Research on Preparation Process and Quality Evaluation of Traditional Chinese Medicine Dispensing Granules and Its Consistency with Traditional Decoction： A Review / 中国实验方剂学杂志

Traditional Chinese medicine dispensing granules（TCMDGs）is the new type of decoction pieces with the development of modernization of TCM， which has received mixed opinions since its practical application. In 2021， the national departments issued Announcement on Ending the Pilot Work of TCMDGs， marking the end of the 28-year pilot work of TCMDGs， and eligible TCM enterprises can produce TCMDGs after filing. However， this does not mean that the preparation process， quality standard and efficacy research of TCMDGs have been developed and matured， on the contrary， there are still some problems that need to be solved and gradually improved. For example， in the production process， there are problems such as unclear， unified and non-standardized preparation parameters. In terms of quality control， there are some problems such as lack of producing area regulation， variety selection and processing specification. In terms of consistency evaluation with traditional decoction， there are problems such as unclear relationship between the chemical constituents and pharmacological effects of the two. Therefore， in view of some prominent problems of TCMDGs at present， this paper takes the published literature as the main data source and combines the specific requirements of the code or technical standards such as the 2020 edition of Chinese Pharmacopoeia， Publicity of the Unified Standard on the Varieties of TCMDGs， Quality Control and Standard Formulation Technical Requirements of TCMDGs. The production process of TCMDGs， the origin and variety of raw materials， the processing of decoction pieces， the quality control standard and the consistency evaluation of formula granules and traditional decoction were sorted out and visualized by literature mining， data analysis and list comparison. Based on the analysis results， the following suggestions were made. In terms of preparation process， the completeness and standardization of process parameters should be strengthened. In terms of quality evaluation， attention should be paid to the relationship between the authenticity， variety， processing and quality of medicinal materials. In the consistency evaluation of formula granules and traditional decoction， the deep difference and mechanism between TCMDGs and traditional decoction were discussed by combining structural Chinese medicine， quality marker（Q-Marker） theory and physicochemical characterization， so as to provide reference for the application and development of TCMDGs.

Correlation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with lower extremity arterial disease in type 2 diabetes mellitus / 中国医师杂志

Objective:To explore the correlation of neutrophil-to-lymphocyte ratio(NLR) and platelet-to-lymphocyte ratio (PLR) with lower extremity arterial disease (LEAD) in type 2 diabetes mellitus (T2DM).Methods:A total of 314 T2DM patients hospitalized in Tengzhou Central People′s Hospital from January 2018 to December 2019 were collected and divided into LEAD group (168 cases) and control group (146 cases) according to the results of color Doppler ultrasound of lower extremity arteries. General clinical data were collected. Fasting venous blood samples were collected to detect blood routine and biochemical indicators. NLR and PLR values were calculated. Patients were divided into 4 groups according to the NLR and PLR quartiles. The differences of data in each group were analyzed; Spearman correlation was used to analyze the correlation between NLR, PLR and each index; The risk factors of LEAD in T2DM patients were analyzed by logistic regression. The receiver operating characteristic (ROC) curve was used to determine the efficiency of the model predicting LEAD in T2DM patients.Results:The age, white blood cells count (WBC), neutrophil count, NLR, PLR and C-reactive protein (CRP) in LEAD group were significantly higher than those in control group (all P<0.05). With the increase of NLR and PLR quartiles, the age, body mass index, WBC, neutrophils and platelets increased gradually ( P<0.05), and the lymphocytes decreased gradually ( P<0.05). Spearman correlation analysis showed that NLR and PLR were positively correlated with age, neutrophils and platelets (all P<0.01), but negatively correlated with lymphocytes (all P<0.01). Logistic regression analysis showed that age, NLR, PLR, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and CRP were the risk factors of LEAD in T2DM patients (all P<0.01). The area under the curve (AUC) of NLR, PLR, CRP and age were 0.813, 0.683, 0.668 and 0.630, respectively; The sensitivity was 82.49%, 84.37%, 72.58% and 62.87%, respectively. Conclusions:NLR and PLR are closely related to LEAD in T2DM patients. NLR is superior to PLR and CRP in the diagnosis of LEAD.

Improvement effects and mechanism of thalidomide on Alzheimer ’s disease model of Caenorhabditis elegans / 中国药房

OBJECTIVE To study the improvement effects and mechan ism of thalidomide on Alzheimer ’s disease （AD）model of Caenorhabditis elegans . METHODS In this study ，the BR 5270 strain of C. elegans was used as AD model and BR 5271 strain as the control. The effects of thalidomide （0.5，2.0，6.0，15.0 mg/mL）on the motility of BR 5270 strains of C. elegans were studied by the basal slowing response assay ；the effects of thalidomide （0.5，2.0，6.0，15.0 mg/mL）on the survival time of BR 5270 strain of C. elegans were studied by life assay ；the effects of thalidomide （0.5，2.0，6.0 mg/mL）on learning and memory ability of BR 5270 strain of C. elegans were studied by short-term and long-term learning and memory assay. RT-PCR technology was used to study the effects of thalidomide （0.5，2.0，6.0 mg/mL）on mRNA expression of phosphatidylinositol 3-kinase（PI3K）/protein kinase B （Akt）signal pathway related genes （Age-1，Akt-1，Gsk-3）and calpain homologous gene （Clp-1）in BR 5270 strain of C. elegans . RESULTS After the intervention of thalidomide ，oscillation times of BR 5270 strain of C. elegans increased significantly within 30 s （except for 0.5 mg/mL group ），and the 10％ of maximum life span was prolonged significantly （only 0.5 mg/mL group ）；the short-term and long-term learning indexes were improved significantly （only 6.0 mg/mL group ）；mRNA expression of Age-1 and Akt-1（except for 0.5，2.0 mg/mL groups ）were increased significantly ，mRNA expression of Gsk-3（except for 0.5 mg/mL group ） and Clp-1 were decreased （P＜0.05 or P＜0.01）. CONCLUSIONS Thalidomide can ameliorate the dyskinesia of AD model of C. elegans，prolong the lifespan of this strain ，and enhance its learning and memory ability. Its mechanism of action may be related to activation of PI 3K/Akt signaling pathway and inhibition of calpain.

Anti-aging Effect Study of Ethyl Acetate Extract from Folygonum multiflora on Caenorhabditis Elegans / 中国药房

OBJECTIVE:To study the lifespan effect of ethyl acetate extract from Polygonum multiflora(EPM)on caenorhab-ditis elegans,and to investigate its anti-aging effect. METHODS:EPM low-concentration,medium-concentration and high- concen-tration groups(25,37.5,50 mg/L,calculated by crude drug)and blank group(0 mg/L)were established to investigate the effects of EPM on the lifespan of caenorhabditis elegans. EPM group(37.5 mg/L)and blank group(0 mg/L)were established to perform re-productive test,acute heat stress test and acute oxidative stress test of caenorhabditis elegans. The effects of EPM on reproductive capacity and pressure stress of caenorhabditis elegans were investigated. RESULTS:The lifespan test,average lifespan of cae-norhabditis elegans in EPM low-concentration,medium-concentration and high-concentration groups were prolonged significantly, compared to blank group(P<0.05 or P<0.01),especially in EPM medium-concentration group. In reproductive test,the number of offspring of caenorhabditis elegans in EPM group on the second and third day were increased significantly,compared to blank group (P<0.05). In acute heat stress test and acute oxidative stress test,average survival time of caenorhabditis elegans in EPM group was prolonged significantly(P<0.05). CONCLUSIONS:37.5 mg/L EPM can retard the aging process of caenorhabditis ele-gans and doesn’t damage the reproductive capacity.

Clinical research of Xin bao drug edible of herbal medicine granule on coronary heart disease with heat-blood stagnation syndrome / 重庆医学

Objective To observe the effect of drug edible of herbal medicine granule on vascular endothelial function in patients with coronary heart disease(CHD).Methods A total of 200 cases featuring with cardiovascular blood stasis were chosen from patients who were diagnosed with CHD in Zhengzhou hospital of traditional Chinese medicine from January 2015 to January 2016.All cases were divided into observation group(n=98)and control group(n=102).The observation group was given Xin bao drug edible of herbal medicine granule and conventional drugs,and the control group was given conventional drugs.After 8 weeks of observation,the levels of endothelin(ET-1),nitric oxide(NO)and angiotensin Ⅱ(AngⅡ)were measured by enzyme-linked immunosorbent assay(ELISA).The serum levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL),and TCM clinical symptom score were compared between the two groups.Results The level of TC of the control group was decreased after treatment(P<0.05);the levels of TC,TG and LDL in the observation group were lower than those in the control group(P<0.05).After treatment,the levels of NO,ET-1,Ang-Ⅱ and FMD in the observation group were significantly different from those before treatment(P<0.05).The levels of NO and FMD in the observation group were higher than those in the control group,and the levels of ET-1 and Ang-Ⅱ were lower than those in the control group(P<0.05).After treatment,the scores of TCM clinical symptoms in the observation group were lower than those before treatment(P<0.05).Compared with the control group,the total score of palpitations,the times of shortness of breath and clinical symptoms were lower than those in the observation group(P<0.05).Conclusion Xin bao drug edible of herbal medicine granule could relieve coronary heart disease blood stasis type of patients with vascular tension,reduce its endothelial cell damage and improve its clinical symptoms.

Role of Rab proteins in glucose transporter 4 translocation:research advances / 中国药理学与毒理学杂志

Insulins maintain blood glucose homeostasis in the body by stimulating glucose uptake into muscle and adipose tissues through glucose transporter type 4 (GLUT4)translocation. Recent studies have showed that Rab proteins,as a key regulatory factor for the translocation of GLUT4 to the cell membrane,participate in the formation,translocation and fusion of GLUT4 vesicles. This paper describes several types Rab proteins and the Rab GTPase activating protein,protein kinase B substrate of 160 kU(AS160)in terms of regulatory mechanisms for GLUT4 translocation. Studies on the translocation mechanism by which GLUT4 is regulated by Rabs aim to explain the mechanism of insulin resistance in type 2 diabetes,and provide a new approach to diabetes.

Investigation on production process quality control of traditional Chinese medicine--Banlangen granule as an example / 中国中药杂志

For the quality management system of herbal medicines, intermediate and finished products it exists the " short board" effect of methodologies. Based on the concept of process control, new strategies and new methods of the production process quality control had been established with the consideration of the actual production of traditional Chinese medicine an the characteristics of Chinese medicine. Taking Banlangen granule as a practice example, which was effective and widespread application, character identification, determination of index components, chemical fingerprint and biometrics technology were sequentially used respectively to assess the quality of Banlangen herbal medicines, intermediate (water extraction and alcohol precipitation) and finished product. With the transfer rate of chemical information and biological potency as indicators, the effectiveness and transmission of the above different assessments and control methods had been researched. And ultimately, the process quality control methods of Banlangen granule, which were based on chemical composition analysis-biometric analysis, had been set up. It can not only validly solute the current status that there were many manufacturers varying quality of Banlangen granule, but also ensure and enhance its clinical efficacy. Furthermore it provided a foundation for the construction of the quality control of traditional Chinese medicine production process.

Agglutinated activity bioassay method for the determination of antivirus potency of Banlangen granula / 药学学报

To establish a bioassay method and quality standard of Banlangen granula, agglutinated activity assay was used in the analysis of the traditional Chinese medicine, Banlangen granula. It showed that masculined effect could be picked up effectively and the products quality of different pharmaceutical factories and different batch numbers from the same factory could be revealed conveniently, accurately, quickly and directly with this method (valence value was between 2 and 11). The established bioassay method had a good reproducibility with RSD = 2%. The dependablity of the activity of red cell agglutination and restrainting influenza virus NA was conspicuous (r2 = 0.878 3). In conclusion, this bioassay method is suitable to control and evaluate the quality of Banlangen granula. Thus the method may provide a simple and effective technique in supervising and examining the quality of other traditional Chinese medicine.

Hemagglutination activity of radix isatidis detected by microcalorimetry / 药学学报

In this study, microcalorimetry was adopted to establish a novel method for detecting the hemagglutination process of Radix Isatidis (Banlangen in Chinese, BLG), and to evaluate the hemagglutination activity diversity of BLG from various habitats. The hemagglutination biothermokinetics curves of positive reagent (phytohemagglutinin, PHA) and 8 batches BLG from different regions of the hemagglutination with 20% rabbit erythrocyte were recorded by microcalorimetry, then biothermokinetics parameters were abstracted, the hemagglutination utility of samples were calculated and analyzed by principal component analysis (PCA) and cluster analysis (CA), meanwhile the results were authenticated by micro-plate agglutination. It showed that the hemagglutination was an exothermic reaction, the reaction rate constant (k: 0.039-73.6 min(-1)), maximum reaction power (Pmax: -1 140.2 - 988.2 microW) and reaction enthalpy (Hi: -529.9 - 717.9 microJ) had good linear correlation with BLG extraction concentration (0.2-1.0 g mL(-1), r > 0.97), and PCA showed Pmax (531-1 335 microW) and Ht (585.2-989.2 microJ) could represent the hemagglutination activity diversity of BLG samples, just confirming with the results of micro-plate agglutination (the agglutination dilution was 3-11 respectively). According to the hemagglutination utility, the BLG samples from Good Agriculture Practice (GAP) regions, main producing area and general regions could be clustered correctly; meanwhile, the biothermokinetics curves with perfect distinctive fingerprint and specificity could give out more information for the quality control and evaluation for BLG. In conclusion, the microcalorimetry method established for detecting the hemagglutination activity of BLG samples on rabbit erythrocyte is sensitive and reliable, and could be adopted as an effective technique in detection aggulatination precisely, quantitatively and consecutively; and provide a novel approach for examining and evaluating quality for Chinese herbal medicine with aggulatinative activity such as BLG.

Application of bioassay in quality control of Chinese materia medica-taking Radix Isatidis as an example / 中国中药杂志

Bioassay, which construct the characteristics consistents with Chinese medical science, is the core mode and methods for the quality control of Chinese materia medica. Taking the bioassay of Radix Isatidis as an example, the contribution, status and application of bioassay in the quality control of Chinese materia medica were introduced in this article, and two key issue (the selection of reference and measurement methods) in the process of establishing bioassay were also explained. This article expects to provide a reference for the development and improvement of the bioassay of Chinese materia medica in a practical manipulation level.