1.Optimization of purification process and component analysis of alkaloids from Zanthoxylum bungeanum Maxim
Heying YANG ; Caiping LUO ; Ting PENG ; Wenyi LIANG ; Songzhang SHEN ; Juan SU
Journal of Pharmaceutical Practice and Service 2025;43(2):75-81
Objective To optimize the process conditions and analyze the components of alkaloids from Zanthoxylum bungeanum Maxim(Z. bungeanum)using macroporous resin. Methods Combining single factor tests and orthogonal tests, the content of hydroxy-α-sanshool(HAS)and hydroxy-β-sanshool(HBS)were considered as indexes to determine the best process parameters. Ultra-performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry(UPLC-Q-TOF-MSE)was used to identify the structures of alkaloids. Results The optimal conditions were Mitsubishi HP-20 macroporous resin, the loading solution concentration was 0.2 g crude drug/ml, the ratio of crude drug to resin volume was 1 g∶2.5 ml, the diameter/height ratio of resin column was 1∶7, the dynamic adsorption flow rate was 4 times of bed volume(BV)per hour, and the adsorption time was 1 h. Impurities were removed by using 2 BV of 20% ethanol, 5 BV of 80% ethanol was used to elution, and the content of HAS and HBS was 4.71% and 1.02%, respectively. A total of 20 alkaloids were identified from Z. bungeanum. Conclusion This method was stable and feasible, obtaining high purity and various kinds of alkaloids, which could be used for the enrichment and purification of alkaloids from Z. bungeanum.
2.Rapid characterization and identification of non-volatile components in Rhododendron tomentosum by UHPLC-Q-TOF-MS method.
Su-Ping XIAO ; Long-Mei LI ; Bin XIE ; Hong LIANG ; Qiong YIN ; Jian-Hui LI ; Jie DU ; Ji-Yong WANG ; Run-Huai ZHAO ; Yan-Qin XU ; Yun-Bo SUN ; Zong-Yuan LU ; Peng-Fei TU
China Journal of Chinese Materia Medica 2025;50(11):3054-3069
This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry*
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Chromatography, High Pressure Liquid/methods*
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Drugs, Chinese Herbal/chemistry*
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Mass Spectrometry/methods*
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Plant Leaves/chemistry*
3.Formula-S: Situated Visualization for Traditional Chinese Medicine Formula Learning.
Zhi-Yue WU ; Su-Yuan PENG ; Yan ZHU ; Liang ZHOU
Chinese Medical Sciences Journal 2025;40(1):57-67
OBJECTIVES:
The study of medicine formulas is a core component of traditional Chinese medicine (TCM), yet traditional learning methods often lack interactivity and contextual understanding, making it challenging for beginners to grasp the intricate composition rules of formulas. To address this gap, we introduce Formula-S, a situated visualization method for TCM formula learning in augmented reality (AR) and evaluate its performance. This study aims to evaluate the effectiveness of Formula-S in enhancing TCM formula learning for beginners by comparing it with traditional text-based formula learning and web-based visualization.
METHODS:
Formula-S is an interactive AR tool designed for TCM formula learning, featuring three modes (3D, Web, and Table). The dataset included TCM formulas and herb properties extracted from authoritative references, including textbook and the SymMap database. In Formula-S, the hierarchical visualization of the formulas as herbal medicine compositions, is linked to the multidimensional herb attribute visualization and embedded in the real world, where real herb samples are presented. To evaluate its effectiveness, a controlled study (n=30) was conducted.Participants who had no formal TCM knowledge were tasked with herbal medicine identification, formula composition, and recognition. In the study, participants interacted with the AR tool through HoloLens 2. Data were collected on both task performance (accuracy and response time) and user experience, with a focus on task efficiency, accuracy, and user preference across the different learning modes. Results The situated visualization method of Formula-S had comparable accuracy to other methods but shorter response time for herbal formula learning tasks. Regarding user experience, our new approach demonstrated the highest system usability and lowest task load, effectively reducing cognitive load and allowing users to complete tasks with greater ease and efficiency. Participants reported that Formula-S enhanced their learning experience through its intuitive interface and immersive AR environment, suggesting this approach offers usability advantages for TCM education.
CONCLUSIONS
The situated visualization method in Formula-S offers more efficient and accurate searching capabilities compared to traditional and web-based methods. Additionally, it provides superior contextual understanding of TCM formulas, making it a promising new solution for TCM learning.
Medicine, Chinese Traditional/methods*
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Humans
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Learning
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Drugs, Chinese Herbal
4.Progress in the Application of Stellate Ganglion Block in Non-Analgesic Fields.
Peng-Cheng YE ; Ying REN ; Wen-Liang SU ; Hao KONG
Acta Academiae Medicinae Sinicae 2025;47(3):462-469
Stellate ganglion block (SGB) is a specific type of peripheral nerve block in which local anesthetics and/or steroids are injected around the stellate ganglia.In the past,SGB was mainly used to alleviate pain-related syndromes.With the development of ultrasound technology,SGB has been widely used in non-analgesic fields,demonstrating significant therapeutic effects on arrhythmias,hot flashes,psychiatric disorders,cerebrovascular diseases,insomnia,and post coronavirus disease-2019 conditions in recent years.This study reviews the progress in the application of SGB in the non-analgesic fields.
Stellate Ganglion
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Humans
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Autonomic Nerve Block/methods*
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Anesthetics, Local/administration & dosage*
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COVID-19
5.Analysis of the Role of Pepsin in Vocal Cord Polyp and Vocal Cord Cancer
Jingyu GAO ; Renjing LUO ; Biao RUAN ; Chaowu JIANG ; Zhuohui LIU ; Ruiqing LONG ; Qiulin LIANG ; Ce ZHANG ; Lu SU ; Peng LI
Journal of Audiology and Speech Pathology 2024;32(1):21-24
Objective To investigate the expression of pepsin in vocal cord polyps and vocal cord cancer,and to compare the difference of pepsin expression.Methods From May 2020 to December 2021,27 patients with vocal cord polyp,27 patients with vocal cord cancer and 23 healthy volunteers were selected.RSI and RFS scoring scales were used for scoring,pepsin detection kit was used for saliva pepsin detection,and immunohistochemical methods were used to detect the expression of pepsin in vocal cord tissues of patients with vocal cord polyps and vocal cord cancer.Results The RSI score,RFS score and pepsin test kit results of vocal cord polyp group and vocal cord canc-er group were higher than those of non-vocal cord disease group,and the differences of the three indexes were statis-tically significant(P<0.05).RSI score,pepsin detection kit results and pepsin immunohistochemistry results of vocal cord polyp group showed no significant difference compared with vocal cord cancer group(P>0.05).The RFS score of vocal cord polyp group was significantly different from that of vocal cord cancer group(P<0.05).Conclusion Pepsin may be an important pathogenic factor of vocal cord polyp and vocal cord cancer,and play an im-portant role in the occurrence of these two diseases.The difference of pepsin expression in vocal cord polyp and vo-cal cord cancer suggests that pepsin may have different pathogenesis.
6.Effect of balance training on chronic ankle instability:a meta-analysis
Yuetong WANG ; Liang PENG ; Yuying SU ; Jiajun LIU
Chinese Journal of Tissue Engineering Research 2024;28(24):3930-3936
OBJECTIVE:Chronic ankle instability is mainly characterized by symptoms such as muscle weakness,intermittent pain,and repeated sprains,which seriously affect exercise and daily life.Loss of proprioception,prolongation of fibular reaction time,and weakening of valgus force may be the main symptoms of chronic ankle instability,so exercise intervention can effectively improve the symptoms related to ankle instability.Meta-analysis was used to quantitatively evaluate the effect of balance training on the rehabilitation intervention of chronic ankle instability,providing a reliable theoretical basis and practical basis for chronic ankle instability patients to scientifically formulate exercise prescriptions. METHODS:The randomized controlled trial of balance training on symptom rehabilitation and dynamic equilibrium of patients with chronic ankle instability was retrieved on CNKI,VIP,Web of Science,and PubMed.The literature was published from the inception to November 23,2022.Two reviewers were included to evaluate the quality of the included literature based on the physical therapy evidence scale.The primary outcome measure is the Self Functional Rating Scale,and the secondary outcome measure is the Star Shift Balance Test,both of which are continuous variables.Forest mapping,meta-regression,subgroup analysis,sensitivity analysis,and publication bias evaluation were performed on the included literature using RevMan 5.3 and Stata-SE 15 software. RESULTS:(1)A total of 18 articles of randomized controlled trials were screened and 641 patients with chronic ankle instability were included in the study.Overall,the methodological quality of the literature was relatively high.(2)Meta-analysis results showed that balance training improved the functional rehabilitation effect of chronic ankle instability patients(SMD=0.82,95%CI:0.41-1.23,P<0.000 1).Meta-regression exhibited that intervention time might be the main reason for heterogeneity(P=0.008).(3)The subgroup analysis results revealed that 6 weeks of intervention(SMD=0.98,95%CI:0.31-1.65,P=0.03),more than 3 interventions per week(SMD=0.87,95%CI:0.30-1.44,P=0.003),and each intervention time less than 20 minutes(SMD=0.89,95%CI:0.61-1.66,P<0.000 1)were the best rehabilitation plans to improve the functional rehabilitation effect of chronic ankle instability patients.(4)Meta-analysis results also showed that balance training improved the stretching degree of the anterior side(SMD=0.56,95%CI:0.31-0.80,P<0.05),posterior inner side(SMD=0.88,95%CI:0.45-1.32,P<0.05),and posterior outer side(SMD=0.84,95%CI:0.22-1.46,P<0.05)of the star shift balance test. CONCLUSION:Current clinical evidence shows that balance training can improve ankle instability symptoms and elevate dynamic equilibrium ability in chronic ankle instability patients.It is recommended to intervene more than 3 times a week,with each intervention lasting less than 20 minutes,to achieve better rehabilitation effects.
7. Optimization and identification of a low density and high purity method for primary hippocampal neuron culture from fetal rats
Peng SU ; Xing-Yi WANG ; Jing-Yan LIANG ; Tian-Qing XIONG ; Jing-Yan LIANG ; Tian-Qing XIONG
Acta Anatomica Sinica 2024;55(1):113-119
Objective To establish a low density, high purity and high stability in vitro culture method of primary hippocampal neurons of fetal rats by co-culturing hippocampal and cortical cells, so as to obtain higher purity and better vitality of primary hippocampal neurons disease. Methods The fetal rat hippocampal tissue was isolated from 16-18 days pregnant SD rats, then cut and digested by 0.125% trypsin. The obtained cell suspension was filtered by 200 mesh cell sieve, and then the obtained cell suspensions were then inoculated into the inner layer and outer ring of the culture plate in a surrounding form. They were co-cultured in DMEM/F12 medium containing 10% horse serum. After 4-6 hours of cell adhesion, the culture medium was changed to maintenance medium (Neurobasal+2% B27+0.5 mmol/L glutamine). Then the cell viability was detected with CCK-8 kit and the purity of hippocampal neurons was detected by immunofluorescent staining. Results Hippocampal neurons grew well and formed crisscross neural networks after 5 days. And it could survive for 3 weeks. The purity of hippocampal neurons was up to 98%. Conclusion The method of co-culturing hippocampal and cortical cells can obtain high-purity, high activity, high survival rate, and high stability primary hippocampal neurons from fetal rats, which can provide certain experimental conditions for the study of hippocampal neuron related diseases in the nervous system and is worthy of promotion and application.
8.Clinical comparative analysis of robot-assisted and DSA-guided percutaneous balloon compression for the treatment of trigeminal neuralgia
Fuhai SU ; Yunpeng CHEN ; Youming LIANG ; Shuiqing BI ; Peng XU ; Shengyong LAN
Chinese Journal of Nervous and Mental Diseases 2024;50(8):470-475
Objective To compare the advantages of robot assisted and DSA guided PBC for the treatment of trigeminal neuralgia.Methods A retrospective clinical analysis was conducted on 85 patients(28 in robot group and 57 in DSA group)who underwent robot assisted and DSA guided PBC surgery in a same center from September 2021 to February 2024.The single puncture success rate,improvement rate of VAS score,clinical efficacy rate,incidence of complications,average surgical time and fluoroscopy time were compared between the two groups.Results There was no statistically significant difference between the two groups in terms of single puncture success rate(96.43% vs.84.21% ),VAS improvement rate[88.9% (77.78%,100.00% )vs.88.89% (55.56%,100.00% )],clinical effective rate(92.86% vs.94.74% ),and total incidence of complications(35.09% vs.42.11% )(P>0.05).The average surgical time was significantly higher in the robot group[38.50(35.00,48.00)min]than the DSA group[19.00(15.00,25.50)min],and the average fluoroscopy time in the robot group[13.00(12.00,15.75)s]was significantly lower than the DSA group[194.00(152.50,259.50)s].The difference in average surgical and fluoroscopy time between the two groups was statistically significant(P<0.05).Conclusion DSA guided surgery has more advantages in centers with a large number of patients and a pursuit of efficiency.The robot assisted surgical puncture process is safe and controllable and patient radiation exposure time is short,thereby having high clinical application and promotion value.
9.Multicenter evaluation of the diagnostic efficacy of jaundice color card for neonatal hyperbilirubinemia
Guochang XUE ; Huali ZHANG ; Xuexing DING ; Fu XIONG ; Yanhong LIU ; Hui PENG ; Changlin WANG ; Yi ZHAO ; Huili YAN ; Mingxing REN ; Chaoying MA ; Hanming LU ; Yanli LI ; Ruifeng MENG ; Lingjun XIE ; Na CHEN ; Xiufang CHENG ; Jiaojiao WANG ; Xiaohong XIN ; Ruifen WANG ; Qi JIANG ; Yong ZHANG ; Guijuan LIANG ; Yuanzheng LI ; Jianing KANG ; Huimin ZHANG ; Yinying ZHANG ; Yuan YUAN ; Yawen LI ; Yinglin SU ; Junping LIU ; Shengjie DUAN ; Qingsheng LIU ; Jing WEI
Chinese Journal of Pediatrics 2024;62(6):535-541
Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).
10.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

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