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Lipoprotein(a) is associated with coronary atheroma progression: analysis from a serial coronary computed tomography angiography study

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Journal of Geriatric Cardiology 2021年第12期18卷 996-1007页

作者： Xi WANG Dong-Kai SHAN Guan-Hua DOU Yi-Pu DING Jing JING He-Bin CHE Jun-Jie YANG Yun-Dai CHEN Medical School of Chinese PLA BeijingChina Department of Cardiology the Sixth Medical CentreChinese PLA General HospitalBeijingChina Department of Cardiology the Second Medical CentreChinese PLA General HospitalBeijingChina School of Medicine Nankai UniversityTianjinChina Medical Big Data Research Centre Chinese PLA General HospitalBeijingChina

BACKGROUND Lipoprotein(a)[Lp(a)]has been closely related to coronary atherosclerosis and might affect perivascular in-flammation due to its proinflammatory ***,there are limited data about Lp(a)and related perivascular inflam-mation on coronary atheroma ***,this study aimed to investigate the associations between Lp(a)and the peri-vascular fat attenuation index(FAI)with coronary atheroma progression detected by coronary computed tomography angio-graphy(CCTA).METHODS Patients who underwent serial CCTA examinations without a history of revascularization and with available data for Lp(a)within one month before or after baseline and follow-up CCTA imaging scans were considered to be *** quantitative analyses were performed to obtain the total plaque volume(TPV)and the perivascular *** plaque pro-gression(PP)was defined as a≥10%increase in the change of the TPV at the patient level or the presence of new-onset coronary atheroma *** associations between Lp(a)or the perivascular FAI with PP were examined by multivariate logistic *** A total of 116 patients were ultimately enrolled in the present study with a mean CCTA interscan interval of 30.80±13.50 *** the 116 patients(mean age:53.49±10.21 years,males:83.6%),32 patients presented PP during the follow-up ***(a)levels were significantly higher among PP patients than those among non-PP patients at both baseline[15.80(9.09−33.60)mg/dL vs.10.50(4.75−19.71)mg/dL,P=0.029]and follow-up[20.60(10.45−34.55)mg/dL vs.8.77(5.00−18.78)mg/dL,P=0.004].However,there were no differences in the perivascular FAI between PP group and non-PP group at either baseline or *** logistic regression analysis showed that elevated baseline Lp(a)level(OR=1.031,95%CI:1.005−1.058,P=0.019)was an independent risk factor for PP after adjustment for other conventional *** Lp(a)was independently associated with coronary atheroma pr

关键词： Lp(a) coronary elevated

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Skeletal phenotypes in secreted frizzled-related protein 4 gene knockout mice mimic skeletal architectural abnormalities in subjects with Pyle's disease from SFRP4 mutations

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Bone Research 2023年第1期11卷 193-200页

作者： Robert Brommage Jeff Liu David R.Powell Department of Metabolism Research Lexicon PharmaceuticalsThe WoodlandsTX77381USA

Mutations in SFRP4 cause Pyle’s bone disease with wide metaphyses and increased skeletal *** WNT signaling pathway plays important roles in determining skeletal architecture and SFRP4 is a secreted Frizzled decoy receptor that inhibits WNT *** cohorts of male and female Sfrp4 gene knockout mice,examined through 2 years of age,had a normal lifespan but showed cortical and trabecular bone *** human Erlenmeyer flask deformities,bone cross-sectional areas were elevated 2-fold in the distal femur and proximal tibia but only 30%in femur and tibia *** cortical bone thickness was observed in the vertebral body,midshaft femur and distal *** trabecular bone mass and numbers were observed in the vertebral body,distal femur metaphysis and proximal tibia *** femurs retained extensive trabecular bone through 2 years of *** bodies had increased compressive strength,but femur shafts had reduced bending ***,but not cortical,bone parameters in heterozygous Sfrp4mice were modestly *** resulted in similar declines in both cortical and trabecular bone mass in wild-type and Sfrp4 KO ***4 is critical for metaphyseal bone modeling involved in determining bone ***4 KO mice show similar skeletal architecture and bone fragility deficits observed in patients with Pyle’s disease with SFRP4 mutations.

关键词： SFRP4 skeletal elevated

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The double face of miR-320:cardiomyocytes-derived miR-320 deteriorated while fibroblasts-derived miR-320 protected against heart failure induced by transverse aortic constriction

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Signal Transduction and Targeted Therapy 2021年第3期6卷 950-961页

作者： Xudong Zhang Shuai Yuan Huaping Li Jiabing Zhan Feng Wang Jiahui Fan Xiang Nie Yan Wang Zheng Wen Yanghui Chen Chen Chen Dao Wen Wang Division of Cardiology Tongji HospitalTongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic DisordersHuazhong University of Science and TechnologyWuhan 430030China

MicroRNAs(miRNAs)are aberrantly expressed in the pathophysiologic process of heart failure(HF).However,the functions of a certain miRNA in different cardiac cell types during HF are scarcely reported,which might be covered by the globe effects of it on the *** the current study,Langendorff system was applied to isolate card io myocytes(CMs)and cardiac fibroblasts(CFs)from transverse aortic constriction(TAC)-induced *** increase of miR-320 expression was observed in the whole heart tissue of TAC ***,miR-320 was significantly elevated in CMs but decreased in CFs from TAC mice at different time ***,recombinant adeno-associated virus 9 with cell-type-specific promoters were used to manipulate miR-320 expressions in *** in vitro and in vivo experiments showed the miR-320 overexpression in CMs exacerbated cardiac dysfunction,whereas overexpression of miR-320 in CFs alleviated cardiac fibrosis and ***,downstream signaling pathway analyses revealed that miR-320 might induce various effects via targeting PLEKHM3 and IFITM1 in CMs and CFs,***,miR-320 mediated effects could be abolished by PLEKHM3 re-expression in CMs or IFITM1 re-expression in ***,miR-320 treated CFs were able to indirectly affect CMs function,but not vice ***,upstream signaling pathway analyses showed that miR-320 expression and decay rate were rigorously manipulated by Ago2,which was regulated by a cluster of cell-type-specific TFs distinctively expressed in CMs and CFs,***,we demonstrated that miR-320 functioned differently in various cell types of the heart during the progression of HF.

关键词： miR elevated transverse

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Sclerostin antibody improves alveolar bone quality in the Hyp mouse model of X-linked hypophosphatemia

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International Journal of Oral Science 2023年第4期15卷 640-648页

作者： Kelsey A.Carpenter Delia O.Alkhatib Bryan A.Dulion Elizabeth Guirado Shreya Patel Yinghua Chen Anne George Ryan D.Ross Department of Anatomy&Cell Biology Rush University Medical CenterChicagoILUSA Department of Oral Biology The University of Illinois at ChicagoChicagoILUSA Department of Orthopedic Surgery Rush University Medical CenterChicagoILUSA Department of Microbial Pathogens and Immunity Rush University Medical CenterChicagoILUSA

X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads tohypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence ofdental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including thealveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (SclAb) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mousemodel of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male andfemale wild-type and Hyp littermates were injected with 25 mg·kg−1 of vehicle or Scl-Ab twice weekly beginning at 12 weeks of ageand euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineraldensity in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active(nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effecton the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend towardincreased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were notaffected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.

关键词： alveolar impaired elevated

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Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2586-2599页

作者： Yuan Hou Yadi Zhou Michaela U.Gack Justin D.Lathia Asha Kallianpur Reena Mehra Timothy A.Chan Jae U.Jung Lara Jehi Charis Eng Feixiong Cheng Genomic Medicine Institute Lerner Research InstituteCleveland ClinicClevelandOHUSA Florida Research and Innovation Center Cleveland ClinicPort Saint LucieFLUSA Department of Cardiovascular and Metabolic Science Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA Department of Population and Quantitative Health Sciences Case Western Reserve UniversityClevelandOHUSA Neurological Institute Cleveland ClinicClevelandOHUSA Center for Immunotherapy and Precision Immuno-Oncology Cleveland ClinicClevelandOHUSA Department of Cancer Biology Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Genetics and Genome Sciences Case Western Reserve University School of MedicineClevelandOHUSA Case Comprehensive Cancer Center Case Western Reserve University School of MedicineClevelandOHUSA

Sex differences in the susceptibility of SARS-CoV-2 infection and severity have been controversial,and the underlying mechanisms of COVID-19 in a sex-specific manner remain *** we inspected sex differences in SARS-CoV-2 infection,hospitalization,admission to the intensive care unit(ICU),sera inflammatory biomarker profiling,and single-cell RNA-sequencing(scRNA-seq)profiles across nasal,bronchoalveolar lavage fluid(BALF),and peripheral blood mononuclear cells(PBMCs)from COVID-19 patients with varying degrees of disease *** propensity score-matching observations revealed that male individuals have a 29%elevated likelihood of SARS-CoV-2 positivity,with a hazard ratio(HR)1.32(95%confidence interval[Cl]1.18-1.48)for hospitalization and HR 1.51(95%Cl 1.24-1.84)for admission to *** from male patients at hospital admission had elevated neutrophil-lymphocyte ratio and elevated expression of inflammatory markers(C-reactive protein and procalcitonin).We found that SARS-CoV-2 entry factors,including ACE2,TMPRSS2,FURIN,and NRP1,have elevated expression in nasal squamous cells from male individuals with moderate and severe *** observed male-biased transcriptional activation in SARS-CoV-2-infected macrophages from BALF and sputum samples,which offers potential molecular mechanism for sex-biased susceptibility to viral ***-cell interaction network analysis reveals potential epithelium-immune cell interactions and immune vulnerability underlying male-elevated disease severity and mortality in ***,monocyte-elevated expression of Toll-like receptor 7{TLR7)and Bruton tyrosine kinase{BTK)is associated with severe outcomes in males with *** summary,these findings provide basis to decipher immune responses underlying sex differences and designing sex-specific targeted interventions and patient care for COVID-19.

关键词： elevated epithelium analysis

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Positive association between triglyceride glucose index and central systolic blood pressure among hypertensive adults

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Journal of Geriatric Cardiology 2022年第10期19卷 753-760,I0002页

作者： Li WANG Tian-Yu CAO Jin-Qiao LI Cong-Cong DING Jun-Pei LI Hua-Bo YING Li-Shun LIU Xiao HUANG Department of Nephrology the Fourth Hospital of Harbin Medical UniversityHarbinChina Biological Anthropo-logy University of California Santa BarbaraCaliforniaUSA Department of Urology Surgery Graduate School of the Fourth Hospital of Harbin Medical UniversityHarbinChina Department of Cardiology the Second Affiliated Hospi-tal of Nanchang UniversityNanchangChina Institute of Biomedicine Anhui Medical UniversityHefeiChina Instit-ute of Biomedical and Health Engineering Graduate School at ShenzhenTsinghua UniversityShenzhenChina Shen-zhen Evergreen Medical Institute ShenzhenChina

BACKGROUND While studies have suggested the association between triglyceride-glucose(TyG)index,a reliable surrogate for insulin resistance and hypertension data are limited to the correlation of TyG and central blood *** study aims to test the hypothesis that a higher TyG index is associated with elevated central systolic blood pressure(cSBP).METHODS A total of 9249 Chinese hypertensive adults from the H-type Hypertension and Stroke Prevention and Control Project were analyzed in this *** was measured noninvasively using an A-Pulse CASPro *** index was calculated as ln[fasting triglycerides(mg/dL)×fasting glucose(mg/dL)/2].Smoothing curve and multivariate linear regression models[beta coefficient(β)with 95%CI]were applied to analyze the association between TyG index and *** analyses were conducted to explore potential modifications to such a *** The overall mean TyG index is 8.8±0.7,and the total mean cSBP is 131.3±12.8 *** index was observed to be independently and positively associated with cSBP among the total population(β=0.92,95%CI:0.53–1.31,P<0.001),and participants who do not use antihypertensive drugs(β=1.03,95%CI:0.46–1.60,P<0.001),which is in accordance with the result of the smoothing *** association between TyG index and cSBP appears robust in all tested *** TyG index is positively and independently associated with cSBP among hypertensive *** study result suggests that TyG index might serve as an effective marker for vascular function.

关键词： hypertensive elevated systolic

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Confocal visible/NIR photoacoustic microscopy of tumors with structural, functional, and nanoprobe contrasts

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Photonics Research 2020年第12期8卷 1875-1880页

作者： JIANGBO CHEN YACHAO ZHANG XIAOZHEN LI JINGYI ZHU DENGFENG LI SHENGLIANG LI CHUN-SING LEE LIDAI WANG Department of Biomedical Engineering City University of Hong Kong999077 Hong Kong SARChina Center of Super-Diamond and Advanced Films(COSDAF)and Department of Chemistry City University of Hong Kong999077 Hong Kong SARChina City University of Hong Kong Shenzhen Research Institute Shenzhen 518057China

Distinguishing early-stage tumors from normal tissues is of great importance in cancer *** report fiberbased confocal visible/near-infrared(NIR)optical-resolution photoacoustic microscopy that can image tumor microvasculature,oxygen saturation,and nanoprobes in a single *** develop a cost-efficient single laser source that provides 532,558,and 1064 nm pulsed light with sub-microseconds wavelength switching *** dual-fiber illumination,we can focus the three beams to the same *** optical and acoustic foci are confocally aligned to optimize the *** visible and NIR wavelengths enable simultaneous tumor imaging with three different contrast *** show obvious angiogenesis,significantly elevated oxygen saturation,and accumulated nanoparticles in the tumor regions,which offer comprehensive information to detect the *** approach also allows us to identify feeding and draining vessels of the tumor and thus to determine local oxygen extraction *** the tumor region,the oxygen extraction fraction significantly decreases along with tumor growth,which can also assist in tumor detection and ***-based confocal visible/NIR photoacoustic microscopy offers a new tool for early detection of cancer.

关键词： visible elevated saturation

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Elaiophylin triggers paraptosis and preferentially kills ovarian cancer drug-resistant cells by inducing MAPK hyperactivation

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3925-3939页

作者： Guan-Nan Li Xue-Jiao Zhao Zhen Wang Meng-Shi Luo Shen-Nan Shi Dan-Mei Yan Hua-Yi Li Jia-Hao Liu Yang Yang Jia-Hong Tan Ze-Yu Zhang Ru-Qi Chen Hui-Ling Lai Xiao-Yuan Huang Jian-Feng Zhou Ding Ma Yong Fang Qing-Lei Gao Cancer Biology Research Center(Key Laboratory of the Ministry of Education) Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030 WuhanHubeiChina National Clinical Research Center for Obstetrics and Gynecology Department of Gynecological OncologyTongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030 WuhanHubeiChina Department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030 WuhanHubeiChina Department of Gynecology the Sixth Affiliated HospitalSun Yat-Sen University510000 GuangzhouGuangdongChina

Finely tuned mitogen-activated protein kinase(MAPK)signaling is important for cancer cell *** that push cells out of the MAPK fitness zone result in cell ***,in a screen of the North China Pharmaceutical Group Corporation’s pure compound library of microbial origin,we identified elaiophylin as an autophagy ***,we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum(ER)stress,ER-derived cytoplasmic vacuolization,and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer ***-wide CRISPR/Cas9 knockout library screening identified SHP2,an upstream intermediary of the MAPK pathway,as a critical target in elaiophylin-induced *** cellular thermal shift assay(CETSA)and surface plasmon resonance(SPR)assay further confirmed the direct binding between the SHP2 and *** of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy ***,elaiophylin markedly increased the alreadyelevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK *** overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum,taxane,or PARPi,suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.

关键词： cancer activation elevated

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Membranous NOX5-derived ROS oxidizes and activates local Src to promote malignancy of tumor cells

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1111-1122页

作者： Jie Chen Yan Wang Weimin Zhang Di Zhao Lingyuan Zhang Jiawen Fan Jinting Li Qimin Zhan Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&Institute100142 BeijingChina

Reactive oxygen species(ROS)localized at the precise subcellular compartments are essential for regulating the activity of signaling ***,ROS are master regulators of tumor malignant progression that respond to a diverse set of environmental stress,especially *** oxidases(NOXs)appear to be activated within discrete subcellular compartments to facilitate local ROS ***,the subcellular function of NOXs in hypoxic tumor is still *** this study,we demonstrated that NOX5 was greatly upregulated in clinical esophageal squamous cell carcinoma(ESCC)tumors,ESCC cell lines or primary ESCC cells,and elevated NOX5 was correlated to malignancy of ESCC tumors and poor ***5 induced the malignant progression of ESCC by activating Src,especially under hypoxic ***,we showed that hypoxia promoted the interaction between NOX5 and Pyk2 on cell membrane via facilitating Ca^(2+)-mediated Pyk2 Tyr^(402)site ***,Pyk2 acted as a scaffold for c-Abl phosphorylating the catalytic domain of NOX5 Tyr^(476/478)sites,which in turn upregulated hydrogen peroxide(H_(2)O_(2))inside the Pyk2/NOX5 complex to oxidize and activate local *** findings provide insights into the biological significance of NOX5 in the development of ESCC.

关键词： malignancy elevated esophageal

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Association between clustering of cardiovascular risk factors and resting heart rate in Chinese population:a cross-sectional study

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Journal of Geriatric Cardiology 2022年第6期19卷 418-427页

作者： Fu-Yu JING Xiu-Ling WANG Jia-Li SONG Yan GAO Jian-Lan CUI Wei XU Yang YANG Li-Juan SONG Hai-Bo ZHANG Jia-Peng LU Xi LI Xin ZHENG National Clinical Research Center for Cardiovascular Diseases NHC Key Laboratory of Clinical Research for Cardiovascular MedicationsState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Center for Cardiovascular DiseasesBeijingChina National Clinical Research Center for Cardiovascular Diseases ShenzhenCoronary Artery Disease CenterFuwai Hospital Chinese Academy of Medical SciencesShenzhenChina

BACKGROUND Epidemiologic studies have explored the association between a single cardiovascular risk factor(CVRF)and resting heart rate(RHR),but the research on the relation of multiple risk factors with RHR remains *** study aimed to explore the associations between CVRFs clustering and the risk of elevated *** In this cross-sectional study,adults aged 35-75 years from 31 provinces were recruited by the China PEACE Million Persons Projects from September 2015 to August *** focused on seven risk factors:hypertension,diabetes mellitus,dyslipidemia,obesity,smoking,alcohol use,and low physical *** logistic regression was used to calculate odds ratios(OR)for elevated RHR(>80 beats/min).RESULTS Among 1,045,405 participants,the mean age was 55.67±9.86 years,and 60.4%of participants were *** OR(95%CI)for elevated RHR for the groups with 1,2,3,4 and≥5 risk factor were 1.11(1.08-1.13),1.36(1.33-1.39),1.68(1.64-1.72),2.01(1.96-2.07)and 2.58(2.50-2.67),respectively(Ptrendelevated RHR was much more pronounced in young males than in other age-sex *** comprising more metabolic risk factors were associated with a higher risk of elevated RHR than those comprising more behavioral risk *** There was a significant positive association between the CVRFs clustering number and the risk of elevated RHR,particularly in young *** clusters comprising more behavioral risk factors,clusters comprising more metabolic risk factors were associated with a higher risk of elevated *** may serve as an indicator of the cumulative effect of multiple risk factors.

关键词： elevated cardiovascular sectional

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