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    10 November 2019
    Volume 57 Issue 11
    Comparison of DNA methylation levels between three-dimensional and two-dimensional cultured umbilical cord mesenchymal stem cells
    HUANG Jinxian, LI Dong, LI Cong, SHI Qing, JU Xiuli
    Journal of Shandong University (Health Sciences). 2019, 57(11):  1-8.  doi:10.6040/j.issn.1671-7554.0.2019.813
    Abstract ( 604 )   PDF (5809KB) ( 227 )   Save
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    Objective To explore the effects of three-dimensional(3D)culture on the whole genome DNA methylation profile of umbilical cord mesenchymal stem cells(UC-MSCs). Methods UC-MSCs were isolated from umbilical cords using tissue adherent culture. Their phenotypes were identified with flow cytometry. Then UC-MSCs were cultured in 3D polyvinyl fluoride nested scaffolds and 2D conventional culture flask, respectively. Acridine orange was used to observe UC-MSCs on the scaffold. Methylated DNA immunoprecipitation(MeDIP-Seq)method was used to detect the whole genome DNA methylation of UC-MSCs. Results UC-MSCs were successfully isolated from umbilical cords and able to grow on the 3D scaffold. The genomic DNA methylation level of UC-MSCs increased after 3D culture. Gene ontology analysis showed that the up-regulated differential methylation genes were involved in protein metabolism, membrane-related organelle composition, and enzyme activity regulation. Down-regulated differential methylation genes were involved in vesicle trafficking and cGMP metabolic processes regulating. According to pathway analyses, differential methylation genes were involved in RNA transport, neuroactive ligand-receptor interaction, cellular communication, and 山 东 大 学 学 报 (医 学 版)57卷11期 -黄金献,等.三维和二维培养的脐带间充质干细胞DNA甲基化水平比较 \=-vesicle secretion-related pathways. Conclusion 3D culture changes the DNA methylation profile of UC-MSCs. The up-regulated methylation levels will alter the function of cell migration and proliferation. 3D culture reduces the methylation level of immune regulation and secretion of vesicle-related genes in UC-MSCs.
    Risk factors of slow or no coronary flow in 182 patients with acute ST-segment elevation myocardial infarction 30 days after operation
    ZHANG Wei, ZHAO Hongyan, DU Fengli, SU Guoying
    Journal of Shandong University (Health Sciences). 2019, 57(11):  9-15.  doi:10.6040/j.issn.1671-7554.0.2019.358
    Abstract ( 611 )   PDF (1065KB) ( 18 )   Save
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    Objective To study the risk factors of slow coronary flow/ no coronary flow(SCF/NCF)after the emergency percutaneous coronary intervention(PCI)in the patients with acute ST-segment elevation myocardial infarction 山 东 大 学 学 报 (医 学 版)57卷11期 -张伟,等.182例急性ST段抬高型心肌梗死患者术后30 d冠脉慢血流/无复流危险因素分析 \=-(STEMI), and to explore the influences of SCF/NCF on the patients 30 days after the emergency PCI. Methods A total of 334 patients with STEMI and emergency PCI were analyzed retrospectively. They were divided into the SCF/NCF group(n=182)and control group(the patients with normal coronary flow after PCI,n=152). The multivariate Logistic regression analysis was used to study the risk factors correlated with SCF/NCF after emergency PCI. The follow-up was made to explore the incidence of major adverse cardiac events(MACE), myocardial re-infarction, cardiac death, all-cause death and instent thrombosis between the two groups 30 days after PCI. Results (1) The factors with statistical differences between the two groups showed that the elevation of serum creatinine(P=0.034, OR=1.009, 95%CI: 1.001-1.017), high TIMI frame counts after pre-dilation(P=0.025, OR=1.038, 95%CI: 1.005-1.072), the high maximum stent release pressure(P=0.006, OR=1.525, 95%CI: 1.130-2.060), the high thrombus score(P=0.030, OR=1.324, 95%CI: 1.028-1.705)were the risk factors of SCF/NCF phenomenon. Non-right coronary artery as the target vessel(P<0.001, OR=0.071, 95%CI: 0.025-0.200), the high maximum pre-dilation pressure(P=0.033, OR=0.864, 95%CI: 0.755-0.989), the usage of sodium nitroprusside(P=0.006, OR=0.126, 95%CI: 0.029-0.548)and IIb/IIIa receptor antagonist(P=0.043, OR=0.438, 95%CI: 0.197-0.974)during the procedure were the protection factors of the SCF/NCF phenomenon. Among these protection factors, non-right coronary artery as the target vessel and the usage of sodium nitroprusside were dominant. (2) After 30 days of the follow-up, there were no significant differences in the incidence of MACE(14 vs 8 cases, χ2=0.753, P=0.385), cardiac death(12 vs 8 cases, χ2=0.243, P=0.622), all-cause death(12 vs 8 cases, χ2=0.243,P=0.622)and in-stent thrombosis(2 vs 0 cases, χ2=1.675, P=0.196)between the two groups. Compared with the control group, the incidence of myocardial re-infarction in SCF/NCF group was higher(6 vs 0 cases, χ2=5.087, P=0.024). (3) The causes of death were cardiac shock, in-stent thrombosis, cardiac rupture and acute heart failure. Cardiac shock is the first cause of death which accounts for 70%. Conclusion The elevation of serum creatinine, high TIMI frame count after pre-dilation, the high maximum stent release pressure and the high thrombus score are positivly correlated to the SCF/NCF phenomenon. Non-right coronary artery as the target vessel, the high maximum pre-dilation pressure, the usage of sodium nitroprusside and IIb/IIIa receptor antagonist during the procedure are negativly correlated to the SCF/NCF phenomenon. The incidence of myocardial re-infarction in the SCF/NCF group was higher than that in the control group.
    Microsurgical resection of giant para-sagittal meningioma in the functional area in the elderly
    TIAN Hailong, WEI Zhaosheng, LIU Bin, GUO Wenqiang, ZHANG Hongying, WANG Chaochao, WANG Zhigang
    Journal of Shandong University (Health Sciences). 2019, 57(11):  16-19.  doi:10.6040/j.issn.1671-7554.0.2019.500
    Abstract ( 449 )   PDF (3620KB) ( 4 )   Save
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    Objective To investigate the clinical efficacy of microsurgery in the resection of giant para-sagittal meningioma in the elderly. Methods The clinical data of 32 elderly patients with giant meningioma(diameter >5 cm)involving the cortex of the functional area treated with microsurgery in our hospital during Jan. 2014 and Aug. 2018 were retrospectively analyzed. The patients aged >60 years(mean 63.4±2.5 years, maximum 78 years). The clinical outcomes and surgical skills were summarized. Results Hypertension was detected in 11 cases, coronary heart disease in 5 cases, diabetes mellitus in 8 cases, intracranial vascular stenosis in 4 cases, syringomyelia in 2 cases, and 2 cases had no complications. Motor/sensory evoked potentials were monitored throughout the operation. Simpson I resection was performed in 11 cases, Simpson II resection in 9 cases(2 cases were recurrent meningioma), Simpson III resections in 9 cases(3 cases were recurrent meningioma), and Simpson IV resection in 3 cases(2 cases were recurrent meningioma). Patients with WHO II tumor, WHO III tumor, residual tumor, or meningioma with active proliferative tumor cells received radiotherapy after operation. During the follow-up of 4-43 months, 1 case had relapse in month 11 and recov- 山 东 大 学 学 报 (医 学 版)57卷11期 -田海龙,等.老年功能区矢状窦旁巨大脑膜瘤的显微手术治疗 \=-ered after a second operation and adjuvant radiotherapy. In no-death cases during operation, 14 manifested with hemiplegia and hemidysesthesia, in which 12 recovered; 3 cases developed hemiplegia, 1 of which was complicated with pneumonia, and recovered after 7-21 days; 8 patients with epilepsy took antiepileptic drugs and no seizure recurred. Conclusion In the microsurgical excision of giant para-sagittal meningioma in elderly patients, the protection of cortex and drainage veins in functional area is very important. As the complications affect clinical outcomes, due attention should be paid to the perioperative comorbidities and complications.
    Clinical effect of gefitinib combined with chemotherapy on patients with advanced non-small cell lung cancer
    WANG Jianli, WANG Xiaojing, SUN Yulian, HU Xiaole, LUAN Xiaorong
    Journal of Shandong University (Health Sciences). 2019, 57(11):  20-26.  doi:10.6040/j.issn.1671-7554.0.2018.1470
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    Objective To observe the efficacy of gefeitinib combined with chemotherapy on the advanced non-small cell lung cancer(NSCLC)patients, and to compare the changes of serum carcinoembryonic antigen(CEA), neuron-specific enolase(NSE), squamous cell cancer-related antigen(SCC)and disease control rate before and after treatment. Methods A total of 100 lung adenocarcinoma patients with epidermal growth factor receptor(EGFR)mutation-positive were divided into observation group(n=50)and control group(n=50)according to different treatment regimens. The observation group was treated with pemetrexed + carboplatin combined with gefeitinib, and the control group was treated with pemetrexed + carboplatin for 4 cycles to evaluate the clinical efficacy and the changes of CEA, NSE and SCC in the serum of patients, as well as to compare the difference in progression-free survival(PFS)between the two groups. Results Compared with the control group, the objective effective rate(60.0% vs 36.0%, χ2=5.769, P=0.027)and disease control rate(86.0% vs 66.0%, χ2=5.482, P=0.034)were higher. After treatment, the levels of CEA and NSE in serum decreased compared with those before treatment in both groups(t=-10.370, P<0.001; t=-4.802, 山 东 大 学 学 报 (医 学 版)57卷11期 -王建丽,等.吉非替尼联合化疗治疗50例晚期非小细胞肺癌患者的疗效 \=-P<0.001). The median PFS in the observation group was longer than that in the control group(10.9 months vs 7.9 months, χ2=45.183, P<0.001). The COX multivariate analysis showed that smoking history, ECOG score and case grouping had statistical significance on PFS. The median PFS of patients without smoking history was longer than those with smoking history(HR=1.929, 95%CI: 1.126-3.306, P=0.017); the median PFS of patients with ECOG scores being 0-1 was longer than those with ECOG scores≥2(HR=2.059, 95%CI: 1.267-3.348, P=0.004); the median PFS of patients in the observation group(HR=0.195, 95%CI)is longer than those in the control group(HR=0.195, 95%CI:0.118-0.320,P=0.001). The incidence of adverse reactions in the observation group was higher than those in the control group without the statistical difference(46.0% vs 36.0%, χ2=1.033, P=0.309). Conclusion Gefitinib combined with chemotherapy is effective in the treatment of advanced NSCLC patients with better disease control rate, decreased serum CEA and NSE levels and prolonged PFS of patients. The method is safe and has fewer adverse reactions, worthy of promoting clinically.
    A Meta-analysis of the efficacy and safety of clarithromycin in adjuvant treatment of asthma
    WANG Haixia, LI Yizhang, BAI Chenxiao, JIANG Di, WANG Liwen, CHEN Ou
    Journal of Shandong University (Health Sciences). 2019, 57(11):  27-33.  doi:10.6040/j.issn.1671-7554.0.2019.484
    Abstract ( 676 )   PDF (7083KB) ( 24 )   Save
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    Objective To systematically evaluate the efficacy and safety of clarithromycin in the adjuvant treatment of asthma. Methods Randomized controlled trials(RCTs)on the efficacy and safety of clarithromycin in treating asthma were searched in CNKI, Wanfang, VIP, China Biomedical Literature Database, Pubmed, Cochrane Library, EMbase and Web of Science from the establishment of databases to March 31, 2019. The quality of the literature was evaluated with Cochrane bias risk assessment tool. The subjects were divided into clarithromycin group and control group. The outcome indicators were forced expiratory volume in one second(FEV1%), forced vital capacity(FEV1/FVC), FEV1(L), peak expiratory flow rate(PEFR)(L/min), asthma control questionnaire(ACQ)score and asthma control test(ACT)score. Meta-analysis was performed using RevMan 5.5 software. Results Altogether 11 RCTs were enrolled, including 4 in English and 7 in Chinese. Meta results showed: (1) There was no significant difference in FEV1% and FEV1(L)between the clarithromycin group and control group(P>0.05), while there was significant difference in FEV1/FVC and PEFR(L/min)(P<0.05). (2) There was significant difference in ACQ score between the two groups 山 东 大 学 学 报 (医 学 版)57卷11期 -王海霞,等.克拉霉素辅助治疗哮喘疗效及安全性的Meta分析 \=-(P<0.05). (3) There was no significant difference in ACT score between the two groups(P>0.05). (4) Only 2 RCTs reported adverse reactions such as exacerbation of acute asthma, gastrointestinal reactions and respiratory infection. Conclusion Clarithromycin can improve the lung function [FEV1/FVC% and PEFR(L/min)] and asthma control(ACQ score). It also may cause some adverse reactions, such as exacerbation of acute asthma, gastrointestinal reactions and respiratory infection.
    Clinical application of the fully automatic chemiluminescence to detect interferon-γ test in diagnosis of tuberculosis
    LI Xiaofei, LIU Hongwei, ZI Min, LV Songqin, LUO Feng, QIU Wan, HUANG Shan
    Journal of Shandong University (Health Sciences). 2019, 57(11):  34-41.  doi:10.6040/j.issn.1671-7554.0.2019.1048
    Abstract ( 1096 )   PDF (2406KB) ( 142 )   Save
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    Objective To explore the clinical application value of the fully automatic chemiluminescence to detect interferon-γ test in diagnosis of tuberculosis. Methods To compare the diagnostic performance of the fully automatic chemiluminescence to detect interferon-γ test and T-cell spot of Tuberculosis(T-SPOT.TB)test in diagnosis of tuberculosis.The tuberculosis group(n>150), non-tuberculosis group easily confused with tuberculosis group(n>100), and healthy controls(n>150)were enrolled in the prospective and synchronous blind study. The diagnostic values of the two tests were compared with receiver operator characteristic(ROC)curve, and consistency of the results was evaluated with Kappa test. Results A total of 400 samples were collected, and 364 were valid, including 141 in tuberculosis group, 43 in non-tuberculosis group, and 180 healthy controls. The area under ROC curve(AUC)of the fully automatic chemiluminescence to detect interferon-γ test was 0.897, AUC of T-SPOT.TB test [early secreted antigenic target-6(ESAT-6)hole and culture filtrate protein-10(CFP-10)hole] was 0.884 and 0.879, respectively, and Kappa value was about 0.75. Conclusion The results of the fully automatic chemiluminescence to detect interferon-γ test and T-SPOT.TB test are consistent in diagnosis of tuberculosis. As the fully automatic chemiluminescence to detect interferon-γ test is automatically operated, it will have better clinical application value.
    Bladder neck suspension with pyramidalis in the management of pediatric urinary incontinence
    MA Nan, WANG Ruoyi, LIU Qian, LUO Juan, LI Jinliang, CHEN Weixiu
    Journal of Shandong University (Health Sciences). 2019, 57(11):  42-46.  doi:10.6040/j.issn.1671-7554.0.2019.759
    Abstract ( 850 )   PDF (4127KB) ( 8 )   Save
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    Objective To evaluate the clinical efficacy of bladder neck suspension with pyramidalis in the treatment of urinary incontinence in children with sphincteric incompetence. Methods Clinical data of 29 children with urinary incontinence who underwent bladder neck suspension with pyramidalis during 2004 and 2018 were retrospectively analyzed. All patients received urodynamic examinations and voiding cystourethrography(VCUG), and filled in ICI-Q-SF scale before and after operation. The differences in the indexes were analyzed with paired samples t test and Wilcoxon rank sum test. Results VCUG showed the bladder necks were raised in all patients and the funnel-shaped openings were corrected. The functional urethral length and maximum urethral closure pressure increased by 1.04 cm(P<0.001)and 11.69 cmH2O(P=0.001), respectively, while the maximum urethral pressure had no improvement after surgery(P>0.05). The ICI-Q-SF score showed that incontinence was significantly improved(P<0.05), 11 patients(37.93%)gained good control with adjuvant clean intermittent catheterization(CIC)and oral anticholinergic drugs, and the other 18 patients showed CIC problems. Complications were observed in 7 patients(24.14%), and 2 patients(6.90%)complications were caused by bladder neck suspension. Conclusion Bladder neck suspension with pyramidalis is effective to treat children with sphincteric incompetence if standardized CIC and anticholinergic medication are provided.
    An analysis of the imaging information of 85 patients with recurrent varicose veins in lower extremity
    WU Mengtao, GUO Yanan, TANG Dianjun, WANG Suzhen, ZHOU Tao, LI Fandong
    Journal of Shandong University (Health Sciences). 2019, 57(11):  47-51.  doi:10.6040/j.issn.1671-7554.0.2019.542
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    Objective To investigate the risk factors of recurrent varicose veins in lower extremity. Methods The hemodynamic data of 85 patients(85 limbs)with recurrent varicose veins in lower extremity treated during June 2013 and June 2018 were retrospectively analyzed. The color Doppler ultrasound and CT imaging results were analyzed to investigate the causes of recurrence. The classification in clinical, etiological, anatomical, pathophysiological classification(CEAP)was used as the dependent variable. The relationship between the dependent variable and causes of recurrence was analyzed with ordinal logistic regression, and the risk factors of recurrence were explored. Results In 85 patients, 37.6% had residual or recanalization of the great saphenous vein and its branches, 30.6% had venous stenosis or obstruction, 23.5% had penetrating venous insufficiency, and 8.2% had small saphenous vein insufficiency. Logistic regression analysis showed that penetrating venous insufficiency(OR=10.465, 95%CI: 2.980-36.782, P<0.001), deep 山 东 大 学 学 报 (医 学 版)57卷11期 -吴梦涛,等.85例复发性下肢静脉曲张影像学检查相关分析 \=-venous system stenosis(OR=9.554, 95%CI: 2.933-31.094, P<0.001), recurrence time(OR=1.684, 95%CI: 1.335-2.123, P<0.001)and age(OR=0.930, 95%CI: 0.877-0.985, P=0.014)had statistically significant effects on the CEAP classification of recurrent varices, while gender(OR=1.068, 95%CI: 0.439-2.596, P=0.885)and residual great saphenous vein(OR=0.758, 95%CI: 0.239-2.406, P=0.638)had no significant effects. Conclusion Perforating venous insufficiency, deep venous stenosis and recurrence time are independent risk factors while age is a protective factor for recurrent lower extremity varices.
    Robot-assisted minimally invasive treatment of pelvic ring injuries: a clinical analysis of 108 cases
    LIU Huashui, DUAN Shengjun, ZHAO Guohui, ZHANG Zhen, ZHU Liming, WANG Xueguang, JIA Fengshuang, LIU Shidong, LIU Mincen, LI Ming, CHEN Hua
    Journal of Shandong University (Health Sciences). 2019, 57(11):  52-59.  doi:10.6040/j.issn.1671-7554.0.2019.252
    Abstract ( 703 )   PDF (12589KB) ( 23 )   Save
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    Objective To explore the surgical strategies, techniques and precautions of robot-assisted minimally invasive surgery for pelvic ring injuries. Methods The clinical data of 108 cases of pelvic ring injuries treated with robot-assisted minimally invasive surgery were reviewed. There were 71 male and 37 female, average age was 41.6 years(range, 21-79 years), including 6 cases of isolated anterior pelvic ring injuries and 102 cases of combined anterior and posterior pelvic ring injuries. The surgical plans were formulated based on the type and degree of injuries, effectiveness of the reduction, and integrity of the osseous channel. The surgical complications and efficacy were recorded. Results Percutaneous cannulated screw fixation of the pubic ramus was performed in 6 patients with isolated anterior pelvic ring injuries. Percutaneous cannulated sacroiliac screw fixation and open screw or plate fixation of the symphysis pubis was performed in 7 patients with posterior pelvic ring injuries combined with symphysis pubis separation. Percutaneous cannulated 山 东 大 学 学 报 (医 学 版)57卷11期 -刘华水,等.骨科手术机器人辅助微创治疗骨盆环损伤108例临床分析 \=-sacroiliac screw and pubic ramus screw fixation was performed in 40 patients with posterior pelvic ring injury combined with unilateral anterior pelvic ring injury. For the 55 patients with posterior pelvic ring injury combined with bilateral anterior pelvic ring injury, cannulated screw fixation alone was performed in 14 cases, INFIX fixation in 24 cases, and “hybrid surgery” in 17 cases. A total of 344 screws were inserted with robotic assistance, of which 326 were successfully inserted to a satisfactory position on the first attempt. The average operation time was 106 minutes. Fluoroscopies were performed with an average of 29.2 times, and it took 6.1 s to place one screw. There were 18 unsatisfactory guiding needle placements during the surgeries, 6 of which remained in the bone tunnel and were not re-planned, 7 cut out, 4 penetrated the cortex and were re-planned to satisfactory position, 1 penetrated the pubic cortex, causing hemorrhage of the “crown of death” and was changed to “hybrid surgery”. During the follow-up of 4.2 months, 2 fixation failures were observed, and the average Majeed score was 89.4 points. Conclusion Robot-assisted surgery provides a novel modality for the minimally invasive treatment of pelvic ring injuries when the surgical strategy is properly formulated and surgeons have good techniques.
    Talar neck approach for debridement and bone grafting to treat talar cyst
    XU Wenpeng, HU Yong, LI Zhengxun, ZHANG Ning, CHENG Ruilin, HUANG Zheng
    Journal of Shandong University (Health Sciences). 2019, 57(11):  60-64.  doi:10.6040/j.issn.1671-7554.0.2019.659
    Abstract ( 941 )   PDF (6811KB) ( 88 )   Save
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    Objective To explore the application and efficacy of talar neck approach for debridement and bone grafting in the treatment of talar cyst. Methods Clinical data of 9 cases of talar cysts treated during Jul. 2014 and Dec. 2017 were retrospectively analyzed, including 7 males and 2 females, aged 11~47 years, average 30.6 years. The lesions involved 5 left feet and 4 right feet. X ray, CT and MRI were performed before operation to evaluate the size of cysts and articular surfaces involved. During operation, all lesions were debrided with talar neck approach, and bone defects were repaired with autologous cancellous bones harvested from iliac crests. After operation, the functions of ankles were evaluated with AOFAS score. Results All 9 cases were followed up for 8-20 months, average 12.4 months. All bone defects were repaired, and ankle pain was significantly alleviated. The AOFAS score rose from 70.2(60-82)to 92(85-100). The ankles could function normally. No infection, recurrence or complication were observed. Conclusion Talar neck approach for debridement and bone grafting is effective to treat talar cyst. This non-traumatic way does not damage the articular cartilage or adjacent ligament tissues, does not affect blood supply of the talus, and can shorten the hospitalization time.
    Risk factors of early childhood caries in 3-5 years old children in Jinan, Shandong
    QIN Xiurong, SHAO Linqin, ZHANG Lixia, MA Long, XIONG Shijiang
    Journal of Shandong University (Health Sciences). 2019, 57(11):  65-70.  doi:10.6040/j.issn.1671-7554.0.2019.397
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    Objective To compare the risk factors of early childhood caries(ECC)and non-caries among children aged 3 to 5 years in Jinan. Methods A total of 606 children aged 3~5 years [293 males, 313 females, mean age:(4.210±0.816)years] were included in the study. A questionnaire was designed to collect social demographics, feeding habits and oral hygiene behaviors. Primary caries was examined and recorded by decayed, missing, filled teeth(dmft)index. The subjects were divided into two groups as caries-risk group(dmft>0,n=360)and caries-free group(dmft=0,n=246). Multiple logistic regression analysis was used to explore the factors related to dental caries. Results Multiple logistic regression analysis showed that the incidence of dental caries was significantly associated with long-duration breastfeeding(OR=2.454, 95%CI: 1.422-4.233, P=0.001), high frequency of bedtime dessert intake(OR=5.721, 95%CI:1.253-26.131, P=0.024), and high frequency of sweet snack intake(OR=2.057, 95%CI: 0.966-4.880, P=0.062). Conclusions Long-duration breastfeeding, high frequency sweets consumption and eating sweets before sleep- 山 东 大 学 学 报 (医 学 版)57卷11期 -秦秀荣,等.济南市3~5岁低龄儿童龋相关危险因素分析 \=-ing are important susceptibility factors of early childhood caries. While promoting long-duration breastfeeding, we should balance the harm of dental caries in children and control the time and frequency of sweet food intake in order to reduce the risk of dental caries in children.
    Isolation, culture and identification of labial stem cells from patients with dry mouth caused by maxillofacial radiotherapy
    SHEN Beiyong, WANG Xiaofei, LI Junxin, ZHOU Qi
    Journal of Shandong University (Health Sciences). 2019, 57(11):  71-77.  doi:10.6040/j.issn.1671-7554.0.2019.345
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    Objective To explore the proliferative characteristics and multi-directional differentiation potential of mesenchymal stem cells(MSCs)derived from labial glands in patients with dry mouth caused by maxillofacial radiotherapy. Methods Labial glands from the lower lip obtained during biopsy from 5 patients with dry mouth were excised under sterile conditions. MSCs were isolated and cultured using tissue adherent method. The cell proliferation curve was detected with CCK-8. Expressions of MSCs-related markers were examined in isolated cells with flow cytometry. After osteogenic differentiation, the proliferation medium group and osteogenic medium group were used as the control and osteogenic induction group, respectively. The osteogenic differentiation potential was assessed with alkaline phosphatase(ALP)staining and alizarin red staining. The mRNA expression of osteogenic-related genes was determined with real time-PCR. After adipogenic differentiation, the proliferation medium group and adipogenic medium group served as the control and adipogenic induction group, respectively. Then the adipogenic potential was observed with oil red-O staining, and the mRNA 山 东 大 学 学 报 (医 学 版)57卷11期 -沈倍勇,等.颌面部放疗致口干5例患者唇腺干细胞的分离培养与多向分化潜能鉴定 \=-expression of adipogenic-related genes were detected with real time PCR. Results MSCs were successfully obtained. CCK8 assay showed the growth curve of MSCs presented an “S” shape, which was similar to other stem cells. The surface markers of CD29, CD44, CD73, CD90 and CD105 were positively expressed, while CD34, CD45 and CD106 were negatively expressed. After 7 days of osteogenic induction, ALP staining and alizarin red staining showed strong expression of ALP and mineralized nodules in the osteogenic stem cells compared with the control group. Real time PCR results showed the expression of osteogenic-related genes in the osteogenic induction group and control group were statistically significant. After 21 days of adipogenic induction, the results of oil red-O staining showed that lipid droplets of different sizes could be seen in stem cells of osteogenic induction group. There was significant difference in the expression of adipogenic-related genes between the adipogenic induction group and control group. Conclusion MSCs can be isolated from labial glands in patients with dry mouth caused by maxillofacial radiotherapy. The MSCs have the potential for proliferation and multi-directional differentiation. The labial stem cells can be used as seed cells for salivary gland function reconstruction.
    A case report and literature review of complex heterozygous SYNE1 mutation with autosomal recessive cerebellar ataxia type1
    HU Liping, WANG Le, JIN Liang, LIU Yanxia, CUI Dongqing, CAO Lili
    Journal of Shandong University (Health Sciences). 2019, 57(11):  78-82.  doi:10.6040/j.issn.1671-7554.0.2019.482
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    Objective To search for the disease-causing gene in a family with autosomal recessive cerebellar ataxia type 1(ARCA1). Methods The young female with chronic progressive ARCA received clinical examination, neuroimaging, target region capture and high-throughput sequencing. Results Target region capture sequencing yielded compound heterozygous mutations in exon 67 at codon 10 887(c.10887dupT)and exon 41 at codon 5 995(c.5995A>2T, p. K1999X)of the SYNE1 gene. The results of Sanger sequencing were identified in the patients parents. Conclusion Two novel compound heterozygous mutations in SYNE1 are identified and an ARCA1 family with novel SYNE1 gene mutation is reported for the first time in China.
    Effects of cumulative childhood adversity on depressive symptoms among nurses
    WANG Ying, YANG Bei, WANG Juan, LI Yanyan, CAO Fenglin
    Journal of Shandong University (Health Sciences). 2019, 57(11):  83-89.  doi:10.6040/j.issn.1671-7554.0.2019.566
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    Objective To explore the relationship between cumulative childhood adversity and emerging depressive symptoms among nurses. Methods A nested case-control study was conducted among subjected with PHQ-9≥10. A total of 74 subjects who had depressive symptoms were selected as the case group, and 518 subjects were included in the control group. Data were collected using PHQ-9, ACEQ-R and Nurse Job Stressors Inventory. The relationship between cumulative childhood adversity and emerging depressive symptoms was assessed with multivariate Logistic regression analysis. The mediation of work stress was analyzed with Spearman rank correlation and causal steps. Results The PAR% of cumulative childhood adversity was 8.0%. After nurses work stress and family burden were adjusted, the risk of imaging depressive symptoms for those with cumulative childhood adversity was 2.60 times of those without childhood adversity(OR=2.60, 95%CI:1.12-6.01). Work stress could partially mediate cumulative childhood adversity and emerging depression symptoms. Conclusion It is noteworthy that cumulative childhood adversity increases the risk of emerging depressive symptoms in nurses. Measures should be taken to reduce exposure to childhood adversity.
    Changes of enterovirus spectrum and epidemiological characteristics of hand, foot and mouth disease in Jinan, China, 2012-2017
    GUAN Hengyun, WANG Chunrong, LIU Lanzheng, YANG Guoliang, ZHAO Huailong, SUN Jie, CHENG Hongqi
    Journal of Shandong University (Health Sciences). 2019, 57(11):  90-97.  doi:10.6040/j.issn.1671-7554.0.2019.558
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    Objective To clarify the composition and changes of enterovirus spectrum in hand, foot and mouth disease in Jinan, China, from Jan. 2012 to Dec. 2017, further to analyze the epidemiological characteristics of different types of enterovirus. Methods A total of 4 929 specimens were collected from clinically diagnosed hand, foot and mouth disease cases in Jinan from 2012 to 2017. All specimens were detected for Enterovirus A71(EV-A71), Coxsackievirus(CV)-A16, CV-A6 and CV-A10 by real-time reverse transcription-polymerase chain reaction(RT-PCR). For unclassified specimens, reverse transcription nested PCR based on the 5'-untranslated region(5'-UTR)sequence was performed and the types of enterovirus were determined by nucleotide sequencing. Results A total of 27 types of enterovirus were identified in 4 929 specimens, including not only EV-A71, CV-A16, CV-A6 and CV-A10, but also CV-A2, 4, 5, 9, 12, 13, 21, 22, 24, CV-B1-5 and E3, 6, 7, 9, 11, 18, 24, 25, 30. The constituent ratios were different between 山 东 大 学 学 报 (医 学 版)57卷11期 -关恒云,等.济南市2012~2017年手足口病肠道病毒谱变化及流行特征 \=-mild and severe cases. The top four types of enterovirus for mile cases were CV-A16(29.03%), EV-A71(25.67%), CV-A6(17.58%)and CV-A10(3.10%), and for severe cases were EV-A71(77.64%), CV-A16(5.59%), CV-A6(1.86%)and CV-A10(1.24%). The cases with CV-A6 and CV-A10 infections were younger than EV-A71 and CV-A16 infections(F=3.659, P=0.003), and they were(3.02±2.43),(2.87±1.67),(3.29±2.34)and(3.36±2.18)years, respectively. The incidence peak of EV-A71 and CV-A16 appeared usually in the second or fourth quarter, CV-A6 mostly occurred from June to December, and CV-A10 from June to August. The positive detection rate of enteroviruses was higher in Pingyin county and Zhangqiu district(93.49% and 91.99%, respectively). Conclusion EV-A71, CV-A16, CV-A6 and CV-A10 were the dominant types of enteroviruses associated with hand, foot and mouth disease in Jinan, and 27 types of enteroviruses coexisted from 2012 to 2017. The epidemiological characteristics of non-EV-A71 and non-CV-A16 enterovirus should be monitored year-by-year. To clarify the changes of enterovirus spectrum clearly will help health authorities to early provide prevention and control measures for epidemics.
    Localization of basic inspection equipment in primary hospitals of Shandong Province
    GONG Kongzhen, SUN Xiaojie, DU Lutao, QIN Tingting, WANG Yahui, YIN linlin, WANG Chuanxin
    Journal of Shandong University (Health Sciences). 2019, 57(11):  98-102.  doi:10.6040/j.issn.1671-7554.0.2019.550
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    Objective To investigate the status quo of four basic medical inspection equipment in the Laboratory Departments of grass-root medical institutions in Shandong Province, and to provide reference for the promotion of domestic medical inspection equipment. Methods The allocation and utilization of four medical inspection equipment, including biochemical analyzer, blood cell analyzer, urine analyzer and chemiluminescence analyzer, in the Laboratory Departments of 48 district-level and county-level hospitals in Shandong Province, were surveyed with stratified random sampling method. The data were entered with EPIDATA 3.0 and analyzed with SPSS 19.0. Results There were differences in the localization rate of the four types of equipment among hospitals of different levels. The different places of origin had significant impact on the price of blood cell analyzer(P=0.047), urine analyzer(P=0.028)and chemilu- 山 东 大 学 学 报 (医 学 版)57卷11期 -巩孔臻,等.山东省基层医疗机构基本检验设备国产化现状 \=-minescence analyzer(P=0.004). The imported equipment had a greater rate of extended use than domestic equipment. The grass-root medical institutions had a certain demand for domestic inspection equipment. Conclusion Domestic inspection equipment is able to meet the demands of primary hospitals. Due governmental support should be given to the manufacturers. Grassroots hospitals need to be encouraged to purchase domestic equipment in order to improve its market share.
    A Mendelian randomization study on the causal relationship between waist circumference and incidence of coronary heart disease
    LIU Xinhui, LI Hongkai, LI Mingzhuo, YU Yuanyuan, SI Shucheng, HOU Lei, LIU Lu, LI Wenchao, YUAN Tonghui, LI Yunxia, ZHOU Yuchang, XUE Fuzhong
    Journal of Shandong University (Health Sciences). 2019, 57(11):  103-109.  doi:10.6040/j.issn.1671-7554.0.2019.322
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    Objective To explore the causality between waist circumference(WC)and incidence of coronary heart disease(CHD)using 2-sample mendelian randomization(2MR). Methods Mutually independent genetic variants which were closely related to WC were chosen as instrumental variable(IV)from Genome Wide Association Study(GWAS)databases. By using odds ratio(OR)as outcome indicator, the causal relationship between WC and CHD was analyzed using 2MR methods, including Wald ratio method, inverse-variance weighted(IVW)method, mendelian randomization-Egger(MR-Egger)regression and weight median method. Results WC dataset of 232 101 Europeans and CHD dataset of 86 995 Europeans were used. Totally 39 SNPs were selected as IV. Similar effect estimations were obtained using 2MR methods, of which IVW results showed that the OR between WC and CHD was 1.531(95%CI:1.248- 山 东 大 学 学 报 (医 学 版)57卷11期 -刘新辉,等.腰围和冠心病因果关系的孟德尔随机化研究 \=-1.877;P<0.001). Besides, results of MR-Egger regression indicated that genetic pleiotropy did not bias the effect estimation(slope=0.003, P=0.768). Conclusion This large study using 2MR, shows there is a causal relationship between WC and incidence of CHD, and the risk of CHD will increase by approximately 50% when WC increases one standard deviation(SD=12.5cm).