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Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade

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Signal transduction and targeted therapy 2024年第7期9卷 2936-2952页

作者： Liang Zhao Yizhen Pang Yangfan Zhou Jianhao Chen Hao Fu Wei Guo Weizhi Xu Xin Xue Guoqiang su Long sun Hua Wu Jingjing Zhang Zhanxiang Wang Qin Lin Xiaoyuan Chen Haojun Chen Department of Nuclear Medicine and Minnan PEt Center Xiamen Key Laboratory of RadiopharmaceuticalsThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingaporeSingapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Radiation Oncology Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of Colorectal tumor surgery Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of Cardiothoracic surgery Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingChina Nanomedicine translational Research Program NUS Center for NanomedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Neurosurgery and Department of Neuroscience Fujian Key Laboratory of Brain Tumors Diagnosis and Precision TreatmentXiamen Key Laboratory of Brain Centerthe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstituteChinese Academy of SciencesXiamenChina

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor *** radionuclide therapy delivers radiation directly to tumor ***1004 is a fibroblast activation protein(FAP)-target.ng radiopharmaceutical,conjugated with the albumin binder Evans Blue,which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical ***,we demonstrate that^(68)Ga/^(177)Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3t3-FAP and Ct26/NIH3t3-FAP tumor *** therapy with^(177)Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor *** combination of^(177)Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3t3-FAP tumor-bearing mice,with mice showing 100%tumor rejection upon ***,single-cell RNA sequencing(scRNA-seq),and tCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication,CD8^(+)t-cell activation and expansion,M1 macrophage counts,antitumor activity of neutrophils,and t-cell receptor diversity.A preliminary clinical study demonstrated that^(177)Lu-LNC1004 was well-tolerated and effective in patients with refractory ***,scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade *** was emphasized by the observed increase in antigen processing and presentation juxtaposed with t cell *** conclusion,our data supported the efficacy of immunotherapy combined with^(177)Lu-LNC1004 for cancer patients with FAP-positive tumors.

关键词： immunity retention holds

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taurine attenuates activation of hepatic stellate cells by inhibit.ng autophagy and inducing ferroptosis

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World Journal of Gastroenterology 2024年第15期30卷 2143-2154页

作者： Sen Li Qian-Jun Ren Can-Hao Xie Yang Cui Li-tao Xu Yi-Dan Wang su Li Xing-Qiu Liang Bin Wen Ming-Kun Liang Xiao-Fang Zhao Department of Basic Science Guangxi University of Chinese MedicineNanning 541100Guangxi Zhuang Autonomous RegionChina Department of Science and technology Ruikang Hospital Affiliated to Guangxi University of Chinese MedicineNanning 541100Guangxi Zhuang Autonomous RegionChina traditional Chinese Medicine Specialty Office Ruikang Hospital Affiliated to Guangxi University of Chinese MedicineNanning 541100Guangxi Zhuang Autonomous RegionChina

BACKGROUND Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury,and finally leads to liver cirrhosis or even hepatocellular *** pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells(HSCs),which can transdiffer-entiate into myofibroblasts to produce an excess of the extracellular matrix(ECM).Myofibroblasts are the main source of the excessive ECM responsible for hepatic ***,activated hepatic stellate cells(aHSCs),the principal ECM producing cells in the injured liver,are a promising therapeutic target for the treatment of hepatic *** to explore the effect of taurine on aHSC proliferation and the mechanisms *** Human HSCs(LX-2)were randomly divided into five groups:Normal control group,platelet-derived growth factor-BB(PDGF-BB)(20 ng/mL)treated group,mmol/L,respectively)with PDGF-BB(20 ng/mL)treated *** Count.ng Kit-8 method was performed to evaluate the effect of taurine on the viability of ***-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species(ROS),malondialdehyde,glutathione,and iron *** electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in *** real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression ofα-SMA,Collagen I,Fibronectin 1,LC3B,AtG5,Beclin 1,PtGS2,SLC7A11,and *** taurine promoted the death of aHSCs and reduced the deposition of the *** with taurine could alleviate autophagy in HSCs to inhibit their activation,by decreasing autophagosome formation,downregulat.ng LC3B and Beclin 1 protein expression,and upregulat.ng p62 protein ***,treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized b

关键词： Hepatic stellate cells Autophagy Ferroptosis Molecular docking taurine

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Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective noncomparative study

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1248-1254页

作者： Hai-Shuang Lin Xiao-Ping Xu Xuan-Li Zheng Ji-Bing Wang su-Jie Fan Zuo-HongWu su-Mian Cheng Li-Jun Zhao Qin-Hua Cai Shao-Dan Zhang Shan-Shan Liu Ai-Guo Lyu Ying Zhang Hong Chen Dan-Ni Jiang Wu-Liang Li Nathan Congdon Clement C tham Ming-Guang He Yuan-Bo Liang the Malignant Glaucoma treatmenttrial Study(MGtt)Group Wenzhou Medical University Wenzhou 325027Zhejiang ProvinceChina Ningbo Eye Hospital Ningbo 315100Zhejiang ProvinceChina Weifang Eye Hospital Weifang 261000Shandong ProvinceChina Handan Eye Hospital Handan 056000Hebei ProvinceChina Aier Eye Hospital(Wuhan) Wuhan 430061Hubei ProvinceChina Hebei Eye Hospital Xingtai 054001Hebei ProvinceChina the third People’s Hospital of Dalian Dalian 116033Liaoning ProvinceChina First Affiliated Hospital of suzhou University Suzhou 215031Jiangsu ProvinceChina National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina Glaucoma Research Institute Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina Centre for Public Health Queen’s University BelfastBelfast BT71NNUK Orbis International New YorkUSA Department of Ophthalmology and Visual Sciences the Chinese University of Hong KongHong Kong SAR 999077China Centre for Eye Research Australia University of MelbourneRoyal Victorian Eye and Ear HospitalEast Melbourne 3000VICAustralia 不详

AIM:to report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma ***:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in *** were followed up at 1wk,1,3,6,and *** pressure(IOP),number of glaucoma medications,anterior chamber depth(ACD),and complications were *** success was defined as the reformation of the anterior chamber based on slit-lamp *** was defined by the presence of a shallow orﬂat anterior chamber after initial recovery from ***:A total of 34 eyes received *** IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg(Pth 2.9±1.6 medications(P=0.046)at 1d,and 17.4±6.7 mm Hg(Pth 1.3±1.7 medications(Pt *** ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo,respectively.A total of 32(94.1%)eyes achieved initial anatomical *** follow-up,2(5.9%)eyes failed and 8(23.5%)eyes relapsed,yielding a 12-month anatomical success rate of 64.3%.Complications including anterior synechia(8.82%),choroidal/ciliary detachment(5.88%)and hypopyon(2.94%)were observed within ***:LCP is simple,safe,and effective in reforming the anterior chamber in malignant glaucoma.

关键词： anterior chamber reformation intraocular pressure low-dose laser cycloplasty malignant glaucoma anatomical success

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完全隐含能源与碳强度研究进展综述

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北京理工大学学报（社会科学版） 2024年第1期26卷 47-57页

作者：孙亚方 su Bin 李莹珠於世为中国地质大学(武汉)能源环境管理与决策研究中心湖北武汉430074 新加坡国立大学能源研究所新加坡119620 浙江大学公共管理学院浙江杭州310058

节能减排是应对全球气候变暖的重要举措。由于不同国家和地区的经济发展水平存在明显差异,近年来能源与碳强度成为度量节能减排绩效的重要指标,受到了社会各界的广泛关注。在生产端强度控制的基础上,如何从根源上在消费端降低完全隐含... 详细信息

节能减排是应对全球气候变暖的重要举措。由于不同国家和地区的经济发展水平存在明显差异,近年来能源与碳强度成为度量节能减排绩效的重要指标,受到了社会各界的广泛关注。在生产端强度控制的基础上,如何从根源上在消费端降低完全隐含能源与碳强度的研究越来越受到重视。针对消费端完全隐含能源与碳强度的研究特征与发展趋势展开综述,结果发现:(1)主要呈现出国家层面研究为主、全球层面研究显著增加、省市层面研究开始出现的特征,且国家或省市层面主要聚焦于中国;(2)相比完全隐含能源强度,现有文献更为关注完全隐含碳强度;(3)研究由不区分终端消费向细分各终端消费发展,隐含在出口中的完全隐含碳强度受到了重点讨论;(4)部分研究侧重于局部,比如深度参与到全球生产网络的部分经济部门或能源消费与碳排放在生产网络中传输的关键层级;(5)进行完全隐含碳强度变动的驱动因素的研究主要基于乘性结构分解分析模型,从时间轴和空间轴展开剖析。现有研究框架未来可以扩展到能源环境相关领域的其他指标。

关键词：完全隐含能源强度完全隐含碳强度投入产出分析结构分解分析

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Evidence for distortion-induced local electric polarization in α-RuCl_(3)

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Science China(Physics,Mechanics & Astronomy) 2024年第9期67卷 165-173页

作者： Xinrun Mi De Hou Xiao Wang Sabreen Hammouda Caixing Liu Zijian Xiong Han Li Yan Liu Guiwen Wang Aifeng Wang Yisheng Chai Yang Qi Wei Li Xiaoyuan Zhou Yixi su DIKhomskii Mingquan He Zhigao Sheng Young sun College of Physics Center of Quantum Materials and DevicesChongqing UniversityChongqing 401331China Anhui Key Laboratory of Condensed Matter Physics at Extreme Conditions High Magnetic Field LaboratoryHefei Institutes of Physical ScienceAnhuiChinese Academy of SciencesHefei 230031 China University of Science and technology of China Hefei 230026China Jülich Centre for Neutron Scienceat Heinz Maier-Leibnitz Zentrum(JCNS-MLZ) Forschungszentrum Jülich GmbHGarching D-85747Germany School of Physics Beihang UniversityBeijing 100191China Analytical and test.ng Center Chongqing UniversityChongqing 401331China State Key Laboratory of surface Physics Department of PhysicsFudan UniversityShanghai 200433China CAS Key Laboratory of theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China Ⅱ.Physikalisches Institut Universität zu KölnKöln D-50937Germany

the spin-orbit assisted Mott insulator α-RuCl_(3) is a prime candidate for material realization of the Kitaev quantum spin *** little attention has been paid to charge degrees of freedom,charge effects,such as electric polarization,may arise in this ***,we report distortion-induced local electric polarization in α-RuCl_(3) as evidenced by single-crystal X-ray diffraction,second harmonic generation(SHG)and dielectric *** SHG signal appears at room temperature and develops substantially in the Kitaev paramagnetic state when short-range spin correlations come into *** sizable pyroelectric currents in the Kitaev paramagnetic state,the absence of hysteresis in the polarization-electric field(P-E)points to the shortrange nature of electric *** localized electric polarization is likely the result of distortion-induced charge dimerization,achieved through virtual hopping-induced charge *** addition,the electric polarization is boosted by short-range spin correlations via spin-phonon coupling in the Kitaev paramagnetic *** results emphasize the importance of charge degrees of freedom in α-RuCl_(3),which establish a novel platform to investigate charge effects in Kitaev materials.

关键词： Mott insulator Kitaev quantum spin liquid electric polarization

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物理生物医学——原创交叉研究的新领域

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科学通报 2024年第15期69卷 2008-2014页

作者：杜全生粟硕戴慧李舟国家自然科学基金委员会交叉科学部北京100085 中国科学院北京纳米能源与系统研究所北京101400 上海市重大传染病和生物安全研究院复旦大学公共卫生学院上海200032 北京大学基础医学院免疫学系北京100191

物理生物医学是物理学与生物医学深度融合的新兴交叉研究领域,融入了材料学、化学、信息科学、机械工程等多个领域物质科学的知识和技术.它的科学内涵在于揭示生命现象的物理规律,并利用物理的方法和技术实现对生命过程的调控.因此,物... 详细信息

物理生物医学是物理学与生物医学深度融合的新兴交叉研究领域,融入了材料学、化学、信息科学、机械工程等多个领域物质科学的知识和技术.它的科学内涵在于揭示生命现象的物理规律,并利用物理的方法和技术实现对生命过程的调控.因此,物理生物医学既要解析伴随生命活动所产生的内源性物理信号的奥秘.

关键词：信息科学生物医学深度融合物理规律物理信号机械工程交叉研究物理学

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Pancreatic β-cell failure,clinical implications,and therapeutic strategies in type 2 diabetes

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Chinese Medical Journal 2024年第7期137卷 791-805页

作者： Daxin Cui Xingrong Feng Siman Lei Hongmei Zhang Wanxin Hu Shanshan Yang Xiaoqian Yu Zhiguang su Molecular Medicine Research Center and Department of Endocrinology and Metabolism West China HospitalSichuan UniversityChengduSichuan 610041China State Key Laboratory of Biotherapy West China HospitalSichuan UniversityChengduSichuan 610041China Clinical translational Innovation Center West China HospitalSichuan UniversityChengduSichuan 610041China

Pancreaticβ-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes(t2D).Reserving insulin-producingβ-cells and hence restoring insulin production are gaining attention in translational diabetes research,andβ-cell replenishment has been the main focus for diabetes *** findings inβ-cell proliferation,transdifferentiation,pluripotent stem cell differentiation,and associated small molecules have served as promising strategies to regenerateβ-*** this review,we summarize current knowledge on the mechanisms implicated inβ-cell dynamic processes under physiological and diabetic conditions,in which genetic factors,age-related alterations,metabolic stresses,and compromised identity are critical factors contribut.ng toβ-cell failure in *** article also focuses on recent advances in therapeutic strategies for diabetes treatment by promot.ngβ-cell proliferation,inducing non-β-cell transdifferentiation,and reprograming stem cell *** a significant challenge remains for each of these strategies,the recognition of the mechanisms responsible forβ-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenousβ-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

关键词： Pancreaticβ-cell regeneration Diabetes Insulin Dedifferentiation transdifferentiation Stem cell

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MEttL3 regulates glucose transporter expression in placenta exposed to hyperglycemia through the mtOR signaling pathway

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Chinese Medical Journal 2024年第13期137卷 1563-1575页

作者： Jie Ning Jing Huai Shuxian Wang Jie Yan Rina su Muqiu Zhang Mengt.ng Liu Huixia Yang Department of Obstetrics and Gynaecology Peking University First HospitalBeijing 100034China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus Beijing 100034China Peking University Beijing 100034China

Background:Alterations in the placental expression of glucose transporters(GLUts),the crucial maternal-fetal nutrient transporters,have been found in women with hyperglycemia in pregnancy(HIP).However,there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUts expression in ***:We quantitatively evaluated the activity of mammalian target of rapamycin(mtOR)and expression of GLUts(GLUt1,GLUt3,and GLUt4)in the placenta of women with normal pregnancies(CtRL,n=12)and pregnant women complicated with poorly controlled type 2 diabetes mellitus(t2DM,n=12)by *** addition,BeWo cells were treated with different glucose concentrations to verify the regulation of ***,changes in the expression of GLUts following the activation or suppression of the mtOR pathway were also assessed using MHY1485/rapamycin(RAPA)treatment or small interfering RNA(siRNA)-mediated silencing ***,we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3(MEttL3)when exposed to ***:mtOR,phosphorylated mtOR(p-mtOR),and GLUt1 protein levels were upregulated in the placenta of women with t2DM compared with those *** BeWo cells,mtOR activity increased with increasing glucose concentration,and the expression of GLUt1,GLUt3,and GLUt4 as well as GLUt1 cell membrane translocation were upregulated by hyperglycemia to varying *** the drug-mediated and genetic depletion of mtOR signaling in BeWo cells suppressed GLUts expression,whereas MHY1485-induced mtOR activation upregulated GLUts ***,high glucose levels upregulated MEttL3 expression and nuclear translocation,and decreasing MEttL3 levels suppressed GLUts expression and mtOR activity and vice ***,in MEttL3 knockdown BeWo cells,the inhibitory effect on GLUts expression was eliminated by activat.ng the mtOR signaling pathway using ***:High-g

关键词： Glucose transporters Hyperglycemia type 2 diabetes mellitus Pregnancy Mammalian target of rapamycin Methyltransferase-like 3

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Effects of typical karst tourist town on the Lijiang River water: from heavy metals to N-nitrosamines

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Journal of Earth Science 2024年

作者： Yuanyu Shan Yuru su Xinli Xing Bingquan Zhu Honghu Zeng Yuan Zhang Junyu Li Xiaoyu Yan Wenwen Chen Benjian Li College of Environmental Science and Engineering， Guilin University of technology School of Environmental Studies， China University of Geosciences State Key Laboratory of Biogeology and Environmental Geology， China University of Geosciences College of arts， Guilin University of technology College of arts and communication， China University of Geosciences 430070 China

N-nitrosamines are nitrogenous organic pollutants with high carcinogenicity to human. Heavy metal pollution in aquatic system is currently a major environmental problem. tourism in typical karst areas may influence the environment through wastewater discharge. However， it remains unclear whether these activities would cause water pollution. to evaluate the impact of tourism activities in typical tourist towns， this study investigated the occurrence and sources of 18 N-nitrosamines， eight heavy metals （HMs）， and dissolved inorganic nitrogen （DIN） in the Lijiang River and its tributaries. Seven N-nitrosamines were detected as the dominant compounds in N-nitroso-N-ethylaniline （NEA， average of 24.8 ng/L） and N-nitroso-l-proline （NPRO， 20.4 ng/L）， while especially low concentrations of HMs （Mn， Cu， As， Ni， Cr， Co， Pb， and Cd） and DIN (NH4+-N， NO2--N， and NO3--N) were observed. the most important influencing factors were seasonal factors， followed by land-use type and mainstem and tributary factors. Principal component analysis revealed that in the city with developed tourism and relatively less heavy industry， aquaculture and agricultural wastewater were identified as the primary sources of N-nitrosamines. Meanwhile， domestic sewage and agricultural wastewater were found to be the main sources of HMs and DIN， respectively. the ecological risk assessments for all pollutants are relatively low （therefore， N-nitrosamines， HMs， and DIN pollution caused by tourist activities pose a negligible risk to the Lijiang River.

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Efficacy and safety of Qingfei Huatan formula in the treatment of acute exacerbation of chronic obstructive pulmonary disease: A multi-centre,randomised, double-blind, placebo-controlled trial

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Journal of Integrative Medicine 2024年第5期22卷 561-569页

作者： Hui-zhi Zhu Cheng-yi Li Liang-ji Liu Jia-bing t.ng Zhi-hui Lan Shu-guang tian Qiao Li Xiang-li t.ng Ji-feng Wu Zhen-gang Zhu su-yun Li Jian-sheng Li Department of Respiratory Medicine the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine Graduate School Anhui University of Traditional Chinese Medicine Department of Respiratory Medicine Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine Department of Respiratory Diseases the First Affiliated Hospital of Henan University of Traditional Chinese Medicine Department of Pulmonary Diseases Taihe Hospital of Traditional Chinese Medicine Affiliated to Anhui University of Traditional Chinese Medicine Department of Respiratory and Critical Care Medicine Jiangxi Province Hospital of Integrated Chinese and Western Medicine Department of Respiratory Medicine the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine Collaborative Innovation Center for Respiratory Disease Diagnosis and treatment and Chinese Medicine Development of Henan Province

Background: Chronic obstructive pulmonary disease(COPD), a common respiratory disease, can be effectively treated by traditional Chinese medicine(tCM). Qingfei Huatan, a tCM formula, has been reported to effectively alleviate the clinical symptoms of COPD patients. However, there is a lack of multi-centre,randomised, double-blind, controlled clinical trials document.ng the clinical efficacy and safety of this formula in the treatment of acute exacerbation of COPD(AECOPD).Objective: this study evaluated the efficacy and safety of Qingfei Huatan formula in the treatment of AECOPD, thereby providing high-quality clinical ***, sett.ng, participants and interventions: A total of 276 patients with AECOPD were included in this multi-centre, randomised, double-blind, placebo-controlled trial and were randomised into treatment and control groups at a ratio of 1:1. Patients in the treatment and control groups took Qingfei Huatan granules or simulated Qingfei Huatan granules twice a day, for 14 days, in addition to Western medicine treatment. All patients were followed up for 3 *** outcome measures: the primary outcome was time taken to symptom stabilisation. the secondary outcomes included duration of antibiotic use, clinical symptom and sign score, tCM syndrome score, dyspnoea score, and quality of life(QOL) score. Meanwhile, the safety of the formula was assessed through routine urine and stool tests, electrocardiograms, liver and kidney function tests, and the observation of adverse events throughout the ***: the time taken for effective stabilisation(P tabilisation(P the duration of antibiotic use(P tly shorter in the treatment group than in the control group. On days 6, 9, 12 and 14 of treatment, clinical symptom and sign score decreased in both groups,particularly in the treatment group(P treatment, the tCM syndrome scores of both groups were reduced(P

关键词： Acute exacerbation of chronic obstructive pulmonary disease Clinical trial Syndrome of phlegm-heat congest.ng lung Qingfei Huatan formula traditional Chinese medicine

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