1. Mechanism and experimental validation of Zukamu granules in treatment of bronchial asthma based on network pharmacology and molecular docking
Yan-Min HOU ; Li-Juan ZHANG ; Yu-Yao LI ; Wen-Xin ZHOU ; Hang-Yu WANG ; Jin-Hui WANG ; Ke ZHANG ; Mei XU ; Dong LIU ; Jin-Hui WANG
Chinese Pharmacological Bulletin 2024;40(2):363-371
Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I
2. Preparation of tripterygium glycoside nanoparticles and therapeutic effect on arthritis rats
Zhi-Rong WANG ; Man LI ; Zhen-Qiang ZHANG ; Min YAN ; Xiang-Xiang WU ; Hua-Hui ZENG
Chinese Pharmacological Bulletin 2024;40(1):125-132
Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.
3.Two new dalbergiphenols from Zhuang medicine Dalbergia rimosa Roxb
Cheng-sheng LU ; Wei-yu WANG ; Min ZHU ; Si-si QIN ; Zhao-hui LI ; Chen-yan LIANG ; Xu FENG ; Jian-hua WEI
Acta Pharmaceutica Sinica 2024;59(2):418-423
Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of
4.Clinical Observation on Acupuncture Combined with Guanxinning Tablets in the Treatment of Heart Vessel Obstruction Type of Chest Obstruction Syndrome
Rui LEI ; Ping YAN ; Hui-Min DING ; Hua YU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):937-943
Objective To observe the clinical efficacy of acupuncture combined with Guanxinning Tablets in the treatment of heart vessel obstruction type of chest obstruction syndrome.Methods Eighty patients with heart vessel obstruction type of chest obstruction syndrome were randomly divided into the observation group and the control group,with 40 cases in each group,the control group was given conventional western medicine treatment,the observation group was given acupuncture combined with Guanxinning Tablets on the basis of the treatment in the control group,and the patients in the two groups were treated continuously for 30 days.The clinical efficacy of the two groups was evaluated after 1 month of treatment.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes in the traditional Chinese medicine(TCM)scores,including chest tightness,palpitations,stabbing pains in the chest,and dark complexion,as well as the frequency and duration of angina pectoris were observed before and after the treatment in the two groups.The changes of serum monocyte chemotactic factor 1(MPC-1),hs-CRP,tumor necrosis factor α(TNF-α),mitogen-activated protein kinase(MAPK),and Toll-like receptor 4(TLR4)were observed before and after treatment in the two groups.Results(1)The total effective rate was 95.00%(38/40)in the observation group and 75.00%(30/40)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,the TCM syndrome scores of patients in the two groups,including chest tightness and palpitations,chest tingling,and dark complexion,were significantly improved,and the observation group was significantly superior to the control group in improving the TCM syndrome scores of chest tightness and palpitations,chest tingling,and dark complexion,and the difference was statistically significant(P<0.05).(3)After treatment,the frequency and duration of angina attacks in the two groups were significantly improved,and the observation group was significantly superior to the control group in improving the frequency and duration of angina attacks,and the difference was statistically significant(P<0.05).(4)After treatment,the serum hs-CRP,MPC-1,and TNF-α levels of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the serum hs-CRP,MPC-1 and TNF-α levels,and the difference was statistically significant(P<0.05).(5)After treatment,the serum MAPK and TLR4 levels of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving serum MAPK and TLR4 levels,and the difference was statistically significant(P<0.05).Conclusion Acupuncture combined with Guanxinning Tablets for the treatment of heart vessel obstruction type of chest obstruction syndrome can significantly improve the clinical symptoms of the patients,effectively alleviate the body's inflammatory response,reduce the level of serum MAPK and TLR4,and the clinical efficacy is remarkable.
5.Research on the mechanism of Danhong injection in the treatment of acute myocardial infarction based on network pharmacology and molecular docking
Chang-Hu KE ; Ya-Qing WU ; Hui-Min HUANG ; Hui YAN
The Chinese Journal of Clinical Pharmacology 2024;40(5):668-672
Objective To predict the mechanism of Danhong injection in acute myocardial infarction based on network pharmacology and molecular docking.Methods The chemical ingredients of Danhong injection were collected by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),while Swiss Target Prediction was used to predict the corresponding targets of ingredients.The targets of acute myocardial infarction were retrieved in human gene database(GeneCards),online Mendelian inheritance in man(OMIM)and gene-disease association database(DisGeNET).Venny 2.1 online software was used to obtain the common targets of drugs-disease,and then the"drug-compound-target-disease"network diagram was constructed by using the software Cytoscape 3.8.2.The STRING database was used to draw the protein-protein ineraction network,and the perform gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out through the database for annotation,visualization,and integrated discovery(DAVID),and the AutoDock platform was applied in verifying the molecular docking of active components and protein targets.Results The 63 active components of Danhong injection could regulate 137 targets and 132 pathways to treat acute myocardial infarction.Przewaquinone C,luteolin,baicalein,sclareol,kaempferol,quercetagetin and other active compounds,which could mediate C-type lectin receptor,tumor necrosis factor,endocrine resistance,prolactin,phosphatidylinositol-3-kinases-serine/threonine protein kinase,Janus-activated kinase singal transducers and activators of transcriprion and other signaling pathways through tumor necrosis factor,RAC-alpha serine/threo-nine protein kinase,interleukin-1 beta,steroid receptor coactivator,mitogen-activated protein kinase 3,signal transducer and activator of transcription 3 and other key target proteins.The result of molecular docking showed that the targets and the components had a certain degree of binding.Conclusion Danhong injection can participate in the treatment of acute myocardial infarction through multiple components,targets and pathways,which provides a theoretical basis for the clinical application of Danhong injection and the mechanism of its treatment of acute myocardial infarction.
6.Effects of liver-specific knockout of AMPKα on glycometabolism genes in mice
Hui-Ming ZHANG ; Qian GAO ; Yan-Bo HU ; Xiao-Ru ZHANG ; Zhong-Yue ZHANG ; Yan YANG ; Feng GAO ; Min-Jie WANG
The Chinese Journal of Clinical Pharmacology 2024;40(8):1184-1188
Objective To investigate the effects of liver-specific knockout of adenosine 5'-monophosphate-activated protein kinase α(AMPKα)on pancreatic function and glucose metabolism-related genes in mice.Methods AMPKα1/α2flox/flox mice were divided into blank group(common feed)and model group(60%high fat choline deficiency feet)with eight mice in each group,and another 8 AMPKα1/α2flox/flox/Alb-Cre+mice were divided into the knockout group(60%high fat choline deficiency feet).The kit detected the levels of blood lipids and liver function indexes.The differential genes in the mouse pancreas were detected by transcriptome sequencing.The expression of differential genes in mice was detected by real-time fluorescence quantitative polymerase chain reaction and Western blotting.Results The levels of triglyceride in the blank group,model group and knockout group were(0.94±0.11),(0.71±0.14)and(1.05±0.17)mmol·L-1;the levels of triglyceride and high-density lipoprotein were(1.62±0.07),(0.44±0.08)and(0.90±0.06)mmol·L-1;the levels of glutamic oxaloacetic transaminase were(7.02±5.87),(15.60±3.15)and(22.70±2.14)U·L-1;the levels of glutamic pyruvic transaminase were(14.56±11.55),(48.64±15.84)and(75.40±11.96)U·L-1;the expression levels of phosphoenolpyruvate carboxykinase 1(PCK1)mRNA were 1.00±0,1.37±0.25 and 0.31±0.18;the relative expression levels of PCK1 protein were 0.77±0.27,1.23±0.43 and 0.51±0.40,respectively.Significant differences existed in the above indexes between the knockout group and the model group(all P<0.05).Conclusion PCK1 gene may be an essential gene mediating the effect of liver AMPKα on islet function.
7.Clinical Effectiveness and Safety of Bairui Granules (百蕊颗粒) in Treating Patients with Acute Pharyngitis with Wind-Heat Syndrome: A Multi-Center, Double-Blind, Double-Simulation, Randomized Controlled Trial
Siming LIU ; Hui ZHOU ; Qiang LI ; Min ZHOU ; Qixiang WU ; Shanjun YANG ; Jun WANG ; Jingjing YUAN ; Ying ZHANG ; Ziqi ZHU ; Jingyi HU ; Shuang WU ; Mengting LI ; Zhanfeng YAN
Journal of Traditional Chinese Medicine 2024;65(11):1139-1145
ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules (百蕊颗粒) in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter, double-blind, double-simulation, randomised controlled trial was conducted, in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited, and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group, 108 cases were orally administered with Bairui Granules plus Reyanning Granules (热炎宁颗粒) simulant, and in the control group, 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days, with a follow-up visit on the 6th day. Full analysis set (FAS) analysis and per protocol set (PPS) were used for analysis, respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment; the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment, as well as the visual analogue score (VAS) of sore throat before treatment, every day during the treatment, and follow-up on day 6, and the traditional Chinese medicine (TCM) syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6, and the changes of vital signs, blood routine, urine routine, liver functions, kidney function, the adverse events before and after the treatment were recorded, and safety analysis set (SS) was analysed. Results162 patients entered the FAS and SS analyses, and 158 cases (105 cases in the trial group and 53 cases in the control group) entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% (87/108) in the trial group and 64.81% (35/54) in the control group, and the difference between groups was statistically significant (χ2 = 5.10, P = 0.0239). PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% (84/105) in the trial group and 64.15% (34/53) in the control group, and the difference between groups was statistically significant (χ2 =4.85, P = 0.0277). FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant (P>0.05). Compared with those before treatment, the VAS scores of sore throat were lower in both groups during treatment on day 2, 3, 4, 5, and follow-up on day 6 (P<0.01), but the difference between groups at each time point was not statistically significant (P>0.05). TCM syndrome scores of both groups at the follow-up were lower than that before treatment, and those of the trial group were lower than those of the control group (P<0.01). The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group (P<0.01). There was no significant difference in blood routine, urine routine, liver function, kidney function between groups before and after treatment (P>0.05), and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome, and it could significantly improve the clinical symptoms, accelerate the disappearance time of sore throat with good safety.
8.Association between high body fat mass and elevated blood pressure in children
YAN Yujiao, YANG Hui, CHENG Anlan, ZHAO Min, XI Bo
Chinese Journal of School Health 2024;45(10):1393-1398
Objective:
To examine the association between high body fat mass and elevated blood pressure in children,so as to provide scientific evidence for the prevention and treatment of childhood hypertension.
Methods:
Participants were recruited from the second follow up survey of the Huantai Childhood Cardiovascular Health Cohort Study conducted in 2021 in Huantai County, Zibo City, Shandong Province, China. A total of 1 266 children aged 10-15 years old were included. The study categorized fat mass (FM), fat mass percentage (FMP), fat mass index (FMI), subcutaneous fat mass (SFM), and visceral fat mass (VFM), respectively, into normal and elevated groups based on age and gender specific median values ( P 50 ) in the study population. The multivariate Logistic regression model was used to analyze the association between the status of body mass and elevated blood pressure. A restrictive cubic spline (RCS) model was used to examine the dose response relationship between the levels of body mass and elevated blood pressure.
Results:
The detection rates of elevated blood pressure in children with elevated FM, elevated FMP, elevated FMI, elevated SFM, and elevated VFM were all significantly higher than those in the normal group ( P <0.05). After adjusting for all potential covariates, compared to the normal group, elevated FM ( OR =4.51, 95% CI =3.28-6.28), elevated FMP ( OR =4.51, 95% CI =3.28-6.27), elevated FMI ( OR =4.40, 95% CI =3.20-6.12), elevated SFM ( OR =4.52, 95% CI =3.29- 6.30 ), and elevated VFM ( OR =4.48, 95% CI =3.28-6.18) were all positively associated with elevated blood pressure ( P <0.05). The RCS analysis demonstrated that the high levels of FM, FMP, FMI, and SFM showed linear doseresponse relationships with elevated blood pressure ( P non linear >0.05), and elevated VFM was associated with elevated blood pressure in a nonlinear dose response relationship ( P non linear <0.05).
Conclusions
Children with elevated body fat have a higher risk of elevated blood pressure. There was a dose response relationship between high body mass content and elevated blood pressure in children. It is essential to take appropriate measures to reduce the elevated body fat in children, in order to prevent the occurrence of high elevated blood pressure in children.
9.Discrete element modeling and breakage behavior analysis of oral solid dosage form particles
Lin-xiu LUO ; Tian-bing GUAN ; An-qi LUO ; Zeng LIU ; Yu-ting WANG ; Yan-ling JIANG ; Zheng LU ; Jing-cao TANG ; Shuang-kou CHEN ; Hui-min SUN ; Chuan-yun DAI
Acta Pharmaceutica Sinica 2024;59(4):1057-1066
The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.
10.Epidemiological characteristics of human respiratory syncytial virus among acute respiratory infection cases in 16 provinces of China from 2009 to 2023
Aili CUI ; Baicheng XIA ; Zhen ZHU ; Zhibo XIE ; Liwei SUN ; Jin XU ; Jing XU ; Zhong LI ; Linqing ZHAO ; Xiaoru LONG ; Deshan YU ; Bing ZHU ; Feng ZHANG ; Min MU ; Hui XIE ; Liang CAI ; Yun ZHU ; Xiaoling TIAN ; Bing WANG ; Zhenguo GAO ; Xiaoqing LIU ; Binzhi REN ; Guangyue HAN ; Kongxin HU ; Yan ZHANG
Chinese Journal of Preventive Medicine 2024;58(7):945-951
Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.


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