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| 1 | Epac2-deficiency leads to more severe retinal swelling, glial reactivity and oxidative stress in transient middle cerebral artery occlusion induced ischemic retinopathy显示文摘Ischemia occurs in diabetic retinopathy with neuronal loss, edema, glial cell reactivity and oxidative stress. Epacs, consisting of Epac1 and Epac2, are c AMP mediators playing important roles in maintenance of endothelial barrier and neuronal functions. To investigate the roles of Epacs in the pathogenesis of ischemic retinopathy, transient middle cerebral artery occlusion(t MCAO) was performed on Epac1-deficient(Epac1-/-) mice, Epac2-deficient(Epac2-/-) mice, and their wild type counterparts(Epac1+/+ and Epac2+/+). Two-hour occlusion and 22-hour reperfusion were conducted to induce ischemia/reperfusion injury to the retina. After t MCAO, the contralateral retinae displayed similar morphology between different genotypes. Neuronal loss, retinal edema and increase in immunoreactivity for aquaporin 4(AQP4), glial fibrillary acidic protein(GFAP), peroxiredoxin 6(Prx6) were observed in ipsilateral retinae. Epac2-/- ipsilateral retinae showed more neuronal loss in retinal ganglion cell layer, increased retinal thickness and stronger immunostaining of AQP4, GFAP, and Prx6 than those of Epac2+/+. However, Epac1-/- ipsilateral retinae displayed similar pathology as those in Epac1+/+ mice. Our observations suggest that Epac2-deficiency led to more severe ischemic retinopathy after retinal ischemia/reperfusion injury. | LIU Jin YEUNG Patrick Ka Kit CHENG Lu LO Amy Cheuk Yin CHUNG Stephen Sum Man CHUNG Sookja Kim | 2015 | Science China(Life Sciences)2015，58，6： | 12 |
| 2 | Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine显示文摘AIM: To investigate the reduction in hepatitis B virus(HBV) covalently closed-circular DNA(ccc DNA) with entecavir(ETV) or lamivudine(LAM). METHODS: This analysis included patients who had participated in the randomized Phase Ⅲ study ETV-022 comparing ETV vs LAM in nucleos(t)ide-naive, HBe Agpositive patients. Patients received ETV(0.5 mg daily) or LAM(100 mg daily) for a minimum of 52 wk. Patients were eligible to participate in this sub-study if they had paired biopsies at baseline and week 48 with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA. The main objective was to compare changes in hepatic HBV ccc DNA and total hepatic HBV DNA at week 48 of ETV or LAM treatment, which was a secondary endpoint of study ETV-022. Additional post hoc analyses included linear regression analyses to assess associations of baseline levels and on-treatment changes of ccc DNA with other baseline factors [sex,age, serum HBV DNA, alanine aminotransferase(ALT), Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBV genotype], or ontreatment factors(changes from baseline at week 48 in serum HBV DNA, ALT, Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBe Ag loss at week 48).RESULTS: Overall, 305 patients(ETV = 159; LAM = 146) of ETV-022 had paired baseline and week 48 liver biopsies with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA, and were included in this analysis. Baseline demographics and disease characteristics were comparable between the two arms. After 48 wk, ETV resulted in significantly greater reductions in hepatic HBV ccc DNA [-0.9 log10 copies/human genome equivalent(HGEq) vs-0.7 log10 copies/HGEq; P = 0.0033] and total hepatic DNA levels(-2.1 log10 copies/HGEq vs-1.6 log10 copies/HGEq; P < 0.0001) than LAM. Virologic, biochemical, and histologic response rates at week 48 were also greater with ETV than with LAM. Baseline HBV ccc DNA levels were positively associated with baseline levels of serum HBV DNA and total hepatic HBV DNA, and negatively associated with HBV genotype F. On-treatment changes in HBV ccc DNA levels were negatively associated with baseline levels of serum HBV DNA and baseline ALT, and were positively associated with on-treatment changes in the levels of serum HBV DNA, total hepatic HBV DNA levels, and ALT, change in Knodell necroinflammatory score, and HBe Ag loss.CONCLUSION: Forty-eight weeks of ETV resulted in greater reductions in ccc DNA and total hepatic HBV DNA than LAM, but long-term therapy may be needed for ccc DNA elimination. | Scott Bowden Stephen Locarnini Ting-Tsung Chang You-Chen Chao Kwang-Hyub Han Robert G Gish Robert A de Man Miao Yu Cyril Llamoso Hong Tang | 2015 | World Journal of Gastroenterology2015，21，15： | 11 |
| 3 | Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis显示文摘The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer types.Although a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely understood.Here,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive microenvironment.Using an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)cells.Depletion of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,respectively.Mechanistically,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic mice.Accordingly,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation donors.In summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic immunosurveillance.Our findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention. | Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan Ka Fai To Stephen Lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng | 2021 | Cellular & Molecular Immunology2021，18，4： | 5 |
| 4 | Targeted hepatitis C screening among ex‐injection drug users in the community显示文摘 | Vincent Wai‐Sun Wong Grace Lai‐Hung Wong Angel Mei‐Ling Chim Tsz‐Fai Cheng Shirley Wing‐Yan Cheung Carol Man‐Sze Lai Kylie Joan‐Yi Szeto Sharon Tsang Stephen Ho‐Chun Wu Kenneth Kar‐Lung Yan Alex Yui Hui Desmond Chi‐Him Yiu Brian Bing‐Ying Wu David Cheung | 2014 | J Gastroenterol Hepatol2014，，1： | 1 |
| 5 | Magnetic Resonance Cholangiopancreatography Accurately Detects Common Bile Duct Stones in Resolving Gallstone Pancreatitis显示文摘 | Ali H. Hallal Jose D. Amortegui Igor M. Jeroukhimov Javier Casillas Carl I. Schulman Ronald J. Manning Fahim A. Habib Peter P. Lopez Stephen M. Cohn Danny Sleeman | 2005 | Journal of the American College of Surgeons2005，，6： | 1 |
| 6 | The role of pharmacists in HIV/STD prevention evaluation of an STD syndromic management intervention in Nepal显示文摘 | Sidhartha Man Tuladhar Stephen Mills | 1998 | AIDS1998，12，2： | 1 |
| 7 | Diagnostic technique for power system sutilizing infrared thermal imaging显示文摘 | Merry man Stephen A Nelms R M | 1995 | IEEE Transactions on Industrial Electronics1995，42，6： | 1 |
| 8 | CIA' s Kent School: Improving Training for New Analysts 显示文摘 | Stephen Man'in | 2003 | International Journal of Intelligence and Counterintelligence2003，16，4： | 1 |
| 9 | Exosomal miR-1290 and miR-375 as Prognostic Markers in Castration-resistant Prostate Cancer显示文摘 | Xiaoyi Huang Tiezheng Yuan Meihua Liang Meijun Du Shu Xia Rachel Dittmar Dian Wang William See Brian A. Costello Fernando Quevedo Winston Tan Debashis Nandy Graham H. Bevan Sherri Longenbach Zhifu Sun Yan Lu Tao Wang Stephen N. Thibodeau Lisa Boardman Man | 2014 | European Urology2014，，： | 1 |
| 10 | Estimated prevalence and trends in smoking among adolescents in South Korea,2005-2021:a nationwide serial study显示文摘Background Although smoking is classified as a risk factor for severe COVID-19 outcomes,there is a scarcity of studies on prevalence of smoking during the COVID-19 pandemic.Thus,this study aims to analyze the trends of prevalence of smoking in adolescents over the COVID-19 pandemic period.Methods The present study used data from middle to high school adolescents between 2005 and 2021 who participated in the Korea Youth Risk Behavior Web-based Survey(KYRBS).We evaluated the smoking prevalence(ever or daily)by year groups and estimated the slope in smoking prevalence before and during the pandemic.Results A total of 1,137,823 adolescents participated in the study[mean age,15.04 years[95%confidence interval(CI)15.03-15.06];and male,52.4%(95%CI 51.7-53.1)].The prevalence of ever smokers was 27.7%(95%CI 27.3-28.1)between 2005 and 2008 but decreased to 9.8%(95%CI 9.3-10.3)in 2021.A consistent trend was found in daily smokers,as the estimates decreased from 5.4%(95%CI 5.2-5.6)between 2005 and 2008 to 2.3%(95%CI 2.1-2.5)in 2021.However,the downward slope in the overall prevalence of ever smokers and daily smokers became less pronounced in the COVID-19 pandemic period than in the pre-pandemic period.In the subgroup with substance use,the decreasing slope in daily smokers was significantly more pronounced during the pandemic than during the pre-pandemic period.Conclusions The proportion of ever smokers and daily smokers showed a less pronounced decreasing trend during the pandemic.The findings of our study provide an overall understanding of the pandemic's impact on smoking prevalence in adolescents. | Hyoin Shin Sangil Park Hyunju Yon Chae Yeon Ban Stephen Turner Seong Ho Cho Youn Ho Shin Jung U.Shin Ai Koyanagi Louis Jacob Lee Smith Chanyang Min Young Joo Lee So Young Kim Jinseok Lee Rosie Kwon Min Ji Koo Guillaume Fond Laurent Boyer Jong Woo Hahn Namwoo Kim Sang Youl Rhee Jae Il Shin Ho Geol Woo Hyeowon Park Hyeon Jin Kim Yoonsung Lee Man S.Kim Eléa Lefkir Vlasta Hadalin Jungwoo Choi Seung Won Lee Dong Keon Yon Sunyoung Kim | 2023 | World Journal of Pediatrics2023，19，4： | 1 |
| 11 | Using Two-point Correlation Functions to Char- acterize Microgeometry and Estimate Permeabilities of Sandstones and Porous Glass 显示文摘 | Stephen C Blair Patricia A Berge James G Berry- man | 1996 | Journal of Geophys- ical Research1996，101，20： | 1 |
| 12 | Rhinitis therapy and the prevention of hospital care for asthma显示文摘 | Jonathan Corren Beatrice E. Manning Stephen F. Thompson Sean Hennessy Brian L. Strom | 2004 | The Journal of Allergy and Clinical Immunology2004，，： | 1 |
| 13 | Molecular records of microbialites following the end-Permian mass extinction in Chongyang, Hubei Province, South China显示文摘 | Lin Chen Yongbiao Wang Shucheng Xie Stephen Kershaw Man Dong Hao Yang Hao Liu Thomas J. Algeo | 2010 | Palaeogeography, Palaeoclimatology, Palaeoecology2010，，1： | 1 |
| 14 | The role of pharmacists in HIV/STD prevention evaluation of an STD syndromic managementint intervention in Nepal显示文摘 | Sidhartha Man Tuladhar Stephen Mills | 1998 | AIDS1998，12，2： | 1 |
| 15 | Therapy-related acute promyelocytic leukemia after chemoradiotherapy with capecitabine for rectal adenocarcinoma显示文摘 | Armin Rashidi Louise Man John R. Howard Daniel Atienza Stephen I. Fisher | 2014 | Leukemia & Lymphoma2014，，3： | 1 |
| 16 | Intelligence Studies Versus Intelligence School 2008 显示文摘 | Stephen Man'in | 2009 | Chronicle Review of Higher Education2009，55，28： | 1 |
| 17 | Using a Product Manifold distance for unsupervised action recognition显示文摘 | Stephen O’Hara Yui Man Lui Bruce A. Draper | 2011 | Image and Vision Computing2011，，3： | 1 |
| 18 | Diagnostic technique for power systems utilizing infrared thermal imaging 显示文摘 | Merry man Stephen A Nelms R M | 1995 | IEEE Transactions on Industrial Electronics1995，2，6： | 1 |
| 19 | 凉风有信 莫负秋浓显示文摘当听到“凉风有信”,大家似乎总能脱口而出接出下句“秋月无边”,这两句是经典南音《客途秋恨》中最开始的两句歌词,后来这首名曲被多次翻唱,其中哥哥张国荣版本的最为有名。《客途秋恨》曲词凄美委婉,听起来有一种抑郁的苍凉。是的,秋天总与“萧瑟”“凋零”“凄清”这样带着悲伤色彩的词语联系在一起,这似乎是这个季节的“性格”。但秋天里有的只是萧瑟和寂寥吗?它其实也有美好宜人的一面。 | Stephen Burks Man Made Alma Design STUDIOFOR MADESIGNLAB KETTAL B-Line Dan Vakhrameyev Ward Wijnant GANDIABLASCO 李薇 范嘉苑 | 2016 | 现代装饰(家居)2016，0，10： | 0 |
| 20 | A new osteogenic protein isolated from Dioscorea opposita Thunb accelerates bone defect healing through the mTOR signaling axis显示文摘Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2 have been recognized as one of the powerful osteogenic substances that promote mesenchymal stem cells (MSCs) to osteoblast differentiation and are widely applied clinically for bone defect repairs. However, recent reports show that BMP-2 treatment has been associated with clinical adverse side effects such as ectopic bone formation, osteolysis and stimulation of inflammation. Here, we have identified one new osteogenic protein, named ‘HKUOT-S2’ protein, from Dioscorea opposita Thunb. Using the bone defect model, we have shown that the HKUOT-S2 protein can accelerate bone defect repair by activating the mTOR signaling axis of MSCs-derived osteoblasts and increasing osteoblastic biomineralization. The HKUOT-S2 protein can also modulate the transcriptomic changes of macrophages, stem cells, and osteoblasts, thereby enhancing the crosstalk between the polarized macrophages and MSCs-osteoblast differentiation to facilitate osteogenesis. Furthermore, this protein had no toxic effects in vivo. We have also identified HKUOT-S2 peptide sequence TKSSLPGQTK as a functional osteogenic unit that can promote osteoblast differentiation in vitro. The HKUOT-S2 protein with robust osteogenic activity could be a potential alternative osteoanabolic agent for promoting osteogenesis and bone defect repairs. We believe that the HKUOT-S2 protein may potentially be applied clinically as a new class of osteogenic agent for bone defect healing. | John Akrofi Kubi Augustine Suurinobah Brah Kenneth Man Chee Cheung Yin Lau Lee Kai-Fai Lee Stephen Cho Wing Sze Wei Qiao Kelvin Wai-Kwok Yeung | 2023 | Bioactive Materials2023，，9： | 0 |
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