1.Investigation of Anisakis infections in coastal marine fishes and awareness of anisakiasis control knowledge among residents in Yantai City in 2021
Yao CHEN ; Dan LI ; Longjiang WANG ; Cancan BU ; Yuejin LI ; Yongbin WANG ; Yan XU ; Ge YAN ; Benguang ZHANG
Chinese Journal of Schistosomiasis Control 2024;36(1):74-78
Objective To investigate the prevalence of Anisakis infections in coastal marine fishes and awareness of anisakiasis control knowledge among local residents in Yantai City, Shandong Province in 2021, so as to provide insights into formulation of anisakiasis control interventions. Methods Marine fishes were purchased from Shunxin Port, Yantai City, Shandong Province in November 2021, and the presence of Anisakis was detected in different species of fishes and different fish sites. The correlations between body length and weight of marine fish and intensity of Anisakis infections were examined using Spearman’s rank correlation analysis, and the dietary habits and anisakiasis control knowledge were investigated using questionnaire surveys among local residents. Results A total of 201 marine fishes belonging to 20 species were dissected, and Anisakis was detected in 77 marine fishes (38.31%) belonging to 11 species (55.00%), with a mean infection intensity of 45.04 parasites per fish (3 468/77). Spearman’s rank correlation analysis revealed that the body length (rs = 0.74, P < 0.05) and weight (rs = 0.79, P < 0.01) of the monkfish correlated positively with the intensity of Anisakis infections, and the body length (rs = 0.68, P < 0.05) of the flatfish correlated positively with the intensity of Anisakis infections, while no correlations were examined between the body length or weight of other marine fishes and the intensity of Anisakis infections. Of all respondents, 53.38% men and 56.67% women did not know anisakiasis control knowledge at all, and there was a significant difference in the proportion of respondents using separate chopping boards for raw and cooked food from different villages (χ2 = 17.89, P < 0.01), while there was an age-specific proportion of respondents with habitats of eating raw or semi-raw seafood (χ2 = 28.27, P < 0.01). Conclusions The prevalence and intensity of Anisakis infections were high in coastal marine fishes in Yantai City in 2021, and the awareness of anisakiasis control knowledge was low among local residents. Intensified health education pertaining to anisakiasis control knowledge is recommended to reduce the risk of Anisakis infections.
2.Effect of Nobiletin on LPS-Induced Inflammatory Injury of Mesangium Cells by Regulating AMPK/NLRP3 Signaling Pathway
Dan LUO ; Yan WANG ; Xu DING ; Yao HU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(2):224-229
Objective To investigate the effect of nobiletin(Nb)on lipopolysaccharide(LPS)-induced inflammatory injury of mesangium cells(HBZY-1)by regulating AMP-activated protein kinase(AMPK)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods HBZY-1 cells were separated into 5 groups:normal control(NC)group,LPS group(100 ng·mL-1 LPS),and Nb group(100 ng·mL-1 LPS+40 μmol·L-1 Nb),Rapamycin(Rap,AMPK/NLRP3 signaling pathway inhibitor)group[100 ng·mL-1 LPS+0.5 μmol·L-1 Rap],and Nb+Rap group(100 ng·mL-1 LPS+40 μmol·L-1 Nb+0.5 μmol·L-1 Rap).MTT was applied to detect the cytotoxicity and proliferation of HBZY-1 cells.ELISA was applied to detect the contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),catalase(CAT),superoxide dismutase(SOD),and glutathione(GSH)in HBZY-1 cells.Flow cytometry was used to detect cell apoptosis.Western Blot was applied to detect the protein levels of AMPK/NLRP3 signaling pathway.Results Compared with the NC group,the levels of CAT,SOD,GSH,cell OD value,and the level of AMPK protein in the LPS group were significantly reduced(P<0.05).The apoptosis rate,contents of IL-1β,IL-6,TNF-α,and the level of NLRP3 protein were significantly increased(P<0.05).Compared with the LPS group,the levels of CAT,SOD,GSH,OD value,and the level of AMPK protein in the Nb group were significantly increased(P<0.05).The apoptosis rate,contents of IL-1β,IL-6,TNF-α,and the level of NLRP3 protein were significantly decreased(P<0.05),while the above indicators in the Rap group showed an opposite trend to the Nb group(P<0.05).Compared with the Nb group,the above indicators in the Nb+Rap group also showed an opposite trend to the Nb group(P<0.05).Conclusion Nb may alleviate LPS-induced inflammatory injury to MC cells by up-regulating the AMPK/NLRP3 signaling pathway.But down-regulation of the AMPK/NLRP3 signaling pathway may eliminate the improvement effect of Nb on LPS-induced inflammatory injury in MC cells.
3.IDH1R132H Mutant Glioma and Its Compensatory Mechanisms for Maintaining Telomeres
Si-Xiang YAN ; Yi-Fan LI ; Yao LI ; Yi-Xuan LI ; Xiang-Xiu LI ; Jin-Kai TONG ; Shu-Ting JIA ; Ju-Hua DAN
Progress in Biochemistry and Biophysics 2024;51(11):2845-2852
Isocitrate dehydrogenase 1 (IDH1) R132H is the most common mutated gene in grade II-III gliomas and oligodendrogliomas. Instead of activating telomerase (a reverse transcriptase which using RNA as a template to extend telomere length), the majority of IDH1R132H mutant glioma maintain telomere length through an alternative mechanism that relies on homologous recombination (HR), which is known as alterative lengthening of telomere (ALT).The phenotype of ALT mechanism include: ALT associated promyelocytic leukemia protein (PML) bodies (APBs); extrachromosomal telomeric DNA repeats such as C- and T-loops; telomeric sister chromatid exchange (T-SCE), etc. The mechanism of ALT activation is not fully understood. Recent studies have shown that mutation IDH1 contributes to ALT phenotype in glioma cells in at least three key ways. Firstly, the IDH1R132H mutation mediates RAP1 down-regulation leading to telomere dysfunction, thus ensuring persistent endogenous telomeric DNA damage, which is important for ALT activation. Spontaneous DNA damage at telomeres may provide a substrate for mutation break-induced replication (BIR)‑mediated ALT telomere lengthening, and it has been demonstrated that RAP1 inhibits telomeric repeat-containing RNA, transcribed from telomeric DNA repeat sequences (TERRA) transcription to down-regulate ALT telomere DNA replication stress and telomeric DNA damage, thereby inhibiting ALT telomere synthesis. Similarly, in ALT cells, knockdown of telomere-specific RNaseH1 nuclease triggers TERRA accumulation, which leads to increased replication pressure. Overexpression of RNaseH1, on the other hand, attenuates the recombination capacity of ALT telomeres, leading to telomere depletion, suggesting that RAP1 can regulate the level of replication pressure and thus ALT activity by controlling TERRA expression. Secondly, the IDH1R132H also alters the preference of the telomere damage repair pathway by down-regulating XRCC1, which inhibits the alternative non-homologous end joining (A-NHEJ) pathway at telomeres and alters cellular preference for the HR pathway to promote ALT. Finally, the IDH1R132H has a decreased affinity for isocitric acid and NADP+ and an increased affinity for α ketoglutarate (α‑KG) and NADPH, so that the mutant IDH1R132H catalyzes the hydrogenation of α‑KG to produce 2-hydroxyglutarate (2-HG)in a NADPH-dependent manner. Because 2-HG is structurally similar to α‑KG, which maintains the trimethylation level of H3k9me3 by competitively inhibiting the activity of the α‑KG-dependent histone demethylase KDM4B, and recruits heterochromatin protein HP1α to heterochromatinize telomeres, and promote ALT phenotypes in cooperation with the inactivating of ATRX. In addition, it has been shown that APBs contain telomeric chromatin, which is essentially heterochromatin, and HP1α is directly involved in the formation of APBs. Based on these studies, this article reviews the mechanism of IDH1R132H mediated telomere dysfunction and the preference of DNA repair pathway at telomeres in cooperate with ATRX loss to promote ALT, which may provide references for clinical targeted therapy of IDH1R132H mutant glioma.
4.The health effect and its mechanism of family doctor contract services:Evidence from 1 191 rural residents with chronic diseases in 12 counties of 6 provinces
Yan-Ping HE ; Xiao-Dan ZHANG ; Qiang YAO
Chinese Journal of Health Policy 2024;17(8):19-27
Objective:To explore the effect and mechanism of family doctor contract services on the health of rural residents with chronic diseases.Methods:From June to August 2023,1 191 valid samples from 12 counties in 6 provinces were collected through face-to-face questionnaire survey.Tobit model and KHB method were used to analyze the effect of family doctor contract services on EQ-5D-5L utility index scores and its path.Results:The family doctor contract rate was 59.19%and the utility index score was 0.831.Family doctor contract services significantly improved the health utility index scores of chronic disease patients(β=0.047,P<0.05);The utility index score was affected completely through public health services(β=0.028,P<0.01,95%CI=0.009~0.047),and the indirect effect accounted for 66.77%of the total effect.Conclusion:The family doctor contract rate of rural residents with chronic diseases is low in China,and the health-related quality of life is not good.The family doctor contract services can improve the health-related quality of life of patients with chronic diseases mainly by improving public health services.It is urgent to strengthen the effects of family doctor contract services on medical service utilization and individual health behavior,so as to give full play to the health effects of family doctor contract services.
5.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
6.Value of different assessment scales in the diagnosis of drug-induced liver injury
Jiaxi MA ; Tiantian YAO ; Hao CHENG ; Dan LIU ; Yuhan ZHANG ; Siyuan DU ; Linfei DONG ; Linhui HU ; Yan WANG ; Guiqiang WANG
Journal of Clinical Hepatology 2024;40(6):1203-1208
Objective To determine the scores of patients with a confirmed diagnosis of drug-induced liver injury(DILI)using Roussel Uclaf Causality Assessment Method(RUCAM),Maria&Victorino assessment scale,and Revised Electronic Causality Assessment Method(RECAM),to compare the accuracy of the three scales in diagnosis,and to investigate their clinical significance in the diagnosis of DILI.Methods A total of 98 patients with a confirmed diagnosis of DILI who were hospitalized in Peking University First Hospital from January 2011 to December 2022 were enrolled,with liver biopsy results supporting DILI and a clear history of medication.Clinical data were collected from all subjects,and the above causality assessment scales were used for scoring.The chi-square test was used to analyze the diagnostic accuracy of the causality assessment scales,and the weighted kappa coefficient was used to analyze the consistency between the three scales.Results For all patients with DILI enrolled,RECAM had the highest accuracy,with a significant difference compared with RUCAM(χ2=5.667,P=0.017).RUCAM and RECAM had moderate consistency in diagnosis(κw=0.469),while RECAM and Maria&Victorino scale had poor consistency(κw=0.156).For the patients with acute DILI,RECAM,RUCAM,and Maria&Victorino scales had a diagnostic inconsistency rate of 3.7%,11.1%,and 42.6%,respectively;for the patients with hepatocellular type DILI,the three scales of a diagnostic inconsistency rate of 8.9%,21.4%,and 62.5%,respectively;for the patients with cholestasis type or mixed type DILI,the three scales of a diagnostic inconsistency rate of 10.0%,22.5%,and 47.5%,respectively.Conclusion The use of RECAM and RUCAM scales in acute DILI can improve diagnostic rate,and for hepatocellular type DILI and DILI with the clinical manifestation of cholestasis(cholestasis type DILI and mixed type DILI),the use of RECAM and RUCAM scales can also improve diagnostic rate.The selection of causality assessment scales with a relatively high accuracy based on the course and clinical classification of the disease may help to further improve clinical diagnostic rate.
7.Analyzing the influencing factors of depressive symptoms among medical staff in Beijing City
Li HU ; Dan LIU ; Shengying YAO ; Zihuan WANG ; Zhifeng SUN ; Liu LIU ; Yan YE
China Occupational Medicine 2024;51(6):665-670
Objective To analyze the current situation of depressive symptoms among medical staff in Beijing City and its correlation with symptoms of anxiety, occupational stress and insomnia. Methods A total of 2 687 medical staff from 28 medical institutions in eight municipal districts of Beijing City were selected as study subjects using multi-stage sampling method. The basic situation, depression symptoms, anxiety symptoms, occupational stress and insomnia symptoms were investigated using the National Occupational Health Literacy Monitoring Questionnaire for Key Groups, Patient Health Questionaire-9, 7-item Generalized Anxiety Disorder Scale, Core Occupational Stress Scale, and Self-Sleep Management Questionnaire. Results The detection rate of depressive symptoms was 28.3%, and the detection rates of moderate, moderate-severe and severe depressive symptoms were 18.9%, 6.9% and 2.5%, respectively. The detection rate of anxiety symptoms was 41.3%, and the detection rates of mild, moderate and severe anxiety symptoms were 29.7%, 7.7% and 3.9%, respectively. The detection rate of occupational stress was 26.7%. The detection rate of insomnia symptoms was 36.6%. The results of multivariate logistic regression analysis showed that the risk of depressive symptoms in male medical staff was higher than that in female (P<0.05). The risk of depressive symptoms in night shift staff was higher than that in staff without night shift (P<0.05). The more severe the anxiety symptoms, the higher the risk of depressive symptoms (all P<0.01). The risk of depressive symptoms in medical staff with occupational stress was higher than those without occupational stress (P<0.01). The risk of depressive symptoms in medical staff with insomnia symptoms was higher than those without insomnia symptoms (P<0.01). Conclusion The detection rate of depressive symptoms among medical staff in Beijing City is relatively high. Gender, night shift, anxiety symptoms, occupational stress, and insomnia symptoms were independent risk factors of depressive symptoms.
8.Prevalence and risk factors of work-related musculoskeletal disorders in upper back of welders in an automobile factory
Yan YAO ; Yong MEI ; Zhou LI ; Fengmei CHEN ; Dan FU ; Jiabing WU ; Ruijie LING
Journal of Environmental and Occupational Medicine 2023;40(2):171-175
Background China's automobile manufacture is a labor-intensive industry, and most of the welding tasks are manual operations. It is often necessary to observe the solder joints during operation, and there are many adverse health outcome-related factors involved in the work process. However, the research on the prevalence and risk factors of work-related musculoskeletal disorders (WMSDs) in the upper back of welders is still insufficient. Objective To explore the prevalence and risk factors of WMSDs in the upper back of welders from an automobile factory. Methods This was a cross-sectional study. A cluster random sampling method was used to select 972 electric welders from an automobile factory as the study subjects. The Musculoskeletal Disorders Questionnaire was used to estimate the prevalence of WMSDs in the upper back in the past year. Results The prevalence rate of WMSDs in the upper back in the welders was 42.2% (410/972). The positive rates of studied occupational risk factors were 72.5% (705/972) for maintaining same posture for a long time, 71.8% (698/972) for bending and twisting for a long time, and 64.7% (629/972) for repetitive trunk movements. The univariate analysis showed that the prevalence rates of WMSDs were significantly different among workers categorized by gender, working age, twisting and/or bending for a long time, working in the same position for a long time, lifting heavy objects in an uncomfortable position, repetitive trunk movements, being unable to exert energy due to discomfort, work involving cold or temperature changes, personnel shortage, no rest between work, working hours per week, and working in an uncomfortable position (P<0.05). The results of multiple logistic regression indicated that female, working in the same position for a long time, working in an uncomfortable position (frequently), lifting heavy objects in an uncomfortable position, and being unable to exert energy due to discomfort were associated with higher risks of reporting WMSDs in the upper back (OR=2.37, 1.46, 1.76, 1.44, and 1.50, respectively, P<0.05); the risk of reporting WMSDs in the upper back increased by 95%, 157%, and 196% for every 10 h increase in weekly working hours (41-50 h, 51-60 h, ≥61 h vs ≤40 h); adequate rest time was associated with a lower risk for WMSDs in the upper back (OR=0.70, 95%CI: 0.49-0.98). Conclusion The prevalence rate of WMSDs in the upper back of welders in the automobile factory is high, and many occupational risk factors are involved. Measures should be taken for intervention and prevention.
9.Bisphenol A induces testicular oxidative stress in mice leading to ferroptosis.
Li LI ; Min-Yan WANG ; Hua-Bo JIANG ; Chun-Rong GUO ; Xian-Dan ZHU ; Xia-Qin YAO ; Wei-Wei ZENG ; Yuan ZHAO ; Ling-Kan CHI
Asian Journal of Andrology 2023;25(3):375-381
Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.
Male
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Mice
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Animals
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Testis/metabolism*
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Ferroptosis
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Semen
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Oxidative Stress
10.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male
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Female
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Humans
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Aged
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Natriuretic Peptide, Brain
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Simendan/therapeutic use*
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Non-ST Elevated Myocardial Infarction
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Heart Failure/drug therapy*
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Peptide Fragments
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Arrhythmias, Cardiac
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Biomarkers
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Prognosis

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