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World Journal of Clinical Cases 2025年第6期13卷 24-29页

作者： Wen-Jin Yuan Yi-Juan Zheng Bing-Rong Zhang Yi-Jie Lin You Li Yan-Yan Qiu Xue-Ping Yu Department of infection Disease Clinical Medical Research Center for Bacterial and Fungal Infectious Diseases of Fujian provinceFujian Medical University Affiliated First Quanzhou HospitalQuanzhou 362000Fujian ProvinceChina

BACKGROUND Hydroxyurea,an antimetabolite,is frequently prescribed for various hemato-logical disorders,and its common side effects include gastrointestinal problems,cutaneous or mucosal lesions and pyrexia/*** SUMMARY This study reports the case of a 67-year-old woman who developed recurrent abdominal pain after 10 years of continuous hydroxyurea therapy for primary *** revealed an ileocecal *** discontinuing hydroxyurea therapy for 6 months,follow-up colonoscopy showed a significant reduction in the *** We consider cecal ulcers as a rare complication of hydroxyurea therapy which typically resolves upon stopping the drug.

关键词： Hydroxyurea Ulcer Abdominal pain Thrombocythemia Colonoscopy Case report

Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2025年第1期 263-271页

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian cancer Institute Linzhou cancer Hospital center for Disease Control and Prevention of Sheyang County Department of cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Luoshan center for Disease Control and Prevention Office for cancer Control and research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer（GC） in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates（CIRs） of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic（atrophic gastritis/intestinal metaplasia） and neoplastic lesions（low-grade/high-grade dysplasia）, respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients（≥3 risk factors） with non-neoplastic lesions showed higher GC risks（adjusted HR=7.73, 95%CI: 4.29–13.92）, and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions（aHR=3.07, 95%CI: 1.67–5.64） and high-risk patients with mild lesions（aHR=7.29, 95%CI: 3.58–14.86） showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2025年第1期 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal cancer center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University Key Laboratory of Carcinogenesis and cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Epigenetic regulation of the inflammatory response in stroke

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Neural Regeneration research 2025年第11期20卷 3045-3062页

作者： Jingyi Liang Fei Yang Zixiao Li Qian Li School of Basic Medical Sciences Capital Medical UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Laboratory for Clinical Medicine Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical research center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain research BeijingChina research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering research center of Digital Healthcare for Neurological Diseases BeijingChina Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing Key Laboratory of cancer Invasion and Metastasis research Capital Medical UniversityBeijingChina

Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either *** mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral *** the inflammatory response has been shown to mitigate this cascade of events in experimental stroke ***,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for *** may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in *** acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic *** agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of ***,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke *** this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome *** also discuss promising molecular targets for stroke *** evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.

关键词： DNA methylation histone modification intracerebral hemorrhage ischemic stroke neuroinflammation neuroprotection non-coding RNA RNA methylation subarachnoid hemorrhage treatment

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Recurrence after endoscopic piecemeal mucosal resection for large sessile colorectal polyps

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World Journal of Gastroenterology 2010年第22期16卷 2806-2811页

作者： Guh Jung Seo Dae Kyung Sohn Kyung Su Han Chang Won Hong Byung Chang Kim Ji Won Park Hyo Seong Choi Hee Jin Chang Jae Hwan Oh center for Colorectal cancer Research Institute and Hospital National Cancer Center

AIM: To evaluate the safety and outcomes of endoscopic piecemeal mucosal resection (EPMR) for large sessile colorectal polyps. METHODS: The patients enrolled in this study were 47 patients with 50 large sessile polyps (diameter, 2 cm or greater) who underwent EPMR using a submucosal saline injection technique between December 2002 and October 2005. All medical records, including characteristics of the patients and polyps, complications, and recurrences, were retrospectively reviewed. The first follow-up endoscopic examination was performed at 3-6 mo after initial endoscopic resection, and the second at 12 mo postEPMR. Subsequent surveillance colonoscopic examinations were individualized, taking risk factors into account. RESULTS: The patients were 23 men and 24 women,with a mean age of 60 years. Mean polyp size was 30.1 mm. Of 50 polyps identified, 34 (68%) were benign and 16 (32%) were malignant. There were 6 (12%) cases with EPMR-related bleeding: 5 intra-procedural and 1 early post-procedural bleeding. All bleeding episodes were managed by endoscopic clipping or argon beam coagulation. There were no perforations. Recurrence was identified in 5 cases (12.2%): 4 local recurrences detected at 3 mo post-EPMR and 1 local recurrence detected at 14 mo post-EPMR. The recurrence rate after EPMR was 3.1% for benign polyps and 33.3% for malignant polyps (P < 0.05). Median follow-up time was 37 mo. CONCLUSION: EPMR is safe, but should be applied carefully in malignant polyps. Close follow-up endoscopic examinations are necessary for early detection of recurrence.

关键词： Colonoscopy Colorectal neoplasm Endoscopic piecemeal mucosal resection Large sessile polyps

Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational research on Lung cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and cancer (IBMC) Chinese Academy of Sciences Department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteractioncancer therapeutics.

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Unlocking the future:Mitochondrial genes and neural networks in predicting ovarian cancer prognosis and immunotherapy response

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World Journal of Clinical Oncology 2025年第1期16卷 43-52页

作者： Zhi-Jian Tang Yuan-Ming Pan Wei Li Rui-Qiong Ma Jian-Liu Wang Department of Obstetrics and Gynecology Peking University People’s HospitalBeijing 100044China cancer research center Beijing Chest HospitalBeijing 101149China Department of Thoracic Surgery Sichuan Provincial People's HospitalChengdu 610072Sichuan ProvinceChina

BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment *** To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural *** Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The cancer Genome Atlas and Gene Expression *** genes were sourced from the MitoCarta3.0 *** discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation *** the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were *** In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy *** average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation *** average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation *** The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.

关键词： Ovarian cancer Mitochondria Prognosis Immunotherapy Neural network

Myeloid immunosuppression and immune checkpoints in the tumor microenvironment

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Cellular & Molecular Immunology 2020年第1期17卷 1-12页

作者： Kyohei Nakamura Mark J.Smyth Immunology in cancer and infection Laboratory QIMR Berghofer Medical Research InstituteHerston 4006 QLDAustralia

Tumor-promoting inflammation and the avoidance of immune destruction are hallmarks of *** innate immune cells,such as neutrophils,monocytes,and macrophages,are critical mediators for sterile and nonsterile inflammation,persistent inflammation,such as that which occurs in cancer,is known to disturb normal *** disturbance leads to the generation of immunosuppressive myeloid cells,such as myeloid-derived suppressor cells(MDSCs)and tumor-associated macrophages(TAMs).Due to their potent suppressive activities against effector lymphocytes and their abundance in the tumor microenvironment,immunosuppressive myeloid cells act as a major barrier to cancer ***,various therapeutic approaches directed toward immunosuppressive myeloid cells are actively being tested in preclinical and clinical *** include antiinflammatory agents,therapeutic blockade of the mobilization and survival of myeloid cells,and immunostimulatory *** recently,immune checkpoint molecules expressed on tumor-infiltrating myeloid cells have emerged as potential therapeutic targets to redirect these cells to eliminate tumor *** this review,we discuss the complex crosstalk between cancer-related inflammation and immunosuppressive myeloid cells and possible therapeutic strategies to harness antitumor immune responses.

关键词： myeloid macrophage innate immunity immune checkpoint inflammation

Killing of p53-deficient hepatoma cells by parvovirus H-1 and chemotherapeutics requires promyelocytic leukemia protein

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World Journal of Gastroenterology 2008年第24期14卷 3819-3828页

作者： Maike Sieben Kerstin Herzer Maja Zeidler Vera Heinrichs Barbara Leuchs Martin Schuler Jan J Cornelis Peter R Galle Jean Rommelaere Markus Moehler First Department of Internal Medicine Johannes Gutenberg University of Mainz German cancer research center Infection and Cancer ProgramDept.F010 and Institut National de la Santé et de la Recherche Médicale Unité 701 Department of Medicine (cancer research) West German Cancer CenterUniversity Hospital Essen

AIM: To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functional promyelocytic leukemia protein (PML). METHODS: The role of p53 and PML in regulating cy-totoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in two pairs of isogenic human hepatoma cell lines with different p53 status. Further-more,H-1 PV infection was combined with cytostatic drug treatment. RESULTS: While the HCC cells with different p53 status studied were all susceptible to H-1 PV-induced apoptosis,the cytotoxicity of H-1 PV was morepronounced in p53-negative than in p53-positive cells. Apoptosis rates in p53-negative cell lines treated by genotoxic drugs were further enhanced by a treatment with H-1 PV. In flow cytometric analyses,H-1 PV infection resulted in a reduction of the mitochondrial transmembrane potential. In addition,H-1 PV cells showed a significant increase in PML expression. Knocking down PML expression resulted in a striking reduction of the level of H-1 PV infected tumor cell death. CONCLUSION: H-1 PV is a suitable agent to circumvent the resistance of p53-negative HCC cells to genotoxic agents,and it enhances the apoptotic process which is dependent on functional PML. Thus,H-1 PV and its oncolytic vector derivatives may be considered as therapeutic options for HCC,particularly for p53-negative tumors.

关键词： Autonomous parvovirus Apoptosis p53 Promyelooltic leukemia protein Human hepatocellularcarcinoma Hepatooltes