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Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants

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Cancer Biology & Medicine 2024年第6期21卷 473-483页

作者： Shuyi Chen Jing Gu Kaichun Wu Xiaodi Zhao Yuanyuan Lu State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical research Center for Digestive diseases Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’an 710032China School of Basic Medical Sciences Fourth Military Medical UniversityXi’an 710032China

Targeted therapy is crucial for advanced colorectal cancer(CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2(ERBB2), B-Raf proto-oncogene, serine/threonine kinase(BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase(ALK/ROS1), neurotrophic receptor tyrosine kinases(NTRKs), ret proto-oncogene(RET), fibroblast growth factor receptor 2(FGFR2), and epidermal growth factor receptor(EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

关键词： Genetic variation gene mutation gene amplification gene rearrangement targeted therapy

The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes:findings from a prospective,nationwide,and multicenter registry

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Journal of Geriatric Cardiology 2024年第5期21卷 523-533页

作者： Rui FU Ying-Xuan ZHU Kong-Yong CUI Jin-Gang YANG Hai-Yan XU Dong YIN Wei-Hua SONG Hong-Jian WANG Cheng-Gang ZHU Lei FENG Wei WU Kai-HongCHEN Yan-Yan ZHAO Ye LU Ke-Fei DOU Yue-Jin YANG on behalf of the CAMI Registry Investigators Cardiometabolic Medicine Center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Medical research&Biometrics Center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Coronary Heart Disease Center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology Guangzhou Traditional Chinese Medical College First Affiliated HospitalGuangdong ProvinceChina Department of Cardiology Longyan Hospital First HospitalFujian ProvinceChina 不详

OBJECTIVES To evaluate the predictive value of fasting plasma glucose(FPG)for in-hospital mortality in patients with acute myocardial infarction(AMI)with different glucose metabolism *** We selected 5,308 participants with AMI from the prospective,nationwide,multicenter CAMI registry,of which 2,081 were diabetic and 3,227 were *** were divided into high FPG and low FPG groups according to the optim-al cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts,*** primary endpoint was in-hospital *** Overall,94 diabetic patients(4.5%)and 131 nondiabetic patients(4.1%)died during hospitalization,and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L,*** with individuals who had low FPG,those with high FPG were significantly associated with higher in-hospital mortality in diabet-ic cohort(10.1%vs.2.8%;odds ratio[OR]=3.862,95%confidence interval[CI]:2.542-5.869)and nondiabetic cohort(7.4%vs.1.7%;HR=4.542,95%CI:3.041-6.782).After adjusting the potential confounders,this significant association was not ***-more,FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic *** FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic *** This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mor-tality in AMI patients with and without *** might be useful to stratify patients with AMI.

关键词： patients fasting infarction

TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 537-544页

作者： Yu Qian Ying Xiao Qiu-Rong Lin Zhao-Yu Xiang Li-Pu Cui Jia-Qi Sun Si-Cong Li Xin-Ran Qin Hai-Dong Zou Chen-Hao Yang Pei-Yao Jin Department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai First People’s HospitalShanghai 200080China Shanghai Eye diseases Prevention&Treatment Center Shanghai Eye HospitalShanghai 200040China National Clinical research Center for Eye diseases Shanghai Clinical Research Center for Eye DiseasesShanghai Key Clinical SpecialtyShanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghai 200080China Department of Ophthalmology Children’s Hospital of Fudan UniversityShanghai 201102China

●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first *** no participant has DR,retina thinning was used as a surrogate indicator for *** lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were *** DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control *** DMS with a potential role in diabetes were *** second survey included 27 T1DM children,among which four had *** methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

关键词： DNA methylation 850K array pyrosequencing diabetic retinopathy type 1 diabetes children

Understanding autoimmune response after SARS-CoV-2 infection and the pathogenesis/mechanisms of long COVID

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Medical Review 2024年第5期4卷 367-383页

作者： Ming Guo Shunlai Shang Mengfei Li Guangyan Cai Ping Li Xiangmei Chen Qinggang Li Department of Nephrology First Medical Center of Chinese PLA General HospitalState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Diseases ResearchBeijing 100853China Department of Nephrology China-Japan Friendship HospitalBeijingChina Haihe Laboratory of Cell Ecosystem China

COVID-19 posed a major challenge to the healthcare *** and the adoption of numerous prevention and control measures enabled the gradual end of the COVID-19 ***,successive occurrence of autoimmune diseases in patients with COVID-19cannot *** COVID has been themajor focus of research due to the long duration of different symptoms and the variety of systems *** may play a crucial role in the pathogenesis of long ***,we reviewed several autoimmune disorders occurring after COVID-19 infection and the pathogenesis of long COVID.

关键词： COVID-19 SARS-CoV-2 long COVID autoimmunity

Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia:a prospective,single arm,phase I trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2250-2259页

作者： Yunfei Chen Yanmei Xu Ying Chi Ting Sun Yuchen Gao Xueqing Dou Zhibo Han Feng Xue Huiyuan Li Wei Liu Xiaofan Liu Huan Dong Rongfeng Fu Mankai Ju Xinyue Dai Wentian Wang Yueshen Ma Zhen Song Jundong Gu Wei Gong Renchi Yang Lei Zhang State Key Laboratory of Experimental Hematology National Clinical Research Centre for Blood DiseasesHaihe Laboratory of Cell EcosystemTianjin Key Laboratory of Gene Therapy for Blood DiseasesCAMS Key Laboratory of Gene Therapy for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China National Clinical research Center for Hematologic diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhou 215006China National Engineering research Centre of Cell Products Tianjin Key Laboratory of Engineering Technologies for Cell PharmaceuticalAmCellGene Engineering Co.LtdTianjin 300457China School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical College100730 BeijingChina

Patients with refractory immune thrombocytopenia(ITP)frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing *** cord-derived mesenchymal stem cells(UC-MSCs)present a promising alternative,capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune *** prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory *** research design included administering UC-MSCs at escalating doses of 0.5×10^(6)cells/kg,1.0×10^(6)cells/kg,and 2.0×10^(6)cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase,followed by a dose of 2.0×10^(6)cells/kg weekly for the dose-expansion *** events,platelet counts,and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up ***,12(with an addition of three patients in the 2.0×10^(6)cells/kg group due to dose-limiting toxicity)and six patients were enrolled in the dose-escalation and dose-expansion phase,*** patients(13/18,72.2%)experienced one or more treatment emergent adverse *** adverse events occurred in four patients(4/18,22.2%),including gastrointestinal hemorrhage(2/4),profuse menstruation(1/4),and acute myocardial infarction(1/4).The response rates were 41.7%in the dose-escalation phase(5/12,two received 1.0×10^(6)cells/kg per week,and three received 2.0×10^(6)cells/kg per week)and 50.0%(3/6)in the dose-expansion *** overall response rate was 44.4%(8/18)among all enrolled *** sum up,UC-MSCs are effective and well tolerated in treating refractory ITP(*** ID:NCT04014166).

关键词： doses immunity treatment

Bacterial Infections in Acute-on-chronic Liver Failure:Epidemiology,Diagnosis,Pathogenesis,and Management

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Journal of Clinical and Translational Hepatology 2024年第7期12卷 667-676页

作者： Zhaoyu Xu Xiuding Zhang Jiyang Chen Yu Shi Shangwei Ji China-Japan Union Hospital of Jilin University ChangchunJilinChina State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangChina Department of Infectious diseases China-Japan Union Hospital of Jilin UniversityChangchunJilinChina

Acute-on-chronic liver failure(ACLF)is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease,often leading to multi-organ failures and significant short-term *** infection is one of the most frequent triggers for ACLF and a common complication following its *** impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ *** addition,the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use,as well as accurate and prompt microbiological *** review provided an update on recent advances in the epidemiology,diagnosis,pathogenesis,and management of bacterial infections in ACLF.

关键词： Acute-on-chronic liver failure Bacterial infection Multidrug-resistant bacteria Spontaneoous bacterial peritonitis systemic inflammation Antibiotic Albumin

DNA vaccine prime and replicating vaccinia vaccine boost induce robust humoral and cellular immune responses against MERS-CoV in mice

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Virologica Sinica 2024年第3期39卷 490-500页

作者： Xiuli Shen Shuhui Wang Yanling Hao Yuyu Fu Li Ren Dan Li Wenqi Tang Jing Li Ran Chen Meiling Zhu Shuo Wang Ying Liu Yiming Shao National Key Laboratory of Intelligent Tracking and Forecasting for Infectious diseases National Center for AIDS/STD Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China Changping Laboratory Yard 28Science Park RoadChangping DistrictBeijing 102206China State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China

As of December 2022,2603 laboratory-identified Middle East respiratory syndrome coronavirus(MERS-CoV)infections and 935 associated deaths,with a mortality rate of 36%,had been reported to the World Health Organization(WHO).However,there are still no vaccines for MERS-CoV,which makes the prevention and control of MERS-CoV *** this study,we generated two DNA vaccine candidates by integrating MERS-CoV Spike(S)gene into a replicating Vaccinia Tian Tan(VTT)*** to homologous immunization with either vaccine,mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune *** immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012,England1 and KNIH strains of ***-Boost immunization also induced strong MERS-S specific T cells responses,with high memory and poly-functional(CD107a-IFN-γ-TNF-α)effector CD8t T *** conclusion,the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against *** study not only provides a promising set of MERS-CoV vaccine candidates,but also proposes a heterologous sequential immunization strategy worthy of further development.

关键词： MERS-CoV VTT vaccine DNA vaccine Humoral and cellular immune responses Prime/boost strategy

Impact of short-term ambient air pollution exposure on the risk of severe COVID-19

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Journal of Environmental Sciences 2024年第1期135卷 610-618页

作者： Baihuan Feng Jiangshan Lian Fei Yu Dan Zhang Weizhen Chen QiWang Yifei Shen Guoliang Xie Ruonan Wang Yun Teng Bin Lou Shufa Zheng Yida Yang Yu Chen Department of Laboratory Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province Hangzhou 310000China Institute of Laboratory Medicine Zhejiang UniversityHangzhou 310000China Department of Infectious diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China State Key Laboratory for Diagnosis and Treatment of Infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China

Ecological studies suggested a link between air pollution and severe COVID-19 outcomes,while studies accounting for individual-level characteristics are *** the present study,we aimed to investigate the impact of short-term ambient air pollution exposure on disease severity among a cohort of 569 laboratory confirmed COVID-19 patients admitted to designated hospitals in Zhejiang province,China,from January 17 to March 3,2020,and elucidate the possible biological processes involved using *** with mild cases,severe cases had higher proportion of medical conditions as well as unfavorable results in most of the laboratory tests,and manifested higher air pollution exposure *** exposure to air pollutants was associated with increased risk of severe COVID-19 with odds ratio(OR)of 1.89(95%confidence interval(CI):1.01,3.53),2.35(95%CI:1.20,4.61),2.87(95%CI:1.68,4.91),and 2.01(95%CI:1.10,3.69)for PM_(2.5),PM_(10),NO_(2)and CO,*** for NO_(2)remained significant in two-pollutant models after adjusting for other *** analysis showed 884 differentially expressed genes which mainly were enriched in virus clearance related biological processes between patients with high and low NO_(2)exposure levels,indicating that compromised immune response might be a potential underlying mechanistic *** findings highlight the impact of shortterm air pollution exposure,particularly for NO_(2),on COVID-19 severity,and emphasize the significance in mitigating the COVID-19 burden of commitments to improve air quality.

关键词： Air pollution COVID-19 Severity Transcriptomics Immune response

A Wnt10a-Notch signaling axis controls Hertwig’s epithelial root sheath cell behaviors during root furcation patterning

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International Journal of Oral Science 2024年第3期16卷 425-435页

作者： Kai Sun Miao Yu Jiayu Wang Hu Zhao Haochen Liu Hailan Feng Yang Liu Dong Han Department of Prosthodontics Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Chinese Institute for Brain research BeijingChina

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root ***,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig’s epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains *** this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10a^(fl/fl)mice from post-natal day 0.5(PN0.5)to *** assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10a^(fl/fl)mice at PN2.5 and *** staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10a^(fl/fl)***-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10a^(fl/fl)***,after activation of Notch signaling in K14-Cre;Wnt10a^(fl/fl)molars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially *** together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

关键词： Wnt10a Notch impaired