. Results HX43 was resistant to most common clinical antibiotics except carbapenems. Analysis of data revealed resistance genes to β-lactams (blaCMY-42, blaCTX-M-14 and blaOXA-30), aminoglycosides (aac(3)-IIa, aadA5, strA, strB and aac(6′)-Ib-cr), quinolones (aac(6′)-Ib-cr), trimethoprim/sulfonamides(sul1, sul2 and dfrA17), tetracyclines (tet(B)), chloramphenicol (catB3 and cmlA1), macrolides(erm(B) and mph(A)). Sequence analysis of the contig containing blaCMY-42 identified correlations of the gene with ISEcp1 insertion sequences, blc and sugE genes. Plasmid typing identified 5 plasmid incompatibility groups in HX43. MLST analysis found that HX43 belonged to ST3835, a relatively rare sequence type in the world. Conclusion Information of resistance genes can be obtained by high-throughput sequencing, which provides important experimental data for clinical antimicrobial treatment.
目的 氧化苦参碱对视网膜母细胞瘤细胞SM-106凋亡的诱导作用及机制。方法 以不同作用时间(24 h、48 h、72 h)和不同作用浓度(12.5 μl/mL、25 μl/mL、50 μl/mL、100 μl/mL)氧化苦参碱处理视网膜母细胞瘤细胞SM-106,分别采用流式细胞仪及western blot检测视网膜母细胞瘤细胞SM-106细胞凋亡及其凋亡因子(Bax、Bcl-2)蛋白表达。结果 氧化苦参碱可促进SM-106细胞体外凋亡,上调Bax蛋白表达及Bax/Bcl-2蛋白表达比值,下调Bcl-2蛋白表达,并呈现剂量及时间依赖性。结论 氧化苦参碱可诱导视网膜母细胞瘤细胞SM-106凋亡,调控凋亡因子Bax、Bcl-2的表达是其可能作用机制。
Objective To evaluate the apoptosis and its mechanism of retinoblastoma cells SM-106 induced by oxymatrine. Methods Retinoblastoma cells SM-106 were treated with different time(24 h、48 h、72 h)and different concentrations(12.5 μl/mL, 25 μl/mL, 50 μl/mL or 100 μl/mL) of oxymatrine. The apoptosis and protein expression of apoptosis factors (Bax and Bcl-2) were respectively determined by flow cytometry and western blot. Results Oxymatrine significantly promoted the SM-106 cells apoptosis in vitro, raised Bax protein expression and Bax/Bcl-2 protein expression ratio, reduced the Bcl-2 protein expression, and showed the dose and time dependent. Conclusion Oxymatrine is able to induce the apoptosis in retinoblastoma cells SM-106. Regulating apoptosis related gene Bax and Bcl-2 expression may be the mechanism of apoptosis.
目的 初步探讨微泡增强的脉冲式超声治疗脾创伤出血的作用机制。方法 14只健康家犬随机分为3组,超声微泡组(MEUS组)6只、单纯超声组(TUS组)4只、单纯微泡组(MB组)4只。开腹切割脾建立脾破裂出血模型,MEUS组用脉冲式超声治疗仪辐照伤口,同时静脉匀速推注微泡;TUS组超声治疗时静脉推注生理盐水;MB组超声治疗仪假照的同时静脉推注微泡。治疗完毕,进行超声造影评价,并送病理组织学检查。结果 MEUS组造影示靶区造影增强缺损或者低灌注,但较粗大血管仍为增强显影。病理组织学见脾窦、微小血管扩张充血、血管周围组织水肿,血小板聚集,微小血管血栓形成。结论 微小血管血栓形成、微血管淤血扩张、周围组织水肿压迫是超声联合微泡治疗脾创伤出血的可能机理。
Objective To investigate the mechanism of haemostatic effect induced by microbubble(MB)enhanced therapeutic ultrasound(TUS)on splenic trauma. Methods 14 healthy dogs were divided into 3 groups.Six animals were treated by microbubble-enhanced therapeutic ultrasound(MEUS),the other eight animals were treated with TUS only group(n=4)and the MB only(n=4)served as the controls.The spleens of all animals were surgically exposed and a 20 mm long,5 mm deep incision was created on the spleens using scalpel.Contrast enhanced ultrasound(CEUS)was performed to assess the blocking effects of splenic circulation.The targeted spleens were harvested for pathological examination. Results A non-enhanced or perfusion defect region was formed within the treated area.The histological results showed splenic sinus hyperemia,microvascular hyperemia,perivascular tissue edema,platelet aggregation and intravascular thrombosis. Conclusion The mechanism of haemostatic effect on splenic trauma by microbubble enhanced ultrasound maybe intravascular thrombosis,microvascular hyperemia and perivascular tissue edema oppression simultaneously.
