1.Study on anti-atherosclerosis mechanism of blood components of Guanxin Qiwei tablets based on HPLC-Q-Exactive-MS/MS and network pharmacology
Yuan-hong LIAO ; Jing-kun LU ; Yan NIU ; Jun LI ; Ren BU ; Peng-peng ZHANG ; Yue KANG ; Yue-wu WANG
Acta Pharmaceutica Sinica 2025;60(2):449-458
The analysis presented here is based on the blood components of Guanxin Qiwei tablets, the key anti-atherosclerosis pathway of Guanxin Qiwei tablets was screened by network pharmacology, and the anti-atherosclerosis mechanism of Guanxin Qiwei tablets was clarified and verified by cell experiments. HPLC-Q-Exactive-MS/MS technique was used to analyze the components of Guanxin Qiwei tablets into blood, to determine the precise mass charge ratio of the compounds, and to conduct a comprehensive analysis of the components by using secondary mass spectrometry fragments and literature comparison. Finally, a total of 42 components of Guanxin Qiwei tablets into blood were identified. To better understand the interactions, we employed the Swiss Target Prediction database to predict the associated targets. Atherosclerosis (AS) disease targets were searched in disease databases Genecard, OMIM and Disgent, and 181 intersection targets of disease targets and component targets were obtained by Venny 2.1.0 software. Protein interactions were analyzed by String database. The 32 core targets were selected by Cytscape software. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in DAVID database. It was found that the anti-atherosclerosis pathways of Guanxin Qiwei tablets mainly include lipid metabolism and atherosclerosis and AGE-RAGE signaling pathway in diabetic complications and other signal pathways. The core targets and the core compounds were interlinked, and it was found that cryptotanshinone and tanshinone ⅡA in Guanxin Qiwei tablets were well bound to TNF, PPAR
2.Study on the modeling method of general model of Yaobitong capsule intermediates quality analysis based on near infrared spectroscopy
Le-ting SI ; Xin ZHANG ; Yong-chao ZHANG ; Jiang-yan ZHANG ; Jun WANG ; Yong CHEN ; Xue-song LIU ; Yong-jiang WU
Acta Pharmaceutica Sinica 2025;60(2):471-478
The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.
3.Research progress on the structural modification of isosteviol and the biological activities of its derivatives
Li-jun ZHAO ; You-fu YANG ; Tong-sheng WANG ; Yan-li ZHANG ; Ya WU
Acta Pharmaceutica Sinica 2025;60(1):22-36
Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.
4.Effect of Maxing Loushi Decoction on Inflammatory Factors, Immune Function, and PD-1/PD-L1 Signaling Pathway in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Phlegm Turbidity Obstructing Lung Syndrome
Yuexin SHI ; Zhi YAO ; Jun YAN ; Caijun WU ; Li LI ; Yuanzhen JIAN ; Guangming ZHENG ; Yanchen CAO ; Haifeng GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):143-150
ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with phlegm turbidity obstructing lung syndrome, and to investigate its effects on inflammatory factors, immune function, and the programmed death-1(PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway. MethodsA randomized controlled study was conducted, enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital, Beijing University of Chinese Medicine, from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table, with 45 patients in each group. The control group received conventional Western medical treatment, while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy, COPD Assessment Test (CAT) score, modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walk test (6MWT), serum inflammatory factors, T lymphocyte subsets, and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% (33/42) in the control group and 95.35% (41/43) in the observation group, with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant (χ2 = 5.136, P<0.05). After treatment, both groups showed significant reductions in CAT and mMRC scores (P<0.05, P<0.01) and significant increases in 6MWT compared to baseline (P<0.01). The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1(MCP-1), and macrophage inflammatory protein-1α (MIP-1α) were significantly reduced in both groups (P<0.05, P<0.01), with greater reductions in the observation group (P<0.05, P<0.01). CD8+ levels were significantly reduced (P<0.01), while CD3+, CD4+, and CD4+/CD8+ levels were significantly increased in both groups after treatment (P<0.05, P<0.01), with more significant improvements observed in the observation group (P<0.05, P<0.01). Serum PD-1 levels were reduced (P<0.05, P<0.01), and PD-L1 levels were increased significantly in both groups after treatment (P<0.05, P<0.01), with more pronounced changes in the observation group (P<0.05). ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors, improving immune function, and regulating the PD-1/PD-L1 signaling pathway.
5.Effect of Maxing Loushi Decoction on Inflammatory Factors, Immune Function, and PD-1/PD-L1 Signaling Pathway in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Phlegm Turbidity Obstructing Lung Syndrome
Yuexin SHI ; Zhi YAO ; Jun YAN ; Caijun WU ; Li LI ; Yuanzhen JIAN ; Guangming ZHENG ; Yanchen CAO ; Haifeng GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):143-150
ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with phlegm turbidity obstructing lung syndrome, and to investigate its effects on inflammatory factors, immune function, and the programmed death-1(PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway. MethodsA randomized controlled study was conducted, enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital, Beijing University of Chinese Medicine, from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table, with 45 patients in each group. The control group received conventional Western medical treatment, while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy, COPD Assessment Test (CAT) score, modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walk test (6MWT), serum inflammatory factors, T lymphocyte subsets, and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% (33/42) in the control group and 95.35% (41/43) in the observation group, with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant (χ2 = 5.136, P<0.05). After treatment, both groups showed significant reductions in CAT and mMRC scores (P<0.05, P<0.01) and significant increases in 6MWT compared to baseline (P<0.01). The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1(MCP-1), and macrophage inflammatory protein-1α (MIP-1α) were significantly reduced in both groups (P<0.05, P<0.01), with greater reductions in the observation group (P<0.05, P<0.01). CD8+ levels were significantly reduced (P<0.01), while CD3+, CD4+, and CD4+/CD8+ levels were significantly increased in both groups after treatment (P<0.05, P<0.01), with more significant improvements observed in the observation group (P<0.05, P<0.01). Serum PD-1 levels were reduced (P<0.05, P<0.01), and PD-L1 levels were increased significantly in both groups after treatment (P<0.05, P<0.01), with more pronounced changes in the observation group (P<0.05). ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors, improving immune function, and regulating the PD-1/PD-L1 signaling pathway.
6.Association of attention deficit hyperactivity disorder symptoms and bullying behavior in children
TANG Jun, WU Xufang, ZHOU Yang, YANG Weiwei, ZHANG Yan, ZHANG Li, LYU Na, SONG Ranran
Chinese Journal of School Health 2024;45(1):91-94
Objective:
The association between school bullying and attention deficit hyperactivity disorder (ADHD) symptoms among students in primary schools and the moderating role of gender was explored to provide scientific evidence for the prevention and control of school bullying.
Methods:
A total of 4 764 students from 2 primary schools in Wuhan were selected using the convenience sampling method in March 2023. The Olweus Bully/Victim Questionnaire and Strengths and Difficulties Questionnaire were used. A Pearson χ 2 test was used to compare differences in school bullying rates among children with and without ADHD symptoms. Pearson correlation analysis and Process 3.3 were used to analyse the association between ADHD symptoms, and school bullying behaviour and the moderating role of gender.
Results:
The reported rate of bullying victims in primary schools was 24.2% and the rate of bullying perpetration was 3.8%. The rate of ADHD symptom detection among primary school students was 5.9%. ADHD symptoms were positively associated with bullying and bullying victim behaviour ( r =0.16, 0.27, P <0.01). Specifically, the association between ADHD symptoms and bullying behavior tended to be stronger among boys than girls ( β boy =0.17, t =11.13; β girl =0.07, t =4.11, P <0.01).
Conclusions
ADHD symptoms are an important factor influencing school bullying behaviors in students, and gender moderates the association. In the process of preventing and controlling school bullying, ADHD symptoms and gender differences should be emphasized and comprehensive interventions should be implemented.
7.Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production
Wang-long CHU ; Tong-jing LI ; Yan SHANGGUAN ; Fang-tao HE ; Jian-fu WU ; Xiu-ping ZENG ; Tao GUO ; Qing-fang WANG ; Fen ZHANG ; Zhen-zhong ZHONG ; Xiao LIANG ; Jun-yuan HU ; Mu-yun LIU
Acta Pharmaceutica Sinica 2024;59(3):743-750
Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.
8.Self monitoring of blood glucose combined with digital diabetes management to improve clinical relevant indicators in type 2 diabetes
Jun YANG ; Qiuwen ZHU ; Ling WANG ; Yanni WU ; Xia QI ; Mengfei JIANG ; Xiaoyong YAN ; Hongyun MIAO
Chongqing Medicine 2024;53(1):79-83,88
Objective To compare the influence between self-monitoring of blood gluocose(SMBG)combined with digital diabetes management and traditional management mode on the related clinical indexes in the patients with type 2 diabetes mellitus(T2DM).Methods A total of 100 patients with T2DM treated in the endocrinology and metabolism outpatient department of this hospital from January 2022 to June 2022 and meeting the inclusion criteria of this study were successively included.They were divided into the experimental group and control group.The experimental group was managed by SMBG combined with digital diabetes man-agement mode,while the control group adopted the traditional management mode,the outpatient clinic follow up once a month.After 6 months of follow-up,fasting blood glucose,glycosylated hemoglobin(HbA1c),low density lipoprotein cholesterol(LDL-C)and urinary microalbumin/creatinine ratio(UACR)were compared between the two groups.Results The FBG,HbA1c,LDL-C,and UACR of the experimental group decreased after intervention when compared with baseline.Compared with the control group,the FBG[8.7(7.7,9.2)mmol/L vs.10.8(8.8,12.7)mmol/L,Z=-4.660,P<0.001],HbA1c[6.3%(5.3,7.8)%vs.8.5%(7.2,10.0)%,Z=-5.130,P<0.001],LDL-C[2.6(1.8,3.1)mmol/L vs.3.3(2.6,4.0)mmol/L,Z=-4.112,P<0.001],UACR[16.1(3.5,46.5)mg/g vs.58.4(11.9,108.0)mg/g,Z=-2.220,P=0.026]for patients in the expriemental group after intervention were significantly decreased.Conclusion SMBG combined with digital diabetes management model can significantly improve the clinical indicators of patients.
9.Effect and mechanism of Sitravatinib combined with Niraparib on proliferation,apoptosis and autophagy in mucosal melanoma cell lines
Zijin HU ; Yan KONG ; Xiaowen WU ; Qian GUO ; Jun GUO
Basic & Clinical Medicine 2024;44(3):295-302
Objective To investigate the effect of anti-angiogenic drug Sitravatinib combined with poly(adenosine diphosphate[ADP]-ribose)polymerase inhibitor(PARPi)Niraparib on mucosal melanoma cell lines and its possible mechanism.Methods The CCK8 assay was used to detect the maximal half inhibitory concentration(IC50)of Sitravatinib and Niraparib targeting at mucosal melanoma(MM)cell lines.CompuSyn was used to detect the Combination Index(CI)in different concentrations of the two drugs.Flow cytometry was used to detect the effect of drugs on cell apoptosis.Colony formation assay was used to detect the effect of drugs on cell proliferation.Western blot was used to detect the protein expressions and RT-qPCR was used to detect mRNA expression.Results CI values was respectively 0.19 and 0.15 for Sitravatinib(2 μmol/L)in combination with Niraparib(20 μmol/L)in a human vaginal maligant melanoma cell line(HMVII)and a metastasis inguinal lymph node of vulvar malignant melanoma cell line(GAK).Compared with the control group and single-drug groups,the cell proliferation of the combination group was significantly reduced(P<0.05 or P<0.01 or P<0.001).The cell apoptosis rate was signifi-cantly increased(P<0.01 or P<0.001).The protein and mRNA expression of apoptosis-related biomarkers signifi-cantly increased(P<0.001);In addition,the protein and mRNA expression of cell autophagy biomarkers signifi-cantly increased(P<0.01 or P<0.001).The protein expression of DNA damage marker significantly increased.Moreover,compared with the control group,The expression of radiation sensitive protein 51(RAD51)recombinase in the Sitravatinib single-drug group and combination group significantly reduced.As the dose of Sitravatinib gradu-ally increased up to 2 μmol/L,the protein and mRNA expression of RAD51 both significantly reduced(P<0.05 or P<0.01),the mRNA expression of BRCA1 and BRCA2 also significantly reduced(P<0.05 or P<0.01 or P<0.001).Conclusions Sitravatinib combined with Niraparib inhibits the proliferation of mucosal melanoma cells,induces cell apoptosis and promotes autophagy.The mechanism is potentially related to the inhibition of ho-mology-dependent recombination repairs(HRR).
10.Establishment of animal model of cervicofacial venous malformations with external jugular vein in sheep
Xia YANG ; Yanling SHEN ; Jun GUO ; Yuan LIU ; Zhiwei YAN ; Xiangming YANG ; Wei WU ; Yao FENG ; Yaowu YANG
Journal of Practical Stomatology 2024;40(1):43-46
Objective:To establish the animal model of cervicofacial venous malformations(VMs)by surgical reconstruction of exter-nal jugular vein in sheep.Methods:The external jugular veins of 5 sheep were dissected,and the position,course,branch and exter-nal diameter were observed and measured.The models of VMs with draining and returning veins were constructed by suturing or constric-ting the proximal part of main trunk and ligating or constricting the distal part of the jugular or branch veins.The animal model was eval-uated by Doppler ultrasound,gross observation and histological observation at the 4th week after surgery.Results:The external jugular veins of sheep is in the lateral side of bilateral neck,and the main trunk is formed by the maxillary vein and lingual facial vein.The ex-ternal diameter ranges from 6 to 12 mm,with an average external diameter of 9.3 mm.Immediately after the external jugular vein was sutured and narrowed at the proximal part of the main vein,the distal part of the vein branch was ligated or narrowed,the blood flow speed slowed down and the veins in the model area bulged.4 weeks after surgery,gross observation showed that most veins narrowed and thrombosis was formed in part of the venous lumen.The central region of some specimens was dilated,and the peripheral collateral veins were dilated in some models.Doppler ultrasonography showed that the lumens of most veins were dilated and the returning veins and the inflow veins were narrowed.Colored blood flow was seen in the lumen.Histological observation showed that the structure of vein endothelium and wall was close to the normal vein,and the vein vessel wall of some specimens was thickened.Conclusion:The VMs model estab-lished by external jugular vein of sheep basically meets the re-quirements and is expected to be used in the therapeutic meth-odology research of cervicofacial VMs.


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