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Cohort study on the treatment of BRAF V600E mutant metastatic colorectal cancer with integrated Chinese and western medicine

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World Journal of Clinical oncology 2025年第1期16卷 25-33页

作者： Jiang-Yu Bian Yu-Fang Feng Wen-Ting He Tong Zhang department of oncology Xiyuan Hospital of China Academy of Chinese Medical SciencesBeijing 100091China department of oncology The Fourth Clinical Medical College of Xinjiang Medical UniversityUrumqi 830001China department of oncology Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical UniversityUrumqi 830001China

BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor *** the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal ***,we further explored the survival benefits in the population with BRAF V600E mutant *** To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal *** A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December *** patients were divided into two *** A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,*** analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.

关键词： Metastatic colorectal cancer BRAF V600E mutation Integrated Chinese and Western medicine Cohort study

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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,Pinteraction<0.001).Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs（P=0.040） and sqNSCLCs（P=0.014）,*** the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNSCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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Enhancing insights into Global Cancer Statistics 2022: implications for cancer control

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Science China Life Sciences 2025年第1期 294-296页

作者： Jingtong Xu Runtian Wang Xiaoxiang Guan department of oncology the First Affiliated Hospital of Nanjing Medical University Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineNanjing Medical University

Globally, there has been a marked escalation in tumor morbidity and mortality,cementing tumors as the predominant cause of death in numerous *** the current tumor burden across various regions is imperative to discern potential risk factors and formulate efficacious strategies for tumor ***, the International Agency for Research on Cancer(IARC) provided a status report on the global tumor burden,estimating the incidence and mortality of 36 cancers in 185 countries(Bray et al.,2024).

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Carcinosarcoma of the breast:Facing the challenge of a rare nosologic entity

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World Journal of Clinical Cases 2025年第2期13卷 14-20页

作者： Aikaterini Mastoraki Maria Tsamopoulou Foivos-Konstantinos Stamatis Alexios Strimpakos Ero Mouchtouri Christiana Panagi Evgenia Mela Sotiria Mastoraki Aristotelis Kechagias Dimitrios Schizas department of Surgery National and Kapodistrian University of AthensLaikon General HospitalAthens 11527Greece department of Surgery National and Kapodistrian University of AthensAthens 11527Greece department of medical oncology Hygeia HospitalAthens 15123Greece department of radiology Henry Dunant Hospital CenterAthens 11526Greece department of Surgery Athens Metropolitan HospitalAthens 15562Greece

Carcinosarcoma(CS),also known as metaplastic breast carcinoma with mesenchymal differentiation,is one of the five distinct subtypes of metaplastic breast *** is considered as a mixed,biphasic neoplasm consisting of a carcinomatous component combined with a malignant nonepithelial element of mesenchymal origin without an intermediate transition *** cellular origin of this neoplasm remains controversial,most researchers declare that neoplastic cells derive from a cellular structure with potential biphasic *** recent research on the therapeutic strategies against CS neoplastic disorders,surgical resection appears the only potentially curative *** CS metastasize by the lymphatic route,axillary assessment with sentinel lymph node biopsy and/or axillary lymph node dissection is always ***,the tumor also presents a hematogenous metastatic pattern including pleural,pulmonary,liver,brain and less commonly bone ***,surgical removal of breast CS does not necessarily ensure patient’s long-term ***,alternative therapies,such as radio-and chemotherapy proved insufficient and 5-year survival rate is ***,there is evidence that following surgery,the combination of radio and chemotherapy is associated with a better prognosis than either treatment *** aim of this review is to evaluate the results of surgical treatment for breast CS with special reference to the extent of its histological *** features,histogenesis,morphological and immunochemical findings are discussed,while the role of current diagnostic and therapeutic management of this aggressive neoplasm is emphasized.

关键词： Carcinosarcoma Breast Diagnostic approach Therapeutic management Prognostic parameters

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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期 204-218页

作者： Chen Xiong Hong Ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University department of oncology Shanghai Medical CollegeFudan University department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University department of oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

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Machine learning applications in healthcare clinical practice and research

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World Journal of Clinical Cases 2025年第1期13卷 16-21页

作者： Nikolaos-Achilleas Arkoudis Stavros P Papadakos Research Unit of radiology and medical Imaging School of MedicineNational and Kapodistrian University of AthensAthens 11528Greece 2^(nd)department of radiology “Attikon”General University HospitalMedical SchoolNational and Kapodistrian University of AthensChaidari 12462Greece department of Gastroenterology Laiko General HospitalNational and Kapodistrian University of AthensAthens 11527Greece

Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human *** its various applications,it has proven groundbreaking in healthcare as well,both in clinical practice and *** this editorial,we succinctly introduce ML applications and present a study,featured in the latest issue of the World Journal of Clinical *** authors of this study conducted an analysis using both multiple linear regression(MLR)and ML methods to investigate the significant factors that may impact the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results implicated age as the most important determining factor in both groups,followed by lactic dehydrogenase,uric acid,forced expiratory volume in one second,and *** addition,for the NAFLD-group,the 5th and 6th most important impact factors were thyroid-stimulating hormone and systolic blood pressure,as compared to plasma calcium and body fat for the NAFLD+***,the study's distinctive contribution lies in its adoption of ML methodologies,showcasing their superiority over traditional statistical approaches(herein MLR),thereby highlighting the potential of ML to represent an invaluable advanced adjunct tool in clinical practice and research.

关键词： Machine Learning Artificial Intelligence Clinical Practice Research Glomerular filtration rate Non-alcoholic fatty liver disease Medicine

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric medical Research Center BeijingChina department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina department of radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research Center for Geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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Implantable port thrombosis in cancer patients: a monocentric experience

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Cancer Biology & Medicine 2016年第3期13卷 384-388页

作者： Manel Dridi Nesrine Mejri Soumaya Labidi Mehdi Afrit Houda El Benna Khaoula Ben Miled Hamouda Boussen medical oncology department Abderrahmen Mami Hospital radiology department Abderrahmen Mami Hospital

Objective: Implantable port thrombosis(IPT) in cancer patients is a relatively rare but severe complication. Several factors are reportedly associated with the occurrence of thrombosis. We aimed to describe the prevalence and the anatomoclinical features of IPT observed in cancer patients who were treated in a medical oncology department in ***: A total of 600 cancer patients who had port implantation from January 2013 to December 2015 were retrospectively identified. Cases with symptomatic/incidental IPT(radiologically confirmed) were further identified. Epidemiological and anatomoclinical features were collected from patient records and the department ***: We observed that 33 of the 600 patients had IPT; thus, the prevalence was 5.5%. The median age was 57 years, and the gender ratio was 0.43. Overweight or obesity was observed in 73% of the patients. IPT occurred mainly in patients with breast(36.4%) and colorectal(33.3%) cancers, which were mostly nonmetastatic(79%). At least one identified classical thromboembolic risk factor was found in 13 patients(smoking in 9, tamoxifen in 2). IPT was symptomatic in 93% of the cases, occurring within an average time of 56 days. Implantable ports were removed because of infection in 2 cases and nonfunctionality in 3 cases. IPT treatment was based on low-molecular-weight heparins(94%) and antivitamin K(6%) for an average of 130 days. Four patients had post-therapy complications: one thrombosis recurrence and three ***: IPT cases in the 600 patients were observed to occur in obese nonmetastatic cancer patients within the first 3 months after IP implantation.

关键词： Implantable port cancer patients thrombosis

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Integration of perioperative features and intragraft TCF7L2 expression to predict lipid metabolic disorder in liver transplant recipients

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Science China Life Sciences 2025年第1期 297-299页

作者： Junbin Zhou Rongli Wei Guanghan Fan Zhengxing Lian Xuanyu Zhang Linsong Tang Zhetuo Qi Haiyang Xie Shusen Zheng Qiang Wei Xiao Xu department of Hepatobiliary and Pancreatic Surgery People's Hospital of LishuiAffiliated Lishui Hospital of Wenzhou Medical UniversityThe First Affiliated Hospital of Lishui University NHFPC Key Laboratory of Combined Multi-Organ Transplantation Key Laboratory of Integrated oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryHangzhou First People's Hospital department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of Medicine department of Urology The Second Affiliated HospitalZhejiang University School of Medicine department of Hepatobiliary and Pancreatic Surgery Department of Liver TransplantationShulan (Hangzhou) Hospital Hangzhou medical College Zhejiang University School of Medicine

Dear Editor, Liver transplantation(LT) is the only curative therapy for patients with endstage liver disease(He et al., 2023; Ling et al., 2022). Post-transplant hypertriglyceridemia(PTHT), which has an incidence of up to 32.8% in 6 months after LT, is one of the major post-transplant complications(Toshima et al., 2020).

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Persistent alterations in gray matter in COVID-19 patients experiencing sleep disturbances:a 3-month longitudinal study

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Neural Regeneration Research 2025年第10期20卷 3013-3024页

作者： Kaixuan Zhou Gaoxiong Duan Ying Liu Bei Peng Xiaoyan Zhou Lixia Qin Lingyan Liang Yichen Wei Qingping Zhang Xiaocheng Li Haixia Qin Yinqi Lai Yian Lu Yan Zhang Jiazhu Huang Jinli Huang Yinfei Ouyang Bolin Bin Mingming Zhao Jun Liu Jianrong Yang Demao Deng Guangxi Key Laboratory of Special Biomedicine School of MedicineGuangxi UniversityNanningGuangxi Zhuang Autonomous RegionChina department of radiology the People’s Hospital of Guangxi Zhuang Autonomous RegionGuangxi Academy of Medical SciencesNanningGuangxi Zhuang Autonomous RegionChina department of Sleep Medicine the People’s Hospital of Guangxi Zhuang Autonomous RegionNanningGuangxi Zhuang Autonomous RegionChina department of radiology The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Guangxi Clinical Research Center for Sleep Medicine the People’s Hospital of Guangxi Zhuang Autonomous RegionNanningGuangxi Zhuang Autonomous RegionChina

Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 *** studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019(COVID-19).However,neuroimaging studies on sleep disturbances caused by COVID-19 are scarce,and existing studies have primarily focused on the long-term effects of the virus,with minimal acute phase *** a result,little is known about the pathophysiology of sleep disturbances in the acute phase of *** address this issue,we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection,and verified the results using 3-month follow-up data.A total of 26 COVID-19 patients with sleep disturbances(aged 51.5±13.57 years,8 women and 18 men),27 COVID-19 patients without sleep disturbances(aged 47.33±15.98 years,9 women and 18 men),and 31 age-and gender-matched healthy controls(aged 49.19±17.51 years,9 women and 22 men)were included in this *** COVID-19 patients with sleep disturbances were included in a longitudinal *** found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain *** cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index ***,we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy *** 3-month follow-up data revealed indices of altered cerebral structure(cortical thickness,cortical grey matter volume,and cortical surface area)in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep *** findings indicate that the sleep disturbances patients had altered morphology in the cortical an

关键词： brain structure cortical gray matter volume cortical surface area cortical thickness hippocampus magnetic resonance imaging Pittsburgh Sleep Quality Index severe acute respiratory syndrome coronavirus 2 infections sleep disturbances sub-cortical volume

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