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Human cytomegalovirus-encoded US28 may act as a tumor promoter in colorectal cancer

World Journal of Gastroenterology 2016年第9期22卷 2789-2798页

作者： Zhen-Zhai Cai Jian-Gang Xu Yu-Hui Zhou Ji-Hang Zheng Ke-Zhi Lin Shu-Zhi Zheng Meng-Si Ye Yun He Chang-Bao Liu Zhan-Xiong Xue Department of Gastroenterology The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University Department of Surgical Oncology Wenzhou Central Hospital Department of General Surgery The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University Department of Pathology Wenzhou Medical University

AIM: To assess human cytomegalovirus-encoded US28 gene function in colorectal cancer(CRC) ***: Immunohistochemical analysis was performed to determine US28 expression in 103 CRC patient samples and 98 corresponding adjacent noncancerous samples. Patient data were compared by age, sex, tumor location, histological grade, Dukes' stage, and overall mean survival time. In addition, the US28 gene was transiently transfected into the CRC LOVO cell line, and cell proliferation was assessed using a cell counting kit-8 assay. Cell cycle analysis by flow cytometry and a cell invasion transwell assay were also carried ***: US28 levels were clearly higher in CRC tissues(38.8%) than in adjacent noncancerous samples(7.1%)(P = 0.000). Interestingly, elevated US28 amounts in CRC tissues were significantly associated with histological grade, metastasis, Dukes' stage, and overall survival(all P < 0.05); meanwhile, US28 expression was not significantly correlated with age, sex or tumor location. In addition, multivariate Coxregression data revealed US28 level as an independent CRC prognostic marker(P = 0.000). LOVO cells successfully transfected with the US28 gene exhibited higher viability, greater chemotherapy resistance, accelerated cell cycle progression, and increased invasion ***: US28 expression is predictive of poor prognosis and may promote CRC.

关键词： Human cytomegalovirus US28 Colorectal cancer Prognosis Proliferation Invasion

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In vitro protective effect of recombinant prominin-1 combined with microRNA-29b on N-methyl-D-aspartateinduced excitotoxicity in retinal ganglion cells

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International Journal of Ophthalmology(English edition) 2023年第11期16卷 1746-1755页

作者： Jun-Hua Li Guan-Shun Yu Yu-Da Wang Tian-Kun Li eye hospital and School of Ophthalmology and Optometry Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina eye hospital of wenzhou medical university Hangzhou Branch Hangzhou 310020Zhejiang ProvinceChina Tianjin eye hospital Tianjin 300020China

AIM:To determine the in vitro protective effect of recombinant prominin-1(Prominin-1)+microRNA-29b(P1M29)on N-methyl-D-aspartate(NMDA)-induced excitotoxicity in retinal ganglion cells(RGCs).METHODS:RGC-5 cells were cultured,and NMDAinduced excitotoxicity at the range of 100–800μmol/L was assessed using the MTT ***(800μmol/L)was selected as the appropriate concentration for preparing the cell *** evaluate the protective effect of P1M29 on the cell model,Prominin-1 was added at the concentration of 1–6 ng/mL for 48h,and the cell survival was investigated with/without *** obtaining the appropriate concentration and time of P1M29 at 48h,real-time polymerase chain reaction(PCR)was utilized to detect the relative mRNA expression of vascular endothelial growth factor(VEGF)and transforming growth factor(TGF)-β*** blot detection was applied to measure the phosphorylation levels of protein kinase B(AKT)and extracellular regulated protein kinases(ERK)in RGC-5 cells after treatment with *** study of the cell model was conducted by flow cytometry for estimating the anti-apoptotic effect of *** analysis was used to analyze the expression levels of VEGF and TGF-β***:MTT cytotoxicity assays demonstrated that P1M29 group had significantly higher cell survival rate than Prominin-1 group(P<0.05).Real-time PCR data indicated that the expression levels of VEGF were significantly increased in both Prominin-1 and P1M29 groups compared NMDA and microRNA-29b group(P<0.05),while TGF-β2 were significantly decreased in both microRNA-29b and P1M29 groups compared NMDA and Prominin-1 group(P<0.05).Western blot results showed that both Prominin-1 and P1M29 groups significantly increased the phosphorylation levels of AKT and ERK compared to NMDA and microRNA-29b groups(P<0.05).Flow cytometry analysis revealed that P1M29 could prevent RGC-5 cell apoptosis in the early stage of apoptosis,while immunofluorescence results sho

关键词： Prominin-1 microRNA-29b vascular endothelial growth factor transforming growth factor-β2

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Metabolic Acidosis in Critically Ill Cirrhotic Patients with Acute Kidney Injury

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Journal of Clinical and Translational Hepatology 2019年第2期7卷 112-121页

作者： Dan-Qin Sun Lai Zhang Chen-Fei Zheng Wen-Yue Liu Kenneth I.Zheng Xiao-Ming Chen Ming-Hua Zheng Wei-Jie Yuan Department of Nephrology The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical UniversityWuxiChina Department of Nephrology Shanghai General Hospital of Nanjing Medical UniversityShanghaiChina Department of Nephrology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Department of Endocrinology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina NAFLD Research Center Department of Hepatologythe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Zhejiang Engineering Research Center of Intelligent Medicine The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Institute of Hepatology Wenzhou Medical UniversityWenzhouChina Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province WenzhouChina

Background and Aims:The metabolic acid-base disorders have a high incidence of acute kidney injury(AKI)in critically ill cirrhotic patients(CICPs).The aims of our study were to ascertain the composition of metabolic acidosis of CICPs with AKI and explore its relationship with hospital ***:Three-hundred and eighty consecutive CICPs with AKI were eligible for the cohort ***,clinical and laboratory parameters were recorded and arterial acid-base state was analyzed by the Stewart and Gilfix ***:Net metabolic acidosis,lactic acidosis,acidosis owing to unmeasured anions,acidemia,and dilutional acidosis were less frequent in the non-survival group compared to the survival group of *** presence of acidemia,acidosis owing to unmeasured anions,and lactic acidosis were independently associated with increased risk of intensive care unit 30-day mortality,with hazard ratios of 2.11(95%confidence interval(CI):1.43–3.12),3.38(95%CI:2.36–4.84),and 2.16(95%CI:1.47–3.35),*** full adjustment for confounders,the relationship between acidosis owing to unmeasured anions with hospital mortality was still significant,with hazard ratio of 2.29(95%CI:1.22–4.30).Furthermore,arterial lactate concentration in combination with chronic liver failure-sequential organ failure assessment and BEUMA had the strongest ability to differentiate 30-day mortality(area under the receiver operating characteristic curve:0.79,95%CI:0.74–0.83).

关键词： Metabolic acidosis Critically ill cirrhotic patients Acute kidney injury hospital morality

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Short term effect of choroid thickness in the horizontal meridian detected by spectral domain optical coherence tomography in myopic children after orthokeratology

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International Journal of Ophthalmology(English edition) 2018年第6期11卷 991-996页

作者： Wan-Qing Jin Sheng-Hai Huang Jun Jiang Xin-Jie Mao Mei-Xiao Shen Yan Lian eye hospital of wenzhou medical university Wenzhou 325027 Zhejiang Province China Optometry Academy of wenzhou medical university Wenzhou 325027 Zhejiang Province China

AIM： To investigate choroidal thickness changes in the horizontal meridian after orthokeratology. METHODS： This is a prospective cross-sectional observed study. Subjects （n=30; 11.3±1.7y） with low-to-moderate myopia （-1.0 to -6.0 diopters）, wore orthokeratology （Ortho-K） lenses for 3mo. Before and after Ortho-K, OCT scans were made through the fovea in the horizontal meridian. Choroid thickness around the fovea was acquired by custom software. The analyzed regions along the horizontal meridian were divided into 7 equal zones. Ocular parameters were measured by Lenstar LS 900 non-contact biometry. RESULTS： Only the right eye ocular parameters were analyzed in this study. Before Ortho-K, choroidal thickness along the horizontal meridian was 273.7±31.8 μm in the temporal zone, 253.1±38.6 μm in the macula zone, and 194.8±52.2 μm in the nasal zone. After Ortho-K, the choroid was thicker in each horizontal zone （P〈0.05）. The increased thickness was greatest in the temporal zone （13.5±22.5 μm） and least in the nasal zone （8.4±14.2 μm）. The axial length （AL） increased 0.02 mm （P〉0.05）. The choroid thickness change in each horizontal zone was negatively correlated with AL （r, -0.3 to -0.4; P〈0.05） except one of the nasal zones. CONCLUSION： In myopic children, the thickness of the choroid is greatest in the temporal zone and thinnest in the nasal zone. After nightly Ortho-K for 3mo, the thickness increase along the horizontal meridian. The choroid thickness changes are negatively correlated with the change of AL.

关键词： choroid thickness myopia control optical coherence tomography orthokeratology

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Conjunctival flap with auricular cartilage grafting: a modified Hughes procedure for large full thickness upper and lower eyelid defect reconstruction

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International Journal of Ophthalmology(English edition) 2021年第8期14卷 1168-1173页

作者： Ben Chen David Meng-da Woo Jia Liu Xiu-Ying Zhu Yan-Yan Lin Ying-Jie Ma Xi Chen eye hospital of wenzhou medical university Wenzhou 325027Zhejiang ProvinceChina Sydney hospital&Sydney eye hospital SydneyNSW 2220Australia

AIM:To investigate the suitability of a modified Hughes procedure,which consists of conjunctival flap with auricular cartilage grafting in reconstructing large full thickness upper and lower eyelid ***:Patients with full thickness eyelid carcinoma involving more than 50%margin length who underwent surgical resection were retrospectively reviewed in the *** defects were reconstructed using conjunctival flap with auricular cartilage grafting,covered with myocutaneous flap ***-up time ranged from 12 to 24 *** were classified as“good”,“fair”,and“poor”by evaluating the margin appearance,eyelid appearance,and ***:A total of 42 patients were enrolled in the study(26 males,16 females,mean age,68.6±7.7 y,range:53 to 82 y).The mean defect widths measured 23.2±2.9 mm(range,17 to 28 mm).The mean posterior lamellar defect height was 5.5±1.3 mm(4 to 8 mm).Thirty-seven patients had a“good”outcome(88.1%),5 patients had a“fair”outcome(11.9%),and no one had a“poor”***:Conjunctival flap with auricular cartilage grafting and myocutaneous flap grafting is an effective procedure in reconstructing large full thickness upper and lower eyelid *** can not only achieve satisfied reconstruction,but also preserve intact tarsal plate of the opposite eyelid,avoiding retraction or entropion.

关键词： auricular cartilage grafting conjunctival flap full thickness eyelid defect Hughes procedure

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Choroidal thickness and choriocapillaris vascular density in myopic anisometropia

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eye and Vision 2021年第1期8卷 467-476页

作者： Xinting Liu Zhiyi Lin Feifu Wang Xiaoyi Peng Wenwen He Dan Chen Meixiao Shen Fan Lu Jun Jiang School of Ophthalmology and Optometry Eye HospitalWenzhou Medical University270 Xueyuan RoadWenzhou 325027ZhejiangChina

Background:This study aims to examine interocular differences in the choroidal thickness and vascular density of the choriocapillaris in anisometropic myopes and to further explore the relationship between choroidal blood flow and ***:The sample comprised 44 participants with anisometropic myopia,aged 9 to 18 years,with normal bestcorrected visual *** participants underwent a series of examinations,including spherical equivalent refraction(SER)and axial length(AL),measured by a Lenstar optical biometer and optical coherence tomography angiography(OCTA)*** measured the choroidal thickness,vascular density,and flow voids of the choriocapillaris,and a customized algorithm was implemented in MATLAB R2017a with the post-correction of *** choroidal thickness was measured at the fovea and 0.5,1.0,1.5,2.0,2.5,and 3.0 mm nasally,temporally,inferiorly,and superiorly to the *** vascular density and the flow voids of the choriocapillaris were measured at a 0.6-mm-diameter central circle,and the 0.6-2.5 mm diameter circle in the nasal,temporal,inferior,and superior ***-measured ANOVAs were used to analyze the interocular *** correlations with the K value and age adjustments were used to study the relationships between the choroidal thickness,the choriocapillaris vascular density and flow voids,the SER and ***:The choroidal thickness of the more myopic eyes was significantly thinner than less myopic eyes(P≤0.001),and the flow voids in the more myopic eyes were more than less myopic eyes(P=0.002).There was no significant difference in the vascular density of the choriocapillaris between the more and less myopic eyes(P=0.525).However,when anisometropia was more than 1.50 D,the vascular density of choriocapillaris in the more myopic eyes was significantly less than the less myopic eyes(P=0.026).The interocular difference of the choroidal thickness was significantly correlated with the interocular difference in SE

关键词： Myopic anisometropia Choroidal choriocapillaris Choroidal thickness

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2-(2-Benzofuranyl)-2-imidazoline treatment within 5 hours after cerebral ischemia/reperfusion protects the brain

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Neural Regeneration Research 2018年第12期13卷 2111-2118页

作者： Zheng Zhang Jin-Long Yang Lin-Lei Zhang Zhen-Zhen Chen Jia-Ou Chen Yun-Gang Cao Man Qu Xin-Da Lin Xun-Ming Ji Zhao Han Department of Neurology the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Department of Neurology the First Affiliated Hospital of Wenzhou Medical University Department of Neurosurgery Xuanwu Hospital Capital Medical University Department of Neurology Shan Xian Central Hospital Department of Children Rehabilitation the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University China-America Institute of Neuroscience Xuanwu Hospital Capital Medical University

We previously demonstrated that administering 2-（2-benzofuranyl）-2-imidazolin（2-BFI）, an imidazoline I2 receptor agonist, immediately after ischemia onset can protect the brain from ischemic insult. However, immediate administration after stroke is difficult to realize in the clinic. Thus, the therapeutic time window of 2-BFI should be determined. Sprague-Dawley rats provided by wenzhou medical university in China received right middle cerebral artery occlusion for 120 minutes, and were treated with 2-BFI（3 mg/kg） through the caudal vein at 0, 1, 3, 5, 7, and 9 hours after reperfusion. Neurological function was assessed using the Longa＇s method. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride assay. Morphological changes in the cortical penumbra were observed by hematoxylin-eosin staining under transmission electron microscopy. The apoptosis levels in the ipsilateral cortex were examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling（TUNEL） assay. The protein expression of Bcl-2 and BAX was detected using immunohistochemistry. We found the following： Treatment with 2-BFI within 5 hours after reperfusion obviously improved neurological function. Administering 2-BFI within 9 hours after ischemia/reperfusion decreased infarct volume and alleviated apoptosis. 2-BFI administration at different time points after reperfusion alleviated the pathological damage of the ischemic penumbra and reduced the number of apoptotic neurons, but the protective effect was more obvious when administered within 5 hours. Administration of 2-BFI within 5 hours after reperfusion remarkably increased Bcl-2 expression and decreased BAX expression. To conclude, 2-BFI shows potent neuroprotective effects when administered within 5 hours after reperfusion, seemingly by up-regulating Bcl-2 and down-regulating BAX expression. The time window provided clinical potential for ischemic stroke by 2-BFI.

关键词： nerve regeneration ischemia/reperfusion 2-(2-benzofuranyl)-2-imidazoline neuroprotection time window apoptosis Bcl-2 BAX neural regeneration

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Association between Mean Ocular Perfusion Pressure and Diabetic Retinopathy in a Northeastern Chinese Population

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Biomedical and Environmental Sciences 2020年第9期33卷 701-707页

作者： ZHAI Gang LIN Zhong WANG Feng Hua WANG Yu LI Dong WEN Liang DING Xiao Xia JIANG Jing FENG Ke Mi LIANG Yuan Bo XIE Cong Fushun eye hospital Fushun 113006LiaoningChina School of Ophthalmology&Optometry Wenzhou Medical UniversityEye Hospital of Wenzhou Medical UniversityWenzhou 325035ZhejiangChina Beijing Tongren eye Center Beijing Tongren HospitalCapital Medical UniversityBeijing Ophthalmology&Visual Science Key LabBeijing 100730China

Objective To evaluate the association between diabetic retinopathy(DR) and mean ocular perfusion pressure(MOPP) in patients with type 2 diabetes mellitus(T2 DM).Methods Patients from the Fushun Diabetic Retinopathy Cohort Study(FS-DIRECT), a communitybased prospective cohort study conducted in northeast China, were included in this study. The presence and severity of DR were determined by grading fundus photographs according to the Early Treatment Diabetic Retinopathy Study(ETDRS) retinopathy scale. Systolic and diastolic blood pressure(SBP and DBP) were recorded using an electronic sphygmomanometer. Intraocular pressure(IOP) was measured using an iCare rebound tonometer. MOPP was calculated using the formula MOPP = 2/3 [DBP + 1/3(SBP-DBP)]-*** In total, 1,857 patients who had gradable fundus photography and MOPP data were enrolled in this study. Male patients had a higher MOPP than female patients(52.25 ± 8.75 vs. 50.96 ± 8.74 mmHg, P = 0.002). Overall, both male and female patients with any type of DR, non-proliferative DR(NPDR), or non-sight-threatening DR(non-STDR) had significantly higher MOPP relative to patients without DR. Increased MOPP(per 1 mmHg) was in turn associated with the presence of any type of DR[odds ratio(OR) = 1.03, 95% confidence interval(CI) : 1.02–1.04], NPDR(OR = 1.03 95% CI: 1.02–1.04),and non-STDR(OR = 1.03, 95% CI: 1.01–1.04) after adjusting for confounders. Increased MOPP(per 1 mmHg) was also associated with an increased likelihood of macular edema(OR = 1.02, 95% CI:1.01–1.04).Conclusions The results suggest that increased MOPP was associated with DR and macular edema in northeastern Chinese patients with T2 DM.

关键词： Diabetic retinopathy Ocular perfusion pressure Systolic blood pressure Diastolic blood pressure

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Bioinspired self-assembly supramolecular hydrogel for ocular drug delivery

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Chinese Chemical Letters 2021年第12期32卷 3936-3939页

作者： Xianglian Li Hui Liu Ailing Yu Dan Lin Zhishu Bao Yuqin Wang Xingyi Li Institute of Biomedical Engineering School of Ophthalmology OptometryEye HospitalWenzhou Medical UniversityWenzhou 325027China

Based on a recent report concerning endogenous agents(i.e., pyridoxal phosphate, adenosine triphosphate, adenosine monophosphate, folinic acid) that modulate the oligomerization of apoptosis-associated speck-like protein(ASC) via the peptide epitope of KKFKLKL, we rationally designed and synthesized a nonapeptide(Nap FFKKFKLKL), which can co-assemble with dexamethasone sodium phosphate(Dexp) to generate a Nap FFKKFKLKL/Dexp supramolecular hydrogel for ocular drug *** Nap FFKKFKLKL/Dexp hydrogel formed instantly after the complexation of Nap FFKKFKLKL with Dexp in aqueous solution. The formed supramolecular hydrogels were thoroughly characterized by transmission electron microscopy(TEM), fluorescent spectrum, circular dichroism(CD) spectra and rheology. The peptide concentration significantly affected the in vitro release behavior of Dexp from the supramolecular hydrogel, and the higher peptide concentration resulted in the slower drug *** a single intravitreal injection, the proposed Nap FFKKFKLKL/Dexp hydrogel displayed good intraocular biocompatibility without having an adverse impact on the retinal architecture and eyesight functions during one month of follow-up. Using an experimental autoimmune uveitis(EAU) rat model,we demonstrated that the resulting Nap FFKKFKLKL/Dexp hydrogel had potent capacity to alleviate the intraocular inflammation and retain the morphology of retinal architecture. Overall, the resulting Nap FFKKFKLKL/Dexp hydrogel may be a promising drug carrier system to treat various posterior disorders(i.e., uveitis).

关键词： Supramolecular hydrogel Self-assembly Drug delivery Ocular disorder

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4D label-free proteomic analysis of vitreous from patients with rhegmatogenous retinal detachment

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International Journal of Ophthalmology(English edition) 2023年第4期16卷 523-531页

作者： Qiu-Yi Huo Meng-Chao Zhu Wen-Chao Yang Yi-Peng Wang Song Chen wenzhou medical university Wenzhou 325027Zhejiang ProvinceChina Anyang eye hospital Anyang 455000Henan ProvinceChina Tianjin eye hospital Tianjin Eye InstituteTianjin Key Lab of Ophthalmology and Visual ScienceNankai University Affiliated Eye HospitalTianjin 300020China

AIM:To identify metabolites,proteins,and related pathways involved in the etiology of rhegmatogenous retinal detachment(RRD)for use as biomarkers in diagnosing and treating ***:Vitreous specimens were collected and liquid chromatography-tandem mass spectrometry analysis was per formed using the four-dimensional label-free *** significant differentially expressed proteins,gene ontology(GO)terms,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representations,and protein interactions were ***:Nine specimens were subjected to proteomic *** total,161 proteins were identified as differentially expressed proteins(DEPs),including 53 upregulated proteins and 108 downregulated *** functional analysis revealed that some DEPs were enriched in neuron-related terms and membrane protein ***,KEGG analysis indicated that the cell adhesion molecule metabolic pathway was associated with the greatest number of ***,the evaluation of protein-protein interaction network revealed that DEPs were clustered in neuronal adhesion,apoptosis,inflammation and immune responses,correct protein folding,and ***:Proteomic profiling is useful for the exploration of molecular mechanisms that underlie *** study reveals increased expression levels of proteins related to heat shock protein content,glycolysis,and inflammatory responses in *** regarding biomarkers of RRD pathogenesis may help to prevent the occurrence of RRD in the future.

关键词： vitreous rhegmatogenous retinal detachment proteome 4D label-free

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