目的 运用数据挖掘的方法检测奥马珠单抗上市后的不良反应信号,为临床安全合理用药提供参考。方法 本研究采用报告比值比法（ROR）和贝叶斯判别可信区间递进神经网络法（BCPNN）对美国FDA不良事件报告系统（FAERS）中2004年第1季度至2023年第2季度的奥马珠单抗相关不良事件（ADE）报告进行数据挖掘和信号检测。结果 通过数据挖掘和信号检测,涉及奥马珠单抗的ADE报告中提取了186,353份报告,涉及45,383例患者。在这些报告中,女性（65.31%）比例远高于男性（24.97%）。主要报告国家为美国（64.93%）和加拿大（11.96%）。报告者中以消费者（41.35%）和医师（36.97%）为主要群体。研究发现了621个ADE阳性信号,涉及25个系统器官分类（SOC）,主要包括呼吸系统、胸部和纵隔疾病（21.29%）以及感染和侵染类疾病（10.91%）。其中,183个信号被评定为高风险信号,其中包括57个新的高风险信号,如血压升高、易醒型失眠和心律失常等。这些发现有助于更全面地了解奥马珠单抗的安全性和潜在风险。结论 在奥马珠单抗的临床应用过程中,除了要注意药品说明中提到的已知不良反应外,还需特别警惕潜在的不良药物事件,如血压升高、心率升高、中间易醒型失眠、体位性心动过速综合征等。

Objective To use data mining method to detect the adverse reaction signal of omalizumab after marketing,and to provide reference for clinical safety and rational drug use．Methods In this study,the report odds ratio method（ROR）and Bayesian confidence propagation neural network（BCPNN）were used to conduct data mining and signal detection for omalizumab-related adverse event（ADE）reports from the FDA Adverse Event Reporting System（FAERS）from the first quarter of 2004 to the second quarter of 2023．Results Through data mining and signal detection,186,353 reports of ADE involving omalizumab were extracted,involving 45,383 patients．Among these reports,the proportion of women（65.31%）was much higher than that of men（24.97%）．The main reporting countries were the United States（64.93%）and Canada（11.96%）．consumers（41.35%）and doctors（36.97%）were the main groups of reporters．The study identified 621 ADE positive signals across 25 system organ classes（SOCs）,including respiratory,chest,and mediastinal diseases（21.29%）and infectious and infectious diseases（10.91%）．Of these,183 signals were assessed as high risk,including 57 new high-risk signals．These findings contribute to a more complete understanding of the safety and potential risks of omalizumab．Conclusions In the clinical application of omalizumab,in addition to the known adverse reactions mentioned in the drug description,special attention should be paid to potential adverse drug events,such as elevated blood pressure,elevated heart rate,intermediate insomnia,and postatic tachycardia syndrome．

目的 挖掘使用美托洛尔后的药物不良事件（ADE）,为临床合理用药提供参考意见。方法 对美国食品药品管理局（FDA）FDA药物ADE报告系统（FAERS）数据库进行信号挖掘,采用报告比值比法和比例报告比值法,分析FAERS数据库中2004年第1季度至2023年第2季度关于美托洛尔的ADE报告。结果 在FAERS数据库中收集到美托洛尔相关ADE共24 184例、667个阳性信号,共涉及27个系统器官分类。ADE严重报告共16 766（占69.33%）,ADE报告频次排名前3的分别是头晕、心动过缓、呼吸困难。结论 美托洛尔的不良反应主要集中在全身性疾病及给药部位各种反应、心脏器官疾病和各类损伤。在使用美托洛尔过程中发生ADE时,应该及时采取相应的干预措施。

Objective To explore the adverse drug events（ADEs）after the use of metoprolol and provide reference opinions for clinical rational drug use．Methods Signal mining was conducted on the FDA Adverse Event Reporting System（FAERS）database in the United States．The reporting ratio method and proportional reporting ratio method were used to analyze ADEs reports related to metoprolol in the FAERS database from the first quarter of 2019 to the second quarter of 2023．Results A total of 24 184 cases of metoprolol related ADEs were collected in the FAERS database,with 667 positive signals and a total of 27 system organ class involved．Conclusions The adverse reactions of metoprolol mainly focus on systemic diseases,various reactions at the administration site,heart organ diseases,and various injuries．It is recommended that timely intervention measures should be taken when ADE occurs during the use of metoprolol．

目的 基于SEER数据库分析三阴性乳腺癌（TNBC）的预后,并建立Cox回归临床预测模型且进行内部验证。方法 使用SEER*Stat软件（8.4.2版）筛选2010—2015年诊断为TNBC的病例,进行单因素和Cox多因素回归以及向后逐步回归分析,明确与生存相关的独立危险因素,构建预测TNBC患者3年和5年癌症特异生存（CSS）率的Nomogram图,并用受试者工作特征曲线,Harrell’s一致性指数,临床预测模型校准曲线以及决策曲线对该模型进行评估及内部验证,以评估该模型的临床预测效能。结果 共筛选出符合纳入标准的TNBC患者5 564例,按照7∶3的比例随机拆分为训练集（n=3 894）和验证集（n=1 670）。通过单因素,多因素分析显示TNM分期、放射治疗、化学治疗以及手术和其他治疗的先后顺序是与TNBC患者CSS显著相关的独立危险因素（P<0.05）。利用上述预后相关因素建立Nomogram图模型。训练集的C-index为0.731（95%CI：0.712~0.749）,验证集的C-index为0.719（95%CI：0.688~0.749）,训练集和验证集3年和5年生存ROC曲线的曲线下面积均>0.7,区分度较好,且校准曲线拟合良好。结论 TNM分期、放射治疗、化学治疗以及手术和其他治疗的先后顺序是TNBC的独立预后因素,基于此建立的Nomogram图临床预测模型区分度、准确度以及临床适用性较好,能较好地预测TNBC患者的生存预后。

Objective To analyze the prognosis of triple negative breast cancer（TNBC）based on the SEER database,and to establish a Cox regression clinical prediction model with internal validation．Methods Cases diagnosed with TNBC from 2010 to 2015 were screened using SEER*Stat software（version 8.4.2）,and univariate and Cox multifactorial regression as well as backward stepwise regression analyses were performed to identify the independent risk factors associated with survival,and to construct a clinical prediction model for predicting the three- and five-year cancer specific survival（CSV）of TNBC patients．Survival（CSS）rates of TNBC patients at 3 and 5 years,and the model was evaluated and internally validated using the ROC curve,Harrell’s consistency index（C-index）,clinical prediction model calibration curve,and decision-making curve（DCA curve）to assess the predictive efficacy of the model for clinical prediction．Results A total of 5 564 TNBC patients meeting the inclusion criteria were screened and randomly split into a training set（n=3 894）and a validation set（n=1 670）according to a 7∶3 ratio．By univariate,multivariate analysis showed that T-stage,N-stage,M-stage,radiotherapy,chemotherapy,and the sequence of surgery and other treatments were independent risk factors significantly associated with CSS in TNBC patients．The above prognostic-related factors were utilized to build a Nomogram plot model．The C-index was 0.731（95%CI：0.712-0.749）for the training set and 0.719（95%CI：0.688-0.749）for the validation set,and the areas under the curves of the 3- and 5-year survival ROC curves of both the training and validation sets were >0.7,which was a good differentiation,and the calibration curves were well-fitted．Conclusions T-stage,N-stage,M-stage,radiotherapy,chemotherapy,and the sequence of surgery and other treatments are independent prognostic factors for TNBC,and the Nomogram clinical prediction model based on this has good differentiation,accuracy,and clinical utility,and can better predict the survival prognosis of TNBC patients．

目的 构建并验证主动脉夹层B型（TBAD）患者急性期预后的列线图预测模型,帮助临床医生在急性期内更准确地评估TBAD患者的死亡风险,并制定更合适的治疗策略。方法 回顾性分析从重症监护医学信息数据库v2.2 中提取的399例 TBAD患者的人口学资料和临床资料,结局为TBAD患者急性期（≤14 d）内死亡。先采用最小绝对收缩选择算法回归筛选特征变量,再采用多因素分析确定独立预后因素,并据此构建预测模型。通过受试者工作特征曲线、校准曲线、决策曲线分析（DCA）评价列线图预测模型的性能和临床适用性。结果 APS Ⅲ评分、二氧化碳总量、红细胞分布宽度为TBAD患者14 d内死亡的独立预测因素。列线图预测模型在内部验证中的受试者工作特征曲线下面积为0.776（95% CI：0.691 ~ 0.860）,Hosmer-Lemeshow 检验P=0.604,校准曲线和标准曲线高度重合,表明该模型具有良好的区分度和校准度。同时,DCA曲线显示,预测模型在大部分的阈值概率范围内提供了显著的净收益。结论 本研究基于APS Ⅲ评分、二氧化碳总量、红细胞分布宽度构建的列线图预测模型可以较准确地预测TBAD患者14 d内的死亡风险,有助于临床医生制定更合适的个体化治疗策略。

Objective To develop and verify a nomogram for predicting acute phase outcomes in patients with type B aortic dissection（TBAD）,enabling clinicians to more precisely evaluate mortality risk in TBAD patients during the acute stage and to devise better treatment plans．Methods This retrospective study analyzed demographic and clinical data of 399 TBAD patients from the Medical Information Mart for Intensive Care IV v2.2,focusing on mortality within 14 days of the acute phase in TBAD patients． Initially,the Least Absolute Shrinkage and Selection Operator regression was employed for feature variable selection,and then multivariate analysis was used to identify independent prognostic factors for constructing the predictive model．The nomogram predictive model's effectiveness and clinical applicability were assessed via the Receiver Operating Characteristic curve,calibration curve,and Decision Curve Analysis（DCA）．Results Acute Physidogy Score Ⅲ score,total carbon dioxide,and red blood cell distribution width emerged as independent predictors of 14-day mortality in TBAD patients．The internal validation of the nomogram predictive model showed an area under the curve of 0.776（95%CI：0.691-0.860）,with a Hosmer-Lemeshow test P-value of 0.604． The close alignment of the calibration and standard curves suggested the model's strong discriminative power and calibration． Furthermore,the DCA curve revealed that the predictive model offered substantial net benefits within a wide range of threshold probabilities．Conclusions This study's nomogram,developed using APS Ⅲ score,total carbon dioxide,and red blood cell distribution width,accurately predicts the 14-day mortality risk in TBAD patients,assisting clinicians in creating better personalized treatment plans．

目的 血清同型半胱氨酸（Hcy）水平与慢性肾脏病（CKD）的进展相关,但中年人群的非线性关联研究较少,本研究旨在寻找慢性肾脏病危险因素。方法 本研究基于NHANES 1996—2006年数据,纳入5 361例45~65岁参与者,以估算肾小球滤过率（eGFR）<60 mL/（min·1.73 m²）和尿白蛋白/肌酐比值（uACR）≥30 mg/g评估肾功能下降。结果 通过逻辑回归及平滑曲线拟合分析发现,Hcy每升高1 µmol/L,eGFR降低的风险增加8%（OR=1.08,95%CI：1.06~1.10）,uACR升高的风险增加2%（OR=1.02,95%CI：1.00~1.04）。非线性分析显示,Hcy对eGFR的阈值效应拐点为13.4 µmol/L（拐点左侧OR=1.59,95%CI：1.49~1.70;右侧无显著关联）。亚组分析表明,性别、高血压、糖尿病等协变量无交互作用,然而,在敏感性分析中,糖尿病患者中Hcy与eGFR降低的关联更强（交互P=0.015 8）。结论 本研究提示,控制Hcy水平或可延缓美国中年人群（尤其是糖尿病患者）的肾功能衰退。

Objective Elevated serum homocysteine（Hcy）levels are linked to chronic kidney disease（CKD）progression,yet the nonlinear relationship in middle-aged populations remains underexplored．Methods This study analyzed data from 5 361 participants aged 45-65 years in the NHANES 1996-2006 cohort．Renal dysfunction was defined as an estimated glomerular filtration rate（eGFR）<60 mL/min/1.73 m² and urinary albumin-to-creatinine ratio（uACR）≥30 mg/g．Results Logistic regression and smoothed curve fitting revealed that each 1 µmol/L increase in Hcy elevated the risk of reduced eGFR by 8%（OR=1.08,95% CI：1.06-1.10）and uACR by 2%（OR=1.02,95% CI：1.00-1.04）．A nonlinear threshold effect was identified at 13.4 µmol/L,with a stronger association below this threshold（OR=1.59,95% CI：1.49-1.70）and no significant effect above it．Subgroup analyses showed no interactions with gender or hypertension,but a stronger Hcy-eGFR association was observed in diabetics（interaction P=0.0158）．Conclusions These findings suggest that controlling Hcy levels may mitigate renal decline,particularly in diabetic populations,warranting further causal investigations．

目的 分析晚期三阴性乳腺癌(TNBC)的危险因素并建立有效的预后列线图。方法 通过检索美国SEER(surveillance, epidemiology, and end results)数据库筛选晚期TNBC患者,采用单因素和多因素分析来确定晚期TNBC的独立预后因素,并以此构建了列线图,通过校准曲线检验和C指数(C-index)评估已建立的列线图。结果 共纳入4 687例晚期TNBC患者,与同期其他分子分型的乳腺癌相比较,TNBC的预后最差。单因素分析发现,年龄、性别、分期、手术、化疗、放疗、转移与更好的预后相关(P<0.05)。多因素分析发现年龄、性别、种族、分期、手术、化疗、放疗、各器官转移是患者预后的独立影响因素(P<0.05),并以此构建了列线图,其C-index为0.75(95％CI,0.71～0.79),校准图显示了预测的总生存期(OS)与观察到的OS之间的最佳一致性。结论 我们分析了晚期TNBC的临床特征,为TNBC患者的OS提供了一些预后因素,并根据这些预后因素制定了列线图,帮助临床医生进行风险管理并选择TNBC患者的长期生存策略。

Objective To analyze the risk factors of advanced triple-negative breast cancer (TNBC) and establish an effective prognostic nomogram. Methods Screening patients with advanced TNBC by searching the SEER (surveillance, epidemiology, and end results) database, using univariate and multivariate analysis to determine the independent prognostic factors of advanced TNBC, and constructing a nomogram based on it. Results A total of 4 687 patients with advanced TNBC were included. Compared with other types of breast cancer over the same period, TNBC had the worst prognosis. Univariate analysis found that age, gender, stage, surgery, chemotherapy, radiotherapy, and metastasis were associated with a better prognosis (P<0.05). Multivariate analysis found that age, gender, race, stage, surgery, chemotherapy, radiotherapy, and metastasis of the organs were independent factors affecting the prognosis of patients (P<0.05), and constructed a nomogram with a C-index of 0.75 ( 95% CI, 0.71～0.79). The calibration chart showed the best agreement between the predicted overall survival (OS) and the observed OS. Conclusion We analyzed the clinical features of advanced TNBC, provided some prognostic factors for the OS of TNBC patients, and developed a nomogram based on these prognostic factors to help clinicians manage risk and choose long-term survival strategies for TNBC patients.

       目的   构建并验证主动脉夹层B型（TBAD）患者急性期预后的列线图预测模型，帮助临床医生在急性期内更准确地评估TBAD患者的死亡风险，并制定更合适的治疗策略。方法   回顾性分析从重症监护医学信息数据库v2.2 中提取的399例 TBAD患者的人口学资料和临床资料，结局为TBAD患者急性期（≤14 d）内死亡。先采用最小绝对收缩选择算法回归筛选特征变量，再采用多因素分析确定独立预后因素，并据此构建预测模型。通过受试者工作特征曲线、校准曲线、决策曲线分析（DCA）评价列线图预测模型的性能和临床适用性。结果  APS Ⅲ评分、二氧化碳总量、红细胞分布宽度为TBAD患者14 d内死亡的独立预测因素。列线图预测模型在内部验证中的受试者工作特征曲线下面积为0.776（95% CI：0.691 ~ 0.860），Hosmer-Lemeshow 检验P=0.604，校准曲线和标准曲线高度重合，表明该模型具有良好的区分度和校准度。同时，DCA曲线显示，预测模型在大部分的阈值概率范围内提供了显著的净收益。结论   本研究基于APS Ⅲ评分、二氧化碳总量、红细胞分布宽度构建的列线图预测模型可以较准确地预测TBAD患者14 d内的死亡风险，有助于临床医生制定更合适的个体化治疗策略。

       Objective  To develop and verify a nomogram for predicting acute phase outcomes in patients with type B aortic dissection（TBAD），enabling clinicians to more precisely evaluate mortality  risk in TBAD patients during the acute stage and to devise better treatment plans．Methods  This retrospective study analyzed demographic and clinical data of 399 TBAD patients from the Medical Information Mart for Intensive Care IV v2.2，focusing on mortality within 14 days of the acute phase in TBAD patients．Initially，the Least Absolute Shrinkage and Selection Operator regression was employed for feature variable selection，and then multivariate analysis was used to identify independent prognostic factors for constructing the predictive model．The nomogram predictive model’s effectiveness and clinical applicability were assessed via the Receiver Operating Characteristic curve，calibration curve，and Decision Curve Analysis（DCA）．Results  Acute Physidogy Score Ⅲ score，total carbon dioxide，and red blood cell distribution width emerged as independent predictors of 14-day mortality in TBAD patients．The internal validation of the nomogram predictive model showed an area under the curve of 0.776（95%CI：0.691-0.860），with a Hosmer-Lemeshow test P-value of 0.604．The close alignment of the calibration and standard curves suggested the model’s strong discriminative power and calibration．Furthermore，the DCA curve  revealed that the predictive model offered substantial net benefits within a wide  range of threshold probabilities．Conclusions  This study's nomogram，developed using APS Ⅲ score，total carbon dioxide，and  red blood cell distribution width，accurately predicts the 14-day mortality risk in TBAD patients，assisting clinicians in creating better personalized treatment plans．

       目的   血清同型半胱氨酸（Hcy）水平与慢性肾脏病（CKD）的进展相关，但中年人群的非线性关联研究较少，本研究旨在寻找慢性肾脏病危险因素。方法   本研究基于NHANES 1996—2006年数据，纳入5 361例45~65岁参与者，以估算肾小球滤过率（eGFR）＜60 mL/（min·1.73 m² ）和尿白蛋白/肌酐比值（uACR）≥30 mg/g评估肾功能下降。结果   通过逻辑回归及平滑曲线拟合分析发现，Hcy每升高1 µmol/L，eGFR降低的风险增加8%（OR=1.08，95%CI：1.06~1.10），uACR升高的风险增加2%（OR=1.02，95%CI：1.00~1.04）。非线性分析显示，Hcy对eGFR的阈值效应拐点为13.4 µmol/L（拐点左侧OR=1.59，95%CI：1.49~1.70；右侧无显著关联）。亚组分析表明，性别、高血压、糖尿病等协变量无交互作用，然而，在敏感性分析中，糖尿病患者中Hcy与eGFR降低的关联更强（交互P=0.015 8）。结论   本研究提示，控制Hcy水平或可延缓美国中年人群（尤其是糖尿病患者）的肾功能衰退。

        Objective   Elevated serum homocysteine（Hcy）levels are linked to chronic kidney disease（CKD）progression，yet the nonlinear relationship in middle-aged populations remains underexplored．Methods  This  study analyzed data from 5 361 participants aged 45–65 years in the NHANES 1996–2006 cohort．Renal dysfunction was defined as an estimated glomerular filtration rate（eGFR）＜60 mL/min/1.73 m²  and urinary albumin-to-creatinine ratio（uACR）≥30 mg/g．Results  Logistic regression and smoothed curve fitting revealed that each 1 µmol/L increase in Hcy elevated the risk of reduced eGFR by 8%（OR=1.08，95% CI：1.06–1.10）and uACR by 2%（OR=1.02，95% CI：1.00–1.04）．A nonlinear threshold effect was identified at 13.4 µmol/L，with a stronger association below this threshold（OR=1.59，95% CI：1.49–1.70）and no significant effect above it．Subgroup analyses showed no interactions with gender or hypertension，but a stronger Hcy-eGFR association was observed in diabetics（interaction P=0.0158）．Conclusions  These findings suggest that controlling Hcy levels may mitigate renal decline，particularly in diabetic populations，warranting further causal investigations．

  目的   基于SEER数据库分析三阴性乳腺癌（TNBC）的预后，并建立Cox回归临床预测模型且进行内部验证。方法   使用SEER*Stat软件（8.4.2版）筛选2010—2015年诊断为TNBC的病例，进行单因素和Cox多因素回归以及向后逐步回归分析，明确与生存相关的独立危险因素，构建预测TNBC患者3年和5年癌症特异生存（CSS）率的Nomogram图，并用受试者工作特征曲线，Harrell’s一致性指数，临床预测模型校准曲线以及决策曲线对该模型进行评估及内部验证，以评估该模型的临床预测效能。结果   共筛选出符合纳入标准的TNBC患者5 564例，按照7∶3的比例随机拆分为训练集（n=3 894）和验证集（n=1 670）。通过单因素，多因素分析显示TNM分期、放射治疗、化学治疗以及手术和其他治疗的先后顺序是与TNBC患者CSS显著相关的独立危险因素（P＜0.05）。利用上述预后相关因素建立Nomogram图模型。训练集的C-index为0.731（95%CI：0.712~0.749），验证集的C-index为0.719（95%CI：0.688~0.749），训练集和验证集3年和5年生存ROC曲线的曲线下面积均＞0.7，区分度较好，且校准曲线拟合良好。结论  TNM分期、放射治疗、化学治疗以及手术和其他治疗的先后顺序是TNBC的独立预后因素，基于此建立的Nomogram图临床预测模型区分度、准确度以及临床适用性较好，能较好地预测TNBC患者的生存预后。

    Objective  To analyze the prognosis of triple negative breast cancer（TNBC）based on the SEER database，and to establish a Cox regression clinical prediction model with internal validation．Methods  Cases diagnosed with TNBC from 2010 to 2015 were screened using SEER*Stat software（version 8.4.2），and univariate and Cox multifactorial  regression as well as backward stepwise regression analyses were performed to identify the independent risk factors associated with survival，and to construct a clinical prediction model for predicting the three- and five-year cancer specific survival（CSV）of TNBC patients．Survival（CSS）rates of TNBC patients at 3 and 5 years，and the model was evaluated and internally validated using the ROC curve，Harrell’s consistency index（C-index），clinical prediction model calibration curve，and decision-making curve（DCA curve）to assess the predictive efficacy of the model for clinical prediction．Results  A total of 5 564 TNBC patients meeting the inclusion criteria were screened and randomly split into a training set（n=3 894）and a validation set（n=1 670）according to a 7∶3 ratio．By univariate，multivariate analysis showed that T-stage，N-stage，M-stage，radiotherapy，chemotherapy，and the sequence of surgery and other treatments were independent risk factors significantly associated with CSS in TNBC patients．The above prognostic-related factors were utilized to build a Nomogram plot model．The C-index was 0.731（95%CI：0.712-0.749）for the training set and 0.719（95%CI：0.688-0.749）for the validation set，and the areas under the curves of the 3- and 5-year survival ROC curves of both the training and validation sets were ＞0.7，which was a good differentiation，and the calibration curves were well-fitted．Conclusions  T-stage，N-stage，M-stage，radiotherapy，chemotherapy，and the  sequence of  surgery and other treatments are independent prognostic factors for TNBC，and the Nomogram clinical prediction model based on this has good differentiation，accuracy，and clinical utility，and can better predict the survival prognosis of TNBC patients．

       目的   挖掘使用美托洛尔后的药物不良事件（ADE），为临床合理用药提供参考意见。方法   对美国食品药品管理局（FDA）FDA药物ADE报告系统（FAERS）数据库进行信号挖掘，采用报告比值比法和比例报告比值法，分析FAERS数据库中2004年第1季度至2023年第2季度关于美托洛尔的ADE报告。结果   在FAERS数据库中收集到美托洛尔相关ADE共24 184例、667个阳性信号，共涉及27个系统器官分类。ADE严重报告共16 766（占69.33%），ADE报告频次排名前3的分别是头晕、心动过缓、呼吸困难。结论   美托洛尔的不良反应主要集中在全身性疾病及给药部位各种反应、心脏器官疾病和各类损伤。在使用美托洛尔过程中发生ADE时，应该及时采取相应的干预措施。

       Objective  To explore the adverse drug events（ADEs）after the use of metoprolol and provide  reference opinions for clinical rational drug use．Methods  Signal mining was conducted on the FDA Adverse Event Reporting System（FAERS）database in the United States．The  reporting  ratio method and proportional  reporting  ratio method were used to analyze ADEs reports related to metoprolol in the FAERS database from the first quarter of 2019 to the second quarter of 2023．Results  A total of 24 184 cases of metoprolol related ADEs were collected in the FAERS database，with 667 positive signals and a total of 27 system organ class involved．Conclusions  The adverse reactions of metoprolol mainly focus on systemic diseases，various reactions at the administration site，heart organ diseases，and various injuries．It is recommended that timely intervention measures should be taken when ADE occurs during the use of metoprolol．