Objective To evaluate the role and potential mechanism of apolipoprotein E(APOE)in drug resistance of colon cancer by bioinformatic tools and cellular experiments.Methods After downloading the microarray dataset GSE196900 from the GEO database,the online tool GEO2R was used to identify genes that were expressed differently in the drug-resistant and control groups.The differently expressed genes were then examined for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.The STRING database and Cytoscape software were used to build protein-protein interaction(PPI)networks and find hub genes.Hub genes'predictive significance in colon cancer was further assessed.Western blod and qRT-PCR were used to identify changes in APOE expression,whereas Transwell was used to identify changes in the colon cancer cells'capacity for invasion and migration.Results The analysis of GO and KEGG enrichment revealed that the differential genes derived from the GSE196900 dataset were primarily focused on receptor-ligand activity and cytokine-cytokine receptor interaction pathways.Using the CytoNCA plug-in in Cytoscape software,ten hub genes were obtained through PPI construction.Of these,the prognosis of the patients with colon cancer was negatively correlated with the expression of the APOE gene(P<0.05)and the overexpression of the APOE gene might significantly increase the migration and nvasivenessability of colon cancer cells(P<0.05).Conclusion The increased expression of APOE significantly promotes the migration and invasion ability of colon cancer cells,which may be one of the mechanisms by which APOE gene promotes tumor progression in the patients with colon cancer.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

his study was aimed at understanding the drug resistance of Acinetobacter baumannii,exploring the consistency between resistance genes and resistance phenotypes,and providing a basis for the rational use of antibiotics in clinical practice.A total of 88 strains of Acinetobacter baumannii were isolated from hospitals at tertiary level or above within the jurisdiction from 2021 to 2023,and subjected to drug resistance testing and whole genome sequencing.The original data were analyzed for the entire genome process with a Microobench pathogenic microorganism analysis workstation(without reference splicing),and resistance genes were predicted and annotated.The strains were subjected to multi-point sequence analysisand minimum spanning tree construction.Among 88 strains of Acinetobacter baumannii,carbapenem resistant strains(CRAB)accounted for 72.73%,and 98.44%of CRAB showed multidrug resistance.In the past three years,the resistance to multiple drugs has increased.The cgMLST analysis showed that the ST2 type accounted for 89.77%,and a new ST type was discovered.After cgMLST analysis,the minimum spanning tree was generated,and the genetic relationship of the same ST type was closer.The same ST2 type was further divided into four clusters.Binary logistic regression analysis conducted on resistance genes and resistance phenotypes revealed that resistance genes APH(3″)-Ib,armA,ADC-73,sul1,and sul2 positively correlated with resistance phenotypes.The ST2 type was the main Acinetobacter baumannii type,and showed high rates of multidrug resistance and carriage of multiple resistance genes.The drug resistance situation is severe.The consistency between common resistance genes and resistance phenotypes is good.Clinical management of Acinetobacter baumannii infection must be strengthened to prevent outbreaks and transmission.

his study was aimed at understanding the drug resistance of Acinetobacter baumannii,exploring the consistency between resistance genes and resistance phenotypes,and providing a basis for the rational use of antibiotics in clinical practice.A total of 88 strains of Acinetobacter baumannii were isolated from hospitals at tertiary level or above within the jurisdiction from 2021 to 2023,and subjected to drug resistance testing and whole genome sequencing.The original data were analyzed for the entire genome process with a Microobench pathogenic microorganism analysis workstation(without reference splicing),and resistance genes were predicted and annotated.The strains were subjected to multi-point sequence analysisand minimum spanning tree construction.Among 88 strains of Acinetobacter baumannii,carbapenem resistant strains(CRAB)accounted for 72.73%,and 98.44%of CRAB showed multidrug resistance.In the past three years,the resistance to multiple drugs has increased.The cgMLST analysis showed that the ST2 type accounted for 89.77%,and a new ST type was discovered.After cgMLST analysis,the minimum spanning tree was generated,and the genetic relationship of the same ST type was closer.The same ST2 type was further divided into four clusters.Binary logistic regression analysis conducted on resistance genes and resistance phenotypes revealed that resistance genes APH(3″)-Ib,armA,ADC-73,sul1,and sul2 positively correlated with resistance phenotypes.The ST2 type was the main Acinetobacter baumannii type,and showed high rates of multidrug resistance and carriage of multiple resistance genes.The drug resistance situation is severe.The consistency between common resistance genes and resistance phenotypes is good.Clinical management of Acinetobacter baumannii infection must be strengthened to prevent outbreaks and transmission.

Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

AIM To study the chemical constituents from seeds of Canavalia gladiata(Jacq.)DC.,and their estrogen-like activities.METHODS The 75% ethanol extract from the seeds of C.gladiata was isolated and purified by various chromatography,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The estrogen-like activities were evaluated by human breast cancer cells(MCF-7)stably transfected with estrogen receptor reporter gene(ER-Luc).RESULTS Twelve compounds were isolated and identified as biorobin(1),kaempferol 3-O-[O-β-D-apio-D-furanosyl(1→2)-O-[α-L-rhamno-pyranosyl(1 → 6)]-β-D-galactopyranoside(2),kaempferol 3-O-{β-D-glucopyranosyl(1 → 2)-[α-L-rhamonopyranosyl(1→6)]-β-D-galactopyranoside}(3),iso-quercitrin(4),quercetin 3-O-(6″-O-galloyl)-β-D-glucoside(5),isomyricitrin(6),myricetin-3-O-rutinoside(7)(3-ethenylphenyl)-1,2-ethanediol(8),1,3,6-tri-O-galloyl-β-D-glucopyranose(9),breynioside A(10),4-hydroxy-3-methoxyphenol-1-O-β-D-(6′-O-galloyl)glucoside(11),maesopsin-6-O-β-D-glucopyranoside(12).Compounds 1,3-5,8-9 in the concentration of 50 μmol/L,and compounds 2,12 in 100 μmol/L showed estrogen-like activities.CONCLUSION All compounds are isolated from the gene Canavalia for the first time.Compounds 1,3-5,8-9 showed stronger estrogen-like activities than compounds 2 and 12.

AIM To study the chemical constituents from the large polar fraction of the roots of Lindera reflexa Hemsl.and their antitumor activities.METHODS The large polar fraction from the roots of L.reflexa was isolated and purified by silica gel column,Sephadex LH-20 gel column,semi-preparative HPLC and ODS medium pressure column,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT method.RESULTS Thirteen compounds were isolated and identified as 2,6-dimethoxy-4-hydroxyphenyl-1-O-β-D-glucopyranoside(1),3-hydroxy-4,5-dimethoxyphenol-β-D-glucopyranoside(2),syringin(3),1-O-3,4-dimethoxy-5-hydroxyphenyl-(6-O-3,5-dimethoxygalloyl)-β-D-glucopyranoside(4),p-cymen-7-yl β-D-glucopyranoside(5),pisumionoside(6),staphylionoside D(7),dendranthemoside B(8),lynoiside(9),nudiposide(10),icariside B1(11),(2S)-pinocembrin-7-O-(6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside)(12),(+)-N-(methoxycarbonyl)-N-norboldine(13).Compounds 3 and 13 showed obvious cytotoxicity against human lung cancer cells(A549)and human gastric cancer cells(MGC80-3).CONCLUSION Compounds 1-13 are isolated from the roots of L.reflexa for the first time.Compounds 3 and 13 have good anti-tumor activities.

Objective To investigate the dosimetric effects of different calculation grid size(CGS)in helical tomotherapy(HT)planning system on stereotactic body radiation therapy(SBRT)for non-small cell lung cancer(NSCLC).Methods Nine NSCLC patients receiving radiation therapy for the first time at some hospital from March 2019 to December 2022 were selected as the subjects.SBRT planning was carried out through the HT system with three different CGS plans(Fine,Normal,and Coarse)and the same pitch,modulation factor(MF)and optimization conditions,and the target area indexes of the three CGS plans were compared including conformity index(CI),homogeneity index(HI),dosimetric parameters of the organ at risk(OAR),point dose verification pass rate,treatment time,number of monitor units and Sinograms.SPSS 22.0 was used for statistical analysis.Results For target area HI,there weres significant differences between CGS Fine plan and Coarse plan and between CGS Normal plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan(P＞0.05).For target area CI,there were significant differences between CGS Fine plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan and between CGS Normal plan and Coarse plan(P＞0.05).For OAR dosimetric parameters,CGS Fine plan and Coarse plan had significant differences in heart Dmax and Dmean,esophageal Dmax and Dmean,V5,V20,V30 and Dmean of the whole lung and affected lung,V5 and Dmax of the affected lung and heart V10 and V30(P＜0.05),CGS Normal plan and Coarse plan had obvious differences in esophageal Dmax(P＜0.05),and the remained dosimetric parameters were not statistically significant(P＞0.05).Fine,Normal and Coarse plans had the point dose verifica-tion pass rates being 0.96％,1.50％and 1.77％,respectively.In terms of treatment time and number of monitor units,there were significant differences between Fine plan and Coarse plan(P＜0.05)while no statistical differences were found between Fine and Normal plans and between Normal and Coarse plans(P＞0.05).Sinograms analyses showed Fine plan had evenly distributed segment color gradient,Coarse plan had areas of very dark and very light color gradients and Normal plan was somewhere in between.Conclusion Low CGS has to be used as much as possible to obtain accurate dose distribution during SBRT planning for NSCLC patients,which contributes to the execution of the radiation therapy plan and the prevention of ad-verse effects.[Chinese Medical Equipment Journal,2024,45(2):52-57]