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Genes & Diseases 2024年第5期11卷 59-62页

作者： Hongying Zhao Caiyu Zhang Lin Bo Lixia Wang Wangyang Liu Yaopeng Shu Kailai Liu Ying Liu Meiting Fei Li Wang College of Bioinformatics Science and Technology Harbin Medical UniversityHarbinHeilongjiang 150081China Ninth People’s Hospital Shanghai Jiao Tong University School of MedicineShanghai 200125China Shanghai Institute of precision medicine Shanghai 200125China

Enhancer RNAs(eRNAs)are a class of non-coding RNA,which play a critical role in tumor progression.1 Previous studies have indicated abundant CpG methylation,somatic mutation,and copy number variation in eRNA regions in cancers.2,3 We constructed a landscape of genetic alteration-driven eRNAs and provided an integrative pipeline to identify drug candidates that affect eRNA ***,we explored the prognostic value of genetic alteration-driven eRNAs.

关键词： alteration breast targeted

Influence of layer thickness on formation quality,microstructure,mechanical properties,and corrosion resistance of WE43 magnesium alloy fabricated by laser powder bed fusion

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Journal of Magnesium and Alloys 2024年第4期12卷 1367-1385页

作者： Bangzhao Yin Jinge Liu Bo Peng Mengran Zhou Bingchuan Liu Xiaolin Ma Caimei Wang Peng Wen Yun Tian Yufeng Zheng State Key Laboratory of Tribology in Advanced Equipment Beijing100084China Department of Mechanical Engineering Tsinghua UniversityBeijing 100084China Institute for precision medicine Tsinghua UniversityBeijing102218China Department of Orthopaedics Peking University Third HospitalBeijing 100191China Beijing AKEC Medical Co. Ltd.Beijing 102200China School of Materials Science and Engineering Peking UniversityBeijing 100871China Engineering Research Center of Bone and Joint precision medicine Ministry of EducationBeijing 100191China

Laser powder bed fusion(L-PBF)of Mg alloys has provided tremendous opportunities for customized production of aeronautical and medical *** thickness(LT)is of great significance to the L-PBF process but has not been studied for Mg *** this study,WE43 Mg alloy bulk cubes,porous scaffolds,and thin walls with layer thicknesses of 10,20,30,and 40μm were *** required laser energy input increased with increasing layer thickness and was different for the bulk cubes and porous *** tended to occur at the connection joints in porous scaffolds for LT40 and could be eliminated by reducing the laser energy *** thin wall parts,a large overhang angle or a small wall thickness resulted in porosity when a large layer thicknesses was used,and the porosity disappeared by reducing the layer thickness or laser energy input.A deeper keyhole penetration was found in all occasions with porosity,explaining the influence of layer thickness,geometrical structure,and laser energy input on the *** the samples achieved a high fusion quality with a relative density of over 99.5%using the optimized laser energy *** increased layer thickness resulted to more precipitation phases,finer grain sizes and decreased grain *** the similar high fusion quality,the tensile strength and elongation of bulk samples were significantly improved from 257 MPa and 1.41%with the 10μm layer to 287 MPa and 15.12%with the 40μm layer,in accordance with the microstructural *** effect of layer thickness on the compressive properties of porous scaffolds was ***,the corrosion rate of bulk samples accelerated with increasing the layer thickness,mainly attributed to the increased number of precipitation phases.

关键词： Magnesium alloy WE43 Laser powder bed fusion Layer thickness Process optimization

Advances in microfluidic-based DNA methylation analysis

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Nanotechnology and precision Engineering 2024年第1期7卷 116-134页

作者： Jiwen Li Tiechuan Li Xuexin Duan State Key Laboratory of precision Measuring Technology and Instruments Tianjin UniversityTianjin 300072China

DNA methylation has been extensively investigated in recent years,not least because of its known relationship with various *** in analytical methods can greatly increase the relevance of DNA methylation studies to both clinical medicine and scientiﬁc ***ﬂu-idic chips are excellent carriers for molecular analysis,and their use can provide improvements from multiple ***-chip molecular analysis has received extensive attention owing to its advantages of portability,high throughput,low cost,and high efﬁ*** recent years,the use of novel microﬂuidic chips for DNA methylation analysis has been widely reported and has shown obvious superiority to conventional *** this review,weﬁrst focus on DNA methylation and its ***,we discuss advanced microﬂuidic-based methods for DNA methylation analysis and describe the great progress that has been made in recent ***,we summarize the advantages that microﬂuidic technology brings to DNA methylation analysis and describe several challenges and perspectives for on-chip DNA methylation *** review should help researchers improve their understanding and make progress in developing microﬂuidic-based methods for DNA methylation analysis.

关键词： Microﬂuidic chip DNA methylation analysis Molecular analysis High throughput Low cost

β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture

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Bone Research 2024年第2期12卷 302-313页

作者： Jie Huang Tong Wu Yi-Rong Jiang Xuan-Qi Zheng Huan Wang Hao Liu Hong Wang Hui-Jie Leng Dong-Wei Fan Wan-Qiong Yuan Chun-Li Song Department of Orthopedics Peking University Third Hospital100191 BeijingChina Beijing Key Laboratory of Spinal Disease 100191 BeijingChina Engineering Research Center of Bone and Joint precision medicine 100191 BeijingChina

The autonomic nervous system plays a crucial role in regulating bone metabolism,with sympathetic activation stimulating bone resorption and inhibiting bone *** found that fractures lead to increased sympathetic tone,enhanced osteoclast resorption,decreased osteoblast formation,and thus hastened systemic bone loss in ovariectomized(OVX)***,the combined administration of parathyroid hormone(PTH)and theβ-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX *** effect of this treatment is superior to that of treatment with PTH or propranolol *** vitro,the sympathetic neurotransmitter norepinephrine(NE)suppressed PTH-induced osteoblast differentiation and mineralization,which was rescued by ***,NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation,whereas these effects were reversed by ***,PTH increased the expression of the circadian clock gene Bmal1,which was inhibited by NE-βAR ***1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTHstimulated osteoblast *** together,these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.

关键词： blocker metabolism inhibited

Improving the value of molecular testing:current status and opportunities in colorectal cancer precision medicine

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Cancer Biology & medicine 2024年第1期21卷 21-28页

作者： Haiyun Li Linwei Guo Chenchen Wang Xin Hu Ye Xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China precision Cancer Medical Center Affiliated with Fudan University Shanghai Cancer Center Shanghai 201315China

Colorectal cancer(CRC)is the second leading cause of cancer-related deaths *** radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of ***,the transformation of high-throughput sequencing has accelerated the development of precision *** example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in ***,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.

关键词： cancer chemotherapy colorectal

Improving corrosion resistance of additively manufactured WE43 magnesium alloy by high temperature oxidation for biodegradable applications

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Journal of Magnesium and Alloys 2024年第3期12卷 940-953页

作者： Jinge Liu Bangzhao Yin Fei Song Bingchuan Liu Bo Peng Peng Wen Yun Tian Yufeng Zheng Xiaolin Ma Caimei Wang State Key Laboratory of Tribology in Advanced Equipment Beijing100084China Department of Mechanical Engineering Tsinghua UniversityBeijing 100084China Department of Orthopaedics Beijing Tsinghua Changgung HospitalInstitute for Precision MedicineTsinghua UniversityBeijing102218China Department of Orthopaedics Peking University Third HospitalBeijing 100191China Engineering Research Center of Bone and Joint precision medicine Ministry of EducationBeijing 100191China School of Materials Science and Engineering Peking UniversityBeijing 100871China Beijing AKEC Medical Co. Ltd.Beijing 102200China

Laser powder bed fusion(L-PBF)has been employed to additively manufacture WE43 magnesium(Mg)alloy biodegradable implants,but WE43 L-PBF samples exhibit excessively rapid *** this work,dense WE43 L-PBF samples were built with the relativity density reaching 99.9%.High temperature oxidation was performed on the L-PBF samples in circulating air via various heating temperatures and holding *** oxidation and diffusion at the elevated temperature generated a gradient structure composed of an oxide layer at the surface,a transition layer in the middle and the *** oxide layer consisted of rare earth(RE)oxides,and became dense and thick with increasing the holding *** matrix was composed ofα-Mg,RE oxides and Mg_(24)RE_(5) *** precipitates almost disappeared in the transition *** passivation effect was observed in the samples treated by a suitable high temperature *** original L-PBF samples lost 40%weight after 3-day immersion in Hank’s solution,and broke into fragments after 7-day *** casted and solution treated samples lost roughly half of the weight after 28-day *** high temperature oxidation samples,which were heated at 525℃ for 8 h,kept the structural integrity,and lost only 6.88%weight after 28-day *** substantially improved corrosion resistance was contributed to the gradient structure at the *** one hand,the outmost dense layer of RE oxides isolated the corrosive medium;on the other hand,the transition layer considerably inhibited the corrosion owing to the lack of ***,high temperature oxidation provides an efficient,economic and safe approach to inhibit the corrosion of WE43 L-PBF samples,and has promising prospects for future clinical applications.

关键词： Laser powder bed fusion Biodegradable magnesium alloy High temperature oxidation Corrosion resistance WE43.

KHK-A promotes fructose-dependent colorectal cancer liver metastasis by facilitating the phosphorylation and translocation of PKM2

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2959-2976页

作者： Chaofan Peng Peng Yang Dongsheng Zhang Chi Jin Wen Peng Tuo Wang Qingyang Sun Zhihao Chen Yifei Feng Yueming Sun Department of General Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Colorectal Institute of Nanjing Medical University Nanjing 210029China The First School of Clinical medicine Nanjing Medical UniversityNanjing 210029China Jiangsu Province Engineering Research Center of Colorectal Cancer precision medicine and Translational medicine Nanjing 210029China

Excessive fructose diet is closely associated with colorectal cancer(CRC)***,fructose’s specific function and precise mechanism in colorectal cancer liver metastasis(CRLM)is rarely ***,this study reported that the fructose absorbed by primary colorectal cancer could accelerate CRLM,and the expression of KHK-A,not KHK-C,in liver metastasis was higher than in paired primary ***,KHK-A facilitated fructose-dependent CRLM in vitro and in vivo by phosphorylating PKM2 at ***2 phosphorylated by KHK-A inhibited its tetramer formation and pyruvic acid kinase activity but promoted the nuclear accumulation of *** and aerobic glycolysis activated by nuclear PKM2 enhance CRC cells’migration ability and anoikis resistance during CRLM ***-46 treatment,targeting the phosphorylation of PKM2,inhibited the pro-metastatic effect of ***,c-myc activated by nuclear PKM2 promotes alternative splicing of KHK-A,forming a positive feedback loop.

关键词： CRC CRLM Fructose KHK-A PKM2

Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

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Neural Regeneration Research 2024年第6期19卷 1344-1350页

作者： Tianqi Xu Jianhong Yang Yao Xu Xiaofeng Wang Xiang Gao Jie Sun Chenhui Zhou Yi Huang Department of Neurology The First Affiliated Hospital of Ningbo University Department of General Surgery The First Affiliated Hospital of Ningbo University Department of Neurosurgery The First Affiliated Hospital of Ningbo University Key Laboratory of precision medicine for Atherosclerotic Diseases of Zhejiang Province

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation, which is associated with blood-brain barrier disruption. Brain microvascular endothelial cells are a major component of the blood-brain barrier. Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction. In this study, we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells, and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells. We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells. However, post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction. We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier. We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier. In a clinical study, we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation. We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation. These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

关键词： acute ischemic stroke blood-brain barrier brain microvascular endothelial cells mitochondrial transfer stress hyperglycemia

Application of ultrasonography-elastography score to suspect porto-sinusoidal vascular disease in patients with portal vein thrombosis

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 20-24页

作者： Stefania Gioia Adriano De Santis Giulia d’Amati Silvia Nardelli Alessandra Spagnoli Arianna Di Rocco Lorenzo Ridola Oliviero Riggio Department of Translational and precision medicine Sapienza University of RomeRomeItaly Department of Radiological Oncologicaland Pathological SciencesSapienza University of RomeRomeItaly Department of Public Health and Infectious Diseases Sapienza University of RomeRomeItaly

Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal *** PVT may be a consequence of PSVD,in PVT patients at presentation,a pre-existing PSVD should be *** these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management,but it could be *** this setting ultrasonography may be valuable in differential *** aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and“pure”PVT and then to suspect PVT secondary to a pre-existing ***:Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse(ARFI).Results:ARFI was higher and superior mesenteric vein(SMV)diameter was wider in PSVD patients than in PVT ***,a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT(the area under the curve=0.780;95%confidence interval:0.690-0.869).Conclusions:A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.

关键词： Non-cirrhotic portal hypertension Porto-sinusoidal vascular disease Chronic portal vein thrombosis Liver stiffness Portal hypertension Acoustic radiation force impulse

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

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Military Medical Research 2024年第1期11卷 80-97页

作者： Qian-Yun Guo Jia-Qi Yang Xun-Xun Feng Yu-Jie Zhou Beijing Key Laboratory of precision medicine of Coronary Atherosclerotic Disease Beijing Institute of Heart Lung and Blood Vessel DiseaseClinical Center for Coronary Heart DiseaseDepartment of CardiologyBeijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar *** changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health *** personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military *** far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart *** the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart *** have emerged from studies in animal models and early clinical *** interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart *** this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

关键词： Heart regeneration Cardiac disease Therapeutics Signaling mechanisms