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Chinese expert consensus on refined diagnosis, treatment, and management of advanced primary liver cancer (2023 edition)

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Current status of early gastric cancer screening research

Liver Research 2024年第2期8卷 61-71页

作者： Xiufeng Liu Feng Xia Yue Chen Huichuan Sun Zhengqiang Yang Bo Chen Ming Zhao Xinyu Bi Tao Peng Aizier Ainiwaer Zhiwen Luo Fusheng Wang Yinying Lu Department of Medical Oncology Bayi Hospital Affiliated to Nanjing Chinese Medical University Nanjing Jiangsu China Department of Hepatobiliary Surgery Southwest Hospital Army Medical University Chongqing China Senior Department of Hepatology The Fifth Medical Center of PLA General Hospital Beijing China Department of Liver Surgery and Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai China Department of Interventional Therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Minimally Invasive Interventional Therapy Liver Cancer Study and Service Group Sun Yat-sen University Cancer Center Guangzhou Guangdong China Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Hepatobiliary Surgery The First Affiliated Hospital of Guangxi Medical University Nanning Guangxi China Senior Department of Infectious Diseases The Fifth Medical Center of PLA General Hospital Beijing China Comprehensive Liver cancer center The Fifth Medical Center of PLA General Hospital Beijing China

Hepatocellular carcinoma (HCC), commonly known as primary liver cancer, is a major cause of malignant tumors and cancer-related deaths in China, accounting for approximately 85% of all cancer cases in the country. Several guidelines have been used to diagnose and treat liver cancer. However, these guidelines provide a broad definition for classifying advanced liver cancer, with an emphasis on a singular approach, without considering treatment options for individual patients. Therefore, it is necessary to establish a comprehensive and practical expert consensus, specifically for China, to enhance the diagnosis and treatment of HCC using the Delphi method. The classification criteria were refined for Chinese patients with HCC, and the corresponding optimal treatment regimen recommendations were developed. These recommendations took into account various factors, including tumor characteristics, vascular tumor thrombus grade, distant metastasis, liver function status, portal hypertension, and the hepatitis B virus replication status of patients with primary HCC, along with treatment prognosis. The findings and recommendations provide detailed, scientific, and reasonable individualized diagnosis and treatment strategies for clinicians.

关键词： Hepatocellular carcinoma (HCC) Targeted therapy Immunotherapy Refined diagnosis and treatment Expert consensus

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cancer Biology & Medicine 2024年第3期21卷 218-222页

作者： Can Hu Li Yuan Xiangdong Cheng Department of Gastric surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China Key Laboratory of Prevention Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang ProvinceHangzhou 310022China Zhejiang Provincial Research center for Upper Gastrointestinal Tract cancer Zhejiang Cancer HospitalHangzhou 310022China

Gastric cancer is a predominant threat to the health and well-being of China's residents. Data from the World Health Organization(WHO) in 2020 revealed that gastric cancer in China notably accounted for 44.0% of new c... 详细信息

关键词： cancer Gastric gastric

Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

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Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang Xu Zhu Zequn Lu Yimin Cai Bin Li Ying Zhu Xiangpan Li Yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao Department of Epidemiology and Biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China Department of cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China Department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation center for cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly ***,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics *** a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in *** the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in *** subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras ***,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 ***,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC *** summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation

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Chinese Journal of Integrative Medicine 2024年第7期30卷 600-607页

作者： XU Ben ZHANG Jia-en YE Lin YUAN Chang-wei Department of Urology Peking University First Hospital and Institute of UrologyPeking UniversityNational Urological Cancer CenterBeijing100034China

Objective To explore the molecular mechanism by which curcumin affects renal interstitial fibrosis(RIF)progression by regulating ADAM metallopeptidase with thrombospondin type 1 motif 18(ADAMTS18)*** NRK-49F cells RIF model were induced with transforming growth factorβ1(TGF-β1).Effects of different concentrations of curcumin(0,10,20,and 30μmol/L)on cell proliferation,cell cycle,cell apoptosis as well as cyclin D1 expression were analyzed by cell counting kit-8,flow cytometry and Western blot,***18 methylation levels were determined by methylation-specific polymerase chain ***18,fibronectin(FN),type I collagen(Col-I)and alpha-smooth muscle actin(α-SMA)mRNA and protein expressions were analyzed by real-time PCR(RT-PCR)and Western blot,***,cells were treated with 50 mmol/L 5-aza-2′-deoxycytidine(5-aza-dC,demethylation agent)for 72 *** of curcumin on extracellular matrix(ECM)deposition was evaluated by immunochemical staining and Western ***-49F cells were transfected with ADAMTS18 small interfering RNA and grouped into a normal control,ADAMTS18-knock-out(KO),and ADAMTS18-KO+30μmol/L curcumin groups,and whether curcumin can reverse the effect of ADAMTS18 knockdown on RIF was *** Compared with the control group,TGF-β1 significantly inhibited the proliferation of NRK-49F cells,blocked the G1/G0 phase,promoted cell apoptosis and inhibited cyclin D1 expression(P<0.01).Among the different concentrations of curcumin,30μmol/L curcumin significantly reversed these processes(P<0.01).Immunochemical staining and Western blot results showed that curcumin significantly inhibited the deposition of FN,Col-I andα-SMA(P<0.01).Curcumin and 5-zaz-dC had synergistic effects,promoting ADAMTS18 expression,removing ADAMTS18 methylation,and reducing ECM ***18 knockdown promoted ECM accumulation,and curcumin reversed this process(P<0.01).Conclusion TGF-β1-induced fibrosis in NRK-49F ***

关键词： renal fibrosis curcumin Chinese medicine ADAMTS18 methylation modification

Chemoselective labeling-based spermatozoa glycan imaging reveals abnormal glycosylation in oligoasthenotspermia

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Chinese Chemical Letters 2024年第4期35卷 475-480页

作者： Lijia Xu Tong Zhong Wei Zhao Bing Yao Lin Ding Huangxian Ju State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China Department of Reproductive Medical center Jinling HospitalSchool of MedicineNanjing UniversityNanjing 210002China Chemistry and Biomedicine Innovation center(ChemBIC) Nanjing UniversityNanjing 210023China center of Clinical Laboratory Science The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210009China

Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack of in situ imaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid(Sia) and N-acetyl-D-galactosamine(Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/Gal NAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting that in vivo glucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.

关键词： Spermatozoa Glycan Chemoselective labeling Oligoasthenotspermia Fluorescence imaging

Recent Advances in Nickel Catalyzed Carbonylative Reactions via the Insertion of Carbon Monoxide

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Chinese Journal of Chemistry 2024年第2期42卷 177-189页

作者： Xinzhou Chen Gang Chen Zhong Lian Department of Dermatology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduSichuan 610041China

Carbonyl compounds have attracted considerable attention due to their extensive applications in drug ***,they are important synthetic intermediates for the construction of carbon-carbon and carbon-heteroatom ***-metal-catalyzed carbonylation via the insertion of co is one of the most efficient and straightforward strategies to access carbonyl ***,most of the transition-metal-catalyzed carbonylative reactions require expensive and toxic noble-metal ***,there is a growing demand for the exploration of nickel-catalyzed carbonylative reactions via the insertion of CO due to the earth abundance and low cost of *** with the well-established palladium-catalyzed carbonylative reactions,nickel-catalyzed analogous transformations have been relatively *** is primarily because CO strongly binds to nickel,often resulting in catalyst *** recent years,some research groups have focused on using CO surrogates or NN_(2) pincer nickel catalyst to circumvent the formation of Ni(CO)_(4).Nickel-catalyzed carbonylation has been applied in the construction of carbonyl-containing compounds,such as ketones,carboxylic acids,thioesters,acyl chloride and carboxamides.

关键词： Carbonylation Nickel catalysis Carbon monoxide C1 chemistry Carbonyl-containing compounds

Structural analysis of conformational changes in the mpox virus A7 protein

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Virologica Sinica 2024年第2期39卷 331-334页

作者： Xincheng Ni Kai Wang Yinze Han Jian Lei National Clinical Research center for Geriatrics and State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu610041China

Dear Editor,The mpox(formerly known as monkeypox)disease caused by the mpox virus(MPXV)has infected more than 89,700 people and is linked to 157 deaths in 114 countries worldwide as of September 2023(***).Mpox is a zoonotic disease,the first human case of which was reported in 1970(Breman et al.,1980).Common symptoms in mpox-infected individuals include fever,myalgia,fatigue,headache,and a characteristic rash(Isidro et al.,2022).Current treatments for mpox remain limited,and an in-depth investigation of essential viral protein(s)will help to explore novel drug targets.

关键词： infected headache

The BCL-2 inhibitor APG-2575 resets tumor-associated macrophages toward the M1 phenotype,promoting a favorable response to anti-PD-1 therapy via NLRP3 activation

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Cellular & Molecular Immunology 2024年第1期21卷 60-79页

作者： Fan Luo Han Li Wenjuan Ma Jiaxin Cao Qun Chen Feiteng Lu Miaozhen Qiu Penghui Zhou Zengfei Xia Kangmei Zeng Jianhua Zhan Ting Zhou Qiuyun Luo Wentao Pan Lin Zhang Chaozhuo Lin Yan Huang Li Zhang Dajun Yang Hongyun Zhao State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouChina Ascentage Pharma(Suzhou)Co Ltd 218 Xinghu StreetSuzhouJiangsu ProvinceChina

The main challenges in the use of immune checkpoint inhibitors(ICIs)are ascribed to the immunosuppressive tumor microenvironment and the lack of sufficient infiltration of activated CD8+T *** the tumor microenvironment(TME)from“cold”to“hot”and thus more likely to potentiate the effects of ICIs is a promising strategy for cancer *** found that the selective BCL-2 inhibitor APG-2575 can enhance the antitumor efficacy of anti-PD-1 therapy in syngeneic and humanized CD34+mouse *** single-cell RNA sequencing,we found that APG-2575 polarized M2-like immunosuppressive macrophages toward the M1-like immunostimulatory phenotype with increased CCL5 and CXCL10 secretion,restoring T-cell function and promoting a favorable immunotherapy ***,we demonstrated that APG-2575 directly binds to NF-κB p65 to activate NLRP3 signaling,thereby mediating macrophage repolarization and the activation of proinflammatory caspases and subsequently increasing CCL5 and CXCL10 chemokine *** a result,APG-2575-induced macrophage repolarization could remodel the tumor immune microenvironment,thus improving tumor immunosuppression and further enhancing antitumor T-cell *** immunohistochemistry confirmed that patients with better immunotherapeutic efficacy had higher CD86,p-NF-κB p65 and NLRP3 levels,accompanied by lower CD206 expression on ***,these data provide evidence that further study on APG-2575 in combination with immunotherapy for tumor treatment is required.

关键词： BCL-2 APG-2575 ICIs Macrophages NLRP3

Stability and variability of molecular subtypes: comparative analysis of primary and metastatic triple-negative breast cancer

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cancer Biology & Medicine 2024年第9期21卷 784-798页

作者： Xiuzhi Zhu Xiaohan Ying Yin Liu Yunyi Wang Li Chen Zhiming Shao Xi Jin Yizhou Jiang Zhonghua Wang Key Laboratory of Breast cancer in Shanghai Shanghai Institute of Infectious Disease and Biosecurity Department of Oncology Shanghai Medical College Fudan University Department of Breast Surgery Fudan University Shanghai Cancer Center

Objective: Triple-negative breast cancer(TNBC) is a heterogeneous and aggressive cancer. Although our previous study classified primary TNBC into four subtypes, comprehensive longitudinal investigations are ***: We assembled a large-scale, real-world cohort comprised of 880 TNBC patients [465 early-stage TNBC(e TNBC) and 415 metastatic TNBC(m TNBC) patients] who were treated at Fudan University Shanghai cancer center. The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort. Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC ***: The recurrence and metastasis rates within 3 years after initial diagnosis in the e TNBC cohort were 10.1%(47/465). The median overall survival(OS) in the m TNBC cohort was 27.2 months [95% confidence interval(CI), 24.4±30.2 months], which indicated a poor prognosis. The prognostic significance of the original molecular subtypes in both e TNBC and m TNBC patients was confirmed. Consistent molecular subtypes were maintained in 77.5% of the patients throughout disease progression with the mesenchymal-like(MES) subtype demonstrating a tendency for subtype transition and brain metastasis. Additionally, a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE ***: Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression. However, we emphasize the major importance of repeat pathologic confirmation of the MES subtype.

关键词： Triple-negative breast cancer metastasis molecular subtype overall survival primary tumor