1.Effect of body weight and length on carotid artery vascular stenosis induced by balloon strain in rats
Tianwang CHEN ; Jiawei LUO ; Yidan YUAN ; Yimin YANG ; Bo HUANG ; Shangfu XU ; Lisheng LI
Basic & Clinical Medicine 2025;45(8):1034-1040
Objective To investigate the effects of body weight and length of SD rats on the carotid artery balloon injury-induced vascular stenosis model in order to provide a reference for replicating an ideal vascular stenosis mod-el.Methods Male rats were divided into three groups based on body weight and length.The CONQUEROR? SC PTCA balloon catheter was employed,with a fixed balloon inflation volume of 0.2 mL to induce injury in the left common carotid artery,while the right side served as a control.As soon as surgery operation,one rat from each group was selected for Evans Blue dye verification.Fourteen days later,the injured and contra lateral common ca-rotid arteries from remaining rats were harvested for HE staining to check the extent of stenosis.Based on these find-ings,six rats within the optimal range of body weight and length were selected for further validation.Results Rats with body weights ranging from 280 to 380 g(corresponding body lengths of 21.0-26.5 cm)underwent balloon catheter injury,resulting in endothelial detachment and varying degrees of stenosis in the common carotid artery.In rats weighing 280-300 g(body lengths of 21.0-22.5 cm)had severe stenosis or occlusion of the common carotid artery with thrombosis.In rats weighing 320-340 g(body lengths of 23.0-24.5 cm),the internal and external elastic plates of the common carotid artery were ruptured and the vascular morphology was abnormal.Conversely,rats weighing 360-380 g(body lengths of 25.0-26.5 cm)did not show any ruptured elastic laminae or thrombus formation in the common carotid artery,and the extent of vascular stenos in rats with a body weight of 360 g was moderate and uniform.The results of the repeated validation experiments were consistent.Conclusions Rats with a body weight range of 360 g(corresponding body length of 25.0-26.5 cm)are suitable for development of an ideal vascular stenosis model.
2.Comprehensive quality evaluation of Tianma jiannao granules
Jinyan DU ; Jingyuan MO ; Xun XIE ; Xiaoling HUANG ; Xiaoling WU ; Lisheng WANG
China Pharmacy 2024;35(20):2482-2487
OBJECTIVE To establish the fingerprints of Tianma jiannao granules (TJG) and the method for content determination to evaluate the quality of TJG comprehensively combined with chemometric analysis. METHODS High-performance liquid chromatography (HPLC) was used to establish the fingerprints of 13 batches (S1-S3) of TJG and determine the contents of inosine, gastrodin, parishin B and parishin E. Cluster analysis, principal component analysis, and orthogonal partial least squares- discriminant analysis were performed using SPSS 20.0 and SIMCA 18 software; using variable importance projection (VIP) value greater than 1 as a criterion, marker components that affected quality were screened. RESULTS A total of 28 common peaks were identified in the 13 batches of TJG with similarities greater than 0.9, and 7 common peaks were identified, which were gastrodin, p-hydroxybenzyl alcohol, parishin B, parishin E, rhynchophylline, inosine and salidroside. The 13 batches of TJG were clustered into 3 categories, S1-S2, S8-S10 and S12 were clustered into one category; S3 and S7 were clustered into one category; S4-S6, S11 and S13 were clustered into one category. VIP of inosine was greater than 1. The contents of inosine, gastrodin, parishin B and parishin E were 62.637-176.677, 17.821-37.642, 5.748-16.077 and 5.660-13.510 μg/g. CONCLUSIONS The established HPLC fingerprints and content determination method are stable, reliable and highly reproducible, which can be used to evaluate the quality of TJG in combination with chemometric analysis. Inosine may be a marker component that affects the quality of TJG. There are differences in the quality of 13 batches of TJG.
3.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
4.Exploration of the Pharmacological Substance Basis and Action Characteristics of Wenxing Jingjintong Gel Patch in the Treatment of Rheumatoid Arthritis Based on System Pharmacology and LC-MS/MS Technology
Anyu SU ; Weibin HUANG ; Jingyuan MO ; Zixuan ZHANG ; Xun XIE ; Xiaobing HUANG ; Bilian ZHONG ; Yongping ZHANG ; Lisheng WANG ; Chunyi WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(5):706-718
Objective To explore the key active ingredients and action characteristics of Wenxing Jingjintong Gel Patch in the treatment of rheumatoid arthritis(RA)based on the systematic pharmacology and LC-MS/MS technology.Methods The information of active ingredient from Wenxing Jingjintong Gel Patch was established through LC-MS/MS analysis and literature retrieval.The targets of the active ingredients were predicted using Swiss Target Prediction platform and then mapped with the RA-related targets obtained from GeneCards,DrugBank,and OMIM databases to identify the intersecting targets.The"active ingredients-effective targets"network was constructed through the Cytoscape software.The shared targets were imported into STRING database to construct a protein-protein interaction network.GO function and KEGG pathway enrichment analysis were performed using the Metascape database.Molecular docking studies were conducted using AutoDock software to investigate the interactions between key ingredients and target proteins.Results A total of 142 active ingredients were identified in Wenxing Jingjintong Gel Patch by wsing LC-MS/MS,which were further supplemented to 174 through literature retrieval.There were 175 shared targets between the active ingredients and RA.It was anticipated that Wenxing Jingjintong Gel Patch exerted immune regulation and anti-inflammatory and analgesic effects through the interaction between key active ingredients such as berberine,neobavaisoflavone,and palmatine chloride with key targets,including TNF,IL6,and AKT1 to regulate PI3K/Akt1,JAK/STAT,and MAPK signaling pathways.In 1 152 molecular docking validation,94%of them had binding energies less than-5.0 kcal·mol-1,while 51%of them had binding energies less than-7.0 kcal·mol-1.It was indicated that there was a good binding affinity between the potential active ingredients and core targets.Conclusion This study predicted the active ingredients and action characteristics of Wenxing Jingjintong Gel Patch in the treatment of RA,which provided a theoretical basis for further clinical application and quality control.
5.Preparation,Characterization,and In Vitro Evaluation of Dissolvable Microneedles Loaded with Hyaluronic Acid-modified Sinomenine Hydrochloride Liposome
Xun XIE ; Nijun ZHONG ; Jingyuan MO ; Xiaoling HUANG ; Jiaxiang ZOU ; Yongping ZHANG ; Lisheng WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1428-1436
Objective To prepare a dissolvable microneedle(DMN)with a tip-layer loaded with hyaluronic acid(HA)modified sinomenine hydrochloride liposomes(HA-SMH-Lip),as well as characterize,evaluate its in vitro transdermal permeability,cellular uptake ability,and anti-inflammatory ability.Methods HA-SMH-Lip-DMNs were prepared by a two-step casting method,and the drug loading capacity was determined using HPLC.The morphology,skin permeation properties and in vitro transdermal ability were investigated by scanning electron microscopy,puncture assay and Franz diffusion cell method.Fluorescent microneedles were prepared by replacing HA-SMH-Lip with fluorescein isothiocyanate liposomes(HA-FITC-Lip/FITC-Lip).The uptake behavior of inflammation cells on HA-FITC-Lip-DMNs/FITC-Lip-DMNs was investigated using a flow cytometer and a fluorescence microscope.To evaluate the anti-inflammatory activity of HA-SMH-Lip-DMNs,the levels of inflammatory factors including nitric oxide(NO),tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),and IL-10 in cell supernatants were measured using an ELISA kit.Results The prepared HA-SMH-Lip-DMNs have uniform shape and size,integral and visually pleasing array,and an average drug loading of(114.01±1.04)μg.Additionally,they have good puncture ability.The results of in vitro transdermal experiments showed that the accumulated amounts of HA-SMH-Lip-DMNs were(101.47±2.91)μg·cm-2 at 36 hours.Its transdermal ability was better than that of the SMH solution group and SMH liposome group.In vitro cellular uptake results indicated that HA-FITC-Lip-DMNs were more effectively taken up by RAW 264.7 cells(P<0.01).Compared to the model group,HA-SMH-Lip-DMNs group significantly reduced TNF-α,IL-1β,and NO levels while increase IL-10 levels(P<0.01).Conclusion The prepared HA-SMH-Lip-DMNs have a complete and beautiful morphology with excellent cellular uptake capability,remarkable in vitro transdermal performance,and potent anti-inflammatory properties.HA-SMH-Lip-DMNs are expected to become a new type of transdermal drug delivery system.
6.Discussion on diagnosis and treatment of dizziness from cases.
Lisheng YU ; Weijia KONG ; Haiwei HUANG ; Sulin ZHANG ; Xin MA ; Fei LI ; Junjie GUO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(4):302-306
Dizziness or vertigo is a common clinical symptom, and its underlying etiology is complex. Many clinicians are confused about its diagnosis and treatment. This article presents a case about chronic vestibular syndrome. And case appreciation and academic discussion are conducted by well-known domestic neurologists and otologists, so as to provide a good thinking model and basic ideas for the diagnosis and treatment of dizziness or vertigo, hoping to further improve the diagnosis and treatment level among clinicians.
Humans
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Dizziness/therapy*
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Vertigo/etiology*
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Vestibular Diseases/complications*
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Otolaryngologists
8.Influences of age-adjusted Charlson comorbidity index on prognosis of patients undergoing laparoscopic radical gastrectomy: a multicenter retrospective study
Zukai WANG ; Jianxian LIN ; Yanchang XU ; Gang ZHAO ; Lisheng CAI ; Guoxin LI ; Zekuan XU ; Su YAN ; Zuguang WU ; Fangqin XUE ; Yihong SUN ; Dongbo XU ; Wenbin ZHANG ; Peiwu YU ; Jin WAN ; Jiankun HU ; Xiangqian SU ; Jiafu JI ; Ziyu LI ; Jun YOU ; Yong LI ; Lin FAN ; Jianwei XIE ; Ping LI ; Chaohui ZHENG ; Changming HUANG
Chinese Journal of Digestive Surgery 2022;21(5):616-627
Objective:To investigate the influences of age-adjusted Charlson comorbidity index (ACCI) on prognosis of patients undergoing laparoscopic radical gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 242 gastric cancer patients who underwent laparoscopic radical gastrectomy in 19 hospitals of the Chinese Laparoscopic Gastrointestinal Surgery Study Group-04 study, including 54 patients in Fujian Medical University Union Hospital, 32 patients in the First Hospital of Putian City, 32 patients in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 31 patients in Zhangzhou Affiliated Hospital of Fujian Medical University, 17 patients in Nanfang Hospital of Southern Medical University, 11 patients in the First Affiliated Hospital with Nanjing Medical University, 8 patients in Qinghai University Affiliated Hospital, 8 patients in Meizhou People′s Hospital, 7 patients in Fujian Provincial Hospital, 6 patients in Zhongshan Hospital of Fudan University, 6 patients in Longyan First Hospital, 5 patients in the First Affiliated Hospital of Xinjiang Medical University, 5 patients in the First Hospital Affiliated to Army Medical University, 4 patients in the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, 4 patients in West China Hospital of Sichuan University, 4 patients in Beijing University Cancer Hospital, 3 patients in the First Affiliated Hospital of Xiamen University, 3 patients in Guangdong Provincial People′s Hospital, 2 patients in the First Affiliated Hospital of Xi′an Jiaotong University, from September 2016 to October 2017 were collected. There were 193 males and 49 females, aged 62(range, 23?74)years. Observation indicators: (1) age distribution, comorbidities and ACCI status of patients; (2) the grouping of ACCI and comparison of clinicopathological characteristics of patients in each group; (3) incidence of postoperative early complications and analysis of factors affecting postoperative early complications; (4) follow-up; (5) analysis of factors affecting the 3-year recurrence-free survival rate of patients. Follow-up was conducted using outpatient examination or telephone interview to detect postoperative survival of patients up to December 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the nonparametric rank sum test. The X-Tile software (version 3.6.1) was used to analyze the best ACCI grouping threshold. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-Rank test was used for survival analysis. The Logistic regression model was used to analyze the factors affecting postoperative early complications. The COX proportional hazard model was used for univariate and multivariate analyses of factors affecting the 3-year recurrence-free survival rate of patients. Multivariate analysis used stepwise regression to include variables with P<0.05 in univariate analysis and variables clinically closely related to prognosis. Results:(1) Age distribution, comor-bidities and ACCI status of patients. Of the 242 patients, there were 28 cases with age <50 years, 68 cases with age of 50 to 59 years, 113 cases with age of 60 to 69 years, 33 cases with age of 70 to 79 years. There was 1 patient combined with mild liver disease, 1 patient combined with diabetes of end-organ damage, 2 patients combined with peripheral vascular diseases, 2 patients combined with peptic ulcer, 6 patients combined with congestive heart failure, 8 patients combined with chronic pulmonary diseases, 9 patients with diabetes without end-organ damage. The ACCI of 242 patients was 2 (range, 0-4). (2) The grouping of ACCI and comparison of clinicopathological characteristics of patients in each group. Results of X-Tile software analysis showed that ACCI=3 was the best grouping threshold. Of the 242 patients, 194 cases with ACCI <3 were set as the low ACCI group and 48 cases with ACCI ≥3 were set as the high ACCI group, respectively. Age, body mass index, cases with preoperative comorbidities, cases of American Society of Anesthesiologists classification as stage Ⅰ, stage Ⅱ, stage Ⅲ, tumor diameter, cases with tumor histological type as signet ring cell or poorly differentiated adenocarcinoma and cases with tumor type as moderately or well differentiated adenocarcinoma, cases with tumor pathological T staging as stage T1, stage T2, stage T3, stage T4, chemotherapy cycles were (58±9)years, (22.6±2.9)kg/m 2, 31, 106, 85, 3, (4.0±1.9)cm, 104, 90, 16, 29, 72, 77, 6(4,6) in the low ACCI group, versus (70±4) years, (21.7±2.7)kg/m 2, 23, 14, 33, 1, (5.4±3.1)cm, 36, 12, 3, 4, 13, 28, 4(2,5) in the high ACCI group, showing significant differences in the above indicators between the two groups ( t=-14.37, 1.98, χ2=22.64, Z=-3.11, t=-2.91, χ2=7.22, Z=-2.21, -3.61, P<0.05). (3) Incidence of postoperative early complications and analysis of factors affecting postoperative early complications. Of the 242 patients, 33 cases had postoperative early complications, including 20 cases with local complications and 16 cases with systemic complica-tions. Some patients had multiple complications at the same time. Of the 20 patients with local complications, 12 cases had abdominal infection, 7 cases had anastomotic leakage, 2 cases had incision infection, 2 cases had abdominal hemorrhage, 2 cases had anastomotic hemorrhage and 1 case had lymphatic leakage. Of the 16 patients with systemic complications, 11 cases had pulmonary infection, 2 cases had arrhythmias, 2 cases had sepsis, 1 case had liver failure, 1 case had renal failure, 1 case had pulmonary embolism, 1 case had deep vein thrombosis, 1 case had urinary infection and 1 case had urine retention. Of the 33 cases with postoperative early complications, there were 3 cases with grade Ⅰ complications, 22 cases with grade Ⅱ complications, 5 cases with grade Ⅲa complications, 2 cases with grade Ⅲb complications and 1 case with grade Ⅳ complica-tions of Clavien-Dindo classification. Cases with postoperative early complications, cases with local complications, cases with systemic complications were 22, 13, 9 in the low ACCI group, versus 11, 7, 7 in the high ACCI group, respectively. There were significant differences in cases with postoperative early complications and cases with systemic complications between the two groups ( χ2=4.38, 4.66, P<0.05), and there was no significant difference in cases with local complications between the two groups ( χ2=2.20, P>0.05). Results of Logistic regression analysis showed that ACCI was a related factor for postoperative early complications of gastric cancer patients undergoing laparoscopic radical gastrectomy [ odds ratio=2.32, 95% confidence interval ( CI) as 1.04-5.21, P<0.05]. (4) Follow-up. All the 242 patients were followed up for 36(range,1?46)months. During the follow-up, 53 patients died and 13 patients survived with tumor. The 3-year recurrence-free survival rate of the 242 patients was 73.5%. The follow-up time, cases died and cases survived with tumor during follow-up, the 3-year recurrence-free survival rate were 36(range, 2-46)months, 29, 10, 80.0% for the low ACCI group, versus 35(range, 1-42)months, 24, 3, 47.4% for the high ACCI group. There was a significant difference in the 3-year recurrence-free survival rate between the two groups ( χ2=30.49, P<0.05). (5) Analysis of factors affecting the 3-year recurrence-free survival rate of patients. Results of univariate analysis showed that preoperative comorbidities, ACCI, tumor diameter, histological type, vascular invasion, lymphatic invasion, neural invasion, tumor pathological TNM staging, postoperative early complications were related factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy [ hazard ratio ( HR)=2.52, 3.64, 2.62, 0.47, 2.87, 1.90, 1.86, 21.77, 1.97, 95% CI as 1.52-4.17, 2.22-5.95, 1.54-4.46, 0.27-0.80, 1.76-4.70, 1.15-3.12, 1.10-3.14, 3.01-157.52, 1.11-3.50, P<0.05]. Results of multivariate analysis showed that ACCI, tumor pathological TNM staging, adjuvant chemotherapy were indepen-dent influencing factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy ( HR=3.65, 11.00, 40.66, 0.39, 95% CI as 2.21-6.02, 1.40-86.73, 5.41-305.69, 0.22-0.68, P<0.05). Conclusions:ACCI is a related factor for post-operative early complications of gastric cancer patients undergoing laparos-copic radical gastrectomy. ACCI, tumor pathological TNM staging, adjuvant chemotherapy are indepen-dent influencing factors for postoperative 3-year recurrence-free survival rate of gastric cancer patients undergoing laparoscopic radical gastrectomy.
9.Analysis of Epstein-Barr virus activity and clinical characteristics in patients with hemorrhagic fever with renal syndrome
Mingyan XU ; Ying ZHENG ; Yanxin HUANG ; Kaili ZHANG ; Zhaoyu LIU ; Ning MA ; Wei ZHANG ; Lisheng JIANG ; Xin SHENG ; Zhennan TIAN ; Yue ZHAO ; Qiaoyue JIANG ; Lan LIU ; Yinghua LAN ; Yongguo LI
Chinese Journal of Endemiology 2021;40(1):50-54
Objective:To study the Epstein-Barr virus (EBV) activity and its clinical characteristics in patients with hemorrhagic fever with renal syndrome (HFRS). Methods:From January 2016 to August 2017, patients with HFRS who were hospitalized in the First Affiliated Hospital of Harbin Medical University were routinely tested by EBV serology, and were divided into two groups according to their presence or absence of EBV infection, namely EBV active group and non-EBV active group. The clinical data between the two groups were compared and analyzed by SPSS 18.0.Results:A total of 188 HFRS patients were enrolled, including 73 cases in EBV active group and 115 cases in non-EBV active group. The EBV active rate of HFRS patients was 38.83% (73/188). The incidences of lumbago [57.53% (42/73) vs 42.61% (49/115)], abdominal pain [42.47% (31/73) vs 20.00% (23/115)], skin and mucosa congestion [57.53% (42/73) vs 39.13% (45/115)], and conjunctiva edema [50.68% (37/73) vs 28.70% (33/115)] in EBV active group were significantly higher than those in non-EBV active group (χ 2 = 3.983, 11.008, 6.083, 9.239, P < 0.05). There were 10, 7 and 43 patients with acute kidney injury (AKI) stage 1, 2 and 3 in EBV active group and 5, 13 and 53 patients in non-EBV active group. Degree of AKI in EBV active group was higher than that in non-EBV active group, and the difference was statistically significant (χ 2 = 12.615, P < 0.05). In EBV active group, the proportion of patients whose renal function recovery over 15 days [23.29% (17/73)] and white blood cell count [11.26 (3.39 ~ 54.23) × 10 9/L] were significantly higher than those in non-EBV active group [6.96% (8/115), 10.03 (2.91 ~ 66.99) × 10 9/L], and the differences were statistically significant (χ 2 = 10.330, Z = - 2.003, P < 0.05). Conclusion:HFRS patients may cause latent EBV activity, complicate their clinical features, cause severe renal damage and prolong the recovery time of renal function.
10. Analysis on key points for construction of trauma emergency center of Jiangxi Province
Yuanlin ZENG ; Haiming CHEN ; Lisheng LUO ; Xianlai XU ; Haigang XU ; Zhili LIU ; Sheng LIU ; Bin FU ; Xuefeng HUANG ; Zhongping YUAN ; Lidong WU ; Yuhua WAN ; Youjia TANG ; Chunming HUANG ; Peng RAO ; Hongfa ZHONG ; Bohe LI ; Yongan ZHANG ; Jiahua TANG ; Bo YOU
Chinese Journal of Trauma 2019;35(12):1126-1129
Trauma is the leading cause of death for people under 40 years old in the world. At present, the rescue and treatment system of trauma patients in China is not yet well established, and the mortality of trauma patients is higher than those in the developed countries. Improving the treatment system is the key to reducing the trauma mortality. In order to innovate the service mode of trauma first aid, further promote the establishment of regional trauma first aid system, improve the ability of trauma treatment, reduce the mortality and disability rate of trauma patients in Jiangxi Province, recently Health Commission of Jiangxi Province and the First Affiliated Hospital of Nanchang University have reached a consensus on the establishment of Jiangxi trauma first aid center. In order to provide reference for the construction of trauma treatment system, the author analyzes the following aspects including functional positioning, basic requirements, organization management, and evaluation of core indicators.

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