Construction of Inorganic Elemental Fingerprint and Multivariate Statistical Analysis of Marine Traditional Chinese Medicine Meretricis concha from Rushan Bay

Meretricis concha is a kind of marine traditional Chinese medicine(TCM), and has been commonly used for the treatment of asthma and scald burns. In order to investigate the relationship between the inorganic elemental fingerprint and the geographical origin identification of Meretricis concha, the elemental contents of M. concha from five sampling points in Rushan Bay have been determined by means of inductively coupled plasma optical emission spectrometry(ICP-OES). Based on the contents of 14 inorganic elements(Al, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Se, and Zn), the inorganic elemental fingerprint which well reflects the elemental characteristics was constructed. All the data from the five sampling points were discriminated with accuracy through hierarchical cluster analysis(HCA) and principle component analysis(PCA), indicating that a four-factor model which could explain approximately 80% of the detection data was established, and the elements Al, As, Cd, Cu, Ni and Pb could be viewed as the characteristic elements. This investigation suggests that the inorganic elemental fingerprint combined with multivariate statistical analysis is a promising method for verifying the geographical origin of M. concha, and this strategy should be valuable for the authenticity discrimination of some marine TCM.

Inorganic Elemental Determinations of Marine Traditional Chinese Medicine Meretricis concha from Jiaozhou Bay:The construction of Inorganic Elemental Fingerprint Based on Chemometric Analysis

The goal of this paper is to explore the relationship between the inorganic elemental fingerprint and the geographical origin identification ofMeretricis concha, which is a commonly used marine traditional Chinese medicine （TCM） for the treatment of asthma and scald bums. For that, the inorganic elemental contents ofMeretricis concha from five sampling points in Jiaozhou Bay have been determined by means of inductively coupled plasma optical emission spectrometry, and the comparative investigations based on the contents of 14 inorganic elements （A1, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Se and Zn） of the samples from Jiaozhou Bay and the previous reported Rushan Bay were performed. It has been found that the samples from the two bays are ap- proximately classified into two kinds using hierarchical cluster analysis, and a four-factor model based on principle component analysis could explain approximately 75% of the detection data, also linear discriminant analysis can be used to develop a prediction model to distinguish the samples from Jiaozhou Bay and Rushan Bay with accuracy of about 93%. The results of the present investi- gation suggested that the inorganic elemental fingerprint based on the combination of the measured elemental content and chemom- etric analysis is a promising approach for verifying the geographical origin ofMeretricis concha, and this strategy should be valuable for the authenticity discrimination of some marine TCM.

Quantitative similarity assessment of non-linear chemical fingerprint of traditional Chinese medicine by similarity system theory

The similarities of the non-linear chemical （NLC） fingerprints of Radix Glycyrrhizaes from four producing areas and eight other traditional Chinese medicines （TCMs） were calculated, using a systemic similarity calculation method proposed and three other main calculation ones （Euclidean distance, correlation coefficient and included angle cosine）. All of the correlation coefficient similarities of different TCMs are higher than 0.952, and the included angle cosines are all higher than 0.962. So, both the conelation coefficient and included angle cosine similarities are unable to be used as the criteria for quantitatively evaluating the similarities of NLC fingerprints of TCMs. Although all of the Euclidean distance similarities of Berry Liquorices from four producing areas are less than 73, those of the other eight TCMs are all more than 180. The Euclidean distance cannot reflect the relative magnitudes of the feature differences in the NLC fingerprints very correctly. The systemic similarity method is the best among the four ones. All of the systemic similarities of Berry Liquorices from the four producing areas are higher than 0.962, while those of the other eight TCMs are all lower than 0.805, and the systemic similarity can reflect the differences between samples most faithfully, and can be used as a quantitative one evaluating the similarities of NLC fingerprints of TCMs, by which TCM could be distinguished and evaluated quickly, simply and exactly.

An ultra-robust fingerprinting method for quality assessment of traditional Chinese medicine using multiple reaction monitoring mass spectrometry

Chromatographic fingerprinting has been perceived as an essential tool for assessing quality and chemical equivalence of traditional Chinese medicine.However,this pattern-oriented approach still has some weak points in terms of chemical coverage and robustness.In this work,we proposed a multiple reaction monitoring(MRM)-based fingerprinting method in which approximately 100 constituents were simultaneously detected for quality assessment.The derivative MRM approach was employed to rapidly design MRM transitions independent of chemical standards,based on which the large-scale fingerprinting method was efficiently established.This approach was exemplified on QiShenYiQi Pill(QSYQ),a traditional Chinese medicine-derived drug product,and its robustness was systematically evaluated by four indices:clustering analysis by principal component analysis,similarity analysis by the congruence coefficient,the number of separated peaks,and the peak area proportion of separated peaks.Compared with conventional ultraviolet-based fingerprints,the MRM fingerprints provided not only better discriminatory capacity for the tested normal/abnormal QSYQ samples,but also higher robustness under different chromatographic conditions(i.e.,flow rate,apparent pH,column temperature,and column).The result also showed for such large-scale fingerprints including a large number of peaks,the angle cosine measure after min-max normalization was more suitable for setting a decision criterion than the unnormalized algorithm.This proof-of-concept application gives evidence that combining MRM technique with proper similarity analysis metrices can provide a highly sensitive,robust and comprehensive analytical approach for quality assessment of traditional Chinese medicine.

Study on Elemental Fingerprint of Traditional Marine Chinese Medicine Oysters from Jiaozhou Bay,China

In order to investigate the relationship between the trace elements and the characteristics of the oysters, we analyzed the trace elements present in the germplasm of oysters from different producing areas in the Jiaozhou Bay. The element fingerprints were established to reflect the elemental characteristics of the oysters. Concentration patterns of the elements were deciphered by principle component analysis (PCA) and hierarchical cluster analysis (HCA). The six regions were discriminated with accuracy using HCA and PCA based on the concentration of 16 trace elements. The elements were viewed as characteristic elements of the oysters and the fingerprints of these elements could be used to distinguish the quality of the oysters.

Similarity measurement of Chinese medicine ingredients for cold-hot nature identification

Objective:Nature theory of Chinese medicine (CM) is the core basic theory of Traditional Chinese Medicine (TCM), in which cold-hot nature is the focus of research. Studies have found that CM ingredients are the material basis for the production of medicine natures. Therefore, it is speculated that CMs with similar composition of substances should have similar medicinal nature. Modern work studies cold-hot medicine of CMs with chemical fingerprinting technology because the chemical fingerprint data of CM can reflect the whole composition of CM ingredients. Methods:To verify the hypothesis above, in this work, we study quantifying the similarity of CM ingredients to fingerprint similarity, and explore the relationship between the composition of CMs and cold-hot nature. Firstly, we utilize ultraviolet (UV) spectrum technology to analyze 61 CMs, which have clear cold-hot nature (including 30 ‘cold’ CMs and 31 ‘hot’ CMs). Secondly, with the constructed fingerprint database of CMs, a distance metric learning algorithm is studied to metric the similarity of UV fingerprints. Finally, a retrieval scheme is proposed to build a predictive identification model to identify cold-hot nature of CMs. Results:By means of numerous experiment analyses, ultraviolet spectrum data of petroleum ether solvent can better represent CMs to distinguish between cold and hot natures. Comparing with existing classical models, the proposed identification scheme has better predictive performance. Conclusion:The experimental results prove our inference that CMs with similar composition of substances should have similar medicinal nature. The proposed prediction model is proved to be effective and feasible.

Integrated evaluation of HPLC fingerprints for the quality control of Ginseng Yang Rong Wan by multi-wavelength fusion fingerprint method

The aim of this study was to develop comprehensive evaluation methods for the quality control of Ginseng Yang Rong Wan(RSYRW).Multi-wavelength fusion fingerprints were successfully developed by high-performance liquid chromatography,which avoided the one-sidedness of single fingerprinting.Characteristic fingerprints of thirty batches of samples were generated at five wavelengths and evaluated by quantified ratio fingerprint method(QRFM).The results showed that thirty batches of samples were classified into seven grades.The methods established in this paper were found suitable for the analysis of Ginseng Yang Rong Wan.

Determining method and conditional factors of electrochemical fingerprint of Chinese traditional medicine

The thermodynamic systems and kinetic model suitable for the electrochemical token of the compo-nent throng in Chinese traditional medicines have been analyzed. It has been indicated that the damp oscillatory reactions in the non-equilibrium close system and open system without the supplement of dissipative substance have important significance for the throng token and analysis of chemical com-ponents in Chinese traditional medicines. Various factors influencing the electrochemical fingerprint,such as reactant species and their concentrations,electrode types,temperature,stir rate,the kind,dosage and granularity of Chinese traditional medicines,have amply been researched by the B-Z os-cillatory reaction which used malonic acid as a main dissipative substance. In addition,the quantitative information about the chemical components in Chinese traditional medicines has been discussed in detail. The method and its conditions for determining the electrochemical fingerprint used in scientifi-cally distinguishing and evaluating Chinese traditional medicines have successfully been put forward.

Brain organoids are new tool for drug screening of neurological diseases

At the level of in vitro drug screening,the development of a phenotypic analysis system with highcontent screening at the core provides a strong platform to support high-throughput drug screening.There are few systematic reports on brain organoids,as a new three-dimensional in vitro model,in terms of model stability,key phenotypic fingerprint,and drug screening schemes,and particula rly rega rding the development of screening strategies for massive numbers of traditional Chinese medicine monomers.This paper reviews the development of brain organoids and the advantages of brain organoids over induced neurons or cells in simulated diseases.The paper also highlights the prospects from model stability,induction criteria of brain organoids,and the screening schemes of brain organoids based on the characteristics of brain organoids and the application and development of a high-content screening system.

Principle, traits and functions of electrochemical fingerprint of Chinese traditional medicine

In regard to such challenging analysis problems as scientific identification and quality evaluation of Chinese traditional medicine, the electrochemical fingerprint technique of Chinese traditional medi- cine has been researched. The principle, traits, functions, etc., of the electrochemical fingerprint have detailedly been analyzed and discussed by the B-Z oscillatory system using malonic acid as main dissipation substance, characterized by the fact that different influences of different Chinese traditional medicines on the mechanism of the oscillatory reaction cause different changes of the shape of the potential-time curve of the oscillatory system under the conditions of constant tem- perature and pressure. An economical, simple and convenient, easy pushing and effective scientific method for distinguishing and evaluating multifarious Chinese traditional medicines has success- fully been put forward.

Rapid determination of tannin in Danshen and Guanxinning injections using UV spectrophotometry for quality control

A technique for the determination of tannin content in traditional Chinese medicine injections(TCMI)was developed based on ultraviolet(UV)spectroscopy.Chemometrics were used to construct a mathematical model of absorption spectrum and tannin reference content of Danshen and Guanxinning injections,and the model was veried and applied.The results showed that the established UV-based spectral partial least squares regression(PLS)tannin content model performed well with a correlation coefficient(r)of 0.952,root mean square error of calibration(RMSEC)of 0.476
g/ml,root mean square error of validation(RMSEV)of 1.171
g/ml,and root mean square error of prediction(RMSEP)of 0.465
g/ml.Pattern recognition models using linear discriminant analysis(LDA)and k nearest neighbor(k-NN)classiers based on UV spectrum could successfully classify different types of injections and different manufacturers.The established method to measure tannin content based on UV spectroscopy is simple,rapid and reliable and provides technical support for quality control of tannin in Chinese medicine injections.

High-Performance Liquid Chromatography Fingerprint of Marine Traditional Chinese Medicine Haliotidis

Objective: Haliotidis, the dried muscle of abalone, has long been used as a marine traditional Chinese medicine(TCM) due to its high medicinal and nutritive values, whereas few reports contributed to its quality control. This study aimed to establish the high-performance liquid chromatography(HPLC) fingerprints of Haliotidis. Materials and Methods: The HPLC fingerprints of Haliotidis, the manufacturing products of dried muscle of abalone, were analyzed by reverse-phase HPLC, using a YMC HPLC C18 column(250 mm × 4.6 mm, 5 μm).The gradient elution mode was applied with mobile phase starting from 5% acetonitrile and 0.1% phosphoric acid aqueous solution to 100%acetonitrile in 70 min at a flow rate of 1.0 mL/min. The detection wavelength was set at 190 nm. Results: Through compared the HPLC fingerprint chromatograms of 14 batches of Haliotidis, 25 peaks were assigned as the characteristic common peaks, of which one index component L-phenylalanine was identified by comparison with its standard substance. The established HPLC fingerprint analysis method of Haliotidis was validated with good precision, repeatability, and stability. Based on the above study, a reference HPLC fingerprint chromatogram of Haliotidis was proposed. Conclusions: It is the first time to establish the HPLC fingerprint chromatogram of TCM Haliotidis, which could contribute to the establishment of its quality control system.

Micro-piezoelectric pulse diagnoser and frequency domain analysis of human pulse signals

Background:The theory of pulse diagnosis is to assess the physiological condition of the human body using radial pulse.However,pulses can vary markedly from person to person.Further,pulse diagnosis is difficult to learn and requires one-on-one teaching.Methods:To address this problem,we built a home-made pulse diagnoser and measured human pulses for studying the standardization of pulse diagnosis.Our pulse diagnoser was composed of a piezoelectric transducer,differential amplifier,data acquisition instrument,and a Matlab analysis program.The measured pulses were converted into electronic signals by a piezoelectric transducer and saved on a computer.The digitalized data were then refined and analyzed by fast Fourier transform for frequency analysis.Simulations were performed to assess the factors that affected the pulse,including phase shifts of reflected pulse waves (generate sub-peaks in pulses),inconsistent heart rates (deform pulse waves),the vessel stiffness (alter harmonic frequencies of the pulses),and the wave amplitudes (determined by the pulse strength).Results:By comparing a published report and our simulation findings,we characterized the pulse types and the effects of various factors,and then applied the findings to study actual pulses in patients.Three types of pulses were determined from the frequency spectrumchoppy pulse (Se mai) without apparent harmonic peaks,the harmonic frequencies of wiry pulse (Xian mai) that are non-integer multiples of the fundamental frequency,and surging pulse (Hong mai) that exhibit strong amplitudes in the spectrum of frequency.A normal pulse and a slippery pulse were differentiated by a phase shift,but not by assessing the frequency spectrum.Conclusion:These findings confirm that frequency domain analysis can avoid ambiguity arising in assessing the three types of pulses in the time domain.Further studies of other pulses in the frequency domain are required to develop a precise electronic pulse diagnoser.

基于文献计量分析皮内针疗法适宜病症与临床应用进展

目的基于文献计量分析皮内针疗法的临床文献,探讨皮内针疗法的适宜病症与临床应用进展。方法通过计算机检索中国知网(CNKI)、万方数据库(Wanfang data)和维普中文期刊数据库中与皮内针疗法相关的临床研究文献,应用文献计量学的方法对皮内针疗法发文量、病谱和适宜病症进行分析。结果临床涉及论文共2220篇,近10年发文量显著增长。皮内针疗法临床涉及病症208种。一级适宜病症为手术后疼痛、失眠症、偏瘫、面神经麻痹;二级适宜病症为肩痛、颈椎病、癌痛、膝骨关节炎、腰椎间盘移位、便秘、头痛;三级适宜病症为带状疱疹、遗尿、放化疗后不良反应、变应性鼻炎、呃逆、面肌痉挛;四级适宜病症包括痛经、高血压、糖尿病、胃肠功能紊乱、痹证、吞咽障碍、腰扭伤、肥胖症。结论皮内针疗法是近年来的临床研究热点,其治疗疾病以痛症居多,其次为各类慢性病。不同针具中,揿针的应用受到广泛关注。

中医视角下发热门诊2021-2022年7203例患者疾病谱研究

目的研究日常急性发热患者的疾病谱分布、发病时令、年龄、体温峰值特征。方法选取首都医科大学附属北京中医医院发热门诊,2021年1月20日(大寒节气)至2022年1月20日(大寒节气)全年就诊的急性发热患者为研究对象,总结日常急性发热患者的疾病谱分布、发病时令、年龄、体温峰值特征。结果2021年1月20日至2022年1月20日,共有7203例患者就诊于北京中医医院发热门诊,排除仅来门诊筛查且无发热等11类临床症状的患者及复诊患者4052例,最终纳入3151例初诊患者。疾病谱分布情况:上呼吸道细菌感染类疾病957例(30.37%)、感冒(非细菌感染)类疾病801例(25.42%)、胃肠道感染类疾病571例(18.12%)、肺炎等下呼吸道细菌感染类疾病446例(14.15%)、泌尿系感染类疾病149例(4.73%)、皮肤软组织感染类疾病71例(2.25%)、外科相关感染类疾病66例(2.09%)、免疫相关发热疾病27例(0.86%)、其他伴随发热的杂病63例(2.00%)。进一步研究了疾病谱前5种疾病的发病时令、年龄分布、体温峰值特点,结果发现高发时令均在夏季和冬季,不同疾病谱的多发年龄、体温峰值存在统计学差异。结论日常急性发热患者的疾病谱以肺系疾病为主(含上呼吸道细菌感染、感冒、肺炎等),其次为胃肠道和泌尿系疾病;极寒极热时令是日常急性发热性疾病的高发时令;肺炎和泌尿系感染好发于老年人群,且体温峰值较上呼吸道感染、感冒、胃肠道感染更高。

基于徐荣谦教授的《神魂意魄志论》探讨孤独症谱系障碍的中医康复诊疗

孤独症谱系障碍(ASD)的发生涉及多个脏腑功能失调。徐荣谦教授所提出的“神魂意魄志论”可解释ASD的多种核心临床表现,通过深入分析神魂意魄志的功能,挖掘出本病的发生与“五脏神”相关,尤其与心神、肝魂、脾意、肾志的联系密切。临床中将这一“形神并治”的理论体系用来指导治疗ASD能使形气相得,获得较好疗效。

自拟乳康方剂指纹图谱建立及刺桐碱含量测定

为建立乳康方剂中药提取液(王不留行、甘草、蒲公英、黄芪、连翘和当归)高效液相色谱(HPLC)指纹图谱并测定提取液中刺桐碱含量,结合化学模式识别法评价乳康方剂的质量。本试验应用《中药色谱指纹图谱相似度评价系统》(2012年版)绘制10批次乳康方剂提取液的HPLC指纹图谱进行相似度评价,并确认共有峰;应用SPSS 26.0软件的聚类分析以及SIMCA 14.1软件的主成分分析和正交偏最小二乘法判别分析对10批次乳康方剂提取液指纹图谱进行质量评价,筛选引起组间差异的标志物;使用本试验所建立刺桐碱HPLC检测方法检测不同批次乳康方剂提取液中刺桐碱含量。结果显示,10批次乳康方剂提取液中共有28个共有峰,相似度介于0.903~0.938;聚类分析、主成分分析和正交偏最小二乘法判别分析均可将10批乳康方剂提取液分为3类,且分类结果一致;通过正交偏最小二乘法判别分析筛选出可导致组间差异的9个共有峰;使用所建立的刺桐碱HPLC检测方法测得10批次乳康方剂提取液中刺桐碱平均含量为0.0189 mg/mL。结果表明,本试验建立的HPLC指纹图谱分析方法操作简便、检测结果准确,结合多元统计分析可为自拟乳康方剂的质量控制提供科学依据。

推拿不同部位对孤独症谱系障碍模型鼠行为学及肠道菌群的影响

目的探究不同部位的推拿对丙戊酸(VPA)诱导的孤独症谱系障碍(ASD)模型鼠行为学和肠道菌群的影响。方法将20只怀孕12.5天的Sprague Dawley(SD)雌性大鼠随机分为VPA模型组[腹腔注射VPA(600 mg/kg),n=15]和生理盐水组(腹腔注射等量生理盐水,n=5)。将注射生理盐水的子代雄鼠作为对照组,将注射VPA的子代雄鼠随机分为VPA组、背部组和腹部组(n=7)。在出生后第21天,通过三箱社交、旷场实验和埋珠实验观察四组大鼠的社交能力、焦虑行为和刻板行为,并开始对背部组和腹部组进行推拿,每天2次,持续14天。第35天,再次进行行为学检测,并取肠道内容物进行物种组成与结构分析、标志物种与差异物种分析。结果(1)行为学结果显示,与VPA组相比,背部组大鼠社交时间和旷场中心区运动时间显著增加(P<0.05),埋珠数量明显减少(P<0.01),说明其社交、焦虑和刻板行为得到改善;与VPA组相比,腹部组大鼠埋珠数量显著减少(P<0.05),刻板行为改善;埋珠实验中,背部组较腹部组埋珠数量更少,刻板行为改善更显著(P<0.05),而三箱社交和旷场实验两组结果无显著差异(P>0.05)。(2)肠道微生物检测结果显示,在多样性分析中,与VPA组相比,背部组和腹部组肠道菌群丰富度显著增加(P<0.05),多样性增加(背部组P<0.05,腹部组P<0.01);在差异性分析中,在门水平上,与VPA组相比,腹部组厚壁菌门相对丰度呈现较为明显的降低趋势(P<0.05);在属水平上,与VPA组相比,背部组和腹部组的乳杆菌属相对丰度较VPA组显著下降(P<0.05);标志物种分析中,与VPA组相比,背部组布劳特氏菌属显著增加(P<0.05)。结论推拿能对ASD模型大鼠行为学和肠道菌群结构产生影响;推拿背部对ASD模型鼠的社交能力、焦虑行为和刻板行为疗效显著,推拿腹部仅对刻板行为有明显效果;推拿背部与推拿腹部均使ASD模型鼠肠道菌群丰富度和多样性增加,其中推拿腹部对肠道微生物多样性的改善更显著,并使物种分布更均匀。

中药材的不同产地鉴别技术研究概况

目的探讨中药材不同产地鉴别技术的研究现状和发展趋势,为中药材产地研究拓展思路。方法以“中药”“产地”“鉴别”等为关键字,在中国知网、维普网、PubMed、Web of Science等数据库中查询近10年发表的相关研究论文,并以“不同产地”和“鉴别技术”为主旨进行文献综述。结果中药材的不同产地鉴别技术包括性状与显微鉴别、理化鉴别、指纹图谱技术、DNA分子标记鉴别、生物效价评价和结合计算机算法的人工智能鉴别技术等多种方法,其中经验鉴别、显微鉴别和一般理化鉴别等传统鉴别方法简便易行,但依赖经验、专属性差;光谱法、指纹图谱、DNA标记技术等方法用于中药材产地鉴别克服了以上缺点,准确可靠、操作简便;结合计算机算法的人工智能鉴别技术更加准确高效,极大地降低了人工和时间成本,将成为未来发展的重要方向。结论中药材的不同产地鉴别存在一定的难度和不确定性,可以结合多种方法进行综合鉴别,发挥每种鉴别方法的优势,以确保结果的准确性。未来,中药材鉴别将更加智能化和自动化,利用人工智能、机器学习等技术可以提高鉴别效率和准确性。

Chemometrics and modernization of traditional Chinese medicine

Development of chromatographic fingerprinting and its related chemometric methods in the research of quality control of traditional Chinese medicines(TCMs) are discussed. The quality control methods for guarantying the authentication and stability of products and semi-products of TCMs are firstly assessed. The technique based on chromatographic fingerprinting is essentially a kind of high-through put and integral tools to explore the complexity of herbal medicines. In order to further control the comprehensive quality of TCMs,confirmation and identification of their important chemical components are necessary. Some new strategies are proposed to trace the chemical changes of chromatographic fingerprints both in product processing and/or after their administration by modern chromatographic techniques and chemometrics. Combined with systems biology and bioinformatics,it seems possible for one to reveal the working mechanism of TCMs and to further control their intrinsic quality comprehensively.