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| 1 | Jixuecao(Herba Centellae Asiaticae) alleviates mesangial cell proliferation in IgA nephropathy by inducing mitofusin 2 expression显示文摘OBJECTIVE:To investigate the effect of mitofusin 2 (Mfn2) and its downstream signaling pathway on glomerular mesangial cells (GMCs) proliferation in IgA nephropathy (IgAN),as well as the mechanism of action of Jixuecao (Herba Centellae Asiaticae,HCA) in the treatment of IgAN.METHODS:Adenovirus-mediated Mfn2 gene transfection and Mfn2 expression were analyzed by real-time polymerase chain reaction (PCR) and Western blotting.IgA1 induced the proliferation of GMCs,which were then treated with HCA.Cell proliferation was detected with cell counting kit-8 (CCK-8),and Mfn2 expression was analyzed by real-time PCR and western blotting.An IgAN animal model was also established and treated with HCA.GMCs proliferation was detected by hematoxylin-eosin staining,mitochondrial structure was analyzed by electron microscopy,mitochondrial function was determined by the Clark oxygen electrode method,and the expression of Mfn2,Phospho-extracellular regulated protein kinases1/2 (P-ERK1/2),Cyclin-dependent kinase 2 (CDK2),Phospho-p27 (p-p27),and cyclin A was analyzed by Western blotting.RESULTS:In vitro,HCA inhibited GMCs in a concentration-dependent manner in association with the upregulation of Mfn2 expression.The overexpression of Mfn2 inhibited IgA1-induced GMCs proliferation and elevated the effect of HCA.In vivo,treatment with HCA could alleviate albuminuria and creatinine and GMCs proliferation.These effects were related to the upregulation of Mfn2,p-p27 and inhibition of p-ERK1/2,CDK2,and cyclinA.Mitochondrial swelling,vacuolar degeneration,and reduction of respiratory control rate were identified in IgAN,but HCA could improve the mitochondrial structure and function.CONCLUSION:HCA inhibited GMCs proliferation via the upregulation Mfn2 and the inhibition of Ras-Raf-ERK/MAPK.We revealed that changes of mitochondrial structure and function are associated with IgAN,but that HCA can improve these mitochondrial features. | Chen Hongyu Du Yuanyuan Li Yayu Zeng Jiali Miao Jianxia Jiang Xue | 2019 | Journal of Traditional Chinese Medicine2019，39，3： | 6 |
| 2 | Self-propagating high-temperature synthesis of ZrO_2 incorporated Gd_2Ti_2O_7 pyrochlore显示文摘In this research, Zr-doped Gd_2Ti_2O_7 pyrochlores, with the composition of Gd_2(Ti_(1-x)Zr_x)_2O_7, were firstly synthesized by self-propagating high-temperature synthesis plus quick pressing(SHS/QP) using CuO as the oxidant and Ti as the reductant. To improve the radiation resistance of titanate–pyrochlore, up to 35 at% Zr was incorporated to substitute the Ti site of Gd_2Ti_2O_7 pyrochlore(Gd_2(Ti_(0.75)Zr_(0.35))_2O_7). XRD and SEM microstructural characterizations showed the formation of a composite ceramic with the major pyrochlore phase and the minor Cu phase. The generated temperature of samples decreased from 1702to 1011 ℃ with increasing Zr content. The effects of sintering temperature and pressure time on phase composition and microstructure were systematically studied. Besides, the influence of thermal transmission on the whole combustion process was also explored. The pyrochlore-based waste form possessed high bulk density of 6.25 g/cm^3 and Vickers hardness of 10.81 GPa. The MCC-1 leaching test showed the normalized elemental leaching rates(42d) of Cu, Gd, and Zr are 1.27×10^(-2), 1.33×10^(-3), and 8.44×10^(-7)g·m^(-2)·d^(-1), respectively. | Le PENG Kuibao ZHANG Zongsheng HE Dan YIN Jiali XUE Chen XU Haibin ZHANG | 2018 | Journal of Advanced Ceramics2018，7，1： | 5 |
| 3 | Sex-determining region Y box-containing genes: regulators and biomarkers in gynecological cancers显示文摘Sex-determining region Y box-containing genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis.Sex-determining region Y box-containing genes have also been shown to act as regulators and biomarkers in the progression of many different cancers, including gynecological cancers such as ovarian, cervical,and endometrial cancer.In this review, we summarize the contrasting regulatory roles of Sex-determining region Y box-containing genes in different gynecological cancers, as promotors with high expression levels or as suppressors with low expression levels.Expression levels of Sex-determining region Y box-containing genes were also identified as biomarkers of clinical features, including International Federation of Gynecology and Obstetrics stage, histopathologic grade together with disease-free survival, and treatment efficacy in patients with gynecological cancers.An understanding of the mechanisms whereby Sex-determining region Y box-containing genes regulate the progression of gynecological cancers will aid in the development of novel diagnostic and therapeutic strategies, while analysis of Sex-determining region Y box-containing expression levels will help to predict the prognosis of patients with gynecological cancers. | Jiali Hu Ke Li Zhanghuan Li Chao Gao Fei Guo Yingmei Wang Fengxia Xue | 2019 | Cancer Biology & Medicine2019，16，3： | 4 |
| 4 | Combustion synthesis and characterizations of Sm2O3 doped zirconolite-rich waste forms with CuO as oxidant显示文摘Zirconolite is one of the most important matrix materials for nuclear waste immobilization.In this study,Sm was employed as the surrogate of trivalent actinides.Sm-doped zirconolite-rich waste forms were readily prepared by combustion synthesis(CS)using CuO as the oxidant.Two different schemes with or without Al2O3 as the charge compensator were carried out simultaneously.The results demonstrate that Al2O3 addition results in complex phase composition.On the other hand,the samples without Al2O3 addition show desirable products of zirconolite and pyrochlore.The EDX analysis shows that Sm is concurrently incorporated into the Ca and Zr sites of zirconolite,which transforms to pyrochlore structure with high Sm2O3 contents.The aqueous durability of representative Sm-doped sample(Sm-0.6)was investigated.The 42 days normalized leaching rate of Sm is as low as 6.41×10-7 g/(m2 d),which exhibits high durability of Sm-doped sample. | Kuibao Zhang Dan Yin Zongsheng He Jiali Xue Wenwen Zhao Haibin Zhang | 2019 | Journal of Rare Earths2019，37，12： | 2 |
| 5 | Combination of magnesium ions and vitamin C alleviates synovitis and osteophyte formation in osteoarthritis of mice显示文摘Introduction:We previously demonstrated that magnesium ions(Mg^(2+))was a novel therapeutic alternative for osteoarthritis(OA)through promoting the hypoxia inducible factor-1α(HIF-1α)-mediated cartilage matrix synthesis.However,oxidative stress can inhibit the expression of HIF-1α,amplify the inflammation that potentially impairs the therapeutic efficacy of Mg^(2+) in OA.Vitamin(VC),a potent antioxidant,may enhance the efficacy of Mg^(2+) in OA treatment.This study aims to investigate the efficacy of combination of Mg^(2+)and VC on alleviating joint destruction and pain in OA.Material and methods:Anterior cruciate ligament transection with partial medial meniscectomy induced mice OA model were randomly received intra-articular injection of either saline,MgCl2(0.5 mol/L),VC(3 mg/ml)or MgCl2(0.5 mol/L)plus VC(3 mg/ml)at week 2 post-operation,twice weekly,for 2 weeks.Joint pain and pathological changes were assessed by gait analysis,histology,western blotting and micro-CT.Results:Mg^(2+) and VC showed additive effects to significantly alleviate the joint destruction and pain.The efficacy of this combined therapy could sustain for 3 months after the last injection.We demonstrated that VC enhanced the promotive effect of Mg^(2+) on HIF-1αexpression in cartilage.Additionally,combination of Mg^(2+) and VC markedly promoted the M2 polarization of macrophages in synovium.Furthermore,combination of Mg^(2+) and VC inhibited osteophyte formation and expressions of pain-related neuropeptides.Conclusions:Intra-articular administration of Mg^(2+)and VC additively alleviates joint destruction and pain in OA.Our current formulation may be a cost-effective alternative treatment for OA. | Hao Yao Jiankun Xu Jiali Wang Yifeng Zhang Nianye Zheng Jiang Yue Jie Mi Lizhen Zheng Bingyang Dai Wenhan Huang Shuhang Yung Peijie Hu Yechun Ruan Qingyun Xue Kiwai Ho Ling Qin | 2021 | Bioactive Materials2021，6，5： | 1 |
| 6 | Dimension-Enhanced Ultra-High Performance Liquid Chromatography/Ion Mobility-Quadrupole Time-of-Flight Mass Spectrometry Combined with Intelligent Peak Annotation for the Rapid Characterization of the Multiple Components from Seeds of Descurainia sophia显示文摘The complex composition of herbal metabolites necessitates the development of powerful analytical techniques aimed to identify the bioactive components.The seeds of Descurainia sophia(SDS)are utilized in China as a cough and asthma relieving agent.Herein,a dimension-enhanced integral approach,by combining ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry(UHPLC/IMQTOF-MS)and intelligent peak annotation,was developed to rapidly characterize the multicomponents from SDS.Good chromatographic separation was achieved within 38 min on a UPLC CSH C18(2.1×100 mm,1.7μm)column which was eluted by 0.1%formic acid in water(water phase)and acetonitrile(organic phase).Collision-induced dissociation-MS^(2)data were acquired by the data-independent high-definition MS^(E)(HDMS^(E))in both the negative and positive electrospray ionization modes.A major components knockout strategy was applied to improve the characterization of those minor ingredients by enhancing the injection volume.Moreover,a self-built chemistry library was established,which could be matched by the UNIFI software enabling automatic peak annotation of the obtained HDMS^(E)data.As a result of applying the intelligent peak annotation workflows and further confirmation process,a total of 53 compounds were identified or tentatively characterized from the SDS,including 29 flavonoids,one uridine derivative,four glucosides,one lignin,one phenolic compound,and 17 others.Notably,four-dimensional information related to the structure(e.g.,retention time,collision cross section,MS^(1)and MS^(2)data)was obtained for each component by the developed integral approach,and the results would greatly benefit the quality control of SDS. | Simiao Wang Xue Li Boxue Chen Shitong Li Jiali Wang Jing Wang Mingshuo Yang Xiaoyan Xu Hongda Wang Wenzhi Yang | 2022 | Phyton-International Journal of Experimental Botany2022，91，3： | 1 |
| 7 | Structural basis of nucleosome deacetylation and DNA linker tightening by Rpd3S histone deacetylase complex显示文摘In Saccharomyces cerevisiae,cryptic transcription at the coding region is prevented by the activity of Sin3 histone deacetylase(HDAC)complex Rpd3S,which is carried by the transcribing RNA polymerase Ⅱ(RNAPⅡ)to deacetylate and stabilize chromatin.Despite its fundamental importance,the mechanisms by which Rpd3S deacetylates nucleosomes and regulates chromatin dynamics remain elusive.Here,we determined several cryo-EM structures of Rpd3S in complex with nucleosome core particles(NCPs),including the H3/H4 deacetylation states,the alternative deacetylation state,the linker tightening state,and a state in which Rpd3S co-exists with the Hho1 linker histone on NCP.These structures suggest that Rpd3S utilizes a conserved Sin3 basic surface to navigate through the nucleosomal DNA,guided by its interactions with H3K36 methylation and the extra-nucleosomal DNA linkers,to target acetylated H3K9 and sample other histone tails.Furthermore,our structures illustrate that Rpd3S reconfigures the DNA linkers and acts in concert with Hho1 to engage the NCP,potentially unraveling how Rpd3S and Hho1 work in tandem for gene silencing. | Shuqi Dong Huadong Li Meilin Wang Nadia Rasheed Binqian Zou Xijie Gao Jiali Guan Weijie Li Jiale Zhang Chi Wang Ningkun Zhou Xue Shi Mei Li Min Zhou Junfeng Huang He Li Ying Zhang Koon Ho Wong Xiaofei Zhang William Chong Hang Chao Jun He | 2023 | Cell Research2023，33，10： | 1 |
| 8 | Intrinsic PD-L1 promotes antitumor activity of CD8^(+)cytotoxic T lymphocytes via in cis interaction with CD80显示文摘Dear Editor,Programmed cell death-ligand 1(PD-L1)on tumor cells can inhibit CD8+cytotoxic T lymphocyte(CTL)-mediated antitumor response by trans-engagement with programmed death protein 1(PD-1).Besides tumor cells,PD-L1 is expressed on T cells.However,the intrinsic role of PD-L1 in T cells has not been widely studied.PD-L1 expression is essential for the survival of activated CD8+T cells,and PD-L1 blockade at the contraction stage reduced the number of effector T cells[1].CD8+T cell responses to influenza virus infection were also impaired in PD-L1-deficient mice[2]. | Yuming Ding Chaojia Chen Shuaiya Ma Xue Sheng Fangcheng Zhao Jiali Peng Haoqing Dong Chunhong Ma Chunyang Li | 2022 | Cancer Communications2022，42，8： | 0 |
| 9 | Photometric Redshifts and Galaxy Clusters for DES DR2, DESI DR9, and HSC-SSP PDR3 Data显示文摘Photometric redshift(photoz)is a fundamental parameter for multi-wavelength photometric surveys,while galaxy clusters are important cosmological probes and ideal objects for exploring the dense environmental impact on galaxy evolution.We extend our previous work on estimating photoz and detecting galaxy clusters to the latest data releases of the Dark Energy Spectroscopic Instrument(DESI)imaging surveys,Dark Energy Survey(DES)and Hyper Suprime-Cam Subaru Strategic Program(HSC-SSP)imaging surveys and make corresponding catalogs publicly available for more extensive scientific applications.The photoz catalogs include accurate measurements of photoz and stellar mass for about 320,293and 134 million galaxies with r<23,i<24 and i<25 in DESI DR9,DES DR2 and HSC-SSP PDR3 data,respectively.The photoz accuracy is about 0.017,0.024 and 0.029 and the general redshift coverage is z<1,z<1.2 and z<1.6,respectively for those three surveys.The uncertainty of the logarithmic stellar mass that is inferred from stellar population synthesis fitting is about 0.2 dex.With the above photoz catalogs,galaxy clusters are detected using a fast cluster-finding algorithm.A total of 532,810,86,963 and 36,566 galaxy clusters with the number of members larger than 10 is discovered for DESI,DES and HSC-SSP,respectively.Their photoz accuracy is at the level of 0.01.The total mass of our clusters is also estimated by using the calibration relations between the optical richness and the mass measurement from X-ray and radio observations.The photoz and cluster catalogs are available at Science DB(https://www.doi.org/10.11922/sciencedb.o00069.00003)and Paper Data Repository(https://doi.org/10.12149/101089). | Hu Zou Jipeng Sui Suijian Xue Xu Zhou Jun Ma Zhimin Zhou Jundan Nie Tianmeng Zhang Lu Feng Zhixia Shen Jiali Wang | 2022 | Research in Astronomy and Astrophysics2022，22，6： | 0 |
| 10 | Integrated Metabolomics and Transcriptomics Analyses Reveal Metabolic Landscape in Neuronal Cells during JEV Infection显示文摘Japanese encephalitis virus(JEV) is a leading cause of viral encephalitis in endemic regions of Asia. The neurotropism of JEV and its high-efficiency replication in neurons are the key events for pathogenesis. Revealing the interplay between virus and host cells in metabolic facet is of great importance both for unraveling the pathogenesis mechanisms and providing novel antiviral targets. This study took advantage of the integration analysis of metabolomics and transcriptomics to depict the metabolic profiles of neurons during the early stage of JEV infection. Increased glycolysis and its branched pentose phosphate pathway(PPP) flux and impaired oxidative phosphorylation(OXPHOS) in glucose utilization,and the catabolic patterns of lipid metabolism were created to facilitate the biosynthesis of precursors needed for JEV replication in neurons. Pharmacological inhibitions of both glycolysis pathway and PPP in neurons suggested its indispensable role in maintaining the optimal propagation of JEV. In addition, analysis of metabolomic-transcriptomic regulatory network showed the pivotal biological function of lipid metabolism during JEV infection. Several pro-inflammatory lipid metabolites were significantly up-regulated and might partially be responsible for the progression of encephalitis.These unique metabolic reprogramming features might give deeper insight into JEV infected neurons and provide promising antiviral approaches targeting metabolism. | Mengyuan Li Jiali Yang Chuantao Ye Peiyu Bian Xiaofei Yang Haijun Zhang Chuanyu Luo Zhifeng Xue Yingfeng Lei Jianqi Lian | 2021 | Virologica Sinica2021，36，6： | 0 |
| 11 | Correction to: Integrated Metabolomics and Transcriptomics Analyses Reveal Metabolic Landscape in Neuronal Cells During JEV Infection显示文摘Correction to:Virologica Sinica https://doi.org/10.1007/s12250-021-00445-0 In the original version of this article,one image in Fig.4 was accidently duplicated during figure layout and the dilution rate was mislabeled. | Mengyuan Li Jiali Yang Chuantao Ye Peiyu Bian Xiaofei Yang Haijun Zhang Chuanyu Luo Zhifeng Xue Yingfeng Lei Jianqi Lian | 2021 | Virologica Sinica2021，36，6： | 0 |
| 12 | RNA sequencing-based optimization of biological lipid droplets for sonodynamic therapy to reverse tumor hypoxia and elicit robust immune response显示文摘Mitochondria-targeted sonodynamic therapy(SDT)is a promising strategy to inhibit tumor growth and activate the anti-tumor immune responses.Identifying the mechanisms underlying mitochondria-targeted SDT,further optimizing its efficacy,developing novel sonosensitizer carriers with good biocompatibility pose major challenges to the clinical practice of SDT.In this study,we investigated the mechanisms of mitochondria-targeted SDT and demonstrated that it suppressed the mitochondrial electron transport chain(ETC)in pancreatic cancer cells through RNA-sequencing analysis.Based on these findings,we constructed the functional lipid droplets(LDs)(CPI-613/IR780@LDs),which combined mitochondria-targeted SDT with the tricarboxylic acid(TCA)cycle inhibitor CPI-613.CPI-613/IR780@LDs synergistically inhibited the TCA cycle and the ETC of mitochondrial aerobic respiration to reduce oxygen consumption and increase reactive oxygen species(ROS)generation at the tumor site,thus enhancing the efficacy of SDT in hypoxic pancreatic cancer.Moreover,the combination of mitochondria-targeted SDT and anti-PD-1 antibody exhibited excellent tumor inhibition and activated anti-tumor immune responses by increasing tumorinfiltrating CD8+T cells and reducing regulatory T cells,synergistically arresting the growth of both primary and metastatic pancreatic tumors.Meanwhile,lipid droplets are cell-derived biological carriers with natural mitochondrial targeting ability and can achieve efficient hydrophobic drug loading through active phagocytosis.Therefore,the functional lipid droplet-based SDT combined with anti-PD-1 antibody holds great potential in the clinical treatment of hypoxic pancreatic cancer. | Zhan Shi Xue Wang Jiali Luo Yiqing Zeng Qing Wen Yurong Hong Tao Zhang Pintong Huang | 2023 | Nano Research2023，16，5： | 0 |
| 13 | Rapid Profiling and Characterization of the Multicomponents from the Root and Rhizome of Salvia miltiorrhiza by Ultra-High Performance Liquid Chromatography/Ion Mobility-Quadrupole Time-of-Flight Mass Spectrometry in Combination with Computational Peak Annotation Workflows显示文摘Herbal components characterization represents a challenging task because of the co-existing of multiple classes of naturally occurring compounds with wide spans of polarity,molecular mass,and the ubiquitous isomerism.The root and rhizome of Salvia miltiorrhiza have been utilized as a reputable traditional Chinese medicine Salviae Miltiorrhizae Radix et Rhizoma(Dan-Shen)in the treatment of cardiovascular disease.Herein,a dimensionenhanced ultra-high performance liquid chromatography/ion mobility/quadrupole time-of-flight mass spectrometry approach in combination with intelligent peak annotation workflows was established aimed to rapidly characterize the multicomponents from S.miltiorrhiza.Due to the sufficient optimization,satisfactory chromatography separation was enabled on an HSS T3 column within 33 min using 0.1%formic acid in water(A)and acetonitrile(B)as the mobile phase,while the data-independent HDMS^(E) in both the negative and positive electrospray ionization modes was utilized for the high-coverage MS^(2) data acquisition.Streamlined automatic peak annotation by searching an in-house library(recording 198 known compounds)followed by the subsequent confirming steps(e.g.,comparison with the reference compounds,fragmentation pathways analysis,and retention behavior comparison,etc.),allowed us to identify or tentatively characterize a total of 86 components(including 50 terpenoids,21 phenolic acids,and 15 others)from S.miltiorrhiza.Importantly,three-dimensional structure information,such as the retention time,MS^(1) and MS^(2) data,and collision cross section(CCS),was provided,which can facilitate the more reliable characterization of herbal components. | Boxue Chen Hongda Wang Meiyu Liu Wandi Hu Yuexin Qian Jiali Wang Jie Liu Xue Li Jing Wang Wenzhi Yang | 2022 | Phyton-International Journal of Experimental Botany2022，91，5： | 0 |
| 14 | CPAL, as a New Mediator of Cardiomyocyte Metabolic Alterations and Pyroptosis, Regulates Myocardial Infarction Injury in Mice显示文摘Myocardial infarction (MI), the most serious of the ischemic heart diseases, is accompanied by myocardial metabolic disorders and the loss of cardiomyocytes. Increasing evidence has shown that long noncoding RNAs (lncRNAs) are involved in various pathological conditions such as cancer and cardiovascular diseases (CVDs), and are emerging as a novel biomarker for these disorders. This study aims to investigate the regulatory role and mechanisms of lncRNAs in myocardial remodeling in the setting of MI. We find that post-infarcted hearts exhibit a reduction of adenosine triphosphate (ATP) and an alteration of the glucose and lipid metabolism genes cluster of differentiation 36 (CD36), hexokinase 1 (HK1), and clucose transporter 4 (GLUT4), accompanied by cardiomyocyte pyroptosis. We then identify a previously unknown conserved lncRNA, AK009126 (cardiomyocyte pyroptosis-associated lncRNA, CPAL), which is remarkably upregulated in the myocardial border zone of MI mice. Importantly, the adeno-associated virus 9 (AAV9)-mediated silencing of endogenous CPAL by its short hairpin RNA (shRNA) partially abrogates myocardial metabolic alterations and cardiomyocyte pyroptosis during MI in mice. Mechanistically, CPAL is shown to bind directly to nuclear factor kappa B (NFκB) and to act as an activator of NFκB to induce NFκB phosphorylation in cardiomyocytes. We also find that CPAL upregulates caspase-1 expression at the transcriptional level and consequently promotes the release of interleukin (IL)-18 and IL-1β from cardiomyocytes. Collectively, our findings reveal the conserved lncRNA CPAL as a new regulator of cardiac metabolic abnormalities and cardiomyocyte pyroptosis in the setting of MI and suggest CPAL as a new therapeutic target to protect cardiomyocytes against ischemic injury in infarcted hearts. | Jiamin Li Hongru Xue Ning Xu Liling Gong Ming Li Sijia Li Di Huang Qingwei Zhang Pengyu Li Qingsui Li Hang Yu Yining Liu Yadong Xue Haixin Chen Jiali Liu Wanyu Zhang Mingbin Liu Siyu Chang Xianzhi Lang Xingmiao Zhao Weijie Du Benzhi Cai Ning Wang Baofeng Yang | 2023 | Engineering2023，，1： | 0 |
| 15 | 神经细胞内新型谷氨酸生物合成通路参与日光照射改善学习记忆显示文摘文章简介日光照射可以影响情绪、学习以及认知等神经系统相关行为。然而,其分子和细胞水平的机制仍然不清楚。本研究揭示了适度的紫外线照射可提高血液中的尿刊酸水平,随后尿刊酸会透过血脑屏障进入大脑。接下来,研究人员用自主研发的单细胞质谱技术并与同位素示踪技术相结合. | 朱洪影 王宁 Lei Yao Qi Chen Ran Zhang Junchao Qian Yiwen Hou Weiwei Guo Sijia Fan Siling Liu Qiaoyun Zhao Feng Du Xin Zuo Yujun Guo Yan Xu Jiali Li Tian Xue Kai Zhong Xiaoyuan Song 黄光明 熊伟 | 2019 | 科学新闻2019，0，2： | 0 |
| 16 | The optimal anticoagulation strategy for COVID-19,prophylactic or therapeutic?:a meta-analysis,trial sequential analysis,and meta-regression of more than 27,000 participants显示文摘Background:Anticoagulants are promising regimens for treating coronavirus disease 2019(COVID-19).However,whether prophylactic or intermediate-to-therapeutic dosage is optimal remains under active discussion.Methods:We comprehensively searched PubMed,Embase,Scopus,Web of Science,Cochrane Library,ClinicalTrials,and MedRxiv databases on April 26,2022.Two independent researchers conducted literature selection and data extraction separately according to predetermined criteria.Notably,this is the first meta-analysis on COVID-19,taking serious consideration regarding the dosage overlap between the 2 comparison groups of prophylactic anticoagulation(PA)and intermediate-to-therapeutic anticoagulation(I-TA).Results:We included 11 randomized controlled trials(RCTs)and 36 cohort studies with 27,051 COVID-19 patients.By analyzing all the RCTs,there was no significant difference in mortality between the PA and I-TA groups,which was further confirmed by trial sequential analysis(TSA)(odds ratio[OR]:0.93;95%confidence interval[CI]:0.71–1.22;P=0.61;TSA adjusted CI:0.71–1.26).The rate of major bleeding was remarkably higher in the I-TA group than in the PA group,despite adjusting for TSA(OR:1.73;95%CI:1.15–2.60;P=0.009;TSA adjusted CI:1.09–2.58).RCTs have supported the beneficial effect of I-TA in reducing thrombotic events.After including all studies,mortality in the I-TA group was significantly higher than in the PA group(OR:1.38;95%CI:1.15–1.66;P=0.0005).The rate of major bleeding was similar to the analysis from RCTs(OR:2.24;95%CI:1.86–2.69;P<0.00001).There was no distinct difference in the rate of thrombotic events between the 2 regimen groups.In addition,in both critical and noncritical subgroups,I-TA failed to reduce mortality but increased major bleeding rate compared with PA,as shown in meta-analysis of all studies,as well as RCTs only.Meta-regression of all studies suggested that there was no relationship between the treatment effect and the overall risk of mortality or major bleeding(P=0.14,P=0.09,respectively).Conclusion:I-TA is not superior to PA for treating COVID-19 because it fails to lower the mortality rate but increases the major bleeding rate in both critical and noncritical patients. | Mingyue Guo Qi Han Jiaxuan Xing Feng Xu Jiali Wang Chuanbao Li Zechen Shan Yuan Bian Hao Wang Li Xue Qiuhuan Yuan Chang Pan Yanshan De Xingfang Wang Panpan Hao Shengchuan Cao Jiaojiao Pang Yuguo Chen | 2022 | Emergency and Critical Care Medicine2022，2，3： | 0 |
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