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Duration-dependent regulation of autophagy by isoflurane exposure in aged rats

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Neuroscience Bulletin 2015年第4期31卷 505-513页

作者： Zheng-Qian Li Lun-Xu Li Na Mo Yi-Yun Cao Bolati Kuerban Yao-Xian Liang Dong-Sheng Fan De-Hua Chui Xiang-Yang Guo Department of Anesthesiology Peking University Third Hospital Cancer hospital and institute Chinese Academy of Medical Sciences and Peking Union Medical College Department of Neurology Peking University Third Hospital Department of Nephrology Peking University Third Hospital

Current evidence suggests a central role for autophagy in many inflammatory brain disorders, including Alzheimer＇s disease （AD）. Furthermore, it is also well accepted that some inhalation anesthetics, such as isoflurane, may cause AD- like neuropathogenesis and resultant postoperative cognitive dysfunction, especially in the elderly population. However, the impact of inhalation anesthetics on autophagic components in the brain remains to be documented. Hence, our objective was to investigate the effects of different durations of isoflurane exposure on hippocampus-dependent learning and hippocarnpal autophagy in aged rats. Aged Sprague-Dawley rats （20 months old） were randomly exposed to 1.5% isoflurane or 100% oxygen for 1 or 4 h. Animals were then trained in the Morris water maze （4 trials/day for 5 consecutive days）. Hippocampal phagophore formation markers, beclin 1 and protein microtubule-associated protein 1 light chain-3B （LC3B）, as well as p62, an indicator of autophagic flux, were quantified by western blotting. There was no significant difference in the escape latencies and time spent in the target quadrant, as well as hippocampal expression of beclin 1, LC3B- II, and p62 at 24 h post-anesthesia between the 1-h isoflurane-exposed rats and their controls （P 〉0.05）. Four-hour exposure to isoflurane resulted in spatial learning and memory deficits, as evidenced by prolonged escape latencies on days 4 and 5 post- anesthesia and less time spent in the target quadrant than sham-exposed animals （P 〈0.05）. These events were accompanied by a decline in hippocampal expression of LC3B-I, LC3B-II, and beclin 1 24 h after isoflurane （P 〈0.01 and P 〈0.05）. Nevertheless, no significant change in p62 expression was found. Further kinetics study of autophagic changes induced by 4 h of isoflurane showed a transient upregulation of LC3B-I, LC3B-II, and beclin 1 at the end of exposure and a subsequent striking decrease within 12-24 h post-anesthesia （P 〈0.05）. Hippocampal p62

关键词： autophagy phagophore formation cognitive dysfunction

Value of ^(18)F-FDG PET-CT in surveillance of postoperative colorectal cancer patients with various carcinoembryonic antigen concentrations

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World Journal of Gastroenterology 2014年第21期20卷 6608-6614页

作者： Yan Zhang Bin Feng Guo-Li Zhang Man Hu Zheng Fu Fen Zhao Xiao-Li Zhang Li Kong Jin-Ming Yu Graduate school of Tianjin medical university Department of Radiation oncology Shandong Tumor Hospital and Institute (Shandong Academy of Medical Sciences) Affiliated hospital of Shandong Academy of medical sciences Jinan 250031Shandong ProvinceChina Department of Nuclear Medicine Shandong Tumor Hospital and Institute (Shandong Academy of Medical Sciences) medical College Shandong University School of Medicine and Life sciences University of Jinan

AIM:To evaluate the value of positron emission tomography(PET)/computerized tomography(CT)in surveillance of colorectal cancer(CRC)patients with different carcinoembryonic antigen(CEA)***:one hundred and six postoperative CRC patients who had suspected recurrence or metastasis and received fluorodeoxyglucose(FDG)PET/CT within one week were included in this *** final diagnosis was confirmed by histological examination or clinicalfollow-up over at least six ***:The sensitivity,specificity,and accuracy of FDG PET/CT were 95.2%,82.6%,and 92.5%,and94.8%,81.4%and 92.8%,respectively,in the caseand lesion-based *** sensitivity and accuracy of FDG PET/CT significantly differed from CT in both analyses(χ2=8.186,P=0.004;χ2=6.201,P=0.013;χ2=13.445,P=0.000;χ2=11.194,P=0.001).In the lesion-based analysis,the sensitivity,specificity,and accuracy of FDG PET/CT in the abnormal CEA group were97.8%,82.6%,and 95.6%,compared with 81.3%,80%,and 80.6%for patients with normal CEA *** case-based analysis,the sensitivity,specificity,and accuracy of FDG PET/CT were 97.2%,77.8%,and 95%in abnormal CEA *** in lesion-based analysis,the sensitivity and accuracy of FDG PET/CT in the abnormal CEA group were significantly superior to those in the normal CEA group(χ2=6.432,P=0.011;χ2=7.837,P=0.005).FDG PET/CT changed the management in 45.8%of patients with positive ***:FDG PET/CT showed superior diagnostic value and is an advisable option in surveillance of postoperative CRC patients with a vague diagnosis.

关键词： Colorectal cancer Carcinoembryonic antigen Fluorodeoxyglucose positron emission tomography/computed tomography Recurrence Metastasis

The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients

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Cancer Biology & Medicine 2020年第3期17卷 599-611页

作者： Xiaoyang Zhai Jian Zhang Yaru Tian Ji Li Wang Jing Hongbo Guo Hui Zhu Department of Radiation oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China Department of Thoracic Surgery Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China Department of Radiation oncology Shandong Cancer Hospital and Institute affiliated with Shandong UniversityJinan 250012China

Immune checkpoint inhibitors(ICIs)are new and promising therapeutic agents for non-small cell lung cancer(NSCLC).However,along with demonstrating remarkable efficacy,ICIs can also trigger immune-related adverse *** inhibitor pneumonitis(CIP)has been reported to have a morbidity rate of 3%to 5%and a mortality rate of 10%to 17%.Moreover,the incidence of CIP in NSCLC is higher than that in other tumor types,reaching 7%to 13%.With the increased use of ICIs in NSCLC,CIP has drawn extensive attention from oncologists and cancer *** high risk factors for CIP and the potential mechanism of CIP are key points in preventing and monitoring serious adverse *** this review,the results of our analysis and summary of previous studies suggested that the risk factors for CIP may include previous lung disease,prior thoracic irradiation,and combinations with other *** review also explored potential mechanisms closely related toCIP,including increasedT cell activity against associated antigens in tumor and normal tissues,preexisting autoantibodies,and inflammatory cytokines.

关键词： Immune checkpoint inhibitor non-small-cell lung cancer pneumonitis risk factors

Genetic variants involved in gallstone formation and capsaicin metabolism,and the risk of gallbladder cancer in Chilean women

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World Journal of Gastroenterology 2010年第3期16卷 372-378页

作者： Sergio Báez Yasuo Tsuchiya Alfonso Calvo Martha Pruyas Kazutoshi Nakamura Chikako Kiyohara Mari oyama Masaharu Yamamoto Department of Surgery Sótero del Río Hospital Department of Community Preventive Medicine Niigata University Graduate School of Medical and Dental Sciences Department of Anatomic Pathology Sótero del Río Hospital Department of Preventive Medicine Graduate School of Medical SciencesKyushu University Faculty of Health sciences Niigata University of Health and Welfare

AIM:To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC).METHoDS: A total of 57 patients with GBC, 119 patients with gallstones, and 70 controls were enrolled in this study. DNA was extracted from their blood or paraffi n block sample using standard commercial kits. The statuses of the genetic variants were assayed using Taqman SNP Genotyping Assays or Custom Taqman SNP Genotyping ***:The non-ancestral T/T genotype of apolipoprotein B rs693 polymorphism was associated with a decreased risk of GBC (oR:0.14,95% CI:0.03-0.63). The T/T genotype of cholesteryl ester transfer protein (CETP) rs708272 polymorphism was associated with an increased risk of GBC (oR:5.04,95% CI:1.43-17.8).CoNCLUSIoN: Genetic variants involved in gallstone formation such as the apolipoprotein B rs693 and CETP rs 708272 polymorphisms may be related to the risk of developing GBC in Chilean women.

关键词： Genetic risk factor Gallbladder cancer Gallstone Genetic polymorphism Apolipoprotein B Cholesteryl ester transfer protein

Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma

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National Science Review 2024年第5期11卷 170-185页

作者： Yong Zhou Shanlan Mo Heyang Cui Ruifang Sun Weimin Zhang Xiaofei Zhuang Enwei Xu Hongyi Li Yikun Cheng Yongsheng Meng Meilin Liu Ting Yan Huijuan Liu Ling Zhang Bin Yang Yanfeng Xi Shubin Wang Xiaolong Cheng Shuai Cheng Li Zhihua Liu Qimin Zhan Zheng Hu Yongping Cui Cancer institute Department of Pathology Peking University Shenzhen Hospital Shenzhen Peking University-the Hong Kong University of Science and Technology(PKU-HKUST) Medical Center Institute of Cancer ResearchShenzhen Bay Laboratory Key Laboratory of Cellular Physiology of the Ministry of Education Department of Pathology Shanxi Medical University City university of Hong Kong Shenzhen Research institute CAS Key Laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of Sciences Department of Surgery Faculty of Medicine The Chinese University of Hong Kong Department of Tumor Biobank Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital & Institute Research Unit of Molecular Cancer Research Chinese Academy of Medical Sciences Department of Thoracic Surgery Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University Department of Pathology Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University College of Letters & Science University of California Berkeley State Key Laboratory of Molecular oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

Esophageal squamous cell carcinoma（ESCC） is a poor-prognostic cancer type with extensive intra-and inter-patient heterogeneity in both genomic variations and tumor microenvironment（TME）. However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor PREX2,accounting for 22% of ESCCs with frequent somatic mutations or hyper-methylation, which promoted migration and invasion of ESCC cells in vitro. Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution, where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the ***, we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness, suggesting more stringent immune selection. In addition, distinct TMEs were associated with variable genomic and clinical outcomes. Among them, hot TME was associated with high immune evasion and subclonal heterogeneity. We also found that immunoediting, instead of CD8+T cell abundance, acts as an independent prognostic factor of ESCCs. Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted ***, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.

关键词： squamous cell carcinoma heterogeneity multi-omics evolution tumor microenvironment

Enhanced recovery after surgery protocol enhances early postoperative recovery after pancreaticoduodenectomy

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Hepatobiliary & Pancreatic Diseases International 2019年第2期18卷 188-193页

作者： Ramasamy Mahendran Mallika Tewari Vinod Kumar Dixit Hari Shankar Shukla Department of Surgical oncology Institute of Medical Sciences Banaras Hindu University Department of Gastroenterology Institute of Medical Sciences Banaras Hindu University

Background: Enhanced recovery after surgery(ERAS) protocol is a multimodal, multidisciplinary and evidence-based approach to reduce surgical stress and enhance recovery in the postoperative period. This study aimed to analyze the outcome of ERAS protocol in patients after pancreaticoduodenectomy(PD). Methods: A total of 50 consecutive patients with pancreatic/periampullary cancer who underwent PD between January 2016 to August 2017 were included in the study. As per the institute ERAS protocol, nasogastric tube(NGT) was removed on postoperative day(PoD) 1 if output was less than 200 mL and oral sips were allowed; oral liquids were allowed on PoD2; semisolid diet by PoD3; abdominal drain was removed on PoD 4 if output was less than 100 mL with no evidence of postoperative pancreatic fistula(PoPF); normal diet was allowed on PoD5. Discharge criteria on PoD6 were afebrile, tolerating oral normal diet, pain free and no surgery related complications(defined as per the ISGPS definitions). Results: NGT was removed on PoD1 in 45(90%) patients, abdominal drain removed by PoD4 in 41(82%) and 43(86%) patients were discharged on PoD6. There was no 30-day postoperative mortality. Three(6%) patients had delayed gastric emptying(DGE). None had postoperative hemorrhage and PoPF. Readmission rate was 8%. A significant relation was found between the length of hospital stay(LoS) with age( P on between LoS and postoperative albumin( P = 0.05). Conclusions: ERAS protocol can be safely followed in the perioperative care of patients who undergo PD. Early removal of NGT and allowing oral diet restore bowel function early. ERAS decreases the LoS and postoperative complications.

关键词： Enhanced recovery protocol Pancreatic cancer Periampullary cancer Pancreaticoduodenectomy Early discharge

Analysis of the histologic features in the differential diagnosis of intrahepatic neonatal cholestasis

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World Journal of Gastroenterology 2009年第4期15卷 478-483页

作者： Maria Angela Bellomo-Brandao Cecilia AF Escanhoela Luciana R Meirelles Gilda Porta Gabriel Hessel Department of Pediatrics Faculty of Medical SciencesState University of Campinas(UNICAMP) Department of Pathology Faculty of Medical SciencesState University of Campinas(UNICAMP) Department of Pediatrics Children's Institute of Medical School of the University of So Paulo(USP)

AIM:To compare the histologic features of the liver in intrahepatic neonatal cholestasis(IHNC)with infectious,genetic-endocrine-metabolic,and idiopathic etiologies. METHoDS:Liver biopsies from 86 infants with IHNC were *** inclusion criteria consisted of jaundice beginning at 3 mo of age and a hepatic biopsy during the 1st year of *** following histologic features were evaluated:cholestasis,eosinophilia,giant cells,erythropoiesis,siderosis,portal fibrosis,and the presence of a septum. RESULTS:Based on the diagnosis,patients were classified into three groups:group 1(infectious;n=18),group 2(genetic-endocrine-metabolic;n=18),and group 3(idiopathic;n=50).There were no significant differences with respect to the following variables:cholestasis,eosinophilia,giant cells,siderosis,portalfibrosis,and presence of a septum.A significant difference was observed with respect to erythropoiesis,which was more severe in group 1(Fisher's exact test,P=0.016). CoNCLUSIoN:A significant difference was observed in IHNC of infectious etiology,in which erythropoiesis was more severe than that in genetic-endocrine-metabolic and idiopathic etiologies,whereas there were no significant differences among cholestasis,eosinophilia,giant cells,siderosis,portal fibrosis,and the presence of a septum.

关键词： Intrahepatic cholestasis Liver histopathol-ogy Neonatal jaundice Neonatal liver disease

Multi-drug Resistant Uropathogenic Escherichia coli and Its Treatment by Chinese Medicine

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Chinese Journal of Integrative Medicine 2017年第10期23卷 763-769页

作者： LIU Shi-wei XU Xiao-yang XU Jie YUAN Jiu-yun WU Wei-kang ZHANG Ning CHEN Ze-liang Department of Endocrinology Wangjing Hospital China Academy of Chinese Medical Sciences institute of Disease Control and Prevention Academy of Military Medical Sciences Department of Clinical Laboratory The First Affiliated Hospital of Soochow University institute of Integrative Medicine Sun Yat-sen University

objectives： To investigate the resistance and virulence profiles of uropathogenic Escherichia coli（UPEC） and its treatment by Chinese medicine（CM） Fuzheng Qingre Lishi Formula（扶正清热利湿方, FQLF）. Methods： UPEC strains were isolated from recurrent urinary tract infections（UTIs） patients. Patient sensitivities to 17 antibiotics were tested by the disk diffusion method. Virulence genes were screened by plolymerase chain reaction. A mouse model was constructed using a multi-drug resistant and virulent UPEC strain and treated with FQLF or the antibiotic imipenem. The treatment efficacy was evaluated by bacterial clearance from urine and the urinary organs. Results： A total of 90 UPEC strains were collected, and 94.4% of the isolates were resistant to at least 1 antibiotic. Approximately 66.7% of the UPEC strains were multi-drug resistant. More than one virulence gene was found in 85.6% of the isolates. The extended-spectrum β-lactamases（ESBL）-positive strains were more resistant than the negative ones. The virulence gene number was positively correlated with the resistance number（P〈0.05）. A mouse model was successful y constructed using UPEC10. Treatment with either FQLF or antibiotics significantly cleared bacteria from the mouse urine after 14 days. In the untreated control, the bacteria lasted for 28 days. FQLF treatment of the UTI mouse model greatly reduced the bacterial number in the kidney and bladder, but could not completely clear the bacteria. Conclusions： Multi-drug resistance is common among UPEC isolates, and the resistance is positively related with virulence. FQLF could treat UPEC UTIs, but could not completely clear the bacteria from the host.

关键词： urinary tract infection uropathogenic Escherichia coli Chinese medicine multi-drug resistance

Comment on ‘Histological Subtypes of Lung Cancer in Chinese Males from 2000 to 2012'

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Biomedical and Environmental sciences 2014年第1期27卷 1-2页

作者： SUN Yan Cancer institute/hospital Chinese Academy of Medical Sciences

Mortality from lung cancer has dramatically increased in China over the past 4 decades and investigations into its attributing factors should be designated as one of the highest priorities for its prevention and control. It has been shown that different environmental carcinogens have different particular carcinogenesis pathways in humans, resulting in different kinds of cancer or its histological subtypes in various target organs. Although the distribution of lung cancer is changing in many countries, no papers on its epidemiology in China are available. In the present study, 15 427 male lung cancer patients were identified in Cancer hospital of the Chinese Academy of medical sciences, Peking Union Medial Colleg （CHCAMS-PUMC）. The number of lung cancer patients increased between 2000 and 2012 （Zou et al., Table I）, while the relative frequency of squamous cell carcinoma, a pathological sub-type of lung cancer, consistently decreased, especially in those born after 1961 （Zou et al, Figure 2）. on the other hand, the relative frequency of adenocarcinoma, a pathological sub-type of lung cancer, dramatically increased （Zou et al., Figure 2）. Adenocarcinoma has become the major histological sub-type of lung cancer in the 2011-2012 period （Zou et al., Table 3）. These findings provide important information and clues for the etiology of lung cancer and this specific field needs to be further studied.

关键词： lung Histological Subtypes of Lung Cancer in Chinese Males from 2000 to 2012