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NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

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Opto-Electronic Advances 2024年第6期7卷 58-73页

作者： Ziqing Xu Yakun Kang Jie Zhang Jiajia Tang Hanyao Sun Yang Li Doudou He Xuan Sha Yuxia Tang Ziyi Fu Feiyun Wu Shouju Wang Laboratory of Molecular Imaging Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China department of Breast Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China department of Women&Children Research Center The First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune *** these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS *** not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor *** in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/*** such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

关键词： photothermal therapy photodynamic therapy nitric oxide reactive nitrogen species triple-negative breast cancer immune response nanoreactor

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Musculoskeletal ultrasound to evaluate the efficacy of acupuncture: a review

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Journal of Traditional Chinese Medicine 2024年第3期44卷 629-632页

作者： WANG Dingyue YU Yana WANG Yiyuan ZHANG Zhen department of Ultrasound the First Affiliated Hospital of China Medical University

Acupuncture is a typical example of Traditional Chinese Medicine and has been used in China for hundreds of years to treat a wide range of illnesses. However, in the clinic, issues and deficiencies were primarily seen in four areas: loss of accuracy in the operation process; difficulty understanding the depth of acupuncture; difficulty using reinforcing and reducing techniques; and lack of a clear dynamic effect of acupuncture points following acupuncture. Musculoskeletal ultrasonography may quantitatively evaluate the acupuncture location and display the distribution of small nerves near and within the fascia of the acupuncture point in real time. The subjects were asked how they felt about receiving Qi when the needle body reached different depths and different tissues. The Qi obtained from an acupuncture point and the connective tissue of the fascia can be further understood by combining the physiological response of the acupuncture point with the anatomical structure,which offers a new method for defining the nature of the acupuncture point and standardizing the acupuncture point.

关键词： acupuncture De Qi dynamic effect musculoskeletal ultrasound visualization

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Predictive value of neutrophil-to-lymphocyte ratio in coronary chronic total occlusion patients

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Journal of Geriatric Cardiology 2024年第5期21卷 542-549页

作者： Qian LI Yue YU Ya-Qiong ZHOU Yi ZHAO Jin WU Yuan-Jing WU Bin DU Pei-Jian WANG Tao ZHENG department of Cardiovascular Medicine the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina department of Cardiology First Affiliated Hospital of Chengdu Medical CollegeChengduChina department of Neurology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina

BACKGROUND The neutrophil to lymphocyte ratio(NLR)has been reported as a novel predictor for atherosclerosis and car-diovascular *** study aimed to determine the effects of NLR on long-term clinical outcomes of chronic total occlusion(CTO)*** A total of 670 patients with CTO who met the inclusion criteria were included at the end of the follow-up *** were divided into tertiles according to their baseline NLR levels at admission:low(n=223),intermediate(n=223),and high(n=224).The incidence of major adverse cardiac events(MACEs)during the follow-up period,including all-cause death,nonfatal myocardial infarction(MI),or ischemia-driven revascularization,were compared among the three *** Major adverse cardiac events were observed in 27 patients(12.1%)in the low tertile,40(17.9%)in the intermediate tertile,and 61(27.2%)in the high NLR tertile(P<0.001).Kaplan-Meier analysis demonstrated a significantly higher incidence of MACE,ischemia-driven coronary revascularization,non-fatal MI,and mortality in patients within the high tertile than those in the low and intermediate groups(all P<0.001).Multivariable COX regression analysis showed that the high tertile of baseline NLR level showed a strong association with the risk of MACE(hazard ratio[HR]=2.21;95%confidence interval[CI]:1.21-4.03;P=0.009),ischemia-driven coronary revascularization(HR=3.19;95%CI:1.56-6.52;P=0.001),MI(HR=2.61;95%CI:1.35-5.03;P=0.043)and mortality(HR=3.78;95%CI:1.65-8.77;P=0.001).CONCLUSION Our findings suggest that NLR is an inexpensive and readily available biomarker that can independently pre-dict cardiovascular risk in patients with CTO.

关键词： patients coronary occlusion

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Conquer coronary artery perforation with magic hands

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Journal of Geriatric Cardiology 2024年第4期21卷 379-386页

作者： Yi-Lun ZOU Jian-Qiang LI Ding-Yu WANG Yong-Tai GONG Li SHENG Yue LI department of Cardiology the First Affiliated Hospital of Harbin Medical UniversityHarbinChina

Coronary artery perforation(CAP) poses a significant challenge for interventional cardiologists. Management of CAP depends on the location and severity of the perforation. The conventional method for addressing the perforation of large vessels involves the placement of a covered stent, while the perforation of distal and collateral vessels is typically managed using coils, autologous skin, subcutaneous fat, microspheres, gelatin sponge, thrombin or other substances. However, the above techniques have certain limitations and are not applicable in all scenarios. Our team has developed a range of innovative strategies for effectively managing CAP. This article provides an insightful review of the various tips and tricks for the treatment of CAP.

关键词： coronary sponge perforation

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ZIF-8 coated gold nanospheres: A multi-responsive drug delivery system promoting the killing effect of photothermal therapy against osteosarcoma cells

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Nano Research 2024年第3期17卷 1772-1784页

作者： Miao Lei Weiye Cai Luetao Zou Bin Yu Lin Chen Yang Cao Shanlin Xiang Chao Song Jiandu Lei Wei Jiang Zhenming Hu department of orthopedics Orthopedic Laboratory of Chongqing Medical UniversityThe First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China The affiliated Traditional Chinese Medicine hospital of Southwest medical university Luzhou 646699China department of orthopedics The Third Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China department of Radiology The First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China department of orthopedics Chongqing University Three Gorges HospitalChongqing 404000China department of Geriatrics The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550025China Beijing Key Laboratory of Lignocellulosic Chemistry College of Material Science and TechnologyBeijing Forestry UniversityBeijing 100083China

Photothermal therapy(PTT)has been widely used in the treatment of tumors,but its efficacy is greatly limited by the inability of precise drug delivery and the increase of heat shock proteins(HSPs)caused by high *** article describes a therapeutic strategy to enhance PTT with starvation therapy in conjunction with ferroptosis mechanism.A nanoparticle platform ZIF-8@GA was constructed by wrapping together glucose oxidase(GOX)and gold nanospheres(AuNPs)loaded with dihydroartemisinin(DHA)with zeolitic imidazolate framework-8(ZIF-8).This platform can take advantage of the micro-environment of osteosarcoma(OS)cells,featuring low pH and high reactive oxygen species(ROS),for precision drug *** can effectively catalyze glucose to produce gluconic acid and H_(2)O_(2),and DHA can also induce ROS production in OS *** produced by GOX and DHA can further generate lipid peroxidation(LPO)and lead to ferroptosis of OS *** the same time,ROS and LPO produced can inhibit the expression of HSPs,thereby increasing the therapeutic effect of *** vitro experiments show that the nanoparticles are pH and ROS responsive.1μg/mL GOX combined with 0.2μg/mL DHA promotes ferroptosis of OS cells,and increases the killing effect of near-infrared(NIR)on OS *** in vivo experiments showed that the nano drug-delivery platform combined with PTT can effectively inhibit the growth of OS ***,this study provides a new idea for the treatment of OS with biomaterials combined with various treatment methods.

关键词： zeolitic imidazolate framework-8(ZIF-8) gold nanospheres(AuNPs) photothermal therapy(PTT) starvation therapy ferroptosis

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Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano Research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational medical Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer 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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Genetic lineage tracing identifies adaptive mechanisms of pancreatic islet β cells in various mouse models of diabetes with distinct age of initiation

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Science China(Life Sciences) 2024年第3期67卷 504-517页

作者： Qi Fu Yu Qian Hemin Jiang Yunqiang He Hao Dai Yang Chen Zhiqing Xia Yucheng Liang Yuncai Zhou Rui Gao Shuai Zheng Hui Lv Min Sun Kuanfeng Xu Tao Yang department of Endocrinology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

During the pathogenesis of type 1 diabetes(T1D) and type 2 diabetes(T2D), pancreatic islets, especially the β cells, face significant challenges. These insulin-producing cells adopt a regeneration strategy to compensate for the shortage of insulin, but the exact mechanism needs to be defined. High-fat diet(HFD) and streptozotocin(STZ) treatment are well-established models to study islet damage in T2D and T1D respectively. Therefore, we applied these two diabetic mouse models, triggered at different ages, to pursue the cell fate transition of isletβ cells. Cre-LoxP systems were used to generate islet cell type-specific(α, β, or δ) green fluorescent protein(GFP)-labeled mice for genetic lineage tracing, thereinto β-cell GFP-labeled mice were tamoxifen induced. Single-cell RNA sequencing(scRNA-seq) was used to investigate the evolutionary trajectories and molecular mechanisms of the GFP-labeled β cells in STZ-treated mice. STZ-induced diabetes caused extensive dedifferentiation of β cells and some of which transdifferentiated into α or δ cells in both youth-and adulthood-initiated mice while this phenomenon was barely observed in HFD models. β cells in HFD mice were expanded via self-replication rather than via transdifferentiation from α or δ cells, in contrast, α or δ cells were induced to transdifferentiate into β cells in STZ-treated mice(both youthand adulthood-initiated). In addition to the re-dedifferentiation of β cells, it is also highly likely that these “α or δ” cells transdifferentiated from pre-existing β cells could also re-trans-differentiate into insulin-producing β cells and be beneficial to islet recovery. The analysis of ScRNA-seq revealed that several pathways including mitochondrial function, chromatin modification, and remodeling are crucial in the dynamic transition of β cells. Our findings shed light on how islet β cells overcome the deficit of insulin and the molecular mechanism of islet recovery in T1D and T2D pathogenesis.

关键词： islet regeneration lineage tracing high fat diet(HFD) streptozotocin(STZ)

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Profibrotic role of the SOX9-MMP10-ECM biosynthesis axis in the tracheal fibrosis after injury and repair

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Genes & Diseases 2024年第5期11卷 360-373页

作者： Lei Gu Anmao Li Chunyan He Rui Xiao Jiaxin Liao Li Xu Junhao Mu Xiaohui Wang Mingjin Yang Jinyue Jiang Yang Bai Xingxing Jin Meiling Xiao Xia Zhang Tairong Tan Yang Xiao Jing Lin Yishi Li Shuliang Guo department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Soochow UniversitySuzhou 215006China department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Infection Disease The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325000China

Fibroblast activation and extracellular matrix(ECM)deposition play an important role in the tracheal abnormal repair process and *** a transcription factor,SOX9 is involved in fibroblast activation and ECM ***,the mechanism of how SOX9 regulates fibrosis after tracheal injury remains *** investigated the role of SOX9 in TGF-b1-induced fibroblast activation and ECM deposition in rat tracheal fibroblast(RTF)***9 overexpression adenovirus(Ad-SOX9)and siRNA were transfected into RTF *** found that SOX9 expression was up-regulated in RTF cells treated with ***9 overexpression activated fibroblasts and promoted ECM *** SOX9 inhibited cell proliferation,migration,and ECM deposition,induced G2 arrest,and increased apoptosis in RTF ***-seq and chromatin immunoprecipitation sequencing(ChIP-seq)assays identified MMP10,a matrix metalloproteinase involved in ECM deposition,as a direct target of SOX9,which promotes ECM degradation by increasing MMP10 expression through the Wnt/b-catenin signaling ***,in vivo,SOX9 knockdown ameliorated granulation proliferation and tracheal fibrosis,as manifested by reduced tracheal *** conclusion,our findings indicate that SOX9 can drive fibroblast activation,cell proliferation,and apoptosis resistance in tracheal fibrosis via the Wnt/b-catenin signaling *** SOX9eMMP10 eECM biosynthesis axis plays an important role in tracheal injury and *** SOX9 and its downstream target MMP10 may represent a promising therapeutic approach for tracheal fibrosis.

关键词： Extracellular matrix deposition Fibroblast activation MMP10 SOX9 Tracheal fibrosis

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Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke

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Neuroscience Bulletin 2024年第1期40卷 65-78页

作者： Fangxi Liu Xi Cheng Chuansheng Zhao Xiaoqian Zhang Chang Liu Shanshan Zhong Zhouyang Liu Xinyu Lin Wei Qiu Xiuchun Zhang department of Neurology.The first affiliated hospital of China medical university Shenyang 110001China department of Neurology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Stroke Center The First Affiliated Hospital of China Medical UniversityShenyang 110001China

Interactions between brain-resident and periph-eral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ***,con-ventional bulk sequencing makes it challenging to depict this complex immune *** single-cell RNA sequencing,we mapped compositional and transcriptional features of peri-infarct immune *** were the predominant cell type in the peri-infarct region,displaying a more diverse activation pattern than the typical pro-and anti-inflammatory state,with axon tract-associated micro-glia(ATMs)being associated with neuronal *** inference suggested that infiltrated monocyte-derived macrophages(MDMs)exhibited a gradual fate trajectory transition to activated ***-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis,with SOX2 and related Akt/CREB signaling as the underlying *** description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

关键词： Ischemic stroke Monocyte-derived macrophage Microglia Neurogenesis Single-cell sequencing

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