Potential components and mechanism of Liangxue Tuezi Mixture in treating Henoch-Schönlein purpura based on network pharmacology and metabolomics / 中国中药杂志

Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.

Study of incubation period of infection with 2019-nCoV Omicron variant BA.5.1.3 / 中华流行病学杂志

Objective: To study the incubation period of the infection with 2019-nCoV Omicron variant BA.5.1.3. Methods: Based on the epidemiological survey data of 315 COVID-19 cases and the characteristics of interval censored data structure, log-normal distribution and Gamma distribution were used to estimate the incubation. Bayes estimation was performed for the parameters of each distribution function using discrete time Markov chain Monte Carlo algorithm. Results: The mean age of the 315 COVID-19 cases was (42.01±16.54) years, and men accounted for 30.16%. A total of 156 cases with mean age of (41.65±16.32) years reported the times when symptoms occurred. The log-normal distribution and Gamma distribution indicated that the M (Q1, Q3) of the incubation period from exposure to symptom onset was 2.53 (1.86, 3.44) days and 2.64 (1.91, 3.52) days, respectively, and the M (Q1, Q3) of the incubation period from exposure to the first positive nucleic acid detection was 2.45 (1.76, 3.40) days and 2.57 (1.81, 3.52) days, respectively. Conclusions: The incubation period by Bayes estimation based on log-normal distribution and Gamma distribution, respectively, was similar to each other, and the best distribution of incubation period was Gamma distribution, the difference between the incubation period from exposure to the first positive nucleic acid detection and the incubation period from exposure to symptom onset was small. The median of incubation period of infection caused by Omicron variant BA.5.1.3 was shorter than those of previous Omicron variants.

Study on the objectivity and biological mechanism of Psoralea corylifolia Linn.'s 'Great dryness damages the liver' / 药学学报

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Effect of Shaoyaotang on Inflammatory Cytokines and Intestinal Flora in Rats with Dampness-heat Diarrhea / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Shaoyaotang on diarrhea， inflammation， and intestinal flora in rats with dampness-heat diarrhea and explore the mechanism of therapeutic principle "treating incontinent syndrome with dredging method" of Shaoyaotang. MethodThe dampness-heat diarrhea model was induced by high temperature， high humidity， high sugar and fat diet， and pathogenic factors. The rats were divided into normal group， model group （normal saline）， Shaoyaotang group （5.62 g·kg-1）， Rhei Radix et Rhizoma （RRER）-free Shaoyaotang group （5.15 g·kg-1）， and RRER group （0.01 g·kg-1）. The rats were treated correspondingly for five days， twice a day in the morning and evening. The diarrhea index was used to evaluate the antidiarrheal effect of each group three hours after the administration in the evening. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-2， and IL-6 in the serum were detected by enzyme-linked immunosorbent assay （ELISA） three hours after the last administration. The structure of intestinal flora in feces was characterized by 16sDNA. ResultCompared with the model group， the Shaoyaotang group， the RRER-free Shaoyaotang group， and the RRER group showed reduced diarrhea index （P<0.01）， with the onset rates ranking as the Shaoyaotang group>the RRER-free Shaoyaotang group>the RRER group. Those three groups with drug intervention all showed decreased levels of inflammatory factors （P<0.01）， especially the Shaoyaotang group， and no significant difference was observed between the RRER group and the RRER-free Shaoyaotang group. The abundance of pathogenic bacteria and conditioned pathogens （e.g. Escherichia-Shigella， Prevotella， Enterorhabdus， and Bacteroides） was reduced and the proliferation of probiotics （such as Ruminococcus， Turicibacter， and Lachnospiraceae） was increased in the groups with drug intervention （P<0.01）. For the structure of intestinal flora， the RRER group and the Shaoyaotang group were close to the normal group， and the RRER-free Shaoyaotang group was different from the other three groups （P<0.01）. ConclusionShaoyaotang can improve the outcome of rats with dampness-heat diarrhea through anti-inflammation and regulation of intestinal flora disorders. RRER in the prescription plays a key role in reducing the abundance of harmful bacteria and promoting the proliferation of probiotics， which is the key of Shaoyaotang in promoting the re-balance of intestinal flora. It also confirms the scientificity of treating dampness-heat diarrhea with RRER following the therapeutic principle "treating incontinent syndrome with dredging method".

Serum metabolomics of chronic obstructive pulmonary disease with lung-Qi deficiency syndrome / 中国中药杂志

The present study analyzed the potential biomarkers of chronic obstructive pulmonary disease(COPD) with lung-Qi deficiency syndrome by non-targeted metabolomics and explored the biological basis of this syndrome. Blood samples of 96 COPD patients with lung-Qi deficiency syndrome(COPD with lung-Qi deficiency syndrome group) and 106 healthy people(healthy control group) were collected, and the metabolic profiles of both groups were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Multivariate statistical analysis and differential metabolite screening were carried out by using Progenesis QI and Simca-P. Metabolic pathways were constructed through the MetaboAnalyst. Seven potential biomarkers, such as L-cystathionine, protoporphyrinogen Ⅸ, and citalopram aldehyde, were identified. Compared with the results in the healthy control group, the content of citalopram aldehyde, N1-methyl-2-pyridone-5-carboxamide, and 11β,17β-dihydroxy-4-androsten-3-one was significantly up-regulated, while that of the other four compounds such as L-cystathionine, dihydrotestosterone, protoporphyrinogen Ⅸ, and D-urobilinogen was down-regulated. These potential biomarkers involved six metabolic pathways, including cysteine and methionine metabolism, porphyrin and chlorophyll metabolism, drug metabolism of cytochrome P450, steroid hormone biosynthesis, glycine, serine, and threonine metabolism, and nicotinate and nicotinamide meta-bolism. This study is expected to provide a certain scientific basis for the research on traditional Chinese medicine syndrome of COPD with lung-Qi deficiency syndrome from the molecular biology level.

Study on alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury based on network pharmacology and cell experiments / 中国中药杂志

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.

Effects of colloid preload on the incidence of hypotension in spinal anesthesia for cesarean section: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Hypotension is a common complication caused by spinal anesthesia (SA), which may have adverse impacts on the condition of the parturient and fetus. Liquid infusion was found to be relatively effective for reducing the incidence of hypotension. However, the question of whether colloid preload can optimize hemodynamic variables in the cesarean section remains controversial. This study aims to determine the effects of colloid preload on the incidence of hypotension induced by SA in elective cesarean section.@*METHODS@#Related keywords were searched on PubMed, EMBASE, and Cochrane Library from inception dates to May 2020. Studies included were evaluated for eligibility and quality. The primary outcome was the intra-operative incidence of hypotension and severe hypotension. The secondary outcomes included the lowest intra-operative systolic blood pressure, the maximal intra-operative heart rate, the intra-operative needs of ephedrine and phenylephrine, the incidence of maternal nausea and/or vomiting, and neonatal outcomes (umbilical artery pH and Apgar scores). Apart from the above, RevMan 5.3 was used for the data analysis.@*RESULTS@#Altogether nine randomized controlled trials were included in the meta-analysis. There were no significant differences in the incidence of intra-operative hypotension, severe hypotension, or neonatal outcomes between the colloid preload group and control group, except for the umbilical artery pH.@*CONCLUSION@#This meta-analysis suggests that colloid preload does not significantly reduce the incidence of hypotension associated with SA in elective cesarean section.

Screening of serum susceptibility biomarkers in patients with mild liver function abnormalities based on non-targeted metabolomics / 中国中药杂志

In the present study,non-targeted metabolomics technique was used to screen potentially susceptibility biomarkers in patients with mild liver function abnormalities during long-term use of Chinese herbal compound. According to the inclusion and exclusion criteria,we collected 7 cases of patients with abnormal liver function during the period of complete taking Chinese herbal medicine( 60 days),and 18 cases of patients with normal liver function in re-examination from the reproductive medicine center in our hospital. Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF/MS~E) technique combined with Progenesis QI software was used to analyze the differential biomarkers in serum of patients with wild liver function abnormalities and normal liver function. 11 potential biomarkers such as bilirubin,pantothenic acid,hippuric acid,sphingomyelin,palmitic acid,and oleic acid were tentatively identified. Metabolic disorders in patients with herbal-induced mild liver abnormality were mainly related to two pathways: pantothenic acid and coenzyme A biosynthesis and linoleic acid metabolism. It could provide a reference for the early warning of mild liver function abnormalities of patients that may be caused by long-term use of Chinese medicine compound in clinical application,and will lay a foundation for further understanding the endogenous substance changes in different levels of liver injury.

Comparative study on the effect of Danggui-Chuanxiong herb pair on vasoactive substances and adhesion molecules in the serum of acute blood stasis in rats using PLS-DA and multi-attribute comprehensive index methods / 药学学报

We evaluated the effects of Danggui-Chuanxiong (GX) herb pair with different proportions (1∶0, 3∶2, 1∶1, 2∶3, 0∶1) and preparation methods (water extract W, alcohol extract A, and water-alcohol extracts WA) on vasoactive substances and endothelial cell adhesion molecules in the serum of acute blood stasis in rats. An acute blood stasis model was co-replicated by ice water bath and subcutaneous injection of epinephrine hydrochloride in rats. The expressions of vasoactive substances (arachidonic acid metabolites, coagulation-fibrin system index) and adhesion molecules in the serum were detected by enzyme linked immunosorbent assay method; the Spearman method was used to analyze the correlation of those detection indicators; the partial least squares-discriminant analysis and multi-attribute comprehensive index method were used to comprehensively evaluate the total effect of GX herb pair samples with different proportions and preparation methods on vasoactive substances and adhesion molecules. The experimental scheme was approved by the Animal Experimental Ethics Committee of the First Affiliated Hospital of Henan University of Chinese Medicine. The results showed that GX 1∶1_WA had the strongest effect on the improvement of vasoactive substances and adhesion molecules in the serum of acute blood stasis in rats (the total effect value was 6.96). When extraction method was same, the overall effect of GX 1∶1 had better effect than that of other proportions; when the proportion of GX was same, the total effects of GX_WA and GX_A were better than GX_W. The combination of Danggui and Chuanxiong can significantly improve the expressions of vasoactive substances and adhesion molecules in the serum of blood stasis in rats. But the action strength of GX herb pairs was different when the proportions and preparations of GX herb pair were different. These findings provide a basis for clinical rational application of GX herb pair, and lay the foundation for in-depth research on GX herb pair for treatment of blood stasis related diseases.

Effects of propofol, dexmedetomidine, and midazolam on postoperative cognitive dysfunction in elderly patients: a randomized controlled preliminary trial / 中华医学杂志(英文版)

BACKGROUND@#Postoperative cognitive dysfunction (POCD) is a serious complication after surgery, especially in elderly patients. The anesthesia technique is a potentially modifiable risk factor for POCD. This study assessed the effects of dexmedetomidine, propofol or midazolam sedation on POCD in elderly patients who underwent hip or knee replacement under spinal anesthesia.@*METHODS@#The present study was a prospective randomized controlled preliminary trial. From July 2013 and December 2014, a total of 164 patients aged 65 years or older who underwent hip or knee arthroplasty at China-Japan Friendship Hospital and 41 non-surgical controls were included in this study. Patients were randomized in a 1:1:1 ratio to 3 sedative groups. All the patients received combined spinal-epidural anesthesia (CSEA) with midazolam, dexmedetomidine or propofol sedation. The sedative dose was adjusted to achieve light sedation (bispectral index[BIS] score between 70 and 85). All study participants and controls completed a battery of 5 neuropsychological tests before and 7 days after surgery. One year postoperatively, the patients and controls were interviewed over the telephone using the Montreal cognitive assessment 5-minute protocol.@*RESULTS@#In all, 60 of 164 patients (36.6%) were diagnosed with POCD 7 days postoperatively, POCD incidence in propofol group was significantly lower than that in dexmedetomidine and midazolam groups (18.2% vs. 40.0%, 51.9%, χ = 6.342 and 13.603, P = 0.012 and < 0.001). When the patients were re-tested 1 year postoperatively, the incidence of POCD was not significantly different among the 3 groups (14.0%, 10.6% vs. 14.9%, χ = 0.016 and 0.382, P = 0.899 and 0.536).@*CONCLUSION@#Among dexmedetomidine, propofol and midazolam sedation in elderly patients, propofol sedation shows a significant advantage in term of short-term POCD incidence.

Study on mechanism of Cuscutae Semen flavonoids in improving reproductive damage of Tripterygium Glycosides Tablets in rats based on high-throughput transcriptome sequencing / 中国中药杂志

Tripterygium Glycosides Tablets has good anti-inflammatory and immunomodulatory activities,but its reproductive damage is significant. Previous studies of the research group have found that Cuscutae Semen flavonoids can improve spermatogenic cell damage caused by Tripterygium Glycosides Tablets by regulating spermatogenic cell cycle,apoptosis and related protein expression,but the mechanism of action at the gene level is still unclear. In this study,Illumina high-throughput sequencing platform was applied in transcriptional sequencing of spermatogenic cells of rats after the intervention of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets. Differentially expressed genes were screened out and the GO enrichment and KEGG pathway analysis of differentially expressed genes were conducted to explore the mechanism of Cuscutae Semen flavonoids in improving reproductive injury caused by Tripterygium Glycosides Tablets. The results showed that 794 up-regulated genes and 491 down-regulated genes were screened in Tripterygium Glycosides Tablets group compared with the blank group. Compared with Tripterygium Glycosides Tablets,440 up-regulated genes and 784 down-regulated genes were screened in the Cuscutae Semen flavonoids+Tripterygium Glycosides Tablets group. Among them,the gene closely related to reproductive function is DNMT3 L. Analysis of GO function and KEGG signaling pathway enrichment showed that the above differentially expressed genes were mainly enriched in cell,cell process,catalytic activity,binding,ovarian steroid synthesis,thyroid hormone and other functions and pathways. The thyroid hormone signaling pathway was the common enrichment pathway of the two control groups. In a word,Cuscutae Semen flavonoids has a good treatment effect on male reproductive damage caused by Tripterygium Glycosides Tablets. The mechanism may be closely related to up-regulation of DNMT3 L genes and intervention of thyroid hormone signaling pathway. At the same time,the discovery of many different genes provides valuable information for study on the mechanism of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets compatibility decreasing toxicity and increasing efficiency.

Health Literacy and associated factors among primary school students in Shandong province / 中国学校卫生

Objective@#To understand the status of health literacy and its associated factors among primary school students in Shandong Province.@*Methods@#By using stratified cluster sampling method, 9 063 children in grade 1 to 3 from 5 cities in Shandong Province were investigated with self-designed questionnaire. Chi square and multivariate logistic regression were used to analyze associated factors for health literacy.@*Results@#Rate of proficient health literacy among grade 1-3 primary school students was 62.8%(5 689/9 063), with 75.6%(6 850/9 063), 56.3%(5 106/9 063) and 80.1%(7 261/9 063) in dimension of safety emergency, health care and disease prevention and control. Proficient health literacy was 47.7%(4 327/9 063), 88.3%(8 003/9 063) and 73.6%(6 672/9 063) in domain of health knowledge and concept, health behavior and health skills. Univariate analysis showed that the health literacy varied by gender, only-child in the family, grade, living area, cities, self-perceived academic performance, father educational attainment, mother educational attainment, father occupation and mother occupation(χ2=39.66, 161.09, 193.05, 89.23, 1 107.75, 196.35, 99.43, 74.39, 64.86, 16.70, P<0.01). Multivariate analysis found that gender, only-child in the family, grade, living area, city, self-perceived academic performance, father’ s occupation and educational attainment were positively associated with health literacy among elementary students.@*Conclusion@#High level of health literacy has been found among primary school students in Shandong Province, but varied in area and different demographic characteristics, which needs further specific intervention.

Effects of thoracic epidural administration of lidocaine on hemodynamic and arousal responses of double lumen tracheal intubation during induction of anesthesia / 北京大学学报(医学版)

OBJECTIVE@#To compare the effects of thoracic epidural administration of lidocaine on hemodynamic and arousal responses of double lumen tracheal intubation during induction of anesthesia.@*METHODS@#In the study, 40 patients with American Society of Anesthesiologists (ASA) physical statuses I-II, aged 19-66 years, scheduled for elective thoracic surgeries under general anesthesia requiring orotracheal intubation were allocated to either the double-lumen endobronchial intubation (T group) or double-lumen endobronchial intubation after epidural administration of lidocaine (E group). After an intravenous anesthetic induction, the orotracheal double-lumen intubation was performed using a Macintosh direct laryngoscopy (MDLS), respectively. Invasive blood pressure (BP), heart rate (HR) and bispectral index (BIS) were recorded before and after anesthetic induction, immediately after intubation and 5 minutes after intubation with 1-minute interval and the intubation time also noted. The rate pressure product (RPP) was calculated.@*RESULTS@#After anesthetic induction, BP and RPP in the two groups decreased significantly compared with their preinduction values. In comparison with their postinduction values, the orotracheal intubation in the two groups caused significant increases in BPs, HRs and RPP. In comparison with their preinduction values, BPs decreased significantly in E group, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) increased significantly and lasted for 1 min in T group. The HRs of both groups after intubation were significantly higher than their baseline values , and increased in HR and lasted for 1 min and 4 min in E group and T group, respectively. SBP, DBP, MAP, HR and RPP after intubation in T group were significantly higher than those of E group during the observation period. The values of BIS were similar between both the groups. In T group, the incidences of SBP percent increased>30% of the baseline value and RPP more than 22 000 were significantly higher than in E group. None of the patients in group E had SBP more than 130% of the baseline value and RPP more than 22 000.@*CONCLUSION@#During double-lumen endobronchial intubation, epidural administration of lidocaine can provide less hemodynamic response and similar arousal response.

Cytokine analysis of Zhuangguguanjie wan-induced idiosyncratic liver injury based on mathematical modeling / 药学学报

In this study, we used a mathematic-based modeling system to screen the cytokines that are sensitive to Zhuangguguanjie wan (ZGW)-induced idiosyncratic liver injury. The values of 27 cytokines were used as the data source in rat liver of lipopolysaccharide (LPS) + ZGW group. The alanine aminotransferase (ALT) activity value of liver function indexes was used as the outcome evaluation index of liver injury. Cytokines of ZGW-induced idiosyncratic liver injury were screened using Logistic regression, random forest method, LASSO Logistics regression and method of combining rule discovery algorithm with LASSO, and cytokines filtered out were revalued in THP1 macrophage. Susceptible cytokine combinations:interleukin-1β (IL-1β), epidermal growth factor (EGF) and interleukin-18 (IL-18) closely related to ZGW-induced idiosyncratic liver injury were obtained after preliminary screening analysis. The result of revalued in THP1 showed that the ethanolic extract of ZGW (EtZ) combined with IL-1β or IL-18 synergistically enhanced tumor necrosis factor-α (TNF-α) secretion in THP1 macrophage, and EtZ combined with IL-1β significantly enhanced interleukin-6 (IL-6) secretion in THP1 macrophage, but EtZ combined with EGF markedly inhibited IL-6 secretion in THP1 macrophage. The results suggest that the sensitive cytokines that can be characterized in the ZGW-induced idiosyncratic liver injury are IL-1β and IL-18, which provides a basis for screening the ZGW-induced idiosyncratic liver injury patients, and a new experimental evidence for clinical safety medication and risk prevention of ZGW.

Quality consistency evaluation of Fuzi formula granules using determination of multi-component contents by HPLC-MS/MS method / 中国中药杂志

To establish HPLC-MS/MS method for simultaneous determination of 14 toxic or active components in Fuzi formula granules, and further analyze the quality consistency of 29 batches of formula granules by considering the cluster analysis (CA), principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) and other chemometrics methods. Phenomenonex Gemini C18 column (4.6 mm×150 mm, 5 μm) was used with 0.1% formic acid solution (A) -acetonitrile (B) as the mobile phase. The mass spectrum was scanned by ESI⁺ multiple reaction monitoring (MRM) mode. The contents of aconitine, mesaconitine, hypaconitine, Indaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconitine, aconine, fuziline, neoline, talatisamine, songorine, higenamine and salsoline were determined. The results showed that 14 compounds had a good linear relationship within their respective concentration range (R²>0.990 0). The limit of quantification was 2.07-7.71 mg·L⁻¹, and the average recovery was 96.07%-102.2%. The content determination results demonstrated that all batches of Fuzi formula granules had very low hypertoxic ingredients and high safety, while the content of active ingredients was greatly different. CA and PCA results showed that there were significant differences in the formula granules between two manufacturers; even though the different batches of samples from the same manufacturer had certain differences, but the difference in manufacturer A was less than that of B. Further PLS-DA showed that the content of cardiotonic substance salsola in the formula granules from manufacturer A was generally higher, while the contents of analgesic and anti-inflammatory substances benzoylmesaconitine and fuziline were generally lower than those in the products from manufacturer B. In conclusion, the safety of Fuzi formula granules was assured well, but the consistency needed to be improved. We recommend that all manufacturers establish strict standard for decoctions in the production process, and form a unified standard method to produce better Fuzi formula granules.

Study progress on chemical compounds, pharmacological action and clinical application of Naoxintong capsule / 中国中药杂志

Naoxintong capsule (NXTC) is an oral Chinese preparation produced by modern technology, derived from the classic preparation of Buyang Huanwu decoction which was recorded by WANG Qing-ren (Qing dynasty) in Yilingaicuo Juanxia Tanweilun. NXTC is composed of 16 herbs including insect herbs and some blood circulation herbs, with the effects of supplementing Qi and activating blood circulation, dispersing blood stasis and dredging collaterals. In clinical application, it is mainly used for stroke, cerebral infarction, vascular dementia, ischemic cerebrovascular disease, transient ischemic attack, coronary heart disease, angina pectoris, ischemic cardiomyopathy, diabetic cardiomyopathy, myocardial infarction, chronic heart failure, chronic complications of diabetes, essential hypertension, hyperlipidemia and other cardiovascular and cerebrovascular diseases, and has achieved good therapeutic effect on above diseases or their concurrent diseases. Its clinical efficacy is mainly achieved through the improvement in related links of brain protection, neuroprotection, cardioprotection, hemorheology, et al. Nearly 200 chemical constituents identified in NXTC are important pharmacological basis for its functions. At present, however, most of its pharmacological basic researches are focused on plant herbs, and the three kinds of insect herbs remain to be further studied. The researches on clinical effectiveness are more comprehensive; the safety study of long-term application in real world is ongoing by our team, and its results are yet to be published after finishing the study. Through the systematic and comprehensive combing and elaboration of the research progresses on the chemical compositions, pharmacological action and clinical application of NXTC, it can provide a reference for the in-depth study of this preparation, with a great significance for the quality control, secondary development and internationalization promotion of NXTC.

Idiosyncratic hepatotoxicity evaluation of Zhuangguguanjie wan mediated by immune stress / 药学学报

On basis of the idiosyncratic lipopolysaccharide(LPS)-mediated hepatotoxicity model, liver injury induced by Zhuangguguanjie wan(ZGW)was evaluated, and the mechanism was explored. Idiosyncratic hepatotoxicity model was established in rats by injecting LPS at a dosage of 2.8 mg·kg-1. Rats were randomly divided into the normal control group, LPS group, ZGW group and LPS+ZGW group. Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities were analyzed in serum; pathological changes(HE staining)and the content of cytokines of liver were tested; and immune cell subpopulation ration were determined in blood and liver. Compared with the control group, the ZGW group and LPS group had no significant changes in ALT, AST and liver pathology(P> 0.05); while the ZGW+LPS group exhibited an elevation in ALT and AST(P< 0.05). Disorder of liver lobular arrangement and irregular island-like or massive necrosis of liver cells were observed in the group. Several cytokines in the liver were increased in LPS group and ZGW+LPS group(P< 0.05 or P< 0.01), and the level in ZGW+LPS group was higher than that of LPS group. Compared with the control group, the ratio of CD3+ T cell/lymphocyte of blood in LPS group was significantly decreased(P< 0.01); while the percentage of CD3+ T cells in the liver were significantly increased(P< 0.05). The contents of immune cells of blood had no significant changes between LPS group and ZGW+LPS group(P> 0.05). CD3+ T cell in the liver of ZGW+LPS group was significantly increased over the LPS group(P< 0.05). Aggregation or activity of CD3+ T cell was increased by ZGW combined with LPS. These results suggest that ZGW could promote T lymphocyte recruitment to liver under the immune activation state leading to inflammatory response, which may contribute to idiosyncratic liver injury.

Clinical application characteristics of Danggui-Chuanxiong herb pair in Chinese medicines on basis of real-world / 中国中药杂志

To analyze the clinical application characteristics of Danggui-Chuanxiong(DG-CX) herb pair in Chinese medicines on basis of real-world, and provide reference for explaining the inherent compatibility regularity and the relationship between clinical applications and disease species. From April 1, 2014 to June 30, 2014, a total of 8 792 prescriptions with both "DG"and "CX" in a large third-grade class-A traditional Chinese medicine(TCM) hospital were selected to establish the database for analyzing the ratio, dosage, and corresponding disease species of DG-CX herb pair. The results showed that, "DG-CX" with ratio "1∶1" had the highest frequency in clinical application(42.4%); the dosage was mainly of 15 g for both DG and CX; the disease species were mainly of encephalopathy and pulmonary diseases. "DG-CX" herb pairs with a ratio greater than "1∶1" accounted for 33.3% of all the prescriptions, and the ratio "3∶2" appeared to be most frequent among them; the dosage was mainly of 15 g for DG and and 10 g for CX; the disease species were mainly of encephalopathy diseases. "DG-CX" herb pairs with a ratio less than "1∶1" accounted for 24.3% of all the prescriptions, and the ratio "2∶3" appeared to be most frequent among them; the dosage was mainly of 10 g for DG and 15 g for CX; the disease species were mainly of encephalopathy diseases. Statistical method was applied to study the compatibility and application characteristics of Chinese herb pairs in clinical prescriptions, effectively discover the medication regularity, provide theoretical basis for clinical herbal prescriptions and provide scientific guidance and reliable data for modern research of Chinese herb pairs.

Effects of ferulic acid on antioxidant activity in Angelicae Sinensis Radix, Chuanxiong Rhizoma, and their combination / 中国天然药物

The present study aimed at exploring different roles of the same compound in different environment, using preparative HPLC, and the significance to investigating bio-active constituents in traditional Chinese medicine (TCM) on the basis of holism. In this study, the depletion of target component ferulic acid (FA) by using preparative HPLC followed by antioxidant activity testing was applied to investigate the roles of FA in Angelicae Sinensis Radix (DG), Chuanxiong Rhizoma (CX) and their combination (GX). The antioxidant activity was performed by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity testing. FA was successfully and exclusively depleted from DG, CX, and GX, respectively. By comparing the effects of the samples, it was found that FA was one of the main antioxidant constituents in DG, CX and GX, and the roles of FA were DG > CX > GX. Furthermore, the effects of FA varied at different doses in these herbs. This study provided a reliable and effective approach to clarifying the contribution of same compound in different TCMs to their bio-activities. The role of a constituent in different TCMs might be different, and a component with the same content might have different effects in different chemical environments. Furthermore, this study also suggested the potential utilization of preparative HPLC in the characterization of the roles of multi-ingredients in TCM.

Comparative analysis of the promoting blood effects of the combination of different proportions of danggui and honghua by the principal component analysis and multi-attribute comprehensive index methods / 药学学报

The combination of Danggui and Honghua (GH) is a popular herb pair commonly used in clinic for the treatment of blood stasis syndrome in China. To evaluate the activating blood circulation and dissipating blood stasis effects of the combination of different proportions of Danggui and Honghua on acute blood stasis rats, and optimize the proportion of GH to have the best activating blood circulation and dissipating blood stasis effect. Acute blood stasis rat model was induced by subcutaneous injection of adrenaline and ice water bath. The blood stasis rats were administrated intragastrically with GH (1 : 0, 4 : 1, 2 : 1, 3 : 2, 1 : 1, 2 : 3, 1: 2, 1 : 4 and 0 : 1) extracts. The whole blood viscosity (WBV), plasma viscosity (PV), and high shear whole blood relative index (HSWBRI), low shear whole blood relative index (LSWBRI), and erythrocyte aggregation index (EAI) were tested to observe the effects of GH on hemorheology of blood stasis rats. And the maximum aggregation induced by adenosine diphosphate (ADP) was tested to observe the effect of GH on platelet aggregation index of blood stasis rats. In addition, the prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and plasma fibrinogen (FIB) were tested to observe the effects of GH on blood coagulation function of blood stasis rats. Then principal component analysis and multi-attribute comprehensive index methods were both used to comprehensively evaluate the total activating blood circulation and dissipating blood stasis effects of GH. The results showed that the hemorheological indexes and coagulation parameters of model group both had significant differences with normal group. Compared with model group, GH (1 : 0, 4 : 1, 2: 1, 3 : 2, 1 : 1, 2 : 3, 1 : 2, 1 : 4 and 0 : 1) could improve all the blood hemorheology indexes and regulate part indexes of blood coagulation function and platelet aggregation in acute blood stasis rats. Based on principal component analysis and multi-attribute comprehensive index methods, GH 1 : 1 and GH 3 : 2 both had the best effect of blood circulation and dissipating blood stasis, and the effect of GH 1 : 1 was slightly better than GH 3 : 2. These results suggest that GH could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats. The optimized proportion of GH was consistent with regulations of medicine usage that GH 1 : 1 had the highest frequency used in traditional Chinese formulae. It could provide scientific basis for more effective application of the compatibility between Danggui and Honghua in modern clinic medicine.