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1.
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery ; (12): 154-158, 2023.
Article in Chinese | WPRIM | ID: wpr-953773

ABSTRACT

@#Obesity, sleep disorders, psychological stress, sedentary are modifiable cardiovascular risk factors. There is growing evidence that these risk factors may accelerate the chronic inflammatory process of atherosclerosis and lead to myocardial infarction. Studies on the role of immune cells and their related immune mechanisms in atherosclerosis have shown that the above modifiable risk factors can affect the hematopoiesis of the bone marrow system, affect the production of immune cells and phenotypes, and then affect the progress of atherosclerosis. This review will focus on the effects of modifiable cardiovascular risk factors on the progression of atherosclerosis through the role of the innate immune system.

2.
China Journal of Chinese Materia Medica ; (24): 2360-2367, 2023.
Article in Chinese | WPRIM | ID: wpr-981312

ABSTRACT

This study explored the effect and underlying mechanism of Stellera chamaejasme extract(SCE) on multidrug resistance of breast cancer. The chemotherapy-sensitive breast cancer cell line MCF-7 and adriamycin(ADR)-resistant cell line MCF-7/ADR were used as experimental subjects. MTT assay was used to detect cell proliferation activity. Pi staining was used to detect the cell cycle. 4',6-Diamidino-2-phenylindole, dihydrochloride(DAPI) staining and flow cytometry were used to detect apoptosis. Dansylcadaverine(MDC) staining and GFP-LC3B-Mcherry adenovirus transfection were used to detect autophagy. The protein expression of Bcl-2, Bax, caspase-9, caspase-3, LC3B, p62, and Beclin-1 was detected by Western blot. The results showed that SCE could significantly inhibit the proliferation of both sensitive and resistant breast cancer cell lines. The drug resistance factor was 0.53, which was significantly lower than 59 of ADR. Meanwhile, the proportion of sensitive/resistant cells in the G_0/G_1 phase increased significantly after SCE treatment. In addition, DAPI staining showed that a series of apoptosis phenomena such as nuclear pyknosis, staining deepening, and nuclear fragmentation appeared in sensitive/resistant cell lines after SCE administration. Moreover, the results of flow cytometry double staining showed that the proportion of apoptotic cells in sensitive/resistant cell lines increased significantly after SCE administration. Besides, Western blot showed that the protein expression levels of caspase-3, caspase-9, and Bcl-2 significantly decreased and the expression level of Bax protein significantly increased in both breast cancer cell lines after SCE administration. Furthermore, SCE could also increase the positive fluorescent spots after MDC staining and yellow fluorescent spots after GFP-LC3B-mcherry transfection, and up-regulate the expression levels of autophagy-related proteins LC3B-Ⅱ, p62, and Beclin-1 in breast cancer cells. In summary, SCE may play the role of anti-multidrug resistance by blocking the cell cycle of breast cancer multidrug-resistant cells, blocking autophagy flow, and ultimately interfering with the apoptosis resistance of drug-resistant cells.


Subject(s)
Humans , Female , Breast Neoplasms/metabolism , MCF-7 Cells , Caspase 3/metabolism , Caspase 9/metabolism , Beclin-1/pharmacology , Apoptosis , Proto-Oncogene Proteins c-bcl-2/metabolism , Cell Line, Tumor , Drug Resistance, Neoplasm , Cell Proliferation
3.
Chinese journal of integrative medicine ; (12): 665-672, 2023.
Article in English | WPRIM | ID: wpr-982303

ABSTRACT

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.


Subject(s)
Humans , Methamphetamine/adverse effects , Drugs, Chinese Herbal/therapeutic use , Amphetamine/therapeutic use , Behavior, Addictive/drug therapy , Amphetamine-Related Disorders/drug therapy
4.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 192-201, 2023.
Article in Chinese | WPRIM | ID: wpr-969615

ABSTRACT

ObjectiveTo investigate the effects of different cultivation modes on the yield of Gentiana crassicaulis and its microbial diversity and secondary metabolite content in the rhizosphere soil. MethodWith G. crassicaulis of different cultivation modes and its rhizosphere soil as the research objects, the composition of bacterial and fungal communities, dominant bacteria, and differential microorganisms in the rhizosphere soil were analyzed by high-throughput sequencing technology. HPLC was used to determine the content of iridoids in G. crassicaulis with different cultivation modes. ResultCompared with plastic film mulching, planting without mulch and intercropping of peony, white kidney bean, potato, and corn increased the yield of fresh products by 16.11%-17.68%, 22.48%-26.34%, 29.37%-32.19%, 34.82%-36.57%, and 35.34%-39.71%, respectively, and increased the yield of dry products by 19.75%-23.17%, 25.86%-29.32%, 30.18%-34.94%, 35.22%-39.87%, and 39.72%-43.73%. The total content of four iridoids, including gentiopicrin, loganic acid, sweroside, and swertiamarin, increased by 10.17%-37.83%, 5.93%-47.44%, 9.09%-28.84%, and 10.71%-28.57%, respectively. The diversity of bacterial and fungal communities in the rhizosphere soil increased significantly (P<0.05). The relative abundance of pathogenic bacteria such as Sordariomycetes, Leotiomycetes, Tremellomycetes, Eurotiomycetes, Fusarium, and Cladophialophora decreased, and the proportions of beneficial bacteria such as Proteobacteria, Acidobacteria, and Actinobacteriota increased and they gradually became the dominant bacteria. ConclusionDifferent cultivation modes can affect the yield of G. crassicaulis and its microbial diversity and iridoid content in the rhizosphere soil. Cultivation without mulch and intercropping patterns have certain advantages, which can provide theoretical references for the planting of G. crassicaulis.

5.
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery ; (12): 1377-1383, 2023.
Article in Chinese | WPRIM | ID: wpr-996994

ABSTRACT

@#The Chinese Guidelines on Diagnosis and Management of Atrial Fibrillation, jointly formulated by the Chinese Society of Cardiology, Chinese Medical Association and the Heart Rhythm Committee of Chinese Society of Biomedical Engineering, was first released on June 15, 2023. The guidelines elaborate the various aspects of atrial fibrillation management, in which emergency management of atrial fibrillation is also an integral part. This article interpreted the emergency management part in the guidelines in detail by reviewing relevant literature.

6.
Chinese Journal of Nephrology ; (12): 461-464, 2023.
Article in Chinese | WPRIM | ID: wpr-995000

ABSTRACT

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of systemic small vasculitis characterized by the detection of ANCA in serum. Bactericidal permeability enhancing protein (BPI) is one of the target antigens of ANCA. BPI-ANCA-associated vasculitis is not common clinically, and the combination of bronchiectasis is not accidental. The paper reported a case of BPI-ANCA-associated vasculitis with renal damage combined with bronchiectasis. We reviewed relevant literature to explore the characteristics of BPI-ANCA-associated vasculitis and the correlation between bronchiectasis and ANCA-associated vasculitis, so as to improve the clinician's understanding on this disease.

7.
Chinese Journal of Nephrology ; (12): 135-138, 2023.
Article in Chinese | WPRIM | ID: wpr-994957

ABSTRACT

Except for IgA nephropathy, membranous nephropathy (MN) is the most common primary glomerulonephritis in China. Neural epidermal growth factor-like 1 protein (NELL-1) has been currently considered as one of the target antigens for diagnosis of primary MN. Moyamoya syndrome is a syndrome with clinical and imaging manifestations of moyamoya disease and possible vascular stenosis. By far, primary MN complicated with moyamoya syndrome has not been reported internationally. The paper reports a case of NELL-1-related MN complicated with moyamoya syndrome and reviews relevant literature to provide evidence for clinical diagnosis and treatment.

8.
Frontiers of Medicine ; (4): 1-11, 2023.
Article in English | WPRIM | ID: wpr-971632

ABSTRACT

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

9.
Chinese Journal of Emergency Medicine ; (12): 1153-1158, 2022.
Article in Chinese | WPRIM | ID: wpr-954538

ABSTRACT

Objective:To study the value of autoregressive integrated moving average (ARIMA) and autoregressive (AR) models in predicting the daily number of ambulances in prehospital emergency medical services demand in Guangzhou.Methods:Matlab simulation software was used to analyze the emergency dispatching departure records in Guangzhou from January 1, 2021 to December 31, 2021. A time series for the number of ambulances per day was calculated. After identifying the time series prediction model, ARIMA(1,1,1), AR(4) and AR(7) models were obtained. These models were used to predict the number of ambulances per day. ARIMA(1,1,1) model divided the time series into the training set and test set. Prony method was used for parameter calculation, and the demands of number of ambulances of the next few months were forecasted. AR(4) and AR(7) models used uniformity coefficient to forecast the demands of number of ambulances on that very day.Results:ARIMA(1,1,1), AR(4) and AR(7) can effectively predict the number of ambulances per day. The prediction fitting error of ARIMA (1,1,1) decreased with the extension of prediction time. The mean absolute percentage error (MAPE) of forecast results of daily vehicle output of emergency dispatching within two months was less than 6% and the predicted results were almost within the 95% confidence interval. The residual analysis of the model verified that the model was significantly effective.Conclusions:ARIMA model can make a long-term within two months and effective prediction fitting of the daily vehicle output of emergency dispatching, and AR model can make a short-term and effective prediction of the daily vehicle output of emergency dispatching.

10.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 250-259, 2022.
Article in Chinese | WPRIM | ID: wpr-940683

ABSTRACT

Breast cancer, as a kind of malignant tumor with high incidence rate in female population, poses a great threat to people's health. At present, chemotherapy is the main treatment for breast cancer besides surgery and radiotherapy. However, chemotherapy is often accompanied by multidrug resistance (MDR), which results in a series of severe consequences such as low efficacy, relapse of cancer after drug withdrawal, increased consumption of medical resources, and increased burden of medical system. Previous studies showed that the mechanism of MDR in breast cancer was quite complex, involving drug efflux, deoxyribonucleic acid (DNA) damage repair, tumor microenvironment, autophagy, epigenetic regulation, tumor stem cells, lipid metabolism, and so on. In addition, there were extensive connections among the mechanisms of MDR. Therefore, it is necessary to reveal the mechanism of MDR and develop corresponding drugs to reverse MDR, thus improving the effect of chemotherapy on treating breast cancer. Chinese medicine has the advantages of high efficiency, low toxicity, multi targets, and overall regulation. Various studies found that Chinese medicine monomer, single drug, and compound were able to reverse MDR in breast cancer by regulating the expression of drug efflux protein, promoting apoptosis, and regulating autophagy, showing the potential of anti-MDR in breast cancer. This paper summarized the research progress of the mechanism of MDR in breast cancer and the strategies of Chinese medicine in coping with MDR in breas cancer in recent years, and provided references for further research.

11.
Journal of Clinical Hepatology ; (12): 1183-1187, 2022.
Article in Chinese | WPRIM | ID: wpr-924804

ABSTRACT

Drug-induced liver injury (DILI) is one of the common adverse drug reactions and is the main cause of withdrawal of drugs after marketing, which has attracted more and more attention of the public, and herb-induced liver injury (HILI) is a special type of DILI. In recent years, the frequent occurrence of HILI not only seriously endangers the health of patients, but also causes the controversy over the safety of traditional Chinese medicine. Therefore, this article reviews the potential risk factors for HILI from the three aspects of "patient", "drug", and "use", so as to provide a basis for the objective identification, prevention, and control of HILI and a reference for the construction of traditional Chinese medicine pharmacovigilance system represented by liver injury.

12.
Journal of Clinical Hepatology ; (12): 1420-1425, 2022.
Article in Chinese | WPRIM | ID: wpr-924726

ABSTRACT

Liver fibrosis is the common consequence of various chronic liver injuries and is mainly characterized by the imbalance between the production and degradation of extracellular matrix, which leads to the accumulation of interstitial collagen and other matrix components. Matrix metalloproteinases (MMPs) and their specific inhibitors, i.e., tissue inhibitors of metalloproteinases (TIMPs), play a crucial role in collagen synthesis and lysis. Through a literature review, this article reviews the experimental studies of liver fibrosis based on MMPs/TIMPs, summarizes the components that may exert an anti-liver fibrosis effect by affecting the expression or activity of MMPs/TIMPs, and attempts to clarify the mechanism of MMPs/TIMPs in regulating collagen homeostasis, so as to provide support for the development of anti-liver fibrosis drugs.

13.
Journal of Clinical Hepatology ; (12): 942-946, 2022.
Article in Chinese | WPRIM | ID: wpr-923314

ABSTRACT

Inflammasomes play an important role in the innate immunity of the liver; however, the excessive activation of inflammasomes can lead to liver inflammation and injury. The mechanism of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-mediated liver injury has been extensively studied. Related studies have shown that the development of various liver diseases may be associated with the excessive activation of inflammasomes, especially NLRP3 inflammasome. This article reviews inflammasomes, the activation mechanism of NLRP3 inflammasome, and the role of NLRP3 inflammasome in different liver diseases, so as to provide a reference for the treatment targets of liver diseases from the perspective of NLRP3 inflammasome.

14.
Frontiers of Medicine ; (4): 102-110, 2022.
Article in English | WPRIM | ID: wpr-929186

ABSTRACT

Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.


Subject(s)
Humans , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 , Hypertension/drug therapy , Renin-Angiotensin System , Retrospective Studies
15.
China Journal of Chinese Materia Medica ; (24): 4666-4673, 2021.
Article in Chinese | WPRIM | ID: wpr-888170

ABSTRACT

As the main active ingredient of the orchidaceous herb Bletilla striata, B. striata polysaccharide(BSP) has pharmacological activities such as promoting coagulation, anti-inflammation, anti-oxidation, promoting wound healing, anti-tumor, and immunomodulation, and is biodegradable and non-toxic. Additionally, it has the material properties of suspension thickening, film-forming adhesion, coating and solubilizing, targeting and slow releasing, effect-enhancing and toxicity-reducing, etc., playing the role of unification of medicines and excipients. Therefore, BSP has a wide application prospect in the fields of drug delivery system and trauma repair. This paper reviews the research progress of BSP application in new drug delivery systems and biomaterials based on the related li-terature in recent years, with the aim of providing reference for the further research and application of BSP.


Subject(s)
Biocompatible Materials , Drug Delivery Systems , Orchidaceae , Polysaccharides , Wound Healing
16.
Chinese Journal of Infectious Diseases ; (12): 86-91, 2021.
Article in Chinese | WPRIM | ID: wpr-884186

ABSTRACT

Objective:To investigate the prognosis and outcome of patients with chronic hepatitis C (CHC) related cirrhosis after achieved sustained virologic response (SVR) treated with direct-acting antiviral agent (DAA).Methods:Ninety-five patients diagnosed with CHC related cirrhosis who had complete data in Tianjin Second People′s Hospital from January 2014 to June 2017 were retrospectively followed up. Among them, 72 patients were treated with DAA and all of them achieved SVR, and the other 23 patients did not receive any antiviral therapy. The differences of mortality and incidence of hepatocellular carcinoma (HCC) between DAA treatment group and non-antiviral treatment group were compared. Statistical analysis was performed by independent sample t test, Mann-Whitney U test and chi-square test. Results:At the end of follow-up for three to 71 months, patients in DAA treatment group had a significant improvements in alanine aminotransferase, aspartate aminotransferase, albumin and liver stiffness measurement compared with those before treatment (42(23, 61) U/L vs 18(13, 28) U/L, 54(37, 75) U/L vs 23(18, 28) U/L, 39(33, 42) g/L vs 45(41, 48) g/L, 26(18, 37) kPa vs 15(11, 26) kPa, respectively, Z=-6.005, -7.008, -6.057 and -3.162, respectively, all P<0.01). However, there were no significant differences in incidence of HCC (12%(9/72) vs 17%(4/23)) and mortality (3%(2/72) vs 13%(3/23)) between the DAA treatment group and non-antiviral treatment group (both P>0.05). There was no significant difference of cumulative incidence of HCC in DAA treatment group compared with non-antiviral treatment group ( P=0.609). The age of patients progressed to HCC was older than those without HCC ((60.3±3.6) years vs (54.4±9.9) years, t=-3.948, P<0.01). In subgroup analysis, among the six patients with HCC, four had diabetes, the prevalence of diabetes in the patients without HCC was 17%(7/42); the level of fasting blood glucose (FBG) ((7.3±1.9) mmol/L vs (5.9±1.1) mmol/L) were higher in patients progressed to HCC than those without HCC in DAA treatment group with compensated cirrhosis ( χ2=7.430 and t=-2.442, respectively, both P=0.019). Conclusions:DAA treatment could notably improve liver function and alleviate liver fibrosis, but could not reduce the mortality and incidence of HCC in patients with CHC related cirrhosis significantly. Diabetes and high level FBG may be the risk factors for occurrence of HCC in patients with CHC related compensated cirrhosis.

17.
Chinese Journal of Medical Education Research ; (12): 399-402, 2021.
Article in Chinese | WPRIM | ID: wpr-883628

ABSTRACT

Symptomatology and medical history taking are the focuses of diagnostics study. With the improvement of teaching and learning, students can basically master the standard process of clinical inquiry of chief complaints to family history efficiently. However, due to the lack of systematic learning of clinical diseases, it's difficult for most students to form a targeted, logical and speculative inquiry thinking pattern, so they are unlikely to write a medical history of present illness that reflects their thinking on disease inclusion and exclusion. In this study, we come up with the characteristics and defects of symptomatology teaching at present, and put forward a new idea of symptomatology teaching by introducing clinical manifestations of diseases and examples of inquiry.

18.
Chinese Journal of Medical Education Research ; (12): 373-377, 2021.
Article in Chinese | WPRIM | ID: wpr-883622

ABSTRACT

Objective:To explore the method of building the formative assessment (FA) system in diagnostics teaching and investigate its implementation effect.Methods:We planned and formulated the formative assessment system in diagnostics teaching of undergraduate curriculum. The correlation between the scores of the formative assessment and final exam were analyzed. A questionnaire survey on students' attitudes towards FA and an interview on teachers' perspectives were conducted. SPSS 17.0 was used for statistical analysis. Linear correlation analysis was used to compare the final exam scores with formative assessment scores, and Wilcoxon rank sum test was used to compare the scores of questionnaire items.Results:The scores of FA were significantly positive related to the scores of final exam ( r = 0.559, P < 0.001). The questionnaire analysis showed that students significantly valued the formative assessment superior to the summative assessment ( Z = -8.632, P<0.001). It was generally approved of the promotion of FA in students' self-direct learning and self-supervision and the advances in acquirement of knowledge and skills. Conclusion:It is feasible of carrying FA in diagnostics teaching which could provide better learning outcome and might have an extensive prospect of application.

19.
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery ; (12): 376-383, 2021.
Article in Chinese | WPRIM | ID: wpr-876064

ABSTRACT

@#The World Health Organization (WHO) released the WHO 2020 guidelines on physical activity and sedentary behaviour in November 2020. Compared with the 2010 WHO guidelines, this guideline has incorporated more extensive medical evidence and made targeted recommendations for special populations. The main content includes physical activity and sedentary behaviour advice for children and adolescents, adults, older adults, pregnant and postpartum women, people with chronic conditions, and disability. This review will interpret the 2020 WHO guidelines in detail.

20.
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery ; (12): 1346-1351, 2021.
Article in Chinese | WPRIM | ID: wpr-904723

ABSTRACT

@#Objective    To explore the predictive value of a simple prediction model for patients with acute myocardial infarction. Methods    Clinical data of 280 patients with acute ST-segment elevation myocardial infarction (STEMI) in the Department of Emergence Medicine, West China Hospital of Sichuan University from January 2019 to January 2020 were retrospectively analyzed. The patients were divided into a death group (n=34) and a survival group (n=246). Results    Age, heart rate, body mass index (BMI), global registry of acute coronary events (GRACE), thrombolysis in myocardial infarction trial (TIMI) score, blood urea nitrogen, serum cystatin C and D-dimer in the survival group were less or lower than those in the death group (P<0.05). Left ventricle ejection fraction and the level of albumin, triglyceride, total cholesterol and low density lipoprotein cholesterol were higher and the incidence of Killip class≥Ⅲ was lower in the survival group compared to the death group (P<0.05). Multivariate logistic regression analysis showed that age, BMI, heart rate, diastolic blood pressure, and systolic blood pressure were independent risk factors for all-cause death in STEMI patients. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve of simple prediction model for predicting death was 0.802, and similar to that of GRACE (0.816). The H-L test showed that the simple model had high accuracy in predicting death (χ2=3.77, P=0.877). Pearson correlation analysis showed that the simple prediction model was significantly correlated with the GRACE (r=0.651, P<0.001) and coronary artery stenosis score (r=0.210, P=0.001). Conclusion    The simple prediction model may be used to predict the hospitalization and long-term outcomes of STEMI patients, which is helpful to stratify high risk patients and to guide treatment.

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