1.Programmed cell death 10 mediates the migration of glioma cells by regulating the PP2A/p38 signaling pathway
Xueyan WAN ; Jiazhao XIE ; Kai ZHAO ; Fanli KONG ; Qi MEI
Journal of Clinical Surgery 2024;32(7):693-696
Objective To explore the molecular mechanism of programmed cell death 10(PDCD10)mediating glioma migration.Methods A PDCD10-silenced glioma cell line(U251)was constructed by siRNA,and the cells were treated with Okadaic Acid(OA),a protein phosphatase 2A(PP2A)phosphatase inhibitor,to investigate the effect of down-regulation of PDCD10 on the behavior of U251 cells;Western Blot(WB)was applied to detect the expression of PDCD10,PP2A,PP2Ac-307,p38 and pP38 in the control group and PDCD10 down-regulation group of U251 cells,to study the mechanism of PDCD10 regulation of PP2A/p38 signaling.Results Down-regulation of PDCD10 in U251 cells promoted the cells migration(P<0.05),which could be inhibited by PP2A phosphatase inhibitor OA(P<0.01).Further studies showed that down-regulation of PDCD10 promoted glioma cell migration via modulating the phosphorylation of PP2A,which in turn altered the activity of p38(P<0.01).Conclusion PDCD10 may mediate glioma cell migration by regulating PP2A/p38 signaling.
2.Development and Validation of a Pathomics Model Using Machine Learning to Predict CXCL8 Expression and Prognosis in Head and Neck Cancer
Weihua WANG ; Suyu RUAN ; Yuhang XIE ; Shengjian FANG ; Junxian YANG ; Xueyan LI ; Yu ZHANG
Clinical and Experimental Otorhinolaryngology 2024;17(1):85-97
Objectives:
. The necessity to develop a method for prognostication and to identify novel biomarkers for personalized medicine in patients with head and neck squamous cell carcinoma (HNSCC) cannot be overstated. Recently, pathomics, which relies on quantitative analysis of medical imaging, has come to the forefront. CXCL8, an essential inflammatory cytokine, has been shown to correlate with overall survival (OS). This study examined the relationship between CXCL8 mRNA expression and pathomics features and aimed to explore the biological underpinnings of CXCL8.
Methods:
. Clinical information and transcripts per million mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA)-HNSCC dataset. We identified correlations between CXCL8 mRNA expression and patient survival rates using a Kaplan-Meier survival curve. A retrospective analysis of 313 samples diagnosed with HNSCC in the TCGA database was conducted. Pathomics features were extracted from hematoxylin and eosin–stained images, and then the minimum redundancy maximum relevance, with recursive feature elimination (mRMR-RFE) method was applied, followed by screening with the logistic regression algorithm.
Results:
. Kaplan-Meier curves indicated that high expression of CXCL8 was significantly associated with decreased OS. The logistic regression pathomics model incorporated 16 radiomics features identified by the mRMR-RFE method in the training set and demonstrated strong performance in the testing set. Calibration plots showed that the probability of high gene expression predicted by the pathomics model was in good agreement with actual observations, suggesting the model’s high clinical applicability.
Conclusion
. The pathomics model of CXCL8 mRNA expression serves as an effective tool for predicting prognosis in patients with HNSCC and can aid in clinical decision-making. Elevated levels of CXCL8 expression may lead to reduced DNA damage and are associated with a pro-inflammatory tumor microenvironment, offering a potential therapeutic target.
3.Precise assembly of inside-out cell membrane camouflaged nanoparticles via bioorthogonal reactions for improving drug leads capturing.
Xiaolin ZHANG ; Xueyan ZHEN ; Yixuan YANG ; Quan FENG ; Wanqing YUAN ; Xiaoyu XIE
Acta Pharmaceutica Sinica B 2023;13(2):852-862
Cell membrane camouflaged nanoparticles have been widely used in the field of drug leads discovery attribute to their unique biointerface targeting function. However, random orientation of cell membrane coating does not guarantee effective and appropriate binding of drugs to specific sites, especially when applied to intracellular regions of transmembrane proteins. Bioorthogonal reactions have been rapidly developed as a specific and reliable method for cell membrane functionalization without disturbing living biosystem. Herein, inside-out cell membrane camouflaged magnetic nanoparticles (IOCMMNPs) were accurately constructed via bioorthogonal reactions to screen small molecule inhibitors targeting intracellular tyrosine kinase domain of vascular endothelial growth factor recptor-2. Azide functionalized cell membrane acted as a platform for specific covalently coupling with alkynyl functionalized magnetic Fe3O4 nanoparticles to prepare IOCMMNPs. The inside-out orientation of cell membrane was successfully verified by immunogold staining and sialic acid quantification assay. Ultimately, two compounds, senkyunolide A and ligustilidel, were successfully captured, and their potential antiproliferative activities were further testified by pharmacological experiments. It is anticipated that the proposed inside-out cell membrane coating strategy endows tremendous versatility for engineering cell membrane camouflaged nanoparticles and promotes the development of drug leads discovery platforms.
4.Analysis of prenatal phenotype and pathogenetic variant in a fetus with Papillorenal syndrome.
Xiang ZHAO ; Dan YANG ; Yumin JIA ; Yanling SHOU ; Liming WANG ; Xiangzhi WANG ; Jiena FU ; Huafeng GUO ; Jianping ZHAO ; Hao YIN ; Xueyan ZHANG ; Xiwei ZHU ; Lijuan GAO ; Chaojie MA ; Zedan XIE ; Man SHI
Chinese Journal of Medical Genetics 2020;37(9):958-961
OBJECTIVE:
To determine the carrier rate of deafness-related genetic variants among 53 873 newborns from Zhengzhou.
METHODS:
Heel blood samples of the newborns were collected with informed consent from the parents, and 15 loci of 4 genes related to congenital deafness were detected by microarray.
RESULTS:
In total 2770 newborns were found to carry deafness-related variants, with a carrier rate of 5.142%. 1325 newborns (2.459%) were found to carry heterozygous variants of the GJB2 gene, 1071 (1.988%) were found with SLC26A4 gene variants, 205 were found with GJB3 gene variants (0.381%), and 120 were found with 12S rRNA variants (0.223%). Five newborns have carried homozygous GJB2 variants, two have carried homozygous SLC26A4 variants, five have carried compound heterozygous GJB2 variants, and four have carried compound heterozygous SLC26A4 variants. 33 neonates have carried heterozygous variants of two genes at the same time.
CONCLUSION
The carrier rate of deafness-related variants in Zhengzhou, in a declining order, is for GJB2, SLC26A4, GJB3 and 12S rRNA. The common variants included GJB2 235delC and SLC26A4 IVS7-2A>G, which are similar to other regions in China. To carry out genetic screening of neonatal deafness can help to identify congenital, delayed and drug-induced deafness, and initiate treatment and follow-up as early as possible.
5.Central venous catheter-related thrombosis in critically ill patients: a prospective observational study by ultrasonography
Shuhan CAI ; Qin XIE ; Yuqian ZHAO ; Xueyan ZHANG ; Zhifeng LI ; Zhiyong PENG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2019;26(2):167-170
Objective Doppler ultrasonography was used to screen the incidence of central venous catheter (CVC) thrombosis in severe patients to observe the incidences of catheter-related thrombosis (CRT) at subclavian (SC) and internal jugular (IJ) venous insertion sites, and to analyze the factors affecting the thrombosis. Methods One hundred and twenty three adult patients with IJ or SC CVC admitted to the Department of Intensive Care Unit (ICU) of Zhongnan Hospital of Wuhan University from May to December 2015 were enrolled to be the research objects, they were divided into an IJCVC group (35 cases) and a SCCVC group (88 cases) according to different catheterization sites; they were divided into an operation group (85 cases) and a non-operation group (38 cases) according to whether operation was performed or not; and they were also divided into an anticoagulation group (25 cases) and a non-anticoagulation group (98 cases) according to whether anticoagulation therapy was used or not. Doppler ultrasonography was performed every day to observe the incidences of CRT during ICU stay. Results One hundred and twenty-three patients were included in this study. CRT was detected in 11 (8.9%) patients, with an incidence of 22.1 per 1 000 catheter-days. All the 11 cases with CRT were presented within 3 days after the insertion, with 9 cases (81.8%) on the first day and 2 cases (18.2%) on the third day. The incidence of CRT in SCCVC group was significantly lower than that in IJCVC group [5.7% (5/88) vs. 17.1% (6/35), P < 0.05], with the rates of 12.6 and 59.4 per 1 000 catheter-days, respectively. There were no statistical significant differences in the incidences of CRT between operation group and non-operation group [11.8% (10/85) vs. 2.6% (1/38)], and between anticoagulation group and non-anticoagulation group [8.0% (1/25) vs. 9.2% (2/98), both P > 0.05]. Conclusions The incidence of CRT at IJCVC site is estimated to be 3-times higher than that at SCCVC site, anticoagulants or surgical operation may have impacts on the incidence of CRT, although there were no statistically significant differences. The CRT usually occurs within 3 days after the catheter insertion. Frequent bedside ultrasonography in the first 3 days after catheterization can confirm the diagnosis and guide clinical treatment.
6.Relationship between the level of human platelet factor IV and Plasmodium falciparum infection
Dongde XIE ; Jiangtao CHEN ; Eyi Monsuy URBANO ; Matesa Apicante ROCIO ; Maximo Miko Ondo Obono ; Ehapo Sala CARLOS ; Ying LI ; Xueyan LIANG ; Min LIN
The Journal of Practical Medicine 2018;34(1):132-134,139
Objective To investigate the relationship between Plasmodium infection and platelet factor Ⅳ(PF4) and to provide the ideas for the treatment of malaria.Methods The serum PF4 concentration was determined with the Enzyme-linked immunosorbent assay (ELISA) in the malaria group (122 cases of malaria patients)and the control group (399 cases of normal).The average value (mean) and positive rate of PF4 were compared between two groups.Results The PF4 level of malaria group was significantly higher than that in the control group and the difference between two groups was statistical significance (P < 0.05).There was no significant difference in Plasmodium falciparum density between the PF4 high level group and the PF4 normal group in the malaria group.Conclusions The expression of human PF4 level has definite relationship with the plasmodium infection of Equatorial Guinea.
7.Analysis on levels of AA and DHA in breast milk and their influence factors of 514 lactating mothers
Xueyan CHEN ; Yixia WU ; Guoliang LIU ; Zhen DING ; Xiang LI ; Zhenwei GAN ; Lin XIE
Journal of Jilin University(Medicine Edition) 2016;42(2):390-394
Objective:To analyze the levels of arachidonic acid (AA)and docosahexaenoic acid (DHA)in the breast milk of lactating mothers in Changchun City of Jilin Province, and to explore their influence factors. Methods:The lactating mother’s basic information was collected with questionnaire, and the breast milk of lactating mothers on postpartum 22-25 d was obtained and the 3-day 24-hour dietary recall method was used to investigate the dietary intake information of 514 healthy lactating mothers.The Food Composition Table of China 2009 was used to calculate the intakes of five kinds of polyunsaturated fatty acids (PUFAs) in diet of lactating mothers and the gold key nutrition expert system software for corresponding nutrient analysis was used to calculate the amount of various kinds of foods in the lactating mothers’daily diet.The levels of AA and DHA in breast milk were determined with gas chromatography and the linear regression was used to analyze the related factors of AA and DHA levels in breast milk.Results:①The average concentration of AA in breast milk of 514 lactating mothers was (0.08±0.04)g·100 g-1,and the average concentration of DHA was (0.05±0.04)g·100 g-1. ②The single factor correlation analysis results showed that the oil intake was both positively correlated with AA and DHA levels in milk of lactating mothers (r= 0.360,r=0.354,P<0.001),while the intakes of linoleic acid (LA), alpha linolenic acid (ALA),eicosapentaenoic acid (EPA),DHA,dairy and meats and seafood in diet were both negatively correlated with AA (r= -0.321,r=-0.280,r=-0.255,r=-0.299,r=-0.196 ,r=-0.306,P<0.05)and DHA (r=-0.315,r=-0.279,r=-0.175,r=-0.189,r=-0.248,r=-0.142,P<0.05).③The linear regression analysis results showed regression equation that dairy intake (β=-0.265)and EPA intake (β=-0.144)were both negatively correlated with the level of AA (P=0.009),and dairy intake was also negatively correlated with the level of DHA (β=-0.233,P<0.001).Conclusion:The AA and DHA levels in breast milk of lactating mothers didn’t increase with the increasing of intake of milk or dairy products in the study.Moreover there is a competitive relationship between n-6 and n-3 series polyunsaturated fatty acids in the process of metabolism.
8.Pharmackinetics of Reduning injection for nasal administration in rabbits
Zhen XIE ; Xueyan WANG ; Xin ZHAO ; Jingzhao ZHANG ; Xudong TANG
Journal of China Pharmaceutical University 2016;47(5):599-602
Reduning nasal sprays were prepared from Reduning injection to explore the pharmacokinetics of its nasal administration in rabbits. Healthy rabbits were divided into three groups: blank group, nasal administration group, and intravenous injection group. Plasma samples were pretreated using acetonitrite to precipitate proteins. High-performance liquid chromatography(HPLC)was performed for the detection of chlorogenic acid. The results showed that chlorogenic acid was detected in the plasma samples of nasal administration group with the highest concentration occurring in 2-5 min after administration, which indicated that Reduning nasal sprays could be successfully absorbed from nasal mucosa and could rapidly metabolize in blood. Compared with intravenous injection group, nasal administration group had lower concentration of active ingredients, revealing that the transdermal absorption rate of Reduning nasal sprays requires further improvement.
9.Association analysis on polymorphisms of ELOVL2 gene and DHA level in breast milk of lactating mothers
Xiang LI ; Zhen DING ; Yixia WU ; Xueyan CHEN ; Guoliang LIU ; Lin XIE
Journal of Jilin University(Medicine Edition) 2015;(6):1230-1234
Objective To investigate the association between rs2281951 and rs3798753 in ELOVL fatty acid elongase2 (ELOVL2 gene)and the docosahexenoic acid (DHA)level in breast milk,and to clarify the influence of the polymorphisms of ELOVL2 gene in the DHA level of breast milk.Methods 209 healthy maternals were selected and signed the consent form and completed the 3-day 24-hour dietary recall questionaire on one day during the 22nd-the 25th day after partum,and 20 mL breast milk was collected.The DHA level in breast milk was detected with gas chromatography.The milk DNA was extracted and two single nucleotide polymorphisms (SNPs) of ELOVL2 gene were detected by Sequenom Mass Array System. UNPHASED 3.012 genetics software was adopted to analyze the quantitative trait of haplotype and the DHA level in breast milk.Results The distribution of genotypic frequencies of rs2281591 and rs3798713 sites in ELOVL2 gene was consistent with Hardy-Weinberg equilibrium (P > 0.05).The dietary fatty acid intakes and the milk DHA levels of maternals carrying different genotypes had no statistically significant differences (P > 0.05 ). The DHA levels in breast milk of maternals carring different rs3798713 (CG)-rs2281591 (AG)haplotypes had no statistically significant difference (χ2 =3.422,df =5,P =0.635).Conclusion Rs3798713 and rs2281951 and constructed haplotypes in ELOVL2 gene are not related to the DHA levels in breast milk.
10.Influnce of an optimized resuscitation bundle on prognosis of emergency patients with septic shock
Jiangxia XIE ; Shukun YANG ; Kaixiu HUO ; Xueyan LIU ; Dayong SUN ; Kuncheng YU
Chinese Journal of Primary Medicine and Pharmacy 2013;20(13):1999-2001
Objective To evaluate the effects of an optimized resuscitation bundle on prognosis of emergency patients with septic shock.Methods 65 patients with septic shock,admitted into emergency intensive care unit (ICU),were randomly divided into the treatment group(treated by an optimized resuscitation bundle)and the control group(treated by surviving sepsis campaign classics methods)by using random number table.The scores of sepsis-related organ failure assessment(SOFA) scores,the vasoactive agent application times,the mechanical ventilation times,the stay days of ICU,and 28-day mortality of the two groups were observed and compared.Results 3,7 day after erollment the SOFA score of the treatment group was (9.1 ± 2.5) points,(8.2 ± 2.8) points,respectively,which was lower than that of the control group[(10.1 ± 3.3) points,(9.5 ± 3.1) points] at the same time(t =4.52,3.99,all P < 0.05) ; 8-day mortality rate of the treatment group was 28.1%,which was lower than that of the control group (48.5%) (x2 =12.84,P < 0.05).Conclusion Application of an early optimized resuscitation bundle can significantly improve the prognosis of emergency patients with septic shock.

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