Drug discovery from traditional Chinese herbal medicine using high content imaging technology

Traditional Chinese medicine(TCM) has been widely used in China and other Asia countries for thousands of years to treat or prevent human diseases. Chinese herbal medicine, one of the most important components of TCM, has unique diversities in chemical components, and thus results in a wide range of biological activities. However, pharmaceutical industry is facing a major challenge to develop a large population of novel natural products and drugs, and considerable efforts have not resulted in highvolume of novel drug discovery and productivity. At present, increasing attention has been paid to Chinese herb medicine modernization in combination with the cutting-age technologies of drug discovery, especially the high throughput selection. High content imaging is an image-based high throughput screening method by using automated microscopy and image analysis software to capture and analyze phenotypes at a large scale to investigate multiple biological features simultaneously in the biological complex. Here, we described the pipeline of the state-of-the-art high content imaging technology, summarized the applications of the high content imaging technology in drug discovery from traditional Chinese herbal medicine, and finally discussed the current challenges and future perspectives for development of high throughput image-based screening technology in novel drug research and discovery.

Modernization of Chinese herbal compound and the high performance liquid chromatography tandem mass spectrometry (HPLC-MS)

Chinese herbal compound is playing an important role on curing human diseases.And it has been a trend that Chinese herbal compound is being used all over the world in 21 century.However,our Chinese herbal compound is facing serious challenge for the lack of canonical system of quality criterion for Chinese herbal compound so it has been a urgent problem to set up the quality control standards and reveal therapeutic basis of Chinese herbal compound.In order to give full play to the advantages of Chinese herbal compound,modern scientific and technological is used to research of Chinese herbal compound,especially the high performance liquid chromatography tandem mass spectrometry(HPLC-MS),because it is high sensitive,rapid,and obtain more information.It is very necessary that HPLC-MS is uesed to elucidate the effective components of basic substances of Chinese Herbal Compound,and endow traditional Chinese medicine with modern scientific connotation.

Industrial Poverty Alleviation Model in Southwestern High-altitude Mountainous Areas of China——A Case Study of Industrial Poverty Alleviation of Xueshan Township in Luquan County of Yunnan Province through Planting Codonopsis pilosula

Due to the severe restrictions of natural conditions and ecological environment,high-altitude mountainous areas usually become the " hard bones" in the battle against poverty. Xueshan Township,Luquan Yi and Miao Autonomous County of Yunnan Province,located in the alpine valley of Jinsha River,is a major township with wide and deep poverty,and the incidence of poverty is up to 45. 00%. In recent years,Xueshan Township has insisted on the battle against poverty,made effort to develop the Codonopsis pilosula industry,and successfully developed a road to poverty alleviation through C. pilosula industry,and formed a unique industrial poverty alleviation model by the end of 2018,the incidence of poverty dropped to 0. 74%. Based on field survey and interview,this paper analyzes and summarizes the specific practices,main results,practical experience and promotion and application measures of the poverty alleviation model of C. pilosula planting industry in Xueshan Township,in the hope of providing certain reference for the targeted poverty alleviation in similar areas in Yunnan Province and other provinces of China.

Effect of Chinese Herbal Compound Naofucong (脑复聪) on theInflammatory Process Induced by High Glucose in BV-2 Cells

Objective: To determine the effect of medicated serum of Chinese herbal compound Naofucong(脑复聪, NFC) on the microglia BV-2 cells viability and the transcription and expression of interleukin-6(IL-6) and tumor necrosis factor α(TNF-α) in microglia BV-2 cells to further explore the mechanisms underlying the protective effect of NFC on inflammatory process induced by high glucose. Methods: The microglia BV-2 cells incubated in vitrowere divided into different groups: the control group(25 mmol/L glucose), the model group(75 mmol/L glucose), high glucose media containing different dose medicated serum of NFC. After being cultured for 24 h, changes in IL-6 and TNF-α were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The expression of surface marker CD11 b of activated microglia was measured by confocal laser scanning microscope and Western blot. Nuclear factor-κB(NF-κB) p-p65 expression was analyzed by Western blot. Results: The model group obviously increased the expression of microglial surface marker CD11 b and NF-κB p-p65(all P<0.01), induced a significant up-regulation of release and the m RNA expression of IL-6 and TNF-α(P<0.01 or P<0.05). The medicated serum of NFC could obviously down-regulate the transcription and expression of surface marker CD11 b and NF-κB p-p65(all P<0.01), and inhibit the m RNA and protein expression(P<0.01 or P<0.05) of inflammatory cytokines, such as IL-6 and TNF-α, in microglia BV-2 cells cultured with high glucose for 24 h. Conclusions: The inhibition of microglial activation and IL-6 and TNF-α expression induced by high glucose may at least partly explain NFC therapeutic effects on diabetes-associated cognitive decline diseases. Its underlying mechanism could probably be related to the inhibition of NFC on NF-κB phosphorylation.

Treatment of Advanced Non-small Cell Lung Cancer with Extracorporeal High Frequency Thermotherapy Combined with Chinese Medicine

Objective： To observe the clinical efficacy and benefit response of extracorporeal high frequency thermotherapy （EHFT） combined with Chinese medicine （CM） in the treatment of patients with advanced non-small cell lung cancer. Methods： The study adopted a prospective, small sample and randomized controlled method, and the advanced non-small cell lung cancer patients were assigned to two groups according to the table of random digits, one having the treatment of EHFT combined with CM （the treatment group）, the other only with CM （the control group）. The patients in the treatment group were treated with EHFT one hour once per day, together with CM differentiation decoction, 250 mL orally taken, twice daily for 14 days as one cycle, and 3-4 cycles was performed. The patients in the control group were treated only with CM differentiation decoction using the same dose as the treatment group. The efficacies were evaluated after three to four cycles of treatment. Primary endpoints were disease control rate （DCR） and time to progression （TTP）. Secondary endpoints were overall survival time and 1-year survival rate. Results： Sixty-six patients accomplished the study. After the patients underwent different treatments, none of the patients got a complete response or partial response in both groups. In the treatment group, DCR was 72.2%, and 10 had progression of disease （28.8%）, while the DCR of the control group was 63.3%, and 11 had progression of disease （36.7%）; there was a significant statistical difference （P0.05）, suggesting that the combined regimen had superiority on the DCR. As for long-term efficacy, the median survival time （MST） of the treatment group was 7.5 months, TTP was 5.5 months, and 1-year survival rate was 21.4 %; in the control group, the results were 6.8 months, 4.5 months and 16.6% respectively. There was significant statistical difference on TTP （P0.05）, but no difference on MST or 1-year survival rate. Conclusion： EHFT combined with CM differentiation has better tolerance and short-term efficacy in the treatment of patients with advanced NSCLC.

Analysis of active patents to investigate the frequency and patterns of Chinese herbal extract combinations claiming to treat heart disease

Objective:Using Chinese patents in force to investigate the frequency and patterns of Chinese herbal extract combinations claiming to treat heart disease.Methods:Patent documents were retrieved from the official website of the State Intellectual Property Office of the People’s Republic China.Cluster,frequency,and fuzzy cluster analyses were applied.Results:A high number of patents in force included high-frequency herbs such as Salvia miltiorrhiza,Panax ginseng,and Panax notoginseng,as well as high-frequency herbal families such as Araliaceae,Leguminosae,Labiatae,and Umbelliferae.Herb pairs such as P.ginsengþOphiopogon japonicus,S.miltiorrhizaþDalbergia odorifera,and P.ginsengþSchisandra chinensis are also commonly used,as well as herbal family pairs such as AraliaceaeþLiliaceae,LauraceaeþLeguminosae,and AraliaceaeþSchisandraceae.Traditional treatment principles for preventing and treating heart diseases was most-commonly based on simultaneously treating the liver and heart and treating the lung and spleen secondarily for choosing herbal combinations.Conclusion:Most of the high-frequency Chinese herbs in the patents investigated belong to the high-frequency herbal families,and herb pairs were commonly selected to coincide with the commonly-used herbal family pairs.Low-frequency Chinese herbs were also used,but generally belonged to the high-frequency herbal families,and were therefore similar to the highfrequency herbs in terms of traditional categories of taste and channel entered.The results reflect the use of traditional principles of formula composition,and suggest that these principles may indeed be an effective guide for further research and development of Chinese herbal extract combinations to prevent and treat heart diseases.

Effects of Chinese herbal monomers on oxidative phosphorylation and membrane potential in cerebral mitochondria isolated from hypoxia-exposed rats in vitro

Mitochondrial dysfunction is the key pathogenic mechanism of cerebral injury induced by high-altitude hypoxia. Some Chinese herbal monomers may exert anti-hypoxic effects through enhancing the efficiency of oxidative phosphorylation, in this study, effects of 10 kinds of Chinese herbal monomers on mitochondrial respiration and membrane potential of cerebral mitochondria isolated from hypoxia-exposed rats in vitro were investigated to screen anti-hypoxic drugs. Rats were exposed to a low-pressure environment of 405.35 mm Hg （54.04 kPa） for 3 days to establish high-altitude hypoxic models. Cerebral mitochondria were isolated and treated with different concentrations of Chinese herbal monomers （sinomenine, silymarin, glycyrrhizic acid, baicalin, quercetin, ginkgolide B, saffron, pipedne, ginsenoside Rgl and oxymatrine） for 5 minutes in vitro. Mitochondrial oxygen consumption and membrane potential were measured using a Clark oxygen electrode and the rhodamine 123 fluorescence analysis method, respectively. Hypoxic exposure significantly decreased the state 3 respiratory rate, respiratory control rate and mitochondrial membrane potential, and significantly increased the state 4 respiratory rate. Treatment with saffron ginsenoside Rgl and oxymatrine increased the respiratory control rate in cerebral mitochondria isolated from hypoxia-exposed rats in dose-dependent manners in vitro, while ginsenoside Rgl, piperine and oxymatrine significantly increased the mitochondrial membrane potential in cerebral mitochondria from hypoxia-exposed rats. The Chinese herbal monomers saffron, ginsenoside Rgl piperine and oxymatrine could thus improve cerebral mitochondrial disorders in oxidative phosphorylation induced by hypobaric hypoxia exposure in vitro.

痔疮栓联合中药熏洗坐浴对混合痔术后疼痛水肿的治疗作用分析

【目的】探究痔疮栓联合中药熏洗坐浴对混合痔术后疼痛水肿的临床疗效。【方法】将62例拟行手术治疗的混合痔患者随机分为试验组和对照组,每组各31例。2组患者均给予混合痔手术治疗(高位套扎术或混合痔外剥内扎术)和术后常规护理,在此基础上,对照组给予痔疮栓塞肛治疗,试验组给予痔疮栓塞肛联合中药熏洗坐浴(中药熏洗方由红花、桃仁、延胡索、滑石、川楝子、枳壳、黄柏、没药、乳香等组成)治疗,疗程为2周。观察2组患者治疗前后疼痛程度评分和水肿程度评分的变化情况,比较2组患者的症状缓解时间、临床疗效及治疗满意度。【结果】(1)治疗2周后,试验组的总有效率为96.77%(30/31),对照组为80.65%(25/31),组间比较(χ2检验),试验组的疗效明显优于对照组,差异有统计学意义(P<0.05)。(2)治疗后,2组患者的疼痛程度评分和水肿程度评分均较治疗前明显降低(P<0.05),且试验组对疼痛程度评分及水肿程度评分的降低作用均明显优于对照组,差异均有统计学意义(P<0.01)。(3)试验组的疼痛消失时间和水肿消失时间均较对照组明显缩短,差异均有统计学意义(P<0.01)。(4)试验组的总满意率为96.77%(30/31),对照组为77.42%(24/31),组间比较(χ2检验),试验组的治疗满意度明显优于对照组,差异有统计学意义(P<0.05)。【结论】痔疮栓联合中药熏洗坐浴对混合痔术后疼痛水肿的治疗作用显著,可有效改善患者的水肿程度和疼痛感,促进机体康复,提高患者的治疗满意度。

基于高通量测序分析中草药对发酵泡菜亚硝酸盐含量的影响及机制

为了探究金银花、黄柏两种中草药对发酵泡菜亚硝盐含量的影响及机制,基于高通量测序技术分析泡菜微生物群落结构,采用分光光度法分析泡菜中亚硝盐含量。研究结果表明,分别添加5%金银花和5%黄柏的泡菜中亚硝酸盐含量(8.02,5.90 mg/kg)均显著低于对照组(12.87 mg/kg)(P<0.05)。对泡菜样品进行高通量测序,共得到202个可操作分类单元(OTU),分属于11个门、129个属、165个种。添加5%的金银花和5%黄柏发酵10 d的泡菜样品中微生物的Chao 1指数显著低于对照组(P<0.05)。Proteobacteria(变形菌门)是各个样品中的优势菌门,相对含量高达90%。不同中草药处理的微生物在属水平上的优势微生物相对含量相差很大,对照组、添加金银花的发酵泡菜组、添加黄柏的发酵泡菜组中Pseudomonas(假单胞菌属)的相对含量分别为52%、1%、1%;Serratia(沙雷氏菌属)的相对含量分别为15%、0%、1%;Achromobacter(无色杆菌属)的相对含量分别为7%、1%、0%。实验结果表明金银花和黄柏对发酵白菜中亚硝酸盐形成的抑制作用是由于其抑制了肠杆菌科(Serratia、Achromobacter)和Pseudomonas(假单胞菌属)微生物的生长繁殖。

子午工程二期电离层高频多普勒监测仪初步观测结果

子午工程二期计划在漠河、北京、武汉、深圳四地分别建设由一个发射站和三个接收站构成的电离层高频多普勒监测台阵.本文介绍了为此研制的电离层高频多普勒监测仪的进展和试观测期间取得的一些观测结果.通过与电离层测高仪进行交叉对比,设备的性能和探测能力得到了验证.目前该设备已部署7个站点进行试观测,本文报告了该设备探测到的太阳耀斑导致的电离层扰动、电离层行进式扰动、大尺度电场导致的多站同时扰动等多种现象.未来子午工程二期建成后,该设备将具备我国上空北至漠河、南至广东的电离层扰动监测能力,并与其它探测手段融合发挥空间天气综合监测网络的最大效能.

中药复方对绵羊生长性能、血清生化指标、免疫和抗氧化功能的影响

试验旨在研究高精料饲粮中添加中药复方对绵羊生长性能、养分表观消化率、血清生化指标、免疫、抗炎和抗氧化功能的影响。选取30只体重(20.81±1.27)kg的3月龄杜寒杂交公羔,随机分为3组,每组10个重复,每个重复1只羊。基础饲粮精粗比为75∶25,对照组、Z1组和Z3组的中药复方添加量分别为0、10、30 g/d。预试期15 d,正式试验期50 d。结果显示,与对照组相比,添加30 g/d中药复方可以提高绵羊的末重和平均日增重(P<0.05),降低料重比(P<0.05),提高粗蛋白表观消化率(P<0.05),降低血清尿素氮的含量(P<0.05),降低血清中甘油三酯含量(P<0.05),增加低密度脂蛋白胆固醇和高密度脂蛋白胆固醇含量(P<0.05),提高血清中总抗氧化能力以及过氧化氢酶、谷胱甘肽过氧化物酶和总超氧化物歧化酶的活性(P<0.05),降低血清中丙二醛含量(P<0.05),提高血清中酸性磷酸酶、溶菌酶活性以及免疫球蛋白、干扰素-γ含量(P<0.05),降低血清中一氧化氮、脂多糖、白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α含量(P<0.05)。研究表明,在高精料饲粮中添加30 g/d的中药复方可以提高绵羊的抗氧化能力和免疫功能,降低血清促炎因子水平,缓解机体炎症,提高绵羊的日增重和养分表观消化率,对保持绵羊机体健康具有积极影响。

基于TRIZ理论的中药提取工艺创新优化

传统中药提取工艺存在着生物利用率低、材料残渣多、生产成本高和资源浪费等问题。为解决上述问题,基于发明问题解决理论(TRIZ),通过功能模型、因果链和资源分析,分析传统提取工艺中的关键问题及突破点。借助物-场模型、科学效应库、技术矛盾与发明原理、物理矛盾与分离原理等求解方法,提出一种工艺创新解法。与传统提取工艺进行对比,该工艺优化解法在得率上得到显著提升。该工艺优化为克服传统提取困境提供了新思路。

高效液相色谱-串联质谱测定中草药中的赤霉素GA1、GA3、GA4、GA7

利用高效液相色谱-串联质谱技术建立测定中草药中赤霉素GA1、GA3、GA4、GA7残留的方法。样品经1%甲酸乙腈超声提取,氮吹浓缩后,以0.1%甲酸水-甲醇体系为流动相进行梯度洗脱,采用负离子质谱扫描模式进行监测,用基质匹配标准曲线定量。结果表明,4种赤霉素在5~100μg/L范围其线性相关系数大于0.995,检出限为0.005~0.01 mg/kg,定量限为0.025 mg/kg,在低、中、高3个水平的加标回收率在81.5%~115.8%之间,相对标准偏差小于8%,符合方法学验证要求。该方法前处理简单快速,准确性好,可用于筛查和检测中草药中赤霉素的残留。

复方中草药提取物改善高脂饮食诱导的小鼠脂代谢紊乱

研究旨在探究复方中草药方剂中的活性成分对高脂饮食小鼠脂代谢的影响。采用水提醇沉的方法提取复方中草药方剂(柴胡、决明子、泽泻、黄芪、姜黄、陈皮)中的活性成分,并将80只小鼠随机分为对照组(CK组)、高脂日粮组(HFD组)、复方中草药提取物低剂量组(L-CCME组)、复方中草药提取物高剂量组(H-CCME组)4组,试验为期6周。试验期间每周称重;试验结束时采集血清、肝脏和肠道组织,采用试剂盒检测血清三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、谷丙转氨酶(ALT)和谷草转氨酶(AST)含量及肠道中IL-6和TNF-α含量;采用荧光定量PCR和蛋白质免疫印迹检测肝脏脂肪酸合成酶(FAS)和肉碱棕榈酰转移酶-I(CPT-I)表达量。结果表明:与CK组相比,HFD组小鼠血清中ALT、AST、TC和TG含量显著升高(P<0.05),表明造模成功。与HFD组相比,H-CCME组小鼠体重显著降低(P<0.05);试验结束时,与HFD组相比,H-CCME组小鼠TC、TG和LDL-C显著降低,HDL-C显著升高(P<0.05);此外,与HFD组相比,H-CCME组小鼠血清和肠道中IL-6和TNF-α水平显著降低(P<0.05),粪便中脂肪含量升高(P<0.05);与HFD组相比,H-CCME组小鼠肝脏中CPT-I mRNA和蛋白表达水平显著升高,FAS mRNA和蛋白表达水平显著降低(P<0.05)。说明复方中草药提取物能够有效治疗因高脂饲喂导致的脂质代谢异常,且最适添加量为400 mg/kg。

中国原油期货价格波动时段特征分析及预测

关于原油期货价格波动率的预测研究主要集中在国外市场,中国原油期货合约在一个交易日内被分为3个交易时段,这与国外市场有着很大的不同。交易时间分段可能使中国市场上波动率的结构与国外存在差异。通过异质自回归已实现波动率(HAR-RV)模型框架与半秒钟采样频率的高频期货合约交易数据,对价格波动率的结构特征及预测问题进行研究。研究验证了中国市场上预测的时间尺度由日缩小到交易时段尺度的可行性,发现了中国原油期货价格波动率有时段波动的特征,且时段特征的加入显著提高模型的预测性能。此外,研究还发现,预测时间尺度的缩小促进已实现波动序列平稳性的改善,发展了非平稳时序下HAR-RV模型研究问题,波动率的预测结果可为投资者和管理者对中国原油期货市场设计出更为精准的风险管理工具。

多功能黄精产业现状及其高质量发展探究——以千岛湖为例

黄精具有多种功效,黄精产业堪称朝阳产业。以千岛湖为例,分析了黄精基源植物的栽培基地发展和产品加工销售现状,充分发挥黄精作为“淳六味”道地药材优势,对于建设共同富裕区意义重大。黄精产业发展中依然存在生产成本与销售冲突、产业结构失衡、品牌培育不够等难点与痛点问题。提出了加强黄精资源培育关键技术研究与应用、加强黄精加工与营销企业建设、加强黄精品牌与产业融合战略建设等措施推进黄精产业高质量发展。

岭南常用中药材外源性污染物分析研究

目的研究岭南不同产地200批次10种常用中药材(巴戟天、化橘红、何首乌、砂仁、广藿香、南板蓝根、黑老虎、鸦胆子、槟榔、益智)中农药残留、重金属外源性污染物含量,以期为南药质量控制提供依据。方法按照2020年版《中华人民共和国药典》(简称《中国药典》)对10种岭南常用中药材中重金属及有害元素、农药等外源性污染物进行测定并分析测定结果。结果何首乌、南板蓝根、黑老虎、槟榔、益智中农药残留量及铅、砷、镉、汞、铜限量均符合《中国药典》的限量标准,巴戟天、化橘红、砂仁、鸦胆子均存在重金属不符合,广藿香存在农药残留量不符合。结论对于研究的品种,农药残留控制较好,需要重点监控铅、汞元素。

近代汉语与汉语方言中的高频副词“尽/侭着”

元明清典型白话文作品中词语的独特用法具有重要的语言学研究价值。在《红楼梦》《元曲选》等经典近代白话作品中有一个广泛使用的高频率副词“尽/侭着”,相当于普通话的“总是、老是”。方言中也普遍存在“尽着”类高频副词。文章通过对近代汉语语料的考察,结合方言中“尽”类副词的用法,考证了近代汉语“尽/侭着”的来源,进一步揭示语言演变的规律和语言接触的事实。

“双高”背景下基于岗位能力构建高职中药材生产与加工专业核心课程体系

立足中药材产业发展需求,加强中药材生产与加工专业建设,是双高背景下高职院校中药材生产与加工专业的重要发展思路。以“问题提出-构建依据-体系建成”为主线,调研分析了中药材生产与加工专业核心岗位能力及中药材产业对本专业的需求,并基于工作任务开发核心课程,构建了中药材生产与加工专业核心课程体系。

虚词性高频搭配在国际中文教育中的应用研究

随着构式语法及语料库语言学的发展,高频搭配的虚词性组块被认为是小句生成以及语篇构建的框架式构件,更需要优先习得。在国际中文教育领域,高频搭配的虚词性组块研究未得到足够的重视。本文分析了汉语虚词性高频搭配的特点,并进行分类。探讨了虚词性高频搭配在国际中文教育中应用的必要性,如可以降低学生汉语习得的门槛,减轻学生的心理负担;能够提高学生汉语表达的流利度与准确性,增强学生的自信心。提出了虚词性高频搭配在国际中文教育中应用的基本原则,如应分阶段、分层次进行教学;教师在教学中要侧重学生高频搭配意识的培养;要在教学中始终贯穿整体意识等。