1.Opportunities and challenges of pediatric medical education in the new era of China
Dengming LAI ; Jingyi JIN ; Shuang YU ; Jing YE ; Qiang SHU
Chinese Journal of Medical Education Research 2024;23(3):289-293
		                        		
		                        			
		                        			Medical education in China has undergone many changes amid the revolution of medical education worldwide. The Healthy China initiative in the new era highlights the increasing demand for a high-quality children's health service system as well as more excellent pediatricians. This article aims to delve into the current opportunities and challenges of pediatric education in China, summarize the response strategies, and take a look at the new mode of talent cultivation in pediatric medicine. With the rapid shift in the newborn population, the strengthening of multidisciplinary collaboration, the development of medical informatization, and the continuous improvement in scientific research levels, pediatric medical education is facing unprecedented opportunities. However, the late start of pediatrics and the lack of high-level talents have also brought great challenges to pediatric medical education. Therefore, future efforts should be focused on multi-disciplinary cooperation and innovative education and teaching to nurture pediatrician-scientists with innovative abilities and practical experience.
		                        		
		                        		
		                        		
		                        	
2.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.
		                        		
		                        		
		                        		
		                        	
3.Obstetric Diseases Responding Specifically to Traditional Chinese Medicine
Jing-shang WANG ; Xiao-wei LIU ; Xin WANG ; Lan-zhong GUO ; Yu-qin LAI ; Jun ZHAO ; Jun-qin HE ; Xue-juan JIANG ; Ying-dong HE ; Zhan LI ; Dong YANG ; Yu-long DING ; Ying WU ; Wei GAO ; Shu-zhen GUO ; Cang ZHANG ; Yong ZHU ; Si-qi GUAN ; Xiao-xiao ZHANG ; Rui-hua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(20):206-218
		                        		
		                        			
		                        			In recent years, with the change in life style, social environment, and national childbearing policy, the proportion of high-risk pregnant women has increased significantly, triggering the spectrum of obstetric diseases to constantly change, which has brought new challenges to the diagnosis and treatment of obstetrics. Traditional Chinese medicine (TCM) has been proved effective in dealing with a variety of obstetric diseases, and various treatment methods are available, which can serve as alternative means for solving refractory obstetric diseases. However, most obstetric clinicians are currently less aware of the therapeutic effects of TCM, which has significantly hindered its participation in clinical treatment. Therefore, the China Association of Chinese Medicine (CACM) organized the outstanding young obstetricians of TCM and western medicine to discuss 15 obstetric diseases responding specifically to TCM or integrated TCM and western medicine, including hyperemesis gravidarum, threatened abortion, ectopic gestation, cough during pregnancy, pregnancy-induced hypertension syndrome, maternal-fetal ABO incompatibility, postpartum hypogalactia, residual pregnancy tissue in uterine cavity, puerperal infection, pantalgia after childbirth, hematoma/undesirable healing after caesarean section, postpartum urinary retention, ileus after cesarean section, pelvic floor dysfunction, and postnatal depression. The suggestions for their treatment with TCM or integrated TCM and western medicine were also proposed, aiming to provide patients with effective and personalized treatments in clinical practice and improve the diagnosis and treatment effects of obstetric diseases, thus benefiting the public. At the same time, more obstetrical clinicians are expected to understand the therapeutic effects and advantages of TCM and draw on the strengths of both TCM and western, thereby promoting the establishment of an obstetric diagnosis and treatment system with Chinese characteristics.
		                        		
		                        		
		                        		
		                        	
4.Early use of dexamethasone increases Nr4a1 in Kupffer cells ameliorating acute liver failure in mice in a glucocorticoid receptor-dependent manner.
Jing-Wen DENG ; Qin YANG ; Xiao-Peng CAI ; Jia-Ming ZHOU ; Wei-Gao E ; Yan-Dong AN ; Qiu-Xian ZHENG ; Meng HONG ; Yan-Li REN ; Jun GUAN ; Gang WANG ; Shu-Jing LAI ; Zhi CHEN
Journal of Zhejiang University. Science. B 2020;21(9):727-739
		                        		
		                        			BACKGROUND AND OBJECTIVE:
		                        			Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) in mice.
		                        		
		                        			METHODS:
		                        			Male C57BL/6 mice were given LPS and D-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively.
		                        		
		                        			RESULTS:
		                        			A mouse model of ALF can be constructed successfully using LPS/D-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/D-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition.
		                        		
		                        			CONCLUSIONS
		                        			In LPS/D-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Dexamethasone/therapeutic use*
		                        			;
		                        		
		                        			Disease Models, Animal
		                        			;
		                        		
		                        			Kupffer Cells/physiology*
		                        			;
		                        		
		                        			Liver Failure, Acute/pathology*
		                        			;
		                        		
		                        			Male
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		                        			Mice
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		                        			Mice, Inbred C57BL
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		                        			Nuclear Receptor Subfamily 4, Group A, Member 1/physiology*
		                        			;
		                        		
		                        			Receptors, Glucocorticoid/physiology*
		                        			
		                        		
		                        	
5.Novel ACADVL variants resulting in mitochondrial defects in long-chain acyl-CoA dehydrogenase deficiency.
Ting CHEN ; Fan TONG ; Xiao-Yu WU ; Ling ZHU ; Qiu-Zi YI ; Jing ZHENG ; Ru-Lai YANG ; Zheng-Yan ZHAO ; Xiao-Hui CANG ; Qiang SHU ; Ping-Ping JIANG
Journal of Zhejiang University. Science. B 2020;21(11):885-896
		                        		
		                        			
		                        			The pathogenesis of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is highly heterogeneous and still unclear. Additional novel variants have been recently detected in the population. The molecular and cellular effects of these previously unreported variants are still poorly understood and require further characterization. To address this problem, we have evaluated the various functions and biochemical consequences of six novel missense variants that lead to mild VLCAD deficiency. Marked deficiencies in fatty acid oxidation (FAO) and other mitochondrial defects were observed in cells carrying one of these six variants (c.541C>T, c.863T>G, c.895A>G, c.1238T>C, c.1276G>A, and c.1505T>A), including reductions in mitochondrial respiratory-chain function and adenosine triphosphate (ATP) production, and increased levels of mitochondrial reactive oxygen species (ROS). Intriguingly, higher apoptosis levels were found in cells carrying the mutant VLCAD under glucose-limited stress. Moreover, the stability of the mutant homodimer was disturbed, and major conformational changes in each mutant VLCAD structure were predicted by molecular dynamics (MD) simulation. The data presented here may provide valuable information for improving management of diagnosis and treatment of VLCAD deficiency and for a better understanding of the general molecular bases of disease variability.
		                        		
		                        		
		                        		
		                        	
6.The Application of the Technique in the Protection of PCI
Qi LAI ; Xue-Feng GUANG ; Cheng-De HE ; Zhi-Peng CHEN ; Shu-Nan JING ; Jie FANG
Journal of Kunming Medical University 2018;39(8):39-42
		                        		
		                        			
		                        			Objective To explore the treatment of percutaneous coronary intervention (PCI), and to comparatively study on the protection of side support by using the active and passive expansion technique.Method 78 patients with coronary artery disease were protected by using balloon technique, there were two groups: the active expansion group (n=41) and the side support balloon (n=37), the TIMI classification、myocardial perfusion rating (MBG), TIMI myocardial perfusion rating (TMP) and the incidence of marginal vascular interlayer were observed and analyzed. Results After the main support was put in, the proportion of patients with side branches of TIMI、 MBG and TMP was at level 3 and the proportion of patients with active balloon expansion was 93%, the margin expansion group was 84%, the difference was not statistically significant (P>0.05); the incidence of intersecting vascular interlayer in active dilatation group was 24%, the margin expansion group was 8%, and there were statistical differences (P<0.05). Conclusions Using the technique of holding balloon to protect the side branches, both the active expansion of the side support balloon and the expansion of the side support balloon can significantly reduce the risk of the main stent placement in the posterior branch of the blood vessel, however the incidence of side branch vascular interlayer was lower.
		                        		
		                        		
		                        		
		                        	
7.Influence factors of knowledge, attitude and practice of pelvic floor dysfunction during pregnancy and its intervention measures
Tingting TANG ; Peiqian LAI ; Shu CAI ; Jing ZENG
The Journal of Practical Medicine 2017;33(15):2584-2588
		                        		
		                        			
		                        			Objective To investigate the level of knowledge,attitude and practice(KAP)of pelvic floor dysfunction(PFD)and its influencing factors in pregnant women and provide reference for further health education for pregnant women. Methods Totally 637 pregnant women were investigated by Knowledge-Attitude-Practice (KAP)scale for PFD. Results The average scores of KAP in pregnant women were(31.68 ± 7.73),(16.41 ± 4.01) and (10.57 ± 3.00) respectively. About 85.6% of the pregnant women had interest in knowledge of PFD. Educational background,willing to understand knowledge of PFD,and gestational age were dominant factors affecting KAP of women with PFD. Conclusions The awareness rate of PFD and compliance rate of pelvic floor muscle function exercise in pregnant women are low. Effective measures should be taken to prevent PFD for pregnant women.
		                        		
		                        		
		                        		
		                        	
8.EP2A promotes human CD34 +cell homing in vitro but not proliferation
jie Fang LIU ; qun Ya WANG ; Jing TANG ; zhen Hui CHEN ; ping Shu LAI ; Chang SU ; Juan LI ; rong Duo XU
Chinese Journal of Pathophysiology 2017;33(11):2026-2031
		                        		
		                        			
		                        			AIM:To investigate the role of prostaglandin E2receptor 2 agonist (EP2A) in proliferation and homing of human CD34 +cells. METHODS:Bone marrow fluid and peripheral blood containing stem cells were collected from healthy donors mobilized by granulocyte colony-stimulating factor in our department. Human CD34 +cells were isolated by the method of magnetic-activated cell sorting microbeads. Bone marrow mononuclear cells were isolated by Ficoll-Paque centrifugation,and the bone marrow mesenchymal stem cells(BMMSC) were cultured with L-DMEM. Human CD34 +cells and BMMSC were divided into 4 groups,and treated with PGE2(as positive control),DMSO(as negative control),EP2A and EP2A+prostaglandin E2receptor 2 antagonist (EP2AA),respectively. After exposed to the reagents,human CD34 +cell viability was measured by CCK-8 assay,the number of colonies was evaluated by colony-formation assay,the cell cycle distribution was analyzed by flow cytometry,and the protein expression of survivin,β-catenin and CXC chemokine receptor 4 (CXCR4) was detrmined by Western blot. Moreover, the concentration of stromal cell-derived factor-1α (SDF-1α) in the BMMSC was detected by ELISA. RESULTS:The cell viability and the colony number of human CD34 +cells in EP2A group were not higher than those in negative control group. Furthermore,the proportion of human CD34 +cells treated with EP2A in G2/M phase was not elevated compared with negative control group. The protein expression of survivin and β-cate-nin did not up-regulated in human CD34 +cells exposed to EP2A,but the protein expression of CXCR4 in human CD34 +cells and the concentration of SDF-1α in BMMSC were elevated. CONCLUSION:EP2A promotes human CD34 +cell homing in vitro but not proliferation.
		                        		
		                        		
		                        		
		                        	
9.Efficacy of ultrasound-guided lauromacrogol sclerotherapy for benign thyroid cysts and factors affecting the therapeutic effect.
Zhi-Jiang CHEN ; Long WANG ; Yi-Jing HUANG ; Shui-Qing LAI ; Hong-Mei CHEN ; Jian-Hao PEI ; Shu-Zhen CONG ; Jian KUANG
Journal of Southern Medical University 2016;36(12):1694-1699
OBJECTIVETo evaluate the clinical efficacy of ultrasound-guided lauromacrogol sclerotherapy for benign thyroid cysts and analyze the factors affecting the efficacy.
METHODSUltrasound-guided lauromacrogol sclerotherapy was performed in 97 patients with a total of 99 benign thyroid cysts. The changes in cystic volume and other thyroid parameters were evaluated at 1, 3, 6, and 12 months after sclerotherapy. According to changes in the cystic volume, the efficacy of sclerotherapy was defined as therapeutic failure (with a volume reduction <50%), treatment success (volume reduction ≥50%) and cure (volume reduction ≥90%). The factors of affecting the efficacy of sclerotherapy was analyzed using COX regression.
RESULTSThe mean cystic volume at 1, 3, 6 and 12 months after sclerotherapy were reduced from the baseline volume of 12.08∓11.56 cmto 5.63∓8.51 cm, 5.96∓8.42 cm, 3.80∓5.50 cmand 2.85∓3.98 cm, respectively, with an average cystic volume reduction rate of (70.02∓33.72)%. Therapeutic success was achieved 82 of the 99 cysts (82.83%) and cure was achieved 63cysts (63.64%) at 12 months after the procedure. A second sclerotherapy was performed for 13 cysts which did not show a volume reduction at 1-3 months after the initial procedure. A disease course of over 12 months was an independent risk factor for a second sclerotherapy (23.7% [9/38] vs 6.6% [4/61], OR=4.473 [1.238-16.169], P=0.022). The efficacy of sclerotherapy was related to cystic cavity separation, cystic fluid viscosity, cystic/solid ratio and cystic wall thickness. COX regression analysis revealed that cystic cavity separation (HR=2.25, 95%CI: 1.19-4.25) and cystic fluid viscosity (HR=2.02, 95%CI: 1.19-3.43) were the major factors affecting the treatment efficacy.
CONCLUSIONUltrasound-guided lauromacrogol sclerotherapy is effective and safe for treatment of benign thyroid cysts, and the maximal treatment effect can be achieved at 6 months after sclerotherapy and in cases of uncomplicated cysts with non-viscous cystic fluid, no solid cystic cavity separation and a disease course of less than 12 months.
10.A multicenter study of fracture in patients with rheumatoid arthritis in China
Lizhi WANG ; Caihong WANG ; Xiaofeng LI ; Xiangcong ZHAO ; Wenpeng ZHAO ; Xiuru WANG ; Yin SU ; Yuan AN ; Yunshan ZHOU ; Ping ZHU ; Lina CHEN ; Guochun WANG ; Xin LU ; Hongtao JIN ; Yongfu WANG ; Rong YANG ; Zhuoli ZHANG ; Guangtao LI ; Xiangyuan LIU ; Lin SUN ; Fengxiao ZHANG ; Jiemei TAO ; Zhenbin LI ; Jing YANG ; Jinying LIN ; Meiqiu WEI ; Liufu CUI ; Rong SHU ; Xiaomin LIU ; Dan KE ; Shaoxian HU ; Cong YE ; Xiuyan YANG ; Hao LI ; Cibo HUANG ; Ming GAO ; Bei LAI ; Xingfu LI ; Lijun SONG ; Zhanguo LI
Chinese Journal of Rheumatology 2012;16(2):102-106
		                        		
		                        			
		                        			ObjectiveTo examine the clinical features of fractures and related risk factors in patients with rheumatoid arthritis(RA) in China.MethodsSix hundred and eighty-one RA patients were randomly selected from department of rheumatology of 18 hospitals of China.Data were obtained from the questionnaire,including age,sex,disease duration,the involvement of joints,treatment regimen,features of fractures etc.The possible risk factors of fracture in patients with RA were analyzed with a multi-variate Logistic regression analysis.Results① In 681 RA patients of the survey,48 patients had 54 fractures,and the incidence of fractures was about 8%.② Fractures occurred at various sites.Foot/ankle,femur,spine and wrist were the mostfrequent sites.③ The Logistic regression analysis showed that several factors increased the risk of fracture in RA patients,including long disease duration (OR:1.245,95%CI:0.987-1.570,P=0.065),male gender(OR:0.433,95%CI:0.199-0.942,P=0.035),more deformed joints(OR:1.042,95%CI:1.006-1.079,P=0.023),family history of RA (OR:2.201,95%CI:0.984-4.923,P=0.055),and high scores of SF-36(OR:1.017,95%CI:1.002-1.033,P=0.028).④ According to the degree of correlation from strong to weak,the risk factors of fracture were disease duration,SF-36,sex,number of deformed joints and family history of rheumatoid arthritis.ConclusionThe incidence of fracture is high in patients with rheumatoid arthritis.Several factors could increase the risk of fractures in RA patients,including long disease duration,male gender,more deformed joints,and family history of RA.In order to prevent the occurrence of fractures,cautions should be taken to prevent the development of fractures and treat the disease aggressively to suppress the disease activity of RA.
		                        		
		                        		
		                        		
		                        	
            
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