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The First-in-Human Whole-Body Dynamic Pharmacokinetics Study of Aptamer

Research 2024年第1期2023卷 119-130页

作者： Ding Ding Haitao Zhao Dali Wei Qinglai yang cai yang Ruowen Wang Yumei Chen Lianghua Li Shuxian An Qian Xia Gang Huang Jianjun Liu Zeyu Xiao Weihong Tan Institute of Molecular Medicine(IMM) Renji HospitalState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of Medicineand College of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Nuclear Medicine Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Center for Molecular Imaging Probes Cancer Research InstituteUniversity of South ChinaHengyangHunan 421001China The Key Laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China Molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringHunan UniversityChangshaHunan 410082China Shanghai Key Laboratory of Molecular Imaging Shanghai University of Medicine and Health SciencesShanghai 201318China Department of Pharmacology and Chemical Biology Shanghai Jiao Tong University School of MedicineShanghai200127China

Serving as targeting ligands,aptamers have shown promise in precision ***,the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers’clinical *** bridge this gap,here we report the first-in-human pharmacokinetics study of protein tyrosine kinase 7 targeted SGC8 aptamer via in vivo PET tracking of gallium-68(^(68)Ga)radiolabeled *** specificity and binding affinity of a radiolabeled aptamer,named ^(68)Ga[Ga]-NOTA-SGC8,were maintained as proven in *** preclinical biosafety and biodistribution evaluation confirmed that aptamers have no biotoxicity,potential mutation risks,or genotoxicity at high dosage(40 mg/kg).Based on this result,a first-in-human clinical trial was approved and carried out to evaluate the circulation and metabolism profiles,as well as biosafety,of the radiolabeled SGC8 aptamer in the human *** advantage of the cutting-edge total-body PET,the aptamers’distribution pattern in the human body was acquired in a dynamic fashion.

关键词： metabolism dosage Whole

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Identification of Key Blood Biomarkers Linking Di(2-ethylhexyl)Phthalate and Autoimmune Diseases in Adolescents Mice

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Biomedical and Environmental Sciences 2024年第5期37卷 521-525页

作者： XU Xiao Mei LI Xiao Lu HU Die cai Xiao Yue LI Qi Meng ZHENG Yuan Zhuo cai yang QI Yin Yin XU Tao ZHAO Ling Li NING Xia Department of Infectious Diseases Anhui Provincial Children’s HospitalHefei 231000AnhuiChina Department of Toxicology School of Public HealthKey Laboratory of Environmental Toxicology of Anhui Higher Education InstitutesAnhui Medical UniversityHefei 231000AnhuiChina School of Biology Food and EnvironmentHefei UniversityHefei 230601AnhuiChina

Di(2-ethylhexyl)phthalate(DEHP)is a widely used plasticizer known for its reproductive developmental and immune system toxicity,mainly through esophagal,dermal,and respiratory exposure^([1-3]).Maternal exposure to DEHP during pregnancy can lead to adverse birth outcomes in offspring,including impacts on the thyroid system of adolescent offspring^([2-4]).

关键词： Blood respiratory pregnancy

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Species-level Microbiota of Biting Midges and Ticks from Poyang Lake

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Biomedical and Environmental Sciences 2024年第3期37卷 266-277,I0001-I0003页

作者： GONG Jian WANG Fei Fei LIU yang Qing PU Ji DONG Ling Zhi ZHANG Si Hui HUANG Zhen Zhou HUANG Yu Yuan LI Ya Ben yang cai Xin TAO Yuan Meihui ZHAO Li Jun JIN Dong LIU Li Yun yang Jing LU Shan Department of Epidemiology School of Public HealthShanxi Medical UniversityTaiyuan 030001ShanxiChina National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Jiangxi Provincial Key Laboratory of Animal-Origin and Vector-Borne Diseases Nanchang Center for Disease Control and PreventionNanchang 330038JiangxiChina Research Units of Discovery of Unknown Bacteria and Function Chinese Academy of Medical SciencesBeijing 100730China

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and *** Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang *** A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new ***,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus *** found that Proteobacteria was the most dominant group in both midges and ***,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant *** sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ***,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick *** identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod *** Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide

关键词： Biting midge Tick Microbiota Pantoea Coxiella

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Jianqu,a traditional Chinese medicine,alleviates functional dyspepsia in high-calorie and high-protein diet mice

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Traditional Medicine Research 2024年第6期9卷 42-54页

作者： Jing-Yan yang Xiao-Xing Li Juan Chen Yan-Jun Liu Yue-Hong Wu Ning-Yu Luo cai-Xia yang yang Li Si-Jing Liu Jin-Lin Guo College of Medical Technology Chengdu University of Traditional Chinese MedicineChengdu 611137China Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine Chengdu 611137China Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China College of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China

Background:Jianqu has been used to alleviate symptoms in patients with functional dyspepsia,but its specific anti-functional dyspepsia effect is still ***,our study aimed to investigate the impact of Jianqu on functional dyspepsia in ***:The phytochemical profile of Jianqu was analyzed by ***,Kunming mice were fed a high-calorie or high-protein diet(HCHP)for 7 days,and then orally treated with vehicle or Jianqu(1.62 g/kg body weight(b.w.)and 3.25 g/kg b.w.)for 10 days.A carbon powder solution was used to detect the gastric emptying and intestinal transit *** pathological changes in stomach and duodenum were evaluated by hematoxylin-eosin *** occludin,claudin-1,ZO-1 and CD45 expression was measured by immunocytochemical ***,the serum gastrointestinal hormones were detected by *** addition,the gut microbiota composition was determined using 16S rRNA gene *** cecal short chain fatty acids were assessed by gas ***:In general,17 phytochemical compounds were identified from Jianqu,which significantly improved the gastric emptying rate and intestinal transit rate(p<0.01),increased the body weight and food intake(p<0.0001)in HCHP mice as *** HCHP did not cause significant pathological lesions in the gastrointestinal tract,increased the expression of CD45 in the duodenum(p<0.05)was ***,Jianqu attenuated this abnormal expression of CD45(p<0.05).The levels of serum gastrointestinal hormones were significantly normalized by Jianqu intervention(p<0.05).Moreover,Jianqu increased the relative abundance of Roseburia as well as short chain fatty acids levels in cecum(p<0.05).Conclusion:The present results showed that Jianqu alleviated dyspeptic symptoms in HCHP mice possibly through reducing the duodenal leukocyte infiltration,and regulating the expression of gastrointestinal *** effects may be partly related to the increasing cecal short ch

关键词： herbal formula dyspepsia gastrointestinal hormones gastric emptying intestinal transit

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Molecular phylogenetic relationships based on mitochondrial genomes of novel deep-sea corals(Octocorallia:Alcyonacea):Insights into slow evolution and adaptation to extreme deep-sea environments

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Zoological Research 2024年第1期45卷 215-225页

作者： Zhan-Fei Wei Kai-Wen Ta Nan-Nan Zhang Shan-Shan Liu Liang Meng Kai-Qiang Liu Chong-yang cai Xiao-Tong Peng Chang-Wei Shao National Key Laboratory of Mariculture Biobreeding and Sustainable Goods Yellow Sea Fisheries Research InstituteChinese Academy of Fishery SciencesQingdaoShandong 266071China BGI-Qingdao BGI-ShenzhenQingdaoShandong 266555China Institute of Deep-Sea Science and Engineering Chinese Academy of SciencesSanyaHainan 572000China

A total of 10 specimens of Alcyonacea corals were collected at depths ranging from 905 m to 1633 m by the manned submersible Shenhai Yongshi during two cruises in the South China Sea(SCS).Based on mitochondrial genomic characteristics,morphological examination,and sclerite scanning electron microscopy,the samples were categorized into four suborders(Calcaxonia,Holaxonia,Scleraxonia,and Stolonifera),and identified as 9 possible new cold-water coral *** of GC-skew dissimilarity,phylogenetic distance,and average nucleotide identity(ANI)revealed a slow evolutionary rate for the octocoral mitochondrial *** nonsynonymous(Ka)to synonymous(Ks)substitution ratio(Ka/Ks)suggested that the 14 protein-coding genes(PCGs)were under purifying selection,likely due to specific deep-sea environmental *** analysis of the median Ka/Ks values of five gene families and environmental factors indicated that the genes encoding cytochrome b(cyt b)and DNA mismatch repair protein(mutS)may be influenced by environmental factors in the context of deep-sea species *** study highlights the slow evolutionary pace and adaptive mechanisms of deep-sea corals.

关键词： Mitochondrial genome Alcyonacea Ka/Ks evolution Environmental factors

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Computed tomography radiogenomics:A potential tool for prediction of molecular subtypes in gastric stromal tumor

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1296-1308页

作者： Xiao-Nan Yin Zi-Hao Wang Li Zou cai-Wei yang Chao-Yong Shen Bai-Ke Liu Yuan Yin Xi-Jiao Liu Bo Zhang Gastric Cancer Research Center West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Paediatric Surgery West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Radiology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Gastrointestinal Surgery Sichuan University West China HospitalChengdu 610041Sichuan ProvinceChina

BACKGROUND Preoperative knowledge of mutational status of gastrointestinal stromal tumors(GISTs)is essential to guide the individualized precision *** To develop a combined model that integrates clinical and contrast-enhanced computed tomography(CE-CT)features to predict gastric GISTs with specific genetic mutations,namely KIT exon 11 mutations or KIT exon 11 codons 557-558 *** A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 *** models were constructed using selected clinical features,conventional CT features,and radiomics features extracted from abdominal CE-CT *** models were developed:ModelCT sign,modelCT sign+rad,and model CTsign+rad+*** diagnostic performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis and the Delong *** The ROC analyses revealed that in the training cohort,the area under the curve(AUC)values for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic)for predicting KIT exon 11 mutation were 0.743,0.818,and 0.915,*** the validation cohort,the AUC values for the same models were 0.670,0.781,and 0.811,*** predicting KIT exon 11 codons 557-558 deletions,the AUC values in the training cohort were 0.667,0.842,and 0.720 for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic),*** the validation cohort,the AUC values for the same models were 0.610,0.782,and 0.795,*** on the decision curve analysis,it was determined that the model_(CT sign+rad+clinic)had clinical significance and *** Our findings demonstrate that the combined modelCT_(sign+rad+clinic)effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 *** combined model has the potential to be valuable in assessing the genotype of GISTs.

关键词： Gastrointestinal stromal tumor Radiomics Gene mutation Computed tomography Model

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Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1833-1848页

作者： Fan Mu Liang-Shuo Hu Kun Xu Zhen Zhao Bai-cai yang Yi-Meng Wang Kun Guo Jian-Hua Shi Yi Lv Bo Wang Department of Hepatobiliary Surgery First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Anaesthesiology First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Gynaecology Wenzhou Medical University Affiliated Jiaxing Women and Children HospitalJiaxing 314000Zhejiang ProvinceChina

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related *** To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related *** A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was *** the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy *** Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two *** analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

关键词： Hepatectomy Hepatitis B virus Antiviral therapy Hepatocellular carcinoma Hepatitis B virus-DNA

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应用型高校本科思政课教学高质量实施:视域与进路

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黑龙江高教研究 2024年第5期42卷 101-106页

作者：蔡扬波重庆三峡学院重庆404020

新文科建设对思政课教学质量提出新要求:体现思政课程之间、思政学科与其他学科之间教学融通,注重实践教学、知识生产、服务社会等三者应用性结合,强调现代信息技术在思政课教学中有效运用,彰显应用型高校办学特色寓于思政课教学之中,... 详细信息

新文科建设对思政课教学质量提出新要求:体现思政课程之间、思政学科与其他学科之间教学融通,注重实践教学、知识生产、服务社会等三者应用性结合,强调现代信息技术在思政课教学中有效运用,彰显应用型高校办学特色寓于思政课教学之中,关注高校学生现实生活、实际需求和就业发展。目前,思政课教学对知识生产、社会服务、现代信息技术重视不够,课程学科融合创新、部门贯通在思政课教学中贯彻力度不强,实践教学、应用能力培养与“新文科、应用型”目标结合不紧密。针对上述问题进行深层分析,提出质量提升策略:落实新文科视域下思政课教学课前、课中、课后科学一体化,在思政课教学中贯彻课程、学科融合创新,盘活思政课教学实施主体交叉贯通、协同创新系统,重构新文科视域下思政课教学目标体系,探索新文科背景下思政课教学评价、考核和奖励机制。

关键词：新文科建设应用型高校本科思政课教学质量

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颜色编码液滴阵列的机器学习解码及其在多重数字化核酸分析中的应用

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分析化学 2024年第2期52卷 198-207页

作者：刘云帆蔡东洋桂林电子科技大学数学与计算科学学院华南理工大学附属第二医院检验科

为了解决数字化核酸分析的通量限制问题，在三原色组合液滴编码技术基础上，本研究发展了一种基于机器学习的颜色编码液滴阵列自动化解码方法。此方法借助机器学习赋予计算机程序自动获取液滴颜色-位置-数量信息的能力，通过关联核酸扩... 详细信息

为了解决数字化核酸分析的通量限制问题，在三原色组合液滴编码技术基础上，本研究发展了一种基于机器学习的颜色编码液滴阵列自动化解码方法。此方法借助机器学习赋予计算机程序自动获取液滴颜色-位置-数量信息的能力，通过关联核酸扩增前后液滴颜色-位置-数量信息，快速确定每种检测靶标对应的阳性液滴比例。将这种液滴解码策略用于多重数字化核酸分析，实验结果表明，本方法快速、准确，其解码流程可在2 min内完成，液滴识别准确率> 99%。基于此液滴解码方法获得的核酸定量分析结果与商品化数字PCR仪的定量分析结果具有良好的相关性（R2> 0.99）。

关键词：机器学习液滴编码解码多重数字化核酸分析

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Toripalimab in combination with chemotherapy effectively suppresses local recurrence and metastatic sarcomatoid renal cell carcinoma:A case report

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World Journal of Clinical Cases 2024年第28期12卷 6230-6236页

作者： Ming-Zhu Gao Nian-Fei Wang Jin-You Wang Li Ma Yu-cai yang Department of Oncology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China Department of Urology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China Department of Pathology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

BACKGROUND Sarcomatoid renal cell carcinoma(SRCC)is a rare variant of renal cell carcinoma associated with an unfavorable *** efficacy of conventional chemo-therapy and targeted therapies are limited,whereas the emergence of immune checkpoint inhibitor has introduced new avenues for managing advanced *** SUMMARY A 77-year-old female patient was referred to our hospital following the incidental detection of a right kidney tumor without specific *** tumor was successfully resected,and subsequent pathological examination confirmed *** experienced both local recurrence and distant metastasis eight months after the initial laparoscopic *** six cycles of toripalimab combined with pirarubicin chemotherapy,the patient achieved a partial ***-quently,the patient attained an almost-complete continuous response to toripa-limab monotherapy maintenance for an additional six *** has not experienced disease progression for 15 months,and her overall survival has reached 24 months thus *** Combination therapy with programmed death 1 antibodies and cytotoxic agents may be a recommended first-line treatment approach for SRCC.

关键词： Renal cell carcinoma Sarcomatoid dedifferentiation Immune checkpoint inhibitor Chemotherapy Case report

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