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Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain

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Science China(Life Sciences) 2024年第1期67卷 67-82页

作者： Chun-Kui Zhang Pan Wang Yuan-Yuan Ji Jian-Shuai Zhao Jun-Xiang Gu Xian-Xia Yan Hong-Wei Fan ming-ming Zhang Yu Qiao Xiao-Die Liu Bao-Juan Li ming-Hui Wang Hai-Long Dong hao-Hong Li Peng-Cheng Huang Yun-Qing Li Wu-Gang Hou Jin-Lian Li Tao Chen Department of Anatomy and K.K.Leung Brain Research Centre Fourth Military Medical UniversityXi’an 710032China Beijing Institute of Basic Medical Sciences Beijing 100850China Key Laboratory of Ministry of Public Health for Forensic Science Xi’an Jiaotong UniversityXi’an 710061China Department of Anesthesiology Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Neurosurgery the Second Affiliated Hospital of Xian Jiaotong UniversityXi’an 710004China School of Biomedical Engineering Fourth Military Medical UniversityXi’an 710032China Affiliated Mental Health Centre and Hangzhou Seventh People’s Hospital Zhejiang University School of MedicineHangzhou 310013China The MOE Frontier Research Center of Brain&Brain-machine Integration Zhejiang University School of Brain Science and Brain MedicineHangzhou 310058China Department of Neurology The First Affiliated Hospital of Nanchang UniversityNanchang 330006China Department of Anatomy School of MedicineNorthwest UniversityXi’an 710069China

Chronic pain often develops severe mood changes such as ***,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely *** we found that depression-like behaviors could only be observed in 67.9%of mice with chronic neuropathic pain,leaving 32.1%of mice with depression *** determined that the spike discharges of the ventral tegmental area(VTA)-projecting lateral habenula(LHb)glutamatergic(Glu)neurons were sequentially increased in sham,resilient and susceptible mice,which consequently inhibited VTA dopaminergic(DA)neurons through a LHbGlu-VTAGABA-VTADA ***,the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic *** of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic *** study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

关键词： chronic pain depression lateral habenula ventral tegmental area dopamine susceptibility

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Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1647-1659页

作者： Ju-Hang Chu Lu-Yao Huang Ya-Ru Wang Jun Li Shi-Long Han hao Xi Wen-Xue Gao Ying-Yu Cui ming-Ping Qian Department of General Surgery Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghai 200072China Department of Interventional and Vascular Surgery Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghai 200072China Department of Pathology Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghai 200072China Clinical Research Management Office Shanghai Tenth People’s HospitalShanghai 200072China Department of Cell Biology Institute of Medical GeneticsState Key Laboratory of CardiologyTongji University School of MedicineShanghai 200331China

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical *** demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced *** SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal *** computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/***,he was judged to have advanced *** treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of *** the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be *** pathological diagnosis indicated a complete *** patient recovered well after the operation,and no tumor recurrence was *** Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant *** drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

关键词： Hepatocellular therapy Conversion hepatectomy Interventional therapy Epclusa Lenvatinib Sintilimab Case report

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Long-term tadalafil once daily in Chinese men with erectile dysfunction:a 2-year final analysis of a post-marketing,multicenter,randomized,open-label trial

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Asian Journal of Andrology 2024年第3期26卷 282-287页

作者： Hui Jiang Lian-ming Zhao Su Yan Ji-Hong Liu Zhao-Hui Zhu Jin-Dan Luo Yu-Tian Dai Fu-Biao Li hao-Cheng Lin Zhi-Chao Zhang Department of Urology Peking University First HospitalBeijing 100000China Department of Urology Peking University Third HospitalBeijing 100191China Department of Urology Peking Union Medical College HospitalBeijing 100730China Department of Urology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Urology Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Urology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Departmentof Andrology Nanjing Drum Tower HospitalNanjing 210008China Department of Andrology The First Hospital of Jilin UniversityChangchun 130021China Andrology Center Department of UrologyPeking University First HospitalBeijing 100034China

The long-term safety and effectiveness of once-daily tadalafil is crucial,but limited data are available in Chinese patients witherectile dysfunction(ED).In this post-marketing,multicenter,randomized,open-label trial with 2-year follow-up,635 ED caseswere randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months,of whom 580 continued once-daily tadalafil 5 mg for21 ***-emergent adverse events in the 12-month and 24-month period were similar,with the most common beingviral upper respiratory tract infection,upper respiratory tract infection,and *** improvement from baseline inthe International Index of Erectile Function-Erectile Function(IIEF-EF)score was detected at month 12(least squares mean[LSM]change:7.9,95%confidence interval[CI]:7.5–8.4,Pdurable improvement in sexual performance and satisfaction.

关键词： clinical trial erectile dysfunction long-term safety once-daily dosing tadalafil

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Washed microbiota transplantation for Crohn’s disease:A metagenomic,metatranscriptomic,and metabolomic-based study

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World Journal of Gastroenterology 2024年第11期30卷 1572-1587页

作者： Shi-Ju Chen Da-Ya Zhang Xia Wu Fa-ming Zhang Bo-Ta Cui Yi-hao Huang Zu-Lun Zhang Rui Wang Fei-Hu Bai Graduate School Hainan Medical UniversityHaikou 571199Hainan ProvinceChina Department of Microbiota Medicine&Medical Center for Digestive Diseases The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210011Jiangsu ProvinceChina Department of Gastroenterology The Second Affiliated Hospital of Hainan Medical UniversityHaikou 570216Hainan ProvinceChina

BACKGROUND Fecal microbiota transplantation(FMT)is a promising therapeutic approach for treating Crohn’s disease(CD).The new method of FMT,based on the automatic washing process,was named as washed microbiota transplantation(WMT).Most existing studies have focused on observing the clinical ***,the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome,metatranscriptome,and metabolome-has not yet been *** To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to *** We conducted a prospective,open-label,single-center clinical *** CD patients underwent *** clinical responses(defined as a decrease in their CD Activity Index score of>100 points)and their microbiome(metagenome,metatranscriptome)and metabolome profiles were evaluated three months after the *** Seven of the 11 patients(63.6%)showed an optimal clinical response three months *** microbiome diversity significantly increased after WMT,consistent with improved clinical *** of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains,such as Faecalibac-terium prausnitzii,Roseburia intestinalis,and Escherichia *** addition,metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the ***,levels of vital amino acids that may be associated with disease progression(e.g.,L-glutamic acid,gamma-glutamyl-leucine,and prolyl-glutamine)were reduced after *** WMT demonstrated therapeutic efficacy in CD treatment,likely due to the effective reconstruction of the patient’s ***-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

关键词： Crohn’s disease Clinical trials Fecal microbiota transplant Metagenome Metatranscriptome Metabolome

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Disaster effects of climate change in High Mountain Asia:State of art and scientific challengesDisaster effects of climate change in High Mountain Asia:State of art and scientific challenges

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Advances in Climate Change Research 2024年第3期15卷 367-389页

作者： hao Wang Bin-Bin Wang Peng Cui Yao-ming Ma Yan Wang Jian-Sheng hao Yu Wang Ya-Mei Li Li-Jun Sun Jiao Wang Guo-Tao Zhang Wei-Mo Li Yu Lei Wen-Qing Zhao Jin-Bo Tang Chao-Yue Li Institute of Mountain Hazards and Environment Chinese Academy of SciencesChengdu 610041China State Key Laboratory of Tibetan Plateau Earth System Environment and Resources(TPESER)Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100101China Institute of Geographic Sciences and Natural Resources Research Chinese Academy of SciencesBeijing 100101China China‒Pakistan Joint Research Center on Earth Sciences Chinese Academy of SciencesIslamabad 45320Pakistan College of Earth and Planetary Sciences University of Chinese Academy of SciencesBeijing 100049China College of Atmospheric Science Lanzhou UniversityLanzhou 730000China National Observation and Research Station for Qomolongma Special Atmospheric Processes and Environmental Changes Dingri 858200China

High Mountain Asia(HMA)shows a remarkable warming tendency and divergent trend of regional precipitation with enhanced meteorological *** rapid thawing of the HMA cryosphere may alter the magnitude and frequency of nature *** reviewed the influence of climate change on various types of nature hazards in HMA region,including their phenomena,mechanisms and *** reveals that:1)the occurrences of extreme rainfall,heavy snowfall,and drifting snow hazards are escalating;accelerated ice and snow melting have advanced the onset and increased the magnitude of snowmelt floods;2)due to elevating trigger factors,such as glacier debuttressing and the rapid shift of thermal and hydrological regime of bedrock/snow/ice interface or subsurface,the mass flow hazards including bedrock landslide,snow avalanche,ice-rock avalanches or glacier detachment,and debris flow will become more severe;3)increased active-layer detachment and retrogressive thaw slumps slope failures,thaw settlement and thermokarst lake will damage many important engineering structures and infrastructure in permafrost region;4)multi-hazards cascading hazard in HMA,such as the glacial lake outburst flood(GLOF)and avalanche-induced mass flow may greatly enlarge the destructive power of the primary hazard by amplifying its volume,mobility,and impact force;and 5)enhanced slope instability and sediment supply in the highland areas could impose remote catastrophic impacts upon lowland regions,and threat hydropower security and future water *** future,ongoing thawing of HMA will profoundly weaken the multiple-phase material of bedrock,ice,water,and soil,and enhance activities of nature *** and cascading hazards of high magnitude will prevail in *** the glacier runoff overpasses the peak water,low flow or droughts in lowland areas downstream of glacierized mountain regions will became more frequent and *** escalating hazards in the HMA region requires tackling s

关键词： High Mountain Asia Climate change Cryosphere degradation Nature hazards Disaster risk

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Crosstalk among Oxidative Stress,Autophagy,and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells:A Mixed Computational and Experimental Study

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Current Medical Science 2024年第3期44卷 578-588页

作者： Yi-miao LUO Shu-sen LIU ming Zhao Wei WEI Jiu-xiu YAO Jia-hui SUN Yu CAO hao LI Department of Geriatrics Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan)Beijing100901China Department of Integration of Chinese and Western Medicine Peking University Health Science CenterBeijing100191China School of Pharmacy Harbin University of CommerceHarbin150028China Xiyuan Hospital China Academy of Chinese Medical ScienceBeijing100901China Wangjing Hospital China Academy of Chinese Medical ScienceBeijing100102China

Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. Methods An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis (GSEA),Gene Ontology (GO) classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,protein-protein interaction network analysis,and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. Results Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically,GRb1 was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62),autophagy related 5 (ATG5),and hypoxia-inducible factor 1-alpha (HIF-1α) were identified,highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. Conclusion GRbl protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy. The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.

关键词： ischemic stroke ginsenoside Rb1 brain microvascular endothelial cells oxidative stress autophagy apoptosis bioinformatic analysis

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NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 153-164页

作者： Bo Shi Cheng-Jie Lyu Zhen-Kai Le hao-Sen Ji Yi Xiao Yuan-Yuan Zhang Shou-Jiang Huang Lin-Jun Yu Qiang Shu Jin-Fa Tou Deng-ming Lai Department of Neonatal Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Pulmonology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Thoracic and Cardiovascular Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China

Background Macrophages are involved in various immune inflammatory disease *** study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western *** pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3^(-/-))model of *** mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various ***,intestinal epithelial cell injuries,and IL-1β release were *** Compared to the gut“healthy”patients,the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3,caspase-1,and IL-1β ***,in vivo,the survival rate of Nlrp3^(-/-)NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC ***3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell *** Macrophage activation may be essential for NEC ***3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.

关键词： Caspase-1 Interleukin-1β Macrophage Necrotizing enterocolitis NLRP3

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Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer

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World Journal of Gastroenterology 2024年第2期30卷 158-169页

作者： Yue-hao Luo Zhe-Cheng Yan Jia-Ying Liu Xin-Yi Li ming Yang Jun Fan Bo Huang Cheng-Gong Ma Xiao-Na Chang Xiu Nie Department of Pathology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022Hubei ProvinceChina

BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II ***,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort ***,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk *** To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV *** The clinical data of 547 CRC patients were collected for this retrospective *** at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference *** Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV ***,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive *** TB has an independent predictive prognostic value in patients with stage III-IV *** is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

关键词： Tumor budding Tumor infiltrating lymphocytes Colorectal cancer Survival analysis Prognosis

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Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease:A meta-analysis

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World Journal of Hepatology 2024年第3期16卷 477-489页

作者： Xiang-hao Cai Yun-ming Tang Shu-Ru Chen Jia-Hui Pang Yu-Tian Chong Hong Cao Xin-Hua Li Department of Infectious Disease Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina

BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated ***,some studies have contested the prognostic value of NLR in *** To investigate the ability of NLR to predict *** Databases,such as Embase,PubMed,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Weipu,and Wanfang,were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with *** sizes were calculated using comprehensive meta-analysis software and SATAT *** A total of thirty studies involving patients with end-stage liver disease(ESLD)were included in the *** the pooled results of eight studies,it was observed that the Neutrophil-to-Lymphocyte Ratio(NLR)was significantly higher in non-survivors compared to survivors(random-effects model:standardized mean difference=1.02,95%confidence interval=0.67-1.37).Additionally,twenty-seven studies examined the associations between NLR and mortality in ESLD patients,reporting either hazard ratios(HR)or odds ratios(OR).The combined findings indicated a link between NLR and ESLD mortality(randomeffects model;univariate HR=1.07,95%CI=1.05-1.09;multivariate HR=1.07,95%CI=1.07-1.09;univariate OR=1.29,95%CI=1.18-1.39;multivariate OR=1.29,95%CI=1.09-1.49).Furthermore,subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality,with Asian studies demonstrating a more pronounced *** Increased NLR in patients with ESLD is associated with a higher risk of mortality,particularly in Asian *** is a useful prognostic biomarker in patients with ESLD.

关键词： Neutrophil-to-lymphocyte ratio End stage liver diseases Prognosis Meta-analysis Mortality

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基于全局与序列混合变分Transformer的多样化图像描述生成方法

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电子学报 2024年第4期52卷 1305-1314页

作者：刘兵李穗刘明明刘浩中国矿业大学计算机科学与技术学院江苏徐州221116 矿山数字化教育部工程研究中心江苏徐州221116

多样化图像描述生成已成为图像描述领域研究热点.然而,现有方法忽视了全局和序列隐向量之间的依赖关系,严重限制了图像描述性能的提升.针对该问题,本文提出了基于混合变分Transformer的多样化图像描述生成框架.具体地,首先构建全局与序... 详细信息

多样化图像描述生成已成为图像描述领域研究热点.然而,现有方法忽视了全局和序列隐向量之间的依赖关系,严重限制了图像描述性能的提升.针对该问题,本文提出了基于混合变分Transformer的多样化图像描述生成框架.具体地,首先构建全局与序列混合条件变分自编码模型,解决全局与序列隐向量之间依赖关系表示的问题.其次,通过最大化条件似然推导混合模型的变分证据下界,解决多样化图像描述目标函数设计问题.最后,无缝融合Transformer和混合变分自编码模型,通过联合优化提升多样化图像描述的泛化性能.在MSCOCO数据集上实验结果表明,与当前最优基准方法相比,在随机生成20和100个描述语句时,多样性指标m-BLEU(mutual overlap-BiLingual Evaluation Understudy)分别提升了4.2%和4.7%,同时准确性指标CIDEr(Consensus-based Image Description Evaluation)分别提升了4.4%和15.2%.

关键词：图像理解图像描述变分自编码隐嵌入多模态学习生成模型

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