1.Inhibition effect of kudinoside D on lipid deposition in hepatocytes and its mechanism
Cai-Cai XUE ; Yan-Xiang LI ; Xiu-Mei QIAO ; Jin-Yong PENG ; Jin-Hong WANG
Chinese Pharmacological Bulletin 2024;40(9):1688-1694
Aim To investigate the effect of kudinoside D(KD-D)on palmitic acid(PA)-induced lipid depo-sition in hepatocytes.Methods Mouse hepatocytes AML-12 were cultured and randomly divided into the Control group,PA group,PA+KD-D 20 μmol·L-1 group,PA+KD-D 40 μmol·L-1 group and PA+KD-D 80 μmol·L-1 group.AML-12 cells in PA and KD-D groups were treated with PA(0.4 mmol·L-1)for 24 h.AML-12 cells in KD-D groups were incubated with KD-D for 1 h before stimulation with PA.MTT as-say was used to detect cell survival rate,oil red O stai-ning and transmission electron microscopy were used to detect lipid deposition in cells,DCFH-DA fluorescence probe was used to detect intracellular reactive oxygen species(ROS)and MitoSOX mitochondrial superoxide red fluorescence probe was used to detect mitochondrial superoxide content in cells.Results KD-D at differ-ent concentrations improved PA-induced changes in cell morphology significantly.Compared with the Con-trol group,cells in PA group showed a significant in-crease in intracellular lipid droplets.Compared with PA group,the red lipid droplets in KD-D groups de-creased.The results of transmission electron microsco-py demonstrated that KD-D reduced PA-induced hepat-ic steatosis and improved ultrastructure.In addition,KD-D significantly decreased PA-induced cellular ROS level(P<0.01)and reduced mitochondrial superox-ide content(P<0.01).Conclusion KD-D inhibits PA-induced lipid deposition by regulating the cellular oxidative stress levels in AML-12 cells.
2.Study on inhibitory effect of alisol B on non-small cell lung cancer based on network pharmacology and its mechanism
Liu-Yan XIANG ; Wen-Xuan WANG ; Si-Meng GU ; Xiao-Qian ZHANG ; Lu-Yao LI ; Yu-Qian LI ; Yuan-Ru WANG ; Qi-Qi LEI ; Xue YANG ; Ya-Jun CAO ; Xue-Jun LI
Chinese Pharmacological Bulletin 2024;40(12):2375-2384
Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were col-lected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of ali-sol B on NSCLC was explored by KEGG and GO en-richment analysis and the relationship between related genes and immune cells,which was verified by cell-lev-el experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five im-portant genes were identified by network pharmacologi-cal analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that al-isol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclu-sions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvi-ronment and inhibiting NSCLC.
3.Effects of climate change on scrub typhus in Xiamen
Xue-Mei KE ; Jiao-Na CHEN ; Shan-Shan MA ; Si-Han WU ; Chun-Xiang CAI ; Xiao-Yan WANG ; Shi-Jie HUANG
Chinese Journal of Zoonoses 2024;40(10):965-970
This study was aimed at examining the influence of meteorological factors on scrub typhus in Xiamen.Scrub ty-phus monitoring data and meteorological factors were collected in Xiamen from 2005 to 2023.Spearman correlation analysis and nonlinear regression were used to analyze the correlation between scrub typhus incidence and meteorological factors.The inci-dence of scrub typhus first increased and subsequently decreased in Xiamen from 2005 to 2023.The highest incidence was be-tween 2014 and 2016,and the peak incidence was from June to October.The monthly incidence of scrub typhus positively cor-related with daily minimum temperature(r=0.637,P<0.001,daily average temperature(r=0.627,P<0.001),daily maxi-mum temperature(r=0.612,P<0.001),sunshine duration(r=0.405,P<0.001),average relative humidity(r=0.346,P<0.001),and daily rainfall(r=0.207,P=0.002),and negatively correlated with average atmospheric pressure(r=-0.549,P<0.001),whereas no correlation was observed with the average wind speed in Xiamen.The regression equation of scrub ty-phus monthly incidence and meteorological parameters was y=-433.869-11.503x1+0.381x1 2+9.150x2-0.197x2 2+3.936 x3-0.132x3 2+0.881x4+0.035x4 2-1.048x5+0.009x5 2+0.186x6-0.023x6 2+0.421x7+6.210×10-5x8-1.051 × 10-10x8 2 in Xiamen,and the R2 was 0.473,thus indicating good model fit.Scrub typhus incidence correlated with the daily minimum av-erage temperature,average temperature,daily maximum tem-perature,sunshine duration,daily rainfall,relative humidity,and average atmospheric pressure in Xiamen.Various meteoro-logical factors had differing effects on scrub typhus.
4.Detection of avian influenza virus by RAA-CRISPR/Cas13a
Xiangyun LE ; Zhihang FENG ; Yanli FAN ; Qiang ZHANG ; Yicun CAI ; Wei XIONG ; Xiang WANG ; Qingli DONG ; Jian LI ; Junxin XUE ; Yan WANG
Chinese Journal of Veterinary Science 2024;44(10):2153-2158,2171
An innovative on-site real-time avian influenza virus(AIV)detection method was estab-lished by integratingrecombinase-aided amplification(RAA)with the clustered regularly inter-spaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)system.After analy-zing 120 sequences of the M gene of avian influenza viruses of different subtypes publicly available on NCBI,the RAA primers and crRNA were designed based on the identified highly conserved segment and used for RAA nucleic acid amplification.After the amplified products were transferred to a CRISPR/Cas13a detection system,the fluorescence values were monitored throughout the re-action process to indicate the results.The sensitivity and specificity of the RAA-CRISPR/Cas13a method were validated using gradient dilutions(106-100 copies/μL)of positive plasmids and sev-en other avian viruses.Fifty clinical samples were tested using this method and compared with the national standard fluorescence RT-PCR method.The results indicated that the detection limit for RAA-CRISPR/Cas13a method was 102 copies/μL,a two-fold improvement over the standard RAA.Specificity assay showed the established method only detected AIV with no cross-reactivity with other seven avian viruses.Compared to the national standard fluorescence RT-PCR method,this method exhibited 100%specificity,95.24%accuracy,and 98.00%consistency in detection of clinical samples.In conclusion,a universal and rapid RAA-CRISPR/Cas13a for detection of AIV was established with the capacity of achieving detection within 60 minutes at 37 ℃,which provides a rapid,sensitive,and specific on-site detection method for AIV.
5.Quality control method improvement of Zanthoxylum nitidum
Ding-Bang AN ; Qi-Yan LIN ; Xiang ZHAO ; Xue-Mei CHENG ; Chang-Hong WANG
Chinese Traditional Patent Medicine 2024;46(5):1440-1446
AIM To improve the quality control method of Zanthoxylum nitidum(Roxb.)DC.METHODS In the TLC qualitative identification of nitidine chloride,chelerythrine and toddalolactone,the analysis was performed on silica gel GF254 TLC plate,chloroform-methanol-ammonia(30∶1∶0.1)was taken as a developing agent.The HPLC fingerprints for Z.nitidum and its adulterants were established.In the HPLC content determination of magnoflorine,nitidine chloride and chelythrine,the analysis was performed on a 30℃ thermostatic Diamonsil Plus column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%trifluoroacetic acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 273 nm.RESULTS The clear TLC plots demonstrated good separation.The similarities of fingerprints for eighteen batches of medicinal materials were 0.484-0.983,Z.nitidum and its adulterants were effectively distinguished.Three constituents showed good linear relationships within their own ranges(R2=1.000 0),whose average recoveries were 98.9%-103.3%with the RSDs of 1.17%-1.96%.CONCLUSION This simple and reproducible can provide a new method for the quality control of Z.nitidum.
6.Auto-segmentation during online adaptive MRI-guided radiotherapy for prostate cancer
Xue-Na YAN ; Xiang-Yu MA ; Qiang ZENG ; Kuo MEN ; Xin-Yuan CHEN
Chinese Medical Equipment Journal 2024;45(6):59-64
Objective To explore the effect of auto-segmentation based on deep learning(DL)and Atlas during online adaptive MRI-guided radiotherapy.Methods Totally 15 prostate cancer patients undergoing MRI-guided online adaptive radiotherapy at some hospital from January 2020 to September 2021 were selected and divided into a training set(12 cases)and a test set(3 cases)by random sampling method.With the training set data the models of clinical target volume(CTV)and organs at risk(OAR)by DL and Atlas segmentation were established,and with the test set data the two segmentation models were modified and the modification lengths were recorded.DL and Atlas segmentation methods were compared on segmentation efficiency and accuracy in terms of Dice similarity coefficient(DSC),Hausdorff distance(HD)and mean distance to agreement(MDA).A joint auto-segmentation scheme based on combined DL and Atlas was constructed with considerations on the advantages and characteristics of the two methods,which was compared with the schemes respectively based on DL or Atlas from the aspect of the time consumed for segmentation.Results Accuracy comparison showed Atlas segmentation model behaved better significantly than DL model for CTV(P<0.05),while obviously worse than the latter for DSC and MDA in bladder and rectum(P<0.05).The doctor took 9.4 min in average for CTV and OAR modification based on DL model and 12 min in average for Atlas-model-based modification.The joint auto-segmentation scheme only needed 8 min in average for CTV and OAR modification,which gained advantages over the schemes based on DL or Atlas.Conclusion The auto-segmentation based on combined DL and Atlas during online adaptive MRI-guided radiotherapy behaves well in low time consumption,high accuracy and efficiency.[Chinese Medical Equipment Journal,2024,45(6):59-64]
7.Study on the antitussive and expectorant activities and mechanism of platycodin D based on metabolomics method
Xin-yu ZHANG ; Yuan-han ZHONG ; Yan FENG ; Xue-mei ZHANG ; Shou-wen ZHANG ; Jin-xiang ZENG
Acta Pharmaceutica Sinica 2024;59(3):724-734
In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and
8.Rat cardiac fibroblasts inhibit gap junction between cardiomyocytes through increasing matrix metalloproteinase 2 activity
Xue BAI ; Hong GAO ; Xiang HUANG ; Xu YAN ; Tingju HU ; Rui CHEN ; Li AN ; Yuting SONG
Chinese Journal of Pathophysiology 2024;40(3):465-472
AIM:To investigate the effect of conditioned medium from hypoxia/reoxygenation(H/R)-treated rat cardiac fibroblasts(CFs)on gap junction between cardiomyocytes and determine whether its mechanism is related to matrix metalloproteinase 2(MMP2)activity.METHODS:(1)H9c2 cells were randomly divided into five groups:con-trol group,normal group,ARP-100 group,H/R group,and H/R+ARP-100 group.Scrape loading/dye transfer assay was used to assess the gap junction function.Western blot was used to detect the expression and phosphorylation levels of Cx43.Gelatin zymography assay was performed to measure MMP2 activity.(2)SD rats were randomly divided into control group,ARP-100 group,ischemia-reperfusion(I/R)group,and I/R+ARP-100 group,with 8 rats in each group.Micro-electrode array technology was used to record the type and duration of arrhythmia.Immunohistochemistry experiment was performed to assess expression levels and distribution of Cx43 in myocardial tissues.RESULTS:Compared with the con-trol group,the H/R group showed decreased protein expression of Cx43(P<0.01),narrowed distance of lucifer yellow dif-fusion(P<0.01),and increased MMP2 activity(P<0.01).ARP-100 attenuated H/R-induced gap junction dysfunction(P<0.05).The arrhythmia score was also reduced after perfusion with ARP-100(P<0.01).CONCLUSION:H/R-treated rat CFs can inhibit gap junction between cardiomyocytes,and its mechanism may involve increased MMP2 activity.
9.Efficacy and safety of recombinant human anti-SARS-CoV-2 monoclonal antibody injection(F61 injection)in the treatment of patients with COVID-19 combined with renal damage:a randomized controlled exploratory clinical study
Ding-Hua CHEN ; Chao-Fan LI ; Yue NIU ; Li ZHANG ; Yong WANG ; Zhe FENG ; Han-Yu ZHU ; Jian-Hui ZHOU ; Zhe-Yi DONG ; Shu-Wei DUAN ; Hong WANG ; Meng-Jie HUANG ; Yuan-Da WANG ; Shuo-Yuan CONG ; Sai PAN ; Jing ZHOU ; Xue-Feng SUN ; Guang-Yan CAI ; Ping LI ; Xiang-Mei CHEN
Chinese Journal of Infection Control 2024;23(3):257-264
Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P<0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P>0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P>0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.
10.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

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