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Dietary intake and serum levels of copper and zinc and risk of hepatocellular carcinoma:A matched case-control study

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Chinese Medical Journal 2024年第5期137卷 596-603页

作者： Xiaozhan Liu Yaojun Zhang Dinuerguli Yishake Yan Luo Zhaoyan Liu Yuming Chen Huilian Zhu Aiping Fang Guangdong Provincial Key Laboratory of Food Nutrition and HealthSchool of Public HealthSun Yat-sen UniversityGuangzhouGuangdong 510080China State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China

Background:Copper and zinc are involved in the development of multiple malignancies;yet,epidemiological evidence on hepatocellular carcinoma(HCC)is *** study aimed to investigate the association between dietary intake and serum levels of copper and zinc with the risk of ***:A total of 434 case-control pairs matched for sex and age(±1 year)were included in this *** with newly diagnosed HCC were from the Guangdong Liver Cancer Cohort(GLCC)study,and healthy controls were from the Guangzhou Nutrition and health Study(GNHS).A semi-quantitative 79-item food frequency questionnaire(FFQ)was used to assess habitual dietary intakes of copper and *** levels of copper and zinc were measured by using inductively coupled plasma mass *** copper(Cu)/zinc(Zn)ratio was computed by dividing copper levels by zinc *** logistic regression models were performed to calculate the odds ratio(OR)and 95%confidence intervals(CI)for per 1 standard deviation increase(per-SD increase)in copper and zinc ***:Higher dietary intake(OR_(per-SD increase)=0.65,95%CI:0.44,0.96,P_(trend)=0.029)and serum levels of zinc(OR_(per-SD increase)=0.11,95%CI:0.04,0.30,P_(trend)<0.001)were both associated with a lower risk of *** analyses showed that the inverse association was only pronounced in men but not in women(P_(interaction)=0.041 for dietary zinc intake and 0.010 for serum zinc levels).Serum copper levels(OR_(per-SD increase)=2.05,95%CI:1.39,3.03,P_(trend)=0.020)and serum Cu/Zn ratio(OR_(per-SD increase)=6.53,95%CI:2.52,16.92,P_(trend)<0.001)were positively associated with HCC risk,while dietary copper intake and dietary Cu/Zn ratio were not associated with HCC ***:Zinc may be a protective factor for HCC,especially among men,but the effects of copper on HCC risk are not clear.

关键词： Copper Zinc Hepatocellular carcinoma risk Case-control studies Dietary intake Serum

Development of a radiomics model to discriminate ammonium urate stones from uric acid stones in vivo:A remedy for the diagnostic pitfall of dual-energy computed tomography

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Chinese Medical Journal 2024年第9期137卷 1095-1104页

作者： Junjiong Zheng Jie Zhang Jinhua Cai Yuhui Yao Sihong Lu Zhuo Wu Zhaoxi Cai Aierken Tuerxun Jesur Batur Jian Huang Jianqiu Kong Tianxin Lin Department of Urology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationGuangdong Provincial Clinical Research Center for Urological DiseasesGuangzhouGuangdong 510120China Department of Neurology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510120China Department of Radiology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510120China Department of Urology The First People’s Hospital of Kashgar PrefectureKashgarXinjiang 844000China

Background:Dual-energy computed tomography(DECT)is purported to accurately distinguish uric acid stones from non-uric acid ***,whether DECT can accurately discriminate ammonium urate stones from uric acid stones remains ***,we aimed to explore whether they can be accurately identified by DECT and to develop a radiomics model to assist in distinguishing ***:This research included two *** the first purpose to evaluate the accuracy of DECT in the diagnosis of uric acid stones,178 urolithiasis patients who underwent preoperative DECT between September 2016 and December 2019 were *** model construction,93,40,and 109 eligible urolithiasis patients treated between February 2013 and October 2022 were assigned to the training,internal validation,and external validation sets,*** features were extracted from non-contrast CT images,and the least absolute shrinkage and selection operator(LASSO)algorithm was used to develop a radiomics ***,a radiomics model incorporating the radiomics signature and clinical predictors was *** performance of the model(discrimination,calibration,and clinical usefulness)was ***:When patients with ammonium urate stones were included in the analysis,the accuracy of DECT in the diagnosis of uric acid stones was significantly ***-two percent of ammonium urate stones were mistakenly diagnosed as uric acid stones by DECT.A radiomics model incorporating the radiomics signature,urine pH value,and urine white blood cell count was *** model achieved good calibration and discrimination{area under the receiver operating characteristic curve(AUC;95%confidence interval[CI]),0.944(0.899-0.989)},which was internally and externally validated with AUCs of 0.895(95%CI,0.796-0.995)and 0.870(95%CI,0.769-0.972),*** curve analysis revealed the clinical usefulness of the ***:DECT cannot accurately differentiate amm

关键词： Ammonium urate Dual-energy scanned projection radiography Radiomics Uric acid Urolithiasis

Subdiaphragmatic abscess caused by the recently identifi ed pathogen Cutibacterium modestum: a case report

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World Journal of Emergency Medicine 2024年第5期15卷 422-424页

作者： Lian Liang Ni Tan Mingbin Feng Xiaolin Xu Zuyong Li Xiaoxing Tan Tangchun Liu Nengtai Ouyang Yin Zhang Zhengfei Yang Department of Emergency Medicine Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Cellular&Molecular Diagnostics center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Biliary-Pancreatic Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Ultrasound Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China

Subdiaphragmatic abscess is uncommon in patients who undergo resection for hepatocellular *** identifi cation of pathogens and appropriate treatment can be challenging.[1]Herein,we present a case of subdiaphragmatic abscess caused by Cutibacterium modestum.A 66-year-old man was admitted to our hospital with fever,cough,and persistent,dull pain in the right upper quadrant for two *** patient’s medical history included liver cirrhosis,radical resection of hepatocellular carcinoma three months prior to admission,and type 2 diabetes *** examination revealed tachycardia with small moist rales in the right lower *** examination revealed an L-shaped,well-healed surgical incision in the right upper quadrant without intra-abdominal mass or tenderness.

关键词： admitted abscess tachycardia

Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2119-2136页

作者： Li Peng Yanyi Jiang Hengxing Chen Yongqiang Wang Qiusheng Lan Shuiqin Chen Zhanwang Huang Jingyuan Zhang Duanqing Tian Yuntan Qiu Diankui Cai Jiangyun Peng Daning Lu Xiaoqing Yuan Xianzhu Yang Dong Yin Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Medical Research center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Hefei Institutes of Physical Science Chinese Academy of SciencesHefei 230031China Department of Gastrointestinal Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Hepatobiliary Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442China

Transcriptional dysregulation of genes is a hallmark of tumors and can serve as targets for cancer drug ***,it is extremely challenging to develop small-molecule inhibitors to target abnormally expressed transcription factors(TFs)except for the nuclear receptor family of *** is known about the interaction between TFs and transcription cofactors in gastroesophageal adenocarcinoma(GEA)or the therapeutic effects of targeting TF and transcription cofactor *** this study,we found that ETS homologous factor(EHF)expression is promoted by a core transcriptional regulatory circuitry(CRC),specifically ELF3-KLF5-GATA6,and interference with its expression suppressed the malignant biological behavior of GEA ***,we identified Ajuba LIM protein(AJUBA)as a new coactivator of EHF that cooperatively orchestrates transcriptional network activity in ***,we identified KRAS signaling as a common pathway downstream of EHF and ***,dual targeting of EHF and AJUBA by lipid nanoparticles cooperatively attenuated the malignant biological behaviors of GEA in vitro and in *** conclusion,EHF is upregulated by the CRC and promotes GEA malignancy by interacting with AJUBA through the KRAS *** of both EHF and its coactivator AJUBA through lipid nanoparticles is a novel potential therapeutic strategy.

关键词： EHF AJUBA KRAS pathway Enhancer Core transcriptional regulatory circuitry Gastroesophageal adenocarcinoma Gastric adenocarcinoma Esophageal adenocarcinoma Transcription factor Coactivator Lipid nanoparticles

Structural transition,electric transport,and electronic structures in the compressed trilayer nickelate La4Ni3O10

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Science China(Physics,Mechanics & Astronomy) 2024年第11期Mechanics & Astronomy) .卷 13-19页

作者： Jingyuan Li Cui-Qun Chen Chaoxin Huang Yifeng Han Mengwu Huo Xing Huang Peiyue Ma Zhengyang Qiu Junfeng Chen Xunwu Hu Lan Chen Tao Xie Bing Shen Hualei sun Dao-Xin Yao Meng Wang center for Neutron Science and Technology Guangdong Provincial Key Laboratory of Magnetoelectric Physics and Devices School of Physics Sun Yat-sen University center for Materials of the Universe School of Molecular Sciences Arizona State University School of Sciences Sun Yat-sen University

Atomic structure and electronic band structure are fundamental properties for understanding the mechanism of superconductivity. Motivated by the discovery of pressure-induced high-temperature superconductivity at 80 K in the bilayer Ruddlesden-Popper nickelate La3Ni2O7, the atomic structure and electronic band structure of the trilayer nickelate La4Ni3O10under pressure up to 44.3 GPa are investigated. A structural transition from the monoclinic P21/a space group to the tetragonal I4/mmm around 12.6-13.4 GPa is identified, accompanied by a drop of resistance below 7 K. Density functional theory calculations suggest that the bonding state of Ni 3dz2orbital rises and crosses the Fermi level at high pressures, which may give rise to possible superconductivity observed in resistance under pressure in La4Ni3O10. The trilayer nickelate La4Ni3O10shows some similarities with the bilayer La3Ni2O7and has unique properties, providing a new platform to investigate the underlying mechanism of superconductivity in nickelates.

关键词： La4Ni3O10 high pressure synchrotron X-ray diffraction structural transition DFT calculations

Inflammatory Factor IL1αInduces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca^(2+)/CaMK2b Pathway

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Neuroscience Bulletin 2024年第4期40卷 421-438页

作者： Yu Xia Lu Ding Changlin Zhang Qi Xu Ming Shi Tianshun Gao Feng-Quan Zhou David Y.B.Deng Scientific Research center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Department of Gynecology The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Pelvic Floor Disorders center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Big Data center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou310016China Orthopaedic and Neurological Repair center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological ***,the mechanism underlying astrocyte over-proliferation after SCI is ***2c(glutamate ionotropic receptor type 2c)plays an essential role in cell *** bioinformatic analysis indicated that Grin2c and Ca^(2+)transport functions were inhibited in astrocytes after *** of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in *** screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage *** of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation ***,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.

关键词： IL1α Grin2c Astrocyte Spinal cord injury

Current therapies for osteoarthritis and prospects of CRISPR-based genome,epigenome,and RNA editing in osteoarthritis treatment

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Journal of Genetics and Genomics 2024年第2期51卷 159-183页

作者： Yuxi Chen Xiao Luo Rui Kang Kaixin Cui Jianping Ou Xiya Zhang Puping Liang MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdong 510275China center for Reproductive Medicine The Third Affiliated Hospital of Sun Yat-sen UniversitySun Yat-sen UniversityGuangzhouGuangdong 510630China

Osteoarthritis(OA)is one of the most common degenerative joint diseases worldwide,causing pain,disability,and decreased quality of *** balance between regeneration and inflammation-induced degradation results in multiple etiologies and complex pathogenesis of ***,there is a lack of effective therapeutic strategies for OA *** the development of CRISPR-based genome,epigenome,and RNA editing tools,OA treatment has been improved by targeting genetic risk factors,activating chondrogenic elements,and modulating inflammatory *** by cell therapy and in vivo delivery vectors,genome,epigenome,and RNA editing tools may provide a promising approach for personalized OA *** review summarizes CRISPR-based genome,epigenome,and RNA editing tools that can be applied to the treatment of OA and provides insights into the development of CRISPR-based therapeutics for OA ***,in-depth evaluations of the efficacy and safety of these tools in human OA treatment are needed.

关键词： Osteoarthritis Genome editing Epigenone editing RNA editing

RP11-789C1.1 inhibits gastric cancer cell proliferation and accelerates apoptosis via the ATR/CHK1 signaling pathway

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中华医学杂志(英文版) 2024年第15期137卷 1835-1843页

作者： Liu Wenwei Feng Wei Zhang Yongxin Lei Tianxiang Wang Xiaofeng Qiao Tang Chen Zehong Song Wu Digestive Diseases center The Seventh Affiliated Hospital of Sun Yat-sen University Shenzhen Guangdong China Department of Gastrointestinal Surgery The First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Laboratory of General Surgery The First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Department of Gastrointestinal Surgery The Third Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong China

Background: Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully ***: We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC *** vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of ***: Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin ***: In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.

关键词： Long non-coding RNA RP11-789C1.1 Stomach neoplasms ATR CHK1 Oxaliplatin

TP53-specific mutations serve as a potential biomarker for homologous recombination deficiency in breast cancer:a clinical next-generation sequencing study

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Precision Clinical Medicine 2024年第2期7卷 122-131页

作者： Yongsheng Huang Shuwei Ren Linxiaoxiao Ding Yuanling jiang Jiahuan Luo Jjinghua Huang Xinke Yin Jianli Zhao Sha Fu Jianwei Liao Cellular&Molecular Diagnostics center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Clinical Laboratory The Sixth Affliated HospitalSun Yat-sen UniversityGuangzhou 510655China Breast Tumor center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangzhou Regenerative Medicine and health Guangdong LaboratorySun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China

Background:TP53 mutations and homologous recombination deficiency(HRD)occur frequently in breast ***,the characteristics of TP53 pathogenic mutations in breast cancer patients with/without HRD are not ***:Clinical next-generation sequencing(NGS)of both tumor and paired blood DNA from 119 breast cancer patients(BRCA-119 cohort)was performed with a 520-gene ***,tumor mutation burden(TMB),and genomic HRD scores were assessed from NGS *** data from 47 breast cancer patients in the HRD test cohort were analyzed for further ***:All TP53 pathogenic mutations in patients had somatic origin,which was associated with the protein expression of estrogen receptor and progestogen *** to patients without TP53 pathologic mutations,patients with TP53 pathologic mutations had higher levels of HRD scores and different genomic *** frequency of TP53 pathologic mutation was higher in the HRDhigh group(HRD score≥42)relative to that in the HRD-low group(HRD score<42).TP53 has different mutational characteristics between the HRD-low and HRD-high ***53-specific mutation subgroups had diverse genomic features and ***,TP53 pathogenic mutations predicted the HRD status of breast cancer patients with an area under the curve(AUC)of ***53-specific mutations,namely HRD-low mutation,HRD-high mutation,and HRD common mutation,predicted the HRD status of breast cancer patients with AUC values of 0.32,0.72,and 0.58,***,TP53 HRD-high mutation and HRD common mutation combinations showed the highest AUC values(0.80)in predicting HRD ***:TP53-specific mutation combinations predict the HRD status of patients,indicating that TP53 pathogenic mutations could serve as a potential biomarker for poly-ADP-ribose polymerase(PARP)inhibitors in breast cancer patients.

关键词： next-generation sequencing homologous recombination deficiency TP53 breast cancer