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Response Evaluation Using Contrast-Enhanced ultrasound for Unresectable Advanced Hepatocellular Carcinoma Treated With Tyrosine Kinase Inhibitors Plus Anti-PD-1 Antibody Therapy

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ultrasound in Medicine and Biology 2024年第1期50卷 142-149页

作者： Zhao C.-K. Guan X. Pu Y.-Y. Zhou B.-Y. Wang L.-F. Sun Y.-K. Yin H.-H. Xia H.-S. Wang X. Han H. Xu H.-X. department of ultrasound Zhongshan Hospital Institute of Ultrasound in Medicine and Engineering Fudan University Shanghai China Shanghai Institute of medical Imaging Shanghai China central laboratory and department of medical ultrasound Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital University of Electronic Science and Technology of China Chengdu China

Objective: The aim of the work described here was to evaluate the role of contrast-enhanced ultrasound (CEUS) in response evaluation for unresectable advanced hepatocellular carcinoma (HCC) treated with tyrosine kinase inhibitors (TKIs) plus anti-programmed cell death protein-1 (PD-1) antibody therapy. Methods: A prospective cohort of consecutive patients with HCC who received combined TKI/anti-PD-1 antibody treatment for unresectable HCC between January 2022 and October 2022 was included in this study. The patients underwent unenhanced ultrasound (US) and CEUS examinations before treatment and at follow-up. Changes in the largest diameters of the target tumor on unenhanced US and the largest diameters of the enhancing target tumors on CEUS were evaluated. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 with unenhanced US and magnetic resonance imaging/computed tomography (MRI/CT) and modified RECIST (mRECIST) with CEUS and CEMRI/CT were used to assess treatment response. Results: A total of 24 HCC patients (23 men and 1 woman; mean age: 56.5 ± 8.5 y; Barcelona Clinic Liver Cancer stage C, 62.5%; 29 intrahepatic target tumors) were studied. Calculations of degree of necrosis in the target tumors revealed no significant differences between CEUS and CEMRI/CT (44.5 ± 36.2% vs. 45.3 ± 36.8%, p = 0.862). As for the differentiation of responders from non-responders, the agreement between RECIST version 1.1 of unenhanced US and mRECIST-CEUS was poor (κ coefficient = 0.233). Meanwhile, there was a high degree of concordance between mRECIST-CEUS and mRECIST-CEMRI/CT (κ coefficient = 0.812). Conclusion: CEUS proved to be superior to baseline US and is comparable to CEMRI/CT in defining treatment outcome for combined TKI/anti-PD-1 antibody therapy. © 2023 World Federation for ultrasound in Medicine & Biology

关键词： Anti-angiogenic therapy Anti-PD-1 antibody Contrast-enhanced ultrasound Hepatocellular carcinoma

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Stimulated emission-depletion-based point-scanning structured illumination microscopy

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Chinese Optics Letters 2024年第3期22卷 95-100页

作者：汪磊王美婷王璐玮郑晓敏陈嘉杰吴文帅严伟于斌屈军乐高志邵永红 Guangdong Key laboratory for Biomedical Measurements and ultrasound Imaging National-Regional Key Technology Engineering Laboratory for Medical UltrasoundSchool of Biomedical EngineeringShenzhen University Medical SchoolShenzhen 518060China Key laboratory of Opto-electronic Information Science and Technology of Jiangxi Province Nanchang Hangkong UniversityNanchang 330063China College of Physics and Optoelectronics Engineering Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong ProvinceShenzhen UniversityShenzhen 518060China department of Bioengineering and COMSET Clemson UniversityClemson SC 29634US

Wide-field linear structured illumination microscopy(LSIM)extends resolution beyond the diffraction limit by moving unresolvable high-frequency information into the passband of the microscopy in the form of moiré***,due to the diffraction limit,the spatial frequency of the structured illumination pattern cannot be larger than the microscopy cutoff frequency,which results in a twofold resolution improvement over wide-field *** Letter presents a novel approach in point-scanning LSIM,aimed at achieving higher-resolution improvement by combining stimulated emission depletion(STED)with point-scanning structured illumination microscopy(ps SIM)(STED-ps SIM).The according structured illumination pattern whose frequency exceeds the microscopy cutoff frequency is produced by scanning the focus of the sinusoidally modulated excitation beam of STED *** experimental results showed a 1.58-fold resolution improvement over conventional STED microscopy with the same depletion laser power.

关键词： stimulated emission depletion structured illumination microscopy superresolution microscopy

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Switching On/Off of Guide RNA by Photoinduced Strand Displacement for Functional Control of CRISPR/Cas9

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CCS Chemistry 2024年第5期6卷 1338-1351页

作者： Yang Wang Chao-Qun Wu Qiu-Long Zhang Ming Shao Yan Liu Liang-Liang Wang Zun-Yun Wang Juan Du Liang Xu central laboratory department of the Second Affiliated Hospital School of MedicineThe Chinese University of Hong KongShenzhen&Longgang District People’s Hospital of ShenzhenShenzhen 518172 Guangdong Key laboratory for Biomedical Measurements and ultrasound Imaging National-Regional Key Technology Engineering Laboratory for Medical UltrasoundSchool of Biomedical EngineeringShenzhen University Medical SchoolShenzhen 518060 MOE Key laboratory of Bioinorganic and Synthetic Chemistry School of ChemistrySun Yat-sen UniversityGuangzhou 510275 School of Pharmacy and medical Technology Putian UniversityPutian 351100

Functional control of CRISPR/Cas9 is essential for precise gene *** engineering of guide RNA(gRNA)provides diverse approaches for conditional control of CRISPR/Cas9 function with a variety of chemical reactive ***,previous investigations into chemically engineering gRNA only unidirectionally regulated the CRISPR/Cas9 function via stimuli-induced caging/decaging ***,we propose a combinatory strategy to engineer the dynamics of gRNA in which photocontrolled strand-displacement reactions coupled with sequence designs of gRNA can achieve lightinduced switching-on/off control of CRISPR/Cas9 *** analysis and cellular gene regulation indicate this approach is capable of both activating and deactivating CRISPR/Cas9 activities using light ***,photocontrolled multiplex modulations of gene expression for opposite regulatory effects have also been achieved simultaneously under the same cellular *** work establishes an essential principle for construction of stimuli-induced switching-on/off modulations of gRNA that can greatly enrich the versatility of conditional control for a variety of CRISPR/Cas9-based applications.

关键词： modified oligonucleotides gene manipulation optical control CRISPR/Cas9 strand displacement

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Transient receptor potential vanilloid 1 involved in the analgesic effects of total flavonoids extracted from Longxuejie(Resina Dracaenae Cochinchinensis)

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Journal of Traditional Chinese Medicine 2024年第3期44卷 437-447页

作者： MO Xiaoqiang CHEN Yating YIN Qian CHEN Haibo BAN Qiang LI Jun CHEN Su YAO Jinguang department of Stomatology Affiliated Hospital of Youjiang Medical University for Nationalities College of General Practitioners Youjiang Medical University for Nationalities College of Biomedical Engineering South-Central Minzu UniversityKey Laboratory of Cognitive Science of State Ethnic Affairs CommissionHubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment College of Pharmacy South-Central Minzu University

OBJECTIVE: To evaluate the analgesic effects of total flavonoids of Longxuejie(Resina Dracaenae Cochinchinensis)(TFDB) and explore the possible analgesic mechanism associated with transient receptor potential vanilloid 1(TRPV1).METHODS: Whole-cell patch clamp technique was used to observe the effects of TFDB on capsaicin-induced TRPV1 currents. Rat experiments in vivo were used to observe the analgesic effects of TFDB. Western blot and immunofluorescence experiments were used to test the change of TRPV1 expression in DRG neurons induced by ***: Results showed that TFDB inhibited capsaicin-induced TRPV1 receptor currents in acutely isolated dorsal root ganglion(DRG) neurons of rats and the half inhibitory concentration was(16.7 ± 1.6) mg/***(2-20 mg/kg) showed analgesic activity in the phase Ⅱ of formalin test and(0.02-2 mg per paw)reduced capsaicin-induced licking times of rats. TFDB(20 mg/kg) was fully efficacious on complete Freund's adjuvant(CFA)-induced inflammatory thermal hyperalgesia and capsaicin could weaken the analgesic effects. The level of TRPV1 expressions of DRG neurons was also decreased in TFDB-treated CFA-inflammatory pain ***: All these results indicated that the analgesic effect of TFDB may contribute to their modulations on both function and expression of TRPV1 channels in DRG neurons.

关键词： Freund's adjuvant Longxuejie () capsaicin flavonoids formaldehyde inflammatory pain transient receptor potential vanilloid 1

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Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

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Neural Regeneration Research 2024年第7期19卷 1602-1607页

作者： Mingri Zhao Xun Chen Jiangfeng Liu Yanjin Feng Chen Wang Ting Xu Wanxi Liu Xionghao Liu Mujun Liu Deren Hou department of Neurology The Third Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Center for medical Genetics&Hunan Key laboratory of medical Genetics School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina department of Cell Biology School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s ***1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor *** better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 *** found that Sorl1-knocko ut mice displayed deficits in learning and ***,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout *** vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were *** expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their ***,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also *** findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

关键词： brain-derived neurotrophic factor late-onset Alzheimer’s disease N-methyl-D-aspartate receptor sortilin-related receptor 1 synapse

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Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease

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Chinese medical Journal 2024年第4期137卷 450-456页

作者： Yuwen Zhao Lixia Qin Hongxu Pan Tingwei Song Yige Wang Xiaoxia Zhou Yaqin Xiang Jinchen Li Zhenhua Liu Qiying Sun Jifeng Guo Xinxiang Yan Beisha Tang Qian Xu department of Neurology Xiangya HospitalCentral South UniversityChangshaHunan 410008China department of Neurology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Bioinformatics Center National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China department of Geriatrics Xiangya HospitalCentral South UniversityChangshaHunan 410008China Centre for medical Genetics and Hunan Key laboratory of medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China Key laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangshaHunan 410008China

Background:Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease(PD)risk factors;however,no comprehensive analyses of these genes in patients with PD have been ***,we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with ***:Whole-exome sequencing(WES)was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 ***,whole-genome sequencing(WGS)was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 ***:We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts,***-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset ***,the significance did not pass the Bonferroni ***,72 and 1730 common variants were found in the WES and WGS cohorts,***,single-variant logistic association analyses did not identify significant associations between common variants and ***:Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese ***,we highlight the complexity of PD and the need for extensive research elucidating its etiology.

关键词： Parkinson’s disease Transcription factors Dopaminergic neurons Genetic Variants

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Prognostic Nutritional Index Associates with the Severity of Silicosis:A Study from a Tertiary Class A Prevention and Treatment Institute for Occupational Diseases in China

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Biomedical and Environmental Sciences 2024年第1期37卷 122-126页

作者： HE La Gu LIANG Yun Lai YANG Lu Qi YUAN Hua Min medical laboratory department Hunan Prevention and Treatment Institute for Occupational DiseasesChangsha 410000HunanChina laboratory Medicine department Xiangya HospitalCentral South UniversityChangsha 410013HunanChina

Pneumoconiosis is a group of heterogeneous fibrotic lung diseases caused by inorganic mineral dust and includes coal workers’pneumoconiosis and *** involves diffuse or nodular interstitial pulmonary fibrosis caused by exposure to asbestos or silica *** is thought to have the highest number of silicosis cases,with 6,000 new cases reported annually^([1]).Currently,the clinical diagnosis and monitoring of silicosis relies mainly on a history of occupational exposure and radiological abnormalities^([2]).Therefore,determining further indicators is crucial to reflect the severity of silicosis.

关键词： diagnosis lung diseases

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Copper Metabolism and Cuproptosis:Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases

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Current medical Science 2024年第1期44卷 28-50页

作者： Xiao-xia BAN Hao WAN Xin-xing WAN Ya-ting TAN Xi-min HU Hong-xia BAN Xin-yu CHEN Kun HUANG Qi ZHANG Kun XIONG department of Human Anatomy and Neurobiology School of Basic Medical ScienceCentral South UniversityChangsha 430013China department of Endocrinology Third Xiangya HospitalCentral South UniversityChangsha 430013China department of Dermatology Xiangya HospitalCentral South UniversityChangsha 430013China Affiliated Hospital Inner Mongolia Medical UniversityHohhot 010050China Key laboratory of Emergency and Trauma of Ministry of Education Hainan Medical UniversityHaikou 571199China Hunan Key laboratory of Ophthalmology Changsha 430013China

Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human *** normal metabolism,the human body maintains copper *** deficiency or excess can adversely affect cellular ***,copper homeostasis is stringently *** studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular *** induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster *** neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper *** review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative *** offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

关键词： cuproptosis copper metabolism copper homeostasis neurodegeneration neurodegenerativedisease

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Multiple types of disease-associated RNAs identification for disease prognosis and therapy using heterogeneous graph learning

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Science China(Information Sciences) 2024年第8期67卷 341-342页

作者： Wenxiang ZHANG Hang WEI Wenjing ZHANG Hao WU Bin LIU School of Computer Science and Technology Beijing Institute of Technology School of Computer Science and Technology Xidian University department of Teaching and Research Shenzhen University General Hospital Guangdong Key laboratory for Biomedical Measurements and ultrasound Imaging National-Regional Key Technology Engineering Laboratory for Medical UltrasoundSchool of Biomedical Engineering Shenzhen University Medical School Advanced Research Institute of Multidisciplinary Science Beijing Institute of Technology

Identifying disease-associated RNAs is crucial in revealing the pathogenic mechanisms of diseases [1], and biologists have made notable progress in this field [2]. However, more effective computational methods are needed to provide reference disease-associated RNAs, reducing the manpower and material resources required for biological experiments.

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Effects of aspirin on colon cancer usingquantitative proteomic analysis

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Cancer Pathogenesis and Therapy 2024年第2期2卷 121-131页

作者： Yan Zhang Haitao Sun Yu Ji Fang Nie Rong Wang Wei Han central laboratory Beijing Luhe HospitalCapital Medical UniversityBejing 101149China department of General Surgery Beijing Luhe HospitalCapital Medical UniversityBejing 101149China central laboratory Xuanwu HospitalCapital Medical UniversityBeijing 100053China

Background:Colon cancer is one of the most prevalent digestive cancers *** of epidemiological,experimental,and clinical studies suggest that aspirin inhibits the development of colon *** study aimed to systematically elucidate the molecular mechanisms by which aspirin prevents colon ***:We determined the global protein expression profiles of colorectal cancer and aspirin-treated cells using quantitative proteomic *** analyzed the proteomic results using bioinformatics(including differential pro-teins,protein annotation,Kyoto Encyclopedia of Genes and Genomes[KEGG]pathways,and protein-protein inter-action[PPI]network).The viability of the colon cancer cell line and HT29 cells treated with aspirin was determined using the cell counting kit-8 *** differentially expressed proteins,such as p53 and cyclin-dependent kinase 1(CDK1),were quantified using real-time polymerase chain reaction(PCR)and Western *** measured cell cycle distribution and apoptosis in HT29 cells exposed to aspirin using fluorescence-activated cell sorting(FACS).Results:We found that 552 proteins were significantly dysregulated,of which 208 and 334 were upregulated and downregulated,respectively,in colon cancer cells exposed to 10 mmol/L of aspirin(95%confidence interval[CI]:-1.269 to-0.106,P<0.05).Further gene enrichment analysis revealed that cell cycle-related proteins,such as p53 and CDK1,were significantly differentially *** analysis showed that after 24 h of aspirin exposure,the level of p53 increased by 2.52-fold and CDK1 was downregulated to half that of the controls in HT29 cells(95%CI:-0.619 to-0.364,P<0.05).Real-time PCR and Western blotting results showed that p53 was upregulated(95%CI:-3.088 to-1.912,P<0.001)and CDK1 was significantly downregulated after aspirin exposure in colon cancer cells(95%CI:0.576 to 1.045,P<0.05).We observed that aspirin promoted G1/S cell cycle arrest in HT29 *** confirmed that asp

关键词： Colon cancer Proteomics Aspirin Cell cycle Cell apoptosis

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