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    20 July 2020
    Volume 58 Issue 7
    Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury
    SUO Dongyang, SHEN Fei, GUO Hao, LIU Lichang, YANG Huimin, YANG Xiangdong
    Journal of Shandong University (Health Sciences). 2020, 1(7):  1-6.  doi:10.6040/j.issn.1671-7554.0.2020.0392
    Abstract ( 1817 )   PDF (16846KB) ( 206 )   Save
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    Objective To explore the role of T cell immunoglobulin domain and mucin domain protein-3(Tim-3)in acute kidney injury(AKI)and study its mechanism. Methods Six to eight weeks old C57 male mice were randomly divided into the control group(CTRL group), cisplatin group(AKI group), and cisplatin + Tim-3 group(RMT group), 4 in each group. Cisplatin(20 mg/kg)was injected intraperitoneally into the mice in the AKI group to construct the AKI animal model, and kidney injury and Tim-3 expression were detected. In RMT group, the antibody RMT3-23(200 μg/per mouse)was used to block the Tim-3 molecule and to establish an AKI model, and then the kidney injury in the AKI and RMT groups and the expressions of Tim-3 and autophagy-related molecules were detected. Results The renal proximal tubules were damaged. Western blotting results showed that the expression level of Tim-3 in AKI group was higher than that in CTRL group (t=3.876, P=0.008 2). Compared with the AKI group, the expression levels of NGAL and P62 in the RMT group increased without the statistical difference(tNGAL=1.664, P=0.157 0; tP62=1.991, P=0.103 1), while the expression of LC3II decreased with a statistical difference(t=5.901, P=0.002 0). The phagocytosis was inhibited and the renal tubular damage was aggravated(P=0.010 1). Conclusion Tim-3 can reduce AKI renal injury induced by cisplatin by regulating the autophagic activity of renal tubular epithelial cells.
    miR-21-5p targeted TIMP3 to inhibit proliferation and extracellular matrix accumulation of mesangial cells in Type II diabetic nephropathy mice
    ZHANG Baowen, LEI Xiangli, LI Jinna, LUO Xiangjun, ZOU Rong
    Journal of Shandong University (Health Sciences). 2020, 1(7):  7-14.  doi:10.6040/j.issn.1671-7554.0.2019.1007
    Abstract ( 2051 )   PDF (6283KB) ( 163 )   Save
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    Objective To investigate the effects of miR-21-5p on the expression of tissue inhibitor of metalloproteinases-3(TIMP3)in kidney tissue of type 2 diabetic nephropathy(T2DN)mice, and the proliferation and extracellular matrix accumulation of mesangial cells. Methods Ten db/m mice were selected as control group, and other 30 SPF male db/db T2DN mice were randomly divided into model(T2DN)group, miR-21-5p agomir group and miR-21-5p antagomir group with 10 mice in each group. Normal saline, miR-21-5p agomir and miR-21-5p antagomir were injected respectively into tail vein once every three days, 7 times in total. The expression of miR-21-5p was detected by qRT-PCR in kidney tissues of mice. The expression levels of Upro/24 h, Scr and BUN in urine of mice were detected by ELISA assay. The kidney pathological changes were observed by HE staining. The extracellular matrix accumulation was observed by PAS staining. The expression levels of TIMP3, Col IV and FN protein in renal tissue were detected by Western blotting method. Dual luciferase reporter system was used to detect the targeting relationship between miR-21-5p and TIMP3. Results In the T2DN group and miR-21-5p agomir group, the levels of Upro/24 h(t=84.67, P<0.001; t=100.44, P<0.001), Scr(t=16.81, P<0.001; t=36.76, P<0.001), and BUN(t=19.26, P<0.001; t=52.42, P<0.001)increased, mesangial proliferated, basement membrane thickened, relative area of mesangial matrix increased(t=9.10,P<0.001;t=14.16,P<0.001), TIMP3 expression was abnormally lower(t=8.51,P=0.001;t=12.66,P<0.001), and fibrosis protein Col IV expression(t=10.04,P<0.001;t=23.54,P<0.001)and FN expression(t=11.49,P<0.001;t=22.34,P<0.001)was abnormally higher than those in the control group. Compared with T2DN group, the levels of Upro/24 h, Scr and BUN decreased(tUpro/24 h=20.31,P<0.001;tScr=7.902,P<0.001;tBUN=8.913,P<0.001), mesangial hyperplasia and basement membrane thickening alleviated, the relative area of mesangial matrix decreased(t=7.96,P=0.001), TIMP3 expression increased(t=11.71,P<0.001), fibrosis proteins Col IV expression(tCol IV=6.58,P=0.003)and FN expression(tFN=6.27,P=0.003)decreased in the miR-21-5p antagomir group. The biochemical indexes and symptom of glomerular diseases in miR-21-5p antagomir group and miR-21-5p agomir group were opposite. Dual luciferase assay showed that miR-21-5p could target the expression of TIMP3 gene. Conclusion miR-21-5p targeting TIMP3 inhibits the proliferation of mesangial cells and the extracellular matrix accumulation in T2DN mice.
    Effect of Noggin protein on learning and memory abilities and the dentate gyrus structure after cerebral ischemia reperfusion injury in mice
    LONG Tingting, XIE Ming, ZHOU Lu, ZHU Junde
    Journal of Shandong University (Health Sciences). 2020, 1(7):  15-23.  doi:10.6040/j.issn.1671-7554.0.2019.1273
    Abstract ( 1566 )   PDF (9562KB) ( 286 )   Save
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    Objective To investigate the effect of injection of Noggin protein into the lateral ventricle on the learning and memory abilities and the structure of dentate gyrus after cerebral ischemia reperfusion injury(CIRI)in mice, in order to provide new ideas for the prevention and treatment of clinical ischemic cerebrovascular diseases. Methods A total of 240 health mice were randomly divided into the sham group(n=80), the ischemia-reperfusion group(I/R group, n=80), and the Noggin treatment group(Noggin group, n=80). Each group was subdivided into the 1days, 3 days, 7 days and 14 days subgroups. The learning and memory abilities were detected by Y-maze at 1 day before execution. Infarct size was detected by triphenyltetrazolium chloride staining(n=5). The colorimetric method was used to detect the superoxide dismutase(SOD)and malondialdehyde(MDA)activity after the behavior capability determined(n=5). Infarct size was detected by 2,3,5-triphenyl tetrazolium chloride staining(n=5). Glial fibrillary acidic protein(GFAP)immunopositive cells in the DG were observed under a light microscopy and quantitative analysis were performed by cell morphometric technique(n=5). The BMP4 protein expression was detected by Western blotting(n=5). Results Compared with the sham group, the neurological function score of mice in the I/R group and Noggin group increased(Fgroup=21.19, P<0.001; Ftime=25.13, P<0.001), learning and memory abilities declined(Fgroup=216.10, P<0.001; Ftime=260.10, P<0.001)(Fgroup=114.40, P<0.001; Ftime=184.60, P<0.001), and area of cerebral infarction increased(Fgroup=2 374, P<0.001; Ftime=3 292, P<0.001), SOD activity reduced(Fgroup=1 426, P<0.001; Ftime=1 723, P<0.001)and MDA content increased(Fgroup=2.22, P<0.001; Ftime=6.33, P<0.001), number of neurons reduced(Fgroup=148.90, P<0.001; Ftime=485.50, P<0.001), and expression of GFAP positive cells and BMP4 protein increased(Fgroup=40.18, P<0.001; Ftime=141.90, P<0.001)(Fgroup=426.70, P<0.001; Ftime=1 329, P<0.001)with the increase of injury time. At each same time point, compared with the I/R group, the Noggin groups neurological function score decreased(P<0.001), learning and memory abilities increased(P<0.001), and cerebral infarction area decreased(P<0.001), SOD activity increased and MDA content decreased(P<0.001), number of neurons increased and staining was lightened (P<0.001), expression of GFAP positive cells and BMP4 protein decreased(P<0.001). Conclusion Noggin can efficiently improve the learning and memory abilities and decrease the pathological lesion of DG after cerebral ischemia reperfusion injury in mice, and its mechanism may closely related to BMP4 protein expression and glial cells activation.
    Molecular mechanism of Toll-like receptor 4 in the aggravation of blood lipid accumulation by inhibiting the peroxisome proliferator-activate receptor γ
    FU Jieqi, ZHANG Man, ZHANG Xiaolu, LI Hui, CHEN Hong
    Journal of Shandong University (Health Sciences). 2020, 1(7):  24-31.  doi:10.6040/j.issn.1671-7554.0.2020.0102
    Abstract ( 1474 )   PDF (12271KB) ( 103 )   Save
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    Objective To investigate the molecular mechanism of Toll-like receptor 4(TLR4)and peroxisome proliferator-activated receptor γ(PPARγ)in the process of lipid accumulation in rat models of high-fat diet and oxidized low-density lipoprotein(oxLDL). Methods A total of 20 healthy male Wistar rats were randomly divided into control group(n=10)and high fat group(n=10). Total cholesterol(TG), triglycerides(TC), high-density lipoprotein(HDL)and low-density lipoprotein(LDL)levels were measured in both groups. The carotid intima-media thickness ratio was detected with HE staining, and the protein expressions of TLR4 and PPARγ were determined with Western blotting. Rat macrophages RAW264.7 were cultured in vitro and stimulated by oxLDL(50 mg/L)to prepare the macrophage models, and TLR4 factors in the macrophages were silenced with siRNA-TLR4 to prepare the TLR4 silencing models. The cells were divided into blank group(group A), oxLDL group(group B), oxLDL+siRNA group(group C), oxLDL+siRNA-TLR4 group(group D), oxLDL+siRNA-TLR4+PPARγ agonist group(group E)and oxLDL +siRNA-TLR4+PPARγ inhibitor group(group F). The lipid accumulation in macrophages was observed with oil red O staining, cholesterol level in macrophages was quantitatively detected, and protein expressions of TLR4 and PPARγ were tested with Western blotting. Results In the animal model experiments, compared with control group, high fat group had significantly increased levels of TG, TC, LDL, ratio of carotid intima-media thickness, and relative expression of TLR4(P<0.01), but decreased levels of serum HDL and PPARγ(P<0.01), and there was a negative correlation between TLR4 and PPARγ (r=-0.928 1, P<0.001). In the oxLDL exposure to macrophages experiments, compared with group A, groups B and C had significantly increased cholesterol content(P<0.01), oil red O particles, optical density(OD)value and relative expression of TLR4, but decreased relative expression of PPARγ (P<0.05). Besides, there was a negative correlation between TLR4 and PPARγ(r=-0.986 7, P<0.001)in group B. Compared with group B, group C had no significant changes in cholesterol content, oil red O particles, OD value and relative expressions of TLR4 and PPARγ(P>0.05). Compared with group B, group D had significantly decreased cholesterol content, oil red O particles, OD value and relative expression of TLR4(P<0.01), but significantly increased relative expression of PPARγ(P<0.05). Compared with group D, group E had significantly decreased cholesterol content, oil red O particles and OD value(P<0.01), but significantly increased relative expression of PPARγ(P<0.05), and the expression of TLR4 remained unchanged(P>0.05). Compared with group D, group F had significantly increased cholesterol content(P<0.01), oil red O particles and OD value, but significantly decreased relative expression of PPARγ(P<0.05), and the relative expression of TLR4 protein did not significantly change(P>0.05). Conclusion The accumulation of blood lipids in cells is involved in the pathogenesis of atherosclerosis(AS). As a protective factor, PPARγ can inhibit the accumulation of blood lipids in macrophages and then participate in AS regulation. As an upstream regulatory site of PPARγ, TLR4 aggravates lipid accumulation by inhibiting the expression of PPARγ, and then interferes with the progression of AS.
    Effect of miR-27b-3p regulating SMAD1 on osteosarcoma cell proliferation, migration and invasion
    MA Qingyuan, PU Peidong, HAN Fei, WANG Chao, ZHU Zhoujun, WANG Weishan, SHI Chenhui
    Journal of Shandong University (Health Sciences). 2020, 1(7):  32-37.  doi:10.6040/j.issn.1671-7554.0.2020.0096
    Abstract ( 1546 )   PDF (6444KB) ( 189 )   Save
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    Objective To assess the relationship between miR-27b-3p and SMAD1 and to explore the effects of MiR-27b-3p on osteosarcoma cell proliferation, invasion and migration, so as to provide theoretical basis for targeted therapy of osteosarcoma. Methods Candidate target genes were predicted with bioinformatics methods. The targeting relationship between miR-27b-3p and SMAD1 was determined with dual luciferase report experiments. The SAOS-2 osteosarcoma cell line was selected with qRT-PCR. After SAOS-2 cells were transfected with miR-27b-3p, they were divided into 3 groups: miR-27b-3p inhibitor group, blank control group and negative control group. The effects of miR-27b-3p on SAOS-2 cells were detected with MTT, Transwell migration and invasion assay. The expression of SMAD1 after miR-27b-3p silencing was determined with Western blotting. Results Bioinformatics analysis showed there were binding sites of miR-27b-3p and SMAD1-UTR. Dual luciferase experiments showed the miR-27b-3p inhibitor group had higher expression of SMAD1 than the negative control group(P<0.05), and SMAD1 was the target gene of miR-27b-3p. MTT, Transwell migration and invasion assay showed the miR-27b-3p inhibitor group had reduced cell proliferation, migration and migration than the blank control group and negative control group(P<0.05). The miR-27b-3p inhibitor group had significantly lower protein expression of SMAD1 than negative control group(P<0.05). Conclusion miR-27b-3p can promote the proliferation, migration and invasion of osteosarcoma cells by regulating the expression of SMAD1, and may play a role as an oncogene in osteosarcoma cells.
    Expression of LncRNA AL109955.1 in 80 cases of colorectal cancer and its effect on cell proliferation, migration and invasion
    LI Ning, LI Juan, XIE Yan, LI Peilong, WANG Yunshan, DU Lutao, WANG Chuanxin
    Journal of Shandong University (Health Sciences). 2020, 1(7):  38-46.  doi:10.6040/j.issn.1671-7554.0.2020.0557
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    Objective To investigate the expression of long non-codingRNAs(LncRNAs)AL109955.1 in colorectal cancer(CRC)tissues and its effect on cell proliferation, migration and invasion. Methods The cancer genome atlas(TCGA)and genotype-tissue expression(GTEx)were analyzed to screen LncRNAs which were decreased in CRC tissues and related to the poor prognosis of patients, and then the expression in 80 pairs of CRC tissues and adjacent normal tissues was verified by quantitative real-time PCR(RT-qPCR). After that, the cell proliferation, migration and invasion were detected with cell counting kit-8(CCK8)test, wound healing test and Transwell assay, respectively. Finally, the miRNA binding sites and target mRNAs were screened with TargetScan and Tarbase, and a LncRNA-miRNAs-mRNA network was constructed with Cytoscape software(3.7.2). Results A novel LncRNA, AL109955.1, was screened and identified, and its expression was significantly lower in CRC tissues than that in adjacent normal tissues [(1.18±2.46)vs(1.8±1.65), t=2.14, P=0.008]. AL109955.1 expressed differently in CRC tissues with different degrees of differentiation [poorly differentiated: 0.18(0.10~0.55); moderately differentiated: 0.49(0.22~1.81); well differentiated: 0.87(0.15~3.33)]. In addition, AL109955.1 expression decreased with the increase of tumor size [≥5 cm: 0.26(0.11~0.62); <5 cm: 0.49(0.181~1.99), U=570.5, P=0.020)]. CCK8 test showed AL109955.1 could significantly inhibit the proliferation of CRC cells. Wound healing test and Transwell assay showed overexpression of AL109955.1 significantly decreased the migration and invasion of CRC cells. Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis indicated that AL109955.1 played its biological role by affecting classical tumor signaling pathways such as Wnt, p53, Notch and Jak-STAT. Conclusion LncRNA AL109955.1 expression is lower in CRC tissues than that in adjacent normal tissues. LncRNA AL109955.1 can inhibit the proliferation, migration and invasion abilities of CRC cells.
    Construction and application of a miRNAs prognostic risk assessment model of gastric cancer
    SHI Shuang, LI Juan, MI Qi, WANG Yunshan, DU Lutao, WANG Chuanxin
    Journal of Shandong University (Health Sciences). 2020, 1(7):  47-52.  doi:10.6040/j.issn.1671-7554.0.2020.0663
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    Objective To identify microRNAs(miRNAs)biomarkers related to the prognosis of gastric cancer patients, and construct a miRNA risk assessment model for survival prediction. Methods The miRNA expression profile of gastric cancer patients and relevant clinical data were obtained from the Cancer Genome Atlas(TCGA)database. Differentially expressed miRNAs were identified with “DESeq2” package. The miRNAs related to prognosis were screened with univariate Cox regression and Kaplan-Meier analysis, which were analyzed with multivariate Cox regression to construct a prognostic risk assessment model. A receiver operating characteristic(ROC)curve was drawn with “time ROC” package to evaluate the effectiveness of the model. Finally, the messenger RNAs(mRNAs)that miRNAs might bind to were predicted with online database, and the possible functions were predicted with gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG). Results With Log2|Fold Change|>1 and P<0.05 as the standards, 248 differentially expressed miRNAs in gastric cancer tissues were identified. Univariate Cox regression and Kaplan-Meier analysis screened out 6 differentially expressed miRNAs which had significant correlation with prognosis to construct a prognostic risk assessment model. The risk score=0.048 35×miR-181b-1 +0.112 06×miR-548d-1+0.068 00×miR-675+0.075 87×miR-708+1.175 21×miR-4640+0.089 89×miR-4709. Kaplan-Meier analysis showed patients with high risks had a poor prognosis(P<0.001). The area under the ROC curve(AUC)of the 5-year overall survival rate was 0.776, indicating the model was able to predict the prognostic risk. GO and KEGG analysis showed miRNAs were involved in a few signaling pathways of gastric cancer. Conclusion A miRNAs prognostic risk assessment model was successfully constructed based on bioinformatics analysis, which was proved by Kaplan-Meier analysis and ROC curve to have good prediction effects on the survival of gastric cancer patients.
    Comparison of diagnostic efficacy of two kinds of thyroid imagine reporting and data systems
    XIAO Juan, XIAO Qiang, CONG Wei, LI Ting, DING Shouluan, ZHANG Yuan, SHAO Chunchun, WU Mei, LIU Jianing, JIA Hongying
    Journal of Shandong University (Health Sciences). 2020, 1(7):  53-59.  doi:10.6040/j.issn.1671-7554.0.2019.1505
    Abstract ( 2035 )   PDF (1135KB) ( 160 )   Save
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    Objective To compare the diagnostic efficacy of Kwak and ACR(2017)thyroid imaging reporting and data system(TI-RADS). Methods Data of 792 patients with thyroid nodules who underwent surgery during March 2017 and April 2019 were retrospectively collected and 1 940 thyroid nodules were enrolled. Imaging features of thyroid nodules were analyzed by two senior qualified sonographers using Kwak and ACR(2017)TI-RADS. Results The best diagnostic cut-off point of Kwak TI-RADS was ≥4a, and the sensitivity and specificity was 82.71% and 76.06%, respectively. The best diagnostic cut-off point of ACR(2017)TI-RADS was TR5, and the sensitivity and specificity was 68.67% and 85.46%, respectively. The sensitivity of Kwak TI-RADS was higher than that of ACR(2017)TI-RADS(P<0.001)while the specificity of ACR(2017)TI-RADS was higher than that of Kwak TI-RADS(P<0.001). The area under the receiver operating characteristic curve(AUC)of Kwak TI-RADS was 0.826, which was higher than that of ACR(2017)TI-RADS(0.810, P=0.024). Both Kwak and ACR(2017)TI-RADS yielded relatively higher overall diagnostic efficacy in nodules ≥1 cm than in nodules <1 cm(P=0.918). In nodules <1cm, Kwak TI-RADS did better than ACR(2017)TI-RADS(P<0.001). Conclusion The overall diagnostic efficacy of Kwak TI-RADS is slightly higher than that of ACR(2017)TI-RADS. Kwak TI-RADS has better performance in sensitivity while ACR(2017)TI-RADS does better in specificity.
    Correlation of the expression of insulin-like growth factor II in granulosa cells and ovulation induction outcomes of 84 patients with polycystic ovary syndrome
    DING Xiangyun, YU Qingmei, ZHANG Wenfang, ZHUANG Yuan, HAO Jing
    Journal of Shandong University (Health Sciences). 2020, 1(7):  60-66.  doi:10.6040/j.issn.1671-7554.0.2020.0538
    Abstract ( 1581 )   PDF (1305KB) ( 147 )   Save
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    Objective To detect the expression of insulin-like growth factor II(IGF-II)in ovarian granulosa cells of patients with polycystic ovary syndrome(PCOS)and to explore its relationship with ovulation induction outcomes. Methods A total of 84 PCOS patients divided into high response group(n=42)and normal response group(n=42)and 90 controls(the control group)with assisted reproduction treatment due to tubal or male factors were enrolled. The expression of IGF-II in each group was detected with real-time quantitative reverse transcription PCR(qRT-PCR). The differences in IGF-II expressions and ovulation induction related parameters were compared, and the correlation was analyzed. Results The median relative expressions of IGF-II in the control group, PCOS normal response group and PCOS high response group were 1.3(0.5-1.8), 1.7(1.4-2.2)and 3.2(2.5-4.3), respectively. There were statistically significant differences among the three groups(F=88.7, P<0.001). The expression of IGF-II was higher in PCOS normal response group and PCOS high response group than that in the control group(both P<0.001), and the expression of IGF-II was higher in PCOS high response group than in PCOS normal response group(P<0.001). On the day when human chorionic gonadotrophin(HCG)was injected, in PCOS high response group, estradiol(E2)level, number of follicles ≥14 mm, number of oocytes obtained, number of 2 pronucleus(2PN)zygotes, number of high quality embryos, number of cleavages and number of transplantable embryos were significantly higher than those in the control group and PCOS normal response group(P<0.05); however, the luteotropic hormone(LH)level, oocyte recovery rate, fertilization rate and available oocyte rate were significantly lower than those in the control group and PCOS normal response group(P<0.05). In the PCOS normal response group, gonadotropin(Gn)level(P=0.02)and E2 level(P<0.001)were lower than those in the control group. Correlation analysis showed that the expression of IGF-II was positively correlated with E2 level(r=0.163, P=0.032), number of follicles ≥14 mm on HCG day(r=0.286, P<0.001), number of 2PN(r=0.246, P<0.001), number of cleavages(r=0.296, P<0.001), number of high quality embryos(r=0.286, P<0.001), number of oocytes obtained(r=0.386, P<0.001), number of transplantable embryos(r=0.252, P<0.001), and rate of high-quality embryos(r=0.155, P=0.041). Multivariate linear regression analysis revealed that the expression of IGF-II was positively correlated with the number of oocytes obtained(β=0.921, P<0.001)and rate of high-quality embryos(β=0.285, P<0.001), while negatively correlated with number of cleavages(β=-0.283, P<0.001). Conclusion IGF-II is highly expressed in the granulosa cells of PCOS patients undergoing assisted reproductive technology, which is closely related to the number of oocytes obtained and rate of high-quality embryos, and has the potential to promote the development of follicles and early embryos.
    A retrospective analysis of risk factors of cerebral microbleeds in 101 patients with cerebral small vessel disease
    XU Yuxiang, LIU Yudong, ZHANG Peng, DUAN Ruisheng
    Journal of Shandong University (Health Sciences). 2020, 1(7):  67-71.  doi:10.6040/j.issn.1671-7554.0.2020.0486
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    Objective To investigate the independent risk factors of cerebral microbleeds(CMBs)in patients with cerebral small vessel disease(CSVD). Methods A total of 101 patients who met the imaging diagnostic criteria of CSVD were divided into CMBs group and non-CMBs group. The risk factors and protective factors of CMBs were identified with statistical analysis. Results Compared with non-CMBs group, CMBs group had a higher incidence of hypertension(χ2=9.879, P=0.002), higher levels of high-sensitivity C-reactive protein(hs-CRP)(t=2.294, P=0.024), homocysteine(Hcy)(t=2.193, P=0.031), cystatin C(Cys-C)(t=2.160, P=0.034)and lipoprotein a(Lpa)(t=4.247, P<0.001), but lower level of low-density lipoprotein cholesterol(LDL-c)(t=-3.342, P=0.001). Logistic regression analysis showed that hypertension(P=0.002, OR=6.706, 95%CI: 2.011-22.362), hs-CRP(P=0.049, OR=1.279, 95%CI:1.001-1.635), Lpa(P=0.001, OR=1.006, 95%CI:1.003-1.009)and LDL-c(P=0.039, OR=0.472, 95%CI: 0.232-0.963)were independently correlated with CMBs. Conclusion Hypertension, hs-CRP and Lpa are the independent risk factors of CMBs, whereas LDL-c is a protective factor.
    Single-stage end-to-end anastomosis in the management of severe cervical tracheal stenosis
    GUO Zhihua, ZHAO Daqing, XING Yuan, WANG Wei, LIANG Leping, YANG Jing, ZHAO Qianqian
    Journal of Shandong University (Health Sciences). 2020, 1(7):  72-76.  doi:10.6040/j.issn.1671-7554.0.2020.0125
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    Objective To evaluate the efficacy, indications and risk factors of single-stage end-to-end anastomosis in the treatment of severe cervical tracheal stenosis. Methods A retrospective analysis was performed on 29 patients with severe cervical tracheal stenosis treated with single-stage partial tracheal or cricotracheal resection with primary end-to-end anastomosis during Mar. 2015 and Nov. 2019, including 19 male and 10 female, age ranged from 17 to 51(mean 31)years. Tracheotracheal end-to-end anastomosis was performed in 18 cases, cricotracheal end-to-end anastomosis in 9 cases and thyrotracheal anastomosis in 2 cases. The degree of stenosis was classified according to Myer-Cotton classification as grade Ⅲ in 18 cases and grade Ⅳ in 11 cases. Results Length of stenosis was 1-4 cm(mean 2.5 cm). Successful decannulation was achieved in 25 cases(86%). Postoperative complications included subcutaneous emphysema in 1 case, restenosis in 4 cases, anastomosic dehiscence in 1 case, and temporary unilateralvocal fold palsy in 1 case. Conclusion Single-stage end-to-end anastomosis is safe and effective in the management of advanced cervical tracheal stenosis. Careful preoperative evaluation of indications and operators experiences play the most important roles in achieving a positive outcome.
    Application of laparoscopic fine needle catheter jejunostomy in minimally invasive McKeown resection of esophageal cancer
    LYU Longfei, LI Lin, LI Shuhai, QI Lei, LU Ming, CHENG Chuanle, TIAN Hui
    Journal of Shandong University (Health Sciences). 2020, 1(7):  77-81.  doi:10.6040/j.issn.1671-7554.0.2019.1247
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    Objective To analyze the operative methods of laparoscopic fine needle catheter jejunostomy, and to investigate its application effects in minimally invasive McKeown resection of esophageal cancer. Methods Clinical data of 1 023 cases undergoing minimally invasive McKeown resection of esophageal cancer by single-operation group were collected from January 2010 to December 2017. The performance of fine needle catheter jejunostomy under laparoscopy, and the incidence of complications related to jejunostomy, such as postoperative catheter site fistula, tube obstruction, intestinal obstruction and so on, were retrospectively analyzed. Results The fine needle catheter jejunostomy were successfully completed in all patients under laparoscopy, and the average operating time was(14.77±2.99)minutes,the mean bleeding volume was(2.87±0.96)mL. The complications related to jejunostomy occurred in 9 cases(0.88%), of which, 3 cases with catheter site fistula(the enteral nutrition was changed to parenteral nutrition, the dressing was changed in time, the skin around the stoma was kept clean, and zinc oxide ointment was applied locally), 3 cases with tube obstruction(parenteral nutrition support was performed before oral feeding), 1 case with jejunal fistula(a second operation was performed), 1 case with mesenteric torsion(a second operation was performed), and 1 case with incomplete intestinal obstruction(the conservative therapy was performed). Conclusion The laparascopic fine needle catheter jejunostomy is an effective approach to establish postoperative enteral nutrition for patients undergoing minimally invasive McKeown resection of esophageal cancer. The method is simple and convenient, safe and feasible, so worthy of clinical application.
    Application of high tibial osteotomy combined with autologous adipose-derived mesenchymal stem cells injection in the repair of knee cartilage
    LI Songlin, LIU Peilai, LU Qunshan, MA Heran
    Journal of Shandong University (Health Sciences). 2020, 1(7):  82-88.  doi:10.6040/j.issn.1671-7554.0.2020.0261
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    Objective To evaluate the efficacy of high tibial osteotomy(HTO)combined with autologous adipose-derived mesenchymal stem cells injection on cartilage repair in patients with knee osteoarthritis. Methods The clinical data of 2 patients with knee osteoarthritis treated with HTO combined with autologous adipose-derived mesenchymal stem cells injection were retrospectively analyzed, including preoperative and postoperative 1-year X-ray and MRI data, arthroscopic results, visual analogue score, and knee joint function score, so as to evaluate the effects on knee cartilage repair and knee joint function improvement. Results Preoperative MRI and intraoperative arthroscopy indicated knee cartilage injury in both patients. HTO combined with intra-articular injection of autologous adipose-derived mesenchymal stem cells was performed. Knee joint function recovered well 1 year after operation and articular cartilage regenerated. Conclusion For patients with knee osteoarthritis, HTO combined with autologous adipose-derived mesenchymal stem cells injection can effectively promote the repair of knee cartilage and improve the function of knee joint.
    Comparison of the value of mono-exponential mode and diffusion kurtosis imaging mode in grading clear cell renal cell carcinoma using magnetic resonance diffusion-weighted imaging
    LUO Xin, HE Bing, NIE Qingsheng, HOU Zhenbo, DONG Jun, LI Yuhua, ZENG Xiangqin, LIU Wei, KONG Demin, CAO Jinfeng
    Journal of Shandong University (Health Sciences). 2020, 1(7):  89-95.  doi:10.6040/j.issn.1671-7554.0.2020.0089
    Abstract ( 1618 )   PDF (10955KB) ( 75 )   Save
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    Objective To compare the value of diffusion kurtosis imaging(DKI)and diffusion weighted imaging(DWI)mono-exponential mode in grading clear cell renal cell carcinoma(ccRCC). Methods Sixty-one patients with pathologically proven ccRCC were enrolled in this prospective clinical study. The patients were divided into low grade group(10 with grade Ⅰ and 17 with grade Ⅱ)and high-grade group(19 with grade Ⅲ and 15 with grade Ⅳ)according to the Fuhrman classification system. All patients underwent DWI examination by using both mono-exponential mode and DKI mode. The ADC, fractional anisotropy(FA), mean diffusivity(MD), mean kurtosis(MK), axial kurtosis(Ka)and radial kurtosis(Kr)values were measured, respectively. One-way analysis of variance(ANOVA)was used to compare the difference among three groups, and the independent sample t test was used to compare the difference between two groups. The AUC, sensitivity, and specificity of DWI and DKI parameters were calculated by using receiver-operating characteristic(ROC)analysis, then these AUC values were compared by Delong test to evaluate the diagnostic efficacy of the parameters. Results (1)There were statistical differences in ADC, MD, MK, Ka, and Kr values among the normal renal parenchyma, low-grade and high-grade ccRCC groups(P<0.05). The difference in FA value among the three groups was not statistically significant(P>0.05). The ADC values of the normal renal parenchyma, low-grade and high-grade ccRCC were(2.10±0.16)×10-3mm2/s,(1.70±0.34)×10-3mm2/s, and(1.20±0.32)×10-3mm2/s, FA values were 0.26±0.06, 0.26±0.11, and 0.28±0.14, MD values were(6.02±0.43)×10-3mm2/s,(5.10±0.96)×10-3mm2/s, and(3.70±0.76)×10-3mm2/s, MK values were 0.49±0.04, 0.57±0.07, and 0.84±0.20, Ka values were 0.39±0.04, 0.48±0.14, and 0.65±0.19, Kr values were 0.53±0.05, 0.66±0.18, and 0.98±0.29, respectively. Compared with the normal renal parenchyma, the ADC and MD values of patients with low-grade and high-grade ccRCC were gradually decreased, and the MK, Ka, and Kr values were all gradually increased(P<0.05). The difference in FA value was not statistically significant(P>0.05). (2)ROC analysis showed that the cut-off values of ADC, MD, MK, Ka and Kr in predicting pathological grade of ccRCC were 1.50×10-3mm2/s, 4.49×10-3mm2/s, 0.71, 0.51, 0.68, the sensitivity were 85.3%, 87.5%, 79.2%, 83.3%, 95.8%, and the specificity were 75.2%, 90.6%, 100.0%, 85.3%, 75.4%, respectively. The area under the curve(AUC)of ADC, MD, MK, Ka and Kr was 0.831, 0.884, 0.950, 0.832 and 0.874, among which the AUC of the MK value was the highest. Conclusion Compared with DWI mono-exponential mode, DKI mode, especially its derived parameter MK, is more suitable to serve as an imaging technique for predicting the pathological grade of ccRCC.
    Diffuse midline glioma with H3 K27M mutation in the spinal cord: a case report
    XU Jixi, CHEN Weijian
    Journal of Shandong University (Health Sciences). 2020, 1(7):  96-101.  doi:10.6040/j.issn.1671-7554.0.2020.0014
    Abstract ( 2239 )   PDF (8953KB) ( 275 )   Save
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    Objective To explore the clinical characteristics and treatment of diffuse midline glioma with H3K27M mutation. Methods The diagnosis and treatment of a case of diffuse midline glioma with H3K27M mutation were retrospectively analyzed and relevant literature was reviewed. Results The tumor was resected. The boundary between tumor tissues and spinal cord was unclear. The adhesion between tumor and cauda equina was especially hard to strip. Based on the histological characteristics, immunohistochemistry and molecular identification, the tumor was diagnosed as WHO IV diffuse midline glioma with H3K27M mutation. Although the patients back pain was relieved after operation, the prognosis was very poor, and the patient finally died of relapse. Literature review indicated the glioma was primarily found in children and occasionally seen in adults with poor prognosis. The glioma mainly infiltrated the thalamus, brainstem and spinal cord, sometimes the third ventricle, hypothalamus, pineal body and cerebellum. Conclusion Effective treatment of the glioma remains to be explored in spite of advances in modern therapies. The glioma is universally fatal and the 2-year overall survival rate is below 10%.
    A path analysis on the influence of burnout on quality of life among staff in two tertiary hospitals in Qingdao
    JI Yongjuan, XIANG Zini, KUANG Guifang
    Journal of Shandong University (Health Sciences). 2020, 1(7):  102-107.  doi:10.6040/j.issn.1671-7554.0.2020.0022
    Abstract ( 1669 )   PDF (1194KB) ( 150 )   Save
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    Objective To explore the characteristics of burnout and quality of life among staff in two tertiary hospitals, and to analyze the influence of burnout on quality of life. Methods A total of 508 hospital staff in two tertiary hospitals in Qingdao were randomly stratified and surveyed with Maslach Burnout Inventory(MBI), Quality of Life Questionnaire(GQOLI-74)and a self-developed demographic inventory. Results MBI: The rate of burnout was 53.6%; female staff got higher MBI score than male [(36.05±15.89)vs(30.76±15.67), t=3.351, P<0.01; staff without a managerial position displayed more serious burnout compared with those with managerial position [(36.11±15.02)vs(30.13±16.94), t=5.435, P<0.01); burnout in doctors(37.04±15.52), nurses(35.30±16.20)and technicians(35.01±16.78)were all higher than that in functional personnel(24.88±12.63)(F=15.303, P<0.01). GQOLI-74: Staff with less than 10 years of service(55.14±7.02)had reduced GQOLI-74 score than those with more than 10-20 years of service(56.32±6.73)and 20 years of service(57.93±5.86)(F=4.455, P<0.05); staff without a managerial position got lower GQOLI-74 score than those with a managerial position [(55.50±6.31)vs(59.69±5.12), t=9.815, P<0.01)]; GQOLI-74 score of doctors(55.64±7.13), nurses(55.79±6.50)and technicians(55.53±6.23)were lower than that of functional personnel(57.75±5.53), (F=2.931, P<0.05). Correlation, regression and path analysis: All MBI factors demonstrated a negative correlation with mental, physical and social functions in GQOLI-74(r=-0.09 - 0.35, P<0.05); emotional exhaustion and reduced sense of accomplishment in MBI were negative predictors of GQOLI-74(β=-0.126, -0.123, P<0.01); depersonalization and reduced sense of accomplishment in MBI showed statistical significance on the path of psychological, social and physical functions in GQOLI-74(path coefficient: -0.12 - 0.17, P<0.05); emotional exhaustion in MBI displayed statistical significance on the path of psychological and social functions in GQOLI-74(path coefficient was respective -0.15 and -0.16, P<0.05). Conclusion There is a high level of burnout among hospital staff in tertiary hospitals. Characteristics of burnout and quality of life among hospital staff are different in heterogenous subgroups. Depersonalization and reduced sense of accomplishment may be the factors influencing psychological, social and physical functions in quality of life.
    Influencing factors of perceived stress and job retention in national standardized training for resident doctors
    ZHANG Juan, ZHANG Lujia, XIAO Wei, LI Shunping
    Journal of Shandong University (Health Sciences). 2020, 1(7):  108-114.  doi:10.6040/j.issn.1671-7554.0.2020.0739
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    Objective To explore the perceived stress and job retention of resident doctors. Methods The resident doctors in 9 standardized training bases in Shandong Province were surveyed with electronic questionnaire of Perceived Stress Scale and the Intention to Retention Scale. Sample was carried out in 9 departments and 3 528 resident doctors were enrolled. The influencing factors of perceived stress and job retention were analyzed with chi-square test and binary Logistic regression. Results The perceived stress score was(25.19±7.82), and 52.6% of the resident doctors were under health risk pressure; the job retention score was(3.56±0.74), and 51.0% of the resident doctors had medium or low intention of job retention. Binary Logistic regression analysis showed that gender, current status, whether to obtain a doctors qualification certificate, training specialty, average monthly income and average number of bed managed were the influencing factors of perceived stress, while gender, current status, time of training, whether to obtain the doctors qualification certificate, training specialty, average monthly income and perceived stress were the influencing factors of job retention. Conclusion The level of perceived stress of resident doctors in Shandong Province is relatively high, while the level of job retention is medium or low. Due attention should be paid to their occupational and economic pressures so as to reduce their perceived stress and increase the level of job retention.
    Multilevel analysis of health related quality of life of patients with cardiovascular disease and its determinants
    DENG Qingwen, LIU Wenbin
    Journal of Shandong University (Health Sciences). 2020, 1(7):  115-121.  doi:10.6040/j.issn.1671-7554.0.2020.0080
    Abstract ( 1855 )   PDF (952KB) ( 342 )   Save
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    Objective To explore health related quality of life(HRQoL)of patients with cardiovascular disease(CVD)and identify the influencing factors. Methods A total of 1 201 CVD patients eligible for the research requirements were selected from CHARLS investigation. Patients information and regions were collected. HRQoL was measured using EQ-5D-3L scale. Patients information and regions were analyzed with K-W test. With patient as level 1 and region as level 2, a two-level regression model was set up to identify the influencing factors. Results The mean health utility value was 0.749±0.166. Univariate analysis showed that determinants of HRQoL of CVD patients included gender, educational level, marital status, hypertension, heart disease, stroke, sleep duration, smoking status, drinking status, minutes of moderate-intensity physical activity per week, frequency of social activity, body mass index(BMI)and region(P<0.05). Multilevel model results indicated that determinants of HRQoL of CVD patients were gender, education level, marital status, hypertension, dyslipidemia, heart disease, stroke, smoking status, minutes of moderate-intensity physical activity per week, frequency of social activity, BMI and region(P<0.05). Conclusion To improve quality of life of CVD patients, education level, smoking status, BMI and heterogeneity of different regions should be considered so as to develop targeted strategies.