Table of Content

  

10 February 2016
Volume 54 Issue 2

Expression and significance of CCL25/CCR9 in chronic rejection of cardiac allografts in rats

HU Lianlong, SONG Guangmin, ZHAO Xin, BAI Xiao, ZHANG Jian, ZHAO Tinglei, WANG Long

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  1-5.  doi:10.6040/j.issn.1671-7554.0.2015.799

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Objective To investigate the expression and significance of CC chemokine ligand 25(CCL25)and CC chemokine receptor 9(CCR9)in chronic rejection of cardiac allografts in rats. Methods Inbred Wistar rats and inbred SD rats were selected as donors and recipients. Cervical heterotopic heart transplantation was performed with “cuff technique”. The recipients were divided into 3 groups randomly, with 10 rats in each group: CsA group, CsA+IgG group, and CsA+anti-CCL25 group. Au vecipients were received 10 mg/kg cyclosporin A(CsA)immediately after the surgery, then once every other day for 10 times. CsA+IgG group was injected with 0.1 mg/kg IgG isotype Ab immediately after the surgery, then once every other day for 10 times. CsA+anti-CCL25 group was injected with 0.1 mg/kg anti-rat CCL25 Ab immediately after the surgery, then once every other day for 10 times. All allografts were harvested on the 70th day postoperatively. HE and sirus red staining were used to observe the pathologic changes of the allograft myocardia. Additionally, immunohistochemistry and Western blotting were adopted to detect the expressions of CCL25 and CCR9 in the myocardium. Results The myocardial inflammatory response, fibrosis and cardiac allograft vasculopathy(CAV)in CsA group and CsA+IgG group were significantly severer than in CsA+anti-CCL25 group(P<0.05); 山 东 大 学 学 报 (医 学 版)54卷2期 -胡连龙,等.CCL25/CCR9在大鼠心脏移植慢性排斥反应中的表达及意义 \=-CCL25 and CCR9 were expressed in the cardiac allografts; the expression of CCL25 and CCR9 in CsA+anti-CCL25 group was significantly lower than that in the other two groups(P<0.05). Conclusion CCL25 and CCR9 are expressed in the chronic rejection of cardiac allografts in rats. Anti-CCL25 Ab can significantly alleviate the pathologic changes of cardiac allografts through targeted blocking of CCL25/CCR9. Our study indicates that CCL25/CCR9 plays important roles in the chronic rejection of cardiac allografts in rats.

Regulation of microRNA-34a on SH2B3 expression during cardiac fibrosis

XI Fuli, ZHANG Mei

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  6-10.  doi:10.6040/j.issn.1671-7554.0.2015.411

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Objective To explore the pathological mechanism of abnormal SH2B3 expression during cardic fibrosis. Methods After H2C9 cells were treated with transformin growth factor-β1(TGF-β1)at different concentrations(10, 50, and 100 ng/mL)and hypoxia stimulation of various duration(3, 6, 12, 24 and 48 h), the expression of SN2B3 protein was detected with Western blotting, and the SN2B3 mRNA and miR-34a expressions were determined with qRT-PCR. After H2C9 cells were transfected with miR-34a mimic/inhibitor, the SH2B3 expression was examined with Western blotting. The effect of miR-34a on the activity of SH2B3 3'UTR was detected with luciferase activity assay. Results After treatment of TGF-β1 and hypoxia, SH2B3 expression decreased at both mRNA and protein levels(P<0.05), but miR-34a expression increased(P<0.05). The miR-34a could regulate SH2B3 expression by directly binding to 3'UTR(P<0.05). Conclusion SH2B3 participates in the fibrosis process of fibroblasts under the regulation of miR-34a.

Chronic intermittent hypobaric hypoxia enhances the vasodilatation of thoracic aorta via PI3K-dependent eNOS activation in rats

WANG Lixuan, ZHANG Lu, XU Xin, LI Sixue, LIU Min, WANG Yaping, MA Huijuan

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  11-15.  doi:10.6040/j.issn.1671-7554.0.2015.513

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Objective To investigate the effects of chronic intermittent hypobaric hypoxia(CIHH)on the vasodilatation in isolated thoracic aorta and the nitric oxide related mechanism in rats. Methods A total of 80 male adult Sprague-Dawley rats were randomly divided into two groups: control group(CN, n=40)and CIHH group(CIHH, n=40). The rats in CIHH group were exposed to hypoxia simulating at 5000-meter altitude in a hypobaric chamber(P_B=404 mmHg, P_O2=84 mmHg)for 28 days, 6 hours each day. The rats in CN group lived in a normoxic environment for the same period. The vasodilatation of thoracic aorta was recorded by using organ bath technique. The protein expressions of eNOS and PI3K were measured by using Western blotting. Results CIHH could remarkably augment the acetylcholine(ACh)-induced vasodilatation of thoracic aorta(P<0.05)and increase the expression of eNOS in thoracic aorta tissues(P<0.05). Incubation with MEK inhibitor PD98059 did not affect the effects of CIHH on thoracic aorta. Incubation of PI3K inhibitor LY294002 blocked the effects of CIHH(P<0.05). Furthermore, CIHH treatment could improve the expression of PI3K in thoracic aorta tissue(P<0.05). Conclusion CIHH treatment enhances Ach-induced vasodilatation of thoracic aorta by activating eNOS via PI3K pathway.

Inducible nitric oxide synthase contributes to the delayed cardioprotection of ischemic postconditioning in rats

LI Xin, WANG Gongming, WANG Hong, WANG Yan, ZHANG Ligong, ZHANG Le, LIU Bei, ZHANG Mengyuan

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  16-20.  doi:10.6040/j.issn.1671-7554.0.2015.829

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Objective To investigate the delayed cardioprotective effects of ischemic preconditioning(IPO)and the role of inducible nitric oxide synthase(iNOS)in the late phase of IPO. Methods A total of 160 rats were randomized into 5 groups: I/R group, IPO group, IPO+1400W(iNOS inhibitor)group, I/R+1400W group and sham-operated(sham)group. Animals in each group received 3, 24, 48 or 72 h of reperfusion after ischemia(n=8 per each time point). Cardio-infarct size and creatine kinase(CK)activity were measured respectively. Western blotting was used to assess the expressions of phosphorylated endothelial nitric oxide synthase(p-eNOS)and iNOS in the heart. Results At reperfusion 3 h, in the IPO group, the infarct size of left ventricle(LV)decreased significantly compared with I/R group［(18.0±2.3)% vs(30.7±3.1)%, P<0.05). At reperfusion 72 h, the difference between IPO group and I/R group in infarct size was obvious［(25.7±1.1)% vs(34.9±0.8)%, P<0.05］. Difference in the CK activity was positively correlated with the difference in infarct size in all groups. IPO increased p-eNOS levels at R 3 h and R 24 h 山 东 大 学 学 报 (医 学 版)54卷2期 -李欣,等.诱导型一氧化氮合成酶参与大鼠心脏缺血后处理延迟相的保护作用 \=-and iNOS levels at R 48 h and R 72 h. Conclusion IPO has delayed cardioprotective effects on myocardial infarction, and iNOS plays a critical role in the delayed effects against heart injury.

Enalapril inhibits homocysteine-induced smooth muscle cell dedifferentiation and its signal pathway

YANG Bo, LI Ping, MENG Liping, ZHOU Changzuan, PAN Sunlei, CHI Jufang, GUO Hangyuan

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  21-26.  doi:10.6040/j.issn.1671-7554.0.2015.778

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Objective To explore whether enalapril could inhibit homocysteine(Hcy)-induced dedifferentiation of rat aortic vascular smooth muscle cells(VSMCs)and its potential mechanism. Methods The primary culture and identification of rat VSMCs was conducted and VSMCs in passage 4-7 were divided into 4 groups: control group, Hcy(100 μmol/L)group, Hcy+enalapril group, and Hcy+LY-294002 group. The proliferation and migration of VSMCs were detected using MTT, transwell chambers and wound healing, respectively. The morphology of VSMCs was observed with ICC. The expressions of SM-actin, SM-MHC, Calponin, OPN and p-AKT in VSMCs of every group were investigated using Western blotting. Results Compared with those of the control group, the proliferation and migration ability of VSMCs were significantly increased, the expressions of SM-MCH and Calponin were increased, while OPN was decreased in the Hcy group(P<0.01). There was no significant difference in the expression of SM-actin 山 东 大 学 学 报 (医 学 版)54卷2期 -杨博,等.依那普利抑制大鼠血管平滑肌细胞表型转化及可能的信号通路 \=-among the groups. Compared with those of the Hcy group, the proliferation and migration ability of VSMCs were significantly decreased, the expression of SM-MCH and calponin increased, while OPN and pAKT expressions were decreased in enalapril and LY-294002-treated groups(all P<0.01). Conclusion Hcy can induce, while enalapril can inhibit the dedifferentiation of VSMCs, by inhibiting the PI3K/p-AKT signal pathway.

Role of histone acetyltransferase MOF in the pathogenesis of multiple sclerosis

GUAN Jingyun, YANG Yang, QIU Chunhong, LI Xiangzhi

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  27-32.  doi:10.6040/j.issn.1671-7554.0.2015.366

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Objective To investigate the activities of Treg cells and the expression of MOF in the peak and remission periods of experimental allergic encephalomyelitis(EAE)mice and the impact of MOF on the pathogenesis of EAE. Methods On Day 0, twenty 6-8 week old C57BL/6 female mice of similar weight were subcutaneously injected with 200 μg MOG_35-55 or complete freunds adjuvant(CFA)and then intraperitoneally injected with 200 ng pertussis toxin. On Day 2, the above three mice were intraperitoneally injected with 200 ng pertussis toxin. The spleen tissues of the EAE mice in different phases were used, along with the spleen tissues of the mice from control group in the same phases. The protein levels of MOF, FOXP3, and H4K16ac were detected through Western blotting. The mRNA expression levels of MOF, TLRS, and FOXP3 were detected by real-time fluorescent quantitative RT-PCR. Co-immunoprecipitation was performed to assess the binding between MOF and FOXP3 in the spleen tissues. ChIP-qPCR was performed to detect the downstream target genes of MOF. The relationships between the protein expression levels of TLRS, FOXP3 in the HCT116 cells, and MOF regulation were also studied. Results The expression levels of MOF and FOXP3 protein in the spleen of EAE mice were significantly higher than those of the control group. The mRNA levels of FOXP3, 山 东 大 学 学 报 (医 学 版)54卷2期 -关景云,等.组蛋白乙酰转移酶MOF在多发性硬化发病机制中的作用 \=-MOF, IL17, TLR4, TLR5, TLR6, TLR7 and TLR9 in EAE mouse spleen tissue were significantly higher than those of the control group(P<0.05); Co-IP showed that MOF directly interacted with FOXP3 in spleen tissues; ChIP-qPCR showed that MOF combined with FOXP3, TLR3, TLR4, TLR5, TLR6, SMAD2, SMAD3, and RoRγt genes in the spleen. TLR4 and FOXP3 showed higher expression levels in the HCT116 cells compared with the control group when MOF was overexpressed(P<0.05). Conclusion MOF suppresses the occurrence of EAE through its interaction with FOXP3.

Synapse-protective effect of flavonoids extracted from the leaves of Diospyros kaki in APP/PS1 transgenic mice

SHANG Yuying, MA Yingjuan, WU Xiaofan, HOU Xunyao, LUO Dingzhen, CHEN Jian, HONG Yan, SHEN Chao, LIU Xueping

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  33-37.  doi:10.6040/j.issn.1671-7554.0.2015.705

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Objective To investigate the effect of flavonoids extracted from the leaves of Diospyros kaki(FLDK)on cognition levels, synapse structure and the expression of synapse-related proteins in APP/PS1 transgenic mouse. Methods Twenty APP/PS1 mice of four-month old were randomly divided into Alzheimers disease(AD)model group(AD group)and treatment group(AD+FLDK group), ten in each group; ten C57BL/6 mice of four-month old were regarded as normal control group(NC group). AD+FLDK group was treated intragastrically with 80 mg/(kg·d)FLDK, while AD and NC groups were fed intragastrically with the same volume of normal saline. Morris water maze was used to test the escape latency(EL)and number of crossing, transmission electron microscope was used to observe the ultrastructure of synapse, and immunohistochemistry was used to detect the expression levels of synaptophysin and drebrin. Results Compared with NC group, the EL was prolonged, crossing numbers decreased, the synapse ultrastructure was damaged and synapse-related protein levels decreased in AD group. Compared with AD group, EL decreased and crossing number increased obviously, synapse ultrastructure was clearer and synapse-related protein levels increased in AD+FLDK group. Conclusion FLDK can improve cognitive decline in APP/PS1 transgenic mouse, protect the integrity of synapse, and increase the synapse-related protein levels, thus can enhance cognition levels and protect synapse.

Breast tumor deriving VEGF induces vascular endothelial cells to suppress immune functions

LI Ranran, ZHANG Pengfei, YUAN Bing, FANG Feifei, HAN Mingyong

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  38-43.  doi:10.6040/j.issn.1671-7554.0.2015.798

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Objective To explore the effect of breast tumor deriving vascular endothelial growth factor(VEGF)on the immune functions of vascular endothelial cells(VEC). Methods Human umbilical vein endothelial cells(HUVEC)were divided into 4 groups: Media group, T-sup group, VEGF group and SU5416 group. The levels of VEGF, PGE₂, IL-6 and IL-12 in 24 h conditioned cultural supernatants were assayed by ELISA. Experiments of CCK-8, ELISPOT and flow cytometry were processed on peripheral blood T cells after treatment with the 24 h conditioned cultural supernatants. Results The levels of VEGF, PGE₂ and IL-6 were increased in the T-sup group, compared with those in Media group(P<0.05), and the level of IL-12 was decreased in the T-sup group(P<0.05). Compared with Media group, the conditioned media in T-sup group promoted the apoptosis of T-lymphocytes, suppressed the expression of IFN-γ, and reduced the production of IFN-γ in CD8⁺ T cells. The levels of VEGF, PGE₂ and IL-6 were increased and the level of IL-12 was decreased in the VEGF group, compared with those in Media group. But there were no statistically significant differences after the treatment of SU5416, a VEGF receptor antagonist. Conclusion Breast tumor cells suppress the immune fuctions of VEC, which is closely related with the high expression of VEGF.

c-jun affects thapsigargin-induced mouse fibroblasts survival

ZHANG Jie, WANG Aihong, DONG Bo, ZHAO Peng

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  44-48.  doi:10.6040/j.issn.1671-7554.0.2015.077

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Objective To examine the impact of c-jun on thapsigargin-induced mouse fibroblasts survival and its mechanism. Methods Thapsigargin, pCMV-CnA and pSRα-HA-c-jun were used to treat c-jun-/- and c-jun Re mouse fibroblasts. Cell viability was evaluated with trypan blue dye exclusion. Calcineurin assays were performed according to the manufacturers instructions. c-jun, p-c-jun, JNK, p-JNK, Adapt78 and α-tubulin were analyzed with immunoblotting. Results TG treatment led to strong JNK activation and phosphorylation of c-jun in c-jun Re cells. We observed a higher level of calcineurin activity in c-jun-/- cells compared with c-jun Re cells(P<0.05). TG treatment resulted in significantly increased calcineurin activity in c-jun-/- cells but not in c-jun Re cells. Exogenous expression of calcineurin via pCMV-CnA caused increased Adapt78 expression in both c-jun-/- and c-jun Re cells, although TG treatment induced Adapt78 expression only in c-jun Re cells. Adapt78 expression induced by pCMV-CnA in c-jun-/- cells was associated with protection against TG-induced cell death. Overexpression of exogenous c-jun in c-jun-/- cells caused both an autophosphorylation of c-jun in the target cells and exogenous expression of c-jun recovered thapsigargin-induced Adapt78 up-regulation and inhibited TG-induced cell death. Conclusion The change of c-jun gene expression level can affect TG-induced mouse cell survival rate. The changes of calcineurin and Adapt78 protein expression are related to the 山 东 大 学 学 报 (医 学 版)54卷2期 -张洁,等.原癌基因c-jun对毒胡萝卜素内酯处理的小鼠胚胎成纤维细胞生存率的影响 \=-alteration of c-jun gene expression. The increased c-jun gene expression results in enhanced expression of Adapt78 protein, thus weakens the calcineurin activity and produces protective mechanism against TG-induced cell death.

Treatment of atrial septal defect: minimally invasive occlusion procedure vs percutaneous interventional occlusion

LU Zhong, SHEN Yunhua, YAN Zhongya, HUANG Xiangyang, LI Chunsheng, LI Huabao, YANG Dongmei

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  49-52.  doi:10.6040/j.issn.1671-7554.0.2015.223

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Objective To compare the clinical efficacy, advantages and disadvantages between minimally invasive occlusion procedure and percutaneous interventional occlusion for treating patients with atrial septal defect(ASD). Methods The clinical data of 146 ASD patients treated during Jan. 2004 and Aug. 2014 were retrospectively analyzed. The patients were divided into 2 groups: group A(n=43)were treated with minimally invasive occlusion procedure under the guidance of transesophageal echocardiography(TEE); group B(n=103)received percutaneous interventional occlusion guided by TEE and digital subtraction angiography(DSA). Clinical data before and after the surgery were collected; efficacy and cost of both approaches were compared. Results Age, gender, body weight and diameter of ASD were similar between the two groups(all P>0.05). Operation time, postoperative hospital stay and mean total cost were significantly lower in group B than in group A(all P<0.05). All cases in group A were successfully occluded with satisfactory results. The 2 unsuccessful patients in group B switched to emergency surgical operation. No patients in both groups needed blood transfusion and no death occurred. One month after operation, transthoracic echocardiography(TTE)derived diameters of left atrial and left ventricular were smaller than those preoperative(both P<0.05). Incidence of residual shunt, and left ventricular ejection fraction were similar before and 1 month 山 东 大 学 学 报 (医 学 版)54卷2期 -卢中,等.经胸小切口封堵与经皮介入封堵术治疗房间隔缺损的比较 \=-after operation(both P>0.05). Conclusion The two approaches are both minimally invasive operation for treating ASD, which can be performed safely and effectively. Minimally invasive occlusion procedure does not need X-ray, and has higher success rate and wider indications than percutaneous interventional occlusion. Percutaneous interventional occlusion shortens the operation time and hospitalization, has lower medical cost, and provides better cosmetic results.

Clinical efficacy of bosentan in the treatment of babies with congenital heart disease complicated with pulmonary hypertension

PAN Yanyan, SUN Yongchao, ZHAO Cuifen, KONG Qingyu

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  53-56.  doi:10.6040/j.issn.1671-7554.0.2015.743

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Objectives To explore the efficacy and safety of bosentan in the treatment of infants(<3 months)with congenital heart disease complicated with pulmonary hypertension(CHD-PAH). Methods A total of 60 CHD-PAH infants treated in Qilu Hospital of Shandong University and Qilu Childrens Hospital during Jan. 2012 and Dec. 2013 were selected as the observation group and subdivided into bosentan group(n=30)and captopril group(n=30), another 30 healthy infants served as the control group. Endothelin-1(ET-1)and mean pulmonary arterial pressure(mPAP)before treatment, 4 and 8 weeks after treatment were measured with ELISA and echocardiography(UCG)in all infants. Changes of liver enzymes were measured before and after the treatment, and exercise tolerance was evaluated by observing the time changes of feeding 60 mL milk for babies in the observation group. Results ET-1 and mPAP were significantly higher in the observation group than in the control group(P<0.05). ET-1 and mPAP 4 and 8 weeks after bosentan treatment decreased significantly compared to the basement levels(P<0.01). MPAP after captopril treatment declined compared with the control group(P<0.05), while there was no statistical difference in ET-1 concentrations. ET-1 and mPAP in 山 东 大 学 学 报 (医 学 版)54卷2期 -潘艳艳,等.波生坦治疗婴儿先心病合并肺动脉高压的临床观察 \=-the bosentan treatment group decreased significantly compared with those of the captopril group 4 weeks and 8 weeks after treatment(P<0.05). There was no difference in liver enzymes before and after bosentan treatment(P>0.05). The feeding time of 60 mL milk decreased statistically 4 weeks after bosentan treatment. Conclusion Bosentan can not only effectively decrease the mean pulmonary artery pressure of infants with congenital heart disease, but also improve their exercise tolerance. Bosentan is effective and safe in the treatment of CHD-PAH infants.

Effect of the cycle time of myocardial ischemic postconditioning on patients undergoing primary percutaneous coronary intervention

HU Haoran, YUAN Meng, LIANG Lining, JI Xianfei, LI Tao, CHEN Yong, LIU Fuli, BIAN Hongjun, ZHOU Yi, HU Bo, ZHONG Xia, SHANG Deya

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  57-62.  doi:10.6040/j.issn.1671-7554.0.2015.586

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Objective To investigate the impact of different cycle times of myocardial ischemic postconditioning on the clinical outcome and prognosis of patients undergoing primary percutaneous coronary intervention(PCI). Methods A total of 100 patients with acute ST-elevation anterior infarction were randomly assigned to 4 groups. The routine group(n=25)received conventional PCI. The first postconditioning group(IPOC-1 group, n=25)underwent 3 cycles of repetitive balloon deflation and inflation with low pressure(4-6 atm)1 minute after opening the anterior descending, and every cycle lasted for 30 seconds. The second postconditioning group(IPOC-2 group, n=25)received the same operation; however, the first cycle lasted for 30 seconds, the second 60 seconds, and the third 90 seconds. The last 山 东 大 学 学 报 (医 学 版)54卷2期 -胡浩然,等.心肌缺血后适应循环时间对急诊经皮冠状动脉介入治疗患者的影响 \=-postconditioning group(IPOC-3 group, n=25)underwent within 1 minute reflow by 3 cycles of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Blood sampling for the creatine kinase isoenzyme MB(CK-MB), cardiac troponin I(cTNI)and high sensitive C-reactive protein(hs-CRP)were taken at predetermined time after PCI. Corrected Timi Frame Count(CTFC)was calculated by two senior interventional experts. All patients received Doppler ultrasound examination and rest ^99mTc- sestamibi(^99mTc-MIBI)myocardial perfusion single photon emission computed tomography(SPECT)7 days and 3 months after PCI. Results The peak(CK-MB)and cTNI concentration 72 hours after PCI of the IPOC-2 group were lower than those of the routine group, IPOC-1 group and IPOC-3 group(all P<0.05). No differences were observed in the hs-CRP concentration before PCI among the 4 groups, but the hs-CRP concentration 24 hours after PCI was lower in the IPOC-2 group compared with the other groups(all P<0.05). CTFC of the IPOC-2 group significantly reduced compared with other groups(all P<0.05). On day 7 after PCI, the LVEDD, Ea/Aa and LVEF of all 4 groups had no significant differences(all P>0.05), but the SPECT score of the IPOC-2 group was the lowest(P<0.05). After 3 months, no statistical differences were found in the LVEDD of the 4 groups; nevertheless, the LVEF, Ea/Aa and SPECT score of the IPOC-2 group tended to have the best outcome(all P<0.05). The SPECT score was significantly lowered in each group 3 months after PCI in comparison with the corresponding group 7 days after operation(all P<0.05). Conclusion The myocardial ischemic postconditioning can dramatically decrease myocardial infarction size, attenuate myocardial ischemic reperfusion injury and improve cardiac function.

Clinical, pathological and molecular biological study on a Chinese family of Spinocerebellar Ataxia type 6

LUAN Haihui, XU Wei, WANG Muchuan, WU Lin, WANG Lingling, MA Jun, LIU Yiming

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  63-67.  doi:10.6040/j.issn.1671-7554.0.2015.344

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Objective To investigate the clinical, pathological, molecular biological features and the treatment outcome for a pedigree of spinocerebellar ataxia type 6(SCA 6). Methods Physical examinations and gene sequencing were performed. Muscular biopsies were performed in 3 patients. The expression of peroxisomeproliferators activatedreceptor-coactivator-1α(PGC-1α)in the myocyte was detected. Patients were treated with drugs, and the treatment outcome of 4 patients were measured with the scale for the assessment and rating of ataxia scores(SARA)and clinical global impressions scale(CGIS). Results The basic manifestations of the patients were slowly progressive cerebellar ataxia, mainly manifested unstable gait and difficulty in walking straight, and accompanied with nystagmus and dysarthria. nystagmus and dysarthria. An abnormal CAG repeats existed in the SCA6 gene. In muscle biopsies, 2 patients showed mild muscle damage with mitochondrial dysfunction and 1 showed normal. But PGC-1α expression decreased in all patients. The clinical symptoms of the patients were improved markedly. Conclusion Mitochondrial dysfunction and depression of PGC-1α exist in the muscle of SCA6 patients. These findings imply that impaired function of mitochondrial may play a critical role in the process of SCA, and the treatment with mitochondrial protective agents can exert therapeutic benefits.

Effects of P38 mitogen-activated protein kinase signal pathway on the expression of urokinase-type plasminogen activator in ovarian cancer

ZHANG Chunxia, ZOU Cunhua, SONG Dongdong, YU Jiang

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  68-74.  doi:10.6040/j.issn.1671-7554.0.2015.081

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Objective To explore the effects of P38 mitogen-activated protein kinase(P38MAPK)signal pathway on the expression of urokinase-type plasminogen activator(uPA)in ovarian cancer. Methods The expressions of uPA, P38MAPK, extracellular regulated kinase(ERK), and AKT/kinase B in 49 cases of ovarian cancer were detected with immunohistochemistry. The expressions of uPA and P38MAPK in ovarian cancer cell line HO-8910 and HO-8910PM were detected with Western blotting. Changes of uPA were observed after P38MAPK, ERK and AKT signal pathway were blocked by SB203580, U0126 and MK-2206 respectively. Results The results of immunohistochemistry showed that positive expression rates of uPA, P38MAPK, ERK and AKT were 61.22%, 57.14%, 53.06%, and 55.10%, respectively. The expression of the uPA was related to clinicopathologic stage, differentiation and metastasis(P<0.05), and positively correlated with P38MAPK(P=0.01), but not related to ERK or AKT(P>0.05). The expressions of AKT and ERK were related to lymph node metastasis and greater omentum metastasis(P<0.05). The expression of uPA and P38MAPK in HO-8910PM was higher than those in HO-8910, and it reduced when the P38MAPK signal pathway was blocked by SB203580. But it had no significant change after dealing with U0126 and MK-2206 respectively. The postoperative survival rate was negatively correlated with P38MAPK and uPA. Conclusion The 山 东 大 学 学 报 (医 学 版)54卷2期 -张春霞,等.P38MAPK信号通路对卵巢癌中尿激酶型纤维蛋白酶原激活剂的影响 \=-P38MAPK signal pathway are activated in ovarian cancer and it can upregulate the expression of uPA, but ERK and AKT signal pathway are not involved in the regulation of uPA expression, which indicates that P38MAPK and uPA may play an important role in the invasion, metastasis and prognosis assessment of ovarian cancer.

Association of CDKAL1 rs10946398 C/A polymorphism with type 2 diabetes

Muhadasi TUERXUNYIMING, Patamu MOHEMAITI, Tuolanguli MAIMAITIKUERBAN

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  75-85.  doi:10.6040/j.issn.1671-7554.0.2015.1143

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Objective To investigate the relationship between cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1(CDKAL1)gene rs10946398 C/A single neucleotide polymorphism and the susceptibility of type 2 diabetes mellitus(T2DM). Methods Databases including PubMed, Web of Science, CNKI, Wanfang, and VIP were retrieved to search for literature on the association between T2DM and CDKAL1 gene rs10946398 C/A single neucleotide polymorphism. The odds ratio of CDKAL1 gene rs10946398 C/A genotype distributions in type 2 diabetic patients compared with healthy controls were analyzed. Rev-Man 5.3 software was applied for heterogeneity test and data merge. Altogether 16 case control studies were enrolled. Results In the whole population, a significant relationship between CDKAL1 rs10946398 C/A gene polymorphism and T2DM was observed under allelic(OR: 1.58, 95% CI: 1.30-1.93), recessive(OR: 1.14, 95% CI: 1.09-1.20), dominant(OR: 1.05, 95% CI: 1.01-1.09), and homozygous(OR: 1.19, 95% CI: 1.13-1.26), all P<0.01. Conclusion CDKAL1 rs10946398 C/A gene polymorphism is significantly associated with increased T2DM risk. The C allele of the CDKAL1 rs10946398 C/A gene polymorphism may confer susceptibility to T2DM.

Von Hippel-Lindau disease complicated with renal carcinoma: a report of 2 cases

WANG Guangjie, ZU Shulu, ZHANG Xiulin, XU Zhishun, ZHOU Chunwen, LIU Yuqiang, WANG Shaoyong

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  86-89.  doi:10.6040/j.issn.1671-7554.0.2015.748

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Objective To explore the clinical characteristics of Von Hippel-Lindau(VHL)disease complicated with renal carcinoma, in order to find better methods of diagnosis and treatment. Methods Clinical data of 2 cases of VHL disease complicated with renal carcinoma were retrospectively analyzed and relevant literature was reviewed. Results One of the 2 patients had family history and underwent right radical nephrectomy. Pathological examination suggested clear-cell carcinoma. No recurrence was found in this patient after one-year follow-up. The other patient did not have family history. He also underwent right radical nephrectomy. Pathological examination suggested multilocular cystic renal cell carcinoma in the right kidney and pheochromocytoma in the right adrenal gland. Four years later, carcinoma was found in the left kidney and left adrenal gland. Pathological examination of biopsy tissue in the left kidney tumor indicated clear-cell carcinoma. He received sorafenib, a molecular targeted drug, and regular hemodialysis. Conclusion VHL disease is a rare cancer syndrome that involves multiple systems. The characteristics of renal cancer concurrent with VHL are different from sporadic one. Early diagnosis and individualized treatment can improve the quality of patients' life. New treatments should be further explored.

Present situation and existing problems of telemedicine in Shandong Province

WANG Xing, ZHANG Xiyu, LIN Weiwei, LIAN Ying, ZHANG Qingqing, LI Qilong, LI Shixue

JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES). 2016, 54(2):  90-94.  doi:10.6040/j.issn.1671-7554.0.2015.859

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Objective To explore the advantages and existing problems of telemedicine in Shandong Province. Methods Consultation cases of telemedicine and tele-education during 2010 and 2014 were described using constituent ratio and analyzed with Chi-square test. Results From 2010 to 2014, the number of telemedicine consultation increased year by year. Consultation disciplines included 20 clinical and medical departments, and 5 disciplines gained excellent development. Consultations of cases from other provinces, difficult cases, rare cases and tele-education were growing rapidly. Conclusion Telemedicine in Shandong Province develops well, and a large number of consultation and education services are provided to the basic-level hospitals. However, there still exist many problems, such as single operating model, blank legal responsibility, lack of government supervision, and defects in system construction. Telemedicine will achieve a qualitative leap without the restraints.