Opioid analgesics are currently known as the best analgesics. However， toxicity and side effects such as constipation， tolerance and addiction severely limit their clinical application. With the in-depth understanding of the signal transduction mechanism of opioid receptors and the continuous advancement of drug design technology， researchers have managed to develop many promising new methods to get low-toxic and more efficient opioid analgesics， which are different from the traditional morphine skeleton structure modifications. This article focuses on three new research strategies of G-protein biased activation，“ one drug-multiple targets” and peripheral activation. The basic principles of relative separation of analgesic activity and adverse drug reaction by each strategy are introduced， and the latest research progress of representative drugs is briefly reviewed. Among them， the recently approved novel opioid analgesics oliceridine and tegileridine are G-protein biased μ-opioid receptor agonists， Cebranopadol is a typical “one drug-multiple targets” analgesic， and NFEPP is a representative drug of peripheral opioid receptor agonists. The above several strategies complement each other and provide reference for the development of new opioid analgesic drugs.

ObjectiveTo establish a theoretical system of pharmacokinetic and spectrokinetic dose-time characterization of traditional Chinese medicine（TCM）. By analyzing the pharmacokinetic and spectrokinetic behaviors of Lonicerae Flos， Houttuyniae Herba injection， Lonicerae Japonicae Flosand Buyang Huanwutang， this paper compared the similarities and differences of the three methods for characterizing the dose-time relationship， namely half-life， statistical moment and statistics， in order to find the most suitable method for characterizing the relationship. MethodTen mice were randomly selected from 100 Kunming mice as the blank group， and the remaining mice were coated with xylene in the auricle to establish the acute inflammation model of ear swelling. After successful modeling， the mice were gavaged with aqueous extract of Lonicerae Flos（30 g∙kg^-1）， and the blank group was gavaged with an equal volume of normal saline. The plasma of mice was collected at different time points to determine the content changes of components. At the same time， the pharmacokinetic results of Houttuyniae Herba injection， Lonicerae Japonicae Flos and Buyang Huanwutang were included， and the pharmacokinetic and spectrokinetic parameters were calculated. Then the difference in the time of calculating 95% total component content of metabolism by half-life method， statistical moment method and statistical method was compared. ResultOn the basis of the half-life method， the mathematical expressions of statistical moment method and statistical method suitable for the characterization of dose-time relationship of multi-component system of TCM were established. The results showed that the pharmacokinetic parameters of the individual components in Lonicerae Flos varied， with cryptochlorogenic acid and rutin showing a two-compartment model and the other components showing a one-compartment model. After calculation of spectrokinetic similarity， the metabolic patterns among the components contained in Houttuyniae Herba injection， Lonicerae Japonicae Flos， Lonicerae Flos and Buyang Huanwutang were different and varied greatly in vivo. The time to metabolize 95% of the total components of the four research subjects in vivo was calculated by the half-life method， statistical moment method and statistical method， and it was found that the difference between statistical moment method and half-life method was large， and the difference between statistical moment method and statistical method was small. ConclusionStatistical method not only reflects the characteristics of statistical moment method， characterizes the dispersion degree of each component， but also can be associated with fingerprint to form spectrokinetics， characterizing the dose-time relationship of 95% of drug components， which is a more desirable method to characterize the dose-time relationship of the component groups in TCM.

ObjectiveTo study the characteristics of imprinting template of flavonoid clusters in four Chinese medicines attributed to the lung meridian， and to establish an in vitro experimental approach for the study of the attribution of Chinese medicines to the lung meridian. MethodBased on 13 Chinese medicines， including Xanthii Fructus， Houttuyniae Herba， Fagopyri Dibotryis Rhizoma， Belamcandae Rhizoma and so on， which only belong to the lung meridian in Chinese Materia Medica（the 13^th Five-Year planning textbook of general higher education）， we identified four representative Chinese medicines， namely Houttuyniae Herba， Fagopyri Dibotryis Rhizoma， Belamcandae Rhizoma and Mori Cortex， and set up their fingerprints by high performance liquid chromatography（HPLC） and calculated the molecular connectivity indices of various components in the four Chinese medicines， the similarity to their mean value was calculated by included angle cosine method， so as to establish the quantitative relationship of construction versus imprinting ability， and to determine the order of each component in the lung meridian. A total of 7 reference substances， including chlorogenic acid， rutin， quercetin， isoquercitrin， hyperoside， epicatechin， and iridin， were selected to validate the overall conformational relationships of flavonoids of the model， as well as its predictive ability. ResultHouttuyniae Herba， Fagopyri Dibotryis Rhizoma， Belamcandae Rhizoma and Mori Cortex contained a total of 437 chemical components with an average molecular connectivity index similarity of 0.995 6. The four Chinese medicines contained a total of 204 flavonoids with an average molecular connectivity index similarity of 0.978 0， which was second only to the alkaloids with 0.985 1. The retention time（t_R） of the 7 reference substances showed a good conformational relationship with the similarity of the molecular connectivity index（t_R=831.4×S-790.3， r=0.861 4， P<0.01）， which was applicable to the in vitro attribution study of the position， similarity， and relative similarity with t_R of the cluster of 98.04% of flavonoids. Accordingly， the 1^st position was kuwanon D， with a similarity of molecular connectivity index of 0.987 7 and a t_R of 30.88 min， the 200^th position was chlorogenic acid， with a similarity of molecular connectivity index of 0.958 2 and a t_R of 6.36 min. The total first-order moment of the four Chinese medicines calculated by total statistical moment method of fingerprint was 24.26 min， ranked 21， which could characterize 99.19% of the whole， and the total first-order moment of the total peak area of the 7 reference substances in the four Chinese medicines was 20.00 min， with a rank of 46， which could characterize 98.68% of the whole. ConclusionFlavonoid clusters are suitable probes for the characterization of imprinting template for the study of the lung meridian， which can be established a quantitative imprinting method for meridian tropism of Chinese medicines in vitro.

Objective : To compare the accuracies of implants with dynamic real-time navigation versus digital guide navigation to provide a reference for clinical precision dental implants. Methods: Forty-six cases (seventy teeth) with missing teeth admitted to the Department of Stomatology, Wuzhou Red Cross Hospital from April 2018 to December 2019 were randomly divided into two groups (thirty-five teeth in each group) for dynamic real-time navigation and digital guide navigation implantation techniques. To compare the entry point, apex point, depth and angle deviation of the preoperative and postoperative position of implants in the two groups. SPSS 21.0 software was used for statistical analysis. Results : Dental implants were successfully placed in both groups. The deviations of apex point, depth and angle in the dynamic real-time navigation group were all smaller than those in the digital guide navigation group, and the differences were statistically significant (P < 0.05). There was no statistically significant deviation in the entry point between the two groups (P > 0.05). Conclusion In this study, both techniques had good clinical effects. The accuracy of dynamic real-time navigation was higher than that of digital guidance.

With human placed in the whole nature, by following the biologic evolution path, the property of channel structure for "imprinting template" in meridian andwas explored with supramolecular chemistry. In the history of biologic evolution, each molecule in "molecule society" gradually developed into various highly-ordered supramolecular bodies based on self-identification, self-assembly, self-organization, self-replicating of"imprinting template", and thereby the original biochemical system was established, and finally evolved into human. In the forming process of supramolecular bodies, the channel structure of"imprinting template" in guest supramolecular bodies would be kept by host supramolecular bodies, and communicate with the outside to exchange materials, energy, information, otherwise life phenomenon could not continue, for which it was the chemical nature of biolo-gical supramolecular bodies for body to develop meridian. Therefore, the human was a gigantic and complicated supramolecules body in biological nature, and possessed the supramolecules "imprinting template" at each stage of evolution, for which the meridians were formed. When meridians converged, acupoints appeared; when acupointsconverged,appeared. With the promotion of the blood from heart, according to"imprinting template", the guest supramolecular bodies and host meridian produced-analysis, which was the-phenomenon of guest in meridian. It presented asimage of physiology and pathology as well as action regularities of medication and acupuncture tolerance, by which current various meridian viewpoints could be explained and propose the hypothesis of meridian supramolecular bodies. The meridian and its phenomenon was decide by its "imprinting template" of supramolecular bodies and self-reaction regularities, which abided through the living nature. This was the substance for meridian biology.

OBJECTIVETo observe the effects of acupuncture-moxibustion on chronic allograft nephropathy (CAN) and explore the methods of acupoint selection along meridian for transplanted-kidney-related diseases.

METHODSA total of 180 patients of CAN were randomized into a syndrome differentiation group, a spleen-meridian group, a kidney-meridian group and a control group, 45 cases in each one. A total of 33 cases dropped out before the end of the study, including 8 cases in the syndrome differentiation group, 12 cases in the spleen-meridian group, 13 cases in the kidney-meridian group and no case in the control group. Patients in the control group were treated with conventional western medicine; based on this, patients in other three groups were treated with acupuncture-moxibustion. In the syndrome differentiation group, Qihai (CV 6), Hegu (LI 4), Guanyuan (CV 4), Feishu (BL 13), Shenshu (BL 23), etc. were selected for qi deficiency of lung and kidney; Qihai (CV 6), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3), Yinlingquan (SP 9), etc. were selected for deficiency of qi and yin; Ganshu (BL 18), Shenshu (BL 23), Sanyinjiao (SP 6), Taixi (KI 3), Yinlingquan (SP 9), Ququan (LR 8), etc. were selected for yin deficiency of liver and kidney; Zhongji (CV 3), Guanyuan (CV 4), Mingmen (GV 4), Guanyuanshu (BL 26), etc. were selected for yang deficiency of spleen and kidney. In addition, Sanyinjiao (SP 6), Diji (SP 8), Yinlingquan (SP 9), Xuehai (SP 10), etc. were added in the spleen-meridian group; Taixi (KI 3), Zhaohai (KI 6), Fuliu (KI 7), Ciliao (BL 32), etc: were added in the kidney-meridian group. Serum creatinine (Scr), creatinine clearance (Ccr) and 24-hour urinary protein before and after the treatment were com- pared among the four groups.

RESULTSAfter treatment, 24-hour urinary protein in the acupuncture-moxibustion groups and control group were all reduced (all P < 0.05); compared before treatment, the Scr in the spleen-meridian group was significantly reduced (P < 0.05); the difference of Ccr before and after treatment was insignificant in all the groups (all P > 0.05). Compared with the control group, 24-hour urinary protein in spleen-meridian group could relieve or recover the damage of transplant kidney induced by CAN. A new interlink may be established between the transplanted kidneys and the spleen meridians, indicating that transplanted kidney-related diseases can be treated by selecting acupoints of spleen meridian.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Allografts ; physiopathology ; Female ; Graft Rejection ; Humans ; Kidney Transplantation ; adverse effects ; Male ; Meridians ; Middle Aged ; Moxibustion ; Renal Insufficiency, Chronic ; etiology ; therapy ; Transplantation, Homologous ; adverse effects

The paper aims to elucidate and establish a new mathematic model: the total quantum statistical moment standard similarity (TQSMSS) on the base of the original total quantum statistical moment model and to illustrate the application of the model to medical theoretical research. The model was established combined with the statistical moment principle and the normal distribution probability density function properties, then validated and illustrated by the pharmacokinetics of three ingredients in Buyanghuanwu decoction and of three data analytical method for them, and by analysis of chromatographic fingerprint for various extracts with different solubility parameter solvents dissolving the Buyanghanwu-decoction extract. The established model consists of four mainly parameters: (1) total quantum statistical moment similarity as ST, an overlapped area by two normal distribution probability density curves in conversion of the two TQSM parameters; (2) total variability as DT, a confidence limit of standard normal accumulation probability which is equal to the absolute difference value between the two normal accumulation probabilities within integration of their curve nodical; (3) total variable probability as 1-Ss, standard normal distribution probability within interval of D(T); (4) total variable probability (1-beta)alpha and (5) stable confident probability beta(1-alpha): the correct probability to make positive and negative conclusions under confident coefficient alpha. With the model, we had analyzed the TQSMS similarities of pharmacokinetics of three ingredients in Buyanghuanwu decoction and of three data analytical methods for them were at range of 0.3852-0.9875 that illuminated different pharmacokinetic behaviors of each other; and the TQSMS similarities (ST) of chromatographic fingerprint for various extracts with different solubility parameter solvents dissolving Buyanghuanwu-decoction-extract were at range of 0.6842-0.999 2 that showed different constituents with various solvent extracts. The TQSMSS can characterize the sample similarity, by which we can quantitate the correct probability with the test of power under to make positive and negative conclusions no matter the samples come from same population under confident coefficient a or not, by which we can realize an analysis at both macroscopic and microcosmic levels, as an important similar analytical method for medical theoretical research.

This study was aimed to analyze characteristics of Chinese Materia Medica ( CMM ) preparations in order to identify the long-term development direction of this discipline and suggest key questions and strategies to solve the problems. According to the development track of CMM preparation, traditional Chinese medicine (TCM) basic theories and modern new drug research techniques were combined with the author's experiences on modernization study of TCM. This article discussed key issues of CMM preparation development direction, characteristics and is-sues need to be solved and their countermeasures. The results showed that the development direction for CMM preparation discipline should entirety unify CMM preparation system. The medical resource should be convenient which include animal, plant and mineral products. The single determinacy (effectiveness, stability and controlled) and compatibility (prediction, optimization and lowest toxin) will be applied in the guidance of CMM preparation system. In order to achieve goals mentioned above, key issues need to be solved are efficiency categories for in-gredients, genetical stabilities and one sampling charge, emigration rules of properties among ingredients, the ki-netic and stable rules of ingredient extraction, controlled rules for integral models or for disorder and torrent, e-valuation rules in vivo and in vitro, microscopic and macroscopic qualities, determinacy for single administration and compatibility for combination applications. It was concluded that the CMM preparation is a series of integral unified effective ingredient preparations that behave the determinacy for single administration and compatibility for combination applications.

OBJECTIVETo study on the differences of metabolites in the blood of rats after injection or oral administration of volatile oil in Houttuyniae Herba and of 2-undecanone in order to validate hypothesis of network compatability and to establish the theoretical foundation of elucidating metabolic mechanism for multiple constituents in Chinese Material.

METHODA gas chromatography-mass spectrometry method was employed for qualitative determination of the metabolites in blood of rats by injection or oral administration of volatile oil in Houttuyniae Herba and of 2-undecanone, which were compared with the differences between binary two drugs as well as two administration.

RESULTThere were 45 kinds of ingredients in volatile oil for original materials for Houttuyniae Herba, and 53, 69 kinds of metabolites were detected in blood of rats for oral administration of volatile oil in Houttuyniae Herba, and 2-undecanone, respectively, whereas 52, 42 kinds of metabolites were detected for injection administration. Although there were various constitutes, i. e. single versus multiple ingredients, administrated by various ways, i. e. oral versus injection, the metabolites were so similar with each manners, in which alpha-pinene and beta-myrcene occurred in two constitute forms and two administrations, while there were 18, 13 kinds of ingredients for oral or injection administration of volatile oil in Houttuyniae Herba, i. e. 34%, 25% of total ingredients, respectively, and 17, 15 kinds of ingredients, i. e. 24.6%, 35.7% for that of, 2-undecanone, respectively, on average of 29.8% that suggested one of third as co-metabolites.

CONCLUSIONThere are network compatibility existed in metabolism of the houttuynia volatile oil in rats, and similar metabolic pathways in accordance with original plant, among their ingredients no matter alone or multiple constitute forms and oral or injection administration.

Administration, Oral ; Animals ; Gas Chromatography-Mass Spectrometry ; Herb-Drug Interactions ; Houttuynia ; chemistry ; Injections, Intravenous ; Ketones ; administration & dosage ; pharmacokinetics ; Oils, Volatile ; administration & dosage ; pharmacokinetics ; Plants, Medicinal ; chemistry ; Rats

OBJECTIVETo study on the differences between chromatopharmacokinetics (pharmacokinetics with fingerprint chromatography) and chromatopharmacodynamics (pharmacodynamics with fingerprint chromatography) of Chinese materia medica formulae to answer the question whether the pharmacokinetic parameters of multiple composites can be utilized to guide the medication of multiple composites.

METHODOn the base of established four chromatopharmacology (pharmacology with chromatographic fingerprint), the pharmacokinetics, and pharmacodynamics were analyzed comparably on their mathematical model and parameter definition.

RESULTOn the basis of quantitative pharmacology, the function expressions and total statistical parameters, such as total zero moment, total first moment, total second moment of the pharmacokinetics, and pharmacodynamics were analyzed to the common expressions and elucidated results for single and multiple components in Chinese materia medica formulae. Total quantitative pharmacokinetic, i.e., chromatopharmacokinetic parameter were decided by each component pharmacokinetic parameters, whereas the total quantitative pharmacodynamic, i.e., chromatopharmacodynamic parameter were decided by both of pharmacokinetic and pharmacodynamic parameters of each components. The pharmacokinetic parameters were corresponded to pharmacodynamic parameters with an existing stable effective coefficient when the constitutive ratio of each composite was a constant.

CONCLUSIONThe effects of Chinese materia medica were all controlled by pharmacokinetic and pharmacodynamic coefficient. It is a special case that the pharmacokinetic parameter could independently guide the clinical medication for single component whereas the chromatopharmacokinetic parameters are not applied to the multiple drug combination system, and not be used to solve problems of chromatopharmacokinetic of Chinese materia medica formulae.

Chromatography ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Materia Medica ; chemistry