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This article reports a patient with typical Cushing syndrome′s manifestations and extremely low plasma cortisol level, indicating glucocorticoid hypersensitivity syndrome. After treatment with the glucocorticoid receptor antagonist mifepristone, the patient′s Cushing symptoms were significantly relieved, and cortisol levels returned to normal. The aim of this report is to enhance clinical awareness among physicians regarding glucocorticoid hypersensitivity syndrome.
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Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S2 (S2) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S2 for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S2, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S2 resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.
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Objective To investigate the status and influencing factors of sleep in preterm infants at 1 month corrected age.Methods 130 preterm infants admitted to the NICU of 3 tertiary hospitals in Hubei Province were recruited as participants during May 2021 and March 2022.Sleep assessment of preterm infants was conducted at 1 month corrected age.Infants'sleep was assessed using the Brief Infant Sleep Questionnaire(BISQ).Multivariate linear regression model was used to analyze the influencing factors of sleep status(sleep latency,night awakenings,nocturnal sleep duration,daytime sleep duration,24 h sleep duration)of preterm infants.Results A total of 124 preterm infants completed the follow-up at 1 month corrected age.Multiple linear regression analysis showed that feeding patterns and sleep initiation patterns affected the sleep latency;gestational age,mechanical ventilation duration,maternal education level,and sleep initiation patterns were influencing factors of night awakenings;nocturnal sleep duration was influenced by mechanical ventilation duration and feeding patterns;daytime sleep duration and 24 h sleep duration were influenced by feeding patterns and maternal educational level.Conclusion The preterm infant sleep is influenced by gestational age,duration of mechanical ventilation,feeding patterns,maternal education level,and sleep initiation patterns.Neonatology staff should focus on the preterm infants discharged from NICU and develop targeted intervention plans based on the determined influencing factors to improve the sleep status of preterm infants.
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Glycyrrhizae Radix et Rhizoma,a traditional Chinese medicine also known as Gan Cao(GC),is frequently included in clinical prescriptions for the treatment of pneumonia.However,the pharmacological com-ponents of GC for pneumonia treatment are rarely explored.Gan An He Ji oral liquid(GAHJ)has a simple composition and contains GC liquid extracts and paregoric,and has been used clinically for many years.Therefore,GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia.We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days.Using the intelligent mass spectrometry data-processing technologies to analyze the meta-bolism of GC in vivo,we obtained 168 related components of GC in humans,consisting of 24 prototype components and 144 metabolites,with 135 compounds screened in plasma and 82 in urine.After analysis of the metabolic transformation relationship and relative exposure,six components(liquiritin,liquiritigenin,glycyrrhizin,glycyrrhetinic acid,daidzin,and formononetin)were selected as potential effective components.The experimental results based on two animal pneumonia models and the in-flammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase(iNOS).Interestingly,glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo.The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS.Thus,the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.
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Objective:To evaluate the accuracy of lung ultrasound score (LUSS) in predicting emerging hypoxemia after tracheal extubation in the patients in postanesthesia care unit (PACU).Methods:A total of 333 patients of both sexes, aged 18-89 yr, of American Society of Anesthesiologist physical statusⅠ-Ⅲ, scheduled for elective abdominal surgery, were included in the study.Lung ultrasound examinations were performed before operation (T 0) and on admission to PACU (T 1), and the LUSS were recorded as LUSS 0 and LUSS 1.Arterial blood gas analysis was conducted at 20 min after tracheal extubation, and oxygenation index (PaO 2/FiO 2) were recorded.Patients were divided into 2 groups according to the oxygenation index: PaO 2/FiO 2<300 mmHg group (hypoxemia group), and PaO 2/FiO 2≥300 mmHg group (non-hypoxemia group). Multivariate logistic regression analysis and the receiver operating characteristic curve were used to evaluate the accuracy of LUSS 1 in predicting the emerging hypoxemia after extubation in the patients in PACU. Results:The incidence of emerging hypoxemia in PACU after extubation was 9.0%.Multivariate logistic regression analysis indicated that LUSS 1 and body mass index were independent risk factors for emerging hypoxemia after extubation in the patients in PACU.The area under the ROC curve for LUSS 1 was 0.873 ( P<0.001, 95%CI 0.812-0.935). The patients with LUSS 1<7 had a lower risk of hypoxemia after extubation (LR -=0.15, 95%CI 0.05-0.45), and the patients with LUSS 1>10 had a higher risk of hypoxemia after extubation (LR + =17.25, 95%CI 7.35-40.51). Conclusion:LUS can effectively predict the development of hypoxemia after tracheal extubation in the patients in PACU.
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COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.
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Objective:To develop an evaluation index system for dynamic adjustment effect of medical service prices in public hospitals, as a set of quantitative evaluation tools for management departments to keep track of the trend in time, implement dynamic monitoring and guide decision-making.Methods:Based on the evaluation system of price adjustment effect, through the importance assessment of expert consultation and multiple index percentile method, the scoring criteria were formulated and the empirical analysis was carried out.Results:The total scores of hospital A and hospital B were 71.31 and 77.94 respectively, classified as " average" . The evaluation could basically reflect the effect of dynamic adjustment of medical service price in public hospitals.Conclusions:The evaluation has the functions of displaying differences, witnessing achievements and tracing causes. It can be used to evaluate the effect of dynamic adjustment of regional prices, to assist the regulators to keep track of trends, monitor dynamically and guide decision-making in time, and be used by hospitals in self-evaluation to find problems, improve their own operation and promote the healthy development of hospitals.
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Migraine is a common nervous system disease, which could seriously affect the quality of life. However, the medical treatment of migraine cannot meet the clinical needs at present. With the deepening of research, serotonin 1F receptor agonists and drugs targeting CGRP are more and more developed and marketed. In this paper, the mechanism of action, safety and efficacy, metabolic characteristics of these drugs were systematically evaluated to provide a more scientific basis for clinical prevention and treatment of migraine.
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Objective@#To investigate the role of microRNA-96-5p in the proliferation and invasion of gastric cancer cells and its molecular mechanism.@*Methods@#From June 2015 to January 2017, 53 resected specimens were collected. The transcriptional levels of microRNA-96-5p and forkhead box Q1 (FoxQ1) in gastric cancer tissues and the matched para-cancerous tissues were quantified by quantitative real-time PCR (qRT-PCR). The expression of FoxQ1 protein was also detected by immunohistochemistry (IHC). The relationship between microRNA-96-5p expression and the clinicopathological features of gastric cancer and its correlation with FoxQ1 expression were analyzed. The expressions of miRNA-96-5p in gastric cancer tissue and adjacent normal tissue were detected by qRT-PCR. miRNA-96-5p mimics was transfected to BGC-823 gastric cancer cells. The effects of miRNA-96-5p on cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and Transwell assay, respectively. The protein expressions of FoxQ1, E-cadherin and vimentin were determined by western blot. The relationship between FoxQ1 and miRNA-96-5p expressed in BGC-823 cells was detected by dual-luciferase reporter assay.@*Results@#The median expression of miRNA-96-5p in gastric cancer tissue was 1.05, significantly lower than 3.23 of para-cancerous tissues (P<0.05). The positive rate of FoxQ1 expression in gastric cancer tissue was 71.7%, significantly higher than 28.3% of para-cancerous tissues (P<0.05). The expression of FoxQ1 was negatively corelated with the level of miRNA-96-5p (r=-0.613, P=0.006). The expression of miRNA-96-5p in gastric cancer cell BGC-823 was significantly decreased compared with normal gastric epithelial cell (0.96±0.08 vs 2.84±0.15, P<0.05). The results of CCK-8 assay and Transwell assay showed that overexpression of miRNA-96-5p significantly reduced the proliferation and invasion abilities of gastric cancer cells (P<0.05). Overexpression of miRNA-96-5p decreased the protein level of FoxQ1. Moreover, it upregulated the expression of E-cadherin and downregulated the expression of vimentin. The result of dual-luciferase-3′-UTR reporter assay confirmed that miRNA-96-5p binds to the 3′UTR of FoxQ1.@*Conclusion@#miRNA-96-5p may suppress the proliferation, migration and epithelial-mesenchymal transition (EMT) of gastric cancer cell by down-regulation of FoxQ1.
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Objective To construct an index system for evaluating the effectiveness of dynamic pricing adjustment of medical services,for the purpose of providing a set of evaluation tools for price regulatory authorities to evaluate the effectiveness of pricing adjustment of medical services,to keep track of pricing trends,to implement dynamic monitoring and to guide decision-making.Methods Oriented to public hospitals in Guangdong province,literature analysis and Delphi method were used to construct the index system for evaluating the effectiveness of dynamic adjustment of medical service price.Descriptive analysis,consistency test and index importance evaluation were applied to statistical analysis.Results Thirty-two experts evaluated the importance of 41 alternative indicators.The index system for evaluating the effectiveness of dynamic adjustment of medical service price was finally constructed,including six structural indicators,six process indicators and six result indicators.Conclusions Experts are representative,authoritative and well-coordinated.The consultation results are reliable.The evaluation index system has high reliability and validity,and can be used to objectively evaluate the dynamic adjustment effect of medical service price.
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Objective@#To construct an index system for evaluating the effectiveness of dynamic pricing adjustment of medical services, for the purpose of providing a set of evaluation tools for price regulatory authorities to evaluate the effectiveness of pricing adjustment of medical services, to keep track of pricing trends, to implement dynamic monitoring and to guide decision-making.@*Methods@#Oriented to public hospitals in Guangdong province, literature analysis and Delphi method were used to construct the index system for evaluating the effectiveness of dynamic adjustment of medical service price. Descriptive analysis, consistency test and index importance evaluation were applied to statistical analysis.@*Results@#Thirty-two experts evaluated the importance of 41 alternative indicators. The index system for evaluating the effectiveness of dynamic adjustment of medical service price was finally constructed, including six structural indicators, six process indicators and six result indicators.@*Conclusions@#Experts are representative, authoritative and well-coordinated. The consultation results are reliable. The evaluation index system has high reliability and validity, and can be used to objectively evaluate the dynamic adjustment effect of medical service price.
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As d-amino acids play important roles in the physiological metabolism of bacteria, combination of d-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate and activity of d-serine alone and in combination with -lactams against methicillin-resistant (MRSA) strains, and to explore the possible sensitization mechanisms. The activity of d-serine, -lactams alone and in combinations was evaluated both by standard MICs, time-kill curves and checkerboard assays, and by murine systemic infection model as well as neutropenic thigh infection model. An synergistic effect was demonstrated with the combination of d-serine and -lactams against MRSA standard and clinical strains. Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared to -lactam alone groups. Initial mechanism study suggested possible revision of d-alanine-d-alanine residue to d-alanine-d-serine in peptidoglycan by adding of d-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, d-serine had synergistic activity in combination with -lactams against MRSA strains both and . Considering the relatively good safety of d-serine alone or in combination with -lactams, d-serine is worth following up as new anti-MRSA infection strategies.
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Since March 2013,China had experienced five seasonal epidemics related to Avian influenza A (H7N9).An unprecedented outbreak of H7N9 epidemic started from September 2016,with 730 cases reported till June 30th 2017,in mainland China that caused profound influences on both social development and health of the people.As an emerging infectious disease,information on pathogenic characteristics,transmission patterns and other epidemiological features of H7N9 virus somehow remained unclear.Data from previous studies suggested that the live poultry market (LPM) seemed to have served as main places where H7N9 virus got originated,mutated,spread and thus infected the human beings.Hence,closure of LPMs was suggested a major measure to control and prevent H7N9 epidemics in China.However,the effectiveness of different ways of LPM closures on H7N9 epidemics had been controversial.This study systemically summarized the effects of different ways of LPM closures on H7N epidemics from previous studies,aiming to provide references for developing a better program on H7N9 control and prevention in the country.
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Since March 2013,China had experienced five seasonal epidemics related to Avian influenza A (H7N9).An unprecedented outbreak of H7N9 epidemic started from September 2016,with 730 cases reported till June 30th 2017,in mainland China that caused profound influences on both social development and health of the people.As an emerging infectious disease,information on pathogenic characteristics,transmission patterns and other epidemiological features of H7N9 virus somehow remained unclear.Data from previous studies suggested that the live poultry market (LPM) seemed to have served as main places where H7N9 virus got originated,mutated,spread and thus infected the human beings.Hence,closure of LPMs was suggested a major measure to control and prevent H7N9 epidemics in China.However,the effectiveness of different ways of LPM closures on H7N9 epidemics had been controversial.This study systemically summarized the effects of different ways of LPM closures on H7N epidemics from previous studies,aiming to provide references for developing a better program on H7N9 control and prevention in the country.
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(E)-Methyl-4-aryl-4-oxabut-2-enoate (YH-8) is a novel PKnB protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chromatography-tandem mass spectrometric (LC--MS/MS) method has been developed and validated for the quantification of YH-8 in rat plasma for the first time. Samples were pre-treated using a liquid--liquid extraction with ethyl acetate and the chromatographic separation was performed on a C18 column by gradient elution with methanol--water as the mobile phase. YH-8 was detected using a tandem mass spectrometer in positive selected reaction monitoring (SRM) mode. Method validation revealed good linearity over the range of 1-500 ng/mL for YH-8 with a lower limit of quantification (LLOQ) of 1 ng/mL. Intra- and inter-day precision of YH-8 assay in rat plasma samples were 2.0%-6.8%, with accuracy of the method being 100.69%-106.18%. Stability test showed that when spiked into rat plasma, YH-8 was stable for 12 h at room temperature, for up to 15 days at -70 °C, and after three freeze-thaw cycles. Extracted samples were found to be stable over 12 h in an auto-sampler. The method was successfully applied to the pharmacokinetic study of YH-8 in rats after oral administration at 100 mg/kg and 200 mg/kg.
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Objective To investigate the phenotypic and genetic characteristics of the lysostaphin‐resistant Staphylococcus aureus variants induced by recombinant lysostaphin in vitro .Methods Three clinical isolates of S . aureus ,including two resistant to methicillin (MRSA ) and one susceptible to methicillin (MSSA ) were induced by treatment with sub‐MIC of recombinant lysostaphin via one‐step selection in vitro .Susceptibility of the variants to antibiotics were determined and compared with their parental strains .The full length of femABX genes was amplified by polymerase chain reaction and sequenced to identify the potential mutation sites in these genes .The growth‐curve in liquid medium and virulence in a mouse systemic infection model of both parental and variant strains were observed . Results The frequency of lysostaphin resistance in S . aureus was between 10-4 to 10-8 following induction by lysostaphin . Resistance to lysostaphin was associated with a significant decrease in growth rate in vitro and virulence in vivo ,as well as increased susceptibility toβ‐lactams evidenced by the M IC of β‐lactams against the variants as low as 1/4 000 to 1/2 of the M IC against their parental strains . Sequencing of f emA BX genes showed mutation in femA gene in both variants ,which resulted in a premature termination codon .Conclusions Resistance of S . aureus to lysostaphin may develop following induction by recombinant lysostaphin in vitro . The lysostaphin‐resistant S . aureus variants are characteristic of lower growth rate , decreased virulence ,and higher susceptibility to β‐lactams .
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Objective To determine the solubility and apparent oil/ water partition coefficient of sitafloxacin in different solvents. Methods High performance liquid chromatography (HPLC) was used. The column was Dikma Diamonsil C18 (2) (4. 6 mmí250 mm,5 μm). The mobile phase was 0. 05 mol·L-1 KH2 PO4 solution (pH was adjusted with H3 PO4 to 2. 4)-acetonitrile (7030). The column temperature was set at room temperature. The flow rate was 1. 0 mL·min-1 . The detection wavelength was 295 nm and the injection volume was 10 μL. The solubility of sitafloxacin and the apparent oil/ water partition coefficient at pH 2. 0,4. 3,5. 8,6. 6,7. 4,8. 0,10. 0 and 11. 2 were determined. Results The equilibrium solubility of sitafloxacin in water was 0. 44 mg·mL-1 and the apparent oil/ water partition coefficient was 0. 23 (lgP= -0. 64) at (37±2) ℃ . Sitafloxacin has the lowest equilibrium solubility (0. 13 mg·mL-1 ) and the highest apparent oil/ water partition coefficient in pH7. 4 buffer solution system. At pH>10 and pH<5. 8,the solubility of sitafloxacin increased obviously and apparent oil/ water partition coefficient decreased. Conclusion Sitafloxacin is insoluble in water and also poorly soluble in oil,but its solubility could be improved significantly in acidic or alkaline solution.
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The objective of this study was to investigate the genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii clinical isolates from Beijing, China. 173 A. baumannii clinical isolates from hospitals in Beijing from 2006 to 2009 were first subjected to high level aminoglycoside resistance (HLAR, MIC to gentamicin and amikacin>512 µg/mL) phenotype selection by broth microdilution method. The strains were then subjected to genetic basis analysis by PCR detection of the aminoglycoside modifying enzyme genes (aac(3)-I, aac(3)-IIc, aac(6')-Ib, aac(6')-II, aph(4)-Ia, aph(3')-I, aph(3')-IIb, aph(3')-IIIa, aph(3')-VIa, aph(2″)-Ib, aph(2″)-Ic, aph(2″)-Id, ant(2″)-Ia, ant(3″)-I and ant(4')-Ia) and the 16S rRNA methylase genes (armA, rmtB and rmtC). Correlation analysis between the presence of aminoglycoside resistance gene and HLAR phenotype were performed by SPSS. Totally 102 (58.96%) HLAR isolates were selected. The HLAR rates for year 2006, 2007, 2008 and 2009 were 52.63%, 65.22%, 51.11% and 70.83%, respectively. Five modifying enzyme genes (aac(3)-I, detection rate of 65.69%; aac(6')-Ib, detection rate of 45.10%; aph(3')-I, detection rate of 47.06%; aph(3')-IIb, detection rate of 0.98%; ant(3″)-I, detection rate of 95.10%) and one methylase gene (armA, detection rate of 98.04%) were detected in the 102 A. baumannii with aac(3)-I+aac(6')-Ib+ant(3″)-I+armA (detection rate of 25.49%), aac(3)-I+aph(3')-I+ant(3″)-I+armA (detection rate of 21.57%) and ant(3″)-I+armA (detection rate of 12.75%) being the most prevalent gene profiles. The values of chi-square tests showed correlation of armA, ant(3″)-I, aac(3)-I, aph(3')-I and aac(6')-Ib with HLAR. armA had significant correlation (contingency coefficient 0.685) and good contingency with HLAR (kappa 0.940). The high rates of HLAR may cause a serious problem for combination therapy of aminoglycoside with β-lactams against A. baumannii infections. As armA was reported to be able to cause high level aminoglycoside resistance to most of the clinical important aminoglycosides (gentamicin, amikacin, tobramycin, etc), the function of aminoglycoside modifying enzyme gene(s) in A. baumannii carrying armA deserves further investigation.
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Identification and validation of a new target is one of the most important steps for new antituberculosis (TB) drug discovery. Researches have shown that Mycobacterium tuberculosis (Mtb) encodes 20 CYP450 enzymes which play important roles in the synthesis and metabolism of lipid, cholesterol utilization, and the electron transport of respiratory chain in Mtb. With the critical roles within the organism as well as the protein structures of six Mtb CYP450 enzymes being clarified, some of them have been highlighted as potential anti-tuberculosis targets. In this paper, the phylogenetic analysis, the structural features, and the enzymatic functions of Mtb CYPs, as well as the mechanism of interactions with selective inhibitors such as azole antifungal agents for the CYPs have been reviewed and summarized. The druggability of the CYPs has also been analyzed for their further utility as targets in high throughput screening and rational design of more selective inhibitors.
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(0.05)) during dobutamine 5 ?g?kg~(-1)?min~(-1) stage. Blood pressure had significant increase both in dobutamine 10 ?g?kg~(-1)?min~(-1) stage and post-coronary revascularization. The sensitivity,specificity,accuracy of dobutamine 5 and 10 ?g?kg~(-1)?min~(-1) were (73.0)% and (89.6)%, (81.7)% and (82.8)%,(76.9)% and (86.5)%, respectively. Conclusions LDDSE is a simple,safe and no injury means to identify survival myocardium in myocardial infarction.