Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.

Aim To mine the competing ceRNA net-works associated with programmed cell death in the pathophysiological mechanisms of atherosclerosis(AS)based on bioinformatics,in order to identify new targets for the diagnosis and treatment of AS.Methods Firstly,the GSE97210 and GSE28858 datasets were screened from the GEO database.Differentially ex-pressed lncRNA,mRNA and miRNA were identified,following which a IncRNA-miRNA-mRNA regulatory network was constructed in Cytoscape 3.7.2 software based on ceRNA theory.Second,GO and KEGG en-richment analysis of mRNA in the ceRNA network was performed.Finally,the mRNAS within the ceRNA net-work were compared with genes related to autophagy,pyroptosis and ferroptosis to establish a ceRNA network related to programmed cell death.Results A total of 1208 DElncRNAS,4723 DEmRNAS and 139 DEmiR-NAS were identified.A ceRNA network was estab-lished,comprising 64 lncRNAS,8 miRNAS and 167 mRNAS.The mRNAS within the CeRNA network were mainly enriched in biological processes such as positive regulation of transcription and migration,protein bind-ing,and signaling pathways including PI3K-Akt signa-ling pathway,and mTOR signaling pathway.Finally,this study established 7 lncRNA-mediated ceRNA regu-latory pathways associated with pyroptosis and 23 ln-cRNA-mediated regulatory pathways for ferroptosis and autophagy.Conclusion This study has successfully constructed a ceRNA network related to programmed cell death,which helps us understand the mechanism by which programmed cell death leads to AS.

Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.

Aim To mine the competing ceRNA net-works associated with programmed cell death in the pathophysiological mechanisms of atherosclerosis(AS)based on bioinformatics,in order to identify new targets for the diagnosis and treatment of AS.Methods Firstly,the GSE97210 and GSE28858 datasets were screened from the GEO database.Differentially ex-pressed lncRNA,mRNA and miRNA were identified,following which a IncRNA-miRNA-mRNA regulatory network was constructed in Cytoscape 3.7.2 software based on ceRNA theory.Second,GO and KEGG en-richment analysis of mRNA in the ceRNA network was performed.Finally,the mRNAS within the ceRNA net-work were compared with genes related to autophagy,pyroptosis and ferroptosis to establish a ceRNA network related to programmed cell death.Results A total of 1208 DElncRNAS,4723 DEmRNAS and 139 DEmiR-NAS were identified.A ceRNA network was estab-lished,comprising 64 lncRNAS,8 miRNAS and 167 mRNAS.The mRNAS within the CeRNA network were mainly enriched in biological processes such as positive regulation of transcription and migration,protein bind-ing,and signaling pathways including PI3K-Akt signa-ling pathway,and mTOR signaling pathway.Finally,this study established 7 lncRNA-mediated ceRNA regu-latory pathways associated with pyroptosis and 23 ln-cRNA-mediated regulatory pathways for ferroptosis and autophagy.Conclusion This study has successfully constructed a ceRNA network related to programmed cell death,which helps us understand the mechanism by which programmed cell death leads to AS.

Objective:To seed for stable time window of the integrated disease-syndrome animal model based on the counterevidence from Chinese medicinal prescriptions， and to verify syndrome stability and reliability. Method:A model of depression was established by exposing rats to chronic unpredictable mild stress （CUMS）， followed by body weight measurement， sugar water test， behavioral test， and brain 5-hydroxytryptamine（5-HT） detection. The identification of liver depression and spleen deficiency syndrome was conducted after the equivalent transformation of human clinical symptoms into macroscopic representations of rats. Based on the dynamically collected macroscopic representation scale， Xiaoyaosan was used to reversely verify the stability and reliability of the integrated disease-syndrome animal model of depression due to liver depression and spleen deficiency. Result:The sugar water consumption and the number of crossings and the total movement distance in the open field test of 16-week-old rats in the CUMS （eight weeks of CUMS） group were significantly lower than those in the normal group （P<0.05）. According to the immunohistochemical results， the 5-HT content in hippocampal area CA2 of rats in the CUMS group was also significantly lowered as compared with that in the normal group（P<0.05），which indicated that depression was successfully modeled. The liver depression and spleen deficiency syndrome was present in 14-week-old rats （six weeks after CUMS）of the CUMS group， and the number of rats experiencing the liver depression and spleen deficiency syndrome reached the peak in the 16th week （eight weeks after CUMS），accounting for 70% of the total number. Thereafter， the number decreased gradually. The syndrome scores of the 14-， 16-， 18-， 20-， and 22-week-old rats in the Xiaoyaosan group were reduced by 66.6%， 70.7%， 54.8%， 50.4%， and 44.8%， which were graded as effective， marked effective， effective， effective， and effective， respectively. Conclusion:The age of 14-16 weeks（six to eight weeks after CUMS） is considered the stable and reliable time window for depression due to liver depression and spleen deficiency.

We established a multiplex direct PCR for rapid detection of E.coli,Salmonella,Staphylococcus aureus,Listeria and Yersinia enterocolitica bacteria.Multiplex direct PCR primers were designed according to gene sequences of phoA (E.coli),inv A (Salmonella),nuc (S.aureus),hl y (Listeria),and ail (Y.enterocolitica).After the multiplex direct PCR were established,the specificity and sensitivity of primers were detected.Then,multiplex direct PCR was applied to examine 60 swine product samples,the detection specificity,accuracy and positive predictive value were calculated compared with the gold standard culture method.Results showed that multiplex direct PCR primers could be used for specific detection of E.coli,Salmonella,S.aureus,Listeria and Y.enterocolitica,with the minimal detectable limit of 10,1,100,1 and 1 CFU,respectively.For the examination of 60 swine product samples using multiplex direct PCR,15 were positive for E.coli,6 positive for Salmonella,21 positive for S.aureus,20 positive for Listeria,and 35 positive for Y.enterocolitica,with all positive detection rates higher than that of culture.The total detection sensitivity was 100％,accuracy was 94％,and positive predictive value was 81.44％.Multiplex direct PCR could be used for specific and sensitive detection of common food-borne pathogens,and the testing time was shorten to be 3 hours because of saving time for template extraction.Multiplex direct PCR might serve the detection of food-borne pathogens in food safety risk monitoring much better.

BACKGROUNDThe prognostic values of the coronary computed tomography angiography (CCTA) score for predicting future cardiovascular events have been previously demonstrated in numerous studies. However, few studies have used the rich information available from CCTA to detect functionally significant coronary lesions. We sought to compare the prognostic values of Gai's plaque score and the coronary artery calcium score (CACS) of CCTA for predicting functionally significant coronary lesions, using fractional flow reserve (FFR) as the gold standard.

METHODSWe retrospectively analyzed 107 visually assessed significant coronary lesions in 88 patients (mean age, 59.6 ± 10.2 years; 76.14% of males) who underwent CCTA, invasive coronary angiography, and invasive FFR measurement. An FFR <0.80 indicated hemodynamically significant coronary stenosis. Lesions were divided into two groups using an FFR cutoff value of 0.80. We compared Gai's plaque scores and CACS between the two groups and evaluated the correlations of these scores with FFR. The statistical methods included unpaired t-test, Mann-Whitney U-test, and Spearman's correlation coefficients.

RESULTSCoronary lesions with FFR <0.80 had higher Gai's scores than those with FFR ≥0.80. Gai's score had the strongest correlation with FFR (r = -0.48, P < 0.01) and had a greater area under the curve = 0.72 (95% confidence interval: 0.61-0.82; P < 0.01) than the CACS of whole arteries and a single artery.

CONCLUSIONSBoth CACS in a single artery and Gai's plaque score demonstrated a good capacity to assess functionally significant coronary artery stenosis when compared to the gold standard FFR. However, Gai's plaque score was more predictive of FFR <0.80. Gai's score can be easily calculated in daily clinical practice and could be used when considering revascularization.

Aged ; Computed Tomography Angiography ; Coronary Angiography ; Coronary Stenosis ; pathology ; Coronary Vessels ; pathology ; Female ; Fractional Flow Reserve, Myocardial ; physiology ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Vascular Calcification ; pathology

OBJECTIVETo investigate the effect of premature rupture of the membrane (PROM) on neonatal complications in premature infants.

METHODSThe registration information of 7684 preterm infants with gestational age <37 weeks were collected from the cooperative units in the task group between January 1, 2014 to December 31, 2014. Specially trained personnel from each cooperative units filled in the unified form in a standardized format to record the gender, gestational age, birth weight, PROM, placental abruption, antenatal corticosteroid, Apgar score, amniotic fluid pollution, and complications of the infants. The data were analyzed comparatively between the cases with PROM and those without (control).

RESULTSThe preterm mortality rate was significantly lower but the incidences of ICH, NEC, ROP and BPD were significantly higher in PROM group than in the control group (P<0.05). The 95% confidence interval of the OR value was <1 for mortality, and was >1 for ICH, NEC, ROP and BPD. After adjustment for gestational age, birth weight, gender, mode of delivery, placental abruption, placenta previa, prenatal hormones, gestational diabetes mellitus (GDM), gestational period hypertension and 5-min Apgar score <7, the incidences of NEC, ROP and BPD were significantly different between the two groups (P<0.05) with 95% confidence interval of OR value >1, but the mortality rate and incidence of ICH were not significantly different between the two groups (P>0.05).

CONCLUSIONPROM is a risk factor for NEC, ROP and BPD in preterm infants, and adequate intervention of PROM can reduce the incidences of such complications as NEC, ROP and BPD in the infants.

Apgar Score ; Birth Weight ; Female ; Fetal Membranes, Premature Rupture ; pathology ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Infant, Newborn, Diseases ; etiology ; Infant, Premature ; Pregnancy ; Risk Factors

Adult ; Aortic Coarctation ; therapy ; Catheterization ; Humans ; Male ; Platinum ; Stents