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Integrative single-cell multiomics analyses dissect molecular signatures of intratumoral heterogeneities and differentiation states of human gastric cancer

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National Science Review 2023年第6期10卷 96-107页

作者： Shuhui Bian Yicheng Wang Yuan Zhou Wendong Wang Limei Guo Lu Wen Wei Fu Xin Zhou Fuchou Tang Biomedical Pioneering Innovation Center School of Life Sciences Department of General Surgery Third Hospital Peking University State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical University Beijing Advanced Innovation Center for Genomics (ICG) Ministry of Education Key Laboratory of Cell Proliferation and Differentiation Department of Pathology Peking University Third Hospital School of Basic Medical Science Peking University Health Science Center Peking University Third Hospital Cancer Center Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University

Human gastric cancer is a highly lethal disease,but the underlying multiomic mole cular signatures remain largely uncle ar.Here,we performed multi-regional sampling,parallel single-cell multiomics sequencing and integrated analyses of human gastric cancer.We identified common transcrip tomic alterations of gastric cancer cells,such as aberrant down-regulation of genes associated with normal stomach function and up-regulation of KRT7,PI3,S100A4,etc.Surprisingly,aberrant and prevalent up-regulation of genes highly expressed in normal colorectal epithelial cells were also identified in cancer cells,which maybe partially regulated by promoter chromatin accessibility and DNA methylation levels.We reve aled the single-cell DNA methylome landscape of gastric cancer,and identified candidate DNA methylation biomarkers,such as hypermethylated promoters of TMEM240 and HAGLROS,and hypomethylated promoters of TRPM2-AS and HRH1.Additionally,the relationships between genetic lineages,D NA methylation and transcriptomic clusters were systematically revealed at single-cell level.We showed that DNA methylation heterogeneities were mainly among different genetic lineages of cancer cells.Moreover,we found that D NA methylation levels of cancer cells with poorer differentiation states tend to be higher than those of cancer cells with better differentiation states in the primary tumor within the same patient,although still lower than in normal gastric epithelial cells.Cancer cells with poorer differentiation states also prevalently down-regulated MUC1 expression and immune-related pathways,and had poor infiltration of CD 8+T cells.Our study dissected the mole cular signatures of intratumoral heterogeneities and differentiation states of human gastric cancer using integrative single-cell multiomics analyses.

关键词： gastric cancer single-cell multiomics analysis intratumoral heterogeneity tumor differentiation

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Parasympathetic neurogenesis is strongly associated with tumor budding and correlates with an adverse prognosis in pancreatic ductal adenocarcinoma

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Chinese Journal of Cancer Research 2016年第2期28卷 180-186页

作者： Lingfu Zhang Limei Guo Ming Tao Wei Fu Dianrong Xiu Department of General Surgery Peking University Third HospitalBeijing 100191China Department of Pathology Peking University Third HospitalBeijing 100191China

Objective： To investigate the frequency of parasympathetic neurogenesis and determine its association with tumor budding and prognosis in pancreatic ductal adenocarcinoma （PDAC）. Methods： Parasympathetic neurogenesis was defined as the distribution of abnormal parasympathetic nerves in the stroma tissue. Staining of vesicular acetylcholine transporter （VAChT）, as a marker for parasympathetic neurogenesis, was performed on a representative specimen of the tumor for 59 PDAC patients with available clinical, pathologic, and follow-up information. Three specimens containing normal pancreatic tissues were stained in parallel. The number of parasympathetic nerve fibers was counted in five high-power microscopic fields （5×0.785 mm2）. Cut-offvalues were calculated by receiver operating characteristic curve analysis. Results： VAChT-positive parasympathetic nerve fibers were not seen in the stroma of 3 cases of normal pancreatic tissues. In 59 PDAC cases, the range of parasympathetic neurogenesis was 4-38 fibers/（5×0.785） mm2, with a median of 18 fibers/（5×0.785） mm2. Patients with parasympathetic neurogenesis 〉 15 fibers/（5×0.785） mm2 were defined as the high-density group （39 patients, 66.1%）, and those with parasympathetic neurogenesis 〈15 fibers/（5×0.785） mm2 as the low-density group （20 patients, 33.9%）. The high-density group had a higher occurrence of tumor budding （P=0.001） and a higher rate of early recurrence （P=0.035）. Parasympathetic neurogenesis appeared to be an independent adverse prognostic factor [hazard ratio （HR）=2.45, 95% confidence interval （95% CI）： 1.25-4.81, P=0.009], in addition to American Joint Committee on Cancer （AJCC） stage （P=0.010） and tumor budding （P=0.009）. Conclusions： Parasympathetic neurogenesis is strongly associated with tumor budding and correlates with an adverse prognosis in PDAC.

关键词： Pancreatic ductal adenocarcinoma parasympathetic neurogenesis tumor budding recurrence prognosis

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Preliminary single-arm study of brain effects during transcutaneous auricular vagus nerve stimulation treatment of recurrent depression by resting-state functional magnetic resonance imaging

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Journal of Traditional Chinese Medicine 2022年第5期42卷 818-824页

作者： CHEN limei SUN Jifei guo Chunlei LI Xiaojiao WANG Zhi Hong Yang FANG Jiliang Radiology Department Guang'anmen Hospital of China Academy of Chinese Medical SciencesBeijing 10003China

OBJECTIVE:To examine the brain effects of transcutaneous auricular vagus nerve stimulation(ta VNS)treatment of recurrent depression based on the functional brain network by using resting-state functional magnetic resonance imaging(f MRI).METHODS:Twenty-five patients with recurrent depression were enrolled in a single-arm trial of ta VNS treatment for eight weeks.Clinical results were assessed by 17-item Hamilton Depression Rating Scale(HAMD-17),Hamilton Anxiety Scale(HAMA),Self-Rating Depression Scale(SDS),Self-Rating Anxiety Scale(SAS),and Ruminative Response Scale(RRS)scales.Resting-state f MRI was conducted to explore the brain effects before and after treatment.For the functional connectivity(FC)analysis,the bilateral nucleus accumbens,globus pallidus,caudate,and putamen were selected as seeds.Finally,the correlations between FC and the clinical scale scores were calculated.RESULTS:After treatment,the patients’scores of HAMD-17,HAMA,SDS,SAS,and RRS were significantly decreased(P<0.05).FC was considerably decreased between the following areas:the left globus pallidus and the right postcentral gyrus,inferior parietal gyrus,the right globus pallidus and the left superior marginal gyrus,postcentral gyrus,superior parietal gyrus,inferior parietal gyrus,precuneus,right postcentral gyrus,superior marginal gyrus,and inferior parietal gyrus,between the right caudate and the right lingual gyrus,calcarine gyrus,and cerebellum.Changes in FC between the right globus pallidus and the left inferior parietal gyrus,between the left globus pallidus and the right postcentral gyrus were negatively correlated with HAMD-17 scores change before and after treatment(before,P=0.003,r=-0.6;after,P=0.009,r=-0.54).The change of FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SDS(P=0.026,r=-0.474).The difference in FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SAS(P=0.016,r=-0.513).CONCLUSIONS:Recurrent dep

关键词： recurrence depression magnetic resonance imaging basal ganglia default mode network transcutaneous auricular vagus nerve stimulation

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Gut microbiota and differential genes-maintained homeostasis is key to maintaining health of individuals with Yang-deficiency constitution

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Journal of Traditional Chinese Medicine 2022年第1期42卷 96-101页

作者： ZHANG Huixiang WANG limei guo Jipeng WANG Jiai ZHANG Qianqian WANG Yutao LIU Xun ZHANG Lihuan SHI Lanlan WU Hongxiang CAO Xue Institute of Neuroscience Basic Medical CollegeKunming Medical UniversityKunming 650500China Department of Laboratory Animal Science Kunming Medical UniversityKunming 650500China Department of Laboratory Animal Science Kunming Medical UniversityState Key Laboratory for Conservation and Utilization of Bio-Resources in YunnanYunnan UniversityKunming 650500Chin Faculty of Rehabilitation Medicine Kunming Medical UniversityKunming 650500China School of Electrical and Information Technology Yunnan Minzu UniversityKunming 650500China School of Medicine Kunming UniversityKunming 650214China Basic Medical College Kunming Medical UniversityKunming 650500China Department of Anatomy Histology and EmbryologyBasic Medical CollegeKunming Medical UniversityKunming 650500China

OBJECTIVE:Yang-deficiency constitution(YADC)is a common unbalanced constitution that predisposes individuals to certain diseases.However,not all people with YADC manifest develop diseases.This calls for delineation of the underlying molecular mechanisms.Previous studies suggested that the gut microbiota and gene differential expression should be considered.METHODS:In the present study,we compared profiles of gut microbiota between four healthy YADC individuals and those of five healthy balanced constitution(BC)counterparts,based on 16 S r RNA gene sequence analysis.Furthermore,YADC relevant genes identified by comparing 62 healthy YADC and 58 healthy BC individuals in total to perform intersection analysis,functional clustering and pathway enrichment analyses.RESULTS:The levels of harmful gut microbiota(Prevotellaceae,LDA score>4.0,P=0.0141)and beneficial gut microbiota(Ruminococcaceae,LDA score>4.0,P=0.0025,Faecalibacterium,LDA score>4.0,P=0.0484)were both elevated in healthy YADC individuals.Also,we found that the specific metabolic pathway with 2,6-Dichloro-p-hydroquinone 1,2-Dioxygenase(Pcp A)as the core in gut microbiota and the glutathione transferase activity has been enriched by YADC relevant genes in healthy YADC individuals were both responsible for the detoxification of halogenated aromatic hydrocarbon substances.CONCLUSIONS:Both beneficial and harmful factors had been detected in healthy YADC individuals,functionally,they may have triggered homeostasis to maintain the health of individuals with YADC.The homeostasis may be maintained by beneficial and harmful factors from gut flora and genes.Future studies are expected to focus on halogenated aromatic hydrocarbons and their detoxification processes.

关键词： Yang deficiency physical constitution theory health promotion gastrointestinal microbiome genes hydrocarbons aromatic homeostasis

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Environmental benefits and farmers' adoption of winter cover crops in the North China Plain

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Pedosphere 2024年第1期34卷 159-169页

作者： Shufang guo Yitao ZHANG limei ZHAI Jian LIU Hongyuan WANG Hongbin LIU State Key Laboratory of Efficient Utilization of Arid and Semi-arid Arable Land in Northern China Key Laboratory of Nonpoint Source Pollution ControlMinistry of Agriculture and Rural AffairsInstitute of Agricultural Resources and Regional PlanningChinese Academy of Agricultural SciencesBeijing 100081China Institute of Agricultural Environment and Resources Yunnan Academy of Agricultural SciencesKunming 650205China Shandong Yucheng Agro-ecosystem National Observation Research Station Key Laboratory of Ecosystem Network Observation and ModelingInstitute of Geographic Sciences and Natural Resources ResearchChinese Academy of SciencesBeijing 100101China The Norwegian Institute of Bioeconomy Research(NIBIO) Akershus 1431Norway

The introduction of cover crops into monoculture systems to improve soil health has been widely adopted worldwide. However, little is known about the environmental risks and application prospects of different cover crops in spring maize(Zea mays L.) monocultures proposed in the North China Plain. A pot experiment was conducted to evaluate the effects of different winter cover crops on subsequent maize yield, soil fertility, and environmental risks of nitrogen(N) loss, and a questionnaire survey was conducted to examine factors influencing farmers' willingness to adopt cover crops in the North China Plain. Based on the same fertilization regime during the maize growing period, four winter cover crop treatments were set up, including bare fallow, hairy vetch(Vicia villosa Roth.), February orchid(Orychophragmus violaceus), and winter oilseed rape(Brassica campestris L.). The results indicated that winter cover crops significantly increased subsequent maize yield and soil organic carbon, total N, and microbial biomass carbon and N compared with the bare fallow treatment.The incorporation of cover crops led to a negligible increase in nitrous oxide(N_(2)O) emissions and had a very limited effect on ammonia(NH_(3)) emissions.The incorporation of February orchid and winter oilseed rape decreased nitrate leaching compared with the hairy vetch treatment in the maize growing season.The N losses via N_(2)O and NH_(3) emissions and N leaching accounted for 71%–84% of the N surplus. However, yield increase and environmental benefits were not the main positive factors for farmers to accept cover crops. Financial incentive was rated by 83.9% of farmers as an “extremely important” factor, followed by other costs, when considering winter cover cropping. These results indicate that the environmental benefits depend on the type of cover crop. Maintaining high levels of soil fertility and maize yield, providing sufficient subsidies, and encouraging large-area cultivation of cover crops are critical measures to promote winter cover c

关键词： cover crop N leaching NH_(3)emission N_(2)O emission spring maize willingness to accept

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同轴旋转可压缩气流中黏性液体射流形态研究

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内燃机学报 2024年第1期42卷 53-60页

作者：吕明郭立梅宁智北京交通大学机械与电子控制工程学院北京100044

采用射流线性稳定性分析方法,考虑液体黏性、周围气流的同轴旋转运动以及可压缩性的条件下,建立了描述同轴旋转可压缩气流中黏性液体射流的数学模型,并进行了验证,研究了气流量纲为1旋转强度以及流体物性对液体射流不稳定形态的影响.研... 详细信息

采用射流线性稳定性分析方法,考虑液体黏性、周围气流的同轴旋转运动以及可压缩性的条件下,建立了描述同轴旋转可压缩气流中黏性液体射流的数学模型,并进行了验证,研究了气流量纲为1旋转强度以及流体物性对液体射流不稳定形态的影响.研究表明:周围气流的旋转速度较小时,对射流起促稳作用,继续增大气流量纲为1旋转强度,开始对射流起促分裂作用;且随着气流旋转强度的增大,射流扰动沿周向方向发展,射流柱变的高度不对称.在研究参数范围内,气体可压缩性和气/液密度比均能促进射流的失稳,并会影响射流空间形态,尤其是在周向方向上能够改变射流的占优模式,增强射流的不对称性;液体黏性以及表面张力对射流均具有增强稳定性的作用.

关键词：液体射流气流旋转数学模型射流形态

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Allergic diseases, immunoglobulin E, and autoimmune pancreatitis： a retrospective study of 22 patients

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Chinese Medical Journal 2014年第23期127卷 4104-4109页

作者： guo limei Huang Yonghui Wang Tianli Shi Xueying Chang Hong Yao Wei Huang Xuebiao Department of Gastroenterology Peking University Third Hospital Beijing 100191 China Department of Radiology Peking University Third Hospital Beijing 100191 China Department of Pathology Peking University Health Science Center Beijing 100191 China

Background Autoimmune pancreatitis （ALP） is a chronic inflammatory disease of pancreas.We evaluated the clinical manifestations,imaging,and histological presentations of AlP in Chinese patients,and investigated the roles of immunoglobulin E （IgE） and allergic diseases in the diagnosis and pathogenesis of AIP.Methods The clinical records of 22 patients diagnosed with AlP were reviewed and analyzed.All patients with AlP fulfilled the 2006 revised diagnostic criteria proposed by Japan Pancreas Society or the Korean Criteria for AIP.Results Half （11/22） of AlP patients had allergic diseases.Twenty-one patients had elevated serum IgE levels,and 14 patients had IgE levels more than 3 times that of normal.There were no significant differences between the patients with higher or lower IgE,with or without allergic disease,in clinical features,laboratory tests,diffuse or focal lesions,or the choice of treatment methods; however,more complaints of body weight loss were observed in patients with higher IgE levels.Patients with higher IgE levels and with allergic diseases were more likely to have onset in March,April,May,August,September,or October.IgE levels decreased after therapy,but increased again during recurrence.Increased number of mast cells was found in the pancreatic tissue in AIP.Conclusions IgE maybe a useful marker for monitoring therapeutic response and recurrence of AlP.Allergic processes may play an important role in the pathogenesis of AIP.

关键词： hypersensitivity pancreatitis immunoglobulin E mast cells

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同轴旋拧可压缩气流中黏性液体射流稳定性

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内燃机学报 2022年第5期40卷 471-479页

作者：郭立梅吕明宁智北京交通大学机械与电子控制工程学院北京100044

基于空间线性稳定性分析方法建立了描述同轴旋拧可压缩气流中黏性液体射流稳定性的数学模型,分析了气动力、黏性力、惯性力和表面张力等对射流稳定性的影响.结果表明:气流旋转对旋拧气流式液体射流起致稳作用,射流不稳定性随气流轴向引... 详细信息

基于空间线性稳定性分析方法建立了描述同轴旋拧可压缩气流中黏性液体射流稳定性的数学模型,分析了气动力、黏性力、惯性力和表面张力等对射流稳定性的影响.结果表明:气流旋转对旋拧气流式液体射流起致稳作用,射流不稳定性随气流轴向引射速度A的增大先减小后增大;将气流轴向引射作用分为强引射作用(A>2)和弱引射作用(A≤2),在强引射范围内气流轴向引射速度对旋拧气流式液体射流一直起失稳作用.给定周围气流的旋转速度且增大气流轴向引射作用时,改变物性参数,射流轴对称扰动占优模式不会改变,且气流轴向引射作用对射流稳定性的影响不会发生质变;气体可压缩性以及气/液密度比对旋拧气流式液体射流起失稳作用;液体黏度起致稳作用;随表面张力增大,射流不稳定性先迅速减小后缓慢增大,表面张力较小时有利于射流失稳分裂.

关键词：色散方程旋拧气流射流稳定性

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同轴气流式液体射流分裂液滴粒径研究

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力学学报 2022年第2期54卷 405-413页

作者：郭立梅吕明宁智北京交通大学机械与电子控制工程学院北京100044

针对同轴气流式液体射流分裂液滴粒径预测模型缺乏的现状,结合射流线性稳定性理论,建立了基于临界模数的同轴气流式黏性液体射流分裂液滴粒径表达式,在此基础上,分别研究了气流旋拧(气流同时存在轴向和周向运动)及流体物性(气体可压缩... 详细信息

针对同轴气流式液体射流分裂液滴粒径预测模型缺乏的现状,结合射流线性稳定性理论,建立了基于临界模数的同轴气流式黏性液体射流分裂液滴粒径表达式,在此基础上,分别研究了气流旋拧(气流同时存在轴向和周向运动)及流体物性(气体可压缩性、液体黏性、气液密度比和表面张力)对液滴粒径的影响规律.研究发现:周围气流轴向引射作用和同轴旋转作用均会导致分裂液滴粒径整体呈先增大后减小的趋势;且在气流仅作同轴旋转运动时,相同临界模数下气流旋转对分裂液滴粒径的影响较小.在本文的研究参数范围内,分裂液滴粒径随气体可压缩性和气液密度比的增加而减小,随液体黏度和表面张力的增加而增加;其中,气体可压缩性在气流作同轴旋转运动时作用效果更强,液体黏度在气流作同轴引射运动时效果更为显著.研究结果对同轴气流式液体射流的分裂液滴粒径预测具有一定的理论意义和工程应用价值.

关键词：液体射流同轴气流液滴粒径临界模数

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Moldable and transferrable conductive nanocomposites for epidermal electronics

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npj Flexible Electronics 2022年第1期6卷 363-371页

作者： Myeong Namkoong Heng guo Md Saifur Rahman Daniel Wang Cassandra Jane Pfeil Sophia Hager limei Tian Department of Biomedical Engineering and Center for Remote Health Technologies and SystemsTexas A&M UniversityCollege StationTX 77843USA

Skin-inspired soft and stretchable electronic devices based on functional nanomaterials have broad applications such as health monitoring,human-machine interface,and the Internet of things.Solution-processed conductive nanocomposites have shown great promise as a building block of soft and stretchable electronic devices.However,realizing conductive nanocomposites with high conductivity,electromechanical stability,and low modulus over a large area at sub-100μm resolution remains challenging.Here,we report a moldable,transferrable,high-performance conductive nanocomposite comprised of an interpenetrating network of silver nanowires and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate).The stacked structure of the nanocomposite synergistically integrates the complementary electrical and mechanical properties of the individual components.We patterned the nanocomposite via a simple,low-cost micromolding process and then transferred the patterned large-area electrodes onto various substrates to realize soft,skin-interfaced electrophysiological sensors.Electrophysiological signals measured using the nanocomposite electrodes exhibit a higher signal-to-noise ratio than standard gel electrodes.The nanocomposite design and fabrication approach presented here can be broadly employed for soft and stretchable electronic devices.

关键词： conductive transfer interface

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