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Engineered extracellular vesicles for targeted reprogramming of cancer-associated fibroblasts to potentiate therapy of pancreatic cancer

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3077-3096页

作者： Pengcheng Zhou Xuanlong Du Weilu Jia Kun Feng Yewei Zhang Department of General Surgery Affiliated Hospital of Nantong UniversityNantongChina School of Medicine Southeast UniversityNanjingChina nanjing Medical University NanjingChina Hepatobiliary and Pancreatic Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina

Pancreatic cancer is one of the deadly malignancies with a significant mortality rate and there are currently few therapeutic options for *** tumor microenvironment(TME)in pancreatic cancer,distinguished by fibrosis and the existence of cancer-associated fibroblasts(CAFs),exerts a pivotal influence on both tumor advancement and resistance to *** advancements in the field of engineered extracellular vesicles(EVs)offer novel avenues for targeted therapy in pancreatic *** study aimed to develop engineered EVs for the targeted reprogramming of CAFs and modulating the TME in pancreatic *** obtained from bone marrow mesenchymal stem cells(BMSCs)were loaded with miR-138-5p and the anti-fibrotic agent pirfenidone(PFD)and subjected to surface modification with integrinα5-targeting peptides(named IEVs-PFD/138)to reprogram CAFs and suppress their pro-tumorigenic ***α5-targeting peptide modification enhanced the CAF-targeting ability of ***-138-5p directly inhibited the formation of the FERMT2-TGFBR1 complex,inhibiting TGF-βsignaling pathway *** addition,miR-138-5p inhibited proline-mediated collagen synthesis by directly targeting the FERMT2-PYCR1 *** combination of miR-138-5p and PFD in EVs synergistically promoted CAF reprogramming and suppressed the pro-cancer effects of *** experiments using the orthotopic stroma-rich and patient-derived xenograft mouse models yielded promising *** particular,IEVs-PFD/138 effectively reprogrammed CAFs and remodeled TME,which resulted in decreased tumor pressure,enhanced gemcitabine perfusion,tumor hypoxia amelioration,and greater sensitivity of cancer cells to ***,the strategy developed in this study can improve chemotherapy *** IEVs-PFD/138 as a targeted therapeutic agent to modulate CAFs and the TME represents a promising therapeutic approach for pancreatic cancer.

关键词： inhibited targeted chemotherapy

Clinical Value of the Quantitative Flow Ratio to Predict Long-term Target Vessel Failure in Patients with In-stent Restenosis after Drug-coated Balloon Angioplasty

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Current Medical Science 2024年第3期44卷 561-567页

作者： Xiang-qi WU Long-bo LI Wei YOU Zhi-ming WU Lei ZHAO Zhi-hui WANG Pei-na MENG Bin LIU Fei YE Department of Cardiology Nanjing First HospitalNanjing Medical UniversityNanjing210006China Department of Cardiology The Second Hospital of Jilin UniversityJilin130000China

Objective The study sought to investigate the clinical predictive value of quantitative flow ratio(QFR)for the long-term target vessel failure(TVF)outcome in patients with in-stent restenosis(ISR)by using drug-coated balloon(DCB)treatment after a long-term *** This was a retrospective study.A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were *** QFR of the entire target vessel was measured *** primary endpoint was TVF,including target vessel-cardiac death(TV-CD),target vessel-myocardial infarction(TV-MI),and clinically driven-target vessel revascularization(CD-TVR).Results The follow-up time was 3.09±1.53 years,and 50 patients had *** QFR immediately after percutaneous coronary intervention(PCI)was significantly lower in the TVF group than in the no-TVF *** Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up[hazard ratio(HR):5.15×10−5(6.13×10−8−0.043);P<0.01].Receiver-operating characteristic(ROC)curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925(area under the curve:0.886,95%confidence interval:0.834–0.938;sensitivity:83.40%,specificity:88.00;P<0.01).In addition,QFR≤0.925 post-PCI was strongly correlated with the TVF,including TV-MI and CD-TVR(P<0.01).Conclusion The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty.A lower QFR immediately after PCI was associated with a worse TVF outcome.

关键词： percutaneous coronary intervention in-stent restenosis target vessel failure quantitative flow ratio

Distributed active vibration control for helicopter based on diffusion collaboration

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Chinese Journal of Aeronautics 2024年第8期37卷 208-232页

作者： Yang YUAN Yang LU Xunjun MA Jingliang LI Huiyu YUE National Key Laboratory of Helicopter Aeromechanics Nanjing University of Aeronautics and AstronauticsNanjing 210016China Wuhan second Ship Design and Research Institute Wuhan 430205China

The active vibration control technology has been successfully applied to several helicopter ***,with the increasing of control scale,traditional centralized control algorithms are experiencing significant increase of computational complexity and physical implementation *** address this issue,a diffusion collaboration-based distributed Filtered-x Least Mean Square algorithm applied to active vibration control is proposed,drawing inspiration from the concept of data fusion in wireless sensor *** algorithm distributes the computation load to each node,and constructs the active vibration control network topology of large-scale system by discarding the weak coupling secondary paths between nodes,achieving distributed active vibration *** order to thoroughly validate the effectiveness and superiority of this algorithm,a helicopter fuselage model is designed as the research ***,the excellent vibration reduction performance of the proposed algorithm is confirmed through ***,specialized node control units are developed,which utilize STM32 microcontroller as the processing ***,a distributed control system is constructed based on multi-processor *** on this foundation,a large-scale active vibration control experimental platform is *** on the platform,experiments are carried out,involving the 4-input 4-output system and the 8-input 8-output *** experimental results demonstrate that under steady-state harmonic excitation,the proposed algorithm not only ensures control effectiveness but also reduces computational complexity by 50%,exhibiting faster convergence speed compared with traditional centralized *** time-varying external excitation,the proposed algorithm demonstrates rapid tracking of vibration changes,with vibration amplitudes at all controlled points declining by over 94%,proving the strong robustness and adaptive capability of the algorithm

关键词： Helicopter Active vibration control Diffusion collaboration Distributed control Experiment

Potential clinical application of microRNAs in bladder cancer

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Journal of Biomedical Research 2024年第4期38卷 289-306页

作者： Pei Wang Xiaowei Wei Xiaojun Qu Yefei Zhu Laboratory Medicine Center the Second Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210011China School of Biological Science and Medical Engineering Southeast UniversityNanjingJiangsu 210096China

Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent ***,cystoscopy and urine cytology serve as the established diagnostic methods for ***,their efficacy is limited by their invasive nature and low ***,the development of highly specific biomarkers and effective noninvasive detection strategies is imperative for achieving a precise and timely diagnosis of BC,as well as for facilitating an optimal tumor treatment and an improved ***(miRNAs),short noncoding RNA molecules spanning around 20–25 nucleotides,are implicated in the regulation of diverse carcinogenic *** altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of *** into aberrant miRNAs derived from blood,urine,or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC,enabling miRNAs to monitor the progression and predict the recurrence of the ***,the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of *** review comprehensively analyzes biological roles of miRNAs in tumorigenesis and progression,and systematically summarizes their potential as diagnostic and prognostic biomarkers,as well as therapeutic targets for ***,we evaluate the progress made in laboratory techniques within this field and discuss the prospects.

关键词： bladder cancer microRNAs biomarker diagnosis detection method

Subclinical impairment of left ventricular myocardium function in type 2 diabetes mellitus patients with or without hypertension

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World Journal of Diabetes 2024年第6期15卷 1272-1279页

作者： Zeng-Guang Chen Guang-An Li Jun Huang Li Fan Department of Cardiology The Affiliated Changzhou Second People’s Hospital with Nanjing Medical UniversityChangzhou 213000Jiangsu ProvinceChina Department of Echocardiography The Affiliated Changzhou Second People’s Hospital with Nanjing Medical UniversityChangzhou 213000Jiangsu ProvinceChina

BACKGROUND Cardiovascular disease has been the leading cause of morbidity and mortality for type 2 diabetes mellitus(T2DM)patients over the last *** To determine whether layer-specific global longitudinal strain(GLS)combined with peak strain dispersion(PSD)can be used to assess left ventricle(LV)myocardium systolic dysfunction in T2DM patients or without hypertension(HP).METHODS We enrolled 97 T2DM patients,70 T2DM+HP patients and 101 healthy ***-specific GLS and PSD were calculated by EchoPAC software in apical three-,four-and two-chamber *** of the epimyocardial,middle-layer and endomyocardial(GLSepi,GLSmid,and GLSendo)were measured and *** operating characteristic analysis was performed to detect LV myocardium systolic dysfunction in T2DM *** There were significant differences in GLSepi,GLSmid,GLSendo,and PSD between healthy subjects,T2DM patients and T2DM patients with HP(PT2DM patients>T2DM with HP patients in the absolute values of GLSepi,GLSmid and GLSendo(P<0.001),while PSD was ranked healthy subjects

关键词： Type 2 diabetes mellitus Hypertension Speckle tracking echocardiography Global longitudinal strain Peak strain dispersion

3'-Deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome

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Neural Regeneration Research 2024年第10期19卷 2270-2280页

作者： Yize Qi Yao Zhou Jiyang Li Fangyuan Zhu Gengni Guo Can Wang Man Yu Yijie Wang Tengfei Ma Shanwu Feng Li Zhou Institute for Stem Cell and Neural Regeneration and Key Laboratory of Cardiovascular&Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Anesthesiology The Second People’s Hospital of LianyungangLianyungangJiangsu ProvinceChina Department of Anesthesiology Women’s Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjingJiangsu ProvinceChina

Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

关键词： 3′-deoxyadenosin hippocampus long-term potentiation methamphetamine NOD-like receptor family pyrin domain containing-3(NLRP3)inflammasome synaptic plasticity

Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome

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Journal of Pharmaceutical Analysis 2024年第1期14卷 152-155页

作者： Shuyu Zheng Yanlin Xin Jiamin Lin Zejuan Xie Keyu Cheng Shanshan Wang Wenli Lu Hao Yang Tianming Lu Jun Li Ruogu Qi Yuanyuan Guo Department of Biochemistry and Molecular Biology School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing210023China Department of Neurosurgery The Second Affiliated HospitalZhejiang UniversityHangzhou310009China

The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget *** a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(***)and is used as an expectorant for pulmonary disease in Asia[2].

关键词： NSCLC eIF4E treatment

Application value of indocyanine green fluorescence imaging in guiding sentinel lymph node biopsy diagnosis of gastric cancer: Meta-analysis

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1883-1893页

作者： Qi-Jia Zhang Zhi-Cheng Cao Qin Zhu Yu Sun Rong-Da Li Jin-Long Tong Qin Zheng Department of Oncology The Second Hospital of NanjingAffiliated to Nanjing University of Chinese MedicineNanjing 210003Jiangsu ProvinceChina Department of Gastrointestinal Surgery Qilu Hospital of Shandong UniversityJinan 250063Shandong ProvinceChina

BACKGROUND Gastric cancer is a common malignant tumor of the digestive system worldwide,and its early diagnosis is crucial to improve the survival rate of *** green fluorescence imaging(ICG-FI),as a new imaging technology,has shown potential application prospects in oncology *** meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical *** To assess the diagnostic efficacy of optical imaging in conjunction with indocya-nine green(ICG)-guided sentinel lymph node(SLN)biopsy for gastric *** Electronic databases such as PubMed,Embase,Medline,Web of Science,and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN *** 12.0 software was used for analysis by combining the"bivariable mixed effect model"with the"midas"*** true positive value,false positive value,false negative value,true negative value,and other information from the included literature were extracted.A literature quality assessment map was drawn to describe the overall quality of the included literature.A forest plot was used for heterogeneity analysis,and P50%),meta-regression analysis and subgroup analysis were *** were *** Optical imaging involves two methods:Near-infrared(NIR)imaging and fluorescence imaging.A combination of optical imaging and ICG-guided SLN biopsy was useful for *** positive likelihood ratio was

关键词： Gastric neoplasms Sentinel lymph nodes Near infrared imaging Fluorescence imaging Indocyanine green Meta-analysis

Precise nano-system-based drug delivery and synergistic therapy against androgen receptor-positive triple-negative breast cancer

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2685-2697页

作者： Fangyan Gao Yueyao Wu Runtian Wang Yuhui Yao Yiqiu Liu Lingling Fan Jingtong Xu Jian Zhang Xin Han Xiaoxiang Guan Department of Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing 210023China Department of Oncology the Second Hospital of NanjingNanjing University of Chinese MedicineNanjing 210023China Department of Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China

Targeting androgen receptor(AR)has shown great therapeutic potential in triple-negative breast cancer(TNBC),yet its efficacy remains ***,we aimed to identify promising targeted agents that synergize with enzalutamide,a second-generation AR inhibitor,in *** using a strategy for screening drug combinations based on the Sensitivity Index(SI),we found that MK-8776,a selective checkpoint kinase1(CHK1)inhibitor,showed favorable synergism with enzalutamide in AR-positive *** combination of enzalutamide and MK-8776 was found to exert more significant anti-tumor effects in TNBC than the single application of enzalutamide or MK-8776,***,a nanoparticle-based on hyaluronic acid(HA)-modified hollow-manganese dioxide(HMnO_(2)),named HMnE&M@H,was established to encapsulate and deliver enzalutamide and *** HA-modified nanosystem managed targeted activation via pH/glutathione ***&M@H repressed tumor growth more obviously than the simple addition of enzalutamide and MK-8776 without a ***,our study elucidated the synergy of enzalutamide and MK-8776 in TNBC and developed a novel tumor-targeted nano drug delivery system HMnE&M@H,providing a potential therapeutic approach for the treatment of TNBC.

关键词： Triple-negative breast cancer Androgen receptor Checkpoint kinase 1 Enzalutamide MK-8776 Synergy HMnO_(2) Nanodrug delivery system