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Branched glycopolymer prodrug-derived nanoassembly combined with a STINg agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin Li Qianfeng Zhang Zhiqian Li Long Ren Dayi Pan Qiyong gong Zhongwei gu Hao Cai Kui Luo department of radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China department of radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their *** address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor *** this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STINg)agonist was encapsulated into *** internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP ***,diABZI effectively activated the STINg *** with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STINg agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

关键词： glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STINg pathway Immuno-supportive microenvironment Immunotherapy

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Chinese expert consensus on refined diagnosis,treatment,and management of advanced primary liver cancer(2023 edition)

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肝脏研究（英文） 2024年第2期8卷 61-71页

作者： Xiufeng Liu Feng Xia Yue Chen Huichuan Sun Zhengqiang Yang Bo Chen Ming Zhao Xinyu Bi Tao Peng Aizier Ainiwaer Zhiwen Luo Fusheng Wang Yinying Lu National Clinical Research center for Infectious Diseases Society of Hepatology,Beijing Medical Association Translational Medicine Branch,China Association of gerontology and geriatrics department of Medical Oncology Bayi Hospital Affiliated to Nanjing Chinese Medical University NanjingJiangsuChina department of Hepatobiliary Surgery Southwest HospitalArmy Medical University ChongqingChina Senior department of Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina department of Interventional Therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Minimally Invasive Interventional Therapy Liver Cancer Study and Service GroupSun Yat-sen University Cancer CenterGuangzhouGuangdongChina department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Hepatobiliary Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxiChina Senior department of Infectious Diseases The Fifth Medical Center of PLA General HospitalBeijingChina Comprehensive Liver Cancer center The Fifth Medical Center of PLA General HospitalBeijingChina

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85％of all cancer cases in the *** guidelines have been used to diagnose and treat liver ***,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual ***,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi *** classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were *** recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment *** findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.

关键词： Hepatocellular carcinoma (HCC) Targeted therapy Immunotherapy Refined diagnosis and treatment Expert consensus

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Spotlight on eltrombopag concentration in pediatric immune thrombocytopenia:A single-center observational study in China

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Pediatric Investigation 2024年第1期8卷 44-52页

作者： Shuyue Dong Zhifa Wang Nan Wang Jingyao Ma Jinxi Meng Yixin Sun Xiaoling Cheng Runhui Wu Hematology Oncology center Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina department of Pharmacy Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina

Importance:Eltrombopag has been recommended for pediatric immune thrombocytopenia(ITP).Response and adverse drug reactions(ADRs)varied widely between individuals,even at the same dose of *** appropriate eltrombopag concentration in ITP has not been ***:This study aims to explore the appropriate eltrombopag concentration in pediatric ***:This was a single-center,prospective cohort *** diagnosed with refractory persistent/chronic ITP and platelet countg and followed up for at least 2 *** was detected by high-performance liquid chromatography-mass spectrometry at least 2 weeks after *** clinical characteristics-concentration,concentration-response,and concentration-ADRs were ***:A total of 30 patients were enrolled,comprising 13 males and 17 females,with a median age of 72(45-94)*** median dose and concentration were 1.39(1.09-1.56)mg/kg and 2.70(2.25-4.13)mg/L,*** the enrolled patients,14 responded to treatment,whereas 16 did ***,five experienced adverse drug *** linear correlation was observed between eltrombopag concentration and clinical *** concentration was lower in the response group than in the nonresponse group,but there was no significant difference(t=0.755,P=0.457).Patients who experienced ADRs had a higher concentration than those without ADRs(t=2.538,P=0.017).The area under the receiver operating characteristic curve of ADRs was 0.78(95%confidence interval:0.56-1.00).Youden’s index identified the cutoff point as 4.33 mg/L,with a sensitivity of 88%and a specificity of 60%.Logistic regression analysis demonstrated that a higher platelet count before eltrombopag predicted a favorable ***:Eltrombopag proves efficacious and well-tolerated for treating pediatric ***,prolonged and high-dose administration may increase the likelihood of ***,examining

关键词： Concentration Efficacy Eltrombopag Immune thrombocytopenia Pedi-atrics Safety

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Aberrant Hippocampal Development in Early‑onset Mental Disorders and Promising Interventions:Evidence from a Translational Study

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Neuroscience Bulletin 2024年第6期40卷 683-694页

作者： Jingyu Yang Huiling guo Aoling Cai Junjie Zheng Juan Liu Yao Xiao Sihua Ren Dandan Sun Jia Duan Tongtong Zhao Jingwei Tang Xizhe Zhang Rongxin Zhu Jie Wang Fei Wang Early Intervention Unit Department of PsychiatryAffiliated Nanjing Brain HospitalNanjing Medical UniversityNanjing 210029China School of Biomedical Engineering and Informatics NanjingMedical UniversityNanjing 211166China The Affiliated Changzhou Second People’s hospital of Nanjing Medical university Changzhou Second People’s HospitalChangzhou Medical CenterNanjing Medical UniversityChangzhou 213004China department of radiology First Hospital of China Medical UniversityShenyang 110002China department of Cardiac Function The People’s Hospital of China Medical University and the People’s Hospital of Liaoning ProvinceShenyang 110067China Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanWuhan Institute of Physics and MathematicsInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of Sciences-Wuhan National Laboratory for OptoelectronicsWuhan 430064China Institute of Neuroscience and Brain Diseases Xiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyang 441021China Functional Brain Imaging Institute of Nanjing Medical university Nanjing 210029China

Early-onset mental disorders are associated with disrupted neurodevelopmental processes during *** methylazoxymethanol acetate(MAM)animal model,in which disruption in neurodevelopmental processes is induced,mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological *** conducted longitudinal structural magnetic resonance imaging(MRI)scans during childhood,adolescence,and adulthood in MAM rats to identify specific brain regions and critical windows for ***,the effect of repetitive transcranial magnetic stimulation(rTMS)intervention on the target brain region during the critical window was *** addition,the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders(diagnosed with major depressive disorder or bipolar disorder)to evaluate its clinical translational *** results demonstrated that,compared to the control group,the MAM rats exhibited significantly lower striatal volume from childhood to adulthood(all Pgnificant differences during childhood(P>0.05)but was significantly lower than the control group from adolescence to adulthood(both Pg *** MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group(Pged(P>0.05).In the clinical trial,adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline(Pges were associated with improvement in depressive symptoms(r=−0.524,P=0.018).These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervent

关键词： Early-onset Mental disorder Neurodevelopment Animal model Hippocampus Repetitive transcranial magnetic stimulation

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In vitro bench testing using patient-specific 3D models for percutaneous pulmonary valve implantation with Venus P-valve

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Chinese Medical Journal 2024年第8期137卷 990-996页

作者： Yu Han Zehua Shao Zirui Sun Yan Han Hongdang Xu Shubo Song Xiangbin Pan Peter P.T.de Jaegere Taibing Fan gejun Zhang department of Structure Heart Disease Central China Fuwai Hospital of Zhengzhou UniversityZhengzhouHenan 451460China Children’s Heart center Central China Fuwai Hospital of Zhengzhou UniversityZhengzhouHenan 451460China department of Anesthesiology Central China Fuwai Hospital of Zhengzhou UniversityZhengzhouHenan 451460China department of Structure Heart Disease Fuwai Hospital Chinese Academy of Medical SciencesBeijing 100037China department of Cardiology Erasmus MCRotterdam 3015 GDNetherlands

Background:Due to the wide variety of morphology,size,and dynamics,selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation(PPVI).This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional(3D)-printed models for planning PPVI with the Venus ***:Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai hospital of Zhengzhou ***:3D model bench testing altered treatment strategy in all patients(100%).One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor *** the remaining 14 patients,valve size and/or implantation location was altered to avoid valve migration and/or compression coronary *** four patients,it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract(RVOT)(n=2)or risk of compression coronary artery(n=2).Concerning sizing,we found that an oversize of 2-5 mm *** of the valve was dictated by the flaring of the in-and outflow portion in the pulmonary *** was successful in all 14 patients(absence of valve migration,no coronary compression,and none-to-mild residual pulmonary regurgitation[PR]).The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group(36[2]vs.32[4],Z=-3.77,Pg indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique,as 2-5 mm sufficed.

关键词： Heart valve prosthesis implantation Percutaneous pulmonary valve intervention Pulmonary regurgitation bench testing 3D printing Venus P-valve

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Engagement of N^(6)-methyladenisine methylation of gng4 mRNA in astrocyte dysfunction regulated by CircHECW2

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1644-1660页

作者： Ying Bai Di Chang Hui Ren Minzi Ju Yu Wang Biling Chen Han Li Xue Liu Daxing Li Xinchen Huo Xiaofei guo Mengze Tong Ying Tan Honghong Yao Bing Han department of Pharmacology Jiangsu Provincial Key Laboratory of Critical Care MedicineSchool of MedicineSoutheast UniversityNanjing 210009China department of radiology Zhongda HospitalJiangsu Key Laboratory of Molecular and Functional ImagingMedical School of Southeast UniversityNanjing 210009China Co-Innovation center of Neuroregeneration Nantong UniversityNantong 226001China Institute of Life Sciences Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjing 210096China center for global Health School of Public HealthNanjing Medical UniversityNanjing 211166China

The N^(6)-methyladenosine(m^(6)A)modification is the most prevalent modification of eukaryotic mRNAs and plays a crucial role in various physiological processes by regulating the stability or function of target *** evidence has suggested that m6A methylation may be involved in the pathological process of major depressive disorder(MDD),a common neuropsychiatric disorder with an unclear ***,we found that the levels of the circular RNA HECW2(circHECW2)were significantly increased in the plasma of both MDD patients and the chronic unpredictable stress(CUS)mouse ***,the downregulation of circHECW2 attenuated astrocyte dysfunction and depression-like behaviors induced by ***,we demonstrated that the downregulation of circHECW2 increased the expression of the methylase WTAP,leading to an increase in gng4 expression via m^(6)A *** findings provide functional insight into the correlation between circHECW2 and m^(6)A methylation,suggesting that circHECW2 may represent a potential target for MDD treatment.

关键词： N^(6)-Methyladenosine Depression circHECW2 Astrocyte WTAP Ubiquitination gNg4 Dysfunction

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global geoepidemiology of gastrointestinal surgery rates in Crohn’s disease

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World Journal of gastrointestinal Surgery 2024年第6期16卷 1835-1844页

作者： Simcha Weissman Muhammad Aziz Ayrton Bangolo Vignesh K Nagesh Htat Aung Midhun Mathew Lino garcia Shiva A Chandar Praveena Karamthoti Harinder Bawa Aseel Alshimari Yabets Kejela Nazish Mehdi Chrishanti A Joseph Athri Kodali Rohan Kumar Priya goyal Sanya Satheesha Fnu Nivedita Nicole Tesoro Tanni Sethi gurpreet Singh Areej Belal Alina Intisar Hirra Khalid Samuel Cornwell Suchith B Suresh Kareem Ahmed Karabo K Marole Om P Anand Rahat B Reshi Tej I Mehta Sameh Elias Joseph D Feuerstein department of Medicine Hackensack Meridian Health Palisades Medical CenterNorth BergenNJ 07047United States Division of gastroenterology and Hepatology University of Toledo Medical CenterToledoOH 43614United States department of Medicine University of WashingtonSeattleWA 98195United States department of radiology Johns Hopkins University HospitalBaltimoreMD 21218United States Division of gastroenterology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215United States

BACKgROUND Data regarding the worldwide gastrointestinal surgery rates in patients with Crohn’s disease(CD)remains *** To systematically review the global variation in the rates of surgery in *** A comprehensive search analysis was performed using multiple electronic databases from inception through July 1,2020,to identify all full text,randomized controlled trials and cohort studies pertaining to gastrointestinal surgery rates in adult patients with *** included continent based demographic data,CD surgery rates over time,as well as the geoepidemiologic variation in CD surgery *** analyses were conducted using *** Twenty-three studies spanning four continents were *** median proportion of persons with CD who underwent gastrointestinal surgery in studies from North America,Europe,Asia,and Oceania were 30%(range:1.7%-62.0%),40%(range:0.6%-74.0%),17%(range:16.0%-43.0%),and 38%*** clear association was found regarding the proportion of patients undergoing gastrointestinal surgery over time in North America(R^(2)=0.035)and Europe(R^(2)=0.100).A moderate,negative association was seen regarding the proportion of patients undergoing gastrointestinal surgery over time(R^(2)=0.520)in *** There appears to be significant inter-continental variation regarding surgery rates in *** evidencebased guidelines accounting for the geographic differences in managing patients with CD is ***,as a paucity of data on surgery rates in CD exists outside the North American and European continents,future studies,particularly in less studied locales,are warranted.

关键词： gastrointestinal surgery Crohn’s disease geoepidemiology Inflammatory bowel disease Prevalence

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Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X(HBX)genetransfected hepatic stellate cells

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 499-512页

作者： Hongyi LIU Yuanyuan ZHOU Peng gUO Xiongwei ZHENg Weibin CHEN Shichao ZHANg Yu FU Xu ZHOU Zheng WAN Bin ZHAO Yilin ZHAO department of Oncology and Vascular Interventional radiology Zhongshan Hospital Affiliated to Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361004China School of Medicine Xiamen UniversityXiamen 361102China Xiamen Health and Medical Big Data center Xiamen 361008China Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma(Zhongshan hospital Affiliated to Xiamen university) Xiamen 361004China Xiamen Key Laboratory of Cellular Intervention and Interventional Medical Materials Xiamen 361004China

Artificial vascular graft(AVg)fistula is widely used for hemodialysis treatment in patients with renal ***,it has poor elasticity and compliance,leading to stenosis and *** ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery,which is primarily maintained by collagen in the extracellular matrix(ECM)of arterial *** have revealed that in hepatitis B virus(HBV)-induced liver fibrosis,hepatic stellate cells(HSCs)become hyperactive and produce excessive ECM ***,mechanical stimulation can encourage ECM secretion and remodeling of a fiber *** on the above factors,we transfected HSCs with the hepatitis B viral X(HBX)gene for simulating the process of HBV ***,these HBX-HSCs were implanted into a polycaprolactonepolyurethane(PCL-PU)bilayer scaffold in which the inner layer is dense and the outer layer consists of pores,which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the *** obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after ***,the vessel scaffold was implanted into a rabbit’s neck arteriovenous fistula *** exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit’s *** study demonstrates the use of human cells to create biomimetic dialysis blood vessels,providing a novel approach for creating clinical vascular access for dialysis.

关键词： Composite bilayer bionic blood vessel Extracellular matrix(ECM) Hepatic stellate cells(HSCs) Hepatitis B viral X(HBX)gene Mechanical force

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Incidences and Risk Factors for Surgical Site Infections in Koutiala, Mali

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Surgical Science 2024年第7期15卷 465-469页

作者： Mahamadou Coulibaly Moussa Diassana Issiaka Diarra Bréhima Bengaly Birama Togola Drissa Ouattara Souleymane Sanogo Samuel Kletigui Dembélé Cheick Aka Waigalo Brehima Ballo Drissa Traoré Nouhoum Ongoiba Faculty of Medicine University of Science Technique and Technologies of Bamako Bamako Mali department of Surgery Koutiala Hospital Koutiala Mali department of Surgery Sikasso Hospital Sikasso Mali Dpartement de Chirurgie Hpital Commune I Bamako Mali department of Surgery University Hospital Center Point G Bamako Mali department of Surgery Tominian Hospital Tominian Mali

Purpose: This paper aims to assess the incidences and risk factors for surgical site (ISO) infections in the general surgery department of the Koutiala District hospital. Patients and Methods: This was a prospective and descriptive study from August 1, 2017 to October 31, 2020 involving all patients who underwent laparotomy in the general surgery department of the Koutiala District hospital. Patients who were not operated on and who did not have a laparotomy were not included. Age, sex, frequency, patient history, National Nosocomial Infections Surveillance (NNIS) index, time to occur, bacteriological test results and course of infection were analyzed. Results: Fifty patients were registered. The average age was 34.2 ± 21.2 years old. Eleven patients were 60 years old or older. The hospital incidence rate was 4.3% and the community incidence rate was 6.1 cases per 100,000 population. The concept of smoking was noted in 15 patients. Patients were operated on in emergency 84% of cases. Peritonitis was the most common initial lesion with 32% of cases. Our patients had an NNIS index greater than 0 in 84% of cases. The time to develop infection from the surgical site was less than 3 days in 8 patients (16% of cases). Depending on the depth of the infection, it was superficial (cutaneous) in 39 patients (78%) and deep (subcutaneous and organic) in 11 patients (22%). Escherichia coli was the most common germ with 72% followed by staphylococcus aureus at 24%. We noted 22% morbidity. The median length of hospitalization was 9 ± 2.2 days. Conclusion: ISO is common in our service. Prevention and mastery require knowledge of risk factors.

关键词： Surgical Site Infection Incidence Risk Factors Surgery

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Research progresses of dual-layer spectral detector CT for preoperative evaluation on colorectal cancer

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中国医学影像技术 2024年第8期40卷 1262-1265页

作者： LI Pengqiang LIU Nianjun ZHANg Yanli WANg Yanfei LAN Jinhui REN Huling DOU Yu LEI Junqiang The First Clinical Medical College of Lanzhou university Lanzhou 730000China department of radiology the First Hospital of Lanzhou UniversityIntelligent Imaging Medical Engineering Research Center of Gansu ProvinceAccurate Image Collaborative Innovation International Science and Technology Cooperation Base of Gansu ProvinceRadiological Clinical Medicine Research Center of Gansu ProvinceIntelligent Imaging Medical Industry Technology Center of Gansu ProvinceLanzhou 730000China

Dual-layer spectral detector CT is a new spectrum CT imaging technology based on detector being able to obtain both images similar to true plain and spectral images in one time *** reconstructed multi-parameter spectral images can not only improve image quality,enhance tissue contrast,increase the visualization and detection ability of occult lesions,but also provide qualitative and quantitative analysis of the lesions,so as to provide more imaging information and multi-dimensional diagnostic *** research progresses of dual-layer spectral detector CT for preoperative evaluation on colorectal cancer were reviewed in this article.

关键词： colorectal neoplasms tomography,X-ray computed

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