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Immunotherapies for well-differentiated grade 3 gastroenteropancreatic neuroendocrine tumors:A new category in the World Health Organization classification

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World Journal of Gastroenterology 2021年第47期27卷 8123-8137页

作者： Jun-Xi Xu De-Hao Wu Li-Wei Ying han-guang hu Department of Medical Oncology The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009Zhejiang ProvinceChina Cancer Institute The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009Zhejiang ProvinceChina Department of Orthopedic Taizhou HospitalWenzhou Medical UniversityLinhai 317000Zhejiang ProvinceChina

According to the 2019 World Health Organization(WHO)classification,welldifferentiated grade 3(G3)gastroenteropancreatic(GEP)neuroendocrine tumors(NETs)are a new category of cancer of the digestive system.G3 GEP-NET research and treatment are not as robust as those of lower grade(G1/2)NETs and poorly differentiated neuroendocrine carcinomas(NECs).Previously,the management of high-grade NETs was mainly based on NEC therapies,as highgrade NETs were classified as NECs under the previous WHO *** this,G3 GEP-NETs are significantly less responsive to platinum-based chemotherapy regimens than NECs,due to their distinct molecular pathogenesis and course of pathological grade *** with advanced G3 GEPNETs,who have progressed or are intolerant to chemotherapy regimens such as capecitabine plus temozolomide,have limited treatment *** has helped patients with a variety of cancers attain long-term survival through the use of immune checkpoint ***,either alone or in combination with other therapies,do not have a clear function in the treatment of G3 ***,the majority of immunotherapy studies,both prospective and retrospective,do not reliably differentiate G3 GEP-NETs from *** contrast,a significant number of studies include non-GEP neuroendocrine neoplasms(NENs).Therefore,there is an urgent need to summarize and evaluate these data to provide more effective therapeutic approaches for patients with this rare *** purpose of this mini-review was to screen and summarize information on G3 GEP-NETs from all studies on NENs immunotherapy.

关键词： Gastrointestinal tract Pancreas Immune checkpoint inhibitors Immunotherapy Neuroendocrine tumors Cytotoxic T-lymphocyte-associated protein 4 antigen

Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2010年第9期11卷 647-653页

作者： Yan-qin huANG Ying YUAN Wei-ting GE han-guang hu Su-zhan ZhanG Shu ZHENG Key Laboratory of Cancer Prevention and Intervention of Ministry of Education Key Laboratory of Molecular Biology in Medical Science of Zhejiang Province Cancer Institute the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China

Objective:The purpose of this study was to determine the unique and universal features of microsatellite instability-high(MSI-H) colorectal cancer(CRC) and MSI-H gastric cancer(GC) in the Chinese ***:A new panel of mononucleotide MSI markers,BAT25,BAT26,NR21,NR24,and MONO-27,was used to define MSI status in 303 CRC and 288 GC *** features of both types of MSI-H tumors were *** analysis in the hMLH1 promoter region by methylation specific polymerase chain reaction(PCR) and mutation detection of hMSH2/hMLH1 genes by denaturing high-performance liquid chromatography(DHPLC) were carried out ***:MSI-H CRCs and MSI-H GCs account for 11.9% and 8.0% of unselected sporadic CRCs and GCs,***-H CRCs are strongly characterized by early onset,right-side location,low differentiation,mucinous tumor,less infiltration,less lymphatic metastasis,and more often familial ***-H GCs only showed site preference for the antrum and less lymphatic *** and epigenetic analyses were positive in 6/36 MSI-H CRCs and 0/23 MSI-H GCs with pathological mutation in major mismatch repair genes,and in 7/36 MSI-H CRCs and 18/23 MSI-H GCs with methylated hMLH1 promoter(P<0.01),***:Although there are many differences in the genetic basis and clinicopathological features between MSI-H CRC and MSI-H GC,when compared with their microsatellite stable(MSS) counterparts,site preference and lymphatic metastasis are features common to both types of MSI-H tumors.

关键词： Microsatellite instability Colorectal cancer Gastric cancer Mutation DNA methylation

Effect of SNC19/ST14qene overexpression on invasion of colorectal cancer cells

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World Journal of Gastroenterology 2005年第36期11卷 5651-5654页

作者： Ke-Feng Ding Li-Feng Sun Wei-Ting Ge han-guang hu Su-Zhan Zhang Shu Zheng Surgery of Oncology The Second Affiliated Hospital School of Medicine Zhejinag UniversityHangzhou 310009 Zhejiang Province China Cancer Institute School of Medicine Zhejinag University Hangzhou310009 Zhejiang Province China

AIM： TO study the effect of SNC19/ST14gene overexpression on invasion in vitro of colorectal cancer cells. METHODS： The adhesion of SlVC19/ST14gene-transfected cells to ECM was measured by MTT assay. The cell movement was evaluated by wound healing assay. Cell invasion and migration were determined by invasion assay in vitro. RESULTS： SNC19/ST14 gene overexpression could enhance invasion of colorectal cancer cells in vitro significantly and influence early cell adherence to ECM, but could not change cell movement significantly. CONCLUSION： SNC19/ST14 gene overexpression increases the local invasion of colorectal cancer cells in vitro. 2005 The WJG Press and Elsevier Inc. All rights reserved.

关键词： Gene SNC19/ST14 Colorectal cancer Invasion

Prognostic and survival analysis of 837 Chinese colorectal cancer patients

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World Journal of Gastroenterology 2013年第17期19卷 2650-2659页

作者： Ying Yuan Mo-Dan Li han-guang hu Cai-Xia Dong Jia-Qi Chen Xiao-Fen Li Jing-Jing Li Hong Shen Department of Medical Oncology 2nd Hospital of Zhejiang University College of Medicine

AIM:To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). METHODS:Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined asP < 0.05. RESULTS:The survival rate was 74% at 3 years and 68% at 5 years. The results of univariate analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P < 0.05). Lymph node ratio (LNR) was also a strong prognostic factor in stage Ⅲ CRC (P < 0.0001). We divided 341 stage Ⅲ patients into three groups according to LNR values (LNR1, LNR ≤ 0.33, n = 211; LNR2, LNR 0.34-0.66, n = 76; and LNR3, LNR ≥ 0.67, n = 54). Univariate analysis showed a significant statistical difference in 3-year survival among these groups:LNR1, 73%; LNR2, 55%; and LNR3, 42% (P < 0.0001). The multivariate analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the speci

关键词： Colorectal cancer Prognostic factors Cox proportional hazard regression Lymph node ratio

SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer

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World Journal of Gastroenterology 2011年第15期17卷 2028-2036页

作者： Shu-Jing Yu Jie-Kai Yu Wei-Ting Ge han-guang hu Ying Yuan Shu Zheng Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education Key Laboratory of Molecular Biology in Medical Science Zhejiang Province China) the Second Affiliated Hospital Zhejiang University College of Medicine Hangzhou 310009 Zhejiang Province China Cancer Institute (Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education Key Laboratory of Molecular Biology in Medical Science Zhejiang Province China) the Second Affiliated Hospital Zhejiang University College of Medicine Hangzhou 310009 Zhejiang Province China Department of Medical Oncology the Second Affiliated Hospital Zhejiang University College of Medicine Hangzhou 310009 Zhejiang Province China

AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers. RESULTS: Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P han others (P < 0.001). CONCLUSION: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging.

关键词： Colorectal cancer Prognosis SPARCL1 p53 Bioinformatics

Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao hu Si Wang Weiqi Zhang Jing Qu guang-hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

Clinical significance of K-ras and BRAF mutations in Chinese colorectal cancer patients

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World Journal of Gastroenterology 2011年第6期17卷 809-816页

作者： Hong Shen Ying Yuan han-guang hu Xiao-Xian Ye Mo- Dan Li Xian Zhong Wei-Jia Fang Shu Zheng Department of Oncology Second Affiliated Hospital Zhejiang University College of Medicine Hangzhou 310009 Zhejiang Province China Department of Internal Medicine Bin Jiang Hospital Hangzhou 310052 Zhejiang Province China Department of Medical Oncology First Affiliated Hospital Zhejiang University College of Medicine Hangzhou 310003 Zhejiang Province China KeyLaboratory of Cancer Prevention and Intervention of Ministry of Education Cancer Institute Second Affiliated Hospital Zhejiang University College of Medicine Hangzhou 310009 Zhejiang Province China

AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and ***:Genomic DNA was isolated from frozen *** analysis was conducted to detect mutations in the K-ras (codons 12,13,and 61) and BRAF genes (codon 600).Statistical analysis was carried out using SPSS-15.0 ***:Among the 118 colorectal cancer patients,we detected 41 (34.7%) mutations in the K-ras *** frequencies at codon 12 and codon 13 were 23.7% (28/118) and 10.2% (12/118),*** one patient harbored a point mutation at codon 61 (0.8%,1/118).Gender was the only factor that showed an obvious relationship with K-ras gene mutation (female 44.7% vs male 28.2%,P=0.037).Other clinicopathological features,such as age,location of the tumor,tumor differentiation,Tumor,Node and Metastases classification,and the Union for International Cancer Control staging,showed no positive relationship with K-ras gene *** significant correlation was observed between the presence of K-ras mutations (codons 12,13,and 61) and the survival of the *** mutations were rare,and only two patients (1.7%) harbored a detectable mutation at codon ***:K-ras gene mutation is a common event in our 118 Chinese CRC patients,with an obvious relationship with ***,it seems not to be an independent prognostic factor in CRC *** BRAF gene is rarely mutated in Chinese CRC patients.

关键词： K-ras BRAF Colorectal cancer Mutation

Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo Qi han Tang Jianian hu Siying Kang Song Qin Department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

Deep eutectic solvents for separation and purification applications in critical metal metallurgy:Recent advances and perspectives

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 1-19页

作者： Shuo Chen Shengpeng Su Yanfang huang Bingbing Liu hu Sun Shuzhen Yang Guihong han School of Chemical Engineering Zhengzhou UniversityZhengzhou 450001China Zhongyuan Critical Metals Laboratory Henan ProvinceZhengzhou 450001China

Solvent extraction,a separation and purification technology,is crucial in critical metal *** solvents commonly used in solvent extraction exhibit disadvantages,such as high volatility,high toxicity,and flammability,causing a spectrum of hazards to human health and environmental *** solvents have been recognized as potential alternatives to these harmful organic *** the past two decades,several neoteric solvents have been proposed,including ionic liquids(ILs)and deep eutectic solvents(DESs).DESs have gradually become the focus of green solvents owing to several advantages,namely,low toxicity,degradability,and low *** this critical review,their classification,formation mechanisms,preparation methods,characterization technologies,and special physicochemical properties based on the most recent advancements in research have been systematically ***,the major separation and purification applications of DESs in critical metal metallurgy were comprehensively ***,future opportunities and challenges of DESs were explored in the current research *** conclusion,this review provides valuable insights for improving our overall understanding of DESs,and it holds important potential for expanding separation and purification applications in critical metal metallurgy.

关键词： deep eutectic solvents preparations properties separation and purification critical metal metallurgy