地理标志保护策略在特色关药产业发展中的作用分析

关药道地产区主要包括东三省及内蒙古自治区东北部地区,其形成得益于独特的区域气候、水文和土壤条件。人参、鹿茸、五味子、刺五加等代表性关药品种在滋补、保健等方面具有优势,其余品种也多属临床常用大宗药材,具备支撑大健康产业发展的良好物质基础。地理标志保护策略在关药品种挖掘、产学研一体化推进、品牌战略发展等方面具实用价值,服务区域经济发展和“一带一路”倡议。

特色关药标本馆建设及发展趋势

关药为山海关以北,东北三省和内蒙古东北部地区所产的道地药材,为我国道地药材十大药系之一。目前,未有完善的关药信息的主要保存地,打造特色关药标本馆能够承载着关药资源的收集,科普宣传,对关药馆建设进行介绍,挖掘关药资源,推动关药全品种集中展示,打造"关药"品牌的聚合力和传播力,服务民生,助力药材集散地与关药经济发展。

钠钙交换器抑制药在心律失常治疗中的应用

心肌钠钙交换在调节心肌细胞内外钠、钙平衡中发挥重要作用。钠钙交换分为前向型和逆向型2种。在心力衰竭、心肌缺血、心肌再灌注等病理情况下,通过钠钙交换器的离子交换可产生致心律失常性的一过性内向电子流,引起延迟后除极和非折返激动型的室性心动过速。钠钙交换器抑制药在预防这些病理情况下的心律失常具有潜在的作用。

推入式基本药管残片留膛原因查找及解决措施

推进式迫击炮发射装药发射过程中可能出现基本药管残片留在膛内的故障,通过理论分析、实验验证,证明推入式基本药管后退是导致残片留膛的主要原因,基本药管的纸管强度低是造成基本药管后退的原因;基本药管的纸管水分含量低是造成纸管强度低的原因;通过排查,找出了导致基本药管后退的原因,并采取了针对性的措施,消除了基本药管后退的隐患,解决了基本药管残片留膛问题。

多药耐药相关蛋白4过表达对脂多糖诱导血管内皮高渗透性的影响及其机制

目的 探讨多药耐药相关蛋白4（MRP4）基因过表达对脂多糖（LPS）诱导大鼠肺微血管内皮细胞（PMVECs）渗透性的影响及其分子机制.方法 体外培养PMVECs细胞,待细胞传至3~6代后分为3组：LPS组无血清培养基培养24 h后,用10μg/mL LPS刺激细胞;Ad-shRNA组用腺病毒空白载体转染细胞2 h,无血清培养基培养24 h后,用10μg/mL LPS刺激细胞;Ad-MRP4组用携带MRP4的重组腺病毒载体转染细胞2 h,无血清培养基培养24 h后,用10μg/mL LPS刺激细胞.于LPS刺激2、6、12、24 h采用Transwell小室法检测单层细胞渗透性;采用酶联免疫吸附试验（ELISA）检测细胞内环磷酸腺苷（cAMP）水平;激光共聚焦荧光显微镜下观察细胞内纤维型肌动蛋白（F-actin）形态及分布情况.于LPS刺激12 h收集细胞,采用蛋白质免疫印迹试验（Western Blot）检测PMVECs中MRP4、β-连环蛋白（β-catenin）、血管内皮-钙黏蛋白（VE-cad）和紧密连接蛋白（ZO-1）的表达水平.结果 ①LPS刺激后PMVECs细胞渗透性及细胞内cAMP水平逐渐增加,12 h达到高峰,24 h开始下降.用携带MRP4的重组腺病毒载体转染PMVECs后,细胞渗透性较LPS组及Ad-shRNA组显著增加〔12 h渗透性（A值）：1.88±0.06比1.12±0.17、1.10±0.18〕,细胞内cAMP水平显著降低〔12 h cAMP（μg/L）：2.39±0.02比2.97±0.01、3.00±0.02,均P〈0.05〕;而LPS组与Ad-shRNA组各时间点各指标差异均无统计学意义（均P〉0.05）.② 激光共聚焦荧光显微镜下显示,3组细胞均出现F-actin重构、应力纤维形成,但Ad-MRP4组细胞破坏程度较LPS组和Ad-shRNA组更加严重.③ 与LPS组和Ad-shRNA组比较,Ad-MRP4组PMVECs中MRP4蛋白表达显著上调（灰度值：0.76±0.03比0.44±0.02、0.43±0.02,均P〈0.05）,β-catenin、VE-cad和ZO-1蛋白表达显著下调〔β-catenin（灰度值）：0.14±0.03比0.23±0.04、0.23±0.03;VE-cad（灰度值）：0.21±0.01比0.34±0.02、0.35±0.04;ZO-1（灰度值）：0.14±0.02比0.37±0.06、0.33±0.07,均P〈0.05〕;而LPS组与Ad-shRNA组间各蛋白表达差异无统计学意义（均P〉0.05）.结论 MRP4基因过表达可降低细胞内cAMP水平,下调细胞间连接蛋白表达,从而增加LPS诱导的血管内皮渗透性.

3D-QSAR Analysis of DDPH Derivatives for α_1-Adrenoceptor Antagonist Activity

Aim and methods The study of three-dimensional quantitative structure-activity relationship （3D-QSAR） of DDPH and its derivatives has been performed using Apex-3D programme. Results The result indicates that substituents of para- and ortho-positions in phenyl ring of aryloxyalkylamine greatly influence the bioactivity. Conclusion The biophore model and 3D-QSAR equation help us not only further understand receptor-ligand interactions, but also design new compounds with better bioactivity.

Development of Cardiovascular Drugs Based on Isoquinoline Compounds from Chinese Medicinal Materials

By using active principles of Chinese medicinal materials as lead compounds soquinoline derivatives have been designed and synthesized.Their chemical structures include bisbenzylisoquinoline,benzyl-isoquinoline and protoberberine.Their cardiovascular effects were studied involving α-adrenoceptor,adenosine A_1,A_2 and DPH-calcium channel radioreceptor assays.In addition,calmodulin inhibiting,calcium antagonistic potassium channel blocking and antiplatelet aggre- gation activities were also performed.It was found that compound VI_(19) was a new potassium channe blocker with α-adrenoceptor antagonism,compound V_9,and V_(21) lowered blood pressure on various animal models with negative chronotropic action,compound VI_(13)possessed antiarrhythmic and antifi- brillation action,and it may be a candidate tot clinic evaluation.The structure-activity relationships deduced may provide a theoretical basis for further development of new agents.

Pharmacokinetics of two modified release system of dipyridamole in beagle dogs

A novel floating osmotic pump controlled release system （FOP） and traditional matrix sustained release tablets （MT） of dipyridamole （DIP） were characterized in terms of pharmacokinetics, drug release, and in vitro-in vivo correlation. In vivo study was performed by a three-crossover study in six beagle dogs relative to the conventional tablet （CT）. A HPLC method for the determination of DIP in the plasma was developed. Cumulative percent of absorption fraction was compared to that of in vitro cumulative release. Both FOP and MT displayed obvious extended release characteristic in vivo while FOP showed a better extended release behavior. The bioavailability of FOP was higher than that of MT and a zero-order release linear correlation of DIP between fraction absorbed in vivo and fraction dissolved in vitro was established for FOP while not for MT. The results indicated the existence of an absorption window in upper part of the GI track of DIP, which meant that floating system could be excellent for the drug delivery. In addition, the in vitro model was a good choice for depicting in vivo absorption and for optimization of the formulation of FOP if it is needed to be bio-equivalent to MT.

Proposal and evaluation of a new norm index-based QSAR model to predict pEC50 and pCC50 activities of HEPT derivatives

The search and development of anti-HIV drugs is currently one of the most urgent tasks of pharmacological studies. In this work, a quantitative structure-activity relationship （QSAR） model based on some new norm indexes, was obtained to a series of more than 150 HEPT derivatives （1-[（2-hydroxyethoxy）methyl]-6-（phenylthio）thymine） to find their pEC50 （the required effective concentration to achieve 50% protection of MT-4 cells against the cytopathic effect of virus） and pCC50 （the required cytotoxic concentration to reduce visibility of 50% mock infected cell） activities. The model efficiencies were then validated using the leave-one-out cross validation （LOO-CV） and y- randomization test. Results indicated that this new model was efficient and could provide satisfactory results for prediction of pECso and pCC50 with the higher R2 train and the higher Rt2est. By using the leverage approach, the applicability domain of this model was further investigated and no response outlier was detected for HEFT derivatives involved in this work. Comparison results with reference methods demonstrated that this new method could result in significant improvements for predicting pEC50 and pCC50 of anti-HIV HEPT derivatives. Moreover, results shown in this present study suggested that these two absolutely different activities pECso and pCC50 of anti-HIV HEPT derivatives could be predicted well with a totally similar QSAR model, which indicated that this model mizht have the potential to be further utilized for other biological activities of HEFT derivatives.

Studies on the Analytical Method for a New Antiarrhythmic Guanfu Base A in Rabbit Plasma

Guan-fu base A(GFA),a new antiarrhythmic alkaloid with a structure of C_(20)-diterpenoid could react rapidly and quantitatively with trifluoroacetic anhydride(TFAA) to produce GFA—TFAA of which the structure was identified by GC—MSD.There was a wide linear range of the GC-ECD method from 10 to 20000ng/ml(r=0.9984).The average recovery of GFA from the spiked plasma was 97.52%.The coefficients of variation of within-day and between-day were less than 7% and 9%,respectively.The method was used in the preclinical experiment of pharmacology of GFA and the results showed that GFA con- centrations in rabbits' plasma within 6 hours after the administration ranged from 0.338± 0.014 to 13.459±5.393μg/ml for dosage 10mg/kg,from 0.133±0.038 to 2.546±0.480 μg/ml for dosage 2mg/kg and from 45.25±10.34 to 535.86±24.36ng/ml for dosage 0.4 mg/kg.

Effects of two medicinal plants Psidium guajava L. (Myrtaceae) and Diospyros mespiliformis L. (Ebenaceae) leaf extracts on rat skeletal muscle cells in primary culture

Crude decoction, aqueous and ethanolic extracts of two medicinal plants （Psidiura guajava and Diospyros raespiliformis）, widely used in the central plateau of Burkina Faso to treat many diseases were evaluated for their antagonistic effects on caffeine induced calcium release from sarcoplasmic reticulum of rat skeletal muscle cells. These different extracts showed a decrease of caffeine induced calcium release in a dose dependent manner. Comparison of the results showed that Psidiura guajava leaf extracts are more active than extracts of Diospyros mespiliformis and that crude decoctions show better inhibitory activity. The observed results could explaine their use as antihypertensive and antidiarrhoeal agents in traditional medicine, by inhibiting intracellular calcium release.

Structure-activity Relationship of Phenothiazines for Inhibition of Protein Kinase C and Reversal of Multidrug Resistance

Studies on structure-activity relationship of phenothiazines (PTZs) forinhibition of protein kinase C (PKC) and reversal of multidrug resistance (MDR) has been made invitro. The results showed that the order of potency of reversal effect of PTZs on MDR is as follows:2-COC_3 H_7 > 2-CF_3 > 2-COCH_3 > H. The type of piperazinyl substitution also significantlyaffected potency against MDR. The results show the order: CH_3 > COOC_2 H_5 > C_2 H_4 OH. Inaddition, PKC plays a marked role in diverse cellular process including MDR. Some derivatives of PTZwas tested for inhibition of PKC, of which PTZ11 showed the highest inhibitory effect of MDR andPKC, implying a potential reversal agent of MDR for tumor therapy in the future. We also tried toexplore the possible binding model of PTZs to PKC. Our molecular-modeling study preliminarilysuggests how these PTZs bind to PKC and provides a structural basis for the design of high affinityPKC-modulator. The infor-mation may be used in the rational design of more effective drugs.

Screening for metronidazole-resistance associated gene fragments of H pylori by suppression subtractive hybridization

AIM： To screen for metronidazole （MTZ）-resistance associated gene fragments of H pylori by suppression subtractive hybridization （SSH）. METHODS： Five MTZ-resistant （tester, T） and 1 MTZ- susceptible （driver, D） clinical H pylori isolates were selected. Genomic DNAs were prepared and submitted to Rsa I digestion. Then two different adaptors were ligated respectively to the 5＇-end of two aliquots of the tester DNA fragments and SSH was made between the tester and driver DNAs. The specific inserts of tester strains were screened and MTZ-resistance related gene fragments were identified by dot blotting. RESULTS： Among the randomly selected 120 subtractive colonies, 37 DNA fragments had a different number of DNA copies （≥ 2 times） in resistant and susceptible strains and 17 of them had a significantly different number of DNA copies （≥ 3 times）. Among the sequences obtained from the 17 DNA fragments, new sequences were found in 10 DNA fragments and duplicated sequences in 7 DNA fragments, representing respectively the sequences of depeptide ABC transporter periplasmic dipeptide-binding protein （dppA）, permease protein （dppB）, ribosomal protein S4 （rps4）, ribonuclease Ⅲ （rnc）, protease （pqqE）, diaminopimelate epimerase （dapF）, acetatekinase （ackA）, H pylori plasmid pHP51 and Hpylori gene 1334. CONCLUSION： Gene fragments specific to MTZ-resistant H pylori strains can be screened by SSH and may be associated with MTZ-resistant Hpylori.

Preliminary Investigation on Regulating Effects of Different TCM Treatments on Transcription of the Correlated Genes of Liver Cancer in Rats

The regulating effects of TCM treatments including clearing away heat and toxic materials,promoting blood circulation and removing blood stasis,and strengthening the spleen and regulating qi on the oncogene transcription were observed in the liver cancer model rats.The preliminary results indicated that the mRNA levels of H-ras N-ras and K-ras,and signal molecules correlated with the ras/MAPK signal transduction pathway were down-regulated by the different TCM treatments in varying degrees.Also,the regulating effects of the treatments on differently-displayed genes were discrepant.It is suggested that the molecular mechanisms of the TCM treatments for liver cancer was complex with different target genes.

The expression and significance of the multidrug resistance-related proteins P-gp, MRP and LRP in human non-small cell lung cancer tissues

Objective: To explore the expression and significance of the multidrug resistance-related proteins P-glycopro-tein (P-gp), multidrug resistance-related protein (MRP), lung resistance protein (LRP) in human non-small cell lung cancer (NSCLC) tissues and paratumor tissues. Methods: Immunohistochemistry (IHC) was used to examine the expression level of proteins P-gp, MRP and LRP in 43 samples of NSCLC and 15 samples of paratumor tissues. Results: The expression rates of P-gp, MRP and LRP in 43 tumor tissues were 74.42% (32/43), 67.44% (29/43) and 88.37% (38/43), respectively, while in 15 paratumor tissues were 13.33% (2/15), 20.00% (3/15) and 6.67% (1/15), respectively. There was significant difference in the expression of proteins (P-gp, MRP and LRP) between lung cancer tissues and paratumor tissues (P < 0.05). The expres-sion of proteins P-gp, LRP in lung adenocarcinoma were higher than that in other pathological carcinomas (P < 0.05). The expression of protein MRP was not related to pathological type, clinical stage and classification of histodifferentiation (P > 0.05). Conclusion: Multidrug resistance is more common in NSCLC. The proteins of P-gp, MRP and LRP participated in the formation of multidrug resistance in lung cancer. Detection of multidrug resistance-related proteins in lung cancer tissues may be useful to choice drugs.

TCM Treatment for 40 Cases of Rheumatoid Arthritis with Channel Blockage due to Yin Deficiency

To verify the therapeutic effects of the method of softening and lubricating the joints,and calming the endogenous wind in case of rheumatoid arthritis (RA) with the syndrome of channel blockage due to yin deficiency,60 RA patients with the syndrome of channel blockage due to yin deficiency were randomly divided into a treatment group (40 cases) and a control group (20 cases) and treated respectively by the above method for the former and with Zheng Qing Feng Tong Ning Tablets (正清风痛宁片) for the latter. The result turned out to be that the effect in the treatment group was very satisfying.The treatment group obtained a better result in the accumulated points of syndrome and RA,morning rigidity of the joints,grip strength,20m walking time and erythrocyte sedimentation rate (ESR) (P<0.01 or P<0.05).The above indicates that channel blockage due to yin deficiency is an important pathogenesis of RA,and calming the endogenous wind is a method of choice for treating RA.

Intermediate and Late Rheumatoid Arthritis Treated by Tonifying the Kidney, Resolving Phlegm and Removing Blood Stasis

Eighty-seven cases of intermediate and late rheumatoid arthritis were treated with Instant Shu GuanWen Jing Granules(疏关温经冲剂 Relaxing Joints by Warming Channels)and Instant Shu GuanQing Luo Granules(疏光清络冲剂 Relaxing Joints by Removing Heat from the Lung Channel)totonify the kidney resolve phlegm and remove blood stasis,and compared with 41 cases treated withInstant Wang Bi Granules(尪痹冲剂 Prescription for Arthralgia-syndrome).The treatment produceda clinical cure rate of 54.0% and a total effective rate of 90.8% as in against 29.3% and 73.2%respectively in the control group.The difference was significant(P<0.01).Improvement in mainsymptoms and laboratory findings in the treatment group was all more marked than that in thecontrol group (P<0.05 or P<0.01),with no side effects observed.

Bio-characteristic profiling related to clinic:A new technology platform for quality evaluation of Chinese materia medica

Quality evaluation is a bottleneck restricting the modernization and internationalization of Chinese materia medica (CMM). Due to characteristics of multi-component, multi-efficacy, multi-target, the existing quality evaluation system still cannot fully meet quality control needs of CMM. Hence, the author put forward “Bio-characteristic profiling related to clinic, BPRC” academic concept, meanwhile, fully take the advantage of analysis method with clinical monitoring superiority or profiling characteristics, build up “BPRC” new technology platform, in order to realize “real-time, dynamic and full-range monitoring” new technologies of CMM quality evaluation system and promote the further development of CMM industry.

Stakeholder Perspectives on Use,Trade,and Conservation of Medicinal Plants in the Rasuwa District of Central Nepal

People's livelihood in several Himalayan regions largely depends on collection,use,and trade of medicinal plants.Traditional use is generally not a problem,but commercial gathering of selected species to meet increasing national and international demand can result in over-exploitation.Sustainable management of medicinal plants requires a clear understanding of the respective roles,responsibilities and viewpoints of the various stakeholders involved.Through personal interviews and group discussions,this study aimed at investigating the views of two stakeholder groups on use,trade and conservation of medicinal plants in the Rasuwa district of Nepal.Local people and district and national organizations agreed that medicinal plants are collected for a combination of commercial and personal uses.Perceptions on market availability differed significantly:100 % of the respondents from district and national organizations saw markets as easily available,against only 36 % for local people.This could explain why medicinal plants were perceived by local people to contribute less to income generation than to livelihood improvement.Different viewpoints were also expressed concerning the status of medicinal plants in the district:81 % of the respondents from district and national organizationsconsidered that medicinal plants were threatened,compared to only 28 % for local people.Despite this disparity,both stakeholder groups agreed upon potential threats to medicinal plants:over-harvesting;habitat loss due to land-use change and deforestation;and over-grazing by livestock.Several challenges were identified regarding sustainable management of medicinal plants,such as ambiguous policies;lack of resources,information and infrastructures;habitat degradation;and over-exploitation.Despite these challenges,respondents agreed that the medicinal plants sector offers huge opportunities in the Rasuwa district,given resource availability,community awareness and motivation,and the priority given to the sector by governments and other agencies.Proper collaboration,communication and coordination among stakeholders are needed to grab these opportunities.

Use of antiarrhythmic drugs in elderly patients

Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intmcellular Ca2＋ overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhytbanics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient＇s physiology, disease processes, and medication regimen.