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Cytokines are early diagnostic biomarkers of graft-versus-host disease in liver recipients

Hepatobiliary & Pancreatic Diseases International 2017年第1期16卷 45-51页

作者： Xue-Qin Meng Xin-Hua Chen Zayd Sahebally Yu-Ning Xu Sheng-Yong Yin li-ming wu Shu-Sen Zheng Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases the First Affiliated Hospital Zhejiang University School of Medicine 79 Qingchun Road Hangzhou 310003 China

BACKGROUND： Graft-versus-host disease （GVHD） is associated with high mortality. Early diagnosis is essential to start treatment and to improve outcomes. Because of the inflammatory nature, we hypothesis that cytokine profile of patients with GVHD may serve as diagnostic markers. The present study was to evaluate the role of cytokine profile in the diagnosis of GVHD. METHODS： An immunoassay was used to detect 29 cytokines simultaneously in the serum; the measuring sensitivity of all cytokines was pg/mL. Healthy subjects undergoing annual routine physical examinations served as negative controls; 23 patients with hepatocellular carcinoma （HCC） who had undergone liver transplantation （the LT group） comprised the test subjects. A total of 22 kidney recipients with biopsyconfirmed GVHD （the RT group） were included for comparison. HCC patients with radical surgery （the HCC group, n=22） served as positive control. The liver contents of the three cytokines, IL-2, IL-18, and IFN-γ, were detected with immunohistochemistry. Serum granzyme B and perforin were measured by flow cytometry.RESULTS： Of the 29 cytokines, the levels of IL-2 and IL-18 were increased significantly in liver recipients with GVHD compared with healthy controls （P〈0.05）. The serum levels of these three cytokines in the healthy, HCC, LT, and RT groups were IL-2： 0.90±0.02, 4.14±0.61, 5.10±0.89, and 1.48±0.09 pg/mL; IL-18： 80.61±9.35, 109.51±10.93, 230.11±12.92, and 61.98±7.88 pg/mL; IFN-γ： 24.06±3.88, 24.84±3.21, 40.37±5.88, and 15.33±4.72 pg/mL, respectively. Immunohistochemistry showed that these 3 cytokines expressions in the liver were parallel to the serum cytokine. After standard anti-GVHD treatment, the expressions of IL-2, IL-18, and IFN-y were de- creased in the liver （P〈0.05）. Serum granzyme B and perforin were significantly increased in GVHD patients （P〈0.05）. CONCLUSIONS： IL-2, IL-18 and IFN-γ were from liver and might serve as biomarkers for monitoring GVHD develop- ment and the effects of anti-GVHD treatment. Granzyme B and perforin may play

关键词： cytokines graft-versus-host disease transplantation multiplex immunoassay high-throughput

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Oncogenic role of microRNA-423-5p in hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2015年第6期14卷 613-618页

作者： li-ming wu Jian-Song Ji Zhe Yang Chun-Yang Xing Ting-Ting Pan Hai-Yang Xie Feng Zhang li Zhuang lin Zhou Shu-Sen Zheng Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health Key Laboratory of Organ Transplantation of Zhejiang Province Division of Hepatobiliary and Pancreatic Surgery First Affiliated HospitalZhejiang University School of Medicine lishui Hospital of Zhejiang University

BACKGROUND： It has been found that microRNA-423-5p （miR423-Sp） is an oncogenic factor and frequently upregulated in gastric carcinoma. However, the involvement of miR423- 5p in hepatocellular carcinoma （HCC） has been rarely reported. The aim of this study was to assess whether miR423-Sp is aberrantly expressed in HCC tissues, and to characterize its roles in the cancerous biology of HCC.

关键词： hepatocellular carcinoma miR423-5p proliferation invasion oncogene

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Characterization of physicochemical and immunogenic properties of allergenic proteins altered by food processing:a review

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Food Science and Human Wellness 2024年第3期13卷 1135-1151页

作者： Enning Zhou Qiangqiang li Dan Zhu Gang Chen liming wu Institute of Apicultural Research Chinese Academy of Agricultural SciencesBeijing 100093China Department of Food Science University of OtagoDunedin 9016New Zealand School of Food and Health Beijing Technology and Business UniversityBeijing 100048China

Food allergens are mainly naturally-occurring proteins with immunoglobulin E(IgE)-binding epitopes.Understanding the structural and immunogenic characteristics of allergenic proteins is essential in assessing whether and how food processing techniques reduce allergenicity.We here discuss the impacts of food processing technologies on the modification of physicochemical,structural,and immunogenic properties of allergenic proteins.Detection techniques for characterizing changes in these properties of food allergens are summarized.Food processing helps to reduce allergenicity by aggregating or denaturing proteins,which masks,modifies,or destroys antigenic epitopes,whereas,it cannot eliminate allergenicity completely,and sometimes even improves allergenicity by exposing new epitopes.Moreover,most food processing techniques have been tested on purified food allergens rather than food products due to potential interference of other food components.We provide guidance for further development of processing operations that can decrease the allergenicity of allergenic food proteins without negatively impacting the nutritional profile.

关键词： Food allergens Protein structural characterization Immunogenicity evaluation Food processing modification

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Allergen degradation of bee pollen by lactic acid bacteria fermentation and its alleviatory effects on allergic reactions in BALB/c mice

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Food Science and Human Wellness 2024年第1期13卷 349-359页

作者： Shuting Yin Qiangqiang li Yuxiao Tao Enning Zhou Kun Wang Wanwen Chen Xiangxin li liming wu Institute of Apicultural Research Chinese Academy of Agricultural SciencesBeijing 100093China Department of Animal Science McGill UniversityQuebec H9X 3V9Canada State Key Laboratory of Food Science and Technology School of Food Science and TechnologyJiangnan UniversityWuxi 214122China

Food allergy as a global health problem threatens food industry.Bee pollen(BP)is a typical food with allergenic potentials,although it performs various nutritional/pharmacological functions to humans.In this study,lactic acid bacteria(LAB)were used to ferment Brassica napus BP for alleviating its allergenicity.Four novel allergens(glutaredoxin,oleosin-B2,catalase and lipase)were identified with significant decreases in LAB-fermented BP(FBP)than natural BP by proteomics.Meanwhile,metabolomics analysis showed significant increases of 28 characteristic oligopeptides and amino acids in FBP versus BP,indicating the degradation of LAB on allergens.Moreover,FBP showed alleviatory effects in BALB/c mice,which relieved pathological symptoms and lowered production of allergic mediators.Microbial high-throughput sequencing analysis showed that FBP could regulate gut microbiota and metabolism to strengthen immunity,which were closely correlated with the alleviation of allergic reactivity.These findings could contribute to the development and utilization of hypoallergenic BP products.

关键词： Alleviatory effects Lactic acid bacteria fermentation Bee pollen allergen Gut microbiota Host metabolism

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π-Extended giant dimeric acceptor as a third component enables highly efficient ternary organic solar cells with efficiency over 19.2%

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Journal of Energy Chemistry 2024年第8期95卷 263-270页

作者： Mengran Peng Haotian wu liming wu Jianhua Chen Ruijie Ma Qunping Fan Hua Tan Weiguo Zhu Hongxiang li Junqiao Ding School of Chemical Science and Technology Yunnan University Department of Electrical and Electronic Engineering Research Institute for Smart Energy (RISE) Guangdong-Hong Kong-Macao (GHM) Joint Laboratory for Photonic-Thermal-Electrical Energy Materials and Devices The Hong Kong Polytechnic University State Key Laboratory for Mechanical Behavior of Materials Xi'an Jiaotong University School of Materials Science and Engineering Jiangsu Engineering Laboratory of Light-Electricity-Heat Energy-Converting Materials and Applications Changzhou University College of Polymer Science and Engineering State Key Laboratory of Polymer Materials Engineering Sichuan University

Ternary strategy with a suitable third component is a successful strategy to improve the photovoltaic performance of organic solar cells(OSCs). Very recently, Y-series based giant molecule acceptors or oligomerized acceptors have emerged as promising materials for achieving highly efficient and stable binary OSCs, while application as third component for ternary OSCs is limited. Here a novel π-extended giant dimeric acceptor, GDF, is developed based on central Y series core fusion and rigid BDT as linker, and then incorporated into the state-of-the-art PM1:PC6 system to construct ternary OSCs.The GDF has a near planar backbone, resulting in increased π-conjugation, excellent crystallinity, and good electron transport capacity. When GDF is introduced into the PM1:PC6 system, it ensues in a cascade like the lowest unoccupied molecular orbitals(LUMO) energy level alignment, a complementary absorption band with PM1 and PC6, higher and balanced hole and electron mobility, slightly smaller domain size, and a higher exciton dissociation probability for PM1:PC6:GDF(1:1.1:0.1) blend film. As a consequence, the PM1:PC6:GDF(1:1.1:0.1) ternary OSC achieves a champion PCE of 19.22%, with a significantly higher open-circuit voltage and short-circuit current density, compared to 18.45% for the PM1:PC6(1:1.2) binary OSC. Our findings show that employing a π-extended giant dimeric acceptor as a third component significantly improves the photovoltaic performance of ternary OSCs.

关键词： Giant dimeric acceptor Ternary organic solar cells Third component

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Laboratory Safety of Dupilumab,and Its Effect on Inflammatory Biomarkers,in Chinese Adults With Moderate-to-Severe Atopic Dermatitis:An Analysis of a Randomized,Double-Blind Phase III Study

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International Journal of Dermatology and Venereology 2022年第4期5卷 218-225页

作者： Yan Zhao li-ming wu Qian-Jin Lu Xing-Hua Gao Xiao-Hong Zhu Xu Yao lin-Feng li Wei li Yang-Feng Ding Zhi-Qiang Song ling-ling liu Ning-Ning Dang Chun-Lei Zhang Xiao-ming liu Jun Gu Jin-Yan Wang Song-Mei Geng Quan-Zhong liu Yi-Feng Guo li Dong Shelley li Christine Xu John T.O’Malley Elizabeth Laws Nikhil Amin Ashish Bansal Min Wang Jian-Zhong Zhang Department of Dermatology Peking University People’s HospitalBeijing 100044China Hangzhou First People’s Hospital HangzhouZhejiang 310006China The Second Xiangya Hospital of Central South University ChangshaHunan 410011China The First Hospital of China Medical University ShenyangLiaoning 110001China wuxi Second People’s Hospital WuxiJiangsu 214002China Hospital for Skin Diseases Institute of DermatologyChinese Academy of Medical SciencesNanjingJiangsu 210042China Beijing Friendship Hospital Capital Medical UniversityBeijing 100050China Huashan Hospital Fudan UniversityShanghai 200040China Shanghai Skin Disease Hospital Shanghai 200040China The Southwest Hospital of AMU Chongqing 400038China Peking University First Hospital Beijing 100034China Jinan Central Hospital JinanShandong 250013China Peking University Third Hospital Beijing 100191China University of Hong Kong-Shenzhen Hospital ShenzhenGuangdong 518040China Changhai Hospital of Shanghai Shanghai 200433China Ningbo No.2 Hospital NingboZhejiang 315099China The Second Affiliated Hospital of Xi’an Jiaotong University Xi’anShaanxi 710004China Tianjin Medical University General Hospital Tianjin 300052China Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200092China Research&Development SanofiBridgewaterNJ 08807USA Research&Development RegeneronTarrytownNY 10591USA Medical Sanofi ChinaShanghai 200040China.

Objective:limited information is available on the use of dupilumab for the treatment of atopic dermatitis(AD)in the Chinese population.Methods:We analyzed laboratory data from a previously published randomized,double-blind phase III trial(NCT03912259)to provide further insight into the safety of dupilumab in Chinese adults with moderate to severe AD.The trial participants received either 300 mg of dupilumab or placebo every 2 weeks for 16 weeks.Hematology,blood chemistry,serum thymus and activation-regulated chemokine(TARC),and total immunoglobulin E(IgE)were evaluated.Results:In total,82 participants received dupilumab and 83 received placebo.With the exception of eosinophil counts of>0.8×109/L,which were found less frequently with dupilumab(9.8%)than with placebo(18.7%),the hematology and blood chemistry values were generally stable in both treatment groups.There were no clinically significant differences between the dupilumab and placebo groups,and no participants developed treatment-emergent abnormalities of potential clinical significance.However,compared with placebo,greater decreases in serum lactate dehydrogenase(mean change,−97.4 vs.−33.5 IU/L),TARC(median percent change,−78.6%vs.−30.8%),and total IgE(median percent change,−53.4%vs.−0.2%)were observed with dupilumab than placebo at week 16.Conclusion:Dupilumab demonstrated a favorable laboratory safety profile in Chinese adults with moderate to severe AD.

关键词： atopic dermatitis dupilumab laboratory safety Chinese

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Lack of association between genetic polymorphisms in cytokine genes and tumor recurrence in patients with hepatocellular carcinoma undergoing transplantation

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Hepatobiliary & Pancreatic Diseases International 2013年第1期12卷 54-59页

作者： li-ming wu lin Zhou Jun Xu Ba-Jin Wei Jun Cheng Xiao Xu Bin Xi Hai-Yang Xie Shu-Sen Zheng Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health Key Laboratory of Organ Transplantation Zhejiang Province and Division of Hepatobiliary and Pancreatic Surgery First Affiliated HospitalZhejiang University School of Medicine

BACKGROUND:Recurrence of hepatocellular carcinoma(HCC) after liver transplantation(LT) remains one of the most common causes of poor long-term survival.However,the host genetic factors affecting increased risk of tumor recurrence after transplantation have not been thoroughly elucidated.The present study was designed to investigate the association of cytokine gene polymorphisms with the risk of tumor recurrence in LT patients for HCC.METHODS:Eleven single-nucleotide polymorphisms within the promoter regions of 7 cytokine genes,i.e.,the IL-1 family(IL-1α and IL-1β),IL-6,IL-8,IL-10,TNF-α,and TGF-β1,were genotyped in 93 HCC patients treated with LT using DNA sequencing.The association between these polymorphisms and the risk of tumor recurrence was evaluated while controlling confounding clinical variables.RESULTS:The genotype frequency of IL-10-1082 A/G in patients with and without recurrence of HCC was AA 83.3%,GA 16.7% and AA 97.6%,GA 2.4%,respectively.The association between IL-10-1082 GA and recurrence was significant(P=0.033).No other single-nucleotide polymorphism in the cytokine gene was found to be associated with recurrence.Kaplan-Meier survival curves showed that the homozygous AA patients had a significantly longer mean recurrence-free survival than heterozygous GA patients(23.5 vs 5.7 months,P=0.001).However,multivariate analysis failed to reveal that the GA genotype of IL-10-1082 A/G was an independent indicator of recurrence.CONCLUSIONS:This study suggests the lack of association of selected cytokine gene polymorphisms with HCC recurrence after LT in the Han Chinese population.The finding does not exclude the idea that other cytokine polymorphisms could act as candidate biomarkers of disease prognosis.

关键词： hepatocellular carcinoma cytokine polymorphism recurrence

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Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis:A multicenter,randomized,double-blind,placebo-controlled phase 2b trial

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Chinese Medical Journal 2024年第2期137卷 200-208页

作者： Yan Zhao Jianzhong Zhang Bin Yang Jingyi li Yangfeng Ding liming wu litao Zhang Jinyan Wang Xiaohong Zhu Furen Zhang Xiaohua Tao Yumei li Chunlei Zhang linfeng li Jianyun Lu Qingchun Diao Qianjin Lu Xiaoyong Man Fuqiu li Xiujuan Xia Hao Cheng Yingmin Jia Guoqing Zhao Jinchun Yan Bo Chen Department of Dermatology Peking University People’s HospitalBeijing 100044China Department of Dermatology Dermatology HospitalSouthern Medical UniversityGuangzhouGuangdong 510091China Department of Dermatology West China HospitalSichuan UniversityChengduSichuan 610041China Department of Dermatology Shanghai Skin Disease HospitalInstitute of PsoriasisTongji University School of MedicineShanghai 200443China Department of Dermatology Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China Department of Dermatology Tianjin Academy of Traditional Chinese Medicine Affiliated HospitalTianjin 300120China Department of Dermatology Ningbo No.2 HospitalNingboZhejiang 315010China Department of Dermatology The Wuxi Second Affiliated Hospital of Nanjing Medical UniversityWuxiJiangsu 214002China Shandong Provincial Hospital for Skin Diseases&Shandong Provincial Institute of Dermatology and Veneorology Shandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250022China Center for Plastic&Reconstructive Surgery Department of DermatologyZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)HangzhouZhejiang 310014China Department of Dermatology Affiliated Hospital of Jiangsu UniversityZhenjiangJiangsu 212001China Department of Dermatology Peking University Third HospitalBeijing 100191China Department of Dermatology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Dermatology The Third Xiangya Hospital of Central South UniversityChangshaHunan 410013China Department of Dermatology Chongqing Traditional Chinese Medicine HospitalChongqing 400011China Hunan Key Laboratory of Medical Epigenomics Department of DermatologyThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China Department of Dermatology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Departme

Background:Atopic dermatitis(AD)affects approximately 10%of adults worldwide.CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling.This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods:This multicenter,randomized,double-blind,placebo-controlled,phase 2b trial was conducted in 21 medical institutions in China from February to November 2021.Totally 120 eligible patients were enrolled and randomized(1:1:1)to receive subcutaneous injections of 300 mg CM310,150 mg CM310,or placebo every 2 weeks for 16 weeks,followed by an 8-week follow-up period.The primary endpoint was the proportion of patients achieving≥75%improvement in the Eczema Area and Severity Index(EASI-75)score from baseline at week 16.Safety and pharmacodynamics were also studied.Results:At week 16,the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups(70%[28/40]for high-dose and 65%[26/40]for low-dose)than that in the placebo group(20%[8/40]).The differences in EASI-75 response rate were 50%(high vs.placebo,95%CI 31%-69%)and 45%(low vs.placebo,95%CI 26%-64%),with both P valueslife Quality Index compared with placebo.CM310 treatment reduced levels of thymus and activation-regulated chemokine,total immunoglobulin E,lactate dehydrogenase,and blood eosinophils.The incidence of treatment-emergent adverse events(TEAEs)was similar among all three groups,with the most common TEAEs reported being upper respiratory tract infection,atopic dermatitis,hyperlipidemia,and hyperuricemia.No severe adverse events were deemed to be attributed to CM310.Conclusion:CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Tria

关键词： CM310 Moderate-to-severe atopic dermatitis Interleukin-4 receptor alpha Adults

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采用仿海鸥翼型叶片提升轴流风机气动性能的研究

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风机技术 2024年第2期66卷 1-7页

作者：李跃飞姜怡欣吴立明田晨晔吴彦东刘小民广东美的暖通设备有限公司西安交通大学能源与动力工程学院太原学院机电与车辆工程系

为提升轴流风机的气动性能,受到具有良好滑行飞行性能的海鸥翅膀独特的翼型结构的启发,本文研究通过提取海鸥翅膀特定截面位置处的翼型结构应用于轴流风机的叶片设计中,考察了叶片仿生设计对空调器用轴流风机气动性能的影响。首先采用... 详细信息

为提升轴流风机的气动性能,受到具有良好滑行飞行性能的海鸥翅膀独特的翼型结构的启发,本文研究通过提取海鸥翅膀特定截面位置处的翼型结构应用于轴流风机的叶片设计中,考察了叶片仿生设计对空调器用轴流风机气动性能的影响。首先采用数值计算方法求解定常流动雷诺时均Navier-Stokes方程,对仿海鸥翼型叶片的轴流风机的气动性能及其内部流场进行分析,然后采用大涡模拟方法和FW-H声类比方法对轴流风机的气动噪声进行数值预测。结果表明:在相同的设计转速下,仿海鸥翼型叶片的轴流风机的气动效率提高了3.1%;在相同风量条件下,仿海鸥翼型叶片的轴流风机的噪声相比于原型风机降低了约1.0dB(A)。采用仿海鸥翼型叶片,风机叶片表面的静压分布均匀,叶片中段的压力脉动明显减少。同时,在风机进口轮毂处和叶顶区域,流动分离被抑制,叶片尾迹涡脱落引起的气流脉动和气流不均匀性相对减弱,这就有效提升了轴流风机的气动性能。

关键词：轴流风机海鸥翼型叶片仿生设计流动控制气动性能噪声

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Serum procalcitonin levels are associated with rhabdomyolysis following exertional heatstroke: an over 10-year intensive care survey

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World Journal of Emergency Medicine 2024年第1期15卷 23-27页

作者： li Zhong Feifei Shuai Conglin Wang lipeng Han Zhifeng liu ming wu Department of Traditional Chinese Medicine the First Affi liated HospitalGuizhou University of Chinese MedicineGuiyang 550001China Department of Medical Critical Care Medicine General Hospital of Southern Theatre Command of People’s Liberation ArmyGuangzhou 510010China Department of Infection and Critical Care Medicine Shenzhen Second People’s Hospital&First Affi liated Hospital of Shenzhen UniversityHealth Science CenterShenzhen 518035China Department of Nosocomial Infection Prevention and Control Shenzhen Second People’s HospitalShenzhen 518035China Key Laboratory of Hot Zone Trauma Care and Tissue Repair of People's liberation Army General Hospital of Southern Theatre Command of People's Liberation ArmyGuangzhou 510010China

BACKGROUND:Heatstroke has become a common emergency event in hospitals.Procalcitonin(PCT)is used as a biomarker of infection in the emergency department(ED),but its role in rhabdomyolysis(RM)following exertional heatstroke(EHS)remains unclear.METHODS:A retrospective cohort study enrolled patients with EHS from the intensive care unit(ICU).We collected RM biomarkers,inflammation markers,critical disease scores at admission,24 h,48 h,and discharge,and 90-day mortality.Correlation analysis,linear regression and curve fi tting were used to identify the relationship between PCT and RM.RESULTS:A total of 162 patients were recruited and divided into RM(n=56)and non-RM(n=106)groups.PCT was positively correlated with myoglobin(Mb),acute hepatic injury,disseminated intravascular coagulation(DIC),Sequential Organ Failure Assessment(SOFA)score,and Acute Physiology and Chronic Health Evaluation II(APACHE II)score,with correlation coefficients of 0.214,0.237,0.285,0.454,and 0.368,respectively(all Plinear relationship between PCT and RM,and a two-piecewise linear regression model showed that PCT was related to RM with an odds ratio of 1.3 and a cut-off oflity compared to non-RM cases(P=0.0093).CONCLUSION:High serum PCT concentrations are associated with RM after EHS in critically ill patients.Elevated PCT concentrations should be interpreted cautiously in patients with EHS in the ED.

关键词： Procalcitonin Myoglobin Rhabdomyolysis Exertional heatstroke

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