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Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia

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Frontiers of Medicine 2024年第2期18卷 327-343页

作者： Niu Qiao Yizhu Lyu Feng Liu Yuliang zhang Xiaolin Ma Xiaojing Lin Junyu Wang Yinyin Xie Ruihong zhang Jing Qiao Hongming Zhu Li Chen Hai Fang tong Yin Zhu Chen Qiang Tian Saijuan Chen Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Second Hospital of Dalian Medical UniversityDalian116021China

The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine research.Though an altered microenvironment is a general cancer hallmark,how APL blasts shape their plasma composition is poorly understood.Here,we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters,proteomes,and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy.Our study revealed the two prominent features of the APL plasma,suggesting a possible involvement of APL blasts in modulating plasma composition.One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts,and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA.Furthermore,results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage,which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins.Overall,our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

关键词： acute promyelocytic leukemia plasma proteomics plasma metabolomics cross-sectional correlation network pathogenesis treatment

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An Algorithm for Short-Circuit Current Interval in Distribution Networks with Inverter Type Distributed Generation Based on Affine Arithmetic

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Energy Engineering 2024年第7期121卷 1903-1920页

作者： Yan zhang Bowen Du Benren Pan GuannanWang Guoqiang Xie tong Jiang Electric Power Research Institute State Grid Jiangxi Electric Power Co.Ltd.Nanchang330096China School of Electrical and Electronic Engineering North China Electric Power UniversityBeijing102206China

During faults in a distribution network,the output power of a distributed generation(DG)may be uncertain.Moreover,the output currents of distributed power sources are also affected by the output power,resulting in uncertainties in the calculation of the short-circuit current at the time of a fault.Additionally,the impacts of such uncertainties around short-circuit currents will increase with the increase of distributed power sources.Thus,it is very important to develop a method for calculating the short-circuit current while considering the uncertainties in a distribution network.In this study,an affine arithmetic algorithm for calculating short-circuit current intervals in distribution networks with distributed power sources while considering power fluctuations is presented.The proposed algorithm includes two stages.In the first stage,normal operations are considered to establish a conservative interval affine optimization model of injection currents in distributed power sources.Constrained by the fluctuation range of distributed generation power at the moment of fault occurrence,the model can then be used to solve for the fluctuation range of injected current amplitudes in distributed power sources.The second stage is implemented after a malfunction occurs.In this stage,an affine optimization model is first established.This model is developed to characterizes the short-circuit current interval of a transmission line,and is constrained by the fluctuation range of the injected current amplitude of DG during normal operations.Finally,the range of the short-circuit current amplitudes of distribution network lines after a short-circuit fault occurs is predicted.The algorithm proposed in this article obtains an interval range containing accurate results through interval operation.Compared with traditional point value calculation methods,interval calculation methods can provide more reliable analysis and calculation results.The range of short-circuit current amplitude obtained by this algorithm is slightly larger than

关键词： Short circuit calculation inverter type distributed power supplies affine arithmetic distribution network

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Enhancing zinc-air battery performance by constructing threedimensional N-doped carbon coating multiple valence Co and MnO heterostructures

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Nano Research 2024年第6期17卷 5104-5113页

作者： Qi Liu Panzhe Qiao Miaomiao tong Ying Xie Xinxin zhang Kuo Lin Zhijian Liang Lei Wang Honggang Fu Key Laboratory of Superlight Materials and Surface Technology of the Ministry of Education of the People’s Republic of China Harbin Engineering UniversityHarbin 150080China Key Laboratory of Functional Inorganic Material Chemistry Ministry of Education of the People’s Republic of China Heilongjiang UniversityHarbin 150080China Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201204China

Developing highly-efficient bifunctional oxygen evolution reaction(OER)and oxygen reduction reaction(ORR)electrocatalysts is crucial for the widespread application of rechargeable Zn-air batteries(ZABs).Herein,an efficiency electrodeposition and pyrolytic strategy to synthesize the three-dimensional(3D)N-doped carbon coating multiple valence Co and MnO heterostructures supported on carbon cloth substrate(Co-MnO@NC/CC).It contains Co-Co,Co-N,and Co-O bonds,which synergistically enhance the oxygen reaction activity with MnO.It exhibits a working potential of 1.473 V at 10 mA·cm^(−2)for OER and onset potential of 0.97 V for ORR.Theory calculations demonstrate that the synergy between cobalt and manganese species could optimize the d-band center and reduce the energy barrier of Co-MnO@NC/CC for both OER and ORR processes.Besides,the MnO acts as the main OER active site could significantly optimize the energy barrier of O*→OOH*,thus further promoting the OER activity.It can be directly used as the air-cathode for both liquid-state and solid-state ZABs,which could afford a small voltage gap of 0.75 V at 10 mA·cm^(−2),a high power density of 172.5 mW·cm^(−2)and a long-term durability for 400 h,surpassing those of the Pt/C+RuO_(2)-based ZAB.Importantly,the assembled batteries show potential applications in portable devices.

关键词： heterostructure synergy valence cobalt manganese oxide Zn-air battery

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Development of a droplet digital polymerase chain reaction assay for the sensitive detection of total and integrated HIV-1 DNA

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Chinese Medical Journal 2024年第6期137卷 729-736页

作者： Lin Yuan Zhiying Liu Xin zhang Feili Wei Shan Guo Na Guo Lifeng Liu Zhenglai Ma Yunxia Ji Rui Wang Xiaofan Lu Zhen Li Wei Xia Hao Wu tong zhang Bin Su Beijing Key Laboratory for HIV/AIDS Research Clinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:Total human immunodeficiency virus(HIV)DNA and integrated HIV DNA are widely used markers of HIV persistence.Droplet digital polymerase chain reaction(ddPCR)can be used for absolute quantification without needing a standard curve.Here,we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.Methods:The limit of detection,dynamic ranges,sensitivity,and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat(LTR)and human CD3 gene(for total HIV DNA)and ACH-2 cells(for integrated HIV DNA).Forty-two cases on stable suppressive antiretroviral therapy(ART)were assayed in total HIV DNA and integrated HIV DNA.Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive(CD4^(+))T-cell counts,CD8^(+)T-cell counts and CD4/CD8 T-cell ratio,respectively.The assay linear dynamic range and lower limit of detection(LLOD)were also assessed.Results:The assay could detect the presence of HIV-1 copies 100%at concentrations of 6.3 copies/reaction,and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction(95%confidence intervals[CI]:3.6-6.5 copies/reaction)with linearity over a 5-log_(10)-unit range in total HIV DNA assay.For the integrated HIV DNA assay,the LLOD was 8.0 copies/reaction(95%CI:5.8-16.6 copies/reaction)with linearity over a 3-log 10-unit range.Total HIV DNA in CD4^(+)T cells was positively associated with integrated HIV DNA(r=0.76,P<0.0001).Meanwhile,both total HIV DNA and integrated HIV DNA in CD4^(+)T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8^(+)T-cell counts.Conclusions:This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity.It can be readily adapted for measuring HIV DNA with non-B clades,and it could be beneficial for testing in clinical trials.

关键词： Human immunodeficiency virus HIV Integrated HIV-1 DNA Total HIV DNA Droplet digital polymerase chain reaction HIV reservoir Antiretroviral therapy

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Generation of mitochondrial replacement monkeys by female pronucleus transfer

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Zoological Research 2024年第2期45卷 292-298页

作者： Chun-Yang Li Xing-Chen Liu Yu-Zhuo Li Yan Wang Yan-Hong Nie Yu-Ting Xu Xiao-tong zhang Yong Lu Qiang Sun Institute of Neuroscience Center for Excellence in Brain Science and Intelligence TechnologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai 200031China Key Laboratory of Genetic Evolution and Animal Models Chinese Academy of SciencesKunming 650201China University of Chinese Academy of Sciences Beijing 100049China

Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe disorders.Mitochondrial replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA diseases.While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously reported.In this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear transfer.These individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during development.The successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

关键词： Non-human primates Mitochondrial replacement Female pronuclear transfer

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Application and mechanisms of Sanhua Decoction in the treatment of cerebral ischemia-reperfusion injury

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World Journal of Clinical Cases 2024年第4期12卷 688-699页

作者： Ya-Kuan Wang Huang Lin Shu-Rui Wang Ru-Tao Bian Yang tong Wen-Tao zhang Ying-Lin Cui Department of Encephalopathy The Second Clinical College of Henan University of Chinese MedicineZhengzhou 450000Henan ProvinceChina Department of Encephalopathy Henan Provincial Hospital of Integrated Chinese and Western MedicineZhengzhou 450000Henan ProvinceChina Department of Traditional Chinese Medicine Classics Henan Provincial Hospital of Traditional Chinese Medicine(The Second Affiliated Hospital of Henan University of Chinese Medicine)Zhengzhou 450000Henan ProvinceChina Department of Central Laboratory Zhengzhou Traditional Chinese Medicine HospitalZhengzhou 450000Henan ProvinceChina Department of Encephalopathy Henan Provincial Hospital of Traditional Chinese Medicine(The Second Affiliated Hospital of Henan University of Chinese Medicine)Zhengzhou 450000Henan ProvinceChina Famous Doctor Hall Henan Provincial Hospital of Traditional Chinese Medicine(The Second Affiliated Hospital of Henan University of Chinese Medicine)Zhengzhou 450000Henan ProvinceChina

Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system.,and has accordingly been a focus of extensive clinical research.As a traditional Chinese medicinal formulation,Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases.Its main constituents include Citrus aurantium,Magnolia officinalis,rhubarb,and Qiangwu,which are primarily used to regulate qi.In the treatment of neurological diseases,the therapeutic effects of the Sanhua Decoction are mediated via different pathways,including antioxidant,anti-inflammatory,and neurotransmitter regu-latory pathways,as well as through the protection of nerve cells and a reduction in cerebral edema.Among the studies conducted to date,many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects.In addition,as a natural treatment,the Sanhua Decoction has received widespread attention,given that it is safer and more effective than traditional Western medicines.Consequently,research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance.In this paper,we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction.We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion,and provide a scientific basis for its application in clinical practice.

关键词： Sanhua Decoction Cerebral ischemia-reperfusion Mechanism of action Application progress Traditional Chinese medical science Review

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Graphene binding on black phosphorus enables high on/off ratios and mobility

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National Science Review 2024年第2期11卷 188-195页

作者： Fanrong Lin Zhonghan Cao Feiping Xiao Jiawei Liu Jiabin Qiao Minmin Xue Zhili Hu Ying Liu Huan Lu Zhuhua zhang Jens Martin Qingjun tong Wanlin Guo Yanpeng Liu Key Laboratory for Intelligent Nano Materials and Devices of Ministry of Education State Key Laboratory of Mechanics and Control of Mechanical Structures and Institute for Frontier Science Nanjing University of Aeronautics and Astronautics Centre for Advanced 2D Materials National University of Singapore School of Physics and Electronics Hunan University Centre for Quantum Physics Key Laboratory of Advanced Optoelectronic Quantum Architecture and MeasurementSchool of PhysicsBeijing Institute of Technology Leibniz Institute für Kristallzüchtung

Graphene is one of the most promising candidates for integrated circuits due to its robustness against short-channel effects, inherent high carrier mobility and desired gapless nature for Ohmic contact, but it is difficult to achieve satisfactory on/off ratios even at the expense of its carrier mobility, limiting its device applications. Here, we present a strategy to realize high back-gate switching ratios in a graphene monolayer with well-maintained high mobility by forming a vertical heterostructure with a black phosphorus multi-layer. By local current annealing, strain is introduced within an established area of the graphene, which forms a reflective interface with the rest of the strain-free area and thus generates a robust off-state via local current depletion. Applying a positive back-gate voltage to the heterostructure can keep the black phosphorus insulating, while a negative back-gate voltage changes the black phosphorus to be conductive because of hole accumulation. Then, a parallel channel is activated within the strain-free graphene area by edge-contacted electrodes, thereby largely inheriting the intrinsic carrier mobility of graphene in the on-state. As a result, the device can provide an on/off voltage ratio of >10～3 as well as a mobility of ～8000 cm2V-1s-1at room temperature, meeting the low-power criterion suggested by the International Roadmap for Devices and Systems.

关键词： graphene on/offratio mobility black phosphorus reflective interface

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Prognostic value of cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis:A systematic review and meta-analysis

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Cancer Innovation 2024年第3期3卷 22-32页

作者： Wenhua Song Nan zhang tonglian Lv Yang Zhao Guangping Li Gary Tse tong Liu Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of CardiologySecond Hospital of Tianjin Medical UniversityTianjinChina Department of Radiology Second Hospital of Tianjin Medical UniversityTianjinChina School of Nursing and Health Studies Hong Kong Metropolitan UniversityHong KongChina Cardiac Electrophysiology Unit Cardiovascular Analytics GroupPowerHealth LimitedHong KongChina

Background:The role of surgery in metastatic breast cancer(MBC)is currently controversial.Several novel statistical and deep learning(DL)methods promise to infer the suitability of surgery at the individual level.Objective:The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required.Methods:We introduced the deep survival regression with mixture effects(DSME),a semi-parametric DL model integrating three causal inference methods.Six models were trained to make individualized treatment recommendations.Patients who received treatments in line with the DL models'recommendations were compared with those who underwent treatments divergent from the recommendations.Inverse probability weighting(IPW)was used to minimize bias.The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference.Results:In total,5269 female patients with MBC were included.DSME was an independent protective factor,outperforming other models in recommend-ing surgery(IPW-adjusted hazard ratio[HR]=0.39,95%confidence interval[CI]:0.19–0.78)and type of surgery(IPW-adjusted HR=0.66,95%CI:0.48–0.93).DSME was superior to other models and traditional guidelines,suggesting a higher proportion of patients benefiting from surgery,especially breast-conserving surgery.The debiased effect of patient characteristics,including age,tumor size,metastatic sites,lymph node status,and breast cancer subtypes,on surgery decision was also quantified.Conclusions:Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed.This method can facilitate the development of efficient,reliable treatment recommendation systems and provide quantifiable evidence for decision-making.

关键词： breast surgery causal inference deep learning metastatic breast cancer

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General Psychiatry 2024年第1期37卷 73-82页

作者： Qian Lu Sisi Huang Tianjiao zhang Jie Song Manyu Dong Yilun Qian Jing Teng tong Wang Chuan He Ying Shen Department of Rehabilitation Medicine The Affiliated Jiangsu Shengze Hospital of Nanjing Medical UniversitySuzhouChina Rehabilitation Medicine Center The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina

Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences in long-term potentiation(LTP)-like plasticity and short-latency afferent inhibition(SAl)between older and younger individuals,alongside their correlation with cognitive function using transcranial magnetic stimulation(TMS).Methods The cross-sectional study involved 31 younger adults aged 18-30 and 46 older adults aged 60-80.All participants underwent comprehensive cognitive assessments and a neurophysiological evaluation based on TMS.Cognitive function assessments included evaluations of global cognitive function,language,memory and executive function.The neurophysiological assessment included LTP-like plasticity and SAl.Results The findings of this study revealed a decline in LTP among the older adults compared with the younger adults(wald χ^(2)=3.98,p=0.046).Subgroup analysis further demonstrated a significant reduction in SAl level among individuals aged 70-80 years in comparison to both the younger adults(SAI(N20)):(t=-3.37,p=0.018);SAl(N20+4):(t=-3.13,p=0.038)and those aged 60-70(SAl(N20)):(t=3.26,p=0.025);SAl(N20+4):(t=-3.69,p=0.006).Conversely,there was no notable difference in SAl level between those aged 60-70 years and the younger group.Furthermore,after employing the Bonferroni correction,the correlation analysis revealed that only the positive correlation between LTP-like plasticity and language function(r=0.61,p<0.001)in the younger group remained statistically significant.Conclusions During the normal ageing process,a decline in synaptic plasticity may precede cholinergic system dysfunction.In individuals over 60 years of age,there is a reduction in LTP-like plasticity,while a decline in cholinergic system function is observed in those over 70.Thus,the cholinergic system may play a vital role in preventing cognitive decline during normal ageing.In younger individuals,LTP-like plasticit

关键词： function younger plasticity

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Prevention of urinary tract infection using a silver alloy hydrogel-coated catheter in critically ill patients: A single-center prospective randomized controlled study

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Journal of Intensive Medicine 2024年第1期4卷 118-124页

作者： Menglong Zhao Shike Geng Lei zhang Xiaoqin Fan Fei tong Xianlin Meng Tianfeng Wang Xiaowei Fang Qing Mei Aijun Pan Department of Intensive Care Unit The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001AnhuiChina

Background:A new type of silver alloy hydrogel-coated(SAH)catheter has been shown to prevent bacterial adhesion and colonization by generating a microcurrent,and to block the retrograde infection pathway.However,these have only been confirmed in ordinary patients.This study aims to evaluate the effectiveness of a SAH catheter for preventing urinary tract infections in critically ill patients.Methods:This was a prospective single-center,single-blind,randomized,controlled study.A total of 132 patients requiring indwelling catheterization in the intensive care unit(ICU)of the First Affiliated Hospital of the University of Science and Technology of China between October 2022 and February 2023 and who met the study inclusion/exclusion criteria were randomly divided into two groups.Patients in the SAH catheter group received a SAH catheter,while patients in the conventional catheter group received a conventional siliconized latex Foley catheter.The main outcome measure was the incidence of catheter-associated urinary tract infections(CAUTIs).Secondary outcome indicators included urine positivity for white blood cells and positive urine cultures on 3 days,7 days,10 days,and 14 days after catheterization,number of viable bacteria in the catheter biofilm on day 14,pathogenic characteristics of positive urine cultures,length of ICU stay,overall hospital stay,ICU mortality,and 28-day mortality.All the data were compared between the two groups.Results:A total of 68 patients in the conventional catheter group and 64 patients in the SAH catheter group were included in the study.On day 7 after catheter placement,the positivity rate for urinary white blood cells was significantly higher in the conventional catheter group than in the SAH catheter group(33.8%vs.15.6%,P=0.016).On day 10,the rates of positive urine cultures(27.9%vs.10.9%,P=0.014)and CAUTIs(22.1%vs.7.8%,P=0.023)were significantly higher in the conventional catheter group than in the SAH catheter group.On day 14,the numbers of viable bacteria isolated from the cathete

关键词： Catheter coating Effectiveness evaluation Biofilm Catheter-associated urinary tract infection Outcome

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