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Neuroscience Bulletin 2021年第11期37卷 1609-1624页

作者： Qiongqiong Wu Xiaoyi Wang Ying Wang yu-jun long Jing-Ping Zhao Ren-Rong Wu National Clinical Research Center for Mental Disorders Department of PsychiatryThe Second Xiangya Hospital of Central South UniversityChangsha 410011China Shanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai 200031China

The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last *** first part of this review summarizes the pathogenesis of schizophrenia,especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and *** second part describes the novel medications and several advanced physical therapies(e.g.,transcranial magnetic stimulation and transcranial direct current stimulation)for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.

关键词： Schizophrenia Genetics Epigenetics Negative symptoms Cognitive dysfunction Physical therapy

Precision medicine: In need of guidance and surveillance

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World Journal of Gastroenterology 2017年第28期23卷 5045-5050页

作者： Jian-Zhen Lin jun-yu long An-Qiang Wang Ying Zheng Hai-Tao Zhao Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical College State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical ScienceUniversity of Macao

Precision medicine,currently a hotspot in mainstream medicine,has been strongly promoted in recent years. With rapid technological development,such as next-generation sequencing,and fierce competition in molecular targeted drug exploitation,precision medicine represents an advance in science and technology; it also fulfills needs in public health care. The clinical translation and application of precision medicine-especially in the prevention and treatment of tumors-is far from satisfactory; however,the aims of precision medicine deserve approval. Thus,this medical approach is currently in its infancy; it has promising prospects,but it needs to overcome numbers of problems and deficiencies. It is expected that in addition to conventional symptoms and signs,precision medicine will define disease in terms of the underlying molecular characteristics and other environmental susceptibility factors. Those expectations should be realized by constructing a novel data network,integrating clinical data from individual patients and personal genomic background with existing research on the molecular makeup of diseases. In addition,multi-omics analysis and multi-discipline collaboration will become crucial elements in precision medicine. Precision medicine deserves strong support,and its development demands directed momentum. We propose three kinds of impetus(research,application and collaboration impetus) for such directed momentum toward promoting precision medicine and accelerating its clinical translation and application.

关键词： Precision medicine Clinical translation Development Targeted therapy Immunotherapy

Prognostic significance of combined preoperative fibrinogen and CA199 in gallbladder cancer patients

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World Journal of Gastroenterology 2018年第13期24卷 1451-1463页

作者： Wei-yu Xu Hao-Hai Zhang Xiao-Bo Yang Yi Bai Jian-Zhen Lin jun-yu long Jian-Ping Xiong jun-Wei Zhang Xin-Ting Sang Hai-Tao Zhao Department of Liver Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

AIM To investigate the prognostic value of the combination of preoperative plasma fibrinogen and CA199 in patients with gallbladder carcinoma(GBC).METHODS The clinicopathological data of 154 GBC patients were retrospectively reviewed after surgery. A receiver operating characteristic(ROC) curve was plotted to verify the optimum cut-off values for plasma fibrinogen and CA199. Univariate and multivariate survival analyses were performed to identify the factors associated with GBC prognosis. based on the HRs calculated via multivariate survival analyses, patients with elevated plasma fibrinogen and CA199 levels were allocated a score of 2.1; those with an elevated plasma fibrinogen level only were allocated a score of 1, those with an elevated CA199 level only were allocated a score of 1.1, and those with neither of these abnormalities were allocated a score of *** ROC curve analysis showed that the optimum cut-off values for preoperative plasma fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively. Multivariate analysis indicated that elevated preoperative plasma fibrinogen and CA199 levels were significantly correlated with worse overall survival(OS)(HR = 1.711, 95%CI: 1.114-2.627, P = 0.014, and HR = 1.842, 95%CI: 1.111-3.056, P = 0.018). When we combined these two parameters, the area under the ROC curve increased from 0.735(for preoperative plasma fibrinogen only) and 0.729(for preoperative CA199 only) to 0.765. When this combined variable was added to the multivariate analysis, the combination of plasma fibrinogen and CA199(P < 0.001), resection margin(P < 0.001) and TNM stage(P = 0.010) were independent prognostic factors for *** The combination of plasma fibrinogen and CA199 may serve as a more efficient independent prognostic biomarker for postoperative GBC patients than either parameter alone.

关键词： Prognostic factor Plasma fibrinogen CA199 Survival Gallbladder cancer

Clinical outcomes of lenvatinib plus transarterial chemoembolization with or without programmed death receptor-1 inhibitors in unresectable hepatocellular carcinoma

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World Journal of Gastroenterology 2023年第10期29卷 1614-1626页

作者： Yan-yu Wang Xu Yang yun-Chao Wang jun-yu long Hui-Shan Sun Yi-Ran Li Zi-yu Xun Nan Zhang Jing-Nan Xue Cong Ning jun-Wei Zhang Cheng-Pei Zhu long-Hao Zhang Xiao-Bo Yang Hai-Tao Zhao Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of General Surgery Digestive Disease HospitalAffiliated Hospital of Zunyi Medical UniversityZunyi 563003Guizhou ProvinceChina

BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional *** To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)*** terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 *** the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with *** to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression *** evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v *** key adverse events(AEs)after the initiation of combination therapy were *** Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of

关键词： Lenvatinib Programmed death receptor-1 inhibitor Immunotherapy Hepatocellular carcinoma Transarterial chemoembolization Combination therapy

Threonine and tyrosine kinase may serve as a prognostic biomarker for gallbladder cancer

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World Journal of Gastroenterology 2017年第31期23卷 5787-5797页

作者： yuan Xie Jian-Zhen Lin An-Qiang Wang Wei-yu Xu jun-yu long yu-Feng Luo Jie Shi Zhi-Yong Liang Xin-Ting Sang Hai-Tao Zhao Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Pathology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical College

AIM To detect the expression of threonine and tyrosine kinase(TTK) in gallbladder cancer(GBC) specimens and analyze the associations between TTK expression and clinicopathological parameters and clinical *** A total of 68 patients with GBC who underwent surgical resection were enrolled in this study. The expression of TTK in GBC tissues was detected by immunohistochemistry. The assessment of TTKexpression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of TTK in the cytoplasm and nucleus was scored separately to achieve respective H-s c o r e v a l u e s. T h e c o r r e l a t i o n s b e t w e e n T T K expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox *** In both the nucleus and cytoplasm, the expression of TTK in tumor tissues was significantly lower than that in normal tissues(P longer overall survival. TTK is a favorable prognostic biomarker for patients with GBC.

关键词： Threonine and tyrosine kinase Biomarker Prognosis Gallbladder cancer

Albumin-to-alkaline phosphatase ratio: A novel prognostic index of overall survival in cholangiocarcinoma patients after surgery

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World Journal of Gastrointestinal Oncology 2019年第1期11卷 39-47页

作者： Jian-Ping Xiong jun-yu long Wei-yu Xu Jin Bian Han-Chun Huang Yi Bai Yi-Yao Xu Hai-Tao Zhao Xin Lu Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical College

AIM To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio(AAPR) in cholangiocarcinoma(CCA) subjects receiving *** In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics(including AAPR) were analyzed to determine predictors of postoperative overall survival and recurrence-free survival(RFS). In addition,univariate and multivariate Cox proportional hazards models were conducted,followed by application of time-dependent receiver operating curves to identify the optimal *** Univariate and multivariate analyses revealed both decreased overall survival[hazard ratio(HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival(HR: 2.31,95%CI: 1.40–3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253(83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low(< 0.41) AAPR group, which were significantly lower than those in the high(≥ 0.41) AAPR group(81.7%, 53.9%, and 33.4%,respectively)(P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor *** Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.

关键词： Albumin-to-alkaline phosphatase ratio Cholangiocarcinoma Prognosis Surgery Survival

Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China

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World Journal of Gastroenterology 2020年第30期26卷 4465-4478页

作者： Dong-Xu Wang Xu Yang Jian-Zhen Lin Yi Bai jun-yu long Xiao-Bo Yang Samuel Seery Hai-Tao Zhao Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Humanities Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

BACKGROUND Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma(aHCC).Several recent real-world studies appear to have confirmed this;however,there are etiological *** necessitates further real-world studies of lenvatinib across diverse populations,such as in *** To investigate the efficacy and safety of lenvatinib in a Chinese HCC patient population under real-world *** This is a retrospective and multiregional study involving patients with aHCC receiving lenvatinib *** was assessed using the Response Evaluation Criteria in Solid Tumors version *** characteristics and adverse events(AEs)were recorded throughout the entire *** In total,54 HCC patients treated with lenvatinib monotherapy were included for final *** objective response rate was 22%(n=12)with a progressionfree survival(PFS)of 168 d;however,AEs occurred in 92.8%of *** analysis showed that the Barcelona Clinic Liver Cancer stage[hazard ratio(HR)0.465;95%CI:0.23-0.93;P=0.031],portal vein tumor thrombus(HR 0.38;95%CI:0.15-0.94;P=0.037)and Child-Pugh classifications(HR 0.468;95%CI:and specificity(83.3%)of decreasing serum biomarkers including alphafetoprotein were calculated in order to predict tumor size *** sequencing also provided insights into potential gene mutation signatures related to the effect of *** Our findings confirm previous evidence from the phase III REFLECT *** majority of patients in this Chinese sample were suffering from concomitant hepatitis B virus-related ***,further analysis suggested that baseline characteristics,changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib *** large-scale prospective studies that incorporate more basic medical science measures should be conducted.

关键词： Lenvatinib Real-world study Hepatocellular carcinoma Efficacy Safety Treatment

Signature based on molecular subtypes of deoxyribonucleic acid methylation predicts overall survival in gastric cancer

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World Journal of Gastroenterology 2020年第41期26卷 6414-6430页

作者： Jin Bian jun-yu long Xu Yang Xiao-Bo Yang Yi-Yao Xu Xin Lu Xin-Ting Sang Hai-Tao Zhao Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

BACKGROUND Gastric cancer(GC) ranks as the third leading cause of cancer-related death worldwide. Epigenetic alterations contribute to tumor heterogeneity in early *** To identify the specific deoxyribonucleic acid(DNA) methylation sites that influence the prognosis of GC patients and explore the prognostic value of a model based on subtypes of DNA *** Patients were randomly classified into training and test sets. Prognostic DNA methylation sites were identified by integrating DNA methylation profiles and clinical data from The Cancer Genome Atlas GC cohort. In the training set, unsupervised consensus clustering was performed to identify distinct subgroups based on methylation status. A risk score model was built based on Kaplan-Meier, least absolute shrinkage and selector operation, and multivariate Cox regression analyses. A test set was used to validate this *** Three subgroups based on DNA methylation profiles in the training set were identified using 1061 methylation sites that were significantly associated with survival. These methylation subtypes reflected differences in T, N, and M category, age, stage, and prognosis. Forty-one methylation sites were screened as specific hyper-or hypomethylation sites for each specific subgroup. Enrichment analysis revealed that they were mainly involved in pathways related to carcinogenesis, tumor growth, and progression. Finally, two methylation sites were chosen to generate a prognostic model. The high-risk group showed a markedly poor prognosis compared to the low-risk group in both the training [hazard ratio(HR) = 2.24, 95% confidence interval(CI): 1.28-3.92, P < 0.001] and test(HR = 2.12, 95%CI: 1.19-3.78, P = 0.002) *** DNA methylation-based classification reflects the epigenetic heterogeneity of GC and may contribute to predicting prognosis and offer novel insights for individualized treatment of patients with GC.

关键词： Gastric cancer Deoxyribonucleic acid methylation Molecular subtypes Prognosis Risk score The Cancer Genome Atlas

Multidisciplinary management of hepatobiliary tumors in the era of precision medicine

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Hepatobiliary & Pancreatic Diseases International 2018年第5期17卷 381-382页

作者： Jian-Zhen Lin Yi Bai An-Qiang Wang jun-yu long Wei-yu Xu Ke Hu Lin Zhao Jie Pan Xin-Ting Sang Hai-Tao Zhao Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Gastrointestinal Surgery Peking University Cancer Hospital and InstituteBeijing 100142China Center of Radiotherapy Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Medical Oncology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Radiology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Hepatobiliary tumor (HBT), one of the leading causes of cancer deaths globally, is more frequent in East Asia including China [1].HBTincludeslivercancer,cholangiocarcinomaandgallbladder *** ***isB-typevirus

关键词： Multidisciplinary management of hepatobiliary tumors in the era of precision medicine HBT

Nomogram to predict overall survival after gallbladder cancer resection in China

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World Journal of Gastroenterology 2018年第45期24卷 5167-5178页

作者： Yi Bai Zhi-Song Liu Jian-Ping Xiong Wei-yu Xu Jian-Zhen Lin jun-yu long Fei Miao Han-Chun Huang Xue-Shuai Wan Hai-Tao Zhao Department of Liver Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Statistics Tianjin University of Finance and Economics Pearl River College

AIM To integrate clinically significant variables related to prognosis after curative resection for gallbladder carcinoma(GBC) into a predictive *** One hundred and forty-two GBC patients who underwent curative intent surgical resection at Peking Union Medical College Hospital(PUMCH) were included. This retrospective case study was conducted at PUMCH of the Chinese Academy of Medical Sciences and Peking Union Medical College(CAMS & PUMC) in China from January 1, 2003 to January 1, 2018. The continuous variable carbohydrate antigen 19-9(CA19-9) was converted into a categorical variable(cCA19-9) based on the normal reference range. Stages 0 to IIIA were merged into one category, while the remaining stages were grouped into another category. Pathological grade X(GX) was treated as a missing value. A multivariate Cox proportional hazards model was used to select variables to construct a nomogram. Discrimination and calibration of the nomogram were performed via the concordance index(C-index) and calibration plots. The performance of the nomogram was estimated using the calibration curve. Receiver operating characteristic(ROC) curve analysis and decision curve analysis(DCA) were performed to evaluate the predictive accuracy and net benefit of the nomogram, *** Of these 142 GBC patients, 55(38.7%) were male, and the median and mean age were 64 and 63.9 years, respectively. Forty-eight(33.8%) patients in this cohort were censored in the survival analysis. The median survival time was 20 months. A series of methods, including the likelihood ratio test and Akaike information criterion(AIC) as well as stepwise, forward, and backward analyses, were used to select the model, and all yielded identical results. Jaundice [hazard ratio(HR) = 2.9; 95% confidence interval(CI): 1.60-5.27], cCA19-9(HR = 3.2; 95%CI: 1.91-5.39), stage(HR = 1.89; 95%CI: 1.16-3.09), and resection(R)(HR = 2.82; 95%CI: 1.54-5.16) were selected as significant predictors and combi

关键词： Nomogram Survival Prognosis Gallbladder cancer Resection