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Engineered nanoparticles for precise targeted drug delivery and enhanced therapeutic efficacy in cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3432-3456页

作者： Xueqiang Peng Jianjun Fang Chuyuan Lou liang Yang Shaobo Shan Zixian wang.Yutong Chen Hangyu Li Xuexin Li Department of General Surgery The Fourth Affiliated HospitalChina Medical UniversityShenyang 110032China Department of Ophthalmology Xi’an People’s Hospital(Xi’an Fourth Hospital)Xi’an 710004China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 10050China Department of medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangzhou 510060China Department of Pathology Medical CollegeJinan UniversityGuangzhou 510632China Department of Physiology and Pharmacology Karolinska InstitutetStockholm SE-17177Sweden

The advent of cancer immunotherapy has imparted a transformative impact on cancer treatment paradigms by harnessing the power of the immune ***,the challenge of practical and precise targeting of malignant cells *** address this,engineered nanoparticles(NPs)have emerged as a promising solution for enhancing targeted drug delivery in immunotherapeutic interventions,owing to their small size,low immunogenicity,and ease of surface *** comprehensive review delves into contemporary research at the nexus of NP engineering and immunotherapy,encompassing an extensive spectrum of NP morphologies and strategies tailored toward optimizing tumor targeting and augmenting therapeutic ***,it underscores the mechanisms that NPs leverage to bypass the numerous obstacles encountered in immunotherapeutic regimens and probes into the combined potential of NPs when co-administered with both established and novel immunotherapeutic ***,the review evaluates the existing limitations of NPs as drug delivery platforms in immunotherapy,which could shape the path for future advancements in this promising field.

关键词： Engineered nanoparticles Cancer immunotherapy Drug delivery Bloodebrain barrier Tumor-barrier Nanomedicine Nanomaterial Cancer

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The new insights of hyperbaric oxygen therapy:focus on inflammatory bowel disease

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Precision Clinical Medicine 2024年第2期7卷 159-169页

作者： Leilei Chen Yan wang.Huihui Zhou Yi liang Fengqin Zhu Guangxi Zhou Cheeloo College of Medicine Shandong UniversityJinan 250012China Department of Gastroenterology Affliated Hospital of jining Medical University Jining Medical UniversityJining 272000China Department of Hyperbaric Oxygen Affliated Hospital of jining Medical UniversityJining Medical UniversityJining 272000China

Inflammatory bowel diseases(IBD),with an increasing incidence,pose a significant health *** there have been significant advances in the treatment of IBD,more progress is still *** oxygen therapy(HBOT)has been shown to treat a host of conditions such as carbon monoxide poisoning,decompression sickness,and gas *** the last few years,there has been an increase in research into the use of HBOT as an adjunct to conventional treatment for *** research has shown that HBOT may exert its therapeutic effects by decreasing oxidative stress,inhibiting mucosal inflammation,promoting ulcer healing,influencing gut microbes,and reducing the incidence of IBD *** paper aims to provide a comprehensive review of experimental and clinical trials exploring HBOT as a supplement to IBD treatment strategies.

关键词： hyperbaric oxygen therapy inflammatory bowel disease mucosal inflammation

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A new autophagy-related nomogram and mechanism in multiple myeloma

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Genes & Diseases 2024年第5期11卷 29-32页

作者： Hanying Huang Yang Li Ziang Zhu Yang Liu Weida wang.Shuzhao Chen Xiaoping Wu Yun wang.Yanzhou Chen Huanxin Lin Yang liang Lingling Shu State Key Laboratory of Oncology in South china Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China Department of Hematologic Oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China Department of Radiation Oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China Key Laboratory of Neurosurgery in Guangdong Province Southern Medical UniversityGuangzhouGuangdong 510060China Department of Neurosurgery Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong 510060China State Key Laboratory of Pharmaceutical Biotechnology The University of Hong KongHong Kong 999077China

Multiple myeloma(MM)is the second most common hematological *** is characterized by high drug resistance,easy recurrence,and poor prognosis,and remains *** models or scoring modalities can be used to predict the survival prognosis of MM patients;however,these predictions are still not accurate *** have previously found that scorings related to bone marrow microenvironment metabolism can improve predictive efficacy.

关键词： metabolism prognosis myeloma

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EBV-associated lymphoproliferative disease post-CAR-T cell therapy

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Frontiers of Medicine 2024年第2期18卷 394-398页

作者： Shiyuan Zhang Xiaoxi Zhou Shangkun Zhang Na wang.Tongcun Zhang Donghua Zhang Qilin Ao Yang Cao liang Huang Department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Immunotherapy Research Center for Hematologic Diseases of Hubei Province Wuhan430030China Institute of Biology and Medicine College of Life and Health SciencesWuhan University of Science and TechnologyWuhan430081China Department of Pathology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin300020China Tianjin Institutes of Health Science Tianjin301600China

Epstein–Barr virus(EBV)-associated lymphoproliferative diseases(EBV-LPDs)are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation(HSCT).However,their occurrence and treatment post-chimeric antigen receptor-modified T(CAR-T)cell therapy has not been *** patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of *** receiving CAR-T cell therapy in tandem with autologous HSCT,the patients achieved complete ***,with a median time of 38.5 months after CAR-T cell therapy,B-cell-derived EBV-LPDs were diagnosed,and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting ***,our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy,especially in patients who previously had EBV-positive disorders,and they can be resolved by immune normalization strategy or B-cell depleting therapy.

关键词： EBV-associated lymphoproliferative disease chimeric antigen receptor T-cell autologous stem cell transplantation immune checkpoint inhibitor

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FGF4 protects the liver from immune-mediated injury by activating CaMKKβ-PINK1 signal pathway to inhibit hepatocellular apoptosis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 1605-1623页

作者： Zhifeng Huang Tongtong Pan liang Xu Lu Shi Xiong Ma Liya Zhou Luyao wang.Jiaojiao wang.Guoqing Zhu Dazhi Chen Lingtao Song Xiaomin Pan Xiaodong wang.Xiaokun Li Yongde Luo Yongping Chen Hepatology Diagnosis and Treatment Center Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseasesthe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)&School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035China School of Laboratory Medicine and Life Sciences Wenzhou Medical University&Key Laboratory of Laboratory MedicineMinistry of EducationWenzhou Medical UniversityWenzhou 325035China Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Hangzhou medical College Hangzhou 311300China

Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine;however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca^(2+)/calmodulin-dependent protein kinasekinase 2 (CaMKKβ) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

关键词： Fibroblast growthfactor 4 Fibroblast growth factor receptor 4 Immune liver injury Ca^(2+)/Calmodulin dependent protein

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Decitabine induces IRF7-mediated immune responses in p53-mutated triple-negative breast cancer:a clinical and translational study

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Frontiers of Medicine 2024年第2期18卷 357-374页

作者： Haoyu wang.Zhengyuan wang.Zheng wang.Xiaoyang Li Yuntong Li Ni Yan Lili Wu Ying liang Jiale Wu Huaxin Song Qing Qu Jiahui Huang Chunkang Chang Kunwei Shen Xiaosong Chen Min Lu Department of General Surgery Comprehensive Breast Health CenterRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine(Shanghai)Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Shanghai Institute of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200025China

p53 is mutated in half of cancer ***,no p53-targeting drugs have been ***,we reposition decitabine for triple-negative breast cancer(TNBC),a subtype with frequent p53 mutations and extremely poor *** a retrospective study on tissue microarrays with 132 TNBC cases,DNMT1 overexpression was associated with p53 mutations(P=0.037)and poor overall survival(OS)(P=0.010).In a prospective DEciTabinE and Carboplatin in TNBC(DETECT)trial(NCT03295552),decitabine with carboplatin produced an objective response rate(ORR)of 42%in 12 patients with stage IV *** the 9 trialed patients with available TP53 sequencing results,the 6 patients with p53 mutations had higher ORR(3/6 vs.0/3)and better OS(16.0 vs.4.0 months)than the patients with wild-type *** a mechanistic study,isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type *** the DETECT trial,decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line(upregulation by 16-fold)and the most responsive patient with *** integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词： p53 mutation triple-negative breast cancer decitabine DNMT1 IRF7 innate immune response

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Casein kinase-2 inhibition promotes retinal ganglion cell survival after acute intraocular pressure elevation

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Neural Regeneration Research 2024年第5期19卷 1112-1118页

作者： Meng wang.Shi-Qi Yao Yao Huang Jia-Jian liang Yanxuan Xu Shaowan Chen Yuhang wang.Tsz Kin Ng Wai Kit Chu Qi Cui Ling-Ping Cen Joint Shantou International Eye Center of Shantou university and The Chinese university of Hong Kong ShantouGuangdong ProvinceChina Shantou university medical College ShantouGuangdong ProvinceChina Beijing Tongren Eye Center Beijing Tongren HospitalCapital Medical UniversityBeijingChina Department of Ophthalmology and Visual Sciences The Chinese University of Hong KongHong Kong Special Administrative RegionChina

Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma,the leading cause of irreversible *** previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve *** investigate the underlying mechanism,in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor(4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole)by intravitreal *** found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating *** analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 ***,casein kinase-2 inhibition downregulated the expression of genes(Cck,Htrsa,Nef1,Htrlb,Prph,Chat,Slc18a3,Slc5a7,Scn1b,Crybb2,Tsga10ip,and Vstm21)involved in intraocular pressure *** data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.

关键词： casein kinase-2 glaucoma intraocular pressure elevation macrophages retinal ganglion cells

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A pan‐cancer analysis of Wnt family member 7B in human cancers

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Cancer Innovation 2024年第5期3卷 84-101页

作者： Rui wang.Ni‐sha Wu Li wang.Zhi‐zhao Zhang Cheng‐fang wang.Yan wang.Yan liang Yi Zhang Xiao‐wei Qi Department of Breast and Thyroid Surgery Southwest HospitalArmy Medical UniversityChongqingChina 2Department of InfectionChina Academy of Chinese medical Sciences Guang'anmen HospitalBeijingChina

Background: Previous studies have highlighted the crucial role of Wnt7B inthe development of various cancers, including breast, pancreatic, and gastriccancers. However, research into the involvement of Wnt7B is often confined tospecific tumor types, with a noticeable lack of comprehensive studies spanningmultiple cancer forms. The potential of Wnt7B as a diagnostic or prognosticcancer biomarker has not been fully ***: In this study, we combined bioinformatics and immunohistochemistryanalyses to examine the expression patterns and functions of Wnt7B in cancerousand adjacent noncancerous tissues across a range of ***: Our data indicate that Wnt7B may serve as a novel prognosticbiomarker and therapeutic target in certain ***: We found significant upregulation of Wnt7B expression levels in themajority of cancer cases examined. Furthermore, Wnt7B can influence cancerprognosis by modulating the tumor microenvironment, immune cell infiltration,and tumor stemness, among other factors. Additionally, we examined theassociations between anticancer drug sensitivity and Wnt7B expression, whichcould aid in the development of more precise clinical therapies.

关键词： bioinformatics immune infiltration immunotherapy pan‐cancer analysis Wnt7B

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Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer

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Journal of Integrative Medicine 2024年第3期22卷 295-302页

作者： Zhengting Deng Shufang liang Guokai Huang Yuqian wang.Xiaoyu Tu Yani Zhang Shu Li Tao Liu Binbin Cheng Taizhou Hospital of Traditional Chinese Medicine Nanjing University of Chinese MedicineTaizhou 225300Jiangsu ProvinceChina Oncology Department of Traditional Chinese Medicine The First Affiliated Hospital of Naval Medical UniversityShanghai 200433China School of Traditional Chinese Medicine Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina Department of Gastroenterology Baoshan Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 201900China

Objective: The effects of arsenic trioxide(As2O3) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3-induced apoptosis in liver cancer ***: The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum. The rate of apoptosis in liver cancer cells treated with As2O3was evaluated using flow cytometry, Hoechst 33258 staining, and TUNEL assays. The rate of autophagy among liver cancer cells treated with As2O3was detected using immunofluorescence, Western blot assay and transmission electron ***: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time-and dose-dependent manner. The apoptosis rates of both liver cancer cell lines increased with the concentration of As2O3, as shown by flow cytometry. Apoptosis in liver cancer cells treated with As2O3was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax ***, As2O3treatment induced autophagy in liver cancer cells;this finding was supported by Western blot, immunofluorescence of LC3-II and beclin 1, and transmission electron microscopy. In liver cancer cells, As2O3inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-methyladenine partially reversed the negative effects of As2O3on cell *** starvation increased autophagy and amplified the effect of As2O3on cell ***: As2O3induces apoptosis and autophagy in liver cancer cells. Autophagy induced by As2O3may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights

关键词： Apoptosis Arsenic trioxide Autophagy Primary liver cancer

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Hongjin Xiaojie Capsule,a Chinese patent medicine,for treating moderate to severe cyclical breast pain:A single-blind randomized controlled trial

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Journal of Integrative Medicine 2024年第5期22卷 552-560页

作者： Qiong Zhang Ying-yi Fan Xue-qing Wu Yan-dan Huo Chun-hui wang.Shi-bing liang Ting wang.Rong Zhong Xuan wang.Bao-yong Lai Xiao-hua Pei Jian-ping Liu Graduate School Beijing University of Chinese MedicineBeijing 100029China Department of Breast Beijing University of Chinese Medicine Third Affiliated HospitalBeijing 100029China Department of Breast Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 200021China Department of Breast Sichuan Second Hospital of Traditional Chinese MedicineChengdu 610014Sichuan ProvinceChina Department of Breast Xiamen HospitalBeijing University of Chinese MedicineXiamen 361015Fujian ProvinceChina Center for Evidence-Based Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China

Background Moderate to severe breast pain has major effects on the quality of life for *** Chinese medicines are widely used in the treatment of breast pain due to their stable dosage form and good *** To evaluate the beneficial effects and safety of Hongjin Xiaojie Capsule(HJXJC),a Chinese patent medicine,for the treatment of cyclical breast ***,setting,participants and intervention This is a multicenter,single-blind randomized controlled trial conducted in 3 medical centers in china from 2019 to *** with moderate to severe cyclic breast pain were randomly divided into the intervention group(who took HJXJC,four capsules per dose,three times a day for 12 weeks)and the control group(waiting for the treatment)in a 1:1 *** outcome measures The primary outcome was pain duration,and the patients recorded measurements at baseline and at the end of weeks 4,8,12 and 16 on a patient log *** The full analysis set(FAS)population included 298 participants(intervention group,n=150;control group,n=148),while the per-protocol analysis set(PPS)included 274 *** 12 weeks,the duration of breast pain was significantly shorter in the intervention group(FAS:mean difference,–6.69;95%CI,–7.58 to–5.80;P0.05).At weeks 8 and 12,th

关键词： Hongjin Xiaojie Capsule Cyclical breast pain Randomized controlled trial Traditional Chinese medicine

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