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Epidemiologic characteristics of oral cancer:single-center analysis of 4097 patients from the sun yat-sen university Cancer Center

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Chinese Journal of Cancer 2016年第4期35卷 190-195页

作者： Ji Zhang Fan Gao An-Kui Yang Wen-Kuan Chen Shu-Wei Chen Huan Li Xing Zhang Zhong-Yuan Yang Xin-Lin Chen Ming Song State Key Laboratory of Oncology in South China Collaborative Innovation Center of Cancer MedicineSun Yat-sen University Cancer Center Department of Head and Neck Surgery Sun Yat-sen University Cancer Center Department of Intensive Care Sun Yat-sen University Cancer Center Department of Preventive Medicine and Biostatistics School of Basic Medical ScienceGuangzhou Higher Education Mega CenterGuangzhou University of Chinese Medicine

Background:Oral cancer is a common type of head and neck cancers.Knowing its epidemiologic characteristics is crucial to preventing,diagnosing,and treating this cancer.This study aimed to explore the epidemiologic characteristics of oral cancer in South China.Methods:We retrospectively analyzed data from 4097 oral cancer patients treated at the sun yat-sen university Cancer Center between 1960 and 2013.We compared the age of onset,sex ratio,pathologic type,and primary tumor location among three subcultural areas(Guangfu,Hakka,and Chaoshan) and between an economically developed region and a less-developed one in Guangdong.Results:Overall,oral cancer had a male-to-female ratio of approximately 2:1,and this ratio decreased over time.Oral cancer occurred mostly in patients of 45-64 years old(54.5%),and the percentage of older patients gradually increased over time.The most common tumor location was the tongue.Squamous cell carcinoma was the predominant pathologic type.The percentage of blood type O in oral cancer patients was lower than that in the healthy population.The male-to-female ratio in the Chaoshan area was higher than that in the Guangfu and Hakka areas,whereas the age of disease onset in Guangfu was higher than that in Hakka and Chaoshan.The male-to-female ratio was lower and the age of disease onset was higher in the economically developed region than in the less-developed region.Conclusion:The incidence of oral cancer in South China presents typical characteristics to which doctors should pay attention when diagnosing and treating oral cancer patients.

关键词： Oral cancer Epidemiology Guangdong

Nanomedicine targeting ferroptosis to overcome anticancer therapeutic resistance

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Science China(Life Sciences) 2024年第1期67卷 19-40页

作者： Jing Cai Xiaoding Xu Phei Er Saw Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Nanhai Translational Innovation Center of Precision Immunology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityFoshan 528200China

A potential reason for the failure of tumor therapies is treatment resistance.Resistance to chemotherapy,radiotherapy,and immunotherapy continues to be a major obstacle in clinic,resulting in tumor recurrence and metastasis.The major mechanisms of therapy resistance are inhibitions of cell deaths,like apoptosis and necrosis,through drug inactivation and excretion,repair of DNA damage,tumor heterogeneity,or changes in tumor microenvironment,etc.Recent studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell death.Some ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor therapy.Notably,versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance,including directly triggering ferroptosis and feedback regulation.Herein,we provide a detailed description of the design,mechanism,and therapeutic application of ferroptosis-mediated synergistic tumor therapeutics.We also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.

关键词： ferroptosis cancer therapy therapy resistance nanoinducers

Maximizing conditional independence for unsupervised domain adaptation

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Science China(Information Sciences) 2024年第5期67卷 136-149页

作者： Yiming ZHAI Chuanxian REN Youwei LUO Daoqing DAI sun yat-sen university School of Mathematics

Unsupervised domain adaptation(UDA) studies how to transfer a learner from a labeled source domain to an unlabeled target domain with different distributions. Existing methods mainly focus on matching marginal distributions of the source and target domains, which probably leads to a misalignment of samples from the same class but different domains. In this paper, we tackle this misalignment issue by achieving the class-conditioned transferring from a new perspective. Specifically, we propose a method named maximizing conditional independence(MCI) for UDA, which maximizes the conditional independence of feature and domain given class in the reproducing kernel Hilbert spaces. The optimization of conditional independence can be viewed as a surrogate for minimizing class-wise mutual information between feature and domain. An interpretable empirical estimation of the conditional dependence measure is deduced and connected with the unconditional case. Besides, we provide an upper bound on the target error by taking the class-conditional distribution into account, which provides a new theoretical insight for class-conditioned transferring. Extensive experiments on six benchmark datasets and various ablation studies validate the effectiveness of the proposed model in dealing with UDA.

关键词： conditional independence kernel method domain adaptation class-conditioned transferring

Enhanced piezoelectric performance of Cr/Ta non-equivalent co-doped Bi_(4)Ti_(3)O_(12)-based high-temperature piezoceramics

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Journal of Advanced Ceramics 2024年第3期13卷 263-271页

作者： Xuanyu Chen Ziqi Ma Bin Li Yejing Dai School of Materials Sun Yat-sen UniversityShenzhen 518107China

In this study,(Cr_(1/3)/Ta_(2/3))non-equivalent co-doped Bi_(4)Ti_(3)O_(12)(BIT)ceramics were prepared to solve the problem that high piezoelectric performance,high Curie temperature,and high-temperature resistivity could not be achieved simultaneously in BIT-based ceramics.A series of Bi_(4)Ti_(3-x)(Cr_(1/3)Ta_(2/3))_(x)O_(12)(x=0-0.04)ceramics were synthesized by the solid-state reaction method.The phase structure,microstructure,piezoelectric performance,and conductive mechanism of the samples were systematically investigated.The B-site non-equivalent co-doping strategy combining high-valence Ta^(5+)and low-valence Cr^(3+)significantly enhances electrical properties due to a decrease in oxygen vacancy concentration.Bi_(4)Ti_(2.97)(Cr_(1/3)Ta_(2/3))_(0.03)O_(12)ceramics exhibit a high piezoelectric coefficient(d_(33)=26 pC·N^(-1))and a high Curie temperature(TC=687℃).Moreover,the significantly increased resistivity(ρ=2.8×10^(6)Ω·cm at 500℃)and good piezoelectric stability up to 600℃are also obtained for this composition.All the results demonstrate that Cr/Ta co-doped BIT-based ceramics have great potential to be applied in high-temperature piezoelectric applications.

关键词： high temperature piezoelectricity co-doped Bi_(4)Ti_(3)O_(12)(BIT)

High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

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Neural Regeneration Research 2024年第8期19卷 1772-1780页

作者： Jing Luo Yuan Feng Zhongqiu Hong Mingyu Yin Haiqing Zheng Liying Zhang Xiquan Hu Department of Rehabilitation Medicine The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Hepatobiliary Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for

关键词： AKT/β-catenin signaling brain stimulation Ca2+influx cell proliferation ischemic stroke middle cerebral artery occlusion neural stem cells neurological rehabilitation repetitive transcranial magnetic stimulation

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 development.However,it is extremely challenging to develop small-molecule inhibitors to target abnormally expressed transcription factors(TFs)except for the nuclear receptor family of TFs.Little is known about the interaction between TFs and transcription cofactors in gastroesophageal adenocarcinoma(GEA)or the therapeutic effects of targeting TF and transcription cofactor complexes.In 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 cells.Importantly,we identified Ajuba LIM protein(AJUBA)as a new coactivator of EHF that cooperatively orchestrates transcriptional network activity in GEA.Furthermore,we identified KRAS signaling as a common pathway downstream of EHF and AJUBA.Applicably,dual targeting of EHF and AJUBA by lipid nanoparticles cooperatively attenuated the malignant biological behaviors of GEA in vitro and in vivo.In conclusion,EHF is upregulated by the CRC and promotes GEA malignancy by interacting with AJUBA through the KRAS pathway.Targeting 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

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 life.The balance between regeneration and inflammation-induced degradation results in multiple etiologies and complex pathogenesis of OA.Currently,there is a lack of effective therapeutic strategies for OA treatment.With 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 regulators.Supported by cell therapy and in vivo delivery vectors,genome,epigenome,and RNA editing tools may provide a promising approach for personalized OA therapy.This 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 treatment.Moreover,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

A Reliable Iteration Algorithm for One-Bit Compressive sensing on the Unit Sphere

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Acta Mathematicae Applicatae Sinica 2024年第3期40卷 801-822页

作者： Yan-cheng LU Ning BI An-hua WAN School of Mathematics Sun Yat-sen UniversityGuangzhou 510275China

The one-bit compressed sensing problem is of fundamental importance in many areas,such as wireless communication,statistics,and so on.However,the optimization of one-bit problem coustrained on the unit sphere lacks an algorithm with rigorous mathematical proof of convergence and validity.In this paper,an iteration algorithm is established based on difference-of-convex algorithm for the one-bit compressed sensing problem constrained on the unit sphere,with iterating formula■,where C is the convex cone generated by the one-bit measurements andη_(1)>η_(2)>1/2.The new algorithm is proved to converge as long as the initial point is on the unit sphere and accords with the measurements,and the convergence to the global minimum point of the l_(1)norm is discussed.

关键词： one-bit compressed sensing difference of convex algorithm iteration algorithm ■1-minimization

Targeted therapies for lupus nephritis:Current perspectives and future directions

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Chinese Medical Journal 2024年第1期137卷 34-43页

作者： Xiuzhi Jia Yuewen Lu Xunhua Zheng Ruihan Tang Wei Chen Department of Nephrology The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510080China NHC Key Laboratory of Clinical Nephrology(sun yat-sen university) and Guangdong Provincial Key Laboratory of NephrologyGuangzhouGuangdong 510080China

Lupus nephritis(LN),a severe manifestation of systemic lupus erythematosus,poses a substantial risk of progression to end-stage renal disease,with increased mortality.Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids,mycophenolate mofetil,and calcineurin inhibitors.Although therapeutic regimens have evolved over the years,they have inherent limitations,including non-specific targeting,substantial adverse effects,high relapse rates,and prolonged maintenance and remission courses.These drawbacks underscore the need for targeted therapeutic strategies for LN.Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity.This review provides an overview of the current evidence on targeted therapies for LN,elucidates the biological mechanisms of responses and failure,highlights the challenges ahead,and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

关键词： Lupus nephritis Molecular targeted therapies Adaptive immunity Immunity,Innate Cytokines