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Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1665-1674页

作者： Jie Xiong Shu Cheng Xiao Gao Shan-He Yu Yu-Ting Dai Xin-Yun Huang Hui-Juan Zhong Chao-Fu Wang Hong-Mei Yi Hao Zhang Wei-Guo Cao Rong Li Wei Tang Yan Zhao Peng-Peng Xu Li Wang Wei-Li Zhao Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Nuclear Medicine Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Pathology Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Otolaryngology Shanghai Rujin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Radiation Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Hematology Navy Medical Center of PLAShanghaiChina Pole de Recherches Sino-Francais en Science du Vivant et Genomique Laboratory of Molecular PathologyShanghaiChina

Natural killer T cell lymphoma(NKTCL)is highly aggressive,with advanced stage patients poorly responding to intensive *** explore effective and safe treatment for newly diagnosed advanced stage NKTCL,we conducted a phase ll study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab(NCT04096690).Twenty-two patients with a median age of 51 years(range,24-74)were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days,followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 *** complete response and overall response rate after induction treatment were 59%(95%Cl,43-79%)and 68%(95%Cl,47-84%),*** a median follow-up of 30 months,the 2 year progression-free and overall survival rates were 68%(95%Cl,45-83%)and 86%(95%Cl,63-95%),*** most frequently grade 3/4 adverse events were neutropenia(32%,n=7)and hypofibrinogenemia(18%,n=4),which were manageable and led to no discontinuation of *** proportion score of PD-L1,peripheral blood high-density lipoprotein cholesterol,and apolipoprotein A-l correlated with good response,while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab *** conclusion,the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed,advanced stage *** lipid profle and immunosuppressive signature contributed to treatment resistance,providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

关键词： killer metabolism lymphoma

Automated detection of myopic maculopathy from color fundus photographs using deep convolutional neural networks

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Eye and Vision 2024年第4期10卷 11-22页

作者： Jun Li Lilong Wang Yan Gao Qianqian Liang Lingzhi Chen Xiaolei Sun Huaqiang Yang Zhongfang Zhao Lina Meng Shuyue Xue Qing Du zhichun Zhang Chuanfeng LV Haifeng Xu Zhen Guo Guotong Xie Lixin Xie Qingdao Eye Hospital of Shandong First medical University 5 Yanerdao RoadQingdao 266071China State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of OphthalmologyShandong Eye InstituteShandong First Medical University&Shandong Academy of Medical SciencesQingdao 266071China Ping An Healthcare Technology 9F Building BPingAn IFCNo.1-3 Xinyuan South RoadBejing 100027China Shandong Eye Hospital of Shandong First medical University Jinan 250021China Rongcheng Eye Hospital Weihai 264200China Hospital of PLA navy Qingdao 266071China Qilu Hospital of Shandong University(Qingdao) Qingdao 266035China Ping An Healthcare and Technology Company Limited hanghai 200030China ping An International Smart City Technology Company Limited Shenzhen 518000China.

Background:Myopic maculopathy(MM)has become a major cause of visual impairment and blindness worldwide,especially in East Asian *** learning approaches such as deep convolutional neural networks(DCNN)have been successfully applied to identify some common retinal diseases and show great potential for the intelligent analysis of *** study aimed to build a reliable approach for automated detection of MM from retinal fundus images using DCNN ***:A dual-stream DCNN(DCNN-DS)model that perceives features from both original images and corresponding processed images by color histogram distribution optimization method was designed for classification of no MM,tessellated fundus(TF),and pathologic myopia(PM).A total of 36,515 gradable images from four hospitals were used for DCNN model development,and 14,986 gradable images from the other two hospitals for external *** also compared the performance of the DCNN-DS model and four ophthalmologists on 3000 randomly sampledfundus ***:The DCNN-DS model achieved sensitivities of 93.3%and 91.0%,specificities of 99.6%and 98.7%,areas under the receiver operating characteristic curves(AUCs)of 0.998 and 0.994 for detecting PM,whereas sensitivities of 98.8%and 92.8%,specificities of 95.6%and 94.1%,AUCs of 0.986 and 0.970 for detecting TF in two external testing *** the sampled testing dataset,the sensitivities of four ophthalmologists ranged from 88.3%to 95.8%and 81.1%to 89.1%,and the specificities ranged from 95.9%to 99.2%and 77.8%to 97.3%for detecting PM and TF,***,the DCNN-DS model achieved sensitivities of 90.8%and 97.9%and specificities of 99.1%and 94.0%for detecting PMand T,***:The proposed DCNN-DS approach demonstrated reliable performance with high sensitivity,specificity,and AUC to classify different MM levels on fundus photographs sourced from *** can help identify MM automatically among the large myopic groups and show great potenti

关键词： Myopic maculopathy Tessellated fundus Pathologic myopia Deep convolutional neural network Color fundus image

Sorafenib inhibits ossification of the posterior longitudinal ligament by blocking LOXL2-mediated vascularization

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Bone research 2024年第2期12卷 372-389页

作者： Longqing Wang Wenhao Jiang Siyuan Zhao Dong Xie Qing Chen Qi Zhao Hao Wu Jian Luo Lili Yang Spine Center Department of OrthopaedicsShanghai Changzheng HospitalSecond Affiliated Hospital of Naval Medical UniversityShanghai 200003PR China Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center) Tongji University School of MedicineShanghaiPR China Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghaiPR China Department of Orthopaedics No.905 Hospital of PLA NavyShanghaiPR China

Ossification of the Posterior Longitudinal Ligament(OPLL)is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone,resulting in limited spinal mobility and nerve *** both bulk and single-cell RNA sequencing,we elucidate the molecular characteristics,cellular components,and their evolution during the OPLL process at a single-cell resolution,and validate these findings in clinical *** study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in ***,our study identifies LOXL2 as a key regulator in this *** gain-and loss-of-function studies,we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament *** acts via the HIF1A pathway,promoting the secretion of downstream VEGFA and *** function is not related to the enzymatic activity of ***,we identify sorafenib,a broad-spectrum tyrosine kinase inhibitor,as an effective suppressor of LOXL2-mediated vascular *** disrupting the coupling between vascularization and osteogenesis,sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone *** findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.

关键词： LOXL2 ligament finding

Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury:A review

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Chinese Journal of Traumatology 2024年第3期27卷 134-146页

作者： Lin-Fei Cheng Chao-Qun You Cheng Peng Jia-ji Ren Kai Guo Tie-Long Liu medical College.Anhui University of Science and Technology Huainan232000Anhui provinceChina Department of Orthopaedic Oncology Changzheng HospitalNavy Medical UniversityShanghai200003China Department of Orthopaedics The Central Hospital of Shanghai Putuo DistrictShanghai200333China

Spinal cord injury(SCI)is a devastating traumatic disease seriously impairing the quality of life in *** to allow the hopeless central nervous system to repair itself after injury are *** new approaches to regenerate the central nervous system is still the *** derived from mesenchymal stem cells(MSC-Exo)have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI,which are the key processes to rescue damaged spinal cord neurons and restore their ***,MSC-Exo in SCI received scant *** this review,we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying ***,we also focus on the application of exosomes as drug carrier in *** particular,it combs the advantages of exosomes as a drug carrier for SCI,imaging advantages,drug types,loading methods,etc.,which provides the latest progress for exosomes in the treatment of SCI,especially drug carrier.

关键词： Spinal cord injury Mesenchymal stem cell Exosomes Mechanism Drug carrier

Navigating the future of liver disease research:A roadmap for iLIVER

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iLIVER 2024年第1期3卷 1-2页

作者： Lei Cai Ming-Da Wang Tian Yang Institute of Hepatopancreatobiliary Surgery Chongqing General HospitalChongqing UniversityChongqing 401147China Department of Hepatobiliary Surgery Eastern Hepatobiliary Surgery HospitalNavy Medical UniversityShanghai 200438China

The rising global impact of liver disorders,such as non-alcoholic fatty liver disease(NAFLD),viral hepatitis,and hepatocellular carcinoma(HCC),stands as a daunting hurdle in modern *** ailments,now major causes of global morbidity and mortality,exert a profound strain on health systems and affect the life quality of *** World Health Organization's estimates reveal liver conditions lead to around 2 million deaths annually,with viral hepatitis contributing to 1.34 million of these,underscoring the critical need for enhanced research and novel therapeutic ***,the escalating incidence of NAFLD,intertwined with the worldwide obesity crisis,is swiftly rising,affecting about 25%of the global population[1].This surge underscores an urgent call for extensive investigative work across molecular science,clinical applications,and public health initiatives.

关键词： Liver disease Hepatocellular carcinoma Artificial intelligence Liver cancer Non-alcoholic fatty liver disease

Single-cell landscape of malignant ascites frompatients with metastatic colorectal cancer

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Cancer Communications 2024年第7期44卷 713-717页

作者： Haiyang Zhou Jiahui Yin Anqi Wang Xiaomao Yin Taojun Jin Kai Xu Lin Zhu Jiexuan Wang Wenqiang Wang Wei Zhang Xinxiang Li Zhiqian Hu Xinxing Li Division of Colorectal Surgery Changzheng HospitalNavy Medical UniversityShanghaiP.R.China Institute of Higher Education Tongji UniversityShanghaiP.R.China Department of Gastrointestinal Surgery Tongji HospitalTongji University School of MedicineShanghaiP.R.China Department of Gastroenterology Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghaiP.R.China Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiP.R.China

The presence of malignant ascites in colorectal cancer(CRC)patients is associated with a poor prognosis,a high risk of recurrence,and resistance to chemotherapy and immune therapy[1–3].Understanding the complex interactions among different kinds of cells and the ecosystem of peritoneal metastasized colorectal cancer(pmCRC)ascites may provide insights into effective treatment strategies.

关键词： ascites colorectal patients

Enhancing cartilage regeneration and repair through bioactive and biomechanical modification of 3D acellular dermal matrix

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Regenerative Biomaterials 2024年第3期3卷 105-121页

作者： Wei Gao Tan Cheng Zhengya Tang Wenqiang Zhang Yong Xui Min Han Guangdong Zhou Chunsheng Tao Ning Xu Huitang Xia Weijie Sun Qingdao medical College of Qingdao University Qingdao266071China Department of Infectious Diseases The First Affliated Hospital of Anhui Medical UniversityShushanHefei230022China Department of Orthopaedic Surgery Shanghai Sixth People's Hospital Affliated to Shanghai jiao Tong University School of MedicineShanghai200025China Department of Orthopedic Surgery Shanghai Eighth People's HospitalShanghai200235China Department of PlasticSurgery&Jinan Clinicalresearch Center for Tissue Engineering Skin Regeneration and Wound Repair The First Affliated Hospital of Shandong First Medical UniversityJinan266299China Department of Orthopaedics Ninety-seventh Hospital of the Chinese People's Liberation Army NavyQingdao266071China Department of Orthopaedics The First Affliated Hospital of Shandong First Medical UniversityJinan266299China Department of Plastic surgery Shanghai Key Laboratory of Tissue EngineeringShanghai Ninth People's HospitalShanghai jiao Tong University School of MedicineShanghai200023China Department of Thoracic Surgery Shanghai Children's HospitalShanghai Jiao Tong University School of MedicineShaghai200040China Department of Thoracic Surgery Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghai200433China

Acellular dermal matrix(ADM)shows promise for cartilage regeneration and ***,an effective decellularization technique that removes cellular components while preserving the extracellular matrix,the transformation of 2D-ADM into a suitable 3D scaffold with porosity and the enhancement of bioactive and biomechanical properties in the 3D-ADM scaffold are yet to be fully *** this study,we present an innovative decellularization method involving 0.125%trypsin and 0.5%SDS and a 1%Triton X-100 solution for preparing ADM and converting 2D-ADM into 3D-ADM *** scaffolds exhibit favorable physicochemical properties,exceptional biocompatibility and significant potential for driving cartilage regeneration in vitro and in *** further enhance the cartilage regeneration potential of 3D-ADM *** incorporated porcine-derived small intestinal submucosa(SIS)for bioactivity and calcium sulfate hemihydrate(CSH)for biomechanical *** resulting 3D-ADM+SIS scaffolds displayed heightened biological activity,while the 3D-ADM+CSH scaffolds notably bolstered biomechanical *** scaffold types showed promise for cartilage regeneration and repair in vitro and in vivo,with considerable improvements observed in repairing cartilage defects within a rabbit articular cartilage *** summary,this research introduces a versatile 3D-ADM scaffold with customizable bioactive and biomechanical properties,poised to revolutionize the field of cartilageregeneration.

关键词： acellular dermal matrix three-dimensional scaffolds cartilage regeneration small intestinal submucosa calcium sulfate hemihydrate

Subcellular distribution of prohibitin 1 in rat liver during liver regeneration and its cellular implication

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World Journal of Hepatology 2024年第1期16卷 65-74页

作者： Qing-Ju Sun Tao Liu Department of Clinical Laboratory Navy No.971 HospitalQingdao 266072Shandong ProvinceChina Department of Infectious Diseases Navy No.971 HospitalQingdao 266071Shandong ProvinceChina

BACKGROUND The function of prohibitin 1(Phb1)during liver regeneration(LR)remains relatively *** previous research identified downregulation of Phb1 in rat liver mitochondria 24 h after 70%partial hepatectomy(PHx),as determined by subcellular proteomic *** To investigate the potential role of Phb1 during *** We examined changes in Phb1 mRNA and protein levels,subcellular distribution,and abundance in rat liver during LR following 70%*** also evaluated mitochondrial changes and apoptosis using electron microscopy and flow ***-interference-mediated knockdown of Phb1(PHBi)was performed in BRL-3A *** Compared with sham-operation control groups,Phb1 mRNA and protein levels in 70%PHx test groups were downregulated at 24 h,then upregulated at 72 and 168 ***1 was mainly located in mitochondria,showed a reduced abundance at 24 h,significantly increased at 72 h,and almost recovered to normal at 168 ***1 was also present in nuclei,with continuous increase in abundance observed 72 and 168 h after 70%*** altered ultrastructure and reduced mass of mitochondria during LR had almost completely recovered to normal at 168 *** in BRL-3A cells resulted in increased S-phase entry,a higher number of apoptotic cells,and disruption of mitochondrial membrane *** Phb1 may contribute to maintaining mitochondrial stability and could play a role in regulating cell proliferation and apoptosis of rat liver cells during LR.

关键词： Prohibitin 1 Liver regeneration Subcellular proteomic analysis Mitochondrial stability Cell proliferation

Effectiveness of a theory-based tailored mHealth physical activity intervention for women undergoing chemotherapy for breast cancer:A quasi-experimental study

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International Journal of Nursing Sciences 2024年第4期11卷 405-413页

作者： Zhaohui Geng Jingting Wang Weibo Lyu Xinyu Li Wenjia Ye Wei Zheng Juan Yang Li Ning Lingzhi Cai Ying Liu Yingting Zhang Fulei Wu Changrong Yuan School of Nursing Shanghai University of Traditional Chinese MedicineShanghaiChina School of Nursing Navy Medical UniversityShanghaiChina Department of Breast Surgery Longhua HospitalShanghai University of Traditional Chinese MedicineShanghaiChina Department of Breast Surgery Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of Nursing Hangzhou First People’s HospitalHangzhouChina Department of Breast Surgery Hangzhou First People’s HospitalHangzhouChina Department of Nursing Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghaiChina School of Nursing Fudan UniversityShanghaiChina

Objectives:This study aimed to explore the effectiveness of the theory-based tailored mHealth physical activity(PA)intervention among patients with breast cancer undergoing ***:A quasi-experimental study design was adopted.A total of 60 breast cancer patients were selected from two tertiary hospitals in Shanghai and Hangzhou City from September 2019 to August *** to the admission order,30 patients wereﬁrst included in the control group,followed by 30 patients in the intervention group.A smartphone application(app)named“Breast Care”was developed based on social cognitive theory,self-efﬁcacy theory,and the theory of planned *** app integrated various functions,including information browsing,PA monitoring and feedback,symptom reporting,and social *** in the intervention group received three months of personalized online PA guidance in addition to routine *** control group received routine *** and post-intervention investigations after three months were conducted in two groups using the Short Form of International Physical Activity Questionnaire,the Hospital Anxiety and Depression Scale,and the Functional Assessment of Cancer TherapydBreast ***:After three months of intervention,compared to the control group,breast cancer patients in the intervention group showed signiﬁcant improvements in walking,moderate PA,and overall PA(P<0.05).Compared to the baseline data,breast cancer patients in the intervention group had signiﬁcant improvements in walking and overall PA after three months(P<0.05),whereas the control group experienced signiﬁcant declines in walking,moderate PA,and overall PA after three months(P<0.05).There were statistically differences between the two groups in scores for anxiety,overall quality of life,and its dimensions,such as physical well-being,emotional well-being,and additional breast cancer well-being(P<0.05).Conclusions:The theory-based tailored mHealth PA intervention has

关键词： Anxiety Breast cancer Chemotherapy Depression Patients Physical activity Telemedicine