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A self-fused hydrogel for the treatment of glottic insufficiency through outstanding durability,extracellular matrix-inducing bioactivity and function preservation

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Bioactive Materials 2023年第6期24卷 54-68页

作者： Chen-Yu Zou Juan-Juan Hu Dan Lu Qian-Jin li Yan-lin Jiang Rui Wang Hai-Yang Wang Xiong-Xin Lei jesse li-ling Hui Yang Hui-Qi Xie Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteMed-X Center for MaterialsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041PR China Department of Otolaryngology Head and Neck SurgeryWest China HospitalSichuan UniversityChengduSichuan610041PR China Department of Medical Genetics West China Second HospitalSichuan UniversityChengduSichuan610041PR China

Injection laryngoplasty with biomaterials is an effective technique to treat glottic insufficiency.However,the inadequate durability,deficient pro-secretion of extracellular matrix(ECM)and poor functional preservation of current biomaterials have yielded an unsatisfactory therapeutic effect.Herein,a self-fusing bioactive hydrogel comprising modified carboxymethyl chitosan and sodium alginate is developed through a dual-crosslinking mechanism(photo-triggered and dynamic covalent bonds).Owing to its characteristic networks,the synergistic effect of the hydrogel for vocal folds(VFs)vibration and phonation is adequately demonstrated.Notably,owing to its inherent bioactivity of polysaccharides,the hydrogel could significantly enhance the secretion of major components(type I/III collagen and elastin)in the lamina propria of the VFs both in vivo and in vitro.In a rabbit model for glottic insufficiency,the optimized hydrogel(C1A1)has demonstrated a durability far superior to that of the commercially made hyaluronic acid(HA)Gel.More importantly,owing to the ECM-inducing bioactivity,the physiological functions of the VFs treated with the C1A1 hydrogel also outperformed that of the HA Gel,and were similar to those of the normal VFs.Taken together,through a simple-yet-effective strategy,the novel hydrogel has demonstrated outstanding durability,ECM-inducing bioactivity and physiological function preservation,therefore has an appealing clinical value for treating glottic insufficiency.

关键词： Glottic insufficiency Self-fusion Hydrogel Extracellular matrix Physiological function

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Multi-crosslinking hydrogels with robust bio-adhesion and pro-coagulant activity for first-aid hemostasis and infected wound healing

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Bioactive Materials 2022年第10期7卷 388-402页

作者： Chen-Yu Zou Xiong-Xin Lei Juan-Juan Hu Yan-lin Jiang Qian-Jin li Yu-Ting Song Qing-Yi Zhang jesse li-ling Hui-Qi Xie Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteMed-X Center for MaterialsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041PR China Department of Otolaryngology Head and Neck SurgeryWest China HospitalSichuan UniversityChengdu610041PR China Department of Medical Genetics West China Second HospitalSichuan UniversityChengdu610041PR China

Bio-adhesive polysaccharide-based hydrogels have attracted much attention in first-aid hemostasis and wound healing for excellent biocompatibility,antibacterial property and pro-healing bioactivity.Yet,the inadequate mechanical properties and bio-adhesion limit their applications.Herein,based on dynamic covalent bonds,photo-triggered covalent bonds and hydrogen bonds,multifunctional bio-adhesive hydrogels comprising modified carboxymethyl chitosan,modified sodium alginate and tannic acid are developed.Multi-crosslinking strategy endows hydrogels with improved strength and flexibility simultaneously.Owing to cohesion enhancement strategy and self-healing ability,considerable bio-adhesion is presented by the hydrogel with a maximal adhesion strength of 162.6 kPa,12.3-fold that of commercial fibrin glue.Based on bio-adhesion and pro-coagulant activity(e.g.,the stimulative aggregation and adhesion of erythrocytes and platelets),the hydrogel reveals superior hemostatic performance in rabbit liver injury model with blood loss of 0.32 g,only 54.2%of that in fibrin glue.The healing efficiency of hydrogel for infected wounds is markedly better than commercial EGF Gel and Ag+Gel due to the enhanced antibacterial and antioxidant properties.Through the multi-crosslinking strategy,the hydrogels show enhanced mechanical properties,fabulous bio-adhesion,superior hemostatic performance and promoting healing ability,thereby have an appealing application value for the first-aid hemostasis and infected wound healing.

关键词： Bio-adhesion First-aid hemostasis Infected wound healing Polysaccharide-based hydrogel Tannic acid

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Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift,postoperative wound closure and rapid healing

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Bioactive Materials 2023年第9期27卷 461-473页

作者： Xiong-Xin Lei Juan-Juan Hu Chen-Yu Zou Yan-lin Jiang Long-Mei Zhao Xiu-Zhen Zhang Ya-Xing li An-Ni Peng Yu-Ting Song li-Ping Huang jesse li-ling Hui-Qi Xie Department of Orthopedic Surgery and Orthopedic Research Institute Laboratory of Stem Cell and Tissue EngineeringState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China Department of Otolaryngology Head and Neck SurgeryWest China HospitalSichuan UniversityChengduSichuan610041China Institute of Biomedical Engineering and Informatics Ilmenau University of TechnologyGustav-Kirchh Off Str.298693IlmenauGermany Department of Medical Genetics West China Second HospitalSichuan UniversityChengduSichuan610041China

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

关键词： Hydrogel Endoscopic submucosal dissection Mucosa uplift Tissue sealant Wound healing

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Application of antibody-conjugated small intestine submucosa to capture urine-derived stem cells for bladder repair in a rabbit model

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Bioactive Materials 2022年第8期7卷 443-455页

作者： Yu-Ting Song Yan-Qing li Mao-Xuan Tian Jun-Gen Hu Xiu-Ru Zhang Peng-Cheng liu Xiu-Zhen Zhang Qing-Yi Zhang li Zhou Long-Mei Zhao jesse li-ling Hui-Qi Xie Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteMed-X Center for MaterialsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China Department of Aesthetic Surgery The People’s Hospital of PengzhouChengduSichuan611930China Surgery of Spine and Spinal Cord Henan Provincial People’s HospitalZhengzhouHenan450000China Department of Burn and Plastic Surgery West China HospitalSichuan UniversityChengduSichuan610041China Research Core Facility of West China Hospital Sichuan UniversityChengduSichuan610041China Department of Medical Genetics and Prenatal Diagnosis West China Second HospitalSichuan UniversityChengduSichuan610041China

The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes.Biomaterials such as submucosa of small intestine(SIS)have been widely used as patches for bladder repair,but the outcomes are not fully satisfactory.To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization.In this study,we have developed an anti-CD29 antibody-conjugated SIS scaffold(AC-SIS)which is capable of specifically capturing urine-derived stem cells(USCs)in situ for tissue repair and regeneration.The scaffold has exhibited effective capture capacity and sound biocompatibility.In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration.The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.

关键词： Regenerative medicine Bladder tissue engineering Scaffold Antibody-conjugated

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Application of metabolomics in urolithiasis:the discovery and usage of succinate

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Signal Transduction and Targeted Therapy 2023年第2期8卷 771-783页

作者： Xiu-zhen Zhang Xiong-xin Lei Yan-lin Jiang Long-mei Zhao Chen-yu Zou Yun-jin Bai Ya-xing li Rui Wang Qian-jin li Qiu-zhu Chen Ming-hui Fan Yu-ting Song Wen-qian Zhang Yi Zhang jesse li-ling Hui-qi Xie Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteDepartment of OrthopedicsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengduSichuan 610041China Research Core Facility of West China Hospital Sichuan UniversityChengduSichuan 610041China Department of Medical Genetics West China Second University HospitalChengduSichuan 610041China

Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events.It has been shown that the occurrence of calcium oxalate monohydrate(COM)during stone formation is regulated by crystal growth modifiers.Although crystallization inhibitors have been recognized as a therapeutic modality for decades,limited progress has been made in the discovery of effective modifiers to intervene with stone disease.In this study,we have used metabolomics technologies,a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model.By in-depth mining and analysis of metabolomics data,we have screened five differential metabolites.Through density functional theory studies and bulk crystallization,we found that three of them(salicyluric,gentisic acid and succinate)could effectively inhibit nucleation in vitro.We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones.Notably,succinate,a key player in the tricarboxylic acid cycle,could decrease kidney calcium deposition and injury in the model.Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation,inhibition of cell adhesion and osteogenic differentiation.These findings indicated that succinate may provide a new therapeutic option for urinary stones.

关键词： crystallization thereby protective

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Identification and characterization of two morphologically distinct stem cell subpopulations from human urine samples

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Science China(life Sciences) 2020年第5期63卷 712-723页

作者： An-Jing Chen Jin-Kui Pi Jun-Gen Hu Yi-Zhou Huang Hong-Wei Gao Sheng-Fu li jesse li-ling Hui-Qi Xie Laboratory of Stem Cell and Tissue Engineering State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengdu 610041China Key Laboratory of Transplant Engineering and Immunology of Ministry of Health West China HospitalSichuan UniversityChengdu 610041China

Urine-derived stem cells(USCs)have shown potentials for the treatment of skeletal and urological disorders.Based on published literature and our own data,USCs consist of heterogeneous populations of cells.In this paper,we identify and characterize two morphologically distinct subpopulations of USCs from human urine samples,named as spindle-shaped USCs(SS-USCs)and rice-shaped USCs(RS-USCs)respectively.The two subpopulations showed similar clone-forming efficiency,while SS-USCs featured faster proliferation,higher motility,and greater potential for osteogenic and adipogenic differentiation,RS-USCs showed greater potential for chondrogenic differentiation.POU5F1 was strongly expressed in both subpopulations,but MYC was weakly expressed.Both subpopulations showed similar patterns of CD24,CD29,CD34,CD44,CD73,CD90 and CD105 expression,while a higher percentage of RS-USCs were positive for CD133.SS-USCs were positive for VIM,weakly positive for SLC12A1 and UMOD,and negative for KRT18,NPHS1,AQP1 and AQP2,indicating a renal mesenchyme origin;while RSUSCs are positive for VIM,partially positive for KRT18,NPHS1,AQP1,SLC12A1 and UMOD,and negative for AQP2,indicating a nephron tubule origin.The above results can facilitate understanding of the biological characteristics of subpopulations of USCs,and provide a basis for further research and applications of such cells.

关键词： characterization cell subpopulation identification tissue origin urine-derived stem cells

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Procyanidins-crosslinked small intestine submucosa: A bladder patch promotes smooth muscle regeneration and bladder function restoration in a rabbit model

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Bioactive Materials 2021年第6期6卷 1827-1838页

作者： Xiu-Zhen Zhang Yan-lin Jiang Jun-Gen Hu Long-Mei Zhao Qiu-Zhu Chen Yan liang Yi Zhang Xiong-Xin Lei Rui Wang Yi Lei Qing-Yi Zhang jesse li-ling Hui-Qi Xie Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduSichuanChina Research Core Facility of West China Hospital Sichuan UniversityChengduSichuanChina

Currently the standard surgical treatment for bladder defects is augmentation cystoplasty with autologous tissues,which has many side effects.Biomaterials such as small intestine submucosa(SIS)can provide an alternative scaffold for the repair as bladder patches.Previous studies have shown that SIS could enhance the capacity and compliance of the bladder,but its application is hindered by issues like limited smooth muscle regeneration and stone formation since the fast degradation and poor mechanical properties of the SIS.Procyanidins(PC),a natural bio-crosslinking agent,has shown anti-calcification,anti-inflammatory and anti-oxidation properties.More importantly,PC and SIS can crosslink through hydrogen bonds,which may endow the material with enhanced mechanical property and stabilized functionalities.In this study,various concentrations of PC-crosslinked SIS(PC-SIS)were prepared to repair the full-thickness bladder defects,with an aim to reduce complications and enhance bladder functions.In vitro assays showed that the crosslinking has conferred the biomaterial with superior mechanical property and anti-calcification property,ability to promote smooth muscle cell adhesion and upregulate functional genes expression.Using a rabbit model with bladder defects,we demonstrated that the PC-SIS scaffold can rapidly promote in situ tissue regrowth and regeneration,in particular smooth muscle remodeling and improvement of urinary functions.The PC-SIS scaffold has therefore provided a promising material for the reconstruction of a functional bladder.

关键词： Bladder reconstruction Small intestinal submucosa Procyanidins Bio-crosslinking Smooth muscle regeneration

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Growth inhibition and apoptosis induction by alternol in pancreatic carcinoma cells

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World Journal of Gastroenterology 2015年第15期21卷 4526-4535页

作者： Pei-Fang Cong Ying-Chun Qu Jie-Peng Chen li-li Duan Cheng-Jiang lin Xiao-lin Zhu jesse li-ling Mei-Xia Zhang Laboratory of Metabolic Disease Research and Drug Development China Medical University Strand Biotechnology Institute of Research Nanchuan Institute of Biological Research Joint Key Laboratory for Bio-resource Research and Utilization of Sichuan and Chongqing

AIM: To investigate the effect of alternol on pancreatic cancer cells.METHODS: Pancreatic cancer cells PANC-1 and Bx PC3 were treated with various concentrations of alternol for 24, 48 and 72 h. Cell proliferation was measured by cell counting. Cell cycle distribution and mitochondrial membrane potential were determined by flow cytometry. Apoptosis was determined by a Td T-mediated d UTP nick end labeling assay and Hoechst staining. Expression of caspase 3, Bcl-2, p53 and p21 was measured by western blotting.RESULTS: Alternol showed dose- and time-dependent inhibition of the proliferation of PANC-1 and Bx PC3 cells in vitro. Alternol induced apoptosis and cell cycle arrest at S phase and decreased mitochondrial membrane potential. Alternol activated caspase 3, upregulated p53 and p21 expression, and downregulated Bcl-2 expression in a dose-dependent manner.CONCLUSION: Our results suggested that alternol is a candidate for treatment of pancreatic cancer.

关键词： Pancreatic cancer Alternol Chemotherapy Cell cycle Apoptosis

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Micro-flow structure at regime transition from bubbling to turbulent fluidization in a fluidized bed

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Particuology 2024年第6期89卷 117-130页

作者： Chaoyu Yan Yue Yuan Xiaoyang Wei jesse Zhu State Key Laboratory of Heavy Oil Processing Beijing Key Laboratory of Process Fluid Filtration and SeparationCollege of Mechanical and Transportation EngineeringChina University of PetroleumBeijing 102249China China Beacons Institute The University of NottinghamNingbo315100China Department of Chemical and Biochemical Engineering University of Western OntarioLondonOntarioN6A 5B9Canada

Gas-solid fluidized beds have found extensive utilization in frontline manufacturing,in particular as low-velocity beds.The fluidization status,the bubbling or turbulent flow regime and the transition in between,determine the system performance in practical applications.Though the convoluted hydrodynamics are quantitively evaluated through numerous data-processing methodologies,none of them alone can reflect all the critical information to identify the transition from the bubbling to the turbulent regime.Accordingly,this study was to exploit a coupling data processing methodology,in the combination of standard deviation,power spectrum density,probability density function,wavelet transform,and wavelet multiresolution method,to jointly explain the micro-flow structure at the regime transition from bubbling to turbulent fluidization.The transient differential pressure fluctuation was measured for the evaluation in a fluidized bed(0.267 m i.d.×2.5 m height)with FCC catalysts(d_(p)=65μm,ρ_(p)=1780kg/m^(3))at different superficial gas velocities(0.02–1.4 m/s).The results show that the onset of turbulent fluidization starts earlier in the top section of the bed than in the bottom section.The wavelet decomposition displays that the fluctuation of differential pressure mainly concentrates on the sub-signals with an intermediate frequency band.These sub-signals could be synthesized into three types of scales(micro-scale,meso-scale,and macro-scale),representing the multi-scale hydrodynamics in the fluidized bed.The micro-scale signal has the characteristic information of bubbling fluidization,and the characteristic information of turbulent fluidization is mainly represented by the meso-scale signal.This work provides a systematic comprehension of fluidization status assessment and serves as an impetus for more coupling analysis in this sector.

关键词： Flow regime transition Bubbling fluidization Turbulent fluidization Micro-flow structure Differential pressure fluctuation

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Coverage and determinants of infant postnatal care in Nigeria: A population-based cross-sectional study

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儿科学研究(英文) 2024年第1期8卷 27-36页

作者： Egbewale Bolaji Emmanuel Oyedeji Olusola Bump jesse Sudfeld Christopher Robert Department of Global Health and Population Takemi Program in International Health Harvard T. H. Chan School of Public Health Boston Massachusetts USA Department of Community Medicine College of Health Sciences Ladoke Akintola University of Technology Ogbomoso Nigeria Department of Pediatrics and Child Health College of Health Sciences Ladoke Akintola University of Technology Ogbomoso Nigeria

Importance: In 2019, Nigeria had the largest number of under-5 child deaths globally and many of these deaths occurred within the first week of life. The World Health Organization recommends infant postnatal care (PNC) attendance to support newborn survival; however, utilization of PNC is known to be low in many contexts.Objective: This study examined coverage and individual-level determinants of infant PNC attendance in Nigeria.Methods: Nigeria Demographic Health Survey (NDHS) 2018 data were used to evaluate infant PNC coverage and determinants. Infant PNC was defined as receipt of care within 2 days of birth. Children delivered up to 2 years before the 2018 NDHS were included. We examined predictors of infant PNC with modified Poisson regression models to estimate relative risks (RRs).Results: The national coverage of infant PNC was 37.3% (95% confidence interval [CI]: 35.8%–38.7%). Significant heterogeneity in PNC attendance existed at state and regional levels. Facility delivery was strongly associated with the uptake of PNC (RR: 6.07; 95% CI: 5.60–6.58). Greater maternal education, maternal employment, urban residence, female head of household, and greater wealth were also associated with an increased likelihood of PNC visits.Interpretation: The uptake of infant PNC is low and interventions are urgently needed to promote equity in access and increase demand for PNC in Nigeria.

关键词： Infant postnatal care Epidemiology Coverage Determinants Nigeria

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