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Clinical characteristics and treatment of splenic infarction in children with systemic lupus erythematosus

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World Journal of Pediatrics 2024年第5期20卷 525-531页

作者： Yan Li Yu-Rong Piao Tong-Xin Han Hua-Wei Mao Department of Immunology Ministry of Education Key Laboratory of Major Diseases in ChildrenBeijing Key Laboratory for Genetics of Birth DefectsNational Center for Children’s HealthBeijing Children’s HospitalCapital Medical UniversityNo.56 Nan Li Shi LuBeijing100045China

Splenic infarction(SI)is a rare clinical phenomenon that occurs when the blood supply to the spleen is interrupted,resulting in tissue ischemia and necrosis[1].There are many causes of SI;in adult patients,cardioembolism,hematological malignancy,and infectious disease are the most common[2].Rheumatic diseases,especially systemic lupus erythematosus(SLE)and granulomatosis with polyangitis,can also lead to SI[3];however,only a few cases have been *** are currently no statistically meaningful data on the etiology of SI in *** most patients with SI can recover after conservative treatment,a small number of patients develop complications,such as splenic abscess,splenic rupture,splenic hemorrhage,and hemoperitoneum,and may even undergo splenectomy in severe cases.

关键词： erythematosus lupus treatment

Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutation

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Science China Life Sciences 2024年

作者： Qian Hao Jinfeng Li Leng-Siew Yeap Shanghai Institute of Immunology Department of Immunology and Microbiology State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine center for Immune-Related diseases at Shanghai Institute of Immunology Department of Endocrinology and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine

Antibody diversification is essential for an effective immune response, with somatic hypermutation(SHM) serving as a key molecular process in this adaptation. Activation-induced cytidine deaminase(AID) initiates SHM by inducing DNA lesions, which are ultimately resolved into point mutations, as well as small insertions and deletions(indels). These mutational outcomes contribute to antibody affinity *** mechanisms responsible for generating point mutations and indels involve the base excision repair(BER) and mismatch repair(MMR)pathways, which are well coordinated to maintain genomic integrity while allowing for beneficial mutations to occur. In this regard,translesion synthesis(TLS) polymerases contribute to the diversity of mutational outcomes in antibody genes by enabling the bypass of DNA lesions. This review summarizes our current understanding of the distinct molecular mechanisms that generate point mutations and indels during SHM. Understanding these mechanisms is critical for elucidating the development of broadly neutralizing antibodies(bnAbs) and autoantibodies, and has implications for vaccine design and therapeutics.

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B cell development and antibody responses in human immune system mice:current status and future perspective

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Science China(Life Sciences) 2024年第4期67卷 645-652页

作者： Tao Zhang Wentao Liu Yong-Guang Yang Key Laboratory of Organ Regeneration&Transplantation of the Ministry of Education The First Hospital of Jilin UniversityChangchun 130061China National-Local Joint Engineering Laboratory of Animal Models for Human diseases Jilin UniversityChangchun 130061China International center of Future Science Jilin UniversityChangchun 130061China

Humanized immune system(HIS)mice have been developed and used as a small surrogate model to study human immune function under normal or disease *** variations are found between models,most HIS mice show robust human T cell ***,there has been unsuccessful in constructing HIS mice that produce high-affinity human antibodies,primarily due to defects in terminal B cell differentiation,antibody affinity maturation,and development of primary follicles and germinal *** this review,we elaborate on the current knowledge about and previous attempts to improve human B cell development in HIS mice,and propose a potential strategy for constructing HIS mice with improved humoral immunity by transplantation of human follicular dendritic cells(FDCs)to facilitate the development of secondary follicles.

关键词： humanized immune system mouse humoral immunity germinal center B cell follicular dendritic cell

small molecule conjugates with selective estrogen receptor β agonism promote anti-aging benefits in metabolism and skin recovery

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2137-2152页

作者： Tarik Zahr Vijay K.Boda Jian Ge Lexiang Yu Zhongzhi Wu Jianwen Que Wei Li Li Qiang Naomi Berrie Diabetes center Columbia UniversityNew YorkNY 10032USA Department of Molecular Pharmacology and Therapeutics Columbia UniversityNew YorkNY 10032USA Department of Pharmaceutical Sciences College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Drug Discovery center College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Division of Digestive and Liver diseases Columbia UniversityNew YorkNY 10032USA center for Human Development Columbia UniversityNew YorkNY 10027USA Department of Pathology and Cell Biology Columbia UniversityNew YorkNY 10032USA Department of Medicine Columbia UniversityNew YorkNY 10032USA

Estrogen is imperative to mammalian reproductivity,metabolism,and ***,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain *** contrast,ERβis more broadly expressed in metabolic tissues and the ***,it is desirable to generate selective ERβagonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERα***,we report the design and production of small molecule conjugates containing selective non-steroid ERβagonists Gtx878 or *** of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity,visceral adipose integrity,skeletal muscle function,and skin health,with validation in *** further uncovered the benefits of ERβconjugates in the skin using two inducible skin injury mouse models,showing increased skin basal cell proliferation,epidermal thickness,and wound ***,our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.

关键词： Estrogen receptorβ Aging Metabolism Skin injury Muscle metabolism small molecule conjugates Regeneration Adiposity

Chain Extender-induced Hydrogen Bonding Organization Determines the Morphology and Properties of Thermoplastic Polycarbonate Polyurethane

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Chinese Journal of Polymer Science 2024年第1期42卷 87-96,I0009页

作者： Yi-Lang Qin Ping Zhu Chen-Xi Ouyang Xia Dong Fuwai Hospital Chinese Academyof Medical Sciences&Peking Union Medical College/National Center for Cardiovascular DiseasesBejing 100037China CASKey Laboratoryof Engineering Plastics CAS Research/Education Centerfor Excellence in Molecular SciencesInstitute ofChemistryChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

Thermoplastic polycarbonate polyurethanes(PCUs) are multiblock copolymers that have been applied for medical devices for long time. Aliphatic diols are common chain extenders(CE) involved in the composition of the hard segments of PCU. However, limited knowledge was discovered about how the chemical structure of CE affects the hydrogen bonding organization within PCUs and their mechanical *** investigate this problem, a group of PCUs were synthesized respectively by extending the polymer chain with 1,4-butanediol(BDO),aminoethanol(MEA), ethanediol(EO) as three kinds of chain extenders. Tiny differences in the CE chemical structure results in remarkable variations in phase separation, condensed morphologies, thermal and mechanical properties, which are characterized by Fourier transform infrared spectrometer, atomic force microscopy, small-angle X-ray scattering, differential scanning calorimetry, and tensile tests. The microstructural evolution during unilateral deformation and the different mechanism induced by the different CEs was probed and unveil by in situ wide-and small-angle X-ray diffraction. Symmetry of CE can improve the organization of the hydrogen bonding. The coherence strength of the urethane/urea group also plays a key role by comparing the two PCUs with ethanediol and aminoethanol.

关键词： Thermoplastic polycarbonate polyurethane Chain extender Hydrogen bonding Mechanical properties

Characteristics and prognosis of small bowel tumors:A retrospective study

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World Journal of Clinical Cases 2024年第34期12卷 6696-6704页

作者： Fang-Chen Liu Ching-Hsiang Wang Peng-Jen Chen Yu-Lueng Shih Hsuan-Hwai Lin Jung-Chun Lin Wei-Kuo Chang Tsai-Yuan Hsieh Gen-Min Lin Tien-Yu Huang Division of Gastroenterology Department of Internal MedicineTri-Service General HospitalNational Defense Medical CenterTaipei 11490Taiwan Department of Internal Medicine Taoyuan Armed Forces General HospitalTaoyuan 325208Taiwan Department of Medicine Tri-Service General Hospital and National Defense Medical CenterTaipei 114Taiwan Department of Medicine Hualien Armed Forces General HospitalHualien 970Taiwan Taiwan Association for the Study of small Intestinal diseases Taoyuan 33305Taiwan

BACKGROUND small bowel tumors(SBTs)are a heterogeneous group of difficult-to-diagnose tumors that account for 2%-5%of all gastrointestinal ***-balloon enteroscopy greatly enhances the diagnosis and treatment of ***,few epidemiological studies have been conducted in Taiwan to determine the clinical profile of *** To investigate the clinical characteristics,managements and prognosis of SBTs in a medical center in *** The study enrolled 51 patients aged 58.9±8.8 years(range,22-93)diagnosed with SBTs from November 2009 to July *** retrospectively recorded clinical characteristics,indications,endoscopic findings,pathological results,management,and outcomes for further *** A male preponderance was observed(56.8%).The most common indications were suspected small intestinal tumors(52.9%)and obscure gastrointestinal bleeding(39.2%).The most common tumor location was the ileum(41.2%).The performance of imaging studies(P=0.004)and the types of findings(P=0.005)differed significantly between malignant and benign *** most frequent imaging finding was a small intestinal mass(43.1%).The top three malignant tumor types were gastrointestinal stromal tumors(GISTs),adenocarcinomas,and ***,the proportions of benign and malignant tumors were 27.5%and 72.5%,*** survival rates of patients with malignant tumors in the GIST and non-GIST groups differed significantly(P=0.015).Kaplan–Meier survival analysis showed a significant difference in survival between patients in the malignant and benign groups(P=0.04).All patients with lymphoma underwent chemotherapy(n=7/8,87.5%),whereas most patients with GISTs underwent surgery(n=13/14,92.8%).CONCLUSION Patients with GISTs have a significantly higher survival rate than those with other malignant ***,a large-scale nationwide study is warranted to evaluate the population-based epidemiology of SBTs.

关键词： Gastrointestinal bleeding Intestinal neoplasms Single-balloon enteroscopy,survival rate

Isolation and characterization of mpox virus from the first mpox case in Shenzhen,China

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Virologica Sinica 2024年第2期39卷 335-337页

作者： Lin Cheng Liuqing Yang Miao Wang Yabo Peng Haiyan Wang Xiaoxiang Yang Juanjuan Zhao Mingxia Zhang Fuxiang Wang Zheng Zhang Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalShenzhen518112China Department of Infectious diseases Shenzhen Third People's HospitalShenzhen 518112China The Second Affiliated Hospital School of MedicineSouthern University of Science and TechnologyShenzhen 518112China

Dear Editor,Unlike previous outbreaks of the mpox(previously known as monkeypox),which were localized in Africa and resulted in small numbers of infections due to limited human-to-human transmission,the current outbreak beginning in May 2022,has spread rapidly primarily through human-to-human transmission in non-endemic countries(Gong et al.,2022).As of 27 Sep 2023,115 countries and regions have reported cases of mpox to the World Health Organization(WHO),bringing the total number of confirmed cases to 90,618 including 125 *** the number of new cases has decreased in most WHO regions in the second half of 2022,the curves reveal a long outbreak tail in different subregions of the *** worrying,106 mpox cases were reported in the mainland of China in June 2023.

关键词： mainland bringing

Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 854-868页

作者： Yunzhu Lin Xiang Wang Shi He Zhongxin Duan Yunchu Zhang Xiaodong Sun Yuzhu Hu Yuanyuan Zhang Zhiyong Qian Xiang Gao Zhirong Zhang Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationWest China School of PharmacySichuan UniversityChengdu 610041China Department of Pharmacy Evidence-based Pharmacy CenterWest China Second University HospitalKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenSichuan UniversityChengdu 610041China Department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China Department of Radiation Oncology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China West China School of Basic Medical Sciences&Forensic Medicine Sichuan UniversityChengdu 610041China

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor(i PDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of p IL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation,macrophage polarization and DC maturation. The F-DPC/p IL-12/i PDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/p IL-12/i PDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

关键词： IL-12encodinggene Checkpointblocker Nanoparticles Targeted delivery Tumormicroenvironment Immune escape Ovarian cancer Immunotherapy

small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration Research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-Lan Xu Hua Ma Zai-Long Chi State Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National Clinical Research center for Ocular diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles