Table of Content

  

10 October 2017
Volume 55 Issue 10

A call for action to strengthen research on population interventions against Alzheimers disease and senile dementia

QIU Chengxuan, DU Yifeng

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  1-6.  doi:10.6040/j.issn.1671-7554.0.2017.317

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As the absolute number and the proportion of elderly people increase, Alzheimers disease(AD)or senile dementia poses tremendous economic and societal burden to the modern aging society, and has been considered a global public health priority. While there is currently no cure for dementia or AD, epidemiological studies have identified several modifiable factors including cardiovascular risk factors and related disorders and psychosocial factors for the occurrence, development and clinical expression of dementia and AD. Cardiovascular risk factors(e.g., smoking, hypertension, diabetes)can promote the clinical onset of dementia by causing cerebrovascular and neurodegenerative pathologies, whereas psychosocial factors(e.g., educational attainment, rich social network, mentally-stimulating activity)can help maintain late-life cognitive functioning by increasing cognitive reserve. Therefore, in theory, intervention methods targeting these modifiable factors may prevent or postpone the onset of dementia or AD. Recent large-scale intervention studies abroad preliminarily demonstrated that a multidomain intervention program that integrated vascular risk factor monitoring, healthy diet, physical exercise and cognitive training could help maintain cognitive functioning in at-risk elderly people. Our country should attach importance to population intervention studies in order to develop effective intervention programs against AD and dementia that are tailored to ethnic populations in China and thus provide the basis for making proper national strategies against dementia.

Diagnosis and treatment of Alzheimers disease

DU Yifeng, JING Ran

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  7-13.  doi:10.6040/j.issn.1671-7554.0.2017.319

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Alzheimers disease(AD)is a disabling and fatal neurodegenerative disease. AD prevalence is rapidly increasing as the trend of aging population aggravates, which brings about great burden to patients, families and the 山 东 大 学 学 报 (医 学 版)55卷10期 -杜怡峰,等.阿尔茨海默病的诊断与治疗 \=-society. The field of AD research is rapidly growing. Biomarkers and functional imaging are entering clinical practice. Drugs targeting Aβ, tau, insulin pathway and other pathways are under research. In the future, comprehensive therapy combing lifestyle prevention, pharmaceutical treatment and non-pharmacological interventions will bring unprecedented benefits to AD patients.

Evolution of diagnostic criteria for Alzheimers disease: from clinical diagnosis to pathophysiological diagnosis

TANG Yi

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  14-20.  doi:10.6040/j.issn.1671-7554.0.2017.320

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Alzheimers disease(AD)is the leading cause of dementia and the most prevalent neurodegenerative disease in the elderly. The first diagnostic criteria was developed by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimers Disease and Related Disorders Association Work Group in 1984. With the further understanding of pathophysiological mechanism underlying AD, two new sets of research criteria for Alzheimers 山 东 大 学 学 报 (医 学 版)55卷10期 -唐毅.阿尔茨海默病诊断标准:从临床诊断到病理生理诊断 \=-disease were proposed: those published by an International Working Group in 2007, which was updated in 2014, and the recommendations published by the National Institute on Aging and the Alzheimers Association(NIA-AA)in 2011. A comparison of the criteria is needed for clinical practice and research purpose.

Progress in the etiology and pathogenesis of Alzheimers disease

DU Heng, YUAN Xiaodong

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  21-27.  doi:10.6040/j.issn.1671-7554.0.2017.318

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Alzheimers disease(AD)is a neurodegenerative disease majorly attacking aging population. AD is the most common type of aging-related dementia, featured by irreversible cognitive impairments and loss of social function. The 山 东 大 学 学 报 (医 学 版)55卷10期 -杜蘅,等.阿尔茨海默病病因及发病机制研究进展 \=-etiology and pathogenesis of AD have not been fully elucidated yet, which significantly deters the development of strategies for AD prevention and treatment. Here, in summary of the up-to-date research progress, we reviewed the risk factors for AD as well as the mechanisms of the pathogenesis of this neurological disorder.

Effect of Bacillus subtilis gavage on the intestinal microbiota of mice

ZHAO Li, LI Lixiang, CHEN Feixue, ZUO Xiuli, LI Yanqing

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  28-35.  doi:10.6040/j.issn.1671-7554.0.2017.076

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Objective To investigate the effect of Bacillus subtilis B.subtilis gavage on the intestinal microbiota of mice. Methods Eighteen C57BL/6J female mice were randomly divided into three groups including control group(C group), two days intervention group(TW group)and ten days intervention group(TE group). C group was treated with normal saline each day from day 0 to day 9; TW group was treated with live B.subtilis each day from day 0 to day 1, then with normal saline at the same amount from day 2 to day 9; TE group was treated with live B.subtilis at the same amount each day from day 0 to day 9. All mice were given an unrestricted diet from day 0 to day 16.Feces were collected on day 0, day 8 and day 16 to extract DNA, then Illumina Miseq platform was used for high-throughput sequencing. Results After treated with live B.subtilis, the relative abundance of Bacillus genus microbes in TW group and TE group decreased, and in the TE group the difference was significantly different(P=0.039). The relative abundance of Firmicutes increased first then decreased in both TW group and TE group, while Bacteroidetes shows reverse trend. The relative abundance of Verrucomicrobia increased gradually, which in TW group showed significant difference on the sixteenth day and eighth day compared with that before gavage(P=0.001). The relative abundances of Verrucomicrobia in TW group, TE group and C group on the sixteenth day were significantly different(P=0.007). Meanwhile, it was found that the intestinal flora structure of mice on the eighth day was similar to that on the sixteenth day in TE group, while the intestinal flora structure of mice in TW group differed siginificantly. On the sixteenth day, the intestinal flora structure of TW group was similar to that of TE group. Conclusion B.subtilis could regulate intestinal flora structure possibly via interacting with intestinal microbia but not via colonizing. Long-term use of the probiotic 山 东 大 学 学 报 (医 学 版)55卷10期 -赵力,等.枯草芽孢杆菌灌胃对小鼠肠道菌群的影响 \=-changes intestinal flora structure more quickly than short-term does.

Role of mitochondria-associated membranes in the improvement of insulin sensitivity in diabetic rats after sleeve gastrectomy

XIE Haibin, WU Qunzheng, LIU Shaozhuang, HUANG Xin, CHENG Yugang, HU Sanyuan, ZHANG Guangyong

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  36-40.  doi:10.6040/j.issn.1671-7554.0.2017.205

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Objective To investigate the effects of sleeve gastrectomy(SG)on mitochondria-associated membranes in diabetic rats and the mechanism. Methods Models of Wistar rats with type 2 diabetes mellitus were established. A total of 20 models were randomly divided into surgery group(SG, n=10)and sham operation group(SHAM, n=10). The changes of body weight, food intake and insulin sensitivity were measured before and after operation. At the end of week 12 after surgery, liver samples were collected to detect protein expressions of inositol 1,4,5-trisphosphate receptor(IP3R), mitochondrial fusion protein 2(Mfn2), glucose-regulated protein 75(Grp75), and mitochondrial calcium uniporter(MCU)in mitochondria-associated membranes. Results Compared with SHAM group, SG group showed significant food intake reduction from week 4, and weight loss from week 6 postoperatively. In week 2 and 12, the areas under the curve of the oral glucose tolerance test, insulin tolerance test, and homeostasis model assessment of insulin resistance(HOMA-IR)were significantly decreased in SG group. The SG group had lower expressions of IP3R and MCU, which were associated with calcium homeostasis, and Mfn2, which was correlated with connection between mitochondria and endoplasmic reticulum(P<0.05). Conclusion The improvement of insulin sensitivity after SG in diabetic rats may be related to the decreased expression of MAMs proteins associated with calcium channel.

Effort of CD11b⁺ / CD66b^- phenotype myeloid cells on the progression of colon cancer and liver metastasis

WANG Bishi, SHAN Junqi, HOU Qingsheng, GONG Weipeng, ZHU Zhenyu, GUO Hongliang

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  41-45.  doi:10.6040/j.issn.1671-7554.0.2016.1522

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Objective To study the relationship between CD11b⁺/ CD66b^- phenotype myeloid cells and colon cancer progression and liver metastasis. Methods The transcription level, protein translation levels of CD11b, chemokine C-C motif ligand 2(CCL2)and chemokine C-C motif receptor type 2(CCR2)in colonic carcinoma tissues, colorectal cancer tissues and liver metastasis were detected by real-time PCR, Western blotting and immunohistochemistry. The co-immunoprecipitation method was used to detect the relationship between CCL2 and CCR2. Results The expression of CD11b mRNA in colorectal carcinoma and liver metastasis was higher than that in normal tissues(P<0.05). The level of CCL2 mRNA transcription and protein expression in liver metastasis was significantly higher than that in normal colonic tissues and colon cancer tissues(P<0.05). The level of CCR2 mRNA transcription and protein expression in the three were no significant difference(P>0.05). Chemokine ligand CCL2 and chemokine receptor CCR2 can be combined with each other. Conclusion CD11b phenotype myeloid cell is extensive infiltration in colon cancer and liver metastasis of colon cancer tissue, and possibly can promote the progression of colon cancer and liver metastasis of colonic carcinoma by mediating with CCL2-CCR2 axis.

Protective effects of post-conditioning with nicorandil on myocardial, cerebral and renal ischemia-reperfusion injury following cardiac arrest in swine

LIANG Lining, ZHONG Xia, JI Xianfei, HU Haoran, ZHU Fangfang, CHEN Jibin,CHEN Qianqian, SHANG Deya

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  46-51.  doi:10.6040/j.issn.1671-7554.0.2016.1178

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Objective To explore the effects of post-conditioning with nicorandil on myocardial, cerebral and renal ischemia-reperfusion injury following cardiac arrest in a porcine. Methods A total of 22 landrace pigs were randomized into the sham group(n=4)and resuscitation group(n=18). The resuscitation group received ventricular fibrillation induced by electrical stimulation for 4 min and then cardiopulmonary resuscitation. The sham group received surgery only. The resuscitation group was subdivided into saline control group(n=8)and nicorandil(n=8)group. The nicorandil group was given central intravenous injection of nicorandil(150 μg/kg)at onset of restoration of spontaneous circulation(ROSC), followed by 3 μg/(kg·min)intravenous drip until the end of reperfusion. The saline control group was given the same dosage of saline. At baseline, 5 min, 30 min, 3 h and 6 h after ROSC, blood samples were collected to examine the level of cardiac troponin I(cTnI). At 6 h after ROSC, the cardiac apex, parietal-cerebral cortex and upper pole of left kidney were removed for microstructure and ultrastracture studies. Results The cTnI level was significantly 山 东 大 学 学 报 (医 学 版)55卷10期 -梁丽宁,等.尼可地尔后适应对猪心脏骤停后心脑肾缺血再灌注损伤的保护作用 \=-increased in the resuscitation group than in the sham group after ROSC(P<0.05). The cTnI level was significantly decreased in the nicorandil group than in the saline control group(P<0.05). Histopathologic injury was relieved in the nicorandil group. Conclusion Post-conditioning with nicorandil can relieve myocardial, cerebral and renal ischemia-reperfusion injury following cardiac arrest in swine.

Expression and clinical significance of EFEMP2 in endometrial cancer tissues and cell

WANG Tiantian, CHEN Jie

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  52-58.  doi:10.6040/j.issn.1671-7554.0.2017.049

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Objective To investigate expression and the clinical significance of EGF containing fibulin-like extracellular matrix protein 2(EFEMP2)in endometrial cancer tissues and cell lines. Methods Immunohistochemical staining was performed to determine EFEMP2 expression in 200 endometrial carcinoma specimens and 40 normal endometrial tissue specimens. qRT-PCR, Western blotting and immunocytochemistry were performed to investigate EFEMP2 expression in normal endometrial cells compared with four kinds of endometrial carcinoma cell lines including KLE、HEC-1A、HEC-1B and Ishikawa. Growth curve assay and soft agar colony formation assay were used to investigate the proliferation of endometrial cancer cell lines. Transwell assays were used to analyze the invasion and migration of endometrial cancer cell lines. Results EFEMP2 was down-regulated in endometrial cancer tissues and cells compared with normal endometrial tissues and cells(P<0.001), respectively. EFEMP2 low expression was significantly related with high stage, low differentiation and positive lymph node status of endometrial cancer(P<0.05). KLE and HEC-1A cells had higher proliferation, invasion and metastasis abilities compared to HEC-1B and Ishikawa cells(P<0.001). Conclusion EFEMP2 expression was significantly related with tumor stage, tissue differentiation and lymph node status of endometrial cancer. It is possible that EFEMP2 inhibits endometrial cancer cell invasion and migration.

An 11β-HSD1 inhibitor improves insulin sensitivity in db/db mice

LI Hongzhi, SHEN Yongchao, LIU Jieting, ZHAO Xiaojin, CHU Yanhui, YUAN Xiaohuan

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  59-64.  doi:10.6040/j.issn.1671-7554.0.2016.1379

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Objective To explore the effects of H8, an inhibitor of 11β-HSD1, on insulin sensitivity in db/db mice. Methods A total of 40 db/db mice were divided into 5 groups: db/db model group(Dia), rosiglitazone treatment group(Ros), curcumin treatment group(Cur), curcumin analogues H8 treatment group(H8), and db/m control group(Con). H8 was intragastriclly administered once per day for 6 weeks, and then oral glucose tolerance test(OGTT)and intraperitoneal insulin tolerance test(IPITT)were performed at the end of the 6th week. Fasting blood glucose levels, collected from the tail vein, were measured in 0th, 1th, 3th, and 6th week. At the end of the experiment, the inner canthus vein blood was collected to examine HOMA-RI index. The activity of 11β-HSD1 in liver and adipocytes and the level of glucocorticoid in serum were detected with enzyme method and ELISA, respectively. Results The results of OGTT showed that the blood glucose level was significantly reduced in the Ros group and H8 group than in the Dia group. The IPITT results revealed that the blood glucose level was significantly reduced in the Ros group and H8 group than in the Dia group. Fasting blood glucose level of H8 group was significantly lower than that of Dia group from the 1th to 6th week after the treatment. The HOMA-IR indicator of the Ros group, Cur group and H8 group was significantly lower compared with that of the Dia group(P<0.001). Compared with Dia group, H8 had 山 东 大 学 学 报 (医 学 版)55卷10期 -李洪志,等.11β-HSD1抑制剂改善db/db小鼠胰岛素敏感性的实验研究 \=-significantly inhibited 11β-HSD1 activity in liver(P<0.01)and adipocytes(P<0.01), and reduced level of GC(P<0.001). Conclusion H8, an 11β-HSD1 inhibitor, could reduce the hepatic GC level in db/db mice, thereby increasing the sensitivity of insulin.

Perindopril ameliorates cardiac dysfunction via Akt-FoxO1 pathway in diabetic cardiomyopathy

GONG Luwei, ZHOU Lizhen, SU Guohai

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  65-70.  doi:10.6040/j.issn.1671-7554.0.2016.1152

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Objective To investigate the role and potential mechanism of perindopril on myocardial dysfunction in DCM(diabetic cardiomyopathy). Methods A total of 40 male Sprague-Dawley rats(100-120 g)were divided into 3 groups: control(n=10), DCM group(n=15)and DCM+perindopril group(n=15). The control group was fed with basal diet, while the DCM group and DCM+perindopril group were established as diabetic models. After the models were successfully established, the DCM group received intragastric normal saline, and DCM+perindopril group received intragastric perindopril 4 mg/(kg·d). The effect of perindopril on the rats cardiac function, myocardial apoptosis and fibrosis were observed. The protein expressions of p-Akt and p-FoxO1 were examined withWestern blotting. Results Compared with the control group, the DCM group exhibited severe left ventricular dysfunction, myocardial apoptosis and fibrosis, significantly increased p-FoxO1 expressio and decreased p-Akt protein expression(P<0.05). Compared with the DCM group, the DCM+perindopril group had better cardiac function and lower p-Akt protein expression(P<0.05). Conclusion Perindopril protects cardiac function by inhibiting myocardial apoptosis and fibrosis in diabetic rat svia Akt-FoxO1 pathway.

Relevant factors and early complications of significantly elevated enzymes after off-pump coronary artery bypass grafting

LIANG Fei, ZHANG Wenlong, ZHANG Jun, XU Chongen, ZOU Chengwei

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  71-75.  doi:10.6040/j.issn.1671-7554.0.2016.1599

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Objective To explore the relevant factors and early complications of significantly elevated enzymes after off-pump coronary artery bypass grafting(OPCABG), in order to guide the perioperative management of patients. Methods A total of 214 patients who underwent OPCABG in our hospital during Jan. 2015 and June 2016 were enrolled. Postoperative creatine kinase MB(CK-MB)was detected at 12 h, 24 h and 48 h. Patients with CK-MB ≤5.31 ng/mL were classified into group A, and the others with CK-MB >5.31 ng/mL were classified into group B. The clinical data of the two groups were compared and analyzed with Logistic regression analysis. Results The relevant factors included occurrence of angina pectoris 24 h before operation, the graft located at the distal or middle-distal segment of left anterior descending artery(LAD), and operation time for bypass surgery. Group B had higher incidences of ECG ST segment change, hypotention, and perioperative myocardial infarction(PMI)than group A(P<0.05). Conclusions If preoperative angina pectoris is frequent, or the left internal mammary artery is bridged at the distal or middle-distal segment of LAD, or the graft time is too long, early complications such as significantly elevated enzymes, ECG ST segment changes, hypotension, and PMI may occur after OPCABG in patients with graft patency.

Meta-analysis and system evaluation of ¹²⁵I implantation in the treatment of early lung cancer

WANG Lili, HUO Bin, WANG Lei, WANG Hao, HOU Dingkun, HUO Xiaodong, WANG Jinhuan, ZANG Li, CAO Qiang, CHAI Shude, WANG Haitao

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  76-83.  doi:10.6040/j.issn.1671-7554.0.2017.039

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Objective To evaluate the efficacy of sublobar resection(SR)and sublobar resection combined with ¹²⁵I brachytherapy(SRB)in the treatment of early non-small cell lung cancer(NSCLC). Methods The relevant literatures on SR and SRB in the treatment of NSCLC were searched in PubMed, Embase, Cochrane Library, CNKI, Wanfang database, and Chinese CBM database from the inception date to Nov. 2016. The bibliographies of retrieved articles were also enrolled. The studies enrolled were classified, the quality was evaluated, and data were extracted. Results A total of 16 studies(n=1 354)were included, 4 of which compared the efficacy of SR and SRB in the treatment of NSCLC, and 12(n=742)recorded SRB in the treatment of NSCLC. Meta-analysis showed that there was no statistical difference although SRB could reduce local recurrence(P=0.06). For SRB, the local control rate was 96.1%; the probability of local recurrence / distant metastases was 19.1%; the mean survival rate of 1-year, 2-year and 5-year was 84.9%, 74.9% and 32.1%, respectively. Conclusion The evidence shows that SRB is effective in the treatment of NSCLC, which can reduce the local recurrence rate. However, more high-quality studies are needed to confirm the efficacy.

Association between high expression of scavenger receptor class B type I and the prognosis of colon cancer

LIU Huiling, WANG Xingwen, FENG Shaobin, FENG Hong, HAN Junqing

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  84-89.  doi:10.6040/j.issn.1671-7554.0.2017.167

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Objective To explore the association between the expression of scavenger receptor class B type I(SR-BI)and the clinicopathological variables, and to determine whether SR-BI expression was an independent prognostic factor and a potential therapeutic target for colon cancer. Methods A well-documented tissue microarray of 90 patients with colon cancer was purchased from Shanghai Outdo Biotech Co., Ltd. The SR-BI expression in the cancer tissues and para-cancerous tissues were detected with immunohistochemical method. The association between SR-BI expression and the clinicopathological variables, and patients outcome was analyzed. Results In 78.9% of the cases, SR-BI expression was higher in the cancer tissues than in the adjacent non-tumor tissues(P<0.001). The expression of SR-BI in colon cancer tissues had no significant statistical association with the clinicopathological variables. Patients with low SR-BI expression in colon cancer tissues had a shorter overall survival(OS)than those with high SR-BI expression(P=0.042). The multivariate analysis confirmed that high SR-BI expression was an independent favorable prognostic factor for OS(P=0.039). Conclusion Low SR-BI expression is associated with unfavorable prognosis of colon cancer. SR-BI is an independent prognostic factor of colon cancer.

Expression and significance of programmed death-1 and its ligand PD-L1 in adenomyosis

WU Lukanxuan, ZHU Shan, YU Jinxi, LÜ Chunzi, LI Mingjiang

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2017, 55(10):  90-96.  doi:10.6040/j.issn.1671-7554.0.2017.157

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Objective To investigate the expression and significance of PD-1 and its ligand PD-L1 in adenomyosis. Methods The expression level of PD-1 and PD-L1 in normal endometria, eutopic and ectopic adenomyotic endometria were determined by immunohistochemistry and Western blotting(proliferative phase n=15; secretory phase n=15 in each group). In addition, the relationship between different expressions of PD-1/PD-L1 among groups and menstrual cycle was analyzed. Results PD-1/PD-L1 expressed in both normal and adenomyotic endometria of different menstrual cycles. In addition, expressions of PD-1/PD-L1 in both ectopic and eutopic adenomyotic endometria were upregulated(P<0.01). However, there was no difference between proliferative phase and secretory phase in PD-1/PD-L1 expression of eutopic adenomyotic endometria(P=0.12; P=0.45). Conclusion The expressions of PD-1 and PD-L1 are upregulated in adenomyotic endometria, suggesting that the PD-1/PD-L1 pathway may be involved in the immune dysfunctions and pathogenesis of adenomyosis.