青蒿素生物合成与基因工程研究进展

青蒿素因其在植物中的量很低并不能满足患者需求,提高青蒿中青蒿素的量是植物次生代谢研究领域的热点之一。综述了青蒿素生物合成途径的相关酶与基因,青蒿素生物合成的部位及特异性基因表达研究,植物激素和诱导子对青蒿素生物合成的影响,以及利用基因工程对青蒿进行遗传改良;提出了基因工程技术是提高青蒿素的理想途径之一。     

青蒿素生物合成基因的转录谱分析

【目的】研究青蒿素生物合成基因在不同发育时期和不同组织中的表达规律,探讨青蒿素生物合成的时空调节机制。【方法】利用实时荧光定量PCR技术定量追踪分析青蒿素主要及协同合成途径基因在盛叶期、开花前、开花后不同的发育时期,以及在根、茎、叶、花不同组织中的表达模式。【结果】各基因的表达水平在6月份时最低,随后开始上升,在8月份(开花前)达到高峰,与6月份比较,转录水平显著提高3～15倍(均P0.01),其中青蒿素特异合成酶基因ADS和CYP71AV1上升幅度最大,为最低水平的12和15倍,9月份(开花后)则呈下降趋势。处于盛花期的青蒿在根、茎、叶、花各个组织中都能检测到青蒿素合成基因的表达,叶片中ADS基因mRNA水平较其他组织显著升高2倍左右(均P0.01),显示组织表达特异性。【结论】青蒿素生物合成基因的发育表达模式与青蒿素的合成规律一致。ADS和CYP71AV1基因的表达在青蒿素生物合成过程中可能起关键作用。     

青蒿丛生芽诱导影响因素的研究

目的 对影响青蒿丛生芽诱导因素进行基础性研究。方法 把常规的植物组织培养技术应用于调控青嵩中次生代谢产物青蒿素的生物合成代谢。结果 青蒿的基因型，激素和基本培养基对丛生芽的发生有显著影响，而光强在1000～6000 1x和温度在20℃～30℃对丛生芽的发生影响不大；在5种基因型的青蒿中，025丛生芽的诱导率最高；诱导丛生芽的激素组合是6-BA 2．0mg／L和NAA 0．15mg／L；另外，离子在青蒿丛生芽的诱导和青蒿素的生物合过程中起着非常重要的作用。结论 组织培养条件下，青蒿丛生芽的诱导及青蒿素的生物合成可以通过理化因子有效地进行调控。     

青蒿素生物合成的研究进展

青蒿素（artemisinin）是我国自主开发的强效、低毒、无抗性抗疟特效药,尤其是治疗脑型疟疾和抗氯喹恶性疟疾的特效药。青蒿中的青蒿素含量在0.4％-1.0％之间,从天然青蒿中提取青蒿素难以满足市场需求,而青蒿素化学合成的工艺复杂、成本高、毒性大、产率低,至今未能实现工业化生产。目前。青蒿素的生物合成研究正方兴未艾^[1],     

黄花蒿优质种质资源的研究

黄花蒿资源品质（青蒿素含量）具有显著的生态地域性，可能是黄花蒿的不同生态型之间的生理生化特性上的差异的表现。作者从植物生态学的角度，对华中地区中亚热带常绿阔叶林北部亚地区山峡武陵山地所属的川东南、鄂西、湘西及黔东北各地进行了黄花蒿的生态环境调查及青蒿素含量测定。结果表明实验区域内黄花蒿的青蒿素含量普遍较高，平均在4．847‰～8．853‰之间，最高可达10．221‰，说明该区域的生态环境对黄花蒿中青蒿素成分的生物合成与转化有利。     

青蒿素类抗疟药药效的比较及联合用药

疟疾是全球广泛流行的寄生虫病。恶性疟原虫株对常规抗疟药多已产生耐药性。青蒿素类现作为一线抗疟药用于临床。从现有文献着手,本文综述了恶性疟原虫对抗疟药的抗性现状,比较了恶性疟原虫对青蒿素类药物与喹啉类药物的敏感性,提示青蒿素类药物目前作为首选药应用于临床的优点。疟疾治疗的主要困难是耐药性产生,而联合用药是避免或延缓耐药性产生,提高疗效的有效手段,因此本文还综述了以青蒿素类药物为基础的抗疟药联合用药现状及初步比较,提示以青蒿素为基础的联合用药方案有其他可能的组合。     

青蒿素类药物在非疟疾疾病中的研究进展

青蒿素是从中草药青蒿中分离出的一种倍半萜内酯类抗疟药物。近年来,在不同疾病条件下研究发现青蒿素类药物在感染性疾病、自身免疫性疾病和肿瘤等非疟疾疾病中具有显著疗效。本文回顾了近年来国内外相关文献,并总结了青蒿素类药物在非疟疾疾病中的临床应用及其药理作用的研究进展。相信随着药物合成技术和临床药理学的进步,青蒿素类药物会在非疟疾疾病领域发挥更大作用。     

技术

青蒿素首次实现高效人工合成 7月4日,上海交通大学表示,由张万斌教授领衔的科研团队,历时7年,研发出一种常规的化学合成方法,首次实现了抗疟药物青蒿素的高效人工合成,使青蒿素可以实现大规模工业化生产。该研究成果有望解决困扰世界医药产业界30多年的青蒿素高效人工合成重大难题,使青篱素类药物更加更宜、易得。     

恶性疟原虫青蒿素抗疟药抗性研究进展

疟疾是由疟原虫感染引起的一种传染病,是全球最重要的公共卫生问题之一。世界卫生组织 （WHO） 推荐以青蒿素为基础的联合疗法（artemisinin-based combination therapies, ACTs）作为疟疾流行地区的非复杂性恶性疟的一线治疗。青蒿素及其衍生物的应用在降低全球疟疾发病率方面发挥了不可或缺的作用。但近年来,青蒿素类药物抗性的出现与扩散使全球疟疾的控制与消除面临巨大挑战。目前,与青蒿素抗药性关系最为密切的是恶性疟原虫第13号染色体上K13基因的突变,但近些年不断有研究表明K13并不能解释所有的青蒿素抗性。本文综述近年来恶性疟原虫对青蒿素产生抗性研究领域的相关研究进展,包括青蒿素抗药性的定义、检测方法、抗性相关的分子标记等。此外,本文所讨论的某些问题仍存在争议,还需深入研究。     

青蒿素衍生物研究新进展

目的:综述青蒿素衍生物的应用及生产方法研究新进展.方法:查阅相关文献进行分析归纳并提出自己的看法.结果:在青蒿素化学结构基础上开发出一系列衍生物,不仅其抗疟活性大大提高,而且还应用到其它领域;结构简单、易于合成的青蒿素替代物研究也有进展.结论:综合国内外最新动态看,从应用和生产角度研究青蒿素衍生物及其类似物在相当长时期内仍是一研究热点.     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.     

Luo Lingjie's Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.     

Dr.Zhang Ren's Experience in the Acupuncture Treatment of Different Diseases with the Same Therapeutic Principle

Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.