Table of Content

  

10 April 2021
Volume 59 Issue 4

Research on mixed sample test for SARS-CoV-2

DONG Hongjie, ZHANG Junmei, WANG Shuai, WANG Hongwei, ZHANG KundiHU Wei, XIE Xiaohong, XIE Shiling, GU Lichuan

Journal of Shandong University (Health Sciences). 2021, 59(4):  1-5.  doi:10.6040/j.issn.1671-7554.0.2021.0126

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Objective To determine the reasonable sample sizes of diluted mixed sample test and n-in-1 test in the detection of SARS-CoV-2, so as to provide a more efficient scheme for nucleic acid screening of large samples. Methods A method was designed to extract nucleic acid from the preservation solution of large volume samples using a syringe purification column. In both diluted mixed sample test and n-in-1 test, this method was used in the extraction of nucleic acid from the total preservation solution and from 200 μL solution. The test results were compared. Results In diluted mixed sample test, for a single positive sample, the Ct values of ORF1ab gene and N gene were 3.583 and 2.904 lower from the total preservation solution than from the 200 μL solution; when one positive sample was mixed with 9 negative samples and 19 negative samples, there was no statistical difference in Ct values between the two sample sizes(P>0.05); when the number of mixed samples was more than 20, the Ct values increased significantly. In the n-in-1 test, the Ct values of nucleic acid extracted from total preservation solution was significantly lower than that from 200 μL solution(the current scheme). Conclusion In mixed sample detection, using a syringe purification column to extract nucleic acid from the total preservation solution can increase the maximum number of sample size from 20 to 50. With this strategy, the Ct values of nucleic acid test can be significantly reduced, so as to improve the detection rate and reduce the number of false-negative cases in n-in-1 test.

Potential mechanism of Astragalus membranaceus in the prevention of COVID-19 based on network pharmacology and molecular docking

YU Ying, ZHANG Gong, LIU Jing, YAN Shitong, HAN Tao, HUANG Hailiang

Journal of Shandong University (Health Sciences). 2021, 59(4):  6-16.  doi:10.6040/j.issn.1671-7554.0.2020.0491

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Objective To explore the potential molecular mechanism of Astragalus membranaceus in the treatment of coronavirus disease 2019(COVID-19)based on the network pharmacology and molecular docking. Methods The traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and the related literature were searched to obtain the active ingredients and predictive targets of Astragalus membranaceus. The herbal targets were selected based on STRING database for PPI network construction and the results were displayed by Cytoscape software. The key targets were screened through the algorithm of network topology and the network modules were analyzed. Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out on key target genes using Gene Ontology Enrichment Analysis Software Toolkit(GOEAST)and The Database for Annotation, Visualization and Integrated Discovery(DAVID)online tools. Combined with relevant literature, the mechanism of Astragalus membranaceus in the treatment of COVID-19 was analyzed. Results A total of 19 candidate active components and 889 predictive targets of Astragalus membranaceus were selected by oral bioavailability(OB)and drug-likeness(DL)values. The preventive mechanism of Astragalus membranaceus might be closely related to the signal pathways involved in the bodys living nerve ligand receptor interaction, calcium signal, T cell receptor, cAMP signal pathway and chemokines. Conclusion Astragalus membranaceus mainly plays roles in many kinds of targets through multi-approach and multi-signaling pathways.

Quantitative proteomic analysis of epidermal stem cells in oxygen-glucose deprivation conditions

ZHANG Huayu, YIN Siyuan, LIU Jian, MA Jiaxu, SONG Ru, CAO Guoqi, WANG Yibing

Journal of Shandong University (Health Sciences). 2021, 59(4):  17-27.  doi:10.6040/j.issn.1671-7554.0.2021.0288

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Objective To find the key proteins and pathways leading to the dysfunction of epidermal stem cells in oxygen-glucose deprivation(OGD)conditions and to explore the formation mechanism of chronic hard healing wounds. Methods Epidermal stem cells were extracted from newborn mice and cultured normally to the P3 generation. The cells were cultured under OGD conditions for 0, 3, 6, 9 and 12 h, respectively, and then were divided into five goups: 0 h was taken as the control group, and the other groups were taken as the experimental groups. There are four comparison groups: OGD3_vs_OGD0, OGD6_vs_OGD0, OGD9_vs_OGD0 and OGD12_vs_OGD0. Quantitative proteomics determination was performed on different groups of epidermal stem cells using Tandem mass tag(TMT)technology. The four comparison groups were screened for proteins with significantly differential expression. These differentially expressed proteins(DEPs)were analyzed for Gene Ontology(GO)category, KEGG pathway, protein-protein interaction(PPI), gene overlap, and analysis of pathways and proteins related to mitophagy to find the key proteins and pathways in the dysfunction of epidermal stem cells. Results A total of 4 852 quantifiable proteins were detected in the experiment. In the four comparison groups, that is, OGD3_vs_OGD0, OGD6_vs_OGD0, OGD9_vs_OGD0, and OGD12_vs_OGD0, the number of up-regulated DEPs were 1, 225, 346 and 386, respectively, while the number of down-regulated DEPs were 26, 229, 330 and 462, respectively. In the analysis of the comparison group OGD6_vs_OGD0, key pathways included “ribonucleoprotein complex biogenesis(GO: 0022613)”“chromatin binding(GO: 0003682)”“cytoplasmic ribosomal large subunit(GO:0022625)” and “ribosome(ko03010)”,and the 21 hub proteins screened through PPI analysis were all structural proteins of the ribosome, of which the most important seed protein was the mitochondrial ribosomal protein MRPL24. In the comprehensive analysis of the four comparison groups, it was found that there was a large amount of overlap between the DEPs of each comparison group, and key pathways were all related to protein processing. In the analysis of mitophagy-related pathway and proteins, it was found that the expression of Tbc1d15, Rab7a, which were related to lysosomal maturation and p53, continued to be up-regulated, while the expression of LC3 related to the level of autophagy flow did not show a definite trend. Conclusion The key protein “MRPL24” obtained through TMT quantitative proteomics analysis and the pathways related to protein processing are the key to the dysfunction of epidermal stem cells in OGD conditions. They will be the breakthrough points for further research on the formation mechanism of chronic hard healing wounds.

Atg7-siRNA interferes with radiosensitivity of esophageal cancer ECA109 cells by regulating arginine circulation

ZHANG Xiaohong, ZHOU Yun, DU Qiuying, REN Huixin, WANG Chaoqun

Journal of Shandong University (Health Sciences). 2021, 59(4):  28-34.  doi:10.6040/j.issn.1671-7554.0.2020.1295

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Objective To investigate the effects of siRNA interference with autophagy related gene 7(Atg7)on the radiosensitivity of ECA109 cells and the regulation of arginine circulation-related pathways. Methods ECA109 cells were divided into four groups: Ctrl group, siRNA group, Ctrl+R8Gy group(ECA109 cells transfected with Atg7-Ctrl at 8Gy radiation dose)and siRNA+R8Gy group(ECA109 cells transfected with Atg7-siRNA at 8Gy radiation dose). The protein expressions of Atg7, Beclin-1, microtubule associated protein 1 light chain 3 Ⅱ(LC3 Ⅱ), arginine succinate synthetase1(ASS1)and arginine succinic acid lyase(ASL)in each group were detected with Western blotting. The effects of arginine were detected with CCK8 assay. The cell survival curves were drawn at different concentrations of arginine(0, 8, 16, 32, 64, 128 mmol/L). IC50 and IC10 were calculated, and IC10 was set as the action concentration in the subsequent experiments. Cells were treated with arginine and siRNA respectively, and irradiated with 8Gy. After 24 h, the cell mortality was assessed by counting the number of cells. Results siRNA interference down-regulated Atg7 before and after radiotherapy(P<0.01). Compared with the Ctrl group, the Ctrl+R8Gy group had up-regulated levels of Beclin-1 and LC3Ⅱ(P<0.01). Compared with the Ctrl+R8Gy group, the siRNA+R8Gy group had down-regulated levels of Beclin-1 and LC3Ⅱ(P<0.01). Compared with the Ctrl+R8Gy group, the siRNA+R8Gy group had up-regulated levels of ASS1 and ASL(P<0.01). Arginine inhibited the proliferation of ECA109 cells in a concentration and time-dependent manner. Cell death analysis showed that siRNA interference(F=73.59, P<0.001)and arginine addition(F=158.72, P<0.001)increased cell mortality. The cell mortality was at the highest level when siRNA and arginine were used in combination(F=7.88, P=0.02). Conclusion Radiotherapy can induce autophagy in ECA109 cells. The Atg7-siRNA interference effectively antagonizes the radiotherapy-induced increase in autophagy, increases the radiotherapy-induced ECA109 cell death, and enhances the radiosensitivity of ECA109 cells. Atg7 knockdown can regulate the arginine circulation-related pathway proteins of ECA109 cells after radiotherapy, and increasing arginine concentration can enhance radiosensitivity of ECA109 cells.

Effects of curcumin on progesterone resistance in endometrial carcinoma

DING Fei, JIANG Jie

Journal of Shandong University (Health Sciences). 2021, 59(4):  35-41.  doi:10.6040/j.issn.1671-7554.0.2020.1753

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Objective To explore the effects of different concentrations of curcumin on progesterone resistant cells in endometrial carcinoma and to investigate the role of related signaling pathways influencing progesterone resistance. Methods The target genes of curcumin were analyzed in the ETCM and GEPIA databases and the interaction genes related to tumor-drug resistance were screened out. The resistance of an established progesterone-resistance model of Ishikawa cells in endometrial carcinoma(IshikawaPR cell line)was detected. Resistant cells were divided into curcumin(0, 5, 10, 20, 40, 60, 80 μmoL)groups, progesterone(0, 5, 10, 20, 40, 60, 90 μmoL)groups and curcumin+progesterone(the same concentration)groups, according to different treatments. The proliferation of cells in each group was determined with MTT. The effects of curcumin on the resistant cells were assessed with EDU, Transwell and mitochondrial membrane potential. The changes of intracellular protein levels after curcumin stimulation at different concentrations were determined with Western blotting. The potential signaling pathways were analyzed in the databases. Results Analyses of the databases indicated that curcumin target genes were closely related to tumor-drug resistance genes such as PGR and ESR. MTT results showed that curcumin inhibited the growth of drug-resistant cells, leading to a decrease in cell survival rate(F=907.8, P<0.001), and there was an interactive relationship between curcumin and progesterone(F=51.34, P=0.004). When the concentrations of progesterone were 10 μmoL(t=16.13, P=0.026), 20 μmoL(t=33.23, P=0.006), and 40μmoL(t=35.94, P=0.005), combination with curcumin inhibited drug-resistant cells more effectively than the use of progesterone alone. Curcumin treatment(0, 10, 20 μmoL)inhibited the proliferation(F=205.8, P<0.001), invasion(F=13.9, P=0.006)and promoted apoptosis(F=23.3, P=0.002)of drug-resistant cells. Western blotting showed that after curcumin treatment, the levels of CyclinD1, CASP3, MMP2 and p-NFκB decreased while the level of PR increased in resistant cells. Conclusion Curcumin inhibits progesterone resistance in endometrial carcinoma, possibly by mediating inactivation of transcription factor NFκB.

Effect of testosterone on the expression of polycystic ovary syndrome susceptibility gene Tox3 in zebrafish

HAN Xiao, LI Lei, LIU Congcong

Journal of Shandong University (Health Sciences). 2021, 59(4):  42-47.  doi:10.6040/j.issn.1671-7554.0.2021.0056

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Objective To determine the expression of polycystic ovary syndrome(PCOS)susceptibility gene Tox3 in wild-type zebrafish, and explore the effect of testosterone on Tox3 gene expression. Methods About 200 zebrafish embryos and 100 male and female adult zebrafish for control treatment and testosterone(10 ng/mL)treatment were required. Reverse transcription-polymerase chain reaction(RT-PCR)and real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)were used to test the expression of Tox3 gene in zebrafish. The distributions of Tox3 mRNA in zebrafish embryos were observed by whole mount in situ hybridization(WISH). Results In wild-type zebrafish, the level of Tox3 gene expression was high in the nervous system and reproductive system. After treated with 10 ng/mL testosterone, compared with the control group, the Tox3 gene expression of male zebrafish treated with 10 ng/mL testosterone was higher in brain ［(1.01±0.19) vs(1.43±0.35),P=0.043］ and in nest ［(1.05±0.32) vs(1.50±0.30),P=0.015］. Conclusion Tox3 in zebrafish may regulates the synthesis and release of androgen by acting on neuroendocrine systems.

Value of MnFe₂O₄@CNS in the theragnostic of pancreatic cancer

ZHANG Gaorui, ZHANG Yuting, ZHAO Yuxuan, WANG Fangqing, YU Dexin

Journal of Shandong University (Health Sciences). 2021, 59(4):  48-55.  doi:10.6040/j.issn.1671-7554.0.2020.1752

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Objective To investigate the value of MnFe₂O₄-loaded caramelized carbonaceous nanospheres(MnFe₂O₄@CNS)with inducing ferroptosis and synchronous MR monitoring in the theragnostic of pancreatic cancer. Methods After MnFe₂O₄@CNS was prepared, the characterization and relaxivity were detected. The cytotoxicity was determined with cell counting kit-8(CCK-8)assay. The Fenton reaction catalytic activity of different concentrations of MnFe₂O₄@CNS were evaluated. The uptake of MnFe₂O₄@CNS by murine pancreatic adenocarcinoma(Panc02)cells was detected. The imaging ability of MnFe₂O₄@CNS in Panc02 cells was evaluated. After incubation with MnFe₂O₄@CNS, the levels of reactive oxygen species(ROS)and cell death of Panc02 cells were evaluated and the morphological changes were observed with transmission electron microscopy(TEM). Results The average particle size of MnFe₂O₄@CNS was 183nm, and the relaxivity was 512.58 mmol/L·s^-1. After incubation with 50, 100 and 200 μg/mL MnFe₂O₄@CNS, the cell viability of the human pancreatic ductal epithelial cells(hTERT-HPNE)and Panc02 were significantly different(P<0.05). The Fenton reaction of MnFe₂O₄@CNS was high and MnFe₂O₄@CNS could be ingested by cancer cells. With higher concentration of MnFe₂O₄@CNS, the levels of ROS and apoptosis of Panc02 cells increased gradually, and the mitochondrial morphology of Panc02 cells showed classical characteristics of ferroptosis. The MRI of Panc02 cells showed high contrast signal effect of T2 with as incubation time increased(P<0.05). Conclusion Highly biocompatible, MnFe₂O₄@CNS can achieve targeted MRI and induce ferroptosis of pancreatic neoplasms, which is of great value in the theragnostic of pancreatic cancer.

Effects of domestic white light-emitting diodes exposure on rat retina

NAN Li, YANG Kaizhuan, ZHANG Yifan

Journal of Shandong University (Health Sciences). 2021, 59(4):  56-62.  doi:10.6040/j.issn.1671-7554.0.2020.1475

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Objective To investigate the effects of different illumination levels of white light-emitting diodes(LED)light on the retinal structure and function of SD rats, in order to seek a relative safe illumination threshold. Methods A total of 40 rats aged 8-10 weeks were selected and randomly divided into control group and experimental groups(4 subgroups)with 8 animals in each group. After dark adaptation, the SD rats were exposed to 200, 300, 500 and 1 000 lux white LED light respectively in 12 hrs cycle for 7 days. After dark adaptation for 24 hours, the retinal function was evaluated with flash electroretinogram(F-ERG), and the histopathological changes were assessed with hematoxylin-eosin(HE)staining and transmission electron microscopy. Apoptotic cell death was evaluated with reverse transcription-polymerase chain reaction(RT-PCR)via the relative mRNA expressions of Bax, Bcl-2 and Caspase-3. Results Scotopic ERG showed that 500 and 1 000 lux white LED exposure resulted in a decrease in Rod-Rb, Max-Ra, Max-Rb and Ops. In the 1 000 lux group, HE staining revealed massive retinal damage. In the 500 and 1 000 lux groups, transmission electron microscopy showed cell membrane structure damage. RT-PCR showed the relative mRNA expressions of Bax and Caspase-3 increased and the mRNA expression of Bcl-2 decreased after 500 and 1 000 lux irradiation. Conclusion Under daily indoor lighting intensity, 7-day cycle of white LED irradiation has no significant effects on the retinal structure and function of SD rats. Light intensity up to 500 lux can cause retinal photodamage in SD rats in a dose-dependent manner. The apoptosis-related genes Bax and Caspase-3 promote the occurrence and progression of retinal light damage.

Readmission prediction of 152 non-selective adult patients with chronic heart failure

LAN Hongtao, JIA Xu, TONG Zhoujie, ZHENG Man, HU Boang, ZHONG Ming, ZHANG Wei, WANG Zhihao

Journal of Shandong University (Health Sciences). 2021, 59(4):  63-69.  doi:10.6040/j.issn.1671-7554.0.2020.1439

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Objective To explore the influencing factors of readmission of patients with chronic heart failure(CHF). Methods A total of 152 CHF cases treated during May 2016 and Dec. 2018 were enrolled in this retrospective study, including 107 males and 45 females, age 26 to 93 years, average 70.95±14.08 years. Statistical analyses of clinical indicators, laboratory tests and drug use were performed with SPSS 20.0 software. CHF patients were divided into recurrence and non-recurrence groups for bivariate Logistic regression analysis. The readmission interval of patients with multiple admissions was analyzed with linear regression analysis. Results The recurrence rate of CHF was 58.6%. Compared with the non-recurrence group, the recurrence group tended to have a history of coronary heart disease(CHD), abnormal NT-proBNP and creatinine level, and no consumption of angiotensin converting enzyme inhibitor(ACEI)drugs, and the differences were statistically significant(P<0.05). Bivariate Logistic regression analysis revealed history of CHD(OR=3.728, 95%CI=1.902-7.308), use of digoxin(OR=1.320, 95%CI=1.034-1.686)and abnormal NT-proBNP(OR=4.854, 95%CI=2.010-11.723)were risk factors of recurrence, while increased diastolic blood pressure(DBP)(OR=0.982,95%CI=0.971-0.993)was a protective factor. Linear regression analysis showed age(β=-1.501, P=0.001)and history of diabetes(β=-0.810, P=0.036)were negatively correlated with the interval of readmission; gender(β=1.231, P=0.001), heart rate(HR, β=1.546, P=0.001), and taking of aspirin(β=0.477, P=0.001)were associated with prolonged interval of readmission. Conclusion There is a nonstandard administration of CHF patients and the recurrence rate is high. NT-proBNP, heart rate and diastolic blood pressure should be closely monitored to reduce the recurrence rate of CHF.

Effects of lncRNA AC012073.1 on the migration and invasion of human breast cancer cells and its clinical significance

KONG Xue, LI Juan, DUAN Weili, SHI Shuang, LI Peilong, DU Lutao, MAO Haiting, WANG Chuanxin

Journal of Shandong University (Health Sciences). 2021, 59(4):  70-78.  doi:10.6040/j.issn.1671-7554.0.2021.0166

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Objective To explore the expression of long non-coding RNA(lncRNA)AC012073.1 and its effects on the migration and invasion of human breast cancer(BC)cells. Methods The lncRNAs which were upregulated in BC tissues and related to poor prognosis were screened with lncRNA microarray and the cancer genome atlas(TCGA). The expression of AC012073.1 in BC cells and serum was detected with quantitative real-time PCR(qRT-PCR). MDA-MB-231 and MCF-7 cells were transfected with AC012073.1 siRNAs or plasmid and the transfection efficiency was detected with qRT-PCR. Cell migration and invasion were then determined with transwell assay and wound healing assay, respectively. The downstream targets and function enrichment analysis were predicted with TargetScan, and a regulatory network of ceRNA was constructed with Cytoscape software. The diagnostic efficacy of serum AC012073.1 for BC was analyzed with receiver operating characteristic(ROC)curve. Results A novel lncRNA, AC012073.1, was identified, which was significantly upregulated in BC tissues(P<0.001)and associated with poor prognosis(P=0.031). Compared with normal breast epithelial cells, BC cell lines had elevated expression of AC012073.1(P<0.05). Knockdown of AC012073.1 significantly inhibited cell migration and invasion, but overexpression of AC012073.1 promoted cell migration and invasion. The downstream targets and gene ontology(GO)analysis indicated that AC012073.1 promoted BC progression by regulating typical tumor signaling pathways. The qRT-PCR results showed the expression of AC012073.1 significantly increased in BC serum samples(P<0.001). The area under ROC curve(AUC)was 0.833, indicating it had a great diagnostic value for BC. Conclusion Highly expressed in BC, AC012073.1 promotes the migration and invasion of BC cells, and may serve as a potential biomarker for the diagnosis and prognosis of BC.

Identification of differentially expressed genes and Wilms tumor-1 expression in adenomyosis

GENG Chen, YANG Yang, ZHAO Yue, LIU Haoran, CHAO Lan

Journal of Shandong University (Health Sciences). 2021, 59(4):  79-86.  doi:10.6040/j.issn.1671-7554.0.2021.0199

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Objective To screen the differentially expressed genes(DEGs)in adenomyosis from the Gene Expression Omnibus(GEO)database and to explore the expression of Wilms tumor-1(WT1). Methods The candidate genes were screened in the GEO database. The DEGs underwent Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment. The protein and mRNA expressions of WT1 in adenomyosis group and control group were detected with Western blotting and real-time quantitative polymerase chain reaction(qRT-PCR), respectively. The expression position and expression of WT1 in adenomyosis group and control group were determined with immunohistochemical staining. Results KEGG and GO of DEGs were enriched in transcription factor activity, cadherin binding involved in cell-cell adhesion, growth factor binding and other processes. Western blotting and qRT-PCR showed that the protein and mRNA expressions of WT1 were lower in the adenomyosis group than in the control group(P=0.002, P=0.003). Immunohistochemical staining showed that the WT1 staining level in stroma was lower in the adenomyosis group than in the control group(P=0.001), while the WT1 staining level in epithelium was higher(P<0.001); the overall staining level of WT1 in the adenomyosis group was lower than that in the control group(P=0.003). Conclusion The DEGs are screened from the GEO database and underwent KEGG and GO enrichment and WT1 may be involved in the pathogenesis of adenomyosis.

Value of ovarian-adnexal reporting and data system in differentiating 101 benign and malignant ovarian-adnexal masses

WANG Yixuan, LI Fei, HU Rong, WANG Bei

Journal of Shandong University (Health Sciences). 2021, 59(4):  87-92.  doi:10.6040/j.issn.1671-7554.0.2021.0048

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Objective To explore the value of ovarian-adnexal reporting and data system(O-RADS)in differentiating benign and malignant ovarian-adnexal masses. Methods Totally, 101 patients who were diagnosed as ovarian or adnexal diseases were evaluated by ultrasound from November 2018 to November 2020. The ultrasonic images were analyzed retrospectively using O-RADS to categorize the patients. Taken pathological results as the gold standard, the receiver operating characteristic(ROC)curve was described to get the diagnostic efficacy. Results (1) The incidence rate of malignancies of O-RADS 2-5 types were 0%, 3.85%, 27.78%, and 68.75%, respectively. (2) The weighted Kappa coefficient between two different sonographers diagnoses was 0.84, P<0.001. (3) The area under the curve(AUC)of O-RADS was 0.83, cutoff value was O-RADS 5 type. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy were 66.67%, 85.29%, 68.75%, 84.06%, and 79.21%, respectively. Conclusion The value of O-RADS is relatively high in differentiating benign and malignant ovarian-adnexal masses.

Analysis of prognostic factors after radical resection of intrahepatic cholangiocarcinoma and establishment of a nomogram

XIE Tonghui, CHEN Zhiqiang, CHANG Jianhua, ZHAO Danwen, XU Bowen, ZHI Xuting

Journal of Shandong University (Health Sciences). 2021, 59(4):  93-99.  doi:10.6040/j.issn.1671-7554.0.2020.1548

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Objective To explore the prognostic factors after radical resection of intrahepatic cholangiocarcinoma(ICC)and to establish a nomogram to predict postoperative overall survival. Methods The clinicopathological data of 79 ICC patients who underwent radical resection in our hospital during Jul. 2009 and Oct. 2017 were collected. The impacts of clinicopathological characteristics on overall survival and recurrence-free survival were analyzed with Kaplan-Meier and Cox regression models. A survival nomogram was established with R software(version 4.0.1), and the predictive performance of the nomogram was verified with C-index, calibration curve and area under ROC curve(AUC). Results The 1-year, 2-year, and 3-year cumulative recurrence-free survival rates were 43.0%, 26.6% and 20.3%, respectively. The median survival time was 15 months, and the 1-year, 2-year, and 3-year cumulative overall survival rates were 63.3%, 41.8% and 27.8%, respectively. Multivariate analysis demonstrated that CA19-9, lymphovascular invasion and multiple tumors were independent risk factors of overall survival. CA19-9, multiple tumors and differentiation of tumors were independent risk factors of recurrence. The C-index was 0.723(95%CI: 0.66-0.79), and the AUC of 1-year, 2-year, and 3-year survival rates were 0.78(95%CI: 0.68-0.89), 0.85(95%CI: 0.77-0.93), and 0.77(95%CI: 0.67-0.87), respectively. Conclusion ICC has a poor prognosis and low postoperative survival rate. The early symptoms are atypical. CA19-9 and multiple tumors are independent risk factors for both survival and recurrence. The internally validated nomogram can predict the survival rates.

Spiral CT in differentiating benign and malignant tumors with myxoid degeneration

ZHAO Jie, LI Yan, LI Ming, YU Dexin

Journal of Shandong University (Health Sciences). 2021, 59(4):  100-107.  doi:10.6040/j.issn.1671-7554.0.2021.0109

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Objective To explore the value of spiral dynamic enhanced CT in differentiating benign and malignant myxoid soft tissue tumors. Methods The clinical and CT data of 147 patients(52 males and 95 females)with myxoid soft tissue tumors diagnosed by pathology in Qilu Hospital of Shandong University from August 2016 to March 2020 were retrospectively analyzed. The patients were divided into the benign group(n=59)and malignant group(n=88). The plain and tri-phasic dynamic enhanced CT features of tumors were evaluated and recorded by two radiologists, including the maximum/minimum diameter, boundary and shape of lesions, distribution and amount of myxoid or solid part, calcification and liquefaction necrosis within the tumor, enhanced blood vessel, and CT values of myxoid and solid components during the plain and enhanced CT phases. Patients age, gender, location of lesions, and CT features were analyzed to assess the differential diagnostic value. After variables were screened with the variance inflation coefficient(VIF), a multivariable Logistic regression prediction model was established, including the model 0 based on multiple fractional polynomial(MFP)model, model 1 with all variables and model 2 based on akakike information criteria(AIC), the receiver-operating characteristic(ROC)curve was drawn to evaluate the effectiveness of the models. Results Patients age, location of lesions, maximum/minimum diameter, tumor boundary, tumor shape, tumor calcification, enhanced vessels in tri-phasic scanning and solid part on plain CT were statistically different between benign and malignant tumors(P<0.05). The Logistic regression prediction model had certain value in the differentiation of benign and malignant tumors(Model 0: OR=29.714 3, AUC=0.867 8; Model 1: OR=37.142 9, AUC=0.874 6; Model 2: OR=9.730 8, AUC=0.833 6). Conclusion The Logistic regression prediction model based on spiral CT features and clinical data of patients can be used to differentiate benign and malignant myxoid soft tissue tumors.

Clinical value of targeted multiparameter MRI and transrectal ultrasonography fusion prostate biopsy for the detection of PI-RADS≥3 prostate cancer

SUN Dingqi, FU Qiang, ZHANG Hui, LIU Shuai, DIAO Tongxiang, CAO Qingwei, ZHANG Keqin

Journal of Shandong University (Health Sciences). 2021, 59(4):  108-113.  doi:10.6040/j.issn.1671-7554.0.2020.1670

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Objective To evaluate the clinical value of multiparameter magnetic resonance imaging(mpMRI)and transrectal ultrasonography(TRUS)fusion prostate biopsy for the detection of prostate cancer(PCa)and clinical significant prostate cancer(csPCa). Methods A total of 161 patients treated during Sep. 2018 and Jun. 2020 with prostate imaging reporting and data system(PI-RADS)≥3 were enrolled in this study. The patients were randomly assigned to undergo either systematic prostate biopsy(systematic group)or targeted mpMRI/TRUS fusion prostate biopsy + systematic prostate biopsy(combined group). The clinical data and pathological results of biopsies were analyzed. Results The detection rate of PCa by targeted mpMRI/TRUS fusion prostate biopsy was higher than that of systematic prostate biopsy, but there was no significantly difference(χ2=0.627,P=0.429). There were 40 cases in the combined group and 22 in the systematic group diagnosed as csPCa, respectively. The detection rate of csPCa was much higher in the combined group(χ2=8.139, P=0.004). When Gleason score>6, targeted mpMRI/TRUS fusion prostate biopsy had significantly higher detection rate than systematic biopsy(P=0.010). Conclusion In patients with PI-RADS≥3 prostate cancer, targeted mpMRI/TRUS fusion prostate biopsy has higher detection rates of PCa and csPCa than systematic prostate biopsy, but it still misses some cases. Combination of targeted mpMRI/TRUS fusion prostate biopsy and systematic prostate biopsy can improve the detection rate of all prostate cancers, especially csPCa.

A case of congenital disorder of glycosylation caused by SLC35A2 gene mutation

SUN Yu, CHEN Na, MA Aihua

Journal of Shandong University (Health Sciences). 2021, 59(4):  113-116.  doi:10.6040/j.issn.1671-7554.0.2020.1529

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Objective To explore the clinical manifestations and genetic basis of a patient with recurrent epileptic seizures and global developmental delay. Methods The clinical data and genetic test results of the patient were analyzed retrospectively and related literature was reviewed. Results The patient, a boy, whose main clinical features were recurrent epileptic seizures and developmental delay that started from about 1 month after birth. Physical examination showed hypopigmentation on the lower abdomen, right leg and back. Video electroencephalogram(EEG)suggested abnormal infant electroencephalogram, periodic burst inhibition with hypsarrhythmia; cerebral magnetic resonance imaging(MRI)indicated abnormal signal in the bilateral periventricular white matter. Next generation sequencing detected that the patient carried a heterozygous de novo mutation of c.262G>C(P.A88P)in SLC35A2 gene(NM_001042498), which was a spontaneous mutation. After use of antiepileptic drugs such as topiramate, clonazepam, levetiracetam and lamotrigine and treatment with adrenocorticotropic hormone(ACTH)in combination, the seizure frequency was decreased. Conclusion SLC35A2-CDG is a metabolic disease caused by X-linked dominant inheritance of glycoprotein synthesis defects. Currently there is no effective treatment and the suspected cases can get a definite diagnosis by gene detection.

Path analysis of negative life events, rumination and sleep quality on emotional state in ward nurses

WANG Heng, XIANYU Junjie, FENG Shengjie, ZHAO Jing, LI Jiahuan

Journal of Shandong University (Health Sciences). 2021, 59(4):  117-121.  doi:10.6040/j.issn.1671-7554.0.2021.0103

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Objective To explore the influence path of negative life events, rumination and sleep quality on emotional state in ward nurses, so as to provide reference for a targeted intervention. Methods The GAD 7 Scale, PHQ-9 Scale, Ruminative Responses Scale, Pittsburgh Sleep Quality Index and Stressful Life Events Scale and Stressful Life Events Scale were used to investigate 850 ward nurses in a tertiary hospital. SPSS 22.0 and AMOS 21.0 were used to analyze the data. Results Anxiety and depression was positively correlated with negative life events, rumination and sleep quality(r=0.25-0.75, P<0.01). Negative life events directly influenced emotional state, or indirectly influenced emotional state by rumination and sleep quality. The total effect of negative life events on emotional state was 0.34, of which the direct effect was 0.09(26.47%), and the indirect effect was 0.25(73.53%). Conclusion Negative life events, rumination and sleep quality affect the emotional state in multiple pathways.