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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal key laboratory of Biomarker and translational research in Neurodegenerative Diseases BeijingChina key laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

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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01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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Retrospective analysis of interventional treatment of hepatic metastasis from gastroenteropancreatic neuroendocrine tumors

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Chinese Journal of Cancer research 2017年第6期29卷 581-586页

作者： Peng Liu Xu Zhu Jie Li Ming Lu Jiahua Leng Ying Li Jiangyuan Yu key laboratory of carcinogenesis and translational research(ministry of education/Beijing) Department of Interventional Therapy key laboratory of carcinogenesis and translational research(ministry of education/Beijing)Department of Gastroenterological Oncology key laboratory of carcinogenesis and translational research(ministry of education/Beijing)Center of Gastrointestinal Surgery Unit III key laboratory of carcinogenesis and translational research(ministry of education/Beijing)Department of Radiolog key laboratory of carcinogenesis and translational research(ministry of education/Beijing)Department of NuclearMedicine Peking University Cancer Hospital&InstituteB eijing 100142China

Objective： To analyze the angiography appearance of liver metastases from gastroenteropancreatic neuroendocrine tumors （GEP-NETs）, and evaluate the clinical efficacy and prognostic factors of interventional treatment for hepatic metastases. Methods： Fifty GEP-NETs patients with hepatic metastases were treated from January 2012 to December 2016, and received transarterial embolization （TAE） in the hepatic tumor or hepatic arterial infusion chemotherapy （HAIC）. All patients received 179 times of the intervention therapy in total. Results： Blood supplies were identified in the 50 eases with angiography, which showed that 35 cases had abundant vessels, while 15 eases had poor blood supply. Twenty-two cases were found either collateral blood supply, or portal vein invasion or arterial-portal vein fistula. The best curative efficacy was complete remission （CR） in 4 cases, partial remission （PR） in 28 cases and stable disease （SD） in 18 eases during the process of treatment. The angiography （P=0.047） and the frequency of intervention （P=0.037） showed significantly statistical difference with Kaplan-Meier analysis. The Cox analysis showed that more than 3 times of interventional therapy was an independent prognostic factor. Conclusions： Interventional treatment is safe and effective for GEP-NETs, and is beneficial to patients with main hepatic metastases after endocrine therapy.

关键词： Gastroenteropancreatic neuroendocrine tumors hepatic metastasis angiography interventionaltreatment retrospective analysis

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Depth of tumor invasion and tumor-occupied portions of stomach are predictive factors of intra-abdominal metastasis

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Chinese Journal of Cancer research 2017年第2期29卷 109-117页

作者： Ziyu Li Zhemin Li Shuqin Jia Zhaode Bu Lianhai Zhang Xiaojiang Wu Shuangxi Li Fei Shan Xin Ji Jiafu Ji key laboratory of carcinogenesis and translational research (ministry of education/Beijing) Center of Gastrointestinal Surgery key laboratory of carcinogenesis and translational research (ministry of education/Beijing) Center for Molecular Diagnostics Peking University Cancer Hospital & Institute Beijing 100142 China

Objective： Diagnostic laparoscopy is recommended for the pretherapeutic staging of gastric cancer to detect any unexpected or unconfirmed intra-abdominal metastasis. The aim of this study was to evaluate the role and indications of diagnostic laparoscopy in the detection of intra-abdominal metastasis. Methods： Standard diagnostic laparoscopy with peritoneal cytology examination was performed prospectively on patients who were clinically diagnosed with primary local advanced gastric cancer （CT≥2M0）. We calculated the rate of intra-abdominal metastases identified by diagnostic laparoscopy, and examined the relationship between peritoneal dissemination （P） and cytology results （CY）. Split-sample method was applied to find clinical risk factors for intra-abdominal metastasis. Multivariate logistic regression analysis and receiver-operator characteristic （ROC） analysis were performed in training set to find out risk factors ofintra-abdominal metastasis, and then validate it in testing set. Results： Out of 249 cM0 patients, 51 （20.5%） patients with intra-abdominal metastasis were identified by diagnostic laparoscopy, including 20 （8.0%） P1CY1, 17 （6.8%） POCY1 and 14 （5.6%） P1CY0 patients. In the training set, multivariate logistic regression analysis and ROC analysis showed that the depth of tumor invasion on computer tomography （CT） scan ≥21 mm and tumor-occupied 〉2 portions of stomach are predictive factors of metastasis. In the testing set, when diagnostic laparoscopy was performed on patients who had one or two of these risk factors, the sensitivity and positive predictive value for detecting intra-abdominal metastasis were 90.0% and 32.1%, respectively. Conclusions： According to our results, depth of tumor invasion and tumor-occupied portions of stomach are predictive factors ofintra-abdominal metastasis.

关键词： Gastric cancer diagnostic laparoscopy peritoneal dissemination intra-peritoneal free cancer cells pretherapeutic staging

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Intestinal stem cell marker LGR5 expression during gastric carcinogenesis

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World Journal of Gastroenterology 2013年第46期19卷 8714-8721页

作者： Zhi-Xue Zheng Yu Sun Zhao-De Bu Lian-Hai Zhang Zi-Yu Li Ai-Wen Wu Xiao-Jiang Wu Xiao-Hong Wang Xiao-Jing Cheng Xiao-Fang Xing Hong Du Jia-Fu Ji Department of Gastrointestinal Surgery Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital and Institute Department of Pathology Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital and Institute Clinical Gastric Cancer research laboratory Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital and Institute Tissue Bank Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital and Institute

AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and ***:Formalin-fixed biopsy specimens of intestinal metaplasia(n=90),dysplasia(n=53),gastric adenocarcinoma(n=180),metastases in lymph nodes and the liver(n=15),and lesion-adjacent normal gastric mucosa(controls;n=145)were obtained for analysis from the Peking University Cancer Hospital’s Department of Pathology and Gastrointestinal Surgery tissue archives(January 2003 to December 2011).The biopsied patients’demographic and clinicopathologic data were retrieved from the hospital’s medical records *** specimen was subjected to histopathological typing to classify the tumor node metastasis(TNM)stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker *** intergroup differences in LGR5 expression were assessed by Spearman’s rank correlation analysis,and the relationship between LGR5 expression level and the patients’clinicopathological characteristics was evaluated by theχ2test or Fisher’s exact ***:Significantly more gastric cancer tissues showed LGR5+staining than normal control tissues(all P<0.01),with immunoreactivity detected in 72.2%(65/90)and 50.9%(27/53)of intestinal metaplasia and dysplasia specimens,respectively,52.8%(95/180)of gastric adenocarcinoma specimens,and 73.3%%(11/15)of metastasis specimens,but 26.9%(39/145)of lesion-adjacent normal gastric mucosa *** of the intensity of LGR5+staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread(normal tissue

关键词： Leucine-rich repeat-containing G protein-coupled receptor 5 Cancer stem cell Gastric cancer Intestinal metaplasia Tumorigenesis

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Downregulation of miR-193a-5p correlates with lymph node metastasis and poor prognosis in colorectal cancer

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World Journal of Gastroenterology 2014年第34期20卷 12241-12248页

作者： Peng Zhang Deng-Bo Ji Hai-Bo Han Yun-Fei Shi Chang-Zheng Du Jin Gu key laboratory of carcinogenesis and translational research (ministry of education) Colorectal SurgeryPeking University Cancer Hospital and Institute key laboratory of carcinogenesis and translational research (ministry of education) Department of Cell BiologyPeking University Cancer Hospital and Institute key laboratory of carcinogenesis and translational research (ministry of education) Department of PathologyPeking University Cancer Hospital and Institute

AIM: To investigate the correlation of miR-193a-5p with lymph node metastasis and postoperative survival of colorectal cancer (CRC) patients.

关键词： miR-193a-5p Colorectal cancer Lymph node metastasis Prognosis Biomarker

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Utility of CT in differentiating liver metastases of well-differentiated gastroenteropancreatic neuroendocrine neoplasms from poorly-differentiated neuroendocrine neoplasms

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Chinese Journal of Cancer research 2018年第1期30卷 31-39页

作者： Yong Cui Xiaoting Li Shunyu Gao Zhongwu Li Yanling Li Ming Lu Yingshi Sun key laboratory of carcinogenesis and translational research (ministry of education/Beijing) Department of Radiology Beijing 100142 China key laboratory of carcinogenesis and translational research (ministry of education/Beijing)Department of Pathology Beijing 100142 China key laboratory of carcinogenesis and translational research (ministry of education/Beijing)Department of Gastrointestinal Oneology Peking University Cancer Hospital & Institute Beijing 100142 China

Objective： To determine the capability of dynamic enhanced computed tomography（CT） to differentiate liver metastases（LMs） of well-differentiated from poorly-differentiated gastroenteropancreatic neuroendocrine neoplasms（GEP-NENs）.Methods： Patients with LMs of GEP-NENs who underwent dynamic enhanced CT examination in Peking University Cancer Hospital from January 2009 to October 2015 were included and data were retrospectively analyzed. We assessed the qualitative and quantitative CT features to identify the significant differentiating CT features of LMs of poorly-differentiated GEP-NENs from those of well-differentiated GEP-NENs using univariate analysis and a multivariate logistic regression ***： The study included 22 patients with LMs of well-differentiated GEP-NENs and 32 patients with LMs of poorly-differentiated GEP-NENs. Univariate analysis revealed statistically significant differences between the LMs of well-and poorly-differentiated GEP-NENs in terms of feeding arteries（36.4% vs. 75.0%, χ2=8.061,P=0.005）, intratumoral neovascularity（18.2% vs. 59.4%, χ2=9.047, P=0.003）, lymphadenopathy（27.3% vs. 81.2%,χ2=15.733, P〈0.001）, tumor-to-aortic ratio in the hepatic arterial and portal venous phase（T-A/AP： 0.297±0.080 vs.0.251±0.059, t=2.437, P=0.018; T-A/PVP： 0.639±0.138 vs. 0.529±0.117, t=3.163, P=0.003） and tumor-to-liver ratio in the hepatic arterial phase（T-L/AP： 1.108±0.267 vs. 0.907±0.240, t=2.882, P=0.006）. The LMs of poorlydifferentiated GEP-NENs showed more feeding arteries, more intratumoral neovascularity, more lymphadenopathy and a lower tumor-to-aortic ratio. Multivariate analysis suggested that intratumoral neovascularity [P=0.015, OR=0.108, 95% confidence interval（95% CI）, 0.018–0.646], lymphadenopathy（P=0.001,OR=0.055, 95% CI, 0.009–0.323） and T-A/PVP（P=0.004, OR=5.3 E–5, 95% CI, 0.000–0.044） were independent factors for differentiating LMs of poorly-differentiated from well-differentiated ***： Dynamic enhanced CT features

关键词： Diagnosis gastroenteropancreatic neuroendocrine neoplasm neoplasm grading tomography X-ray computed

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Oxaliplatin plus S-1 or capecitabine as neoadjuvant or adjuvant chemotherapy for locally advanced gastric cancer with D2lymphadenectomy: 5-year follow-up results of a phase II-III randomized trial

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Chinese Journal of Cancer research 2018年第5期30卷 516-525页

作者： Kan Xue Xiangji Ying Zhaode Bu Aiwen Wu Zhongwu Li Lei Tang Lianhai Zhang Yan Zhang Ziyu Li Jiafu Ji key laboratory of carcinogenesis and translational research (ministry of education/Beijing) Gastrointestinal Cancer Center Beijing 100142 China key laboratory of carcinogenesis and translational research (ministry of education/Beijing) Department of Pathology Beijing 100142 China key laboratory of carcinogenesis and translational research (ministry of education/Beijing) Department of Radiology Peking University Cancer Hospital & Institute Beijing 100142 China

Objective： To compare the effect of neoadjuvant chemotherapy （NACT） with adjuvant chemotherapy （ACT） using oxaliplatin plus S-1 （sex） or capecitabine （CapeOX） on gastric cancer patients with D2 lymphadenectomy. Methods： This was a two-by-two factorial randomized phase Ⅱ-Ⅲ trial, and registered on ISRCTN registry （No. ISRCTN12206108）. Locally advanced gastric cancer patients were randomized to neoadjuvant sex, neoadjuvant CapeOX, adjuvant sex, or adjuvant CapeOX arms. Primary analysis was performed on an intention- to-treat （ITT） basis using overall survival （OS） as primary endpoint. Results： This trial started in September 2011 and closed in December 2012 with 100 patients enrolled. Treatment completion rate was 56%, 52%, 38% and 30% in the four arms, respectively. NACT group had fewer dropouts due to unacceptable toxicity （P=0.042）. Surgical complication rate did not differ by the four groups （P=0.986）. No survival signifcant difference was found comparing NACT with ACT （P=0.664; 5-year-OS： 70% vs. 74% respectively）, nor between the sex and CapeOX groups （P=0.252; 5-year-OS： 78% vs. 66% respectively）. Subgroup analysis showed sex significantly improved survival in patents with diffuse type （P=0.048）. Conclusions： No significant survival difference was found between NACT and ACT. sex and CapeOX had good safety and efficacy as neoadjuvant regimens. Diffuse type patients may survive longer due to sex.

关键词： SOX CapeOX neoadjuvant chemotherapy adjuvant chemotherapy gastric cancer

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Feasibility of differentiating T3 from T4a gastric cancer in different Lauren classification by determining serosa invasion：Diagnostic performance of high enhanced serosa sign

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Chinese Journal of Cancer research 2018年第2期30卷 263-271页

作者： Rui-Jia Sun Lei Tang Ying Chen Xiao-Ting Li Yu Sun Zi-Yu Li Ying-Shi Sun key laboratory of carcinogenesis and translational research (ministry of education/Beijing) Department of Radiology Beijing 100142 China key laboratory of carcinogenesis and translational research (ministry of education/Beijing) Departrnent of Pathology Beijing 100142 China key laboratory of carcinogenesis and translational research (ministry of education/Beijing) Center of Gastrointestinal Surgery Peking University Cancer Hospital & Institute Beijing 100142 China

Objective： To study the value of high enhanced serosa sign on contrast-enhanced computed tomography（CT）in differentiating T3 from T4a gastric cancer in different Lauren ***： This study included 276 consecutive patients with surgically confirmed p T3 or p T4a gastric *** pre-operative CT images were reviewed by two radiologists blinded. The demonstration of the high enhanced serosa on CT between T3 and T4a was compared with chi-square test. The diagnostic performance of this sign on CT in the differentiation of T4a from T3 in different Lauren classification was ***： The accuracy, sensitivity, specificity, positive predictive value（PPV） and negative predictive value（NPV） for the judgement of serosa invasion using the high enhanced serosa sign on CT was 74.6%, 63.7%, 83.6%,76.0% and 73.8% by one radiologist and 76.4%, 66.1%, 84.9%, 78.1% and 75.4% by the other *** to the intestinal-type, the sensitivity of the judgement of serosa invasion using the high enhanced serosa sign on CT in diffuse-type was significant higher（80% in both readers）, while the specificity trended to be lower（65.9% and 80.5%, respectively）. There is no significant difference in the accuracy of diagnosis between intestinaltype and diffuse-type of gastric cancers（the P-values of two radiologists were 0.968, 0.591, respectively）. The combination of the high enhanced serosa sign with conventional CT signs is significant different in diagnosis of T3 and T4a（P〈0.001）. The diagnostic accuracy was increased in both radiologists after the combination. The two readers achieved substantial agreement, with Kappa coefficient of 0.63, P〈***： The high enhanced serosa sign on CT is associated with serosa involvement. The sensitivity of the judgement of serosa invasion using this sign on CT in diffuse-type was significant higher than that in intestinal-type.

关键词： Computed tomography gastric cancer staging serosa invasion imaging

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Correlation between imaging features on computed tomography and combined positive score of PD-L1 expression in patients with gastric cancer

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Chinese Journal of Cancer research 2022年第5期34卷 510-518页

作者： Zhilong Wang Yinkui Wang Xiaoting Li Yanling Li Zhaode Bu Zhongwu Li Yingshi Sun Jiafu Ji key laboratory of carcinogenesis and translational research(ministry of education/Beijing) Department of RadiologyBeijing 100142China key laboratory of carcinogenesis and translational research(ministry of education/Beijing) Center of Gastrointestinal SurgeryBeijing 100142China key laboratory of carcinogenesis and translational research(ministry of education/Beijing) Department of PathologyPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:To explore the correlation between computed tomography(CT)features and combined positive score(CPS)of programmed cell death ligand 1(PD-L1)expression in patients with gastric cancer(GC).Methods:This study reviewed an institutional database of patients who underwent GC operation without neoadjuvant chemotherapy between December 2019 and September *** CPS results of PD-L1 expression of postoperative histological examination were recorded by *** CT features were measured,and their correlation with CPS 5 or 10 score groups of PD-L1 expression was ***:Data for 153 patients with GC were *** them,124 were advanced GC patients,and 29were early GC *** of the CT features significantly differed between CPS groups with a cutoff score of 5and a score of 10 in patients with early *** advanced GC,the presence of lymph nodes with short diameters>10mm was significantly different(P=0.024)between the CPS10 mm significantly differed between the CPS<10 and CPS≥10 groups in advanced *** sensitivity,specificity and area under receiver operating characteristic(ROC)curve of logistic regression model for predicting CPS≥10 was 71.7%,50.0%and 0.671,*** instability(MSI)status was significantly different in CPS groups with cutoff score of 5 and 10 in advanced GC ***:CT findings of advanced GC patients with CPS≥10 showed greater arterial phase enhancement and larger lymph *** has the potential to help screen patients suitable for immunotherapy.

关键词： Gastric cancer computed tomography combined positive score

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