1.Comparision of Mutational Spectrum between Elderly and Young Adults with Acute Myeloid Leukemia Based on Next Generation Sequencing.
Wei-Min WANG ; Ya-Fei LI ; Ling SUN ; Zhong-Xing JIANG ; Ding-Ming WAN ; Jie MA ; Si-Lin GAN ; Fang WANG ; Wei-Jie CAO ; Hui SUN
Journal of Experimental Hematology 2020;28(1):12-17
OBJECTIVE:
To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS).
METHODS:
The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (<60 years old) were compared.
RESULTS:
The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ=7.180, P=0.007) and (20.0% vs 6.7%) ( χ=8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ=16.653, P=0.000) and (23.6% vs 8.7%)(χ=9.041, P=0.003) respectively.
CONCLUSION
The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.
2.The efficacy and safety of BCG in the prevention of postoperative recurrence of intermediate and high-risk non-muscle invasive bladder cancer: a randomized, controlled, multi-center clinical trial (mid-term report)
Hao YU ; Tianxin LIN ; Xiang LI ; Hailong HU ; Nan LIU ; Jian ZHANG ; Xudong YAO ; Zhaoyang WU ; Xiangbo KONG ; Liqun ZHOU ; Jiacun CHEN ; Wei LI ; Jinjian YANG ; Dongwen WANG ; Xiaodong ZHANG ; Youhan CAO ; Shaozhong WEI ; Ye TIAN ; Huiqing ZHANG ; Benkang SHI ; Zhanpo YANG ; Qingwen LI ; Jinkai SHAO ; Tie ZHONG ; Xiaolin WANG ; Hongxing HUANG ; Liming LI ; Jianhua TIAN ; Zhimin WANG ; Jin YANG ; Lin QI ; Jian HUANG
Chinese Journal of Urology 2019;40(7):485-491
Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1%.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P > 0.05).The 1-year recurrence-free survival rates were 80.0% in the group 1 and 88.3% in the group 2 and 73.7% in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95% CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 % CI 0.31-0.92,P =0.0266;95 % CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5% (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2% (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3% (32/222).The incidence of overall AE in the group 2 was 71.8% (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1% (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7% (26/223).The overall AE rate in the control group was 53.2% (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4% (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8% (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.
3.An exploratory study to perfect the Letournel classification of acetabular fractures
Chengjie ZHONG ; Gang WANG ; Yunping YANG ; Shenglu CAO ; Ziyi ZHONG ; Kai TONG ; Shiyuan LIN
Chinese Journal of Orthopaedics 2019;39(5):271-277
Objectives To put forward the modified Letournel classification of acetabular fractures,and evaluate the guiding role of the modified Letournel classification in clinical work.Methods A retrospective study of 170 patients (178 sides) with acetabular fractures treated at Nanfang Hospital between January 2006 and August 2018 was performed.Among them 129 cases were males and 41 were females.The average age was 40.2±14.2 years (range,14-82 years).According to the Letournel classification,unclassifiable/atypical acetabular fractures were found out with plain Ⅹ-ray and plain CT scan and three-dimensional CT,and then their unclassifiable reasons were analyzed.Based on anatomical landmarks,clear boundaries of acetabular walls were defined on the 3D printed pelvic model.The structure of each column is a trihedron.The wall's fracture and column's fracture were distinguished using a theory that the wall's fracture involved two surfaces of column with interruption of continuity and column's fracture involved three.When column's fracture associated with wall's fracture,lowercase a,p and q were used representing comminuted areas of corresponding anterior and posterior wall,quadrilateral plate respectively.When column's fracture didn't associates with wall's fracture,it is marked with number 0.Finally,all fractures were classified according to the modified Letournel classification.The relationship between fracture type and surgical approach was analyzed.Results There was 51.7% (92 sides) of acetabular fractures that couldn't be classified by the Letournel classification.Incomplete fracture lines (49 sides,53.3%),comminuted fractures (28 sides,30.4%),both of them (15 sides,16.3%) were their unclassifiable reasons.There were 8 types in the modified Letournel classification,including posterior wall fracture,posterior column fracture,anterior wall fracture,anterior column fracture,transverse fracture,T-shaped fracture,anterior column+posterior hemitransverse fracture,and both columns fracture.Posterior column+posterior wall fracture,transverse+posterior wall fracture had respectively become a form of posterior column fracture and of transverse fracture.According to the modified Letournel classification,the reclassification rate of 178 side fractures was 100%,which was significantly higher than 48.3% (86/178) of the traditional Letournel classification,and the difference was statistically significant (x2=124.06,P< 0.001).100% of posterior wall fracture and 80.00% of posterior column fracture were treated by posterior approach.100% of anterior column fracture and 73.68% of both columns fracture were treated by anterior approach.Conclusion All acetabular fractures can be classified by the modified Letournel classification.The orientation of the comminuted walls reflects in part severity of the injury,better helps orthopaedic surgeons understand the morphology of acetabular fractures and select appropriate surgical approach.
4.Effects of MD2 gene silencing on high glucose-induced proliferation inhibition, apoptosis and inflammation in rat cardiomyocytes.
Zhong-Min LIN ; Guo-Rong CHEN ; Quan-Bo ZHANG ; Fang WANG ; Lan-Ting XIANG ; Qiong-Jie CAO
Chinese Journal of Applied Physiology 2019;35(3):273-278
OBJECTIVE:
To investigate the effects of myeloid differentiation-2 (MD2) gene silencing on high glucose-induced proliferation inhibition, apoptosis and inflammation in rat cardiomyocytes.
METHODS:
The immortalized rat cardiomyocyte cell line H9C2 were transfected with MD2 small interfering RNA (si-MD2) and negative control for 24 h, then stimulated with high glucose (HG) for 48 h. RT-qPCR was performed to detect the mRNA levels of MD2 and inflammatory factors TNF-α, IL-1β and IL-6. MTS and flow cytometry were used to evaluate cell proliferation, cell cycle and apoptosis rate. Western blot was used to detect protein expression levels and phosphorylation levels.
RESULTS:
The mRNA and protein levels of MD2 in H9C2 cells were dramatically decreased after transfected with si-MD2 (P<0.01). After stimulation of high glucose, the mRNA levels of inflammatory factors, the cells in G0/G1 phase , the cell apoptosis rate and the protein level of cleaved Caspase-3 were significantly increased, while the cell proliferation ability was decreased (P<0.01). MD2 gene silencing antagonized the effects of high glucose on cell proliferation, cell cycle, cell apoptosis and the mRNA levels of TNF-α, IL-1β , IL-6(P<0.05). Western blot analysis showed that the phosphorylation levels of extracellular signal-regulated kinase(ERK1/2), P38 mitogen-activated protein kinase(P38 MAPK) and C-Jun N-terminal kinase(JNK) protein were increased significantly in H9C2 cells treated with high glucose, which could be reversed by silencing of MD2 (P<0.01).
CONCLUSION
This study demonstrates that MD2 gene silencing reverses high glucose-induced myocardial inflammation, apoptosis and proliferation inhibition via the mechanisms involving suppression of ERK, P38 MAPK, JNK signaling pathway.
Animals
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Apoptosis
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Cell Proliferation
;
Cells, Cultured
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Cytokines
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metabolism
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Gene Silencing
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Glucose
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Inflammation
;
JNK Mitogen-Activated Protein Kinases
;
metabolism
;
Lymphocyte Antigen 96
;
genetics
;
Myocytes, Cardiac
;
cytology
;
Rats
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p38 Mitogen-Activated Protein Kinases
;
metabolism
5.A new fixation and reconstruction method versus arthroscopic reconstruction for treating avulsion fracture at the tibial insertion of the knee posterior cruciate ligament: study protocol for a non-randomized controlled trial and preliminary results
Guang-Dong CHEN ; Yang ZHANG ; Yong-Jian NI ; Hong-Mei DU ; Tong-Jun CAO ; Zhong-Lin SHAN
Chinese Journal of Tissue Engineering Research 2018;22(7):1078-1083
BACKGROUND: Arthroscopic reconstruction for treatment of avulsion fracture at the tibial insertion of the knee posterior cruciate ligament (PCL) can minimize surgical trauma to the largest degree. However, its implants have relatively poor stability; therefore, functional exercise cannot be performed in the early stages after surgery, which is inconducive to knee function recovery. It is extremely challenging to perform traditional open reduction with internal fixation to repair avulsion fractures at the tibial insertion of the knee PCL. Often, the crushed bones cannot be firmly fixed, leading to a poor repair effect. OBJECTIVE: To design a new inverted "L"-shaped incision in the popliteal fossa through which bone plates were inserted to fix the crushed bones and to reconstruct PCL tension, facilitating knee function recovery; to compare the therapeutic effects of this new fixation and reconstruction method, and arthroscopic reconstruction for treating avulsion fracture at the tibial insertion of the knee PCL. METHODS: A prospective, single-center, non-randomized controlled trial. One hundred and eighty patients (knees) with avulsion fracture at the tibial insertion of the knee PCL will be assigned to two groups based on treatment methods: arthroscopic reconstruction group (n = 90;fracture fixation and repair under the arthroscope) and new method group (n = 90; bone plates will be inserted through an "L"-shaped incision in the popliteal fossa to fix the crushed bones and reconstruct PCL tension). After surgery, these patients will be followed up for 6 weeks, 6 months, and 12 months. RESULTS AND CONCLUSION: The primary outcome measure is the excellent and good rate of knee function recovery at 12 months after surgery as evaluated by Lysholm Knee Scoring Scale score (Herein referred to as Lysholm score). The secondary outcome measures are the excellent and good rate of knee function recovery before surgery, 6 weeks and 6 months after surgery; Lysholm score before surgery, 6 weeks, 6 months and 12 months after surgery; Hospital for Special Surgery (HSS) knee score, Visual Analogue Scale (VAS) score, posterior drawer test negative rate, X-ray morphology of the knee before surgery, and 6 weeks, 6 months, and 12 months after surgery and; incidence of adverse events at 6 weeks, 6 months and 12 months after surgery. Results of a preliminary study involving 62 patients (knees) with avulsion fracture at the tibial insertion of the knee PCL showed that posterior drawer test negative rate and Lysholm score were significantly higher in the new method group compared to the arthroscopic reconstruction group (P < 0.05) at 3 months after surgery. This study will be performed to compare the therapeutic effects of bone plate insertion through an "L"-shaped incision made in the popliteal fossa to fix the crushed bones and to reconstruct PCL tension, and traditional fracture fixation and repair under the arthroscope to treat avulsion fracture at the tibial insertion of the knee PCL. We believe that the former method will be superior to the latter one because it can fix the avulsion fracture more firmly, facilitating knee function recovery. This study was approved by Medical Ethics Committee of Cangzhou Central Hospital of China (approval No. 2017-120-01). This study will be performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. Participants provided signed informed consent prior to participation in the study. This study was designed in December 2017. Patient recruitment and data collection will begin in April 2018. Patient recruitment will end in June 2019. Data analysis will be performed in August 2020. The study will be completed in October 2020. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. This trial was registered with the Chinese Clinical Trial Registry (registration number:ChiCTR1800015026). The version of this study protocol is (1.0).
7.Clinical therapeutic effect of a new bundle-to-bundle suturing method for acute Achilles tendon rupture.
Cheng-Lin WANG ; Kai-Xue CAO ; Jun-Zhong YANG
China Journal of Orthopaedics and Traumatology 2018;31(2):183-185
OBJECTIVETo investigate the clinical effect of a new bundle-to-bundle suturing method for acute Achilles tendon rupture.
METHODSFrom April 2013 to January 2015, 15 patients with acute Achilles tendon rupture were treated with a new bundle-to-bundle suturing method including 12 males and 3 females with an average age of 37.5 years old ranging from 27 to 56 years old. All of them were immobilized by cast for 6 weeks on the underlying limbs, and were educated for a rehabilitation training during the follow-up.
RESULTSAll the patients were followed up for 9 to 17.5 months with an average of 13.5 months. According to the American Ankle Surgery Association (AOFAS), ankle and foot score was 93.3±3.5 at 6 months after operation. All patients got incomplete weight-bearing at 1.6 months on average after the operation, and back to primary work position 4.7 months later on average. All the wounds got primary healing. No incisional infection, necrosis of incisional marginal necrosis, rupture of the Achilles tendon, and gastrocnemius injury occurred.
CONCLUSIONSThe surgical treatment of acute Achilles tendon rupture with bundle-to-bundle suturing method has advantages of mini-invasion, a low rate of incision problems and quick function recovery, and was valuable spread in clinic.
8.Combination of Tumor Volume and Epstein-Barr Virus DNA Improved Prognostic Stratification of Stage II Nasopharyngeal Carcinoma in the Intensity Modulated Radiotherapy Era: A Large-Scale Cohort Study.
Qiu Yan CHEN ; Shao Yan GUO ; Lin Quan TANG ; Tong Yu LU ; Bo Lin CHEN ; Qi Yu ZHONG ; Meng Sha ZOU ; Qing Nan TANG ; Wen Hui CHEN ; Shan Shan GUO ; Li Ting LIU ; Yang LI ; Ling GUO ; Hao Yuan MO ; Rui SUN ; Dong Hua LUO ; Chong ZHAO ; Ka Jia CAO ; Chao Nan QIAN ; Xiang GUO ; Mu Sheng ZENG ; Hai Qiang MAI
Cancer Research and Treatment 2018;50(3):861-871
PURPOSE: Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. MATERIALS AND METHODS: By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. RESULTS: Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm³; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm³; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm³) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm³). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. CONCLUSION: Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.
Biomarkers
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Cohort Studies*
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DNA*
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Herpesvirus 4, Human*
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Humans
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Lymph Nodes
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Nasopharynx
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Plasma
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Prognosis
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Radiotherapy*
;
Tumor Burden*
9.New situation and new strategies——research and development and internationalization of new drugs and health products of traditional Chinese medicine
Ning JIANG ; Chun-Hui QI ; Liang CAO ; Lan-Ying CHEN ; Jin-Hui GU ; Yong KANG ; Inkyeom KIM ; Xiao-Yuan LIAN ; Yin LU ; Gui-Yuan LYU ; Ke NIE ; Yun QI ; SCHINI-KERTH VALÉRIE ; SPEDDING MICHAEL ; WAINWRIGHT CHERRY ; Yue-Hua WANG ; Wei XIAO ; Yong YANG ; Lin-Zhong YU ; Dan-Shen ZHANG ; Yong-He ZHANG ; Wen-Xia ZHOU ; Guan-Hua DU ; Yong-Xiang ZHANG
Chinese Journal of Pharmacology and Toxicology 2018;32(1):1-50
The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.
10.Treatment of gouty arthritis of the first metatarsophalangeal joint by Masquelet technique.
Cheng-Lin WANG ; Jun-Zhong YANG
China Journal of Orthopaedics and Traumatology 2017;30(8):763-766
OBJECTIVETo study clinical curative effects of a Masquelet technology in the treatment of gouty arthritis in the first metatarsophalangeal joint.
METHODSFrom February 2012 to May 2016, 7 patients with the gouth arthritis of the first metatarsophalangeal joint were treated by the Masqueket technology. There were 5 males and 2 females, ranging in age from 42 to 58 years old, with an average age of 50 years old. During the regular follow up, the bone healing was assessed by the radiographic imaging, and the orthopaedic foot and ankle Association (AOFAS) ankle function scoring system was used for comprehensive evaluation.
RESULTSAll the patients were followed up, and the duration ranged from 6 to 8 months, with a mean of 7 months. All the wounds obtained first intention healing, and there were no complications such as wound infection, flap necrosis and other soft tissue complications. The time to bone healing was 3 to 4 months, with an average of 3.6 months. The AOFAS score was increased from preoperative 42.5±4.6 to postoperative 85.0±10.5.
CONCLUSIONSThe application of Masquelet technique in the treatment of first metatarsophalangeal joint gouty arthritis achieves obvious symptom relief, has less complications, and can effectively improve the quality of life of patients, which is a new and effective treatment.

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