1.Synthesis of phenylacetamide derivatives and their protective effects on islet cell damage induced by palmitic acid
Ai-Yun LI ; Li GUAN ; Wan-Zhen SU ; Yang-Yang LU ; Sheng-Jie ZHANG ; Wei-Ze LI ; Xiang-Ying JIAO
Chinese Pharmacological Bulletin 2024;40(6):1130-1136
Aim To design and synthesize a series of phenylacetamide derivatives with different substituted phenylacetic acid as raw materials,and to investigate the protective effects of the compound on the damage of pancreatic β cells induced by palmitate acid(PA).Methods Min6 cells were cultured and divided into B blank control group,PA treatment group and PA+compounds group.The viability of Min6 cells was de-tected by CCK-8.The protein expressions of TXNIP and NLRP3 were observed by Western blot.MDA con-tent and SOD activity were detected by MDA and SOD kit.The insulin secretion of Min6 islet cells was meas-ured with insulin ELISA kit.Results A total of 10 phenylacetamide derivatives were designed and synthe-sized.Their structures were confirmed by 1H NMR and ESI-MS.Pharmacological activity study showed that most of the compounds had protective effects on islet βcells,among which LY-6 and LY-8 had stronger pro-tective effects than PA model group,with the cell via-bility of 61.4%,and LY-6 had the highest cell activi-ty,reaching to 104.9%.Compared with PA group,the protein expression of TXNIP and NLRP3 decreased in LY-6 and LY-8 groups,MDA content decreased and SOD activity increased,and insulin secretion of Min6 cell increased.Conclusions LY-6 and LY-8 inhibit TXNIP expression and decrease the activation of NL-RP3 inflammasome,and decrease the production of MDA and increase SOD activity,and thus reducing is-let β cells apoptosis and increasing insulin secretion.Therefore,the compound LY-6 could serve as a poten-tial anti-diabetic new chemical entity.
2.Design of GIS-based 3D playback system for flight human-plane data
La-Mei SHANG ; Yu-Fei QIN ; Wen WANG ; Wan-Qi LI ; Da-Long GUO ; Xiao-Chao GUO ; Juan LIU ; Zhen TIAN ; Ting-Ting CUI ; Yu-Bin ZHOU
Chinese Medical Equipment Journal 2024;45(10):14-19
Objective To develop a GIS-based 3D playback system for the flight human-plane data to realize the fusion of pilots'airborne flight data and physiological data.Methods The 3D playback system was developed with the Browser/Server(B/S)architecture,micro-server model,Java language and Spring Cloud technology framework,which was composed of three functional modules for flight process reproduction,physiological situational awareness and critical event calibration analysis.Results The system developed achieved time synchronization and data fusion of airborne flight data and physiological data with a time synchronization frequency of 1 Hz and a refresh rate of not less than 120 frames/s.Conclusion The system developed with high safety,stability,reliability and accuracy facilitates pilot in-flight physiological monitoring and fusion and simultaneous display of airborne flight data and physiological data,which can be used as an important platform for decision-making support in flight training.[Chinese Medical Equipment Journal,2024,45(10):14-19]
3.Tetrandrine targeting SIRT5 exerts anti-melanoma properties via inducing ROS,ER stress,and blocked autophagy
Ji YACONG ; Li CHONGYANG ; Wan SICHENG ; Dong ZHEN ; Liu CHAOLONG ; Guo LEIYANG ; Shi SHAOMIN ; Ci MINGXIN ; Xu MINGHAO ; Li QIAN ; Hu HUANRONG ; Cui HONGJUAN ; Liu YALING
Journal of Pharmaceutical Analysis 2024;14(10):1468-1483
Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.
4.Research on the Pharmacodynamic Material Basis of Kaixinsan Based on High Performance Liquid Chromatography-Tandem Mass Spectrometry and Mitochondrial Respiratory Function
Ruofan AN ; Zhen LI ; Jun LI ; Yanhua GAO ; Shaojing LI ; Qiman ZHANG ; Ying CHEN ; Huihua WAN ; Wei YANG
Herald of Medicine 2024;43(12):1888-1897
Objective To reveal the pharmacodynamic material basis of Kaixinsan by using high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)and the integrated analysis of"chemical component spectrum-plasma exposure component spectrum-mitochondrial function".Methods Through a review of literature,databases,and previous studies,the chemical components of ginseng,polygala,poria,and acorus were systematically cataloged.A qualitative analysis method for the chemical constituents in the aqueous extract of Kaixinsan was developed,allowing for the identification of its chemical components.A qualitative analysis for rat plasma based on HPLC-MS/MS was established,which was applied to analyze the plasma exposure component spectrum following oral administration of Kaixinsan aqueous extract in rats.Aerobic respiration was evaluated using a seahorse cell energy metabolism analyzer,and the effect of key components of Kaixinsan on mitochondrial aerobic respiration was assessed.Results Four main types of components were identified in the Kaixinsan aqueous extract,including saponins,oligosaccharide esters,xanthones,and triterpenes,comprising a total of 231 identified compounds.Analysis of rat plasma 30 minutes after gavage with Kaixinsan identified 55 compounds.The analysis revealed that ginsenoside Rg1,3,6'-disinapoylsucrose,polygalaxanthone Ⅲ and poricoic acid B could significantly enhance mitochondrial respiratory capacity using in vitro cellular assays to detect aerobic respiration of four main components entered blood.Conclusions Saponins,oligosaccharide esters,xanthones,and triterpenes may be the material basis for the pharmacological effect of Kaixinsan by improving mitochondrial function.The integrated analysis of"chemical component spectrum-plasma exposure component spectrum-mitochondrial function"provides a new approach for in-depth exploration of the material basis underlying the efficacy of traditional Chinese medicine.
5.Expression of cGAS-STING signaling pathway molecules in labial gland tissue of Sj?gren′s syndrome
Xia LI ; Zhen TIAN ; Dongshan WAN ; Yi ZHAO
Chinese Journal of Rheumatology 2024;28(10):723-727
Objective:To investigate the expression of cGAS-STING signaling pathway molecules in labial gland specimen of primary Sj?gren′s syndrome (pSS) patients and its correlation with disease characteristics.Methods:Clinical data and labial gland specimens were collected from 19 patients diagnosed with pSS who visited Xuanwu Hospital, Capital Medical University, from January 2021 to December 2021, along with a control group of 7 gender-and age-matched individuals with isolated xerostomia.We performed immunofluorescence staining for cGAS on labial gland specimens, and Western blot analysis was further utilized to confirm the expression levels of cGAS-STING signaling pathway-related molecules (cGAS, pSTING, pIRF3 and pTBK1) in the labial gland tissues of both groups. For normally distributed data, t test was employed for comparison between groups, while the Mann-Whitney U test was used for non-normally distributed data. And Spearman's correlation analysis was utilized to explore the correlation between clinical characteristics and molecular expression levels. P value<0.05 was considered statistically significant. Results:Immun-ofluorescence analysis showed significant infiltration of cGAS-positive cells in the labial gland tissues of the pSS group, while the control group exhibited no or minimal expression of cGAS-positive cells and there was a statistical difference between the two groups ( t=3.87, P=0.001). Moreover, the expression level of cGAS in labial gland tissues of pSS patients had a positive correlation with the focus scores ( r=0.55, P=0.014). Western blot analysis revealed statistically significant differences in the expression of cGAS and pSTING between the pSS group and the control group in labial gland tissues (0.73±0.39 vs. 0.18±0.05, t=2.38, P=0.049 and 0.91±0.17 vs. 0.23±0.10, t=2.17, P=0.043). Additionally, a correlation between the expression levels of cGAS and pSTING in labial gland tissues was found according to Spearman correlation analysis ( r=0.823, P=0.001). However, there was no correlation between the expression level of cGAS in labial gland tissues and clinical features, serological indicators (IgG level, titer of rheumatoid factor, C3 level and autoantibody positive rate) or disease activity (EULAR Sj?gren′s syndrome disease activity index scores). Conclusion:The cGAS-STING signaling pathway is activated in the labial gland tissue of pSS patients, which may be involved in its pathogenesis.
6.The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"
Wanjie YANG ; Xianduo LIU ; Ximo WANG ; Weiguo XU ; Lei ZHANG ; Qiang FU ; Jiming YANG ; Jing QIAN ; Fuyu ZHANG ; Li TIAN ; Wenlong ZHANG ; Yu ZHANG ; Zheng CHEN ; Shifeng SHAO ; Xiang WANG ; Li GENG ; Yi REN ; Ying WANG ; Lixia SHI ; Zhen WAN ; Yi XIE ; Yuanyuan LIU ; Weili YU ; Jing HAN ; Li LIU ; Huan ZHU ; Zijiang YU ; Hongyang LIU ; Shimei WANG
Chinese Critical Care Medicine 2024;36(2):195-201
The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
7.Research status on the mechanism of drug resistance in pancreatic cancer
Wan-Qin CHEN ; Qiu-Tong GUAN ; Xiao-Xian HUANG ; Min-Jie WEI ; Zhen-Hua LI
The Chinese Journal of Clinical Pharmacology 2024;40(3):454-458
Objective Pancreatic cancer(PC)is a malignant tumor of the digestive tract that is difficult to diagnose early,easily metastasizes and relapses,and resistant to conventional chemotherapy.PC is a very difficult disease to treat.The key regulatory factors of PC resistance,such as epithelial-mesenchymal transition phenotypic cells,tumor stem cells,and miRNAs,have been reviewed in the past few years,and some new regulatory factors have been discovered as supplements.This review mainly focuses on the characteristics and properties of the key regulatory factors of PC chemotherapy resistance including long noncoding RNAs,nuclear factor KB and exosomes,drug resistance mechanisms,and treatment related strategies,and future treatment directions were predicted.
8.Preliminary study of the transport and absorption mechanism of Astragalus polysaccharide-Ⅱ on M cells
Wan-wan LÜ ; Ke LI ; Shi-hong FENG ; Yu-wei WEN ; Xue-mei QIN ; Yu-guang DU ; Zhen-yu LI
Acta Pharmaceutica Sinica 2024;59(10):2820-2827
To explore the absorption mechanism of APS-Ⅱ
9.Characterization and phylogenetic analysis of the complete chloroplast genome of Salvia apiana Jepson
Zhen-xi FANG ; Qian JI ; Jia-dong HU ; Wan-sheng CHEN ; Qing LI
Acta Pharmaceutica Sinica 2024;59(5):1484-1493
italic>Salvia apiana Jepson, commonly known as white sage, is a perennial sub-shrub of the
10.Determination of 19 components in Microctis Folium from different production areas based on UPLC-MS/MS
Min-you HE ; Li-wei WANG ; Lin LIU ; Po-yu ZHANG ; Jin-quan LAN ; Xin-ya WAN ; Zhen-yu LI ; Xiang-dong CHEN ; Dong-mei SUN
Acta Pharmaceutica Sinica 2024;59(5):1374-1381
The paper is to establish an UPLC-MS/MS method for the simultaneous determination of 19 components in Microctis Folium from different production areas. The 50% methanol was used as extraction solvent. The Agilent ZORBAX SB C18 (150 mm × 2.1 mm, 1.8 μm) column was used; mobile phase was acetonitrile - 0.1% acetic acid with gradient elution, flow rate was 0.3 mL·min-1, colume temperature was 30 ℃, and the injection volume was 2 μL; electrospray ionizaton source was used and detected in negative ion mode. The results showed that the established UPLC-MS/MS method could well separate the 19 components, and the methodological investigation results of 19 components were good. By means of orthogonal partial least squares discriminant analysis (OPLS-DA), 28 batches of Microctis Folium samples from different production areas can be divided into three categories, Guangdong, Guangxi and Hainan are each classified into one category, and 10 signature compounds which affecting the quality differences of different production areas were screened out. The established method is accurate, reliable, sensitive and reproducible. It can provide a basis for the establishment of the quality standard of Microctis Folium, as well as for safety and quality research.

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