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    10 October 2022
    Volume 60 Issue 10
    Thyroid stimulating hormone promotes chondrocyte differentiation via anti-inflammatory protein CTRP3
    ZHANG Weiwei, HUA Fang, LIANG Chaoshuai, CHU Miaomiao, SUN Jiayi, FRANK Zaucke, XIN Wei
    Journal of Shandong University (Health Sciences). 2022, 60(10):  1-8.  doi:10.6040/j.issn.1671-7554.0.2022.0439
    Abstract ( 718 )   PDF (12685KB) ( 126 )   Save
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    Objective To investigate the role of thyroid stimulating hormone(TSH)in the differentiation of primary mouse chondrocytes(PMCs)and the underlying mechanism. Methods The expressions of chondrocyte differentiation markers, including extracellular matrix collagen type Ⅱ(Col Ⅱ)and collagen type Ⅹ(Col Ⅹ), and matrix metalloproteinase 3(MMP3)and matrix metalloproteinase 13(MMP13)were detected on both mRNA and protein levels with qRT-PCR, Western blotting and immunofluorescent staining. The changes of interleukin-1β(IL-1β), interleukin-6(IL-6)and tumor necrosis factor-α(TNFα)were detected in TSH stimulated group and control group with qRT-PCR and ELISA. The differentially expressed genes of PMCs treated with TSH were screened with high-throughput RNA-Seq. PMCs were transfected with C1q/tumor necrosis factor-related protein 3(CTRP3)overexpression plasmid o explore the mechanism of TSH regulating PMCs differentiation. Results TSH upregulated the expressions of MMP3(P=0.016, P<0.001), MMP13(P<0.001), IL-1β(P=0.007, P=0.002), IL-6(P<0.001)and TNFα(P=0.006, P<0.001). The differentially expressed gene CTRP3 was screened out with RNA-seq. After CTRP3 overexpression, the expression of Col Ⅱ in PMCs was increased(F=76.062, F=77.085, F=190.115, P<0.001), while the expression of Col Ⅹ was decreased(F=33.494, F=38.424, F=43.351). Compared with simple TSH stimulation, after CTRP3 overexpression, the expressions of MMP3 (F=88.607, F=214.145, F=135.60), MMP13(F=116.561, F=138.674, F=86.865), IL-1β, IL-6 and TNFα were significantly decreased(P<0.001). Conclusion CTRP3 has a protective effect on TSH-induced differentiation of PMCs, and it may become a promising anti-inflammatory therapeutic target for joint injury in patients with subclinical hypothyroidism(SCH).
    Effects and mechanism of interfering MAD2L1 gene expression on the apoptosis of breast cancer cells
    FENG Haigang, LIU Guowen, CAO Hong
    Journal of Shandong University (Health Sciences). 2022, 60(10):  9-16.  doi:10.6040/j.issn.1671-7554.0.2022.0282
    Abstract ( 748 )   PDF (4562KB) ( 80 )   Save
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    Objective To explore the effects of interference with mitotic arrest deficient 2-like protein 1(MAD2L1)gene expression on breast cancer(BC)cell apoptosis and the mechanism. Methods The mRNA expressions of MAD2L1 in normal breast epithelial cell line MCF-10A and BC cell lines, including MDA-MB-231, MCF-7, SK-BR-3 and BT-20, were detected with qRT-PCR. After MAD2L1 siRNA was transfected into MDA-MB-231 cells, the mRNA and protein expressions of MAD2L1 were detected with qRT-PCR and Western blotting; cell proliferation ability was measured with MTT; cell apoptosis was detected with Annexin V-FITC/PI; expressions of Bax, Bcl-2, cleaved-caspase-3, p-p38MAPK(Thr180/Thr182)and p38MAPK were determined with Western blotting. After the above cells were treated with the p38MAPK inhibitor SB203580 in combination, the changes in apoptosis rate were detected with flow cytometry, and changes in the expressions of Bax, Bcl-2, cleaved-caspase-3, p-p38MAPK and p38MAPK were detected with Western blotting. Results The mRNA expression of MAD2L1 in BC cell line, especially in MDA-MB-231 cells, was significantly higher than that in MCF-10A cells. Interference with MAD2L1 gene reduced the mRNA and protein expressions of MAD2L1 in MDA-MB-231 cells(tmRNA=10.51, PmRNA<0.001; tprotein=18.30, Pprotein<0.001), inhibited cell proliferation(Fgroup=243.36, Ftime=44.00, Fgroup × time=9.881, all P<0.001), promoted cell apoptosis(t=9.10, P<0.001), up-regulated the protein expressions of Bax, cleaved-caspase-3 and p-p38MAPK(tBax=15.05, PBax<0.001; tcleaved-caspase-3=5.26, Pcleaved-caspase-3=0.006; tp-p38MAPK=28.46, Pp-p38MAPK<0.001), and down-regulated the protein expression of Bcl-2(tBcl-2=14.23, PBcl-2<0.001). However, SB203580 treatment inhibited the induction of apoptosis by MAD2L1 gene interference on MDA-MB-231 cells(P=0.002). Conclusion Interfering with the expression of MAD2L1 gene can inhibit the proliferation of MDA-MB-231 cells and induce apoptosis, and the mechanism may be related to the activation of the p38MAPK signaling pathway.
    A new method of trajectory screw placement for pelvis and acetabulum
    TIAN Jiguang, WANG Zhiyong, CHENG Lin, SANG Xiguang
    Journal of Shandong University (Health Sciences). 2022, 60(10):  17-26.  doi:10.6040/j.issn.1671-7554.0.2022.0415
    Abstract ( 729 )   PDF (28052KB) ( 143 )   Save
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    Objective To develop a new method of percutaneous screw fixation for pelvis and acetabulum. Based on this method, a device was designed and human specimens were studied to evaluate the efficacy of screw fixation. Methods Based on CT data, this study adopted projection and direction decomposition to accurately locate the screw entry point and entry direction, and designed a set of special location frame. Before surgery, the location frame was fixed to the human specimen pelvis and CT scan was performed to obtain data. The screw path was planned using CT analysis software, and then the required positioning parameters were measured with direction decomposition. Then the screw path was located with the help of the location frame during operation. Results The sacroiliac, LC II and anterograde anterior column screws were successfully inserted by the above method. CT scanning showed postoperative screw paths were highly consistent to the preoperative designed ones, and met the clinical criteria well. Conclusion This new method provides an accurate, convenient, rapid and cost-effective way for pelvis and acetabulum percutaneous screw fixation, and is recommended for clinic application.
    Long non-coding RNA NONHSAT247814.1 expression in 18 childhood with myocarditis and in vitro cellular experimental observation
    FENG Xinxin, HAN Bo, ZHANG Li, MA Mengjie, CHEN Siyu
    Journal of Shandong University (Health Sciences). 2022, 60(10):  27-32.  doi:10.6040/j.issn.1671-7554.0.2022.0152
    Abstract ( 649 )   PDF (2719KB) ( 107 )   Save
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    Objective To explore the potential diagnostic marker of child myocarditis and to clarify the biological functions in human cardiomyocyte inflammation. Methods Long non-coding RNAs(LncRNAs)differentially expressed in the results of pediatric myocarditis gene chips were screened, the sample size was expanded for validation, and the target molecule was identified. The basic data and clinical information of 18 children with myocarditis(myocarditis group)and 18 healthy children(normal control group)were collected, real-time quantitative polymerase chain reaction(qRT-PCR)was used to test the expression of the target molecule, and then the receiver operating characteristic(ROC)curve was plotted to evaluate the value of the target molecule in the diagnosis of pediatric myocarditis. Lipopolysaccharide was utilized to stimulate AC16 cells and then extoblish the model of inflammatory injury, and the small interfering RNA was transfected into AC16 to inhibit the expression of the target molecule. Enzyme-linked immunosorbent assay(ELIAS)was used to test the protein concentration of inflammatory factors and myocardial injury markers in the cell supernatants, and CCK8 was used to detect cellular proliferation. Results NONHSAT247814.1 was identified as the target molecule. The relative expression of NONHSAT247814.1 was higher in the myocarditis group than in normal control group(P<0.001). The relative expression was higher in acute phase than in recovery phase, and positively correlated with NT-pro brain natriuretic peptide in the peripheral circulation(R2=0.40, P=0.005), but negatively correlated with left ventricular ejection fraction(R2=-0.53, P=0.0006). ROC for NONHSAT247814.1 in diagnosing myocarditis was(AUC=0.89, P<0.001, sensitivity=83.33% and specificity=88.89%). At the cellular level, reducing the expression of NONHSAT247814.1 attenuated the release of interleukin-1β, interleukin-6, troponin T and brain natriuretic peptide, while increased the cellular proliferation. Conclusion NONHSAT247814.1 has potential as a diognostic marker for myocarditis in children, inhibiting of NONHSAT247814.1 expression attenuates LPS-induced inflommation iujury in cardiomyocytes effects at the cellular level.
    Proteomic analysis of serum exosomes in pancreatic cancer with different stages of progress
    LI Yanru, LI Juan, LI Peilong, DU Lutao, WANG Chuanxin
    Journal of Shandong University (Health Sciences). 2022, 60(10):  33-41.  doi:10.6040/j.issn.1671-7554.0.2022.0169
    Abstract ( 864 )   PDF (11701KB) ( 397 )   Save
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    Objective To screen the differential proteins of serum exosomes in healthy controls and pancreatic cancer patients with different degrees of progression, draw the profile, and analyze their functions and biological processes. Methods Exosomes were quantitatively analyzed with label-free quantitative proteomic analysis technology. The differential proteins were screened and bioinformatic analysis was performed. The proteins associated with pancreatic cancer progression were serologically verified with Western blotting. Results A total of 2 242 proteins were detected in the control, non-metastatic and metastatic pancreatic cancer samples with label-free quantitative proteomic analysis and a total of 664 proteins with statistically significant differences were identified, which were mainly involved in vesicle-mediated transport, focal adhesion and extracellular cortex matrix(ECM)receptor interaction. Moreover, there were 5 proteins with statistically significant differences among the three groups, of which leucine-rich alpha-2-glycoprotein 1(LRG1)was highly expressed in serum exosomes of metastatic pancreatic cancer. Conclusion There are differences in protein expression patterns among healthy controls, non-metastatic and metastatic pancreatic cancer patients, and the differential proteins are mainly enriched in focal adhesion and ECM-receptor interaction and other signaling pathways. LRG1, which is different in all three groups, may be a serological marker for monitoring the progression of pancreatic cancer.
    Prognostic factors of elderly patients with glioblastoma treated with Stupp treatment
    SHI Xiaohan, LI Huayu, LI Feng
    Journal of Shandong University (Health Sciences). 2022, 60(10):  42-48.  doi:10.6040/j.issn.1671-7554.0.2022.0091
    Abstract ( 682 )   PDF (3008KB) ( 72 )   Save
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    Objective To investigate the prognostic factors of elderly patients with glioblastoma(GBM)treated with Stupp treatment. Methods Clinical data of elderly GBM patients who received Stupp treatment during Jan. 2014 and Jan. 2018 were retrospectively analyzed, including demographic information, clinical characteristics, Karnofsky Performance Scale(KPS)score, molecular marker O6-methyl guanine DNA methyltransferase(MGMT), isocitrate dehydrogenase 1(IDH-1), expression of ki67 and TP53, and so on. Univariate analysis was performed on overall survival(OS)and progression-free survival(PFS)by Kaplan-Meier, and Cox regression model was used for multivariate comparison. Results A total of 91 samples were enrolled, including 49(53.8%)cases of Ki67≥30%, 78(85.7%)cases of IDH wild type, 35(38.5%)cases of MGMT methylation, and 44(48.4%)cases of TP53 protein positive. The 1-year, 3-year and 5-year OS were 41.8 %, 12.8%, and 9.6%, respectively. The 1-year and 3-year PFS were 16.5% and 7.6%, respectively. KPS score(HR=0.445, 95%CI: 0.265-0.745, P=0.002), cognitive function(HR=2.675, 95%CI: 1.051-6.089, P=0.039), MGMT(HR=0.384, 95%CI: 0.218-0.675, P=0.001), Ki67(HR=1.855, 95%CI: 1.157-2.975, P=0.010)were significantly associated with OS. KPS(HR=0.598, 95%CI: 0.358-0.998, P=0.049), MGMT(HR=0.335, 95%CI: 0.187-0.601, P<0.001), IDH-1(HR=0.437, 95%CI: 0.200-0.958, P=0.039), Ki67(HR=1.958, 95%CI: 1.203-3.187, P=0.007)were significantly associated with PFS. Conclusion The prognosis of elderly GBM patients is poor. KPS score, cognitive function, MGMT, IDH-1 and Ki67 can predict the prognosis.
    Distribution characteristics of nasopharyngeal microbiota of 312 healthy infants under 6 months of age detected by MALDI-TOF MS
    GUAN Hengyun, LIU Lanzheng, JIANG Huiyu, BAI Aiying, LIU Hui, ZHAO Xiaodong, GAO Shang, LI Na, RUAN Shiman
    Journal of Shandong University (Health Sciences). 2022, 60(10):  49-56.  doi:10.6040/j.issn.1671-7554.0.2022.0360
    Abstract ( 646 )   PDF (7464KB) ( 67 )   Save
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    Objective To explore the distribution characteristics of nasopharyngeal microflora in healthy infants under 6 months of age using matrix-assisted laser desorption ionization time of flight mass spectrometry(MALDI-TOF MS)so as to provide sample bank information for nasopharyngeal microecology research. Methods Nasopharyngeal swabs were collected from 312 healthy infants during Nov. 2019 and April 2020 in Jinan. The pure strains were obtained after culturing and isolating. The bacterial strains were identified by MALDI-TOF MS to the species-level. The infants were divided into four age groups(≤ 2 months, 3 months group, 4 months group and 5 months group). SPSS 22.0 software was used for chi-square test or Fisher exact test between groups. Results A total of 741 bacterial strains were isolated, including 74 species of 25 genera of bacteria. The dominant genera were Staphylococcus(31.6%), Corynebacterium(30.8%), Streptococcus(18.9%), Moraxella(8.6%)and Dolosicoccus(2.0%). Some uncommon bacteria were also found, such as Abiotrophia defectiva, Rhizobium radiobacter, et al. The detection rate of Staphylococcus aureus was higher in male infants(40.5%)than in female infants(26.4%), while the detection rate of Corynebacterium propinquum was higher in female infants(42.4%)than in male infants(27.4%). In the four age groups, the detection rate of Corynebacterium pseudodiphtheriticum was increased successively(10.8%, 17.7%, 18.9% and 46.7%), as the same for Streptococcus pneumoniae(2.2%, 2.3%, 4.1% and 20.0%). Conclusion The diversity is mainly characterized by dominant bacteria in nasopharyngeal microflora for healthy infants under 6 months of age in Jinan, China. MALDI-TOF MS is a rapid and high-throughput technique for identifying common and uncommon bacterial species. The results can provide valuable reference for the study of nasopharyngeal microecology of children in Jinan.
    Ultrasound-guided fine needle aspiration biopsy and BRAFV600E molecular detection in the diagnosis of thyroid cancer
    LIU Yan, CAO Guanglei, CHEN Li
    Journal of Shandong University (Health Sciences). 2022, 60(10):  57-61.  doi:10.6040/j.issn.1671-7554.0.2022.0876
    Abstract ( 898 )   PDF (1592KB) ( 93 )   Save
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    Objective To investigate the value of ultrasound-guided fine needle aspiration biopsy(FNAB)and molecular detection of v-raf murine sarcoma viral oncogenic homolog B1(BRAF)V600E(BRAFV600E)in the diagnosis of thyroid carcinoma. Methods This study retrospectively analyzed 304 patients with thyroid nodules during Jan. 2019 and Dec. 2021. FNAB cytopathology and BRAFV600E molecular testing were performed. With postoperative pathological diagnosis as the gold standard, the patients were divided into FNAB group(n=138)and FNAB combined with BRAFV600E group(n=166). The receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate the diagnostic efficacy of the two groups. The ultrasound characteristics of Bethseda I and III-V nodules were also analyzed. Results Among the 304 patients, 278 were diagnosed with thyroid carcinoma, including 277 papillary thyroid cancer, 1 medullary thyroid cancer, and 26 benign lesions. There were 53 nodules with uncertain cell diagnosis, and the characteristics of ultrasonography were calcification(28.3%)and nodular size < 1 cm(45.3%)was dominant. According to the postoperative pathological results, efficacy evaluation of FNAB group was as follows: the sensitivity, specificity, and AUC were 93.9%, 57.1% and 0.824, respectively. Efficacy evaluation of FNAB combined with BRAFV600E group was as follows: the sensitivity, specificity, and AUC were 98.0%, 84.2% and 0.911, respectively. And AUC combined analysis> AUCFNAB. Conclusion The diagnostic efficiency of FNAB combined with BRAFV600E is higher than that of FNAB alone.
    Correlation between baseline CT features and progression of abdominal aortic aneurysm in 71 cases
    WANG Ying, GU Hui, YU Xinxin, HU Jinzhuo, WANG Ruopeng, WANG Ximing
    Journal of Shandong University (Health Sciences). 2022, 60(10):  62-67.  doi:10.6040/j.issn.1671-7554.0.2022.0438
    Abstract ( 679 )   PDF (4386KB) ( 98 )   Save
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    Objective To evaluate the baseline CT features associated with the progression of abdominal aortic aneurysm(AAA)so as to provide a reference for the clinical treatment of AAA. Methods Clinical and imaging data of 83 AAA patients who underwent at least two enhanced CT scans during Jan. 2012 and Dec. 2021 were selected for analysis, with an interval of 3 months or more between the two scans. Baseline CT features such as aneurysm diameter, area, length, curvature, and thrombus area were measured, and the annual rate of AAA progression was calculated based on the aneurysm diameter. Patients with progression were divided into slow progression group(progression rate ≤0.25 cm/y)and rapid progression group(progression rate >0.25 cm/y). Independent samples t-test or Mann-Whitney U nonparametric test was used for comparison between groups; univariate and multivariate linear regression analyses were applied to determine baseline CT characteristics associated with AAA progression. Results Progression was present in 71 patients, including 35 in the slow progression group and 36 in the rapid progression group. The baseline aneurysm length was significantly longer in the rapid progression group than in the slow progression group(P=0.03). Multivariate analysis showed that aneurysm area(β=0.048, P=0.020)and length(β=0.051, P=0.007)were independently and positively correlated with the rate of progression, and aneurysm curvature(β=-0.005, P=0.034)and thrombus area(β=-0.034, P=0.013)were independently and negatively correlated with the rate of progression. Conclusion Among the baseline CT features of AAA patients, aneurysm area, length, curvature, and thrombus area are significantly associated with progression.
    Single nucleotide polymorphism microarray analysis of 364 cases of spontaneous abortion during early and middle pregnancy
    GAO Qing, LU Ting, SHAN Shan, TAO jing, JIN Hua
    Journal of Shandong University (Health Sciences). 2022, 60(10):  68-73.  doi:10.6040/j.issn.1671-7554.0.2022.0398
    Abstract ( 634 )   PDF (971KB) ( 181 )   Save
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    Objective To investigate the application of single nucleotide polymorphism microarray(SNP array)in spontaneous abortion in early and middle pregnancy. Methods A total of 364 cases of spontaneous abortion were selected, and the distribution of chromosomal abnormalities leading to spontaneous abortion were analyzed with SNP array. The patients were divided into groups according to the gestational weeks, pregnant age and sex of abortion tissue, including gestational 6-12 weeks group(n=300)and gestational 13-28 weeks group(n=64); under 35 years old group(n=292)and over 35 years old group(n=72); male group(n=147), and female group(n=217). Results Of all 364 cases, 191(52.47%)presented chromosomal abnormalities, including 177 cases of abnormal chromosome number, 11 cases of microdeletion/microduplication, 3 cases of whole chromosome uniparental disomy(pathology revealed hydatidiform moles, paternal). In the gestational 6-12 weeks group, there were 55.33% cases with abnormal chromosome number, 37.00% with trisomy, 8.33% with monosomy, and 6.00% with triploid. In the gestational 13-28 weeks group, there were 17.19% cases with abnormal chromosome number, 9.38% with trisomy, 3.13% with monosomy, and 0% with triploid. There were significant differences between the two groups(P<0.001; P<0.001; P=0.030; P=0.004). In the over 35 years old group, there were 63.88% cases with abnormal chromosome number, and 51.39% with trisomy. In the under 35 years old group, there were 44.86% with abnormal chromosome number, and 27.40% with trisomy. The abnormal rate was significantly higher in the over 35 years group(P=0.048; P=0.005). However, there was no significant difference in the number of chromosome aberration between male and female abortion tissue(P=0.562). Conclusion The rate of chromosomal abnormality is higher in early pregnancy and women with advanced age. Chromosomal abnormality is the main cause of spontaneous abortion. The application of SNP array can detect uniparental diploid that cannot be detected by other methods.
    Three cases of sporadic late-onset nemaline myopathy with monoclonal gammopathy and literature review
    DONG Wenhao, ZHAO Bing, LI Zhao, ZHANG Chen, YUAN Chenglu
    Journal of Shandong University (Health Sciences). 2022, 60(10):  74-81.  doi:10.6040/j.issn.1671-7554.0.2022.0084
    Abstract ( 1033 )   PDF (3601KB) ( 201 )   Save
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    Objective Three patients suspected of sporadic late-onset nemaline myopathy with monoclonal gammopathy were diagnosed by muscle pathological examination and monoclonal protein screening, so as to improve the understanding of this rare disease and explore its diagnosis and treatment. Methods The characteristics of this disease were summarized and relevant literatures were reviewed. Results All of the 3 patients presented with progressively aggravated muscle weakness, which was diagnosed by muscle biopsy as sporadic late-onset nemaline myopathy with monoclonal gammopathy. Autologous hematopoietic stem cell transplantation was effective. Conclusion Sporadic late-onset nemaline myopathy is a rare, subacute progressive myopathy characterized by proximal muscle weakness and atrophy, often complicated with monoclonal gammopathy. Therapies directed at eradication of M protein are effective.
    Cerebral infarction and brain metastasis caused by left atrial myxoma: a case report and literature review
    LIU Zhirui, GUO Wenqiang, HUANG Dezhang, WANG Zhigang
    Journal of Shandong University (Health Sciences). 2022, 60(10):  82-86.  doi:10.6040/j.issn.1671-7554.0.2022.0402
    Abstract ( 791 )   PDF (13685KB) ( 158 )   Save
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    Objective To investigate the clinical manifestations, imaging features and treatment methods of a patient with cerebral infarction and brain metastasis caused by left atrial myxoma. Methods The clinical data of the patient were retrospectively analyzed, and relevant literature was reviewed. Results The patient was a 69-year-old male. Six months before admission, due to acute cerebral infarction, he underwent relevant examinations and left atrial lesion was detected; postoperative pathology after surgery showed left atrial myxoma. Three months before admission, multiple intracranial space-occupying lesions were detected. After admission, relevant examinations were conducted and surgery was performed. Postoperative pathology showed metastasis of atrial myxoma. Conclusion Atrial myxoma can cause multiple acute cerebral infarction and brain metastasis. Cardiac ultrasound is necessary for patients with multiple acute cerebral infarction. Brain metastasis is usually found at the same time or a few months after the diagnosis of cardiac myxoma. Therefore, long-term follow-up is necessary for patients with atrial myxoma.
    Reliability and validity test of the Chinese Body Understanding Measure for Pregnancy Scale
    ZHANG Xuan, WU Liuliu, HAN Jing, CHEN Qingyi, MAO Fangxiang, WANG Juan, SUN Jiwei, ZHANG Guoxiang, CAO Danfeng, CAO Fenglin
    Journal of Shandong University (Health Sciences). 2022, 60(10):  87-91.  doi:10.6040/j.issn.1671-7554.0.2021.1506
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    Objective To sinicize the Body Understanding Measure for Pregnancy Scale(BUMPs)and test its reliability and validity. Methods The English version of BUMPs was translated into Chinese, translated back and culturally adjusted according to the Brislin translation-back translation mode to formulate the Chinese version of BUMPs, which was used to survey 946 pregnant women during May 2020 and April 2021. Results The Chinese version of BUMPs included 3 dimensions of body dissatisfaction, fear of overweight and body load, with a total of 14 items. The results of exploratory factor analysis showed that the cumulative variance contribution rate of the three common factors was 58.89%. The confirmatory factor also supported the three-factor theoretical constructs. The Cronbachs α coefficient of total scale was 0.841. The test-retest reliability coefficient was 0.605. Conclusion The Chinese version of BUMPs has good reliability and validity, which can be used to evaluate the feelings of pregnant women on their body image.
    Study on the individualized efficacy for non-small cell lung cancer patients based on Bayesian Additive Regression Tree model
    DING Zichen, WANG Haohua, ZHOU Liwen, CONG Huiwen, LI Chengsheng, BAO Qihan, YANG Yi, WANG Lianyuan, WANG Suzhen, SHI Fuyan
    Journal of Shandong University (Health Sciences). 2022, 60(10):  92-98.  doi:10.6040/j.issn.1671-7554.0.2021.1507
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    Objective Bayesian Additive Regression Tree(BART)model was applied to personalize efficacy of surgery-only and surgical adjuvant chemotherapy regimens for patients with non-small cell lung cancer(NSCLC), and to identify high yield subgroups. Methods The data of all NSCLC patients from 2012 to 2013 were extracted from the SEER database. With the overall survival time no less than 5 years as the outcome, the treatment regimens were compared. The propensity scores matching method was used to equalize the covariates between the two groups, the BART model was applied to calculate the individual treatment effect(ITE), and subgroup analysis was performed by decision tree model. Results The area under the curve(AUC)of the BART model was larger than 0.8, indicating that the results had high confidence. Most patients had better efficacy with surgical adjuvant chemotherapy regimen. Important subgroup taxonomic features in clinical practice such as AJCC stage, location of primary foci and degree of tumor metastasis were obtained and the subgroup with the best efficacy was derived. Among these subgroups, compared to surgery-only options, surgical adjuvant chemotherapy regimens produced better outcomes in female patients with distant metastasis and primary site in the middle lobe of the lung. Conclusion The constructed BART model can effectively evaluate personalized efficacy of the two treatment regimens for NSCLC patients and provide a basis for personalized medical practice for similar diseases in the future.
    Genes associated with cervical cancer by integrated bioinformatics analysis
    XIU Dejian, GAO Zhengwen, SONG Tingting, CUI Nan, CUI Jing, SUN Jianping
    Journal of Shandong University (Health Sciences). 2022, 60(10):  99-109.  doi:10.6040/j.issn.1671-7554.0.2022.0265
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    Objective To identify the key genes associated with cervical cancer in TCGA and GEO databases, and to explore the molecular mechanism and clinical values. Methods Gene expression profiles of cervical cancer were obtained from TCGA and GEO databases. The differentially expressed genes(DEGs)of cervical cancer were screened with weighted gene co-expression network analysis(WGCNA). Enrich analysis and protein-protein interaction(PPI)network were performed and hub genes were identified. The associations between hub genes and prognosis, and immune cell infiltration were analyzed. Results A total of 88 DEGs were screened out. GO analysis showed that most DEGs were enriched in nuclear chromosome segregation, meiotic nuclear division, condensed chromosome and nuclear chromosome. KEGG pathway analysis showed that those DEGs were enriched in cell cycle, DNA replication, oocyte meiosis, p53 signaling pathway and homologous recombination. A total of 20 hub genes were identified. The lower expression of mitotic arrest deficient 2 like 1(MAD2L1)was associated with longer overall survival(OS)(P=0.013). The lower expression of MAD2L1 was not associated with disease-free survival(DFS)(P>0.05). The protein level of MAD2L1 was up-regulated in cervical cancer. TIMER analysis showed that the level of MAD2L1 was significantly associated with tumor-infiltrating immune cells(P<0.05). Conclusion The candidate gene MAD2L1 associated with cervical cancer was identified, which was associated with the prognosis and immune cell infiltration of patients with cervical cancer, and may become a new target for prognosis and treatment of cervical cancer.