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| 1 | Mutation of kri1l causes definitive hematopoiesis failure via PERK-dependent excessive autophagy induction显示文摘 | Xiao-E Jia Ke Ma Tao Xu Lei Gao Shuang Wu Cong Fu Wenjuan Zhang Zhizhang Wang Kaiyu Liu Mei Dong Changbin Jing Chunguang Ren Zhiwei Dong Yi Chen Yi Jin Qiuhua Huang Xing Chang Min Deng Li Li Lingfei Luo Jun Zhu Yongjun Dang Hung-Chun Chang Leonard I Zon Yi Zhou Saijuan Chen Weijun Pan | 2015 | Cell Research2015，25，8： | 8 |
| 2 | Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblasti显示文摘B-cell precursor acute lymphoblastic leukemia(BCP-ALL)is characterized by genetic alterations with high heterogeneity.Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology.Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes,such as DUX4 rearrangements,MEF2D rearrangements,ZNF384/ZNF362 rearrangements,NUTM1 rearrangements,BCL2/MYC and/or BCL6 rearrangements,ETV6-RUNX1-like gene expression,PAX5alt(diverse PAX5 alterations,including rearrangements,intragenic amplifications,or mutations),and hotspot mutations PAX5(p.Pro80Arg)with biallelic PAX5 alterations,IKZF1(p.Asn159Tyr),and ZEB2(p.His1038Arg).These molecular subtypes could be classified by gene expression patterns with RNA-seq technology.Refined molecular classification greatly improved the treatment strategy.Multiagent therapy regimens,including target inhibitors(e.g.,imatinib),immunomodulators,monoclonal antibodies,and chimeric antigen receptor T-cell(CAR-T)therapy,are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management.We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL. | Jianfeng Li Yuting Dai Liang Wu Ming Zhang Wen Ouyang Jinyan Huang Saijuan Chen | 2021 | Frontiers of Medicine2021，15，3： | 6 |
| 3 | Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection显示文摘The ongoing pandemic of coronavirus disease 19(COVID-19)is caused by a newly discoveredβcoronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination.Here we examined,using ELISA,the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6–7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection.All samples were positive for IgGs against the S-and N-proteins of SARS-CoV-2.Notably,14 samples available at 6–7 months post-infection all showed significant neutralizing activities in a pseudovirus assay,with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2.Furthermore,in 10 blood samples from cases at 6–7 months post-infection used for memory T-cell tests,we found that interferonγ-producing CD4+and CD8+cells were increased upon SARS-CoV-2 antigen stimulation.Together,these results indicate that durable anti-SARS-CoV-2 immunity is common in convalescent population,and vaccines developed from 614D variant may offer protection from the currently predominant 614D variant of SARS-CoV-2. | Yun Tan Feng Liu Xiaoguang Xu Yun Ling Weijin Huang Zhaoqin Zhu Mingquan Guo Yixiao Lin Ziyu Fu Dongguo Liang Tengfei Zhang Jian Fan Miao Xu Hongzhou Lu Saijuan Chen | 2020 | Frontiers of Medicine2020，14，6： | 6 |
| 4 | Back to the spring of 2020: facts and hope of COVID-19 outbreak显示文摘Since December 2019,an atypical pneumonia has occurred in Wuhan,a beautiful city located at the center of China(Fig.1),and the whole country.The origin of the disease remains unclear and the suspected Huanan Seafood Wholesale Market was closed on January 1,2020.Very rapidly,a novel coronavirus was isolated and named first the 2019 novel coronavirus(2019-nCoV)[1]and subsequently severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[2],and is suggested to be named as human coronavirus 2019(HCoV-19)[3].Meanwhile,the disease is chronologically called pneumonia of unknown origin,novel coronavirus pneumonia(NCP),and coronavirus disease-2019(COVID-19)(Fig.2).Superspreading events of this virus have also taken place on the Diamond Princess cruise off the coast of Yokohama,Japan[4].The Chinese central[5]and local governments[6]have been endeavoring unprecedented efforts to constrain the outbreak,and more than 30000 medical professionals especially doctors and nurses outside Wuhan have been joining the local ones to handle this emergency. | Guangbiao Zhou Saijuan Chen Zhu Chen | 2020 | Frontiers of Medicine2020，14，2： | 5 |
| 5 | Advances in COVID-19:the virus,the pathogenesis,and evidence-based control and therapeutic strategies显示文摘Since the outbreak of the COVID-19 pandemic in early December 2019,81174 confirmed cases and 3242 deaths have been reported in China as of March 19,2020.The Chinese people and government have contributed huge efforts to combat this disease,resulting in significant improvement of the situation,with 58 new cases(34 were imported cases)and 11 new deaths reported on March 19,2020.However,as of March 19,2020,the COVID-19 pandemic continues to develop in 167 countries/territories outside of China,and 128665 confirmed cases and 5536 deaths have been reported,with 16498 new cases and 817 new deaths occurring in last 24 hours.Therefore,the world should work together to fight against this pandemic.Here,we review the recent advances in COVID-19,including the insights in the virus,the responses of the host cells,the cytokine release syndrome,and the therapeutic approaches to inhibit the virus and alleviate the cytokine storm.By sharing knowledge and deepening our understanding of the virus and the disease pathogenesis,we believe that the community can efficiently develop effective vaccines and drugs,and the mankind will eventually win this battle against this pandemic. | Guangbiao Zhou Saijuan Chen Zhu Chen | 2020 | Frontiers of Medicine2020，14，2： | 5 |
| 6 | Distinct immune signatures discriminate between asymptomatic and presymptomatic SARS-CoV-2^(pos)subjects显示文摘Increasing numbers of SARS-CoV-2-positive(SARS-CoV-2^(pos))subjects are detected at silent SARS-CoV-2 infection stage(SSIS).Yet,SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease.Here,we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-COV-2^(pos)subjects,47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects,and interrogated them with combined assays of 44-plex CyTOF,RNA-seq and Olink.Notably,both asymptomatic and presymptomatic subjects exhibited numerous readily detectable immunological alterations,while certain parameters including more severely decreased frequencies of CD107a^(low)classical monocytes,intermediate monocytes,non-classical monocytes and CD62L^(hi)CD8^(+)Tnaive cells,reduced plasma STC1 level but an increased frequency of CD4^(+)NKT cells combined to distinguish the latter.Intercorrelation analyses revealed a particular presymptomatic immunotype mainly manifesting as monocytic overactivation and differentiation blockage,a likely lymphocyte exhaustion and immunosuppression,yielding mechanistic insights into SSIS fate determination,which could potentially improve 5ARS-CoV-2 management. | Shanhe Yu Caixia Di Shijun Chen Mingquan Guo Jiayang Yan Zhaoqin Zhu Li Liu Ruixue Feng Yinyin Xie Ruihong Zhang Juan Chen Mengxi Wang Dong Wei Hai Fang Tong Yin Jinyan Huang Saijuan Chen Hongzhou Lu Jiang Zhu Jieming Qu | 2021 | Cell Research2021，31，11： | 4 |
| 7 | Protecting healthcare personnel from 2019-nCoV infection risks:lessons and suggestions显示文摘The outbreak of a novel coronavirus disease(COVID-19,caused by the 2019-nCoV infection)in December 2019 is one of the most severe public health emergencies since the founding of People’s Republic of China in 1949.Healthcare personnel(HCP)nationwide are facing heavy workloads and high risk of infection,especially those who care for patients in Hubei Province.Sadly,as of February 20,2020,over two thousand COVID-19 cases are confirmed among HCP from 476 hospitals nationwide,with nearly 90%of them from Hubei Province.Based on literature search and interviews with some HCP working at Wuhan,capital city of Hubei,we have summarized some of the effective measures taken to reduce infection among HCP,and also made suggestions for improving occupational safety during an infectious disease outbreak.The experience and lessons learned should be a valuable asset for international health community to contain the ongoing COVID-19 epidemic around the world. | Zhiruo Zhang Shelan Liu Mi Xiang Shijian Li Dahai Zhao Chaolin Huang Saijuan Chen | 2020 | Frontiers of Medicine2020，14，2： | 4 |
| 8 | Optimized human factor IX expression cassettes for hepaticdirected gene therapy of hemophilia B显示文摘基因治疗提供潜在的痊愈因为出血不止 B,和重要进步在指导肝的基因转移被完成了由联系 adeno 的病毒的向量调停了。包含优化 codon 的因素 IX (AAV8-hFIXco ) 向量表明了鼓励功效, hFIX 表示在 1% ~ 6% 正常稳定了的自我补足的联系 adeno 的病毒 serotype 8 人的使用的最近的临床的试用在与高向量剂量有关的病人,而是安全担心铺平仍然是现在。因此, AAV 向量的进一步的改进和 hFIX 表示盒子可以断然贡献出血不止 B 基因治疗的最终的成功。在这研究,加强的 hFIX 铺平接受者的凝结剂能力获得更高的表情,人的改正表示向量被升级 codon 改编索引并且调整 GC 内容优化,插入一个 Kozak 序列( GCCACC ),并且介绍一个 gain-of-function 变化, R338L (改正 Padua )。效率屏蔽出版,目前构造的盒子直在 vivo 被比较。另外,在这些盒子控制改正基因表示的规章的元素为肝特定的有效性被屏蔽。在所有构造盒子之中, scAAV-Pre-hFIXco-SIH-R338L ,是在凝血素 enhancer 和 prealbumin 倡导者的控制下面的构造,导致了凝结剂活动的高水平,并且二个构造盒子( scAAV-Chi-hFIXco-SIH-R338L 和 scAAV-Pre-hFIXco-SIH-R338L )的表示层次也比出版盒子( scAAV-LP1-hFIXco-SJ )的高。在摘要,我们的策略在蛋白质水平或一项显著地提高的凝结剂活动在 hFIX 表示导致了实质的增加。因此,这些与 AAV hFIX 重建向量可以潜在地贡献出血不止 B 的有效基因治疗的创造。 | Ru Zhang Qiang Wang Lin Zhang Saijuan Chen | 2015 | Frontiers of Medicine2015，9，1： | 2 |
| 9 | Mutant DNA methylation regulators endow hematopoietic stem cells with the preleukemic stem cell property, a requisite of leukemia initiation and relapse显示文摘基因变化被认为驾驶尖锐 myeloid 的发展白血病(AML ).With 在定序技术的快速的进步,周期性地在 AML 被变异的许多最新报导的基因被发现了管理 AML 的开始和恶化。这些调查结果建议需要区分司机变化,特别最原始的单个变化,从随后的旅客变化。关于 DNA methyltransferase 3A (DNMT3A ) 的最近的研究变化在 AML 病人在 preleukemic 干细胞(最低有效字符前) 的鉴定上提供第一 proof-of-principle 调查。尽管没有引起全面白血病, DNMT3A 变化可以仅仅独自把造血的干细胞转变成最低有效字符前,这个驱动程序变化的函数看起来从 AML 坚持开始直到恶化。因此,识别并且指向 preleukemic 变化,在 AML,例如 DNMT3A 变化是为恶化风险的治疗和减小的有希望的策略。 | Yuting Tan Han Liu Saijuan Chen | 2015 | Frontiers of Medicine2015，9，4： | 2 |
| 10 | CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies显示文摘The current standard of care in hematological malignancies has brought considerable clinical benefits to patients.However,important bottlenecks still limit optimal achievements following a current medical practice.The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders.Consequently,new treatment strategies are necessary to improve clinical outcomes.Chimeric antigen receptor T-cell(CAR T)immunotherapy opens a new path for targeted therapy of hematological malignancies.In this review,through a representative case study,we summarize the current experience of CAR T-cell therapy,the management of common side effects,the causative mechanisms of therapy resistance,and new strategies to improve the efficacy of CAR T-cell therapy. | Jian-Qing Mi Jie Xu Jianfeng Zhou Weili Zhao Zhu Chen J.Joseph Melenhorst Saijuan Chen | 2021 | Frontiers of Medicine2021，15，6： | 2 |
| 11 | Inhibition of the nuclear export of p65 and IQCG in leukemogenesis by NUP98-IQCG显示文摘 | Mengmeng Pan Qiyao Zhang Ping Liu Jinyan Huang YueyingWang Saijuan Chen | 2016 | Frontiers of Medicine2016，10，4： | 1 |
| 12 | Prognostic analysis of chronic myeloid leukemia in Chinese population in an imatinib era显示文摘We evaluated the outcomes of chronic myeloid leukemia(CML)patients receiving imatinib treatment in chronic(CP),accelerated(AP),and blast crisis(BP)phases.The single-institution treatment experiences of Chinese patients with CML were presented.A total of 275 CML patients(CP,210;AP,24;and BP,41)who received imatinib between February 2001 and April 2008 were enrolled in this study.We evaluated the treatment responses(hematologic,cytogenetic,and molecular),overall survival(OS),event-free survival(EFS),and prognostic factors of outcome.At the cut-off point,the complete cytogenetic response(CCyR)and complete molecular response rates of patients in the CP were 84.7% and 61.9%,respectively,which were significantly higher than those of patients in the AP(50% and 29.1%,respectively,both P<0.001)and BP(24.3% and 9.7%,respectively,both P<0.001).The estimated five-year OS and five-year EFS rates were 93.2% and 86.4% for CP patients,as well as 64.5% and 50.9% for AP patients,which were significantly higher than those for BP patients(P<0.001).In CP patients,univariate analysis revealed that early treatment with imatinib,achieving CCyR within 12 months,additional cytogenetic abnormalities,and kinase domain mutations were associated with the treatment outcome.More patients are needed to carry out multivariate analysis. | Haiyan He Yang Shen Yongmei Zhu Saijuan Chen | 2012 | Frontiers of Medicine2012，6，2： | 1 |
| 13 | Primary assessment of the diversity of Omicron sublineages and the epidemiologic features of autumn/winter 2022 COVID-19 wave in Chinese mainland显示文摘With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures,there have been widespread SARS-CoV-2 infections in Chinese mainland.Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai,identifying a large number of sublineages of the SARS-CoV-2 Omicron family.Phylogenetic analysis,coupled with contact history tracing,revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China(BA.5.2 mainly in Guangzhou and Shanghai,and BF.7 mainly in Beijing)and two highly infectious sublineages recently imported from abroad(XBB and BQ.1).Publicly available data from August 31 to November 29,2022 indicated an overall severe/critical case rate of 0.035%nationwide,while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26,2022 showed that 20 cases(0.35%)without comorbidities progressed into severe/critical conditions and 153 cases(2.68%)with COVID-19-exacerbated comorbidities progressed into severe/critical conditions.These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases.Furthermore,mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year,whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023,and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival(January 21,2023).Altogether,these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population,especially in the rural areas,to ensure the country’s smooth exit from the ongoing pandemic and accelerate socio-economic recovery. | Gang Lu Yun Ling Minghao Jiang Yun Tan Dong Wei Lu Jiang Shuting Yu Fangying Jiang Shuai Wang Yao Dai Jinzeng Wang Geng Wu Xinxin Zhang Guoyu Meng Shengyue Wang Feng Liu Xiaohong Fan Saijuan Chen | 2023 | Frontiers of Medicine2023，17，4： | 1 |
| 14 | Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai显示文摘The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic.Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022.Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020,BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood.In particular,severe/critical cases of COVID19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment.Importantly,the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototypeinactivated vaccines,supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records.Furthermore,even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection,vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged≥60 years old.Together,our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines. | Ziyu Fu Dongguo Liang Wei Zhang Dongling Shi Yuhua Ma Dong Wei Junxiang Xi Sizhe Yang Xiaoguang Xu Di Tian Zhaoqing Zhu Mingquan Guo Lu Jiang Shuting Yu Shuai Wang Fangyin Jiang Yun Ling Shengyue Wang Saijuan Chen Feng Liu Yun Tan Xiaohong Fan | 2023 | Frontiers of Medicine2023，17，3： | 1 |
| 15 | Intra-heterogeneity in transcription and chemoresistant property of leukemia-initiating cells in murine Setd2^(-/-) acutemyeloid leukemia显示文摘Background:Heterogeneity of leukemia-initiating cells(LICs)is a major obstacle in acute myeloid leukemia(AML)therapy.Accumulated evidence indicates that the coexistence of multiple types of LICs with different pathogenicity in the same individual is a common feature in AML.However,the functional heterogeneity including the drug response of coexistent LICs remains unclear.Therefore,this study aimed to clarify the intra-heterogeneity in LICs that can help predict leukemia behavior and develop more effective treatments.Methods:Spleen cells from the primary Setd2^(-/-)-AML mouse were transplanted into C57BL/6 recipient mice to generate a transplantable model.Flow cytometry was used to analyze the immunophenotype of the leukemic mice.Whole-genome sequencing was conducted to detect secondary hits responsible for leukemia transformation.A serial transplantation assay was used to determine the self-renewal potential of Setd2^(-/-)-AML cells.A limiting-dilution assay was performed to identify the LIC frequency in different subsets of leukemia cells.Bulk and single-cell RNA sequencing were performed to analyze the transcriptional heterogeneity of LICs.Small molecular inhibitor screening and in vivo drug treatment were employed to clarify the difference in drug response between the different subsets of LICs.Results:In this study,we observed an aged Setd2^(-/-)mouse developing AML with co-mutation of Nras^(G12S) and Braf^(K520E).Further investigation identified two types of LICs residing in the c-Kit^(+)B220^(+)Mac-1^(-)and c-Kit^(+)B220^(+)Mac-1^(+)subsets,respectively.In vivo transplantation assay disclosed the heterogeneity in differentiation between the coexistent LICs.Besides,an intrinsic doxorubicinresistant transcriptional signature was uncovered in c-Kit^(+)B220^(+)Mac-1^(+)cells.Indeed,doxorubicin plus cytarabine(DA),the standard chemotherapeutic regimen used in AML treatment,could specifically kill c-Kit^(+)B220^(+)Mac-1^(−)cells,but it hardly affected c-Kit^(+)B220^(+)Mac-1^(+)cells.Transcriptome analysis unveiled a higher activation of RAS downstream signaling pathways in c-Kit^(+)B220^(+)Mac-1^(+)cells than in c-Kit^(+)B220^(+)Mac-1^(-)cells.Combined treatmentwithDAand RAS pathway inhibitors killed both c-Kit^(+)B220^(+)Mac-1^(−)and c-Kit^(+)B220^(+)Mac-1^(+)cells and attenuated disease progression.Conclusions:This study identified two cell subsets enriched for LICs inmurine Setd2^(-/-)-AML and disclosed the transcriptional and functional heterogeneity of LICs,revealing that the coexistence of different types of LICs in thismodel brings about diverse drug response. | Jiachun Song Longting Du Ping Liu Fuhui Wang Bo Zhang Yinyin Xie Jing Lu Yi Jin Yan Zhou Gang Lv Jianmin Zhang Saijuan Chen Zhu Chen Xiaojian Sun Yuanliang Zhang Qiuhua Huang | 2021 | Cancer Communications2021，41，9： | 0 |
| 16 | Etoposide,dexamethasone,and pegaspargase with sandwiched radiotherapy in early-stage natural killer/T-cell lymphoma:A randomized phase III study显示文摘Methotrexate,etoposide,dexamethasone,and pegaspargase(MESA)with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma,nasal type(NKTCL).We explored the efficacy and safety of reduced-intensity,non-intravenous etoposide,dexamethasone,and pegaspargase(ESA)with sandwiched radiotherapy.This multicenter,randomized,phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China.Patients were randomly assigned(1:1)to receive ESA(pegaspargase 2,500 IU/m^(2)intramuscularly on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4)or MESA(methotrexate 1 g/m^(2)intravenously on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4,and pegaspargase 2,500 IU/m^(2)intramuscularly on day 5)regimen(four cycles),combined with sandwiched radiotherapy. | Huijuan Zhong Shu Cheng Xi Zhang Bing Xu Jiayi Chen Xufeng Jiang Jie Xiong Yu Hu Guohui Cui Juying Wei Wenbin Qian Xiaobing Huang Ming Hou Feng Yan Xin Wang Yongping Song Jianda Hu Yuanhua Liu Xuejun Ma Fei Li Chongyang Wu Junmin Chen Li Yu Ou Bai Jingyan Xu Zunmin Zhu Li Liu Xin Zhou Li Huang Yin Tong Ting Niu Depei Wu Hao Zhang Chaofu Wang Binshen Ouyang Hongmei Yi Qi Song Gang Cai Biao Li Jia Liu Zhifeng Li Rong Xiao Luqun Wang Yujie Jiang Yanyan Liu Xiaoyun Zheng Pengpeng Xu Hengye Huang Li Wang Saijuan Chen Weili Zhao | 2023 | The Innovation2023，4，3： | 0 |
| 17 | Revisiting China’s response to coronavirus disease 2019显示文摘“The rolling Yangtze River flows eastward,washingaway the heroes in its waves.”These words were written by a poet,Shen Yang,500years ago in his poem Immortal by the River.“Countlessevents of the past and present are all turned into laughterand conversation of the white-haired fishermen andwoodcutters.” | Guangbiao Zhou Saijuan Chen Zongjiu Zhang Zhu Chen | 2023 | Frontiers of Medicine2023，17，6： | 0 |
| 18 | A systematic survey of LU domain-containing proteins reveals a novel human gene,LY6A,which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors显示文摘The Ly-6 and uPAR(LU)domain-containing proteins represent a large family of cell-surface markers.In particular,mouse Ly-6A/Sca-1 is a widely used marker for various stem cells;however,its human ortholog is missing.In this study,based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins,we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1.This gene,hereby named LY6A,reversely overlaps with a lncRNA gene in the majority of exonic sequences.We found that LY6A is aberrantly expressed in pituitary tumors,but not in normal pituitary tissues,and may contribute to tumorigenesis.Similar to mouse Ly-6A/Sca-1,human LY6A is also upregulated by interferon,suggesting a conserved transcriptional regulatory mechanism between humans and mice.We cloned the full-length LY6A cDNA,whose encoded protein sequence,domain architecture,and exon‒intron structures are all well conserved with mouse Ly-6A/Sca-1.Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane.Collectively,these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms. | Dan Liu Chunhui Xu Yanting Liu Wen Ouyang Shaojian Lin Aining Xu Yuanliang Zhang Yinyin Xie Qiuhua Huang Weili Zhao Zhu Chen Lan Wang Saijuan Chen Jinyan Huang Zhe Bao Wu Xiaojian Sun | 2023 | Frontiers of Medicine2023，17，3： | 0 |
| 19 | PathogenTrack and Yeskit:tools for identifying intracellular pathogens from single-cell RNA-sequencing datasets as illustrated by application to COVID-19显示文摘Pathogenic microbes can induce cellular dysfunction,immune response,and cause infectious disease and other diseases including cancers.However,the cellular distributions of pathogens and their impact on host cells remain rarely explored due to the limited methods.Taking advantage of single-cell RNA-sequencing(scRNA-seq)analysis,we can assess the transcriptomic features at the single-cell level.Still,the tools used to interpret pathogens(such as viruses,bacteria,and fungi)at the single-cell level remain to be explored.Here,we introduced PathogenTrack,a python-based computational pipeline that uses unmapped scRNA-seq data to identify intracellular pathogens at the single-cell level.In addition,we established an R package named Yeskit to import,integrate,analyze,and interpret pathogen abundance and transcriptomic features in host cells.Robustness of these tools has been tested on various real and simulated scRNA-seq datasets.PathogenTrack is competitive to the state-of-the-art tools such as Viral-Track,and the first tools for identifying bacteria at the single-cell level.Using the raw data of bronchoalveolar lavage fluid samples(BALF)from COVID-19 patients in the SRA database,we found the SARS-CoV-2 virus exists in multiple cell types including epithelial cells and macrophages.SARS-CoV-2-positive neutrophils showed increased expression of genes related to type I interferon pathway and antigen presenting module.Additionally,we observed the Haemophilus parahaemolyticus in some macrophage and epithelial cells,indicating a co-infection of the bacterium in some severe cases of COVID-19.The PathogenTrack pipeline and the Yeskit package are publicly available at GitHub. | Wei Zhang Xiaoguang Xu Ziyu Fu Jian Chen Saijuan Chen Yun Tan | 2022 | Frontiers of Medicine2022，16，2： | 0 |
| 20 | Integrated analysis of gut microbiome and host immune responses in COVID-19显示文摘Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases.Here,to explore the role of the gut microbiome in the host immune responses in COVID-19,we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples.We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones.We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity,such as Enterococcus faecium,Coprococcus comes,Roseburia intestinalis,Akkermansia ntuciniphila,Bacteroides cellulosilyticus and Blautia obeum.We further analyzed the correlation between the abundance of gut microbes and host responses,and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe,including Coprococcus comes that was positively correlated with CD3^(+)/CD4^(+)/CD8^(+)lymphocyte counts.In addition,an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells(PBMCs)showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples.Moreover,a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases,including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19.Together,our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host. | Xiaoguang Xu Wei Zhang Mingquan Guo Chenlu Xiao Ziyu Fu Shuting Yu Lu Jiang Shengyue Wang Yun Ling Feng Liu Yun Tan Saijuan Chen | 2022 | Frontiers of Medicine2022，16，2： | 0 |
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