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Clinical applications of stem cell-derived exosomes

Signal Transduction and Targeted Therapy 2024年第2期9卷 621-651页

作者： Fei Tan Xuran Li Zhao Wang Jiaojiao Li Khawar Shahzad Jialin Zheng department of ORL-HNS Shanghai Fourth People’s Hospitaland School of MedicineTongji UniversityShanghaiChina Plasma medicine and Surgical Implants Center Tongji UniversityShanghaiChina The Royal College of Surgeons in Ireland DublinIreland The Royal College of Surgeons of England LondonUK Center for translational Neurodegeneration and Regenerative Therapy Tongji Hospital affiliated to Tongji University School of MedicineShanghaiChina Shanghai Frontiers Science Center of Nanocatalytic medicine Tongji UniversityShanghaiChina

Although stem cell-based therapy has demonstrated considerable potential to manage certain diseases more successfully than conventional surgery,it nevertheless comes with inescapable drawbacks that might limit its clinical *** to stem cells,stem cell-derived exosomes possess numerous advantages,such as non-immunogenicity,non-infusion toxicity,easy access,effortless preservation,and freedom from tumorigenic potential and ethical *** can inherit similar therapeutic effects from their parental cells such as embryonic stem cells and adult stem cells through vertical delivery of their pluripotency or *** a thorough search and meticulous dissection of relevant literature from the last five years,we present this comprehensive,up-to-date,specialty-specific and disease-oriented review to highlight the surgical application and potential of stem cell-derived *** derived from stem cells(e.g.,embryonic,induced pluripotent,hematopoietic,mesenchymal,neural,and endothelial stem cells)are capable of treating numerous diseases encountered in orthopedic surgery,neurosurgery,plastic surgery,general surgery,cardiothoracic surgery,urology,head and neck surgery,ophthalmology,and obstetrics and *** diverse therapeutic effects of stem cells-derived exosomes are a hierarchical translation through tissue-specific responses,and cell-specific molecular signaling *** this review,we highlight stem cell-derived exosomes as a viable and potent alternative to stem cell-based therapy in managing various surgical *** recommend that future research combines wisdoms from surgeons,nanomedicine practitioners,and stem cell researchers in this relevant and intriguing research area.

关键词： viable stem capable

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Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

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Chinese Journal of Cancer Research 2024年第2期36卷 124-137页

作者： Jialin Zhang Gengshen Yin Chunmiao Ye Man Feng Changhua Ji Wenzhong Zhou Fei Wang Lixiang Yu Shuya Huang Zhigang Yu department of Breast Surgery the Second Hospital of Shandong UniversityJinan 250033China Institute of translational medicine of Breast Disease Prevention and Treatment Shandong UniversityJinan 250033China Shandong Provincial Engineering Laboratory of translational Research on Prevention and Treatment of Breast Disease Jinan 250033China department of Pathology the Third Affiliated Hospital of Shandong First Medical University(Affiliated Hospital of Shandong Academy of Medical Sciences)Jinan 250031China department of Pathology the Second Hospital of Shandong UniversityJinan 250033China

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is ***: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to ***: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft ***: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance

关键词： Breast cancer HER2 pyrotinib trastuzumab primary resistance pertuzumab

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A Transformer-Assisted Cascade Learning Network for Choroidal Vessel Segmentation

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Journal of Computer Science & Technology 2024年第2期39卷 286-304页

作者：温阳吴依林毕磊石武祯刘潇骁许毓鹏许迅曹文明冯大淦 Guangdong Provincial Key Laboratory of Intelligent Information Processing School of Electronics and Information EngineeringShenzhen UniversityShenzhen 518060China Institute of translational medicine Shanghai Jiao Tong UniversityShanghai 200240China department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China School of Information Technologies The University of SydneySydney 2006Australia

As a highly vascular eye part,the choroid is crucial in various eye disease ***,limited research has focused on the inner structure of the choroid due to the challenges in obtaining sufficient accurate label data,particularly for the choroidal ***,the existing direct choroidal vessel segmentation methods for the intelligent diagnosis of vascular assisted ophthalmic diseases are still unsatisfactory due to noise data,while the synergistic segmentation methods compromise vessel segmentation performance for the choroid layer segmentation *** cascaded structures grapple with error propagation during *** address these challenges,we propose a cascade learning segmentation method for the inner vessel structures of the choroid in this ***,we propose TransformerAssisted Cascade Learning Network(TACLNet)for choroidal vessel segmentation,which comprises a two-stage training strategy:pre-training for choroid layer segmentation and joint training for choroid layer and choroidal vessel *** also enhance the skip connection structures by introducing a multi-scale subtraction connection module designated as MSC,capturing differential and detailed information ***,we implement an auxiliary Transformer branch named ATB to integrate global features into the segmentation *** results exhibit that our method achieves the state-of-the-art performance for choroidal vessel ***,we further validate the significant superiority of the proposed method for retinal fluid segmentation in optical coherence tomography(OCT)scans on a publicly available *** these fully prove that our TACLNet contributes to the advancement of choroidal vessel segmentation and is of great significance for ophthalmic research and clinical application.

关键词： choroidal vessel segmentation optical coherence tomography(OCT) Transformer-assisted cascade learning retinal fluid segmentation multi-scale feature extraction

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Mesenchymal stem cells’“garbage bags”at work:Treating radial nerve injury with mesenchymal stem cell-derived exosomes

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World Journal of Stem Cells 2024年第5期16卷 467-478页

作者： Mazhar Mushtaq Doaa Hussein Zineldeen Muhammad Abdul Mateen Khawaja Husnain Haider department of Basic Sciences Sulaiman AlRajhi UniversityAlbukairiyah 52736AlQaseemSaudi Arabia Medical Biochemistry and molecular Biology department Faculty of MedicineTanta UniversityTanta 6632110Egypt

Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal ***,structural and functional recovery is a senile process involving multifaceted cellular and molecular *** contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large *** advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic *** recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.

关键词： Exosome Mesenchymal stem cells Nerve injury Stem cells Secretome Regeneration

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Efficacy and safety of extracorporeal shock wave therapy combined with sodium hyaluronate in treatment of knee osteoarthritis:a systematic review and Meta-analysis

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Journal of Traditional Chinese medicine 2024年第2期44卷 243-250页

作者： ZHOU Mingwang DONG Zhuanli WEI Changhao FENG Lufang WANG Xiaoping LIU Haiping JI Xing YANG Kehu LI Shenghua department of Orthopaedics Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050China department of Quality Management Lanzhou Petrochemical General HospitalLanzhou 730050China department of Orthopaedics Lanzhou Petrochemical General HospitalLanzhou 730050China Evidence-Based Social Science Research Center School of Public HealthLanzhou UniversityLanzhou730000China Evidence-Based medicine Center School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China Key Laboratory of Evidence Based medicine and Knowledge Translation of Gansu Province Lanzhou 730000China Center for translational medicine Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050China department of Orthopaedics Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730000China

OBJECTIVE:To assess the efficacy and safety of extracorporeal shockwave therapy(ESWT)combined with sodium hyaluronate(HA)for the treatment of knee osteoarthritis(KOA).METHODS:PubM ed,Embase,the Cochrane Library,Web of Science,China National Knowledge Infrastructure,Wanfang database,China Science and Technology Journal Database,and SinoMed were searched from inception to July *** quality of the randomized controlled trials was evaluated independently by two reviewers according to the criteria in the Cochrane Collaboration for Systematic *** identified articles were then screened individually using EndnoteX9 for eligibility in this *** heterogeneity among the articles was evaluated using ***:A total of 17 studies,comprising 2000 individuals,were included in this *** results showed that a significant improvement was observed in knee pain and function based on the clinical efficacy of ESWT combined with *** analysis of clinical efficacy showed that[relative risk(RR)=1.21,95%confidence interval(CI)(1.12,1.30),P<0.01].Statistical analysis of visual analog scale showed that[standardized mean difference(SMD)=-2.84,95%CI(-4.01,-1.66),P<0.01].Western Ontario and McMaster University osteoarthritis index statistical analysis showed that[SMD=-1.57,95%CI(-2.52,-0.61),P<0.01].Lysholm score statistical analysis showed that[SMD=1.71,95%CI(0.98,2.44),P<0.01].In addition,only minor side effects,such as redness and swelling of the skin,were ***:Medium to low quality evidence showed that ESWT combined with HA offers an inexpensive,welltolerated,safe,and effective method to improve pain and functionality in patients with ***,tightly controlled,randomized,large multicenter trials are warranted to validate the current findings.

关键词： osteoarthritis knee randomized controlled trial extracorporeal shockwave therapy hyaluronic acid Meta-analysis

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Helicobacter pylori and immunotherapy for gastrointestinal cancer

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The Innovation 2024年第2期5卷 51-60页

作者： Keren Jia Yang Chen Yi Xie Xicheng Wang Yajie Hu Yu Sun Yanshuo Cao Liyan Zhang Yakun Wang Zhenghang Wang Zhihao Lu Jian Li Xiaotian Zhang Lin Shen Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and translational Research(Ministry of Education/Beijing) Department of PathologyPeking University Cancer Hospital&InstituteBeijing 100142China

Helicobacter pylori infection is associated with the risk of gastrointestinal(GI)cancers;however,its impact on immunotherapy for GI cancers remains *** this study,we included 10,122 patients who underwent ^(13)C-urea breath *** 636 patients with Epstein-Barr virus–negative microsatellite-stable gastric cancer(GC)who were treated with anti-PD-1/PD-L1 therapy,***–positive patients exhibited significantly longer immune-related progression-free survival(irPFS)compared with ***–negative patients(6.97 months versus 5.03 months,pmolecular characteristics similar to those of immunotherapy-sensitive ***,***–positive patients with DNA mismatch repair–deficient(dMMR)/microsatellite instability–high(MSI-H)colorectal adenocarcinoma and esophageal squamous cell carcinoma(ESCC)had shorter irPFS compared with ***–negative patients(16.13 months versus not reached,p=0.042,HR 2.26,95%CI 1.13–4.50,p=0.021 and 5.57 months versus 6.97 months,p=0.029,HR 1.59,95%CI 1.14–2.23,p=0.006,respectively).The difference in irOS between ***–positive and–negative patients had the same trend as that between dMMR/MSI-H colorectal adenocarcinoma and ESCC *** also identified a trend of shorter irPFS and irOS in ***–positive liver cancer and pancreatic cancer *** summary,our findings supported that *** infection is a beneficial factor for GC immunotherapy by shaping hot tumor ***,in dMMR/MSI-H colorectal adenocarcinoma and ESCC patients,*** adversely affects the efficacy of immunothera

关键词： immunotherapy gastrointestinal pylori

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OsPDR20 is an ABCG metal transporter regulating cadmium accumulation in rice

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Journal of Environmental Sciences 2024年第2期136卷 21-34页

作者： He Li Chao Li Di Sun Zhi Min Yang department of Biochemistry and molecular Biology College of Life SciencesNanjing Agricultural UniversityNanjing 210095China

Cadmium(Cd)is a non-essential toxic heavy metal,seriously posing high environmental risks to human *** genetic resources relevant to functional genes is important for understanding the metal absorption and accumulation in crops and bioremediation of Cd-polluted *** study investigated a functionally uncharacterized ATP binding cassette transporter G family(ABCG)gene encoding a Pleiotropic Drug Resistance 20(PDR20)type metal transporter which is localized to the plasma membrane of ***20 was transcriptionally expressed in almost all tissues and organs in lifespan and was strongly induced in roots and shoots of young rice under Cd *** expression of OsPDR20 in a yeast mutant ycf1 sensitive to Cd conferred cellular tolerance with less Cd *** of OsPDR20 by RNA interference(RNAi)moderately attenuated root/shoot elongation and biomass,with reduced chlorophylls in rice grown under hydroponic medium with 2 and 10μmol/L Cd,but led to more Cd accumulation.A field trial of rice grown in a realistic Cd-contaminated soil(0.40 mg/kg)showed that RNAi plants growth and development were also compromised compared to wild-type(WT),with smaller panicles and lower spikelet fertility but little effect on yield of ***,OsPDR20 suppression resulted in unexpectedly higher levels of Cd accumulation in rice straw including lower leaves and culm and *** results suggest that OsPDR20 is actively involved in Cd accumulation and homeostasis in rice *** increased Cd accumulation in the RNAi plants has the potential application in phytoremediation of Cd-polluted wetland soils.

关键词： Rice ABCG transporter Cadmium accumulation Phytoremediation

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Alternative splicing and related RNA binding proteins in human health and disease

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Signal Transduction and Targeted Therapy 2024年第3期9卷 839-871页

作者： Yining Tao Qi Zhang Haoyu Wang Xiyu Yang Haoran Mu department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of Medicine200000 ShanghaiChina Shanghai Bone Tumor Institution 200000 ShanghaiChina department of Biochemistry and molecular Cell Biology Shanghai Key Laboratory for Tumor Microenvironment and InflammationShanghai Jiao Tong University School of Medicine200000 ShanghaiChina

Alternative splicing(AS)serves as a pivotal mechanism in transcriptional regulation,engendering transcript diversity,and modifications in protein structure and *** varying tissues,developmental stages,or under specific conditions,AS gives rise to distinct splice *** implies that these isoforms possess unique temporal and spatial roles,thereby associating AS with standard biological activities and *** these,AS-related RNA-binding proteins(RBPs)play an instrumental role in regulating alternative splicing *** physiological conditions,the diversity of proteins mediated by AS influences the structure,function,interaction,and localization of proteins,thereby participating in the differentiation and development of an array of tissues and *** pathological conditions,alterations in AS are linked with various diseases,particularly *** changes can lead to modifications in gene splicing patterns,culminating in changes or loss of protein *** instance,in cancer,abnormalities in AS and RBPs may result in aberrant expression of cancer-associated genes,thereby promoting the onset and progression of *** and RBPs are also associated with numerous neurodegenerative diseases and autoimmune ***,the study of AS across different tissues holds significant *** review provides a detailed account of the recent advancements in the study of alternative splicing and AS-related RNA-binding proteins in tissue development and diseases,which aids in deepening the understanding of gene expression complexity and offers new insights and methodologies for precision medicine.

关键词： organs alterations thereby

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Interparticle energy transfer between NaNdF_(4) and NaYbF_(4) in self-assembled nanostructures

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Journal of Rare Earths 2024年第6期42卷 1029-1035,I0001页

作者： Xinyu Chen Haoze Yang Yuyang Gu Chenqing Wen Yishuo Sun Jiaming Ke Wei Feng department of Chemistry and State Key Laboratory of molecular Engineering of Polymers Fudan University Shanghai200433China

Forster resonance energy transfer(FRET)is a widely used spectroscopic *** development of donor-acceptor combinations is essential to advance this *** make the energy transfer efficiency independent of the external environment,we explored the potential of constructing donor—acceptor combinations with lanthanide ion-doped nanoparticles(LNPs),in which the 4f electrons of the lanthanide ions are shielded by the 5s and 6p ***-radiative energy transfer between LNPs was demonstrated in self-assembled nanostructures and core-shell structure of LNPs was used to control the distance between donor and acceptor in self-assembled *** emission intensity ratio of donor and acceptor illustrates that the energy transfer efficiency decreases significantly with increasing distance and the effective energy transfer distance is 8.5 nm,showing the potential of using LNPs as donor-acceptor pairs in the construction of distance-dependent energy transfer system.

关键词： Lanthanide nanoparticles Self-assembly Energy transfer Distance Epitaxialgrowth Rare earths

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SARS-CoV-2 triggers Dickkopf-1(Dkk-1)modulation of T helper cells and lung pathology in mice

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Genes & Diseases 2024年第4期11卷 9-12页

作者： Yifan Wu Freedom M.Green Stephen A.Shaw Lauren J.Bonilla Shannon E.Ronca Maria Elena Bottazzi Farrah Kheradmand Jill E.Weatherhead department of Pathology&Immunology One Baylor PlazaHoustonTX 77030USA department of Pediatrics One Baylor PlazaHoustonTX 77030USA department of medicine One Baylor PlazaHoustonTX 77030USA National School of Tropical medicine One Baylor PlazaHoustonTX 77030USA molecular Virology&Microbiology One Baylor PlazaHoustonTX77030USA Biologyof Inflammation Center Baylor College of MedicineOne BaylorPlazaHoustonTX77030USA Michael E.DeBakey VA Center for translational Research on Inflammatory Diseases HoustonTX 77030USA

Severe acute respiratory syndrome coronavirus 2(SARSCov-2)is the etiologic agent of the coronavirus disease 19(COVID-19)*** viral infections like SARS-CoV-2,a robust anti-viral type 1 immune response,including upregulation of type 1 CD4+T helper cells(Th1),is required for effective viral clearance while minimizing end-organ pathology and collateral tissue damage.

关键词： pathology acute respiratory

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