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Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

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Science China(Life Sciences) 2024年第4期67卷 663-679页

作者： Yanfang Liu Yan Wang Bing Liu Wenzhong Liu Yuanyuan Ma Yiren Cao Shi Yan Panpan Zhang Lixin Zhou Qimin Zhan Nan Wu Key Laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Department of Thoracic Oncology IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational research(Ministry of education) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China Peking University International Cancer Institute Beijing 100191China Institute of Cancer research Shenzhen Bay LaboratoryShenzhen 518132China

Chemoresistance is a significant barrier to effective cancer *** mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting ***,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of *** analyzing the serum levels of lncRNA16 in a cohort of 35 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive identification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based *** expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of ***16 binds to HBB and promotes HBB accumulation by inhibiting ***16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the ***,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in ***,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.

关键词： chemoresistance lncRNARNA interference ROs chemosensitizer

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Value of multiple models of diffusion-weighted imaging to predict hepatic lymph node metastases in colorectal liver metastases patients

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World Journal of Gastroenterology 2024年第4期30卷 308-317页

作者： Hai-Bin Zhu Bo Zhao Xiao-Ting Li Xiao-Yan Zhang Qian Yao Ying-Shi Sun Key Laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Department of RadiologyPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND About 10%-31% of colorectal liver metastases(CRLM)patients would concomitantly show hepatic lymph node metastases(LNM),which was considered as sign of poor biological behavior and a relative contraindication for liver *** to now,there’s still lack of reliable preoperative methods to assess the status of hepatic lymph nodes in patients with CRLM,except for pathology examination of lymph node after *** To compare the ability of mono-exponential,bi-exponential,and stretchedexponential diffusion-weighted imaging(DWI)models in distinguishing between benign and malignant hepatic lymph nodes in patients with CRLM who received neoadjuvant chemotherapy prior to *** In this retrospective study,97 CRLM patients with pathologically confirmed hepatic lymph node status underwent magnetic resonance imaging,including DWI with ten b values before and after *** parameters,such as the apparent diffusion coefficient from the mono-exponential model,and the true diffusion coefficient,the pseudo-diffusion coefficient,and the perfusion fraction derived from the intravoxel incoherent motion model,along with distributed diffusion coefficient(DDC)andαfrom the stretched-exponential model(SEM),were *** parameters before and after chemotherapy were compared between positive and negative hepatic lymph node groups.A nomogram was constructed to predict the hepatic lymph node *** reliability and agreement of the measurements were assessed using the coefficient of variation and intraclass correlation *** Multivariate analysis revealed that the pre-treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes.A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients,with an area under the curve of ***,parameters from SEM sho

关键词： Colorectal cancer Individualized treatment Diffusion magnetic resonance imaging Intravoxel incoherent motion Liver

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Late corneal ectasia after penetrating and deep anterior lamellar keratoplasty for keratoconus

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1828-1836页

作者： Bora Yüksel Arife Esra Kocakaya Tuncay Küsbeci Fatih Gümüş Department of Ophthalmology University of Health SciencesIzmir Bozyaka Education and Research HospitalIzmir 35110Türkiye

AIM:To investigate tomographic features of late corneal ectasia after keratoplasty for keratoconus and compare penetrating keratoplasty(PK)and deep anterior lamellar keratoplasty(DALK)in terms of incidence,time of onset and risk factors of corneal ***:Sixty eyes with PK and 30 eyes with DALK operated between 1999 and 2021 were *** Pentacam scans were evaluated together with vision and previous *** outcome measures were vision,K values,apparent thinning on graft-host cornea and the difference between opposing quadrants in the thinnest point *** segment optic coherence tomography was performed for further ***:Mean follow-up was 127.2mo(24–282mo)in PK,and 64.3mo(24–144mo)in DALK.K max was higher in DALK(60.6 vs 56.7 D,P=0.012).Inferior recipient was thinner(595.9μm)in PK than DALK(662.2μm,P=0.021),due to longer *** corneal ectasia rate was 20.0%within *** rate was the same(6.7%)in DALK 2/30 and in PK 4/60 in 10y and 13.3%in 12y(4/30 and 8/60,respectively).It increased to 23.3%(14/60)in PK over *** ectasia was not seen before 7y in PK,it could be seen in DALK starting from the 5^(th) *** intervals between keratoplasty and ectasia were 144.5mo in PK and 99mo in *** recipient was significantly thinner in 18 eyes with ectasia(502.7μm)compared to 76 non-ectasia(649.1μm,P=0.000).Inferior graft was thinner(561.0 vs 620.4μm,P=0.006),K max(63.3 vs 56.5 D,P=0.000),and anterior elevation was higher in ectasia(89.1 vs 48.6μm,P=0.002).Accelerated crosslinking was performed on 5 ***:Inferior-superior recipient and inferior graft thinning on tomography,with high K max and anterior elevation emerge as the most reliable criteria for the diagnosis of late *** incidence of corneal ectasia increases with the time.

关键词： keratoconus penetrating keratoplasty deep anterior lamellar keratoplasty corneal ectasia

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FGM-SPCL:Open-Set Recognition Network for Medical Images Based on Fine-Grained Data Mixture and Spatial Position Constraint Loss

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Chinese Journal of Electronics 2024年第4期33卷 1023-1033页

作者： Ruru ZHANG Haihong E Lifei YUAN Yanhui WANG Lifei WANG Meina SONG School of Computer Science Beijing University of Posts and Telecommunications Engineering research Center of Information Networks Ministry of Education Hebei Eye hospital

The current intelligent auxiliary diagnosis models all follow the closed-set recognition setting. After the model is deployed online, the input data is often not completely controlled. Diagnosing an untrained disease as a known category would lead to serious medical malpractice. Therefore, realizing the open-set recognition is significant to the safe operation of the intelligent auxiliary diagnosis model. Currently, most open-set recognition models are studied for natural images, and it is very challenging to obtain clear and concise decision boundaries between known and unknown classes when applied to fine-grained medical images. We propose an open-set recognition network for medical images based on fine-grained data mixture and spatial position constraint loss(FGM-SPCL) in this *** the fine graininess of medical images and the diversity of unknown samples, we propose a fine-grained data mixture(FGM) method to simulate unknown data by performing a mixing operation on known data to expand the coverage of unknown data difficulty levels. In order to obtain a concise and clear decision boundary, we propose a spatial position constraint loss(SPCL) to control the position distribution of prototypes and samples in the feature space and maximize the distance between known classes and unknown classes. We validate on a private ophthalmic OCT dataset, and extensive experiments and analyses demonstrate that FGM-SPCL outperforms state-of-the-art models.

关键词： Analytical models Fine-grained image recognition Prototypes Aerospace electronics Spatial databases Robustness Data models

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Helicobacter pylori and immunotherapy for gastrointestinal cancer

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The Innovation 2024年第2期5卷 51-60页

作者： Keren Jia Yang Chen Yi Xie Xicheng Wang Yajie Hu Yu Sun Yanshuo Cao Liyan Zhang Yakun Wang Zhenghang Wang Zhihao Lu Jian Li Xiaotian Zhang Lin Shen Key Laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Department of PathologyPeking University Cancer Hospital&InstituteBeijing 100142China

Helicobacter pylori infection is associated with the risk of gastrointestinal(GI)cancers;however,its impact on immunotherapy for GI cancers remains *** this study,we included 10,122 patients who underwent ^(13)C-urea breath *** 636 patients with Epstein-Barr virus–negative microsatellite-stable gastric cancer(GC)who were treated with anti-PD-1/PD-L1 therapy,***–positive patients exhibited significantly longer immune-related progression-free survival(irPFS)compared with ***–negative patients(6.97 months versus 5.03 months,p<0.001,hazard ratio[HR]0.76,95%confidence interval[CI]0.62–0.95,p=0.015).Moreover,the ***–positive group demonstrated a trend of 4 months longer median immune-related overall survival(irOS)than the ***–negative ***–positive GC displayed higher densities of PD-L1+cells and nonexhausted CD8+T cells,indicative of a“hot”tumor *** analysis revealed that ***–positive GC shared molecular characteristics similar to those of immunotherapy-sensitive ***,***–positive patients with DNA mismatch repair–deficient(dMMR)/microsatellite instability–high(MSI-H)colorectal adenocarcinoma and esophageal squamous cell carcinoma(ESCC)had shorter irPFS compared with ***–negative patients(16.13 months versus not reached,p=0.042,HR 2.26,95%CI 1.13–4.50,p=0.021 and 5.57 months versus 6.97 months,p=0.029,HR 1.59,95%CI 1.14–2.23,p=0.006,respectively).The difference in irOS between ***–positive and–negative patients had the same trend as that between dMMR/MSI-H colorectal adenocarcinoma and ESCC *** also identified a trend of shorter irPFS and irOS in ***–positive liver cancer and pancreatic cancer *** summary,our findings supported that *** infection is a beneficial factor for GC immunotherapy by shaping hot tumor ***,in dMMR/MSI-H colorectal adenocarcinoma and ESCC patients,*** adversely affects the efficacy of immunothera

关键词： immunotherapy gastrointestinal pylori

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Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers:An open-label,non-randomized,phase II clinical trial

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World Journal of Gastroenterology 2024年第30期30卷 3564-3573页

作者： Ling-Xiao Xu Jia-Jia Yuan Ran Xue Jun Zhou Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment *** To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic *** This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer hospital and the First hospital of China Medical *** patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease *** primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and *** A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were *** response assessment was impeded for one patient due to premature demise from tumor *** the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were *** Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

关键词： Nab-paclitaxel Capecitabine Biliary tract cancer Objective response rate Phase II clinical trial

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Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke

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research 2024年第1期2023卷 369-387页

作者： Hongfei Ge Tengyuan Zhou Chao Zhang Yupeng Cun Weixiang Chen Yang Yang Qian Zhang Huanhuan Li Jun Zhong Xuyang Zhang Hua Feng Rong Hu Department of Neurosurgery and Key Laboratory of Neurotrauma Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina Medical research Center Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina Pediatric research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChildren’s Hospital of Chongqing Medical University400014 ChongqingChina

Cell replacement therapy using neural progenitor cells(NPCs)has been shown to be an effective treatment for ischemic ***,the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after *** acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a(ASIC1a),a subunit of proton-gated cation channels following ischemic ***,the role of ASIC1a in NPCs post-ischemia remains ***,our results indicated that ASIC1a was expressed in NPCs with channel functionality,which could be activated by extracellular *** evidence revealed that ASIC1a activation inhibited NPC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation,which could be primarily reversed by pharmacological or genetic disruption of *** vivo data showed that the knockout of the ASIC1a gene facilitated NPC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke.

关键词： ASIC1a homeostasis inhibited

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Prenatal Diagnosis of an Apically Located Congenital Left Ventricular Aneurysm: A Rare Case

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Congenital heart Disease 2024年第1期19卷 123-129页

作者： Yücel Kaya And Yavuz Hasan Berkan Sayal Büşra Tsakir Gökalp Kabacaoğlu Kadriye NilayÖzcan Department of Perinatology Antalya Education and Research HospitalUniversity of Health SciencesAntalyaTurkey Department of Perinatology Faculty of MedicineSüleyman Demirel UniversityIspartaTurkey

Congenital ventricular aneurysm is a very rare cardiac anomaly.A diagnosis can be made during the prenatal period using fetal *** study presents a very rare apically located left ventricular aneurysm case,and the relevant literature was reviewed and *** this case,a 35-year-old,gravida 2,parity 1 preg-nant woman at 24 weeks of gestation,displayed a wide aneurysmal image in the left ventricular apical wall on fetal *** was a 1.79 mm muscular ventricular septal defect at the apical region of the interven-tricular *** the course of the color Doppler ultrasonography examination,an aberrantﬁbrous band within the left ventricle and consequent turbulentﬂow during systole were *** baby,born via cesarean section at 37 weeks of gestation,is now in its postnatal seventh ***,during echocardiographic follow-ups,changes have been observed,including mild to moderate mitral insufﬁciency and a decrease in systolic *** theseﬁndings,the clinical condition remains *** is of great importance to use a multidis-ciplinary approach in managing these rare cases that could lead to potential adverse outcomes during the antena-tal or postnatal periods.

关键词： heart aneurysm prenatal diagnosis echocardiography congenital heart defects left ventricle

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Memory Trace for Fear Extinction:Fragile yet Reinforceable

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Neuroscience Bulletin 2024年第6期40卷 777-794页

作者： Ying Liu Shuai Ye Xin-Ni Li Wei-Guang Li Department of Rehabilitation Medicine State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceHuashan HospitalInstitute for Translational Brain ResearchFudan UniversityShanghai200032China

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing *** on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear *** brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain *** questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction *** this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.

关键词： Fear extinction memory Memory trace Fear relapse Medial prefrontal cortex Basolateral amygdala Ventral hippocampus Insular cortex Synaptic adaptations

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SH2B1 Tunes Hippocampal ERK Signaling to Influence Fluid Intelligence in Humans and Mice

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research 2024年第3期2023卷 369-389页

作者： Xiujuan Du Yuhua Yan Juehua Yu Tailin Zhu Chu-Chung Huang Lingli Zhang Xingyue Shan Ren Li Yuan Dai Hui LV Xiao-Yong Zhang Jianfeng Feng Wei-Guang Li Qiang Luo Fei Li Developmental and Behavioral Pediatric Department Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children's Environmental HealthXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Developmental and Behavioral Pediatric Department Shanghai Xinhua Children's HospitalShanghai 200092China National Clinical research Center for Aging and Medicine at Huashan hospital Institute of Science and Technology for Brain-lnspired IntelligenceMinistry of Education-Key Laboratory of Computational Neuroscience and Brain-lnspired IntelligenceFudan UniversityShanghai 200433China State Key Laboratory of Medical Neurobiology and Ministry of education Frontiers Center for Brain Science Institutes of Brain Science and Human Phenom InstituteFudan UniversityShanghai 200032China Shanghai Key Laboratory of Brain Functional Genomics(Ministry of education) School of Life SciencesEast China Normal UniversityShanghai 200062China Department of Rehabilitation Medicine Huashan HospitalInstitute for Translational Brain ResearchState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceFudan UniversityShanghai 200032China Center for Experimental Studies and research The First Affliated Hospital of Kunming Medical UniversityKunming 650032China Shanghai research Center for Brain Science and Brain-lnspired Intelligence Shanghai201210China Institute of Cognitive Neuroscience School of Psychology and Cognitive ScienceEast China Normal UniversityShanghai 200062China.

Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1, TUFM, ATP2A1, and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1 in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.

关键词： metabolism impaired reversed

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