Objective To explore the prognostic value of hs-cTnⅠ in patients with suspected acute coronary syndrome(ACS)in emergency department.Methods A large-scale,prospective observa-tional study was conducted on totally 966 patients with suspected ACS admitted in Fuwai Hospi-tal from January 2017 to October 2020.Their baseline serum/plasma hs-cTnⅠ level was detected at admission,conventional treatment was performed,and relevant data were collected.Logistic regression analysis was used to predict the risk of primary and secondary endpoint events within 30 d by hs-TnⅠ concentration,and subgroup analysis was performed.Results Among the 966 patients,the time from chest pain to visit was 5.0(2.5,13.0)h,and 284 patients had primary end-point events within 30 d,including 283 cases of myocardial infarction(99.6％)at the first visit,1 case of recurrent myocardial infarction(0.4％),5 cases of cardiovascular death(1.8％),and 1 case of unplanned revascularization(0.4％).When hs-cTnⅠ was at the minimum detection limit of 2 ng/L,the incidence of adverse events was 5.8％,when the limit of 70 ng/L,the incidence was 49.2％,and when of 316 ng/L,the incidence reached 100％.The model could correctly classify 92.3％of the patients.Conclusion The hs-cTn sequence has a good predictive effect for the risk of short-term cardiovascular adverse events in Chinese population.

The c-ros oncogene 1(ROS1)gene is primarily fused with CD74 and SLC34A in non-small cell lung cancer(NSCLC),and also fused with SDC4,EZR,TPM3,TFG,ZCCHC8,SLMAP,and MYO5C genes.The ROS1 fusion genes retain the tyrosine kinase structural domain of ROS1.When abnormally activated,the ROS1 fusion genes can activate the ROS1 tyro-sine kinase domain and downstream signaling pathways,leading to tumor growth,proliferation,migration,and invasion.Patients with ROS1 fusion-positive NSCLC are characterized by a young age of onset and a likelihood of brain metastasis.The first drug approved in China for ROS1 fusion-positive NSCLC is crizotinib,a ROS1 tyrosine kinase inhibitor.However,crizotinib is prone to developing resistance.Understanding its resistance mechanisms and how to treat ROS1-positive NSCLC after resistance has become an urgent issue that must be addressed.Highly effective and safe multi-targeted drugs bring hope to patients with ROS1-positive NSCLC.This article reviews the multi-targeted drugs for ROS1 gene-positive NSCLC and their resistance mecha-nisms.

Objectives:To compare the diagnostic efficacy of non-ST-segment elevation myocardial infarction (NSTEMI) and the predictive value for major adverse cardiovascular events (MACE) of the 0/3-hour algorithm for high-sensitivity cardiac troponin (hs-cTn) recommended by the 2015 European Society of Cardiology (ESC) guidelines for the management of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and the 2021 "Chinese Expert Consensus on Laboratory Testing and Clinical Application of Cardiac Troponin" in suspected acute coronary syndrome (ACS) patients in the Chinese population. Methods:This is a multicenter prospective observational study,including 1527 patients with suspected ACS from three clinical centers from January 2017 to September 2020.Plasma hs-cTnI levels were measured using the ARCHITECT assay at the time of presentation and 3 hours later in patients with suspected ACS (test determination).Clinical judgment (independent clinical judgment by cardiac experts,independent of the test results) was used as the gold standard to compare the sensitivity,specificity,and consistency of the two diagnostic algorithms,and to analyze their predictive value for MACE at 30 days and 180 days.MACE in this study was defined as a composite event of cardiovascular death,myocardial infarction,and unplanned coronary revascularization. Results:According to clinical judgment,there were 400 patients with NSTEMI and 1127 patients without NSTEMI.The 0/3-hour algorithm recommended by the 2021 Chinese Expert Consensus showed higher sensitivity in diagnosing NSTEMI than the 2015 ESC guidelines (91.50％[95％ CI:88.32％-94.04％]vs.87.75％[95％ CI:84.13％-90.80％]),but slightly lower specificity (93.88％[95％ CI:92.32％-95.21％]vs.95.56％[95％ CI:94.19％-96.69％]),with both differences being statistically significant (both P<0.001).In the follow-up at 30 days and 180 days,the incidence of MACE in patients diagnosed with NSTEMI by both algorithms was higher than in those without NSTEMI (P<0.001).The incidence of MACE at 30 days and 180 days for the group excluded from the diagnosis of NSTEMI by 2015 ESC guidelines was 0.19％ and 1.120％,respectively,and for the NSTEMI group was 2.89％ and 3.68％,respectively;for the group excluded from NSTEMI by the 2021 Chinese Expert Consensus,the incidence was 0.096％ and 0.770％,respectively,and for the NSTEMI group was 2.91％ and 4.36％,respectively.Cox analysis showed that the HR ratio for MACE at 180 days in the NSTEMI group diagnosed by both algorithms was 3.418 and 5.892,respectively,significantly higher than the group excluded from NSTEMI. Conclusions:The 0/3-hour algorithm recommended by the 2021 Chinese Expert Consensus has superior diagnostic sensitivity compared to the 2015 ESC NSTE-ACS guidelines,at the cost of slightly lower specificity.Both algorithms can effectively predict MACE within 180 days,but based on the data from this study,the algorithm recommended by the 2021 Chinese Expert Consensus is more sensitive in predicting the risk of MACE,and patients excluded from the diagnosis of NSTEMI by this method have a lower incidence of MACE,suggesting that its application in clinical practice may be more helpful in terms of long-term safe management of patients.

Objective:This study aims to demonstrate the feasibility of using Bio-layer Interferometry (BLI) for label-free detection of peripheral blood biomarkers, using C-reactive protein (CRP) as a model molecule.Methods:A total of 85 clinical remnant serum samples from routine laboratory tests were collected from Fuwai Hospital, Chinese Academy of Medical Sciences, from July 2021 to May 2022. The biotinylated anti-CRP antibody was immobilized onto streptavidin-functionalized BLI probes. The GatorPrime BLI system was used to detect series of diluted CRP standards in real-time, and to generate dynamic binding curves for establishing standard curves based on the relationship between concentration and initial binding rates. The sensitivity of the method, including the limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ), was evaluated according to Clinical & Laboratory Standards Institute (CLSI) guidelines. Serum samples and third-party quality control materials were used to evaluate the precision, while linearity was verified through the dilution of a high-concentration serum series. Method comparison between the label-free BLI assay and conventional clinical laboratory immunoassays was conducted using Passing-Bablok regression and Spearman correlation analysis.Results:The GatorPrime BLI system demonstrated a dynamic detection range of 0.6-300 mg/L for CRP standards, and the linearity within this range was validated using serum samples. The LoB, LoD, and LoQ for this method were determined to be 0.246 mg/L, 0.573 mg/L, and 2.158 mg/L, respectively. Precision analysis showed that the total laboratory imprecision of the four levels of quality control materials (21.15-57.26 mg/L) ranged from 5.8% to 9.0%, and the total imprecision of the two serum samples (2.32 mg/L and 100.06 mg/L) was 22.3% and 7.4%, respectively. Methodological comparison with two commonly used clinical laboratory immunoassays revealed a strong correlation with our method(Passing-Bablok regression: Y=?1.065+1.119 X and Y=?0.452+1.034 X, r=0.993 and r=0.976, P<0.001). Conclusions:The label-free BLI immunoassay method enables the detection of CRP across a broad concentration range in blood samples, with analytical performance meeting the requirements for laboratory testing. This method shows potential as a reliable and efficient alternative for CRP measurement in clinical practice.

OBJECTIVE To investigate the effect of gene polymorphism on opioid-induced constipation. METHODS The target genes related to opioid-induced constipation were screened out through searching guidelines， databases and evidence-based medical data， and then 100 cancer pain patients who received opioid drugs for analgesia were included as the study subjects. According to whether there were adverse effects of constipation after medication or not， they were divided into test group and control group， with 50 cases in each group. The target gene was detected by PCR or fluorescence in situ hybridization. The SNPStats program was used to carry out Hardy-Weinberg balance test and correlation analysis between gene polymorphism and opioid-induced constipation. The multivariate Logistic regression analysis was used to explore the relevant predictive factors of opioid-induced constipation， and receiver operating characteristic （ROC） curve of subjects was drawn to analyze the effectiveness of each predictive factor in predicting opioid-induced constipation. RESULTS CYP2D6， CYP3A5*3， ABCB1 and OPRM1 were selected as target genes for detection. The results of genotype detection showed that the frequency distribution of CYP2D6 （rs1065852， rs1135822， rs16947， rs28371725， rs28371735）， CYP3A5*3 （058rs776746）， ABCB1 （062rs1045642）， OPRM1 （047rs1799971） alleles were consistent with Hardy-Weinbergbalance test. The correlation analysis results showed that the proportion of genotype GG and AG in CYP3A5*3 （058rs776746， 163.com A＞G） and genotype AA and AG in OPRM1 （047rs1799971， A＞G） of patients was significantly higher in test group than that in the control group （P＜0.05）. Multivariate Logistic regression analysis showed that medication duration， CYP3A5*3 and OPRM1 gene polymorphism could be used as predictors of opioid- induced constipation in patients （P＜0.05）. The ROC curve analysis results showed that the areas under the ROC curves for medication duration and CYP3A5*3， OPRM1 gene polymorphism were 0.648， 0.640 and 0.670， respectively， with the optimal cutoff values of 124.0， 0.5 and 0.5， respectively. CONCLUSIONS Genotype GG and AG in CYP3A5*3 （058rs776746，A＞G） and genotype AA and AG in OPRM1 （047rs1799971，A＞G） are associated with opioid-induced constipation， which are expected to become clinical predictors of opioid-induced constipation， and more attention should be paid to the occurrence of constipation in patients who have been taking opioids for a long time.

Objective:To explore the predictive value of single high-sensitivity cardiac troponin I (hs-cTnI) concentration of 30-day cardiovascular adverse events in patients with suspected acute coronary syndrome (ACS).Methods:This is a multicenter, prospective and observational clinical study. Patients with suspected ACS who were admitted into the emergency department of Fuwai Hospital, the First Affiliated Hospital of Sun Yat-sen University and Nanjing First Hospital from January 2017 to September 2020 were enrolled. hs-cTnI result at the time of visit was obtained from patients with suspected ACS. Patients were followed up for 30 days and patients were divided into no events group and events group according to the presence or absence of 30-day cardiovascular adverse events (acute myocardial infarction (including index), unplanned revascularization and cardiovascular death). The predictive value of single Hs-cTnI at different concentration thresholds on the adverse event was evaluated in terms of sensitivity, negative predictive value (NPV) and 95% confidence interval ( CI). The best threshold was defined as: missed diagnosis rate <2% and NPV >99%. Patients were sub-grouped according to the confounders of hs-cTnI (sex, age, chest pain duration, estimated glomerular filtration rate), and Chi-square test was used to compare sensitivity and NPV among various subgroups. Results:A total of 1 461 patients were included. Among them, 387 patients (26.5%) had 30-day adverse cardiovascular events and 1 074 patients (73.5%) had no adverse cardiovascular events. Mean age was (62±12) years old and 905 were males (61.9%). When the concentration of hs-cTnI was less than 2 ng/L (limit of detection), the missed diagnosis rate of 30-day cardiovascular adverse events was 0.8% (3/387), the sensitivity was 99.2% (95% CI 97.6%-99.8%), and NPV was 98.7% (95% CI 96.0%-99.7%). When hs-cTnI concentration was less than 6 ng/L, the missed diagnosis rate was 1.8%, the sensitivity was 98.2% (95% CI 96.1%-99.2%), and NPV was 99.0% (95% CI 97.9%-99.6%). Subgroup analysis showed that the sensitivity and NPV of single hs-cTnI concentration <6 ng/L for 30-day cardiovascular adverse events were lower in patients with chest pain less than 3 h than those with chest pain time>3 hours ( P<0.05). Conclusions:Single hs-cTnI concentration less than 6 ng/L can predict the risk of 30-day cardiovascular adverse events in suspected ACS patients, but continuous monitoring is recommended for patients with chest pain onset≤3 hours.

Objective:The 97.5th percentile upper reference limit (97.5th URL) of N-terminal prob-type natriuretic peptide (NT-proBNP) is influenced by multiple factors and depends on the inclusion criteria of apparently healthy people. In this study, the reference upper limit of NT-proBNP was established on apparently healthy people in Beijing area with abnormal hs-cTn as the exclusion criterion.Methods:According to the latest expert consensus recommendation standards of natriuretic peptide in the detection and clinical application of heart failure published by the Clinical Application Group of Cardiac Bio-Markers of the International Union of Clinical Chemistry, 1 635 healthy people without abnormal appearance of routine indicators such as sex, age, glycated hemoglobin, estimated glomerular filtration rate and medical history were collected. After excluding participants with potential myocardial injury according to hs-cTnI and/or hs-cTnT concentration>99th URL, NT-proBNP 97.5th URL was established in healthy subjects aged 21-40 years ( n=205), 41-50 years ( n=535), 51-60 years ( n=556) and >60 years ( n=339) based on non-parametric statistics. Results:The level of NT-proBNP was positively correlated with age ( r=0.254, P<0.001). The levels of NT-proBNP were positively correlated with hs-cTnI, hs-cTnT in males ( r=0.377 and r=0.429, both P<0.001). The levels of NT-proBNP were also positively correlated with hs-cTnI, hs-cTnT in females ( r=0.132 and r=0.296, both P<0.001). When hs-cTn>99th URL was used as the criterion to exclude patients with potential myocardial injury, among apparently healthy people aged 21-40 years old, 41-50 years old, 51-60 years old and >60 years old, male NT-proBNP 97.5th URL was 81.9 (90% CI 60.0-588.8), 141.2 (90% CI 100.0-263.6), 272.0 (90% CI 193.0-494.0) and 547.9 (90% CI 311.2-738.6), respectively; For females, the rates were 227.5 (90% CI 81.9-360.8), 153.2 (90% CI 128.2-239.5), 300.6 (90% CI 211.0-376.4) and 395.8 (90% CI 242.3-543.5) ng/L, respectively. Conclusions:This study confirmed that hs-cTn>99th URL can be used as an apparent population screening criterion for natriuretic peptide reference interval studies, which is helpful to remove conventional means to include individuals with occult myocardial injury in apparently healthy patients, so as to establish a more rigorous healthy cohort and establishing solid normal NT-proBNP reference interval.

Objective:To explore the relationship between hematocrit, early fluid therapy, and clinical outcomes in patients with septic shock, and to provide evidence for fluid resuscitation therapy and prognosis assessment in these patients.Methods:The clinical information of patients with septic shock who were diagnosed and treated in the Emergency Intensive Care Unit (EICU) of the First Affiliated Hospital of Wenzhou Medical University from January 1, 2018 to December 31, 2020 were collected. Taking the survival or death of patients 28 days after admission as the end point of clinical research, the patients were divided into the survival and death groups. After analyzing the basic data of the two groups, the univariate and multivariate COX regression analyses were used to analyze the evaluation value of Δ Hematocrit (HCT) d2-d1 and ΔHCT d3-d1 on the prognosis of patients with septic shock. At the same time, the Kaplan-Meier survival curve was used to analyze the overall survival rate of patients with septic shock, and the smooth curve fitting graph was used to verify its relationship with net fluid intake and death. Results:There were 241 cases in the survival group and 67 cases in the death group. Univariate COX analysis showed statistically significant differences between the survival and death groups in acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) ( P=0.0006), red cell volume distribution width (RDW) ( P=0.0043), age ( P=0.0184), ΔHCT d2-d1 ( P=0.0136), ΔHCT d3-d1 ( P=0.0204), and white blood cell (WBC) ( P=0.0444). Multivariate COX analysis showed that ΔHCT d2-d1 ( P=0.0115) and ΔHCT d3-d1 ( P=0.0029) were independent risk factors for death in EICU patients with septic shock. ΔHCT d2-d1 and ΔHCT d3-d1 were divided into three groups according to the three-digit method. The Kaplan-Meier survival curve showed no significant difference among the three groups in the overall survival rate related to ΔHCT d2-d1 ( P=0.16), but there was a statistically significant difference in the overall survival rate among the three groups related to ΔHCT d3-d1 ( P=0.025). The smooth fitting curve of ΔHCT d3-d1, net fluid intake, and prognosis showed that ΔHCT d3-d1 was negatively correlated with net fluid intake, and the middle ΔHCT d3-d1 group had the best prognosis. Conclusions:The value of ΔHCT d3-d1 is related to the net fluid intake of patients with septic shock. An appropriate decrease in HCT on the third day can improve the prognosis of patients with septic shock. The dynamic changes of hematocrit can provide a certain basis for fluid resuscitation and prognosis evaluation in patients with septic shock.

OBJECTIVE To compare five com monly used judgment criteria for potentially inappropriate medication （PIM）in the elderly ，and to provide reference for clinical selection of appropriate PIM evaluation tools for the elderly. METHODS From the aspects of applicable age ，content and scale characteristics ，five commonly used PIM judgment criteria for the elderly at home and abroad were analyzed and compared ，namely Beer ’s criteria ，STOPP/START v 2 criteria，ACOVE 3 criteria，PIM-Check criteria and“Judgment Criteria for Potentially Inappropriate Medication for Chinese Elderly ”（Chinese criteria ）. RESULTS The five standards both overlapped and focused in terms of scale characteristics. In each study ，the incidence of PIM was different according to different standards. Proton pump inhibitors ，diuretics，non-steroidal anti-inflammatory drugs and anticoagulants were the most frequently occurring PIM drugs for the elderly. CONCLUSIONS Combining with the specific conditions of patients and fully considering the benefits and risks of treatment ，rational selection and combination of five PIM judgment criteria ，and necessary supplements to my country ’s PIM judgment criteria ，will help clinicians and pharmacists to improve the efficacy and safety of the medication in the elderly patients.

This article aims to summarize the significance of the establishment of human milk banks, the status of human milk banks in mainland China, analyze the relevant factors that affect the development of human milk banks, and propose corresponding countermeasures to provide a reference for improving the status of human milk banks in mainland China and promoting sustainable development.