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Lupenone improves motor dysfunction in spinal cord injury mice through inhibiting the inflammasome activation and pyroptosis in microglia via the nuclear factor kappa B pathway

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Neural Regeneration Research 2024年第8期19卷 1802-1811页

作者： Fudong Li Xiaofei Sun Kaiqiang Sun Fanqi Kong Xin Jiang Qingjie Kong Department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Orthopedic Surgery Spine CenterShanghai Changzheng HospitalNaval Medical UniversityShanghaiChina Department of Orthopedic Surgery Naval Medical CenterNaval Medical UniversityShanghaiChina Department of Anesthesiology Shanghai Changzheng HospitalNaval Medical UniversityShanghaiChina

Spinal cord injury-induced motor dysfunction is associated with *** have shown that the triterpenoid lupenone,a natural product found in various plants,has a remarkable anti-inflammatory effect in the context of chronic ***,the effects of lupenone on acute inflammation induced by spinal cord injury remain *** this study,we established an impact-induced mouse model of spinal cord injury,and then treated the injured mice with lupenone(8 mg/kg,twice a day)by intrape ritoneal *** also treated BV2 cells with lipopolysaccharide and adenosine5’-triphosphate to simulate the inflammatory response after spinal cord *** res ults showed that lupenone reduced IKBa activation and p65 nuclear translocation,inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B,and enhanced the conve rsion of proinflammatory M1 mic roglial cells into anti-inflammatory M2 microglial ***,lupenone decreased NLRP3 inflammasome activation,NLRP3-induced mic roglial cell polarization,and microglia pyroptosis by inhibiting the nuclear factor kappa B *** findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.

关键词： inflammasome inflammation lupenone microglia polarization pyroptosis spinal cord injury

Improving the value of molecular testing:current status and opportunities in colorectal cancer precision medicine

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Cancer Biology & Medicine 2024年第1期21卷 21-28页

作者： Haiyun Li Linwei Guo Chenchen Wang Xin Hu Ye Xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Gastrointestinal medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Precision Cancer medical Center Affiliated with Fudan university shanghai Cancer Center Shanghai 201315China

Colorectal cancer(CRC)is the second leading cause of cancer-related deaths *** radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of ***,the transformation of high-throughput sequencing has accelerated the development of precision *** example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in ***,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.

关键词： cancer chemotherapy colorectal

Decoupled deep hough voting for point cloud registration

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Frontiers of Computer Science 2024年第2期18卷 147-155页

作者： Mingzhi YUAN Kexue FU Zhihao LI Manning WANG Digital medical Research Center School of Basic Medical SciencesFudan UniversityShanghai 200032China shanghai Key Laboratory of medical Image Computing and Computer Assisted Intervention Shanghai 200032China

Estimating rigid transformation using noisy correspondences is critical to feature-based point cloud ***,a series of studies have attempted to combine traditional robust model fitting with deep *** them,DHVR proposed a hough voting-based method,achieving new state-of-the-art ***,we find voting on rotation and translation simultaneously hinders achieving better ***,we proposed a new hough voting-based method,which decouples rotation and translation ***,we first utilize hough voting and a neural network to estimate *** based on good initialization on rotation,we can easily obtain accurate rigid *** experiments on 3DMatch and 3DLoMatch datasets show that our method achieves comparable performances over the state-of-the-art *** further demonstrate the generalization of our method by experimenting on KITTI dataset.

关键词： point cloud registration robust model fitting deep learning hough voting

Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： Ying-Yan Wang Yun-Qing Zhou Li-Juan Luo Cui-Jin Wang Nan Shen Hao Li Ji-Wen Wang Department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Clinical Research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency *** Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome *** analyzed the patients’convulsions and treatment with antiepileptic *** patients were followed up at different time periods after ketogenic diet *** Six patients with SLC2A1 mutations were included in this *** patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their *** were then treated with a ketogenic diet for at least four *** analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet *** patients were seizure-free within a month of receiving the diet *** patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this *** antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment *** severe adverse events occurred during the *** Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 ***,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 Ketogenic diet SLC2A1

An antibiotic-free platform for eliminating persistent Helicobacter pylori infection without disrupting gut microbiota

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3184-3204页

作者： Yongkang Lai Tinglin Zhang Xiaojing Yin Chunping Zhu Yiqi Du Zhaoshen Li Jie Gao Department of Gastroenterology Shanghai Changhai HospitalNaval Medical UniversityShanghai 200433China Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghai 200433China Department of Gastroenterology Ganzhou People’s Hospital Affiliated to Nanchang UniversityGanzhou 341000China National Key Laboratory of Immunity and Inflammation Naval Medical UniversityShanghai 200433China shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and medical Devices Shanghai 200433China

Helicobacter pylori(***)infection remains the leading cause of gastric adenocarcinoma,and its eradication primarily relies on the prolonged and intensive use of two ***,antibiotic resistance has become a compelling health issue,leading to *** eradication treatment failure ***,the powerlessness of antibiotics against biofilms,as well as intracellular *** and the long-term damage of antibiotics to the intestinal microbiota,have also created an urgent demand for antibiotic-free ***,we describe an antibiotic-free,multifunctional copperorganic framework(HKUST-1)platform encased in a lipid layer comprising phosphatidic acid(PA),rhamnolipid(RHL),and cholesterol(CHOL),enveloped in chitosan(CS),and loaded in an ascorbyl palmitate(AP)hydrogel:AP@CS@Lip@*** platform targets inflammatory sites where *** aggregates through electrostatic ***,hydrolysis by matrix metalloproteinases(MMPs)releases CS-encased nanoparticles,disrupting bacterial urease activity and membrane ***,RHL disperses biofilms,while PA promotes lysosomal acidification and activates host autophagy,enabling clearance of intracellular ***,AP@CS@Lip@HKUST-1 alleviates inflammation and enhances mucosal repair through delayed Cu^(2+) release while preserving the intestinal ***,this platform presents an advanced therapeutic strategy for eradicating persistent *** infection without inducing drug resistance.

关键词： Helicobacter pylori infection Antibiotic-free Biofilms Autophagy Gastric mucosal repair Drug resistance Intestinal microbiota Anti-inflammation

New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-Peng Duan Bao-Dong Qin Xiao-Dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang Department of medical Oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each *** to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol *** recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous *** the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains *** majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial ***,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision ***,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

The gasdermin family:emerging therapeutic targets in diseases

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1905-1937页

作者： Chenglong Zhu Sheng Xu Ruoyu Jiang Yizhi Yu Jinjun Bian Zui Zou Faculty of Anesthesiology Changhai HospitalNaval Medical UniversityShanghai 200433China School of Anesthesiology Naval Medical UniversityShanghai 200433China National Key Laboratory of Immunity&Inflammation Naval Medical UniversityShanghai 200433China d 4 Department of Biochemistry and Molecular Biology College of Basic Medical SciencesNaval Medical UniversityShanghai 200433China

The gasdermin(GSDM)family has garnered significant attention for its pivotal role in immunity and disease as a key player in *** recently characterized class of pore-forming effector proteins is pivotal in orchestrating processes such as membrane permeabilization,pyroptosis,and the follow-up inflammatory response,which are crucial self-defense mechanisms against irritants and *** have been implicated in a range of diseases including,but not limited to,sepsis,viral infections,and cancer,either through involvement in pyroptosis or independently of this *** regulation of GSDM-mediated pyroptosis is gaining recognition as a promising therapeutic strategy for the treatment of various *** strategies for inhibiting GSDMD primarily involve binding to GSDMD,blocking GSDMD cleavage or inhibiting GSDMD-N-terminal(NT)oligomerization,albeit with some off-target *** this review,we delve into the cutting-edge understanding of the interplay between GSDMs and pyroptosis,elucidate the activation mechanisms of GSDMs,explore their associations with a range of diseases,and discuss recent advancements and potential strategies for developing GSDMD inhibitors.

关键词： diseases therapeutic immunity

Evidence-Based Dampness-Heat ZHENG(Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor

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Chinese Journal of Integrative Medicine 2024年第1期30卷 85-95页

作者： JIAO Ju-ying CHENG Chien-shan CAO Zhang-qi CHEN Lian-yu CHEN Zhen Department of Integrative Oncology Fudan University Shanghai Cancer CenterShanghai(200032)China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai(200032)China

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG(syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG(DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

关键词： cancer Chinese medicine syndrome ZHENG dampness-heat syndrome animal model pancreatic tumor evaluation methods

Differential interference contrast phase edging net:an all-optical learning system for edge detection of phase objects

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Chinese Optics Letters 2024年第1期22卷 21-27页

作者：李一鸣李然陈泉栾海涛卢海军杨晖顾敏张启明 Institute of Photonic Chips University of Shanghai for Science and TechnologyShanghai 200093China School of Optical-Electrical and Computer Engineering University of Shanghai for Science and TechnologyShanghai 200093China Nokia shanghai Bell Co. Ltd.Shanghai 201206China College of medical Instruments Shanghai University of Medicine and Health SciencesShanghai 201318China

Edge detection for low-contrast phase objects cannot be performed directly by the spatial difference of intensity *** this work,an all-optical diffractive neural network(DPENet)based on the differential interference contrast principle to detect the edges of phase objects in an all-optical manner is *** information is encoded into an interference light field by dual Wollaston prisms without lenses and light-speed processed by the diffractive neural network to obtain the scale-adjustable *** results show that DPENet achieves F-scores of 0.9308(MNIST)and 0.9352(NIST)and enables real-time edge detection of biological cells,achieving an F-score of 0.7462.

关键词： diffractive neural network edge detection phase objects