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Engineered stem cells by emerging biomedical stratagems

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Science Bulletin 2024年第2期69卷 248-279页

作者： Jinglin Wang Xiaoxuan Zhang Hanxu Chen Haozhen Ren Min Zhou Yuanjin Zhao Department of Vascular surgery.Nanjing Drum Tower Hospital Affliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Division of Hepatobiliary surgery and Transplantation surgery Department of General SurgeryNanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Shenzhen research Institute Southeast UniversityShenzhen 518038China

Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable *** the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various kinds of stem cells are currently utilized in medical *** the achievements,the therapeutic benefits of stem cells for diseases are limited,and the data of clinical researches are *** optimize tthe effectiveness of stem cells,engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities,paving the way for the next generation of stem cell *** review offers a detailed analysis of engineered stem cells,including their clinical applications and potential for future *** begin by briefly introducing the recent advances in the production of stem cells(induced pluripotent stem cells(ipsCs),embryonic stem cells(ESCs),mesenchymal stem cells(MSCs)and hematopoietic stem cells(HSCs).Furthermore,we present the latest developments of engineered strategies in stem cells,including engineered methods in molecular biology and biomaterial fields,and their application in biomedical ***,we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.

关键词： Stem cells Genetic modification Biomaterials Microfluidics Organ-on-a-chip Bioprinting

Skeletal interoception in osteoarthritis

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Bone research 2024年第2期12卷 241-254页

作者： Dinglong Yang Jiawen Xu Ke Xu Peng Xu Department of Joint surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054China Department of Orthopedic surgery and Orthopedic research Institute West China HospitalSichuan UniversityChengdu 610041China

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the *** its various forms,skeletal interoception specifically regulates the metabolic homeostasis of ***(OA)is a complex joint disorder involving cartilage,subchondral bone,and *** subchondral bone undergoes continuous remodeling to adapt to dynamic joint *** findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone,resulting in subchondral bone sclerosis in *** skeletal interoception is also a potential mechanism for chronic synovial inflammation in *** this review,we offer a general overview of interoception,specifically skeletal interoception,subchondral bone microenviroment and the aberrant subchondral *** also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA,as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

关键词： homeostasis inflammation releasing

Cholangiocarcinoma combined with biliary obstruction:an exosomal circRNA signature for diagnosis and early recurrence monitoring

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2642-2654页

作者： Ningyuan Wen Dingzhong Peng Xianze Xiong Geng Liu Guilin Nie Yaoqun Wang Jianrong Xu Shaofeng Wang Sishu Yang Yuan Tian Bei Li Jiong Lu Nansheng Cheng Division of Biliary surgery Department of General SurgeryWest China HospitalSichuan UniversityChengduSichuanChina research Center for Biliary Diseases West China HospitalSichuan UniversityChengduSichuanChina

Cholangiocarcinoma(CCA)is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic *** present a novel system to monitor CCA using exosomal circular RNA(circRNA)via serum and biliary liquid biopsies.A pilot cohort consisting of patients with CCA-induced biliary obstruction(CCA-BO,n=5)and benign biliary obstruction(BBO,n=5)was used to identify CCA-derived exosomal circRNAs through microarray *** was followed by a discovery cohort(n=20)to further reveal a CCA-specific circRNA complex(hsa-circ-0000367,hsa-circ-0021647,and hsa-circ-0000288)in both bile and serum *** vitro and in vivo studies revealed the three circRNAs as promoters of CCA *** and prognostic models were established and verified by two independent cohorts(training cohort,n=184;validation cohort,n=105).An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature(Bile-DS,AUROC=0.947,RR=6.05)and serum exosomal circRNA signature(Serum-DS,AUROC=0.861,RR=4.04)compared with conventional CA19-9(AUROC=0.759,RR=2.08).A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score,verified with bile samples(Bile-ERS,C-index=0.783)and serum samples(Serum-ERS,C-index=0.782).These models,combined with other prognostic factors revealed by COX-PH model,enabled the establishment of nomograms for recurrence monitoring of *** study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

关键词： biliary diagnosis Serum

Piezoelectric film promotes skin wound healing with enhanced collagen deposition and vessels regeneration via upregulation of PI3K/AKT

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Nano research 2024年第8期17卷 7461-7478页

作者： Qi Xu Wufei Dai Peizhe Li Qinglin Li Zhen Gao Xiaoli Wu Wei Liu Wenbo Wang Department of Plastic and Reconstructive surgery Shanghai Key Laboratory of Tissue EngineeringShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China research Institute of Plastic surgery Shandong Second Medical UniversityWeifang 261000China Department of surgery Air Force Medical CenterPLABeijing 100142China

Skin wounds are common in accidental injuries,and the intricacies of wound repair are closely linked to endogenous electric *** stimulation plays a pivotal role in the restorative processes of skin injuries,encompassing collagen deposition,angiogenesis,inflammation,and *** electrical stimulation therapy replicates and enhances the effects of endogenous wound electric fields by applying an external electric field to the wound site,thereby promoting skin wound *** this study,we developed a self-powered repetitive mechanical impacts-electrical stimulation(RMI-ES)system utilizing a BaTiO3/polydimethylsiloxane(PDMS)piezoelectric composite *** to conventional electrical stimulation devices,the fabricated piezoelectric composite film efficiently harvests energy from the pressure applied by the stimulation device and the tensile force occurring during natural rat *** results demonstrated that piezoelectric stimulation generated by the composite membrane expedited the cell cycle,promoting fibroblast ***,piezoelectric stimulation induced favorable changes in fibroblast gene expression,including increased expression of transforming growth factor-β1(TGF-β1),connective tissue growth factor(CTGF),collagen 1,collagen 3,vascular endothelial growth factor(VEGF),and alpha-smooth muscle actin(α-SMA),while reducing interleukin-6(IL-6)*** analysis revealed that piezoelectric stimulation may induce fibroblast migration,proliferation,and collagen expression by influencing PI3K/AKT serine/threonine kinase(AKT)*** confirmation through the addition of the PI3K inhibitor LY294002 validated that piezoelectric stimulation can regulate the repair process after skin injury through the ***,in vivo results demonstrated that the electric field at the wound site effectively promoted wound healing,reduced inflammation,and stimulated collagen deposition and neova

关键词： BaTiO3/polydimethylsiloxane(PDMS)nano-composite membrane piezoelectrical stimulation skin wound healing collagen deposition PI3K/AKT serine/threonine kinase(AKT)signaling pathway

Identifying coronary artery bypass grafting patients at high risk for adverse long-term prognosis using serial health-related quality of life assessments

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Chinese Medical Journal 2024年第9期137卷 1069-1077页

作者： Juncheng Wang Hanning Liu Chao Yue Limeng Yang Kai Yang Yan Zhao Huan Ren Ying Zhang Zhe Zheng National Clinical research Center for Cardiovascular Diseases State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Cardiovascular surgery Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Vascular surgery Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Cardiac surgery Wuhan Asia Heart HospitalWuhanHubei 430022China

Background:Patients who undergo coronary artery bypass grafting(CABG)are known to be at a significant risk of experiencing long-term adverse events,emphasizing the importance of regular *** health-related quality of life(HRQoL)serves as a direct method to gauge *** objective is to ascertain the prognostic significance of consecutive HRQoL assessments using the Physical Component Summary(PCS)and Mental Component Summary(MCS)derived from the Short-Form 36(SF-36)health survey in CABG ***:The study population consisted of 433 patients who underwent isolated elective CABG at Fuwai Hospital between 2012 and ***-36 assessments were conducted during both the hospitalization period and *** primary endpoint of the study was all-cause mortality,while the secondary outcome was a composite measure including death,myocardial infarction,stroke,and repeat *** assessed the relationships between the PCS and MCS at baseline,as well as their changes during the first 6 months after the surgery(referred to asΔPCS andΔMCS,respectively),and the observed ***:The patients were followed for an average of 6.28 years,during which 35 individuals(35/433,8.1%)*** adjusting for clinical variables,it was observed that baseline MCS scores(hazard ratio[HR]for a 1-standard deviation[SD]decrease,1.57;95%confidence interval[CI],1.07-2.30)andΔMCS(HR for a 1-SD decrease,1.67;95%CI,1.09-2.56)were associated with all-cause ***,baseline PCS scores andΔPCS did not exhibit a significant relationship with all-cause ***,there was a dose-response relationship observed betweenΔMCS and the likelihood of all-cause mortality(HRs for the 2nd,3rd and 4th quartiles compared to the 1st quartile,0.33,0.45 and 0.11,respectively).Conclusions:Baseline MCS and changes in MCS were independent predictors for long-term mortality of *** mental health status and recovery indicated better prognosis.

关键词： Coronary artery bypass grafting Coronary artery disease Prognosis Quality of life Short-Form 36 Risk factor Serial measurements

Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

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Journal of Pharmaceutical Analysis 2024年第2期14卷 196-210页

作者： Mariola Olkowicz Khaled Ramadan Hernando Rosales-Solano Miao Yu Aizhou Wang Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of WaterlooWaterlooONCanada Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian UniversityKrakowPoland Latner Thoracic surgery research Laboratories Toronto General Hospital Research InstituteUniversity Health NetworkTorontoONCanada The Jackson Laboratory JAX Genomic MedicineFarmingtonCTUSA Division of Thoracic surgery Department of SurgeryUniversity Health NetworkUniversity of TorontoToronto Lung Transplant ProgramTorontoONCanada

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

关键词： Pulmonary metastases Colorectal cancer Adjuvant chemotherapy In vivo lung chemo-perfusion Solid-phase microextraction(SPME)microprobes Spatial metabolomics

Garg incontinence scores: New scoring system on the horizon to evaluate fecal incontinence. Will it make a difference?

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World Journal of Gastroenterology 2024年第3期30卷 204-210页

作者： Petr Tsarkov Inna Tulina Parvez Sheikh Darya D Shlyk Pankaj Garg Department of Colorectal surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia Department of Oncologic Colorectal surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia Department of Colorectal surgery Saifee HospitalMumbai 400004MaharashtraIndia Department of Colorectal surgery Garg Fistula Research InstitutePanchkula 134113HaryanaIndia

The main aim of this opinion review is to comment on the recent article published by Garg et al in the World Journal of Gastroenterology 2023;29:4593–*** authors in the published article developed a new scoring system,Garg incon-tinence scores(GIS),for fecal incontinence(FI).FI is a chronic debilitating disease that has a severe negative impact on the quality of life of the *** IV criteria define FI as multiple episodes of solid or liquid stool passed into the clothes at least twice a *** associated social stigmatization often leads to significant under-reporting of the condition,which further impairs *** important point is that the complexity and vagueness of the disease make it difficult for the patients to properly define and report the magnitude of the problem to their *** to this,the management becomes even more *** issue is resolved up to a considerable extent by a scoring *** were several scoring systems in use for the last three *** prominent of them were the Cleveland Clinic scoring system or the Wexner scoring system,*** Hospital or Vaizey’s scores,and the FI severity ***,there were several shortcomings in these scoring *** the opinion review,we tried to analyze the strength of GIS and compare it to the existing scoring *** main pitfalls in the existing scoring systems were that most of them gave equal weightage to different types of FI(solid,liquid,flatus,etc.),were not comprehensive,and took only the surgeon’s perception of FI into *** GIS,almost all shortcomings of previous scoring systems had been addressed:different weights were assigned to different types of FI by a robust statistical methodology;the scoring system was made comprehensive by including all types of FI that were previously omitted(urge,stress and mucus FI)and gave priority to patients’rather than the physicians’perceptions while developing the scoring *** to this,GIS in

关键词： Fecal incontinence Scoring system Urge Stress Flatus

Biomarkers in aortic dissection:Diagnostic and prognostic value from clinical research

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Chinese Medical Journal 2024年第3期137卷 257-269页

作者： Yufei Zhao Weiguo Fu Lixin Wang Department of Vascular surgery Zhongshan HospitalFudan UniversityShanghai 200032China Vascular surgery Institute Zhongshan HospitalFudan UniversityShanghai 200032China National Clinical research Center for Interventional Medicine Zhongshan HospitalFudan UniversityShanghai 200032China Department of Vascular surgery Xiamen BranchZhongshan HospitalFudan UniversityXiamenFujian 361015China

Aortic dissection is a life-threatening condition for which diagnosis mainly relies on imaging examinations,while reliable biomarkers to detect or monitor are still under *** advances in technologies provide an unprecedented opportunity to yield the identification of clinically valuable biomarkers,including proteins,ribonucleic acids(RNAs),and deoxyribonucleic acids(DNAs),for early detection of pathological changes in susceptible patients,rapid diagnosis at the bedside after onset,and a superior therapeutic regimen primarily within the concept of personalized and tailored endovascular therapy for aortic dissection.

关键词： Aortic dissection Biomarker Protein Cell-free DNA miRNA Inflammation Lipid-metabolism

NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 153-164页

作者： Bo Shi Cheng-Jie Lyu Zhen-Kai Le Hao-Sen Ji Yi Xiao Yuan-Yuan Zhang Shou-Jiang Huang Lin-Jun Yu Qiang Shu Jin-Fa Tou Deng-Ming Lai Department of Neonatal surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Pulmonology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Thoracic and Cardiovascular surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China

Background Macrophages are involved in various immune inflammatory disease *** study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western *** pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3^(-/-))model of *** mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various ***,intestinal epithelial cell injuries,and IL-1β release were *** Compared to the gut“healthy”patients,the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3,caspase-1,and IL-1β ***,in vivo,the survival rate of Nlrp3^(-/-)NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC ***3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell *** Macrophage activation may be essential for NEC ***3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.

关键词： Caspase-1 Interleukin-1β Macrophage Necrotizing enterocolitis NLRP3