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Cancer cachexia:Focus on cachexia factors and inter-organ communication

Chinese medical Journal 2024年第1期137卷 44-62页

作者： Yongfei Wang Zikai Dong Ziyi An Weilin Jin the first clinical medical college of Lanzhou University LanzhouGansu 730000China Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhouGansu 730000China

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia *** cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer *** cachexia factors are also a potential target for the diagnosis and *** pathogenesis of cachexia is unclear and no clear effective treatment is ***,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently *** the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and *** review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia *** summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.

关键词： Cancer cachexia Cancer cachexia factors Inter-organ communication Tumor ecosystem Tumor microenvironment

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clinical manifestations,diagnosis and long-term prognosis of adult autoimmune enteropathy:Experience from Peking Union medical college Hospital

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World Journal of Gastroenterology 2024年第19期30卷 2523-2537页

作者： Mu-Han Li Ge-Chong Ruan Wei-Xun Zhou Xiao-Qing Li Sheng-Yu Zhang Yang Chen Xiao-Yin Bai Hong Yang Yu-Jie Zhang Peng-Yu Zhao Ji Li Jing-Nan Li Department of Gastroenterology Chinese Academy of Medical Sciences&Peking Union Medical College HospitalBeijing 100730China Department of Pathology Chinese Academy of Medical Scinences&Peking Union Medical College HospitalBeijing 100730China Department of Pathology Tianjin First Central HospitalNankai UniversityTianjin 300192China Affairs Office Chinese Academy of Medical Sciences&Peking Union Medical College Hospital(West campus)Beijing 100032China

BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE *** To improve overall understanding of this disease’s diagnosis and *** We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic *** Diarrhea in AIE patients was characterized by secretory *** common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and *** blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal ***,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte *** patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)*** were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s *** cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,*** Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult *** long-term prognosis is still unsatisfac

关键词： Autoimmune enteropathy clinical manifestations Diagnostic criteria Pathological features Long-term prognosis

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The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第4期19卷 800-806页

作者： Xinxin Wang Yushu Hu Renshi Xu medical college of Nanchang University Department of Neurology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical College

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory ***,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the *** disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized *** TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral *** review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

关键词： amyotrophic lateral sclerosis axonal transport liquid-liquid phase separation noncellular autonomous functions oxidative stress pathogenesis post-translational modification protein quality control system stress granules TAR DNA-binding protein 43(TDP-43)

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Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population:a two-sample bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第1期21卷 64-80页

作者： Xiong-Bin MA Yong-Ming LIU Yan-Lin LV Lin QIAN the first clinical medical college of Lanzhou University LanzhouGansuChina Geriatric Cardiovascular Department and Gansu clinical Research Center for Geriatric Diseases First Hospital of Lanzhou UniversityGansuChina

BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is *** Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction *** Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association *** without myocardial infarction history,HF,or LV ejection fraction(LVEF)<50%(n=16,923)in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome *** dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the *** In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni ***,no significant relationships were observed between other iron and LV *** Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the *** We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.

关键词： fraction function parameters

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Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 557-567页

作者： Sheng ZENG Shaoqiang XING Yifei ZHANG Haifeng WANG Qian LIU Department of Urology Tianjin First Central HospitalTianjin 300192China Department of Urology First Central Clinical CollegeTianjin Medical UniversityTianjin 300192China

Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery,radiotherapy,and chemotherapy,with some promising *** aims to kill tumor cells by mobilizing or stimulating cytotoxic immune ***,the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high ***,nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens,activating targeted T cells,modulating the immunosuppressive tumor microenvironment,and improving the treatment *** Calmette-Gué;rin(BCG)is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis,which was first reported to have antitumor activity in *** therapy can activate the immune system by inducing various cytokines and chemokines,and its specific immune and inflammatory responses exert antitumor *** was first used during the 1970s as an intravesical treatment agent for bladder cancer,which effectively improved immune antitumor activity and prevented tumor *** recently,nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune *** this study,we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.

关键词： Bladder cancer Bacillus Calmette-Gué rin vaccine Nanocarrier Genetic engineering Immunotherapy

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Knockdown of RCN1 contributes to the apoptosis of colorectal cancer via regulating IP3R1

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BIOCELL 2024年第5期48卷 835-845页

作者： XUAN SHI YUFEN WANG CHENYU LI WANGSHU FU XINYUE ZHANG AIXIA GONG Department of Gastroenterology The First Affiliated Hospital of Dalian Medical UniversityDalianChina Department of Gastroenterology The First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina The first clinical college Dalian Medical UniversityDalianChina

Background:The incidence of colorectal cancer(CRC)has been increasing in recent ***,the discovery of factors that can assist in alleviating CRC is urgently ***:To identify a potential factor involved in the development of CRC,we screened the upregulated genes in tumor tissues through four datasets from an online *** expression of reticulocalbin 1(RCN1),a Ca2+-binding protein,was upregulated in the four *** on loss-offunction experiments,the effect of RCN1 on cell viability was assessed by Cell Counting Kit-8(CCK-8)*** regulatory effect of RCN1 on apoptosis was evaluated through Annexin V-fluorescein 5-isothiocyanate(FITC)/propidium iodide(PI)staining assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)assay in RKO and SW480 *** of endoplasmic reticulum(ER)stress signaling pathways was confirmed by estimating the phosphorylation and expression of PRKR-like ER kinase(PERK),inositol-requiring kinase-1(IRE1),transcription factor 6(ACT6),and CCAAT/enhancer-binding protein-homologous protein(CHOP).The intracellular Ca2+homeostasis regulated by RCN1 was determined through the detection of Ca2+concentration and mitochondrial membrane potential(MMP)***,whether inositol 1,4,5-trisphosphate receptor type 1(IP3R1)was involved in the regulation of RCN1 in CRC was verified through the depletion of IP3R1 in RKO ***:Knockdown of RCN1 reduced cell viability and facilitated apoptosis in RKO and SW480 *** of PERK and IRE1,activation of ATF6,and upregulation of CHOP were induced by the absence of RCN1,suggesting that the unfolded protein response(UPR)was activated in CRC *** concentration of Ca2+in mitochondria was increased after RCN1 depletion,followed by reduction in the MMP and release of cytochrome c from mitochondria to the cytoplasm in RKO and SW480 ***,it was demonstrated that IP3R1 mediates the effect of RCN1 on apoptosis i

关键词： Reticulocalbin 1 Unfolded protein response IP3R1 Colorectal cancer

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Circ_0053943 complexed with IGF2BP3 drives uveal melanoma progression via regulating N6-methyladenosine modification of Epidermal growth factor receptor

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Oncology Research 2024年第5期32卷 983-998页

作者： ANDI ZHAO YUE WANG ZIJIN WANG QING SHAO QI GONG HUI ZHU SHIYA SHEN HU LIU XUEJUAN CHEN Department of Ophthalmology The First Affiliated Hospital with Nanjing Medical UniversityNanjing210029China the first clinical medical college Nanjing Medical UniversityNanjing211166China Department of Ophthalmology Nanjing First HospitalNanjing Medical UniversityNanjing210006China

Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple ***,the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma(UM)remain *** this study,we identified a novel circRNA,circ_0053943,through re-analysis of UM microarray data and quantitative ***_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo ***,circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3),thereby enhancing the function of IGF2BP3 by stabilizing its target *** sequencing assays identified epidermal growth factor receptor(EGFR)as a target gene of circ_0053943 and IGF2BP3 at the transcriptional *** assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK)signaling ***,circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex,thus providing a potential biomarker and therapeutic target for UM.

关键词： Uveal melanoma Hsa_circ_0053943 IGF2BP3 EGFR MAPK/ERK signaling pathway

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The Epstein-Barr virus-miRNA-BART6-5p regulates TGF-β/SMAD4 pathway to induce glycolysis and enhance proliferation and metastasis of gastric cancer cells

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Oncology Research 2024年第5期32卷 999-1009页

作者： XUHUI ZHAO XIAOMIN HUANG CHUNYAN DANG XIA WANG YUJIAO QI HONGLING LI the first clinical medical college Gansu University of Traditional Chinese MedicineLanzhou730000China Department of Oncology Gansu People’s HospitalLanzhou730000China The clinical medical college Ningxia Medical UniversityNingxia750004China

Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal ***,their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently *** and Methods:Initially,EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell *** transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45,and downregulation in EBVpositive cells(SUN-719).The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation,migration,and glycolytic processes,with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-β***:EBV-miRNA-BART6-5p exhibits pronounced upregulation in EBV-associated gastric cancer tissues and EBV-positive cells,while its target gene SMAD4 demonstrates downregulated *** of it can promote the proliferation and migration of gastric cancer ***,We found EBV-miRNA-BART6-5p promotes glycolysis of gastric cancer *** of the TGF-β/SMAD4 signaling pathway resulted in suppressed proliferation and migration of gastric cancer cells,concomitant with a diminished glycolytic ***:In this study,we found that EBV-miRNA-BART6-5p can target SMAD4,effectively increasing glycolysis in gastric cancer cells by regulating the TGF-β/SMAD4 signaling pathway,thereby enhancing the proliferation and metastasis of gastric cancer *** findings may offer new insights into the metabolic aspects of gastric cancer.

关键词： EBV TGF-β/SMAD4 Glycolysis Gastric cancer

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Ferritinophagy: A new idea for liver diseases regulated by ferroptosis

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 160-170页

作者： Zi-Bing Qian Jun-Feng Li Wan-Yuan Xiong Xiao-Rong Mao the first clinical medical college of Lanzhou University Lanzhou 730000China Institute of Infectious Diseases The First Hospital of Lanzhou UniversityLanzhou 730000China Department of Infectious Disease The First Hospital of Lanzhou UniversityLanzhou 730000China

Background:The discovery of regulatory cell death has led to a breakthrough in the therapeutic *** forms of cell death,such as necrosis,apoptosis,pyroptosis,autophagy,and ferroptosis,play an important role in the development of liver *** general,more than one form of cell death pathways is responsible for the disease ***,it is particularly important to study the regulation and interaction of various cell death forms in liver *** sources:We performed a PubMed search up to November 2022 with the following keywords:ferritinophagy,ferroptosis,and liver *** also used terms such as signal path,inducer,and inhibitor to supplement the query ***:This review summarized the basic characteristics of ferritinophagy and ferroptosis and the regulation of ferroptosis by ferritinophagy and reviewed the key targets and treatment strategies of ferroptosis in different liver ***:Ferritinophagy is a potential therapeutic target in ferroptosis-related liver diseases.

关键词： Ferritinophagy Ferroptosis Liver disease

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Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 86-102页

作者： Xiaoling Fu Yutong Song Xianquan Feng Zhihong Liu Wenhao Gao Hongtao Song Qian Zhang School of Pharmacy Fujian Medical UniversityFuzhou 350108China Fuzong clinical medical college of Fujian medical University Fuzhou 350025China first school of clinical medicine Nanjing Medical UniversityNanjing 211166China

Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis(RA)***@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia,thus contributing to the repolarization of M1 macrophages into M2 ***,MPM@Lipo could accumulate at inflammatory joints,inhibit the production of inflammatory factors,and protect cartilage in vivo,effectively alleviating RA progression in a rat adjuvant-induced arthritis ***,upon laser irradiation,MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen,resulting in excellent RA treatment ***,the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.

关键词： Polydopamine Thermosensitive liposomes Photothermal therapy Oxygen generation Rheumatoid arthritis

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