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DAPK2 promotes autophagy to accelerate the progression of ossification of the posterior longitudinal ligament through the mTORC1 complex

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BIOCELL 2024年第9期48卷 1389-1400页

作者： Shi, Lei Yin, Jianshi Chen, Yu Shi, Jiangang Miao, Jinhao shanghai changzheng hosp Dept Spine Surg Shanghai 200003 Peoples R China Chinese Peoples Liberat Army Hosp 967 Dept Orthoped Dalian 116000 Peoples R China

Background: Ossification of the posterior longitudinal ligament (OPLL) is a prevalent condition in orthopedics. While death-associated protein kinase 2 (DAPK2) is known to play roles in cellular apoptosis and autophagy, its specific contributions to the advancement of OPLL are not well understood. Methods: Ligament fibroblasts were harvested from patients diagnosed with OPLL. Techniques such as real-time reverse transcriptasepolymerase chain reaction (RT-qPCR) and Western blot analysis were employed to assess DAPK2 levels in both ligament tissues and cultured fibroblasts. The extent of osteogenic differentiation in these cells was evaluated using an alizarin red S (ARS) staining. Additionally, the expression of ossification markers and autophagy markers was quantified. The autophagic activity was further analyzed through LC3 immunofluorescence and transmission electron microscopy (TEM). An in vivo heterotopic bone formation assay was conducted in mice to assess the role of DAPK2 in ossification. Results: Elevated DAPK2 expression was confirmed in both OPLL patient tissues and derived fibroblasts, in contrast to non-OPLL controls. Silencing of DAPK2 significantly curtailed osteogenic differentiation and autophagy in these fibroblasts, evidenced by decreased levels of LC3, and Beclin1, and reduced autophagosome formation. Additionally, DAPK2 was found to inhibit the mechanistic target of the rapamycin complex 1 (mTORC1) complex's activity. In vivo studies demonstrated that DAPK2 facilitates ossification, and this effect could be counteracted by the mTORC1 inhibitor rapamycin. Conclusion: DAPK2 enhances autophagy and osteogenic processes in OPLL through modulation of the mTORC1 pathway.

关键词： Ossification fi cation of the posterior longitudinal ligament DAPK2 Autophagy mTORC1 IMPACT

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Flexible polydimethylsiloxane pressure sensor with micro-pyramid structures and embedded silver nanowires: A novel application in urinary flow measurement

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NANOTECHNOLOGY AND PRECISION ENGINEERING 2024年第3期7卷 1-12页

作者： Wang, Ben-Song Gao, Ang Huang, Song-Wei Ning, Qi-Hong Zhou, Cheng Song, Qi-Xiang Cui, Da-Xiang shanghai Jiao Tong Univ Sch Elect Informat & Elect Engn Shanghai 200240 Peoples R China shanghai Jiao Tong Univ Renji Hosp Sch Med Dept Urol Shanghai 200240 Peoples R China

Flexible pressure sensors are lightweight and highly sensitive, making them suitable for use in small portable devices to achieve precise measurements of tiny forces. This article introduces a low-cost and easy-fabrication strategy for piezoresistive flexible pressure sensors. By embedding silver nanowires into a polydimethylsiloxane layer with micro-pyramids on its surface, a flexible pressure sensor is created that can detect low pressure (17.3 Pa) with fast response (<20 ms) and high sensitivity (69.6 mA kPa(-1)). Furthermore, the pressure sensor exhibits a sensitive and stable response to a small amount of water flowing on its surface. On this basis, the flexible pressure sensor is innovatively combined with a micro-rotor to fabricate a novel urinary flow-rate meter (uroflowmeter), and results from a simulated human urination experiment show that the uroflowmeter accurately captured all the essential shape characteristics that were present in the pump-simulated urination curves. Looking ahead, this research provides a new reference for using flexible pressure sensors in urinary flow-rate monitoring.

关键词： Flexible pressure sensor Silver nanowires Portable device Uroflowmeter Healthcare HIGH-PERFORMANCE UROFLOWMETRY SYMPTOMS

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World Federation of Acupuncture-Moxibustion Societies (WFAS) Technical Benchmark of Acupuncture and Moxibustion: Filiform Needle

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WORLD JOURNAL OF ACUPUNCTURE-MOXIBUSTION 2024年第3期34卷 231-236页

作者： Zhou, Liang Zhang, Si-qi Fang, Meng Dong, Gui-rong Dong, Hong-sheng shanghai Univ Tradit Chinese Med Yueyang Hosp Integrated Tradit Chinese & Western M Shanghai 200437 Peoples R China shanghai Res Inst Acupuncture & Meridian Shanghai 200030 Peoples R China

On December 31, 2023, World Federation of Acupuncture-Moxibustion Societies (WFAS) officially issued Technical Benchmark of Acupuncture and Moxibustion: Filiform Needle. This technical benchmark clarifies terms and definitions, operating procedures and requirements, safety requirements, etc. The promulgation and implementation of this technical benchmark would provide a standard for acupuncture practitioners to apply filiform needle in clinical practice, and may play a positive role in the safe use and promotion of filiform needle. (c) 2024 World Journal of Acupuncture - Moxibustion House. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license ( http://***/licenses/by-nc-nd/4.0/ )

关键词： Acupuncture Filiform needle Academic organization International standards Technical operation Specification

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Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation

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ACTA PHARMACEUTICA SINICA B 2024年第9期14卷 3916-3930页

作者： Mou, Zezhong Chen, Yiling Hu, Jinzhong Hu, Yun Zou, Lujia Chen, Xinan Liu, Shenghua Yin, Qiuping Gong, Jian Li, Shuchen Mao, Shanhua Xu, Chenyang Jiang, Haowen Fudan Univ Huashan Hosp Dept Urol Shanghai 200040 Peoples R China Fudan Univ Fudan Inst Urol Shanghai 200040 Peoples R China Fudan Univ Natl Clin Res Ctr Aging & Med Shanghai 200040 Peoples R China

Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer. In the tumor microenvironment, negative regulatory molecules and various immune cell subtypes suppress antitumor immunity. The inflammatory microenvironment, associated with neutrophils and neutrophil extracellular traps (NETs), promotes tumor metastasis. However, no drugs are currently available to specifically inhibit neutrophils and NETs. In this study, we first demonstrated that icaritin (ICT), a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma, reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment. Mechanistically, ICT binds to and inhibits the expression of PADI2 in neutrophils, thereby suppressing PADI2-mediated histone citrullination. Moreover, ICT inhibits ROS generation, suppresses the MAPK signaling pathway, and inhibits NET-induced tumor metastasis. Simultaneously, ICT inhibits tumoral PADI2-mediated histone citrullination, which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6. The downregulation of IL-6 expression, in turn, forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis. Through a retrospective study of clinical samples, we found a correlation between neutrophils, NETs, UCa prognosis, and immune evasion. Combining ICT with immune checkpoint inhibitors may have synergistic effects. In summary, our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： Icaritin Neutrophil Neutrophil extracellular trap PADI2 Urothelial cancer

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Full process of recommendation formulation for clinical practice guidelines: Taking World Federation of Acupuncture-Moxibustion Societies Clinical Practice Guideline on Acupuncture and Moxibustion: Allergic Rhinitis as an example

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WORLD JOURNAL OF ACUPUNCTURE-MOXIBUSTION 2024年第3期34卷 252-257页

作者： Yang, Chao Wang, Guan-qun Chen, Sheng Du, Shuo Wang, Shan-ze Xie, Xiao-long Peng, Bi-hui Guo, Wei Du, Shi-hao Zhao, Ji-ping Beijing Univ Chinese Med Dongzhimen Hosp Dept Acupuncture & Moxibust Beijing Peoples R China China Acad Chinese Med Sci Inst Acupuncture & Moxibust Beijing 100700 Peoples R China Guangdong Prov hosp Chinese Med Dept Acupuncture & Moxibust Guangzhou 510120 Peoples R China shanghai Jiao Tong Univ Shanghai Peoples Hosp 9 Sch Med Dept Tradit Chinese Med Shanghai 200011 Peoples R China

The formulation of recommendations is a crucial step in the development of clinical practice guidelines, which requires tools provided by the GRADE methodology. These tools include the evidence quality assessment tool, the evidence summary tool, and the evidence-to-decision (EtD) framework. Although there is a methodologically guided standard pathway for formulating recommendations in clinical practice guidelines, it remains unclear how to translate this theoretical pathway into the practical process for formulating recommendations and what the specific steps in this process entail. Therefore, this paper takes the World Federation of Acupuncture-Moxibustion Societies Clinical Practice Guidelines on Acupuncture and Moxibustion: Allergic Rhinitis as an example to detail the full process of formulating recommendations and summaries it into a three-step method. Step one: Collect original materials from different sources to create EtD table. Step two: Distribute and collect EtD table, and preliminarily gather the recommendation voting results. Step three: Organize "salami-slicing pattern" guideline development group consensus meeting to formulate recommendations. The three-step method for formulating recommendations in clinical practice guidelines fully utilizes the GRADE EtD table to provide guideline development group with decision-making foundation and reference from multiple dimensions, including the importance of clinical questions, balance of benefits and harms, quality of evidence, resource required, values and preferences, health equity, acceptability, and feasibility. This approach enhances the scientific and practical nature of guideline recommendations. This paper provides a standard operating procedure to formulate recommendations for the incoming clinical practice guidelines, which aims to establish a standard pathway for the formulation of acupuncture clinical practice guideline recommendations. (c) 2024 World Journal of Acupuncture - Moxibustion House. Pub

关键词： Clinical practice guidelines GRADE Evidence-to-decision (EtD) Acupuncture Moxibustion Allergic rhinitis Paradigm Standard operating procedure (SOP) Three-step method Salami-slicing pattern GRADE

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World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guidelines on Acupuncture and Moxibustion: Female Urinary Incontinence recommendation summaries

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WORLD JOURNAL OF ACUPUNCTURE-MOXIBUSTION 2024年第3期34卷 189-196页

作者： Du, Shi-hao Du, Shuo Chen, Sheng Wang, Shan-ze Wang, Guan-qun Xie, Xiao-long Peng, Bi-hui Guo, Wei Zhao, Ji-ping Yang, Chao Beijing Univ Chinese Med Dongzhimen Hosp Dept Acupuncture & Moxibust Beijing 100700 Peoples R China China Acad Chinese Med Sci Inst Acupuncture & Moxibust Beijing 100700 Peoples R China Guangdong Prov hosp Chinese Med Dept Acupuncture & Moxibust Guangzhou 510120 Peoples R China shanghai Jiao Tong Univ Sch Med Dept Tradit Chinese Med Shanghai Peoples Hosp 9 Shanghai 200011 Peoples R China

Urinary incontinence (UI) is common in women and affects the quality of life in female patients severely. But the clinical consideration and treatment are insufficient. Acupuncture and-moxibustion has been proposed as a potentially effective intervention for female UI. Hence, the World Federation of Acupuncturemoxibustion Societies (WFAS) have initiated a project to develop the clinical practice guideline (CPG) on acupuncture and moxibustion for female UI towards global acupuncture practitioners. The CPG was developed according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development . During the development of the CPG, the guideline development group (GDG) played an important role, which is composed of multi-national and multi-disciplinary experts. The clinical questions, recommendations and therapeutic protocols were all formulated by GDG using the modified Delphi method and basing on the results of the latest systematic review. This article focuses on the recommendations in the CPG. The CPG contains ten recommendations for ten clinical questions, including nine conditional recommendations for the intervention, one conditional recommendations for either the intervention or the comparison. The CPG also provides one conventional filiform needle therapy protocol, two deep puncturing stimulation on lumbosacral acupoints therapy protocols, and four moxibustion therapy protocols, extracted from the included clinical evidence of this CPG. (c) 2024 World Journal of Acupuncture - Moxibustion House. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license ( http://***/licenses/by-nc-nd/4.0/ )

关键词： Acupuncture Moxibustion Clinical practice guideline Clinical question Female urinary incontinence Important outcome OVERACTIVE BLADDER WOMEN ELECTROACUPUNCTURE

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Aloe emodin promotes mucosal healing by modifying the differentiation fate of enteroendocrine cells via regulating cellular free fatty acid sensitivity

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ACTA PHARMACEUTICA SINICA B 2024年第9期14卷 3964-3982页

作者： Bao, Weilian Lyu, Jiaren Feng, Guize Guo, Linfeng Zhao, Dian You, Keyuan Liu, Yang Li, Haidong Du, Peng Chen, Daofeng Shen, Xiaoyan Fudan Univ Sch Pharm Dept Pharmacol Minist Educ Shanghai 201210 Peoples R China Fudan Univ Sch Pharm Key Lab Smart Drug Delivery Minist Educ Shanghai 201210 Peoples R China Fudan Univ Sch Pharm Dept Nat Med Shanghai 201210 Peoples R China shanghai Jiao Tong Univ Xinhua Hosp Dept Colorectal & Anal Surg Sch Med Shanghai 200092 Peoples R China shanghai Colorectal Canc Res Ctr Shanghai 200092 Peoples R China

The proper differentiation and reorganization of the intestinal epithelial cell population is critical to mucosal regeneration post injury. Label retaining cells (LRCs) expressing SRY-box transcription factor 9 (SOX9) promote epithelial repair by replenishing LGR5+ intestinal stem cells (ISCs). While, LRCs are also considered precursor cells for enteroendocrine cells (EECs) which exacerbate mucosal damage in inflammatory bowel disease (IBD). The factors that determine LRC-EEC differentiation and the effect of intervening in LRC-EEC differentiation on IBD remain unclear. In this study, we investigated the effects of a natural anthraquinone called aloe emodin (derived from the Chinese herb rhubarb) on mucosal healing in IBD models. Our findings demonstrated that aloe emodin effectively interfered with the differentiation to EECs and preserved a higher number of SOX9+ LRCs, thereby promoting mucosal healing. Furthermore, we discovered that aloe emodin acted as an antagonist of free fatty acid receptors (FFAR1), suppressing the FFAR1-mediated Gbg/serine/threonine-protein kinase (AKT) pathway and promoting the translo cation of forkhead box protein O1 (FOXO1) into the nucleus,ultimately resulting in the intervention of differentiation fate. These findings reveal the effect of free fatty acid accessibility on EEC differentiation and introduce a strategy for promoting mucosal healing in IBD by regulating the FFAR1/AKT/FOXO1 signaling pathway.

关键词： LRCs ISCs EECs IBD SOX9 Aloe emodin FFAR1 FOXO1 CHRONIC ULCERATIVE-COLITIS EVIDENCE-BASED CONSENSUS INSULIN-SECRETION GRANULE RELEASE DNA-BINDING FOXO1 INDUCTION RECEPTOR DISEASE BETA

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World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guideline on Acupuncture and Moxibustion: Allergic Rhinitis recommendation summaries

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WORLD JOURNAL OF ACUPUNCTURE-MOXIBUSTION 2024年第3期34卷 179-188页

作者： Du, Shi-hao Liu, Jing Chen, Sheng Wang, Shan-ze Wang, Guan-qun Du, Shuo Xie, Xiao-long Peng, Bi-hui Guo, Wei Yang, Chao Zhao, Ji-ping Beijing Univ Chinese Med Dongzhimen Hosp Dept Acupuncture & Moxibust Beijing 100700 Peoples R China China Acad Chinese Med Sci Inst Acupuncture & Moxibust Beijing 100700 Peoples R China Guangdong Prov hosp Tradit Chinese Med Dept Acupuncture & Moxibust Guangzhou 510120 Peoples R China shanghai Jiao Tong Univ Sch Med Shanghai Peoples Hosp 9 Dept Tradit Chinese Med Shanghai 200011 Peoples R China

Clinical Practice Guideline on Acupuncture and Moxibustion: Allergic Rhinitis was revised and released by the Standards Working Committee of World Federation of Acupuncture-Moxibustion Societies (WFAS) on October 9, 2023. This is the first clinical practice guideline (CPG) on acupuncture and moxibustion for allergic rhinitis approved by an international academic organization, which provides evidence-based recommendations and the practical therapeutic protocols for acupuncture practitioners globally. This CPG was developed by following Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, and the principles of the World Health Organization Handbook for Guideline Development . The members in the guideline development group (GDG) were from different countries, with different professions, and they played a critical role in the development of clinical questions, recommendations, and therapeutic protocols. Recommendations are the core of a CPG and the direct answers to clinical questions, due to which this article focuses on the recommendations of this CPG. The recommendations were developed by using the modified Delphi method and the GRADE grid rules, based on the updated systematic reviews of clinical evidence. A total of 15 recommendations for 15 clinical questions were developed in this CPG, including one strong recommendation for intervention based on high-quality evidence, three conditional recommendations for either the intervention or the comparison based on very low quality of evidence, and 11 conditional recommendations for the intervention based on very low quality of evidence. (c) 2024 World Journal of Acupuncture - Moxibustion House. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license ( http://***/licenses/by-nc-nd/4.0/ )

关键词： Allergic rhinitis Acupuncture Moxibustion Clinical practice guideline (CPG) Clinical questions COST-EFFECTIVENESS CONTROLLED-TRIAL MANAGEMENT CONSENSUS SYMPTOMS MEDICINE STRENGTH QUALITY

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Insights into therapeutic peptides in the cancer-immunity cycle: Update and challenges

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ACTA PHARMACEUTICA SINICA B 2024年第9期14卷 3818-3833页

作者： Zhang, Xiaokun Wu, Ye Lin, Jiayi Lu, Shengxin Lu, Xinchen Cheng, Aoyu Chen, Hongzhuan Zhang, Weidong Luan, Xin shanghai Univ Tradit Chinese Med Inst Interdisciplinary Integrat Med Res Shanghai Frontiers Sci Ctr Chinese Med Chem Biol Shanghai 201203 Peoples R China shanghai Univ Tradit Chinese Med Shuguang Hosp Shanghai 201203 Peoples R China Fudan Univ Sch Pharm Dept Pharmacol Shanghai 201203 Peoples R China Chinese Acad Med Sci & Peking Union Med Coll Inst Med Plant Dev Beijing 100193 Peoples R China Second Mil Med Univ Sch Pharm Shanghai 200433 Peoples R China

Immuno therapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer therapy. As vital biological mediators, peptides with high tissue penetration and superior selectivity offer significant promise for enhancing cancer immunotherapies (CITs). However, physicochemical peptide features such as conformation and stability pose challenges to their on-target efficacy. This review provides a comprehensive overview of recent advancements in therapeutic peptides targeting key steps of the cancer-immunity cycle (CIC), including tumor antigen presentation, immune cell regulation, and immune checkpoint signaling. Particular attention is given to the opportunities and challenges associated with these peptides in boosting CIC within the context of clinical progress. Furthermore, possible future developments in this field are also discussed to provide insights into emerging CITs with robust efficacy and safety profiles.

关键词： Cancer-immunity cycle Oncolytic peptide Peptide neoantigen vaccine Peptide mimotope Immune checkpoint blockade Cancer immunotherapy Synthetic long peptide vaccine Peptide-major histocompatibility complex CHECKPOINT BLOCKADE TUMOR-ANTIGENS T-CELLS IMMUNOTHERAPY TIGIT ANTAGONIST RESPONSES STRATEGY BLOCKING TARGETS

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Clinical features analysis of B-cell acute lymphoblastic leukemia with KMT2A::AFF1 gene expression

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China Medical Abstracts(Internal Medicine) 2024年第1期41卷 60-61页

作者：张春玲 Dept Lab Med Shanghai General HospShanghai 200080

Objective To analyze the correlation between clinical features and prognosis or prognostic risk factors in patients with KMT2A::AFF1 gene positive *** Retrospective cohort study was conducted.167cases of B-ALL admitted to the shanghai General hospital and the Naval Medical University Affiliated First hospital from April 1,2011 to July 31.

关键词： admitted prognosis clinical

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