1.WU Hai-Ke's Six-Differentiation Methods for the Syndrome Differentiation and Treatment of Severe Cerebrovascular Disease
Li-Fen GONG ; Shan HUANG ; Xue-Ying ZHANG ; Chen JIANG ; Hai-Ke WU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):2174-2178
		                        		
		                        			
		                        			Severe cerebrovascular disease is a kind of severe cerebrovascular disease involving disturbance of consciousness,which corresponds to the viscera of stroke in traditional Chinese medicine(TCM).Rooted in the TCM classics such as Huang Di Nei Jing(The Yellow Emperor's Inner Classic)and Shang Han Lun(Treatise on Cold Damage),Professor WU Hai-Ke studied the TCM pathogenesis theory recorded in the chapter of Profound and Important Theory in Plain Questions(Su Wen)carefully.Based on its clinical practice and inherited the traditional four diagnostic methods of inspection,auscultation-olfaction,interrogation,and palpation,Professor WU Hai-Ke simplified and created the six-differentiation method for the syndrome differentiation of patients with severe cerebrovascular disease:distinguishing the mind to learn the progression of the disease,distinguishing the complexion to know the exuberance or decline of qi and blood,distinguishing the tongue picture to predict the aggravation or relief of the disease,distinguishing the pulse condition to judge the prognosis,distinguishing the breath to know the deficiency or excess of zang-fu organs,and distinguishing cold-heat to identify the exterior,interior,yin and yang.The six-differentiation method highlights the significance of mind,complexion,tongue picture,pulse condition,breath,and cold-heat in the syndrome differentiation of patients with severe cerebrovascular disease.The clinical information of six-differentiation method is easy to obtain,and the method presents the characteristics and advantages of TCM diagnostic methods in the syndrome differentiation of patients with severe cerebrovascular disease,which will provide reference for the establishment of clinical diagnosis and treatment norms of TCM for severe cerebrovascular disease.
		                        		
		                        		
		                        		
		                        	
2.Asia-Pacific consensus on long-term and sequential therapy for osteoporosis
Ta-Wei TAI ; Hsuan-Yu CHEN ; Chien-An SHIH ; Chun-Feng HUANG ; Eugene MCCLOSKEY ; Joon-Kiong LEE ; Swan Sim YEAP ; Ching-Lung CHEUNG ; Natthinee CHARATCHAROENWITTHAYA ; Unnop JAISAMRARN ; Vilai KUPTNIRATSAIKUL ; Rong-Sen YANG ; Sung-Yen LIN ; Akira TAGUCHI ; Satoshi MORI ; Julie LI-YU ; Seng Bin ANG ; Ding-Cheng CHAN ; Wai Sin CHAN ; Hou NG ; Jung-Fu CHEN ; Shih-Te TU ; Hai-Hua CHUANG ; Yin-Fan CHANG ; Fang-Ping CHEN ; Keh-Sung TSAI ; Peter R. EBELING ; Fernando MARIN ; Francisco Javier Nistal RODRÍGUEZ ; Huipeng SHI ; Kyu Ri HWANG ; Kwang-Kyoun KIM ; Yoon-Sok CHUNG ; Ian R. REID ; Manju CHANDRAN ; Serge FERRARI ; E Michael LEWIECKI ; Fen Lee HEW ; Lan T. HO-PHAM ; Tuan Van NGUYEN ; Van Hy NGUYEN ; Sarath LEKAMWASAM ; Dipendra PANDEY ; Sanjay BHADADA ; Chung-Hwan CHEN ; Jawl-Shan HWANG ; Chih-Hsing WU
Osteoporosis and Sarcopenia 2024;10(1):3-10
		                        		
		                        			 Objectives:
		                        			This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. 
		                        		
		                        			Methods:
		                        			A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. 
		                        		
		                        			Results:
		                        			The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. 
		                        		
		                        			Conclusions
		                        			This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management. 
		                        		
		                        		
		                        		
		                        	
		                				3.Targeted metabolomic analysis of phenylpropanoid metabolites in Astragalus membranaceus  var. mongholicus  in response to Fusarium solani  infection
		                			
		                			Zi-qing ZHAO ; Hai-qing SONG ; Li-mei ZHAO ; Zhen-yu LI ; Rui-jie WU ; Fen GAO
Acta Pharmaceutica Sinica 2023;58(7):1859-1866
		                        		
		                        			
		                        			 Root rot severely restricts the sustainable development of 
		                        		
		                        	
4.Analysis on infection risk in secondary close contacts of COVID-19 patients.
Bo YI ; Yan Ru CHU ; Yi CHEN ; Dong Liang ZHANG ; Yan Wu ZHANG ; Song LEI ; Lu HONG ; Qiao Fang LI ; Xiao Min GU ; Xu Ying LAO ; Hai Bo WANG ; Jun Fen LIN ; Guozhang XU
Chinese Journal of Epidemiology 2022;43(8):1237-1240
		                        		
		                        			
		                        			Objective: To study the infection rate of secondary close contacts of COVID-19 patients, and assess the infection risk in the contacts. Methods: COVID-19 patients' close contacts (with a clear exposure time to index case) with negative nucleic acid test results and secondary close contacts were surveyed in continuous isolation and medical observation in this prospective study. The dynamic nucleic acid test results of the close contacts and secondary contacts of COVID-19 patients were collected to assess their risk of infection. Results: A total of 4 533 close contacts were surveyed, in whom 14 were confirmed as COVID-19 patients with overall secondary attack rate of 0.31%, and 4 201 secondary contacts were tracked, in whom no subsequent infections occurred. Conclusion: Close contacts of COVID-19 patients entered in centralized isolation for medical observation with negative nucleic acid tese results,the secondary close contacts of COVID-19 patients have no risk of infection.
		                        		
		                        		
		                        		
		                        			COVID-19/epidemiology*
		                        			;
		                        		
		                        			Contact Tracing
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Incidence
		                        			;
		                        		
		                        			Nucleic Acids
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			SARS-CoV-2
		                        			
		                        		
		                        	
5.Research advances on the treatment of hydrofluoric acid burns.
Shu Lei MAO ; Yuan Hai ZHANG ; Jun Mei WU ; Chun Jiang YE ; Liang Fang NI ; Xin Gang WANG ; Rong Juan WANG ; Jian Fen ZHANG
Chinese Journal of Burns 2022;38(9):878-882
		                        		
		                        			
		                        			Hydrofluoric acid is a highly dangerous and toxic inorganic acid, which is widely used in industrial fields and daily life. The risk of hydrofluoric acid burns is related to hydrofluoric acid mass fraction, duration of exposure to hydrofluoric acid, burn area, burn depth, and burn site, etc. Hydrofluoric acid has strong toxicity and tissue penetration ability. A small area of hydrofluoric acid burns can cause death in a short time. Therefore, improving the understanding of the mechanism of hydrofluoric acid burns and learning how to treat hydrofluoric acid burns in different sites can further improve the cure rate of hydrofluoric acid burns.
		                        		
		                        		
		                        		
		                        			Burns, Chemical/therapy*
		                        			;
		                        		
		                        			Calcium Gluconate
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hydrofluoric Acid/adverse effects*
		                        			
		                        		
		                        	
6.Preparation of anti-human TIGIT monoclonal antibody and preliminary study of its biological activity
Zhen-hua WU ; Na LI ; Juan CHEN ; Mei-zhu JIANG ; Yao CHEN ; Xiao-fen MEI ; Hai-bin WANG
Acta Pharmaceutica Sinica 2022;57(11):3310-3315
		                        		
		                        			
		                        			 T cell immune receptor with Ig and ITIM domains (TIGIT), a promising new target in cancer immunotherapy, plays a critical role in limiting adaptive and innate immunity against tumors. The extracellular domain of human TIGIT was used to immune BALB/c mice, and a new anti-human TIGIT chimeric antibody (c7D3) was developed. The mice in this study were used in accordance with the international guidelines for the care and use of laboratory animals, and the animal study was approved by the Institutional Animal Ethics Committee of AbMax Biotechnology. The biological activity of c7D3 was studied. The results showed that c7D3 exhibited high affinity for TIGIT and effectively inhibited the interaction between TIGIT and its ligands. Cell-based assays indicated that c7D3 induced strong luciferase signaling in TIGIT/CD155 signaling reporter assay and enhanced cytokine secretion in a T cell stimulation assay. The data showed that c7D3 has high binding affinity and excellent blocking bioactivity, supporting the further advancement for therapeutic application. 
		                        		
		                        		
		                        		
		                        	
7.Relationship between body mass index and sexual development in Chinese children.
Xiao Qin XU ; Jian Wei ZHANG ; Rui Min CHEN ; Jing Si LUO ; Shao Ke CHEN ; Rong Xiu ZHENG ; Di WU ; Min ZHU ; Chun Lin WANG ; Yan LIANG ; Hui YAO ; Hai Yan WEI ; Zhe SU ; Mireguli MAIMAITI ; Hong Wei DU ; Fei Hong LUO ; Pin LI ; Shu Ting SI ; Wei WU ; Ke HUANG ; Guan Ping DONG ; Yun Xian YU ; Jun Fen FU
Chinese Journal of Pediatrics 2022;60(4):311-316
		                        		
		                        			
		                        			Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Body Mass Index
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			China/epidemiology*
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Obesity/epidemiology*
		                        			;
		                        		
		                        			Overweight/epidemiology*
		                        			;
		                        		
		                        			Puberty
		                        			;
		                        		
		                        			Puberty, Precocious
		                        			;
		                        		
		                        			Sexual Development
		                        			
		                        		
		                        	
8.Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development.
Hu LIN ; Hao YANG ; Jun Fen FU ; Jin Na YUAN ; Ke HUANG ; Wei WU ; Guan Ping DONG ; Hong Juan TIAN ; De Hua WU ; Da Xing TANG ; Ding Wen WU ; Li Ying SUN ; Ya Lei PI ; Li Jun LIU ; Li Ping SHI ; Wei GU ; Lu Gang HUANG ; Yi Hua WANG ; Lin Qi CHEN ; Hong Ying LI ; Yang YU ; Hai Yan WEI ; Xin Ran CHENG ; Xiao Ou SHAN ; Yu LIU ; Xu XU ; Shu LIU ; Xiao Ping LUO ; Yan Feng XIAO ; Yu YANG ; Gui Mei LI ; Mei FENG ; Xiu Qi MA ; Dao Xiang PAN ; Jia Yan TANG ; Rui Min CHEN ; Mireguli MAIMAITI ; De Yun LIU ; Xin Hai CUI ; Zhe SU ; Zhi Qiao DONG ; Li ZOU ; Yan Ling LIU ; Jin WU ; Kun Xia LI ; Yuan LI
Chinese Journal of Pediatrics 2022;60(5):435-441
		                        		
		                        			
		                        			Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
		                        		
		                        		
		                        		
		                        			3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics*
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		                        			Child
		                        			;
		                        		
		                        			China/epidemiology*
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		                        			Cryptorchidism/genetics*
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		                        			Disorders of Sex Development/genetics*
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		                        			Female
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		                        			Genital Diseases, Male
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		                        			Genotype
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		                        			Humans
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		                        			Hypospadias/genetics*
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		                        			Male
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		                        			Membrane Proteins/genetics*
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		                        			Penis/abnormalities*
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		                        			Phenotype
		                        			;
		                        		
		                        			Retrospective Studies
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		                        			Steroid 21-Hydroxylase/genetics*
		                        			
		                        		
		                        	
9.Establishment and validation of a new predictive equation with multiple risk factors for the development of cardiorenal syndrome type 1 in patients with acute myocardial infarction.
Cai Hong HE ; Jin Wu LIU ; Zhao He ZHU ; Hong Wei PAN ; Zhao Fen ZHENG ; Jin HE ; Zheng Yu LIU ; Yu ZHANG ; Chang Lu WANG ; Jing Jing RONG ; Yi TANG ; Qing Hai ZHANG
Chinese Journal of Cardiology 2021;49(8):802-808
		                        		
		                        			
		                        			Objective: To investigate the independent risk factors of cardiorenal syndrome type 1 (CRS1) in patients with acute myocardial infarction (AMI) and to build a predictive equation for the development of CRS1 in these patients. Method: Consecutive inpatients with AMI, who hospitalized from January 2017 to December 2018 in the Hunan Provincial People's Hospital, were enrolled in this case-control study. Patients were divided into CRS1 group and non-CRS1 group according to the presence or absence of CRS1.The clinical data were collected through the electronic medical record system of Hunan Provincial People's Hospital. The matching process was conducted with a minimum-distance scoring method and a 1∶1 match between the CRS1 group and the no-CRS1 group, the propensity score was calculated through the logistic regression model. Factors with statistically significant differences in univariate analysis were included in the multivariate logistic regression model to analyze the risk factors of AMI patients with CRS1, then the independent risk factors were used to establish a predicting equation for CRS1 by logistic regression function for model building. Area under the curve (AUC) value and the best cut-off value of the combined predictors was determined according to the ROC curve. Python 3.8 software was used to perform 10-fold cross-validation on modeling samples. Results: A total of 942 patients were included, there were 113 cases in CRS1 group and 829 cases in non-CRS1 group. Ultimately, 99 CRS1 patients were successfully matched to 99 non-CRS1 patient using 1∶1 matching. After propensity score matching, the baseline age and sex along with heart rate, mean arterial pressure, percentage of people with a history of diabetes, hypertension, ST-segment elevation myocardial infarction, myocardial ischemia time, angiotensin converting enzyme inhibitors or angiotensin Ⅱ receptor blockers use, and β receptor blocker use were similar between the two groups(all P>0.05). The contrast agent dosage was also similar between the two groups (P=0.266). The peak cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide(NT-proBNP), white blood cell count, base estimated glomerular filtration rate (eGFR), albumin and hemoglobin levels were statistically significant between the two groups (all P<0.05). Multivariate logistic regression analysis showed that decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count were independent risk factors of CRS1 in AMI patients (all P<0.01).The predicting equation of the combined predictor was established by transforming the logistic model equation, L=0.031×cTnI+0.000 2×NT-proBNP-0.024×eGFR+0.254×white blood cell count, where L represented the combined predictor. ROC curve analysis indicated that the AUC of the peak cTnI, NT-proBNP, baseline eGFR, white blood cell count, and combined predictor were 0.76, 0.85, 0.79, 0.81, and 0.92 respectively (all P<0.05), and the cutoff value of combined predictor was 2.6. The AUC of ROC curve after the model's ten-fold cross validation was 0.89. Conclusions: Decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count are the independent risk factors for CRS1 in AMI patients. The combined predictor equation based on the above 4 biomarkers presents a good predictive value for CRS1 in AMI patients.
		                        		
		                        		
		                        		
		                        	
10.Analysis on the efficacy and safety of fibrinolytic therapy in patients with acute ST-segment elevation myocardial infarction during the COVID-19 epidemic.
Fen WEI ; Xin Xin SHUAI ; Zhi Jian CHEN ; Gui Lan CAO ; Ling WANG ; Ting QIU ; Ting HU ; Ling WU ; Qin ZHANG ; Hai Xia HUANG ; Yan Wan ZHANG ; Lin ZHU ; Xiang CHENG
Chinese Journal of Cardiology 2020;48(6):472-476
		                        		
		                        			
		                        			Objective: To evaluate the efficacy and safety of fibrinolysis strategy in patients with acute ST-segment elevation myocardial infarction (STEMI) during the COVID-19 epidemic, and to provide reference value for optimization of fibrinolytic process on the premise of prevention and control of COVID-19 transmission, including self-protection of medical staff. Methods: The efficacy and safety of fibrinolysis were retrospectively analyzed in 7 patients with acute STEM, who hospitalized from February 29, 2020 to April 3, 2020 in the Department of Cardiology, Wuhan Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. To optimize the fibrinolytic process on the premise of prevention and control of COVID-19 transmission, including self-protection of medical staff, a full-time medical team in charge of fibrinolysis under third-grade protection was established. The acute STEMI patients were treated immediately in a fixed and isolated area in emergency department before receiving green channel fibrinolysis. Blood samples for complete blood count, COVID-19 antibody test and nasopharyngeal swab samples for COVID-19 nucleic acid test were made before fibrinolysis, while the chest CT examination was accomplished after fibrinolysis. By comparing differences of time from the first electrocardiogram (ECG) to fibrinolysis before and after the improvement of fibrinolytic process, the effect of optimization of the fibrinolytic process was evaluated. Results: In the present study, seven patients with acute STEMI received fibrinolysis therapy, 6 of them achieved reperfusion and no bleeding was observed in all of the patients. Five out of the 7 patients were hospitalized after fibrinolysis, and the hospitalization days were 19.6 days on average. By following up to April 14, 2020, none of the 7 patients died. The first 2 patients were treated according to the routine medical procedure and the time from the first ECG to fibrinolysis were 201 and 106 minutes, respectively. After the optimization of the fibrinolytic process, the time from the first ECG to fibrinolysis of the last 5 patients were 42, 46, 51, 43 and 54 minutes, respectively,which was significantly shorter than that before optimization. Conclusions: During the COVID-19 epidemic, fibrinolysis in patients with acute STEMI is safe, effective and easy to implement. Therefore, it is recommended as the top priority for the patients with acute STEMI with indications for fibrinolysis. On the premise of prevention and control of COVID-19 transmission, including self-protection of medical staff, the duration of myocardial ischemia can be shortened by optimization of the fibrinolytic process.
		                        		
		                        		
		                        		
		                        			Betacoronavirus
		                        			;
		                        		
		                        			COVID-19
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		                        			Coronavirus Infections/epidemiology*
		                        			;
		                        		
		                        			Epidemics
		                        			;
		                        		
		                        			Fibrinolytic Agents/therapeutic use*
		                        			;
		                        		
		                        			Humans
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		                        			Pandemics
		                        			;
		                        		
		                        			Pneumonia, Viral/epidemiology*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			SARS-CoV-2
		                        			;
		                        		
		                        			ST Elevation Myocardial Infarction/drug therapy*
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		                        			Thrombolytic Therapy
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		                        			Time Factors
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
            
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