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Epigenetic therapies in acute myeloid leukemia: the role of hypomethylating agents, histone deacetylase inhibitors and the combination of hypomethylating agents with histone deacetylase inhibitors

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Chinese Medical Journal 2020年第6期133卷 699-715页

作者： qing-yu xu Li yu Department of Hematology-Oncology International Cancer CenterShenzhen University General HospitalShenzhen University Health Science CenterShenzhenGuangdong 518000China Department of Hematology and Oncology Medical Faculty MannheimHeidelberg UniversityMannheim 68169Germany

Epigenetic regulation includes changes of DNA methylation and modifications of histone proteins and is essential for normal physiologic functions,especially for controlling gene expression.Epigenetic dysregulation plays a key role in disease pathogenesis and progression of some malignancies,including acute myeloid leukemia(AML).Epigenetic therapies,including hypomethylating agents(HMAs)and histone deacetylase(HDAC)inhibitors,were developed to reprogram the epigenetic abnormalities in AML.However,the molecular mechanisms and therapeutic effects of the two agents alone or their combination remain unknown.An overview of these epigenetic therapies is given here.A literature search was conducted through PubMed database,looking for important biological or clinical studies related to the epigenetic regimens in the treatment of AML until October 15th,2019.Various types of articles,including original research and reviews,were assessed,identified,and eventually summarized as a collection of data pertaining the mechanisms and clinical effects of HMAs and HDAC inhibitors in AML patients.We provided here an overview of the current understanding of the mechanisms and clinical therapeutic effects involved in the treatment with HMAs and HDAC inhibitors alone,the combination of epigenetic therapies with intensive chemotherapy,and the combination of both types of epigenetic therapies.Relevant clinical trials were also discussed.Generally speaking,the large number of studies and their varied outcomes demonstrate that effects of epigenetic therapies are heterogeneous,and that HMAs combination regimens probably contribute to significant response rates.However,more research is needed to explore therapeutic effects of HDAC inhibitors and various combinations of HMAs and HDAC inhibitors.

关键词： Acute myeloid leukemia Decitabine 5-azacytidine Histone deacetylase inhibitors Intensive chemotherapy

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Ecdysone receptor isoforms play distinct roles in larval–pupal–adult transition in Leptinotarsa decemlineata

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Insect Science 2020年第3期27卷 487-499页

作者： qing-yu xu Pan Deng Qiong Zhang Ang Li Kai-yun Fu Wen-Chao Guo Guo-qing Li Education Ministry Key Laboratory of Integrated Management of Crop Diseases and Pests College of Plant ProtectionNanjing Agricultural UniversityNanjingChina Institute of Plant Protection Xinjiang Academy of Agricultural SciencesUrumqiChina Institute of Microbiological Application Xinjiang Academy of Agricultural ScienceUrumqiChina

A heterodimer of two nuclear receptors,ecdysone receptor(EcR)and ultraspiracle,mediates 20‐hydroxyecdysone(20E)signaling to modulate many aspects in insect life,such as molting and metamorphosis,reproduction,diapause and innate immunity.In the present paper,we intended to determine the isoform‐specific roles of EcR during larval–pupal–adult transition in the Colorado potato beetle.Double‐stranded RNAs(dsRNAs)were prepared using the common(dsEcR)or isoform‐specific(dsEcRA,dsEcRB1)regions of EcR as templates.Ingestion of either dsEcR or dsEcRA,rather than dsEcRB1,by the penultimate(3rd)and final(4th)instar larvae caused failure of larval–pupal and pupal–adult ecdysis.The RNA interference(RNAi)larvae remained as prepupae,or became deformed pupae and adults.Determination of messenger RNA(mRNA)levels of EcR isoforms found that LdEcRA regulates the expression of LdEcRB1.Moreover,silencing the two EcR transcripts,LdEcRA or LdEcRB1 reduced the mRNA levels of Ldspo and Ldsad,and lowered 20E titer.In contrast,the expression levels of HR3,HR4,E74 and E75 were significantly decreased in the LdEcR or LdEcRA RNAi larvae,but not in LdEcRB1 depleted specimens.Dietary supplement with 20E did not restore the expression of five 20E signaling genes(USP,HR3,HR4,E74 and E75),and only partially alleviated the pupation defects in dsEcR‐or dsEcRA‐fed beetles.These data suggest that EcR plays isoform‐specific roles in the regulation of ecdysteroidogenesis and the transduction of 20E signal in L.decemlineata.

关键词： ecdysone receptor Leptinotarsa decemlineata metamorphosis RNA interference

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Tailoring electron vortex beams with customizable intensity patterns by electron diffraction holography

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Opto-Electronic Advances 2024年第2期7卷 14-21页

作者： Pengcheng Huo Ruixuan yu Mingze Liu Hui Zhang Yan-qing Lu Ting xu National Laboratory of Solid-State Microstructures and Collaborative Innovation Center of Advanced Microstructures Nanjing UniversityNanjing 210093China College of Engineering and Applied Sciences Key Laboratory of Intelligent Optical Sensing and Manipulation and Jiangsu Key Laboratory of Artificial Functional MaterialsNanjing UniversityNanjing 210093China

An electron vortex beam(EVB) carrying orbital angular momentum(OAM) plays a key role in a series of fundamental scientific researches, such as chiral energy-loss spectroscopy and magnetic dichroism spectroscopy. So far, almost all the experimentally created EVBs manifest isotropic doughnut intensity patterns. Here, based on the correlation between local divergence angle of electron beam and phase gradient along azimuthal direction, we show that free electrons can be tailored to EVBs with customizable intensity patterns independent of the carried OAM. As proof-of-concept, by using computer generated hologram and designing phase masks to shape the incident free electrons in the transmission electron microscope, three structured EVBs carrying identical OAM are tailored to exhibit completely different intensity patterns. Furthermore, through the modal decomposition, we quantitatively investigate their OAM spectral distributions and reveal that structured EVBs present a superposition of a series of different eigenstates induced by the locally varied geometries. These results not only generalize the concept of EVB, but also demonstrate an extra highly controllable degree of freedom for electron beam manipulation in addition to OAM.

关键词： electron vortex beam orbital angular momentum diffraction holography

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Surgical treatment of anomalous origin of coronary artery from the pulmonary artery

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Chinese Medical Journal 2008年第8期121卷 721-724页

作者： WU qing-yu xu Zhong-hua Cardiac Center First Hospital of Tsinghua University School of Medicine Tsinghua University Beijing 100016 China

Background Anomalous origin of coronary artery from the pulmonary artery is a rare congenital cardiac malformation with a mortality rate of up to 90% within the first year of life without surgical intervention. Direct implantation of the anomalous coronary artery （ACA） into the aorta is successful in early life, but it may have increased surgical difficulty and risk with age. This retrospective study summarized our operative experience in direct implantation for treatment of this coronary anomaly in pediatric and adult patients. Methods From August 2000 to January 2003, 4 consecutive patients aged from 9 months to 41 years underwent dual coronary repair. Among them, two children and one infant with anomalous origin of the left coronary artery from the pulmonary artery （ALCAPA） and one adult was anomalous origin of right coronary artery from the pulmonary artery （ARCAPA）. Coronary arteries were directly implanted into the ascending aorta in 4 patients. In a boy with ALCAPA associated with moderate mitral insufficiency （MI）, whose ACA arose remotely from the ascending aorta, we created a tube-shaped graft using part of the pulmonary arterial wall in continuity with the origin of the left coronary artery （LCA）. Concomitant moderate MI was repaired in 2 patients, including this boy, after a dual-coronary repair. Results All patients survived. There were no hospital or late deaths and no major complications as well. Echocardiography revealed that the left ventricular （LV） function including LV end-diastolic dimension （EDD） and ejection fraction （EF） was markedly improved at hospital discharge. At 3-6 years follow-up after surgery all patients were asymptomatic and currently in NYHA class 1. Conclusions The best results are achieved with direct implantation of the ACA into the ascending aorta and simultaneous mitral valve repair if needed. Direct implantation is feasible in pediatric and adult patients with ALCAPA or ARCAPA including the coronary artery in a location remote from the ascending aorta. It is a good

关键词： congenital coronary anomaly surgical treatment

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Surgical treatment of myocardial bridging:report of 31 cases

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Chinese Medical Journal 2007年第19期120卷 1689-1693页

作者： WU qing-yu xu Zhong-hua Cardiac Center First Hospital of Tsinghua University School of Medicine Tsinghua University Beijing 100016 China

Background Myocardial bridging （MB） is usually considered a benign condition but may result in myocardial ischemia, myocardial infarction （MI）, exercise-induced tachycardia, atrioventricular conduction block or even sudden cardiac death. This retrospective study summarizes our operative methods and outcomes for treatment of 31 cases of MB. Methods From January 1997 to December 2006, 31 consecutive patients （24 men and 7 women; aged 35-67 years; mean 52.3 years） with MB underwent surgical treatment. Thirteen patients had MB only and 18 patients had MB associated with other heart diseases. In preoperative cardiac function grading, 5 patients were in NYHA class Ⅰ and 18 in NYHA class Ⅱ and 8 in NYHA class Ⅲ. Among them, 15 underwent myotomy and 16 underwent coronary artery bypass grafting （CABG）. Results All patients survived and recovered uneventfully. Neither hospital or late death nor major complications occurred. Postoperative exercise testing in all patients failed to reveal any persistent ischemia. Follow-up time was 3-115 months （mean 31 months）. Follow-up angiographic studies in 21 patients （68%） demonstrated restoration of coronary blood flow and myocardial perfusion without significant residual compression of the artery. All patients were symptom-free and currently in NYHA class Ⅰ-Ⅱ. Conclusion The patients who are refractory to medication should actively undergo the surgical procedures such as myotomy and CABG. Myotomy should be advocated as the first choice because of its safety and satisfactory results.

关键词： congenital myocardial bridging surgical treatment

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Clinical efficacy and pathological outcomes of transanal endoscopic intersphincteric resection for low rectal cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 933-944页

作者： Zhi-Wen xu Jing-Tao Zhu Hao-yu Bai xue-Jun yu qing-Qi Hong Jun You Department of Gastrointestinal Oncology Surgery The First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361000Fujian ProvinceChina

BACKGROUND Transanal endoscopic intersphincteric resection(ISR)surgery currently lacks sufficient clinical research and reporting.AIM To investigate the clinical effectiveness of transanal endoscopic ISR,in order to promote the clinical application and development of this technique.METHODS This study utilized a retrospective case series design.Clinical and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were included.All patients underwent transanal endoscopic ISR as the surgical approach.We conducted this study to determine the perioperative recovery status,postoperative complications,and pathological specimen charac-teristics of this group of patients.RESULTS This study included 45 eligible patients,with no perioperative mortalities.The overall incidence of early complications was 22.22%,with a rate of 4.44%for Clavien-Dindo grade≥III events.Two patients(4.4%)developed anastomotic leakage after surgery,including one case of grade A and one case of grade B.Postoperative pathological examination confirmed negative circumferential resection margins and distal resection margins in all patients.The mean distance between the tumor lower margin and distal resection margin was found to be 2.30±0.62 cm.The transanal endoscopic ISR procedure consistently yielded high quality pathological specimens.CONCLUSION Transanal endoscopic ISR is safe,feasible,and provides a clear anatomical view.It is associated with a low incidence of postoperative complications and favorable pathological outcomes,making it worth further research and application.

关键词： Intersphincteric resection Transanal Rectal cancer Complications Endoscopic

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Comparison of various prediction models in the effect of laparoscopic sleeve gastrectomy on type 2 diabetes mellitus in the Chinese population 5 years after surgery

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Chinese Medical Journal 2024年第3期137卷 320-328页

作者： Chengyuan yu Liang Wang Guangzhong xu Guanyang Chen qing Sang Qiqige Wuyun Zheng Wang Chenxu Tian Nengwei Zhang Surgery Centre of Diabetes Mellitus Peking University Ninth School of Clinical MedicineBeijing 100038China Department of Surgery Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China

Background:The effect of bariatric surgery on type 2 diabetes mellitus(T2DM)control can be assessed based on predictive models of T2DM remission.Various models have been externally verified internationally.However,long-term validated results after laparoscopic sleeve gastrectomy(LSG)surgery are lacking.The best model for the Chinese population is also unknown.Methods:We retrospectively analyzed Chinese population data 5 years after LSG at Beijing Shijitan Hospital in China between March 2009 and December 2016.The independent t-test,Mann–Whitney U test,and chi-squared test were used to compare characteristics between T2DM remission and non-remission groups.We evaluated the predictive efficacy of each model for longterm T2DM remission after LSG by calculating the area under the curve(AUC),sensitivity,specificity,Youden index,positive predictive value(PPV),negative predictive value(NPV),and predicted-to-observed ratio,and performed calibration using Hosmer–Lemeshow test for 11 prediction models.Results:We enrolled 108 patients,including 44(40.7%)men,with a mean age of 35.5 years.The mean body mass index was 40.3±9.1 kg/m^(2),the percentage of excess weight loss(%EWL)was(75.9±30.4)%,and the percentage of total weight loss(%TWL)was(29.1±10.6)%.The mean glycated hemoglobin A1c(HbA1c)level was(7.3±1.8)%preoperatively and decreased to(5.9±1.0)%5 years after LSG.The 5-year postoperative complete and partial remission rates of T2DM were 50.9%[55/108]and 27.8%[30/108],respectively.Six models,i.e.,"ABCD",individualized metabolic surgery(IMS),advanced-DiaRem,DiaBetter,Dixon et al’s regression model,and Panunzi et al’s regression model,showed a good discrimination ability(all AUC>0.8).The"ABCD"(sensitivity,74%;specificity,80%;AUC,0.82[95%confidence interval[CI]:0.74–0.89]),IMS(sensitivity,78%;specificity,84%;AUC,0.82[95%CI:0.73–0.89]),and Panunzi et al’s regression models(sensitivity,78%;specificity,91%;AUC,0.86[95%CI:0.78–0.92])showed good discernibility.In the Hosmer–Lemeshow goodness-of-fit test,except for DiaRem(P<0.01),Di

关键词： Type 2 diabetes mellitus Risk prediction models External validation Sleeve gastrectomy Bariatric surgery

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Intravitreal conbercept injection with panretinal photocoagulation for high-risk proliferative diabetic retinopathy with vitreous hemorrhage

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1066-1072页

作者： Yao xu qing Ye Wei Shen Department of Ophthalmology the Fourth Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Department of Ophthalmology Suzhou Kowloon HospitalShanghai Jiao Tong University School of MedcineSuzhou 215000Jiangsu ProvinceChina Department of Ophthalmology the First Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina

AIM:To assess the clinical efficacy and safety of combining panretinal photocoagulation(PRP)with intravitreal conbercept(IVC)injections for patients with high-risk proliferative diabetic retinopathy(HR-PDR)complicated by mild or moderate vitreous hemorrhage(VH),with or without diabetic macular edema(DME).METHODS:Patients diagnosed with VH with/without DME secondary to HR-PDR and received PRP combined with IVC injections were recruited in this retrospective study.Upon establishing the patient’s diagnosis,an initial IVC was performed,followed by prompt administration of PRP.In cases who significant bleeding persisted and impeded the laser operation,IVC was sustained before supplementing with PRP.Following the completion of PRP,patients were meticulously monitored for a minimum of six months.Laser therapy and IVC injections were judiciously adjusted based on fundus fluorescein angiography(FFA)results.Therapeutic effect and the incidence of adverse events were observed.RESULTS:Out of 42 patients(74 eyes),29 were male and 13 were female,with a mean age of 59.17±12.74y(33-84y).The diabetic history was between 1wk and 26y,and the interval between the onset of visual symptoms and diagnosis of HR-PDR was 1wk-1y.The affected eye received 2.59±1.87(1-10)IVC injections and underwent 5.5±1.02(4-8)sessions of PRP.Of these,68 eyes received PRP following 1 IVC injection,5 eyes after 2 IVC injections,and 1 eye after 3 IVC injections.Complete absorption of VH was observed in all 74 eyes 5-50wk after initial treatment,with resolution of DME in 51 eyes 3-48wk after initial treatment.A newly developed epiretinal membrane was noted in one eye.Visual acuity significantly improved in 25 eyes.No complications such as glaucoma,retinal detachment,or endophthalmitis were reported.CONCLUSION:The study suggests that the combination of PRP with IVC injections is an effective and safe modality for treating diabetic VH in patients with HR-PDR.

关键词： conbercept panretinal photocoagulation high-risk proliferative diabetic retinopathy vitreous hemorrhage

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A gel polymer electrolyte based on IL@NH_(2)-MIL-53(Al)for high-performance all-solid-state lithium metal batteries

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Chinese Journal of Chemical Engineering 2024年第5期69卷 47-55页

作者： Sijia Wang Ye Liu Liang He yu Sun qing Huang Shoudong xu Xiangyun Qiu Tao Wei School of Energy and Power Jiangsu University of Science and TechnologyZhenjiang 212003China College of Materials Science and Engineering Nanjing Forestry UniversityNanjing 210037China College of Chemical Engineering and Technology Taiyuan University of TechnologyTaiyuan 030024China Power&Energy Storage System Research Center College of Mechanical and Electrical EngineeringQingdao UniversityQingdao 266071China

Solid polymer composite electrolytes possess the benefits of superior compatibility with electrodes and good thermal characteristics for more secure energy storage equipment.Herein,a new gel polymer electrolyte(GPE)containing NH_(2)-MIL-53(Al),[PP_(13)][TFSI],LiTFSI,and PVDF-HFP was prepared using a simple method of solution casting.The effects of encapsulating different ratios of ionic liquid([PP_(13)][TFSI])into the micropores of functionalized metal-organic frameworks(NH_(2)-MIL-53(Al))on the electrochemical properties were compared.XRD,SEM,nitrogen adsorption-desorption isotherms,and electrochemical measurements were conducted.This GPE demonstrates a superior ionic conductivity of 8.08×10^(-4)S·cm^(-1)at 60℃and can sustain a discharge specific capacity of 156.6 mA·h·g^(-1)at 0.2 C for over 100 cycles.This work might offer a potential approach to alleviate the solid-solid contact with the solid-state electrolyte and electrodes and broaden a new window for the creation of all-solid-state batteries.

关键词： Metal-organic frameworks(MOFs) All solid-state lithium batteries(ASSLBs) Ionic liquid NH_(2)-MIL-53(Al) Solid-state electrolytes(SSEs)

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Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

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Military Medical Research 2024年第2期11卷 287-307页

作者： Pan Luo Fu-Qiang Gao Wei Sun Jun-You Li Cheng Wang qing-yu Zhang Zhi-Zhuo Li Peng xu Department of Joint Surgery Honghui HospitalXi'an Jiaotong UniversityXi'an 710054China Department of Orthopedics China-Japan Friendship HospitalBeijing 100029China Department of Orthopaedic Surgery of the Perelman School of Medicine University of PennsylvaniaPhiladelphiaPA 19104USA School of Mechanical Engineering Sungkyunkwan UniversitySuwon 16419South Korea Department of Orthopaedic Surgery Peking University Third HospitalPeking UniversityBeijing 100191China Department of Orthopedics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

关键词： Rheumatoid arthritis Fluorescent probe Imaging Diagnosis Biomarker

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