1.Interpretation of the Guideline for Multi-dimensional and Multi-criteria Comprehensive Evaluation of Chinese Patent Medicine:weighting of evaluation indicators
Haili ZHANG ; Bin LIU ; Weili WANG ; Wenjie CAO ; Yijiu YANG ; Ziteng HU ; Yaxin CHEN ; Ning LIANG ; Huizhen LI ; Qianzi CHE ; Xingyu ZONG ; Zhao CHEN ; Yanping WANG ; Nannan SHI
China Pharmacy 2024;35(7):773-777
OBJECTIVE To provide a detailed report and interpretation of the method and results for determining the weights of the technical indicators from the “multi-dimensional and multi-criteria comprehensive evaluation index system (first edition)” stated in Guideline for Multi-dimensional and Multi-criteria Comprehensive Evaluation of Chinese Patent Medicine. METHODS Normalization calculations were performed on the comprehensive weight values calculated by the analytic hierarchy process and expert weighting method to obtain the objective weights of the indicators. RESULTS The weight results of the six primary dimensions in the current comprehensive evaluation indicator system of Chinese patent medicine showed effectiveness dimension> safety dimension>standard dimension>application dimension>scientific dimension>economic dimension, with weight values of 0.281 0, 0.268 5, 0.195 8, 0.107 3, 0.096 1 and 0.051 3 respectively, consistent with the results of most researches currently. CONCLUSIONS The process of weight determination in this indicator system is scientifically reasonable, with clear methods and clear interpretations, and is worthy of further optimization and widespread application.
2.Rapid Analysis of Chemical Constituents in Shenxianshengmai Oral Liquid by UHPLC-Q Exactive Focus MS/MS
Shiyu ZONG ; Zhibiao DI ; Qiqi LIU ; Zhuangzhuang HUANG ; Hong ZHANG ; Ye LI ; Feng LIU ; Yang LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):218-228
Objective To explore the chemical basis of Shenxianshengmai oral liquid.Method UHPLC-Q Exactive Focus MS/MS technology was used to identify the chemical components of Shenxianshengmai oral liquid.The chromatographic separation was performed on a Thermo Accucore aQ C18 column(150 mm×2.1 mm,2.6 μm)with mobile phase gradient elution of 0.1%formic acid aqueous solution(A)and methanol(B)for 0-13 min,5%-60%B;13-27 min,60%-95%B;27-30 min,95%B,the flow rate was 0.3 mL·min-1,and the column temperature was at 30℃.The mass spectrometry was performed by heating electrospray ionization(H-ESI)with positive and negative ion scanning modes.The scanning range was m/z 120-1800,and the collision energies were 30 eV,50 eV and 70 eV.Result A total of 160 components were identified,including 29 flavonoids,24 organic acids,21 alkaloids,19 terpenoids,15 phenylpropanoids,12 saponins and 40 other components.Six chemical constituents(rutin,psoralenoside,isopsoralenoside,psoralen,isopsoralen and bakuchiol)were confirmed by comparison with reference substances.Conclusion In this study,an UHPLC-Q Exactive Focus MS/MS method has been established for accurate,rapid and systematic identification of the constituents in Shenxian Shengmai oral liquid,which provides an important basis for clarifying the chemical basis and quality control.
3.Screening of hub genes and pathways of idiopathic non-cirrhotic portal hypertension and prediction of traditional Chinese medicine
Yuepei LIU ; Ying ZONG ; Ping ZHANG ; Ranlian YANG ; Yilei LI
China Modern Doctor 2024;62(2):49-53,61
Objective To with analyzing the gene expression profile of idiopathic non-cirrhotic portal hypertension(INCPH)by bioinformatics methods,we may obtain its key genes and signaling pathways to explore the molecular mechanism of INCPH and predict the potential traditional Chinese medicine.Methods The gene microarray dataset GSE77627 on INCPH was downloaded from gene expression omnibus(GEO)database,the data were normalized and screened for differential genes(DEGs)of INCPH using R language,and all DEGs were analyzed for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment using Metascape database,and protein-protein interaction network was constructed by STRING database;meanwhile DEGs with the top 15 Degree values were screened as key genes using CytoHubba plugin.Subsequently,the key genes were mapped to each other with the medical ontology information retrieval platform(coremine medical)to screen potential Chinese herbal medicines for the treatment of INCPH with P<0.05,and the potent components that potential Chinese medicines have were screened from the TCMSP database,imported into Cytoscape software to construct a Chinese medicine correlation network map and predict the key targets.Results A total of 1880 DEGs were screened,including 1061 up-regulated and 819 down-regulated genes.DEGs were analyzed using the protein interaction database STRING and cytoHubba in Cytoscape software to obtain key genes,which were RPS27A,CDC42,EIF4E,MAPK1,PIK3R1,RPS6,RPS9,RPS8,RPL15,RPL27A,RPL24,RPL27,RPL26,RPL12 and MAPK14.The GO and KEGG analysis mainly involved gamete production and AGE-RAGE signaling pathway in INCPH.Conclusion The potential traditional Chinese medicines screened for INCPH are Ginseng Radix et Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Scutellariae Radix,etc,which may be a potential source of molecular drugs for the treatment of INCPH.
4.The expression of System Xc-/ GSH / GPX4 ferroptosis pathway in peripheral blood mononuclear cells of rheumatoid arthritis patients and its effect on the secretion of inflammatory factors
Can Liu ; Wukai Ma ; Changming Chen ; Yang An ; Zong Jiang ; Hai Huang
Acta Universitatis Medicinalis Anhui 2024;59(1):64-70
Objective :
To investigate the expression of genes and proteins in the peripheral blood mononuclear cell ( PBMC) cystine / glutamate antiporter system (System Xc-) / glutathione ( GSH) / glutathione peroxidase 4 ( GPX4) ferroptosis pathway and its influence on inflammatory factors in patients with rheumatoid arthritis ( RA) .
Methods :
30 patients with RA and 30 healthy participants were enrolled.PBMCs were isolated using Ficoll-hypaque density gradient centrifugation.The cells were categorized into the healthy control,RA,ferroptosis inhibitor,ferroptosis in- ducer group.The cell viability was checked using the cell counting kit-8 ( CCK-8) method.Intracellular Fe2 + rela- tive fluorescence intensity and reactive oxygen species (ROS) levels were detected using the FerroOrange and Di- hydroethidium (DHE) fluorescent probes,respectively.Western blot and real-time quantitative PCR (qPCR) de- tected the expression of nuclear factor erythroid 2-related factor 2 ( Nrf2 ) ,solute carrier family 7 member 11 (SLC7A11) ,GPX4 proteins and mRNA.And the flow cytometry quantified the levels of tumor necrosis factor α (TNF-α) ,Interleukin (IL) -1,and IL-6 in the supernatant of each cell group.
Results :
Compared to the healthy control group,the RA group showed a significantly increased Fe2 + concentration and elevated ROS levels,reduced expression of Nrf2,SLC7A11 and GPX4 proteins and mRNA,and increased contents of TNF-α , IL-1 and IL-6 in PBMC supernatant,and the differences were statistically significant.The concentration of Fe2 + and ROS levels in the inhibitor group were lower than those in the RA group,the proteins expressions of Nrf2,SLC7A11 and GPX4 increased,the mRNA expressions of SLC7A11 and GPX4 increased,the content of IL-6 in the PBMC supernatant decreased but the content of TNF-α increased,and the differences were statistically significant.In contrast,the in- ducer group,when compared to the RA group,displayed increased ROS levels,reduced expression of SLC7A11 protein and mRNA and decreased expression of Nrf2 protein,and the contents of TNF-α and IL-1 in the PBMC su- pernatant increased,but the expression of GPX4 protein increased ,and the differences were statistically signifi- cant.The inducer group,compared to the RA group,showed increased cell viability,and the difference was statis-
tically significant (P<0. 000 1) .
Conclusion
The presence of ferroptosis in PBMC in RA patients,inhibiting or inducing PBMC ferroptosis in RA patients,will inhibit or promote the secretion of inflammatory factors.Inhibition of PBMC ferroptosis in RA patients may be helpful in the treatment of RA.
5.Research progress of Fengweiqi from"Qiyao"in Qinling Mountains
Shiyu ZONG ; Yang LIU ; Ye LI ; Shengnan JIANG ; Yuye AN ; Hong ZHANG
China Pharmacist 2024;27(1):171-176
Fengweiqi is the whole plant of Rhodiola dumulosa.It is a kind of natural and precious folk medicinal plant,mainly distributed on hillside rocks and crevasses at the altitude of 1 600-4 100 m.Fengweiqi mainly contains flavonoids,volatile oil,polysaccharides,various amino acids and trace elements.Modern pharmacological studies have shown that Fengweiqi has many significant pharmacological activities,such as anti-oxidation,anti-fatigue,anti-hypoxia and bacteriostasis.In this paper,the textual research,chemical constituents,pharmacological actions and artificial cultivation of Fengweiqi were reviewed in order to provide reference for further research and development of Fengweiqi resources.
6.Effect of Simo decoction on the regulation of NLRP3/Caspase-1/GSDMD signal pathway on duodenal microinflammation in rats with functional dyspepsia
Qin LIU ; Xiao-Yuan LIN ; Ling-Feng YANG ; Qian LUO ; Yun-Zong HAN ; Si-Qing CHEN ; Hai-Yue ZHANG ; Shu ZHOU ; Sai-Nan ZHOU
The Chinese Journal of Clinical Pharmacology 2024;40(1):67-71
Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)%,(29.16±8.37)%,(48.77±6.10)%,(48.35±6.04)%,(48.20±3.49)%and(39.24±4.20)%;the small intestinal propulsion rates were(82.01±7.55)%,(41.95±9.53)%,(64.61±10.18)%,(75.04±9.76)%,(60.58±7.13)%and(45.89±7.40)%;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P<0.01 or P<0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.
7.Efficacy-driving Mechanism of Danhong Injection for Stable Angina Pectoris Based on Composition-activity Relationship of Target Modules
Siwei TIAN ; Wenjing ZONG ; Jun LIU ; Wei YANG ; Qikai NIU ; Siqi ZHANG ; Jing'ai WANG ; Huamin ZHANG ; Zhong WANG ; Bing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):121-128
ObjectiveTo explore the efficacy-driving mechanism of Danhong injection (DHI) in the treatment of stable angina pectoris (SAP) based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency (AF) in the Seattle Angina Questionnaire (SAQ) that was obtained in the previous clinical trial, the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source, and then weighted gene co-expression network analysis (WGCNA) was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition, the On-modules (Z value below 0) were identified by Zsummary. The topological indicators such as density, centrality, and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level, respectively. In addition, the driver genes were screened by the personalized network control (PNC) algorithm. Finally, rat H9C2 cells were used to establish the model of hypoxia/reoxygenation (H/R), which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP, and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally, the driver genes, Klotho and fibroblast growth factor 22 (FGF22), in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data, this study determined the composition-activity relationship of target modules of DHI for SAP, which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.
8.The mechanism of imatinib on the regulation of lipopolysaccharide-induced acute lung injury in mice through the Nrf2/HO-1 signaling pathway
Duanyang LI ; Yaru LIU ; Zhiqing ZHOU ; Hong YANG ; Xiaolong ZONG ; Zhenyu LI
Chinese Journal of Emergency Medicine 2024;33(8):1104-1109
Objective:To evaluate the effect of imatinib on the endotoxemia-induced acute lung injury in mice.Methods:Sixty SPF male, 8-12 weeks, C57BL/6 mice were randomly (random) divided into 4 groups ( n=15 each): control group (group C), imatinib group (groupⅠ), endotoxemia group (group LPS) and imatinib + endotoxemia group (group I+LPS). The endotoxemia model of acute lung injury was established. After 24 hours, the mice were sacrificed. The pathological changes of lung tissues were evaluated, the lung injury scores were calculated, and the wet/dry ratios of lung tissues were measured. ELISA was used to detect the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. Detection kits were used to analyze the levels of malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in lung tissues; The expression levels of phosphorylated nuclear factor-kappa B (p-NF-κB), nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues were analyzed by western blotting. Results:Compared with the group C, the wet/dry (W/D) ratio of lungs [(3.47±0.41) vs. (5.58±0.47)], lung injury scores [(1.25±0.89) vs. (10.25±1.75)], and the levels of TNF-α and IL-6 in serum increased in the group LPS ( P<0.05). The levels of SOD, CAT, GSH and GSH/GSSG decreased, the level of MDA increased, and the expression of p-NF-κB, Nrf2 and HO-1 protein up-regulated ( P<0.05). Compared with the LPS group, the W/D ratio of lungs [(5.58±0.47) vs.(4.62±0.38)] and lung injury scores [(10.25±1.75) vs. (7.00±1.31)] in the I+LPS group decreased ( P<0.05), and the levels of TNF-α and IL-6 in the serum decreased ( P<0.05). In lung tissues, the levels of SOD, CAT, GSH and GSH/GSSG increased (all P<0.05), the level of MDA decreased (all P<0.05), the expression of p-NF-κB protein decreased, and the expression of Nrf2 and HO-1 protein increased ( P<0.05). Conclusions:Imatinib improves sepsis-induced acute lung injury in mice, and the mechanism of actions behind may be related to the inhibition of oxidative stress.
9.Analysis of constituents absorbed into blood and brain from Zhishe Tongluo Capsules
Xiao-Yan ZHANG ; Yang LIU ; Xiao-Ting WANG ; Hai-Feng WANG ; Zhi-Biao DI ; Jian-Fang SONG ; Shi-Yu ZONG ; Hong ZHANG
Chinese Traditional Patent Medicine 2024;46(11):3579-3584
AIM To analyze the constituents absorbed into blood and brain from Zhishe Tongluo Capsules.METHODS Sixteen rats were randomly assigned into four groups and given intragastric administration(3.1 g/kg),after which the cerebral ischemia-reperfusion injury(MACO)model was established,the blood and brain tissues were collected,and UHPLC-Q Exactive Focus MS/MS was adopted in the identification of prototype constituents.RESULTS Total 70 constituents were identified,20 of which were found in the blood,mainly including flavonoids,tanshinones and Ligusticum chuanxiong phthalides,and 7 of them could enter the brain through blood-brain barrier.Compared with the normal administration group,the MACO administration group demonstrated added constituents absorbed into blood containing 3-hydroxybenzoic acid,calycosin-7-glucoside,curcumenol,senkyunolide B,dihydrotanshinone I and cryptotanshinone;removed constituents absorbed into brain containing puerarin,elemicin,sedanolide,and added those containing salvianolic acid A,senkyunolide I,dihydrotanshinone I in the left brain tissues(infarcted side).CONCLUSION The constituents absorbed into blood and brain from Zhishe Tongluo Capsules,along with the enhanced absorptions of phthalides,quinones and phenols in MACO rats in vivo may be the active substances for treating cerebral infarction.
10.Long-term efficacy of oblique lateral interbody fusion combined with vertebral screw fixation for the treatment of lumbar specific infection
Wen-Hui ZHANG ; Yang-Yang DOU ; Feng-Guang YANG ; Zong-Ru HE ; Yu-Ping YANG ; Li-Zhen FAN ; Qing-Hao CHENG ; Jie LIU ; Hui-Ping TAI
China Journal of Orthopaedics and Traumatology 2024;37(9):893-898
Objective To explore medium and long term efficacy of oblique lateral interbody fusion(OLIF)in treating lumbar specific infection.Methods From October 2017 to January 2021,24 patients with lumbar specific infection were treated by OLIF combined with vertebral screw internal fixation,including 15 males and 9 females,aged from 27 to 61 years old with an average of(43.0±15.0)years old;the courses of disease ranged from 6 to 24 months with an average of(14.0±7.0)months;7 patients with L2-L3,12 patients with L3-L4 and 5 patients with L4-L5;19 patients with tuberculosis infection and 5 patients with brucella infection.The amount of intraoperative blood loss,operative time and complications were recorded,and erythro-cyte sedimentation rate(ESR),C-reactive protein(CRP),visual analogue scale(VAS),Japanese Orthopaedic Association(JOA)score and American Spinal Injury Association(ASIA)rating were compared before and one month after opertaion.Re-sults All patients were followed up from 9 to 24 months with an average of(13.0±6.0)months.Operative time was(132.5±21.4)min,and intraoperative blood loss was(227.3±43.1)ml.ESR and CRP were decreased from(82.34±18.62)mmol·h-1 and(53.08±21.84)mg·L-1 before operation to(33.52±17.31)mmol·h-1 and(15.48±8.36)mg·L-1 at one month after opera-tion,respectively(P<0.05).VAS was decreased from(7.52±1.36)before opertaion to(1.74±0.87)at one month after opera-tion(P<0.05).JOA was increased from(17.86±3.95)before operation to(24.72±3.19)at one month after operation(P<0.05).Four patients had neurological symptoms before operation,and were classified to grade D according to ASIA classifica-tion,who were recovered to grade E at 1 month after operation.One patient was suffered from psoas major muscle injury after operation,and returned to normal at 3 weeks.One patient was suffered from abdominal distension and difficulty in defecation,and relieved after gastrointestinal decompression and enema.No complications such as abdominal organ injury and poor wound healing occurred in all patients.Conclusion OLIF combined with vertebral screw internal fixation is a new minimally invasive surgical method for the treatment of lumbar specific infection,especially the lesion located on the middle lumbar vertebra.It has advantages of less trauma,short operation time,less blood loss,convenient operation,complete removal of the lesion,safety and effectiveness,and has good medium-and long-term efficacy for lumbar specific infection.


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