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Acta Pharmaceutica Sinica B 2024年第2期14卷 517-532页

作者： Shuang Xiang Xiaoyun Lu International Cooperative Laboratory of Traditional Chinese medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education(MOE) Guangdong Provincial Key Laboratory of New Drug Design and EvaluationGuangzhou City Key Laboratory of Precision Chemical Drug DevelopmentSchool of PharmacyJinan UniversityGuangzhou 510632China

Neurotrophic receptor kinase(NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors,and tropomyosin receptor kinase(TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these ***,two generations TRK inhibitors have been *** representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target ***,xDFG(TRKAG667C/A/S,homologous TRKCG696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib,and overcoming these resistances represents a major unmet clinical *** this review,we summarize the acquired resistance mechanism of the first-and second-generation TRK inhibitors,and firstly put forward the emerging selective type Ⅱ TRK inhibitors to overcome xDFG mutations mediated ***,we concluded our perspectives on new challenges and future directions in this field.

关键词： NTRK fusions TRK kinase Clinical resistance xDFG mutations Selective type II inhibitors

Gut microbiota-mediated modulation of lipid metabolism by punicic acid in diet-induced hepatic steatosis

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Food Science and Human Wellness 2024年

作者： Liping Chen Yifan Lei Hengqian Lu Yongzhong Wang School of Life Sciences Anhui University Anhui Key Laboratory of Modern Biomanufacturing Key Laboratory of Human Microenvironment and precision medicine of Anhui Higher Education Institutes Anhui University

Pomegranate seed oil (PSO) mainly consisted of punicic acid (PunA)， has gained attention due to rich conjugated linolenic acids and potential application in the improvement of various diseases. The aim of this study was to explore the ability of PunA to modulate lipid metabolism associated with non-alcoholic fatty liver disease (NAFLD) and explore the emerging role of the gut microbiota in modulating hepatic lipid metabolism. In this regard， PunA’s capacity was evaluated through C57BL/6J fed with a choline and L-amino acid defined， high fat diet (CDAHFD). Mice were randomly divided into four groups: NC group， MC group， PSO group and Cur group. Collected results indicated that supplement of PunA improved hepatic lipid profile. PunA administration also ameliorated hepatic steatosis and lipid accumulation. mRNA analysis showed that PunA exerted ameliorative e?ect on hepatic lipid accumulation by downregulating the mRNA expression of Dgat1， Scd-1， Srebp-1c， but increasing expression level of Cpt-1α. Metagenomic analysis discovered that PunA increased species diversity and richness of intestinal microbiota， promoted proliferation of beneficial commensals and restraining the endotoxin-producing microorganisms in cecum of CDAHFD-administrated mice. Furthermore， PunA suppressed lipid accumulation and lipid droplet formation in a cell NAFLD model in vitro. Overall， PunA exhibited anti-lipogenic and lipid-lowering effects， improvement of intestinal flora. In summary， PunA could be a candidate for the exploitation of functional foods or nutraceuticals aiming NAFLD.

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Imiquimod:A potential option for inhibition of repigmentation of congenital melanocytic nevus after laser ablation

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Chinese Journal of Plastic and Reconstructive Surgery 2024年第2期6卷 76-78页

作者： Yifei Zhao Yun Zou Xiangyu Chen Hanlin Zeng Hanru Ying Xiaoxi Lin Hui Chen Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai Institute of precision medicine Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Department of Oncology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine

Congenital melanocytic nevi(CMN) are common skin tumors. Large and specially located nevi cannot be completely removed by surgery, posing the risks of both cosmetic deformities and potential *** treatments, such as laser therapy and physical dermabrasion, can overcome the limitations of surgery;however, the high rate of repigmentation remains an unresolved global challenge. We conducted a self-controlled observational study of a patient with a nevus on the chest. Two areas of the lesion were treated with an Er:YAG laser and 5% imiquimod cream was applied to one of these areas. After nearly 7-months of follow-up, we observed a significant difference in color between the two areas, suggesting that topical imiquimod may inhibit repigmentation and significantly enhance the effectiveness of laser treatment.

关键词： Imiquimod Congenital melanocytic nevus Recurrence Laser

Deficiency of Trp53 and Rb1 in myeloid cell lineage spontaneously develops acute myeloid leukemia in a mouse model

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Genes & Diseases 2024年第1期11卷 4-6页

作者： Yang Li Shu-ting Yang Shuying Yang Department of Basic&Translational Sciences School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Orthopaedic Surgery School of MedicineJohns Hopkins University BaltimoreMD 21205USA Center for Innovation&precision Dentistry School of Dental MedicineSchool of Engineering and Applied SciencesUniversity of PennsylvaniaPhiladelphiaPA 19104USA The Penn Center for Musculoskeletal Disorders School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Acute myeloid leukemia(AML)is a rapidly lethal blood cancer characterized by aberrant proliferation and differentiation of myeloid progenitors in the hematopoietic *** recent decades,AML patients are significantly *** 2019 alone,21,450 new AML cases were diagnosed in the united States,with an estimated 10,920 deaths due to ***’s worse,AML occurs with an increasing incidence with advanced age,and the survival rate remains dismal with a median overall survival of only 5e10 *** great advances in allogenic transplant and chemotherapy,the therapeutic outcomes are unfavorable due to the disease relapse and mortality *** importantly,the development of more specific and effective therapies was hampered in part by the lack of proper animal models for ***,management and elucidation of the pathological mechanism of AML remain an ongoing challenge,and the development of effective AML mouse models and treatment options are urgently needed.

关键词： myeloid Acute leukemia

Manipulating the Phase Transition Behavior of Dual Temperature-Responsive Block Copolymers by Adjusting Composition and Sequence

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Chinese Journal of Polymer Science 2024年第2期42卷 176-187,I0006页

作者： Zhi Zou Xiang Xu Hai-Tao Zhao Jian-Nan Cheng Wei-Wei He Li-Fen Zhang Zhen-Ping Cheng Suzhou key Laboratory of Macromolecular Design and precision Synthesis Jiangsu Key Laboratory of Advanced Functional Polymer Design and ApplicationState and Local Joint Engineering Laboratory for Novel Functional Polymeric MaterialsCollege of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou215123China State Key Laboratory of Radiation medicine and Protection School for Radiological and Interdisciplinary Sciences(RAD-X)and Collaborative Innovation Center of Radiation Medicine of JiangsuSoochow UniversitySuzhou215123China

Temperature-responsive polymers have garnered significant attention due to their ability to respond to external *** this work,dual temperature-responsive block copolymers are synthesized via reversible addition-fragmentation chain transfer polymerization(RAFT)polymerization utilizing zwitterionic monomer methacryloyl ethyl sulfobetaine(SBMA) and N-isopropyl acrylamide(NIPAAm) as *** thermal responsive behaviors can be easily modulated by incorporating additional hydrophobic monomer benzyl acrylate(BN) or hydrophilic monomer acrylic acid(AA),adjusting concentration or pH,or varying the degree of polymerization of the block chain *** cloud points of the copolymers are determined by UV-Vis spectrophotometry,and these copolymers exhibit both controlled upper and lower critical solu bility temperatures(LCST and UCST) in aqueous *** study analyzes and summarizes the influencing factors of dual temperature responsive block copolymers by exploring the effects of various conditions on the phase transition temperature of temperature-sensitive polymers to explore the relationship between their properties and environment and structure to make them more selective in terms of temperature application range and regulation *** is very interesting that the introduction of poly-acrylic acid(PAA) segments in the middle of di-block copolymer PSBMA_(55)-b-PNIPAAm_(80) to form PSBMA_(55)-b-PAA_(x)-b-PNIPAAm_(80) results in a reversal of temperature-responsive behaviors from 'U'(LCST UCST) type,while the copolymer PSBMA_(55)-b-P(NIPAAm_(80)-co-AA_(x)) *** work provides a clue for tuning the phase transition behavior of polymers for manufacture of extreme smart materials.

关键词： Temperature responsive polymers High critical solubility temperature(UCST) Low critical solubility temperature(LCST) Block copolymers

Relationships between blood chromium exposure and liver injury:Exploring the mediating role of systemic inflammation in a chromate-exposed population

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Journal of Environmental Sciences 2024年第9期143卷 224-234页

作者： Zekang Su Yali Zhang Shiyi Hong Qiaojian Zhang Jiayu Xu Guiping Hu Xiaojun Zhu Fang Yuan Shanfa Yu Tianchen Wang Guang Jia Department of Occupational and Environmental Health Sciences School of Public HealthPeking UniversityBeijing 100191China School of Engineering medicine and Beijing Advanced Innovation Center for Big Data-Based precision medicine Beihang UniversityBeijing 100191China National Center for Occupational Safety and Health Beijing 102308China Department of Occupational Health and Radiological Health Chongqing Centers for Disease Control and PreventionChongqing 400042China Henan Institute for Occupational medicine Zhengzhou 450052China Department of Clinical Laboratory Third Hospital of Peking UniversityBeijing 100191China

Hexavalent chromium and its compounds are prevalent pollutants,especially in the work environment,pose a significant risk for multisystem toxicity and *** it is known that chromium accumulation in the liver can cause damage,the dose-response relationship between blood chromium(Cr)and liver injury,as well as the possible potential toxic mechanisms involved,remains poorly *** address this,we conducted a follow-up study of 590 visits from 305 participants to investigate the associations of blood Cr with biomarkers for liver injury,including serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),and direct bilirubin(DBIL),and to evaluate the mediating effects of systemic ***(PLT)and the platelet-to-lymphocyte ratio(PLR)were utilized as biomarkers of systemic *** the linear mixed-effects analyses,each 1-unit increase in blood Cr level was associated with estimated effect percentage increases of 0.82%(0.11%,1.53%)in TBIL,1.67%(0.06%,3.28%)in DBIL,0.73%(0.04%,1.43%)in ALT and 2.08%(0.29%,3.87%)in AST,***,PLT mediated 10.04%,11.35%,and 10.77%increases in TBIL,DBIL,and ALT levels induced by chromate,*** addition,PLR mediated 8.26%and 15.58%of the association between blood Cr and TBIL or *** findings shed light on the mechanisms underlying blood Cr-induced liver injury,which is partly due to worsening systemic inflammation.

关键词： Blood chromate Liver injury Systemic inflammation Mediation analysis

When the vermiform appendix resembles a polyp: Be cautious of an intussuscepted appendix polypectomy

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World Journal of Clinical Cases 2024年第27期12卷 6124-6128页

作者： Raffaele Pellegrino Antonietta Gerarda Gravina Division of Hepatogastroenterology Department of Precision MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy

This article discusses a recently published case report on a rare instance of type IV appendiceal intussusception with a concurrent mucinous adenocarcinoma of the cecum in a young *** report highlights challenges in diagnosing ap-pendiceal intussusception,emphasizing the importance of endoscopic expertise in preventing impulsive decisions such as inappropriate *** rarity of the concurrent intussuscepted appendix and mucinous cecal cancer is under-scored,prompting consideration of malignancy in appendiceal intussusception ***,the report addresses the increasing incidence of early-onset colorectal cancer and the need for a revaluation of diagnostic paradigms in the context of evolving epidemiological *** awareness of potential misinter-pretations and the imperative for further investigation into this rare condition are emphasized.

关键词： Appendiceal intussusception Colorectal cancer Early-onset colorectal cancer Digestive endoscopy Abdominal pain Bloody stools Diarrhea

A distinct“repair”role of regulatory T cells in fracture healing

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Frontiers of medicine 2024年第3期18卷 516-537页

作者： Tingting Wu Lulu Wang Chen Jian Zhenhe Zhang Ruiyin Zeng Bobin Mi Guohui Liu Yu Zhang Chen Shi Department of Pharmacy Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Hubei Province Clinical Research Center for precision medicine for Critical Illness Wuhan430022China Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Regulatory T cells(Tregs)suppress immune responses and ***,we described the distinct nonimmunological role of Tregs in fracture *** recruitment from the circulation pool,peripheral induction,and local expansion rapidly enriched Tregs in the injured *** Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid *** depletion of Tregs compromised the fracture healing process,which leads to increased bone *** addition,bone callus Tregs showed unique T-cell receptor *** was the most overexpressed protein in bone callus Tregs,and it can directly facilitate the proliferation and differentiation of osteogenic precursor cells by activation of phosphatidylinositol 3-kinase/protein kinase B signaling *** results of loss-and gain-function studies further evidenced that amphiregulin can reverse the compromised healing caused by Treg *** also enriched in patient bone callus and amphiregulin can promote the osteogenesis of human pre-osteoblastic *** findings indicate the distinct and nonredundant role of Tregs in fracture healing,which will provide a new therapeutic target and strategy in the clinical treatment of fractures.

关键词： regulatory T cells fracture healing amphiregulin non-union osteogenesis

Y–Z deformable magnetic ring for the treatment of rectal stricture: A case report and review of literature

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World Journal of Gastroenterology 2024年第6期30卷 599-606页

作者： Miao-Miao Zhang Huan-Chen Sha Yuan-Fa Qin Yi Lyu Xiao-Peng Yan Department of Hepatobiliary Surgery The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina National Local Joint Engineering Research Center for precision Surgery&Regenerative medicine The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina

BACKGROUND Treatment of postoperative anastomotic stenosis for colorectal cancer is often challenging,especially for patients who do not respond well to *** cases where patients have undergone an enterostomy,the stenosis can be easily resolved through magnetic ***,common magnetic compre-ssion techniques cannot be performed on those without *** design-ed a novel Y–Z deformable magnetic ring(Y–Z DMR)and successfully applied it to a patient with a stenosis rectal anastomosis and without enterostomy after rectal cancer *** SUMMARY We here report the case of a 57-year-old woman who had undergone a laparo-scopic radical rectum resection(Dixon)for rectal ***,she started facing difficulty in defecation 6 months after *** colonoscopy indicated stenosis of the rectal *** balloon dilation was performed six times on ***,the stenosis still showed a trend of gradual *** the patient did not undergo an enterostomy,the conventional endoscopic magnetic compression technique could not be ***,we imple-mented a Y–Z DMR implemented through the anus under single *** magnetic ring fell off nine days after the operation and the rectal stenosis was *** patient was followed up for six months and reported good *** The Y–Z DMR deformable magnetic ring is an excellent treatment strategy for patients with rectal stenosis and without enterostomy.

关键词： Anastomotic stenosis Colorectal cancer Magnetosurgery Magnetic compression technique Magnetic surgery clinic Case report

High-fat diet impairs gut barrier through intestinal microbiota-derived reactive oxygen species

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Science China(Life Sciences) 2024年第5期67卷 879-891页

作者： Nianyi Zeng Fan Wu Junqi Lu Xiang Li Shaomei Lin Lang Zhou Zhongwei Wang Guangyan Wu Qingfa Huang Daowen Zheng Jie Gao Shan Wu Xiaojiao Chen Muxuan Chen Fanguo Meng Haitao Shang Yan He Peng Chen Hong Wei Zhuang Li Hongwei Zhou Microbiome medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510282China Department of Environmental Health Guangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public Health and Tropical MedicineSouthern Medical UniversityGuangzhou 510515China Redox Medical Center for Public Health Soochow UniversitySuzhou 215301China precision medicine Institute The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Pathophysiology Guangdong Provincial Key Laboratory of ProteomicsSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet(HFD)-associated metabolic ***,the underlying mechanism remains *** the present study,by comparing HFD-and normal diet(ND)-treated mice,we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut *** sequencing revealed that the HFD upregulates gut microbial functions related to redox reactions,as confirmed by the increased reactive oxygen species(ROS)levels in fecal microbiota incubation in vitro and in the lumen,which were detected using in vivo fluorescence *** microbial ROS-producing capability induced by HFD can be transferred through fecal microbiota transplantation(FMT)into germ-free(GF)mice,downregulating the gut barrier tight ***,mono-colonizing GF mice with an Enterococcus strain excelled in ROS production,damaged the gut barrier,induced mitochondrial malfunction and apoptosis of the intestinal epithelial cells,and exacerbated fatty liver,compared with other low-ROS-producing Enterococcus *** administration of recombinant high-stability-superoxide dismutase(SOD)significantly reduced intestinal ROS,protected the gut barrier,and improved fatty liver against the *** conclusion,our study suggests that extracellular ROS derived from gut microbiota play a pivotal role in HFD-induced gut barrier disruption and is a potential therapeutic target for HFD-associated metabolic diseases.

关键词： fatty liver disease gut microbiota gut barrier high-fat diet oxidative stress reactive oxygen species

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