Objective To explore the role of hypoxia inducible factor 1α(HIF-1α)-mediated signaling pathway in angiotensin Ⅱ(Ang Ⅱ)induced renal interstitial fibrosis. Methods Renal tubular epithelial cells were cultured and treated with different concentrations (10-9-10-6 mol/L)of Ang Ⅱ for 24 h and 48 h.Real-time quantitative PCR and Western blotting were preformed to detect the mRNA and protein expressions of HIF-1α,prolyl hydroxylase 2 (PHD2)and tissue inhibitor of metalloproteinase 1 (TIMP-1)in renal tubular epithelial cells. Results HIF-1αmRNA level was increased with Ang Ⅱ treatment in a concentration dependent manner.When cells were treated with Ang Ⅱ concentration at 10-7mol/L for 24 h,the mRNA level was markedly increased by 166%.Furthermore,by real-time quantitative PCR and Western blotting,compared with the control group,Ang Ⅱincreased the mRNA and protein levels of HIF-1α and TIMP-1 (P<0.05,respectively),while the mRNA and protein levels of PHD2 were decreased markedly (P<0.05,respectively)in renal tubular epithelial cells.Conclusion Ang Ⅱ reduces HIF-1αdegradation in renal tubular epithelial cells probably by reducing the expression of PHD2,which increases the expressions of HIF-1α and TIMP-1 involved in renal interstitial fibrosis.

OBJECTIVE To study the effect of nano-alumina(nano-Al2 O3 )on mitophagy in primary cortical neuronal cells from Wistar newborn rats. METHODS The purity of neuronal cells was detected by immunohistochemistry,and the lactate dehydrogenase(LDH)assay was performed to determine the viability of the cells treated with 13 nm nano-Al2 O3 0.5 mmol·L-1 for 12,24 and 48 h,respectively. The mitochondrial membrane potential(MMP)was detected by flow cytometry analysis . The ultrastructure of mitochondria and mitophagy vacuoles was observed by transmission electron microscopy(TEM). Auto-phagic vacuoles were observed by dansylpentanediamine(MDC)staining and the expression of autoph-agy related protein Beclin1 and LC3Ⅱ/ Ⅰ was determined by Western blotting. Mitophagy was observed by Lysotracker and Mitotracker staining respectively. RESULTS More than 95% cells were neuronal cells. The activity of LDH in the supernatant liquid exposed to nano-Al2 O3 for 12 and 24 h groups was sig-nificantly increased compared with the control group(P﹤0.05). After exposure to nano-Al2 O3 ,the mito-chondrial membrane potential was significantly decreased compared with the control group( P ﹤0.01). The results of TEM displayed mitochondrial swelling and the formation of vacuoles and mitophagy in nano-Al2 O3 groups. MDC positive fluorescence particles were observed and the expression of autophagy related protein Beclin1 and LC3Ⅱ/ Ⅰ was increased in nano-Al2 O3 groups compared with the control group( P ﹤ 0. 05 ). The result of Lysotracker and Mitotracker colocalization showed the fusion of mitochondria and lysosomals. CONCULSION Nano-Al2 O3 may induce autophagy and mitochondria damage in neuronal cells while the damaged mitochondria may be removed by mitophagy.

OBJECTIVE To explore the potential neurotoxicity of nano-alu mina (<50 n m)in vivo, we treated the ICR mouse with the nano-alu mina to investigate the mitochondrial da mage of nerve cells on morphology and function.METHODS Adult male mice were exposed to nano-alu mina (<50 n m)of 0,25,50 and 75 mg·kg -1 by nasal instillation for 1 month.Then we observed the mitochondrial ultra-structure of the nerve cells in CA3 region of hippoca mpus,and measured the mean dia meter in every group.The activities of Na +-K +-ATPase and Ca2 +-Mg2 +-ATPase were tested by the determination of the inorganic phosphorus,which was the deco mposition product of ATPase.Western blot analysis was used to detect the expression of COX-Ⅳ,Beclin1 ,LC3Ιand LC3Ⅱ.RESULTS Co mpared with 0 and 25 mg·kg -1 groups exposed to Al2 O3 nanopartilces (Al2 O3 NPs),the mitochondria of CA3 region in hip-poca mpus in 50 mg·kg -1 group beca me ede matous and swollen with sparse and broken cristae sur-rounding the nuclear,and the mean dia meter was higher(0.49 ±0.02 μm,P <0.05).But co mpared with 50 mg·kg -1 group,the mitochondria in 75 mg·kg -1 group beca me s maller with inner cristae of high density,and the mean dia meter was lower(0.36 ±0.02 μm,P<0.05).The enzy me activity of the mito-chondria in cerebral cortex decreased dose-dependently with exposure,the activities of Na +-K +-ATPase in 50 and 75 mg·kg -1 groups(6.37 ±0.22 kU·g -1 protein,5.48 ±1 .53 kU·g -1 protein)and Ca2 +-Mg2 +-ATPase in 50 and 75 mg·kg -1 groups (3.21 ±0.99 kU·g -1 protein,3.28 ±0.15 kU·g -1 protein)were lower than the 0 mg·kg -1 group(P<0.05).Meanwhile,the Ca2 +-Mg2 +-ATPase in 50 and 75 mg·kg -1 groups showed lower activities in co mparison with the 25 mg·kg -1 group.The 75 mg·kg -1 group expressed higher level of the COX-Ⅳ protein 1 .35 ±0.66(P<0.05)than other groups.Both expression of Beclin1 protein and rate of LC3Ⅱ/LC3Ⅰin 75 mg·kg -1 group were more than the 0 mg·kg -1 group. CONCLUSION The mitochondrial dysfunction may be the potential neurotoxicity of nano-alu mina,and the da maged mitochondria were cleared by autophagy.

Objective:To explore the effectiveness of humanism concept in the management of patients with spi-nal cord injury care.Methods:Choose between January 2011 and February 2011 hospitalized in our hospital 112 cases of spinal cord injury patients, randomly divided into control group and observation group ( 56 cases) , com-pared two groups of nursing effect.Control group routine nursing management, observation group will humanistic nursing management idea runs through in the routine nursing management.Results:Aware of knowledge about health education group is significantly higher than the control group, patients satisfaction survey in nursing, be-tween the two groups statistically significant depression levels lower than the control group.Conclusions:In the nursing management of patients with spinal cord injury in the application of humanistic nursing concept effect is good, not only improve the effect of the nursing, and obviously improve the patient′s satisfaction, promote the pa-tient′s psychological adaptability.

Objective To identify the histological features as well as factors influencing the course of HBeAg-negative chronic hepatitis B virus ( HBV)-infected patients with persistently normal alanine amino-transferase (ALT) levels (PNAL). Methods Ninety-eight HBeAg-negative chronic HBV-infected patients with PNAL who underwent percutaneous liver biopsy were recruited from October 2003 to March 2008. The ALT level, HBV markers, HBV DNA level and liver histological changes were detected. Comparison of means was done by t test and single factor analysis of variance. Nonparametric statistics was done by Marm-Whitey U test and Kruskal-Wallis test. Analysis of independent risk factor was done using Logistic model. The dianostic value of ALT level to significant liver histological changes was evaluated by receiver performance curve. Results Twenty-two point four percent and 17.3% of subjects had the histological activity index (HAI)≥4and fibrosis (F) score≥3 respectively. Subgroup analysis showed that subjects with ALT＞0.50 × upper limit of normal (ULN) had a significantly higher rate of HAI≥4 and F score≥3 than those with ALT≤0.50×ULN (HAI≥4:36.4% vs 11.1%, χ2 =8.881, P=0.003;F score≥3:27.3% vs 9.3%, χ2 =5.487, P= 0.019, respectively), and older subjects (more than 45 years old) had a higher proportion of HAI ≥4 than the younger (33.3% vs 13.4%, χ2 =4.923, P=0.027). Multivariate Logistic regression analysis revealed that a decade increase in age was the independent predictor of HAI≥4 (OR=2.410, P=0.023).Receive operating characteristic (ROC) curve showed that 87.0% and 90.7% of subjects with ALT＜0.50× ULN had histological changes of HAI＜4 and F score＜3 respectively. The proportions of HAI≥4 and F score≥3 in subjects with HBV DNA＜1×104 copy/mL were 14.9% and 12.8%, respectively. Conclusions Significant histological changes may be present in part of the subjects with persistently normal ALT and different HBV DNA levels, so that liver biopsy is very important, especially in those with age ＞45 years.Half time the ULN may serve as an appropriate cutoff value of normal ALT level for managing Chinese HBeAg-negative chronic HBV-int'ected patients.

Objective To investigate the expression and function of retinoic acid-inducible gene Ⅰ(RIG-Ⅰ) in monocyte-derived dendritic cells (MoDC) at different stages of hepatitis B virus(HBV)infection and to explore the role of RIG-Ⅰ in the disease progression after HBV infection. Methods Peripheral blood samples were collected from 28 hepatitis B virus-infected persons, including 21 cases of chronic hepatitis B (CHB) and 7 of acute hepatitis B (AHB). Eighteen healthy subjects were recruited as controls. Purified CD14~+ monocytes were isolated by CD14 microbeads. MoDCs were induced from CD14~+ monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 for 7 days, and then were infected with vesicular stomatitis virus (VSV) to stimulate RIG-Ⅰ expression. The mRNA expression levels of RIG-Ⅰ, interferon (IFN )-promoter stimulating factor-1 (IPS-1) and IFN-β at 16 hours and 24 hours after infection with VSV were measured by real-time quantitative polymerase chain reaction (PCR). Data with normal distribution were tested by analysis of variance. Continuous variables between groups were compared using Mann-Whitney U test. Comparison among multiple groups was done by Kruskal-Wallis test. Results The expression levels of RIG-Ⅰ in MoDCs from CHB patients were significantly lower than those in AHB patients and healthy controls at 16 hours (2.44±2.03, 19. 54±3. 15, 21. 48±8. 39, respectively; F=7.451,P=0.002) and 24 hours (2. 68±2. 93, 10. 31 ±3. 88, 14. 01 ±5. 04, respectively, F = 7. 908, P = 0. 001)following VSV stimulation. The IPS-1 levels in both CHB patients and AHB patients were higher than those in healthy controls at 16 hours (2. 05±l. 08, 1. 99±1. 56, 0. 60±0. 31, respectively) F=7.246,P =0.003) and 24 hours (2. 27±2. 16, 3.24 ± 1.21, 1. 08±0. 73, respectively; F= 13. 598, P = 0. 001).Furthermore, the IFN-β expression levels were significantly lower in CHB patients compared to AHB patients and healthy controls at 16 hours and 24 hours after VSV stimulation. Conclusions The expressions of RIG-Ⅰ and IPS-1 in MoDC are abnormal in HBV infected persons, which indicates that RIG-Ⅰ signaling pathway might be blocked by HBV. The impaired function of MoDC may play a role in HBV infection and chronicity.

Objective:To evaluate the diagnostic value of platelet count(PC),PC to mean platelet volume(MPV) ratio(PC/MPV) and plateletcrit(PCT) in chronic periprosthetic joint infection(PJI).Methods:The medical records of 159 patients who underwent hip or knee revisions at Department of Joint Surgery, Affiliated Hospital of Qingdao University from August 2013 to June 2019 were retrospectively reviewed. There were 51 patients(26 knees and 25 hips) in the PJI group,which included 28 males and 23 females,aged (68.0±11.8)years (range:32 to 84 years)with a body mass index(BMI)of (26.1±3.6) kg/m2.There were 116 patients(19 knees and 97 hips) in the aseptic loosening(AL) group,including 67 males and 49 females,aged (70.3±8.9)years(range:49 to 89 years)with a BMI of (25.0±3.6)kg/m2.The plasma C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),PC,MPV,PC/MPV and PCT levels of the two groups were recorded and analyzed. Receiver operating characteristic curve was used to calculate the sensitivity and specificity of each biomarker,expect for MPV,and the diagnostic value of each biomarker was compared according to the area under the curve(AUC).Independent-sample t test or Mann-Whitney U test were used for comparison between groups. Results:Compared with AL group,AJI group had significantly higher levels of CRP,ESR,PC,PC/MPV and PCT(all P<0.05),but lower level of MPV ( P<0.05).The AUCs for CRP,ESR,PC,PC/MPV and PCT were 0.820, 0.829, 0.689, 0.668 and 0.676,respectively. Based on the Youden index,the optimal predictive cutoff for CRP was 11.12 mg/L,with a sensitivity of 74.4% and a specificity of 87.1%.The optimal predictive cutoff for ESR was 17.60 mm/1 h,with a sensitivity of 81.4% and a specificity of 75.3%.The optimal predictive cutoff for PC was 243.00×10 9/L,with a sensitivity of 60.6% and a specificity of 71.8%.The optimal predictive cutoff for PC/MPV was 24.95,the sensitivity was 58.1% and the specificity was 74.1%.And the optimal predictive cutoff for PCT was 0.24%,with a sensitivity of 69.8% and a specificity of 63.5%. Conclusion:PC,PC to MPV ratio and PCT are of limited value to diagnose PJI.

Objective:To evaluate the diagnostic value of platelet count(PC),PC to mean platelet volume(MPV) ratio(PC/MPV) and plateletcrit(PCT) in chronic periprosthetic joint infection(PJI).Methods:The medical records of 159 patients who underwent hip or knee revisions at Department of Joint Surgery, Affiliated Hospital of Qingdao University from August 2013 to June 2019 were retrospectively reviewed. There were 51 patients(26 knees and 25 hips) in the PJI group,which included 28 males and 23 females,aged (68.0±11.8)years (range:32 to 84 years)with a body mass index(BMI)of (26.1±3.6) kg/m2.There were 116 patients(19 knees and 97 hips) in the aseptic loosening(AL) group,including 67 males and 49 females,aged (70.3±8.9)years(range:49 to 89 years)with a BMI of (25.0±3.6)kg/m2.The plasma C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),PC,MPV,PC/MPV and PCT levels of the two groups were recorded and analyzed. Receiver operating characteristic curve was used to calculate the sensitivity and specificity of each biomarker,expect for MPV,and the diagnostic value of each biomarker was compared according to the area under the curve(AUC).Independent-sample t test or Mann-Whitney U test were used for comparison between groups. Results:Compared with AL group,AJI group had significantly higher levels of CRP,ESR,PC,PC/MPV and PCT(all P<0.05),but lower level of MPV ( P<0.05).The AUCs for CRP,ESR,PC,PC/MPV and PCT were 0.820, 0.829, 0.689, 0.668 and 0.676,respectively. Based on the Youden index,the optimal predictive cutoff for CRP was 11.12 mg/L,with a sensitivity of 74.4% and a specificity of 87.1%.The optimal predictive cutoff for ESR was 17.60 mm/1 h,with a sensitivity of 81.4% and a specificity of 75.3%.The optimal predictive cutoff for PC was 243.00×10 9/L,with a sensitivity of 60.6% and a specificity of 71.8%.The optimal predictive cutoff for PC/MPV was 24.95,the sensitivity was 58.1% and the specificity was 74.1%.And the optimal predictive cutoff for PCT was 0.24%,with a sensitivity of 69.8% and a specificity of 63.5%. Conclusion:PC,PC to MPV ratio and PCT are of limited value to diagnose PJI.

Objective To set up the model of deiodinase ( Dio) 3b-/- zebrafish and to observe the effect of which on embryo development. Methods The zebrafish model of Dio3b-/- was set up by CRISPR-Cas9 gene editing technology, PCR and sequencing was used to confirm the efficiency of deletion. The heart rate of embryos at 48 hours post fertilization was counted. The locomotor activity of 5-7 days post fertilization larve was detected using behavior tracking system. Results The model of Dio3b knockout zebrafish was set up successfully. The heart rate of embryos Dio3b-/- increased ( P＜0. 001) and the locomotor activity of 5-7 days post fertilization larves lacking Dio3b gene increased (P＜0.05) significantly compared with that of wild type control respectively. Conclusion The deletion of zebrafish Dio3b gene results in the phenotype of hyperthyroidism and the model of Dio3b-/- is proper for studying the effect of partial excess thyroid hormone on embryo development.

Objective: To investigate the value of ¹⁸F-fluorodeoxyglucose (FDG) PET/CT in differentiation of noninvasive and malignant pancreatic cystic lesions (PCL). Methods: A total of 125 PCL patients (66 males, 59 females, age range: 13-83 years), who had pathology or typical imaging performance with ≥12 months follow-up between August 2010 and December 2015, were enrolled in this retrospective study. The diagnostic effects of ¹⁸F-FDG PET/CT were calculated. The size, maximum standardized uptake value (SUV_max), delayed SUV_max and retention index (RI) of noninvasive and malignant PCL were analyzed. The results of pathological examination and follow-up were used as the gold standard, and Mann-Whitney u test was used to analyze the data. Receiver operating characteristic (ROC) curves of SUV_max, delayed SUV_max and RI were drawn and compared. Results: A total of 132 PCL were found in 125 patients, including 71 malignant PCL and 61 noninvasive PCL. The size, SUV_max, delayed SUV_max, RI of noninvasive and malignant PLC were 2.2 (1.4, 3.8) cm vs 3.9 (3.0, 5.0) cm, 1.5 (1.2, 1.8) vs 6.4 (4.4, 9.3), 1.5 (1.2, 1.9) vs 6.4 (5.4, 11.7), -6.3%(-19.4%, 5.6%) vs 17.5%(7.6%, 29.4%), respectively. All parameters were significantly different between 2 groups (z values: from -9.267 to -4.904, all P<0.05). The area under curve (AUC) and cut-off value of SUV_max were 0.969 and 2.5, and the corresponding accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were 92.4%(122/132), 93.0%(66/71), 91.8%(56/61), 93.0%(66/71), 91.8%(56/61), respectively. The AUC and cut-off value of delayed SUV_max were 0.969 and 2.7, and the accuracy, sensitivity, specificity, PPV, NPV were 94.3%(99/105), 96.7%(58/60), 91.1%(41/45), 93.5%(58/62), 95.3%(41/43), respectively. ROC curves of SUV_max and delayed SUV_max were not significantly different (z=1.799, P>0.05). Conclusion ¹⁸F-FDG PET/CT has good performance in differentiation of noninvasive and malignant PCL, but the delayed scan cannot further improve the efficacy of differential diagnosis.