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.Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione.
Fu'an XIE ; Yujia NIU ; Xiaobing CHEN ; Xu KONG ; Guangting YAN ; Aobo ZHUANG ; Xi LI ; Lanlan LIAN ; Dongmei QIN ; Quan ZHANG ; Ruyi ZHANG ; Kunrong YANG ; Xiaogang XIA ; Kun CHEN ; Mengmeng XIAO ; Chunkang YANG ; Ting WU ; Ye SHEN ; Chundong YU ; Chenghua LUO ; Shu-Hai LIN ; Wengang LI
Journal of Pharmaceutical Analysis 2025;15(1):101068-101068
Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [15N2]-cystine and [13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
3.Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics
Yu-long CHEN ; You ZHAI ; Xiao-yan WANG ; Wei-xia LI ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Xiao-fei CHEN ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Kun LI ; Jin-fa TANG ; Ming-liang ZHANG
Acta Pharmaceutica Sinica 2024;59(2):382-394
Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and
4.Design of a new posterior atlas fracture reduction and internal fixation system
Hegang NIU ; Kun YANG ; Jingjing ZHANG ; Yizhu YAN ; Yinshun ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(9):1399-1402
BACKGROUND:At present,there is a lack of an internal fixation system with good reduction and simple operation for the treatment of atlas burst fracture by posterior single-segment fixation. OBJECTIVE:Based on the atlas CT measurement data,a new posterior atlas fracture reduction and internal fixation system was designed and optimized,which was in line with the characteristics of human local anatomical structure,easy to operate and with good reduction. METHODS:CT images of 347 adults were analyzed retrospectively.In the images,the length of pedicle screw track with a medial inclination of 0°,the angle of the maximum medial inclination angle and the length of pedicle screw track at this time,the height of vertebral artery groove,the distance between the entry points of bilateral pedicle screws and the midline,the radius of the posterior arch of atlas,the distance between the posterior tubercle of the atlas and the posterior edge of the foramen magnum,and the distance between the posterior tubercle of the atlas and the upper surface of the axial arch were measured.The imaging data were analyzed and a reduction and internal fixation system was designed and optimized for atlas fracture in line with human anatomical characteristics. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in the the length of pedicle screw track with a medial inclination of 0°,the maximum medial inclination angle and the length of pedicle screw track at this time,the height of vertebral artery groove,the distance between the entry points of bilateral pedicle screws and the midline,the radius of the posterior arch of atlas,the distance between the posterior tubercle of the atlas and the posterior edge of the foramen magnum,and the distance between the posterior tubercle of the atlas and the upper surface of the axial arch measured on the left and right sides of all subjects(P>0.05).There were statistically significant differences in each index measured between the male and female groups(P<0.05).(2)The new posterior atlas fracture reduction and internal fixation system has been successfully designed and obtained the national patent.The internal fixation system is suitable for the anatomical characteristics of the posterior arch of the atlas.It can not only effectively treat the atlas burst fracture,but also retain the movement function of the occipital atlantoaxial joint.
5.Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly (version 2023)
Yan HU ; Dongliang WANG ; Xiao CHEN ; Zhongmin SHI ; Fengjin ZHOU ; Jianzheng ZHANG ; Yanxi CHEN ; Liehu CAO ; Sicheng WANG ; Jianfei WANG ; Hongliang WANG ; Yong FENG ; Zhimin YING ; Chengdong HU ; Qinglin HAN ; Ming LI ; Xiaotao CHEN ; Zhengrong GU ; Biaotong HUANG ; Liming XIONG ; Yunfei ZHANG ; Zhiwei WANG ; Baoqing YU ; Yong WANG ; Lei ZHANG ; Lei YANG ; Peijian TONG ; Ximing LIU ; Qiang ZHOU ; Feng NIU ; Weiguo YANG ; Wencai ZHANG ; Shijie CHEN ; Jinpeng JIA ; Qiang YANG ; Tao SHEN ; Bin YU ; Peng ZHANG ; Yong ZHANG ; Jun MIAO ; Kuo SUN ; Haodong LIN ; Yinxian YU ; Jinwu WANG ; Kun TAO ; Daqian WAN ; Lei WANG ; Xin MA ; Chengqing YI ; Hongjian LIU ; Kun ZHANG ; Guohui LIU ; Dianying ZHANG ; Zhiyong HOU ; Xisheng WENG ; Yingze ZHANG ; Jiacan SU
Chinese Journal of Trauma 2023;39(4):289-298
Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.
6.Drug-coated balloon for in-stent restenosis in femoropopliteal segment: 1-year clinical outcomes from a multicenter study in China
Bo MA ; Kun XU ; Hao ZHAO ; Xueqiang FAN ; Xia ZHENG ; Jie CHEN ; Zhichao LAI ; Jiang SHAO ; Xin ZHANG ; Bihui ZHANG ; Guochen NIU ; Ziguang YAN ; Bao LIU ; Min YANG ; Zhidong YE
Chinese Journal of General Surgery 2022;37(8):588-591
Objective:To evaluate the safety and efficacy at 1-year follow-up of the use of drug-coated balloon (DCB) for the treatment of femoropopliteal in-stent restenosis (ISR).Methods:This study enrolled 252 patients undergoing Orchid DCB angioplasty for peripheral arterial disease in the femoral-popliteal segment. The clinical data were retrospectively analyzed.Results:Forty-nine patients were eligible, including 29 (59.2%) chronic total occlusions belonging to TransAtlantic Inter-Society Consensus-Ⅱ(TASC Ⅱ) D, 7 (14.3%) thrombosis, and 14 (28.6%) moderate to severe calcifications. The mean lesion length was (215.9±97.1) mm. 69.4% were of occlusive lesions (Tosaka Ⅲ category). Only 1 provisional stent was implanted. 98% patients had severe claudication or even worse. Of these cases, 34 (73.9%) showed improvements in Rutherford category, while 11 (23.9%) did not change and 1 (2.2%) case deteriorated. The average value of ABI was 0.478±0.264 before surgery and 0.907±0.207 at the end of follow-up. The improvement in Rutherford category ( P<0.01) and ABI ( P<0.005) were both significant. The primary patency (PP) was 80.4%, and the freedom from clinically driven TLR was 84.8% at 1 year. During the follow-up period, there was no all-cause death and major limb amputation. Conclusion:This multicenter study demonstrated the effectiveness of DCB as a treatment for complicated and extensive ISR lesions within 12 months.
7.Infrapyloric lymph node metastasis pattern in middle/lower gastric cancer: an exploratory analysis of a multicenter prospective observational study (IPA-ORIGIN).
Tasiken BAHETI ; Ru-Lin MIAO ; Gang ZHAO ; Da-Guang WANG ; Feng-Lin LIU ; Jiang YU ; Shuang-Yi REN ; Kai YE ; Su YAN ; Kun YANG ; Wei-Dong ZANG ; Lin FAN ; Bin LIANG ; Jun CAI ; Wei-Hua FU ; Wei WANG ; Zheng-Rong LI ; Zhao-Jian NIU ; Jun YOU ; Xing-Feng QIU ; Wu SONG ; Lu ZANG
Chinese Medical Journal 2020;133(22):2759-2761
8.Based on PI3K/Akt/mTOR Signaling Pathway to Explore Mechanism of Zhigancao Tang Against MIRI-induced Ventricular Tachycardia and Ventricular Fibrillation in Rats
Xu-ying ZHENG ; Chun-jie MA ; Yong-zhen CHEN ; Cun-xia REN ; Ren-xiu NIU ; Hua LIAN ; Kun CHEN ; Xiao-hui TAN ; Qing-zhi YAN ; Xing ZHANG ; Hao WU
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(17):1-8
Objective:Through phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt)/mammalian rapamycin target protein (mTOR) signaling pathway, explore the effect of Zhigancao Tang on myocardial ischemia-reperfusion injury(MIRI)The role and mechanism of arrhythmia(ventricular tachycardia and ventricular fibrillation). Method:The 72 SD rats were randomly divided into sham operation group,model group, Zhigancao Tang low,medium and high dose group(11.43,22.86,45.72 g·kg-1),Wenxin granule group(2.43 g·kg-1),continuous drug intervention for 10 days. Two hours after the last administration,the MIRI model of rat was prepared by ligating the left anterior descending coronary artery,and the changes of electrocardiogram were recorded. After successful modeling,blood and heart tissue were collected to detect the content of creatine creatine(CK),lactate dehydrogenase(LDH)and aspartate aminotransferase(AST)in the serum, the enzyme-linked immunoassay(ELISA) method was used to detect cardiac troponin(CtnI)content, immunohistochemical detection of myocardial PI3K,Akt,mTOR expression. Western blot was used to detect the myocardial autophagy-related protein microtubule-associated protein 1 light chain 3(LC-3),autophagy markers Beclin1 and PI3K/Akt/mTOR signaling pathway related protein expression and phosphorylated p-PI3K,p-Akt,p-mTOR levels. Result:In model group, 100% of ventricular tachycardia and 91.67% of ventricular fibrillation occurred. Compared with sham operation group, the serum levels of CK,LDH,AST,and CtnI in the model group were significantly increased(
9.Construction and application of effect-related near-infrared spectroscopy for traditional Chinese medicines — Exemplification by rhubarb dispensing granules
Ping ZHANG ; Ming NIU ; Peng TAN ; Yan-zhong HAN ; Ding-kun ZHANG ; Lei SUN ; Ji-xiang FANG ; Yuan-yuan CUI ; Yan-qin MA ; Shuang-cheng MA ; Yong-feng ZHOU
Acta Pharmaceutica Sinica 2019;54(12):2162-2168
Consistency in quality of traditional Chinese medicine granules is an important factor to ensure reproducible clinical efficacy. In this study rhubarb dispensing granules were utilized to construct an efficacious near-infrared spectroscopy (eNIRS) assay by combining NIRS and biopotency. A NIR method for assaying rhubarb dispensing particles was established, and information on different batches was collected. The diarrhea-inducing biopotency of rhubarb dispensing granules was determined based on a constipation model induced by diphenoxylate in mice. The animal protocol was approved by the Animal Ethic Committee of 302 Hospital of Chinese PLA People's Liberation Army (ID: IACUC-2019-0010). Ten anthraquinones were determined in rhubarb dispensing granules by UPLC. The correlation between NIR and biopotency was analyzed and five characteristic bands that correlated highly with bioactivity were identified, including 4 011-4 390, 4 859-5 461, 7 012-7 493, 10 992-11 312 and 11 871-12 489 cm-1. There were some differences in the main bands of different chemical constituents. In summary, five active bands based on NIRS were identified and found to be able to achieve rapid on-line detection of rhubarb dispensing granule quality. This research model may also provide reference for quality control of other Chinese medicine dispensing granules.
10. Efficacy and Mechanism of Danlu Tongdu Tablets on Lumbar Disc Herniation with Kidney Deficiency and Stasis Syndrome
Bin-hong YAN ; Qian NIU ; Zhi-jian FU ; Fan YANG ; Dao-rui YU ; Kun NIU
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(22):66-71
Objective: To observe short-term and long-term efficacies of Danlu Tongdu tablets on lumbar disc herniation (LDH) with kidney deficiency and stasis syndrome, and its effect on nucleus pulposus reabsorption and immunoinflammatory factors. Method: One hundred and sixty patients were randomly divided into control group (80 cases) and observation group by random number table. Patients in control group (80 cases) got acupoint massage and acupuncture, 1 time/day. In addition to the therapy of control group, patients in observation group were also given Danlu Tongdu tablets, 4 tablets/time, 3 times/days. A course of treatment was 12 weeks, and a 9-month follow-up was recorded. Lumbago and leg pain were recorded by visual simulation (VAS) before treatment and at the first, second, third month after treatment. Before and after treatment, Japanese orthopaedic association (JOA), symptoms and signs were scored. During the 9-month follow-up, relapse rate and relapse time were recorded, and VAS and JOA were scored. Absorption of nucleus pulposus was assessed, and levels of interleukin-1 (IL-1), IL-17, tumor necrosis factor-α (TNF-α), matrix metalloproteinases-3 (MMP-3) were detected. Result: By rank sum test, the clinical efficacy in observation group was better than that in control group (Z=2.125, P<0.05), and scores of JOA was better than that in control group (Z=1.924, P<0.05). At the first, second and third months after treatment, VAS scores of low back pain, leg pain were lower than those in control group (P<0.01), while the decline range were more than that in control group (P<0.01). And scores of symptoms and signs were lower than that in control group (P<0.01), whereas scores by dimensions of JOA scale and the total score of JOA were all higher than those in control group (P<0.01). Complete absorptivity of nucleus pulposus in observation group was 61.11%, which was higher than 42.03%in observation group (χ2=5.138, P<0.05). Levels of IL-1, IL-17, TNF-α and MMP-3 were lower than that in control group (P<0.01). Relapse rate in observation group was 23.61%, which was lower than 40.58%in control group (χ2=4.668, P<0.05). Average recurrence time was longer than that in control group (P<0.05), score of VAS was lower than that in control group (P<0.05), and the total score of JOA was higher than that in control group (P<0.05). Conclusion: In addition to acupuncture and massage therapy, Danlu Tongdu tablets can also be used to relieve pain and ameliorate function, improve clinical efficacy, reduce relapse rate, promote nucleus pulposus reabsorption, and relieve inflammation of nerve root.

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