Objective To explore the mechanism of HIF-1α promoting malignant development of nasopharyngeal carcinoma by upregulating PD-L1 expression under hypoxic conditions. Methods CNE2 cells were divided into normoxia (20%O₂), hypoxia (1%O₂), HIF-1α-siRNA+hypoxia and NC-siRNA+hypoxia groups. Cell proliferation, apoptosis, the mRNA levels of HIF-1α, STAT3 and PD-L1, the protein levels of HIF-1α, PD-L1, STAT3 and STAT3 phosphorylation were detected by MTT assay, flow cytometry, RT-PCR and Western blot, respectively. Results Cell proliferation of hypoxia group was significantly higher than that of normoxia group (P=0.000). The cell proliferation rate of HIF-1α-siRNA+hypoxia group was significantly lower than those in other groups (P=0.000). The apoptosis rate of HIF-1α-siRNA+hypoxia group was remarkably higher than those in other groups (P=0.001). RT-PCR detection showed that the mRNA levels of HIF-1α, PD-L1 and STAT3 in the HIF-1α-siRNA+hypoxia group were significantly lower than those in hypoxia group and NC-siRNA+hypoxia group. The protein expression of HIF-1α, PD-L1 and STAT3 showed similar tendency in Western blot assays compared with the mRNA levels. The pSTAT3 protein expression level in HIF-1α-siRNA+hypoxia group was significantly lower than those in hypoxia group and HIF-1α-siRNA+hypoxia group (P=0.001). Conclusion Under hypoxic microenvironment, HIF-1α may up-regulate the expression of PD-L1 through STAT3, thereby promoting the immune escape of cancer cells, leading to the malignant development of nasopharyngeal carcinoma.

Incontinence-associated dermatitis is one of the common complications in critically ill patients.This paper reviews the research progress of risk prediction models for incontinence-associated dermatitis in critically ill patients,introduces and compares the characteristics and application effects of different risk prediction models.The purpose is to provide ideas for constructing a localized risk prediction model and provide evidence for medical staff to identify risk factors of incontinence-associated dermatitis at an early stage and take preventive measures.

Objective To use superparamagnetic iron oxide nanoparticles(SPIONs)to label chimeric antigen receptor(CAR)T cells targeting carcinoembryonic antigen(CEA),and perform magnetic resonance imaging(MRI)to real time trace CEA CAR-T cells in vivo.Methods Appropriate amount of ferumoxytol,heparin sodium and protamine sulfate were mixed at high(ferumoxytol 100 μg/mL,heparin sodium 4 IU/mL,protamine sulfate 120 μg/mL),medium(ferumoxytol 50 μg/mL,heparin sodium 2 IU/mL,protamine sulfate 60 μg/mL),and low(ferumoxytol 25 μg/mL,heparin sodium 1 IU/mL,protamine sulfate 30 μg/mL)concentrations to form a SPIONs complex ferumoxytol/heparin/protamine(FHP),and then co-incubated with CEA CAR-T cells for cell labeling.The biocompatibility of FHP was detected by CCK-8 assay,EdU assay and flow cytometry.The uptake of FHP was detected by Prussian blue staining,and SPIONs content in the cells was quantitatively detected by inductively coupled plasma-mass spectrometry(ICP-MS).Flow cytometry was used to detect the lytic effect of FHP-labeled CEA CAR-T cells on tumor cells,and MRI was employed to scan FHP-labeled CEA CAR-T cells.Results FHP at high,medium,and low concentrations had no significant effect on the activity of CEA CAR-T cells,with cell activity above 100％determined by CCK-8 assay.DNA proliferation was above 94.3％in EdU assays.Prussian blue staining showed that CEA CAR-T cells could take FHP up,with the uptake increased with the increment of FHP concentration.ICP-MS showed that the intracellular Fe content was 440.23±189.36 ng/mL.Tumor cell killing experiment showed that FHP-labeled CEA CAR-T cells had excellent killing capability against tumor cells.MRI scans indicated that T2WI signals of FHP-labeled CEA CAR-T cells were significantly reduced with increasing FHP concentration(P＜0.01).Conclusion SPIONs complex FHP shows good biocompatibility and can effectively label CEA CAR-T cells.SPIONs complex FHP can be used as a magnetic marker for CEA CAR-T cells and a feasible MRI tracer for clinical application.

Objective:To investigate the risk factors of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients in plain-sand areas and loess hilly areas of Gansu province.Methods:A total of 1 599 T2DM patients who participated in chronic disease and risk factors monitoring and basic public health service management were selected by multi-stage stratified random sampling method in the sandy plain areas and loess hilly areas of Gansu province. Questionnaire survey, physical measurement and laboratory tests were performed. Multivariate binary logistic model was used to analyze the influencing factors.Results:The prevalence of DKD was 22.1% (174/787) among T2DM patients in the sandy plain areas and 19.1%(155/812) in the loess hilly area, respectively. Hypertension ( OR=3.022), hyperuricemia ( OR=2.114) and HbA1c≥7%( OR=2.231) were the risk factors for DKD in the plain-sand areas, and the risk of DKD increased with age. In the loess hilly areas, female sex ( OR=0.379) was the protective factor for DKD; while duration of disease≥10 years ( OR=2.476), hyperuricemia ( OR=1.907), HbA1c≥7% ( OR=1.927) were the risk factors for DKD; and the risk of DKD increased with the increase of age, and decreased with the increase of per capita monthly income. Conclusions:The prevalence of DKD and its influencing factors are different between sandy plain areas and loess hilly areas in Gansu province. The prevention and treatment of hypertension should be given more attention in sandy plain areas. In addition, the screening of DKD should be conducted among T2DM patients, particularly for those with old age, hyperuricemia and HbA1c≥7% in both areas of the province.

Aim To investigate the effects of naringenin on atherosclerotic plaque extracellular matrix remodeling and plaque stability.Methods Murine vascular smooth muscle cells were isolated and treated with various doges of naringenin.ApoE-/-mice were fed with high-fat diet and received naringenin by lavage for 16 weeks.Intraplaque nec-rotic core,contents of collagen and fibrous cap thickness were measured by Sirius red-Haematoxylin staining.Elastin was detected by Van Gieson staining.Matrix metalloproteinase(MMP)activity was determined by gelatin zymography and fluorescence-gelatin staining.Results Naringenin(50 μmol/L)increased signal tansducer and activator of transciption 6(STAT6)phosphorylation and promoted tissue inhibitor of metalloproteinase-3(TIMP-3)expression by 3.1-fold(P＜0.001).After naringenin(80 mg/kg)treatment,compared with the control group,the area of plaque necrotic core in aor-tic root decreased by 53％(P＜0.01),the thickness of fibrous caps increased by nearly 50％(P＜0.05),and the degree of elastic fiber degradation decreased.At the same time,naringenin promoted the expression of TIMP-3 in plaques,and corre-spondingly reduced the activity of MMP in plaques.Lentivirus mediated inhibition of TIMP-3 expression in vivo could reduce the protective effect of naringenin on plaque stability.Conclusion Naringin can increase the expression of TIMP-3 in smooth muscle cells,improve the composition of extracellular matrix,and promote the stability of atherosclerotic plaque.

Aim To study the effect of maternal high-fat diet during pregnancy on endothelial to mesenchymal transition of aortic vessels in adult offspring.Methods The pregnant mice were randomly divided into normal diet group and high-fat diet group,and the offspring mice were fed normally for 16 weeks after the mother gave birth.Western blot and RT-qPCR were used to detect the expression and transcription of related proteins,and immunofluorescence and im-munohistochemical staining were used for pathological analysis.Results Compared with the offspring of maternal nor-mal diet during pregnancy,the expressions of vascular inflammatory factors,macrophage infiltration,monocyte-endothelium adhesion were significantly increased in the offspring of maternal high-fat diet(OHF)during pregnancy(P＜0.05).Vas-cular endothelial nitric oxide synthase(eNOS)activity,nitric oxide(NO)level were dramatically reduced(P＜0.05).Immunofluorescence results showed reduced endothelial cell marker CD31 and increased mesenchymal marker α-smooth muscle actin(α-SMA)in OHF.Western blot analysis further confirmed the results,which showed that maternal high fat diet reduced vascular endothelial-cadherin(VE-cadherin)and CD31 and increased α-SMA and Vimentin in the offspring(P＜0.05).The maternal high fat diet increased the extracellular matrix protein disposition and transforming growth factor beta(TGF-β)/Smad signaling in endothelium(P＜0.05).Moreover,the maternal high fat diet reduced Kruppel-like factor 2(KLF2)expression by 76％in mRNA level and 59％in protein level(P＜0.05).Conclusion Maternal high-fat diet during pregnancy lead to a transition of endothelial to mesenchyme in the offspring aorta.The results provide a clue for prevention of vascular disease in early stage.

Objective To provide the experimental basis for the subsequent genetic diversity research through establishing and optimizing the inter-simple sequence repeat PCR (ISSR-PCR) reaction system of Gnaphalium affine. Methods The single-factor experimental method and full experimental method were used to optimize the ISSR-PCR reaction system of Gnaphalium affine. Under the optimal system, after screening primers and corresponding annealing temperatures, the systematic feasibility was verified. Results The optimal ISSR-PCR reaction system was consisted of 10 μl Premix Taq DNA polymerase, 0.3 μmol/L primer, 10 ng DNA template, and sterilized water added to 20 μl. Finally, 10 primers were screened from 100 universal primers, and verification results indicated the system had high stability, good reproducibility, and the selected primers had good polymorphism. Conclusion The ISSR-PCR amplification system of Gnaphalium affine was established for the first time and the primers with appropriate annealing temperatures were filtered out, which provided a reference for the subsequent genetic diversity research of Gnaphalium affine.

Hepatic venous pressure gradient (HVPG) is the "gold standard" for diagnosing portal hypertension and determining its severity, but its wide clinical application is limited due to its invasiveness and difficulties in operation. The replacement of HVPG by noninvasive methods has become a research hotspot in recent years; however, the accuracy of the existing serological and imaging methods remains to be discussed, and such methods cannot completely replace HVPG in clinical practice. Liver biopsy has been widely used in clinical practice for many years and is still an indispensable method for the diagnosis of some liver diseases. Recent studies have found that several pathological indicators after liver biopsy, such as collagen area, fibrous septal thickness, nodule size, microvascular density, and density and area of bile ducts and lymphatic vessels, can not only judge the severity of liver fibrosis, but also have a good correlation with portal venous pressure, which provides new ideas for diagnosing cirrhotic portal hypertension and evaluating the severity of portal hypertension.