1.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.
2.Relaxin-2 Prevents Erectile Dysfunction by Cavernous Nerve, Endothelial and Histopathological Protection Effects in Rats with Bilateral Cavernous Nerve Injury
Kang LIU ; Taotao SUN ; Wenchao XU ; Jingyu SONG ; Yinwei CHEN ; Yajun RUAN ; Hao LI ; Kai CUI ; Yan ZHANG ; Yuhong FENG ; Jiancheng PAN ; Enli LIANG ; Zhongcheng XIN ; Tao WANG ; Shaogang WANG ; Jihong LIU ; Yang LUAN
The World Journal of Men's Health 2023;41(2):434-445
Purpose:
Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI).
Materials and Methods:
The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation.
Results:
Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3.
Conclusions
RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.
3.Effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia: a multicenter study in Hubei Province, China.
Chun-Hua LIU ; Hui WANG ; Si-Cong PENG ; Wen-Xiang WANG ; Rong JIAO ; Sha PAN ; Tian-Jiao ZHU ; Xiao-Ying LUAN ; Xiao-Fang ZHU ; Su-Ying WU ; De-Guo WEI ; Bing-Feng FU ; Rui-Hong YAN ; Shu-Jie YANG ; Ya-Hui LUO ; Gui-Ping LI ; Min YANG ; De-Zhao JIA ; Chuang GAO ; Xiong-Fei XIAO ; Li XIONG ; Jie SUN ; Jia-Peng XIAO ; Bo-Wen LI ; Yan-Ni LI ; Lian-Hong ZHANG ; Tian-Guo LI ; Min CHENG ; Jian-Xin XIA ; Shi-Wen XIA
Chinese Journal of Contemporary Pediatrics 2021;23(12):1208-1213
OBJECTIVES:
To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia.
METHODS:
A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis.
RESULTS:
Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%,
CONCLUSIONS
Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.
Asphyxia
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Asphyxia Neonatorum/epidemiology*
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Humans
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Hyperglycemia
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Infant, Newborn
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Prognosis
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Retrospective Studies
4.Rescued influenza A virus with codon deoptimized NS1 gene is attenuated both in vitro and in vivo.
Shijia LUAN ; Weiqi PAN ; Ting LI ; Huaqiang YANG ; Beiwu ZHANG ; Feng LI ; Ling CHEN
Chinese Journal of Biotechnology 2009;25(5):720-726
Abstract: To develop novel live attenuated influenza vaccine, we explored the feasibility to attenuate influenza virus by codon deoptimization of NS1. According to the codon usage bias in influenza A virus, we designed and synthesized a condon-deoptimized NS gene by substituting codons of 110 amino acids in the NS1 gene of A/Puerto Rico/8/34(H1N1) with unpreferred synonymous codons. The influenza A virus with the codon deoptimized NS1 gene (deoNS virus) was rescued by reverse genetics. Plaque forming assay and virus growth curve showed that the growth of deoNS virus was reduced about 1000 times in MDCK cells compared to that of the wild-type virus. Intranasal inoculation with deoNS virus did not cause death or evident disease in infected BALB/c mice. Furthermore, the virus titer in the lungs of mice infected with deoNS virus was significantly lower (i.e. 100-1000 times) than that of wild-type virus. Our results indicated that influenza virus could be effectively attenuated by synonymous codon deoptimization of NS1 gene. This strategy will be useful to develop new attenuated candidates for the production of live attenuated influenza vaccines.
Animals
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Base Sequence
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Chick Embryo
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Codon
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genetics
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Influenza A virus
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genetics
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pathogenicity
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Influenza Vaccines
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immunology
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Mice
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Mice, Inbred BALB C
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Molecular Sequence Data
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Orthomyxoviridae Infections
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immunology
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prevention & control
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Recombination, Genetic
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Vaccines, Attenuated
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immunology
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Viral Nonstructural Proteins
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genetics
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Virulence
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genetics
5.Comprehensive treatment of 352 cases with hypopharyngeal cancer
Xin-Liang PAN ; Da-Peng LEI ; Da-Yu LIU ; Feng-Lei XU ; Hong-Li WANG ; Tong JIN ; Guang XIE ; Xin-Yong LUAN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2009;44(9):710-715
is restored and the laryngeal function is preserved as far as possible. The preservation of laryngeal function and the laryngeal and pharyngeal reconstruction are based on the premise that the tumor was excised completely.
6.Differentiation of smooth muscle progenitor cells in peripheral blood and its application in tissue engineered blood vessels.
Shang-zhe XIE ; Ning-tao FANG ; Shui LIU ; Ping ZHOU ; Yi ZHANG ; Song-mei WANG ; Hong-yang GAO ; Luan-feng PAN
Journal of Zhejiang University. Science. B 2008;9(12):923-930
BACKGROUNDA major shortcoming in tissue engineered blood vessels (TEBVs) is the lack of healthy and easily attainable smooth muscle cells (SMCs). Smooth muscle progenitor cells (SPCs), especially from peripheral blood, may offer an alternative cell source for tissue engineering involving a less invasive harvesting technique.
METHODSSPCs were isolated from 5-ml fresh rat peripheral blood by density-gradient centrifugation and cultured for 3 weeks in endothelial growth medium-2-MV (EGM-2-MV) medium containing platelet-derived growth factor-BB (PDGF BB). Before seeded on the synthesized scaffold, SPC-derived smooth muscle outgrowth cell (SOC) phenotypes were assessed by immuno-fluorescent staining, Western blot analysis, and reverse transcription polymerase chain reaction (RT-PCR). The cells were seeded onto the silk fibroin-modified poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (SF-PHBHHx) scaffolds by 6x10(4) cells/cm2 and cultured under the static condition for 3 weeks. The growth and proliferation of the seeded cells on the scaffold were analyzed by 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay, scanning electron microscope (SEM), and 4,6-diamidino-2-phenylindole (DAPI) staining.
RESULTSSOCs displayed specific "hill and valley" morphology, expressed the specific markers of the SMC lineage: smooth muscle (SM) alpha-actin, calponin and smooth muscle myosin heavy chain (SM MHC) at protein and messenger ribonucleic acid (mRNA) levels. RT-PCR results demonstrate that SOCs also expressed smooth muscle protein 22alpha (SM22alpha), a contractile protein, and extracellular matrix components elastin and matrix Gla protein (MGP), as well as vascular endothelial growth factor (VEGF). After seeded on the SF-PHBHHx scaffold, the cells showed excellent metabolic activity and proliferation.
CONCLUSIONSPCs isolated from peripheral blood can be differentiated into the SMCs in vitro and have an impressive growth potential in the biodegradable synthesized scaffold. Thus, SPCs may be a promising cell source for constructing TEBVs.
3-Hydroxybutyric Acid ; chemistry ; Animals ; Blood Vessels ; cytology ; Caproates ; chemistry ; Cell Adhesion ; Cell Differentiation ; Cell Proliferation ; Immunophenotyping ; Microscopy, Electron, Scanning ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; RNA, Messenger ; analysis ; Rats ; Tissue Engineering ; Vascular Endothelial Growth Factor A ; genetics
7.Construction of tissue-engineered heart valves by using decellularized scaffolds and endothelial progenitor cells.
Ning-Tao FANG ; Shang-Zhe XIE ; Song-Mei WANG ; Hong-Yang GAO ; Chun-Gen WU ; Luan-Feng PAN
Chinese Medical Journal 2007;120(8):696-702
BACKGROUNDTissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. This study was designed to develop a tissue engineering heart valve by using human umbilical cord blood-derived endothelial progenitor cells (EPCs) and decellularized valve scaffolds.
METHODSDecellularized valve scaffolds were prepared from fresh porcine heart valves. EPCs were isolated from fresh human umbilical cord blood by density gradient centrifugation, cultured for 3 weeks in EGM-2-MV medium, by which time the resultant cell population became endothelial in nature, as assessed by immunofluorescent staining. EPC-derived endothelial cells were seeded onto the decellularized scaffold at 3 x 10(6) cells/cm(2) and cultured under static conditions for 7 days. Proliferation of the seeded cells on the scaffolds was detected using the MTT assay. Tissue-engineered heart valves were analyzed by HE staining, immunofluorescent staining and scanning electron microscopy. The anti-thrombogenic function of the endothelium on the engineered heart valves was evaluated by platelet adhesion experiments and reverse transcription-polymerase chain reaction (RT-PCR) analysis for the expression of endothelial nitric oxide synthase (eNOS) and tissue-type plasminogen activator (t-PA).
RESULTSEPC-derived endothelial cells showed a histolytic cobblestone morphology, expressed specific markers of the endothelial cell lineage including von Willebrand factor (vWF) and CD31, bound a human endothelial cell-specific lectin, Ulex Europaeus agglutinin-1 (UEA-1), and took up Dil-labeled low density lipoprotein (Dil-Ac-LDL). After seeding on the decellularized scaffold, the cells showed excellent metabolic activity and proliferation. The cells formed confluent endothelial monolayers atop the decellularized matrix, as assessed by HE staining and immunostaining for vWF and CD31. Scanning electron microscopy demonstrated the occurrence of tight junctions between cells forming the confluent monolayer. Platelets adhesion experiments suggested that the neo-endothelium was non-thrombogenic. The expression levels of eNOS and t-PA genes in the neo-endothelium were quite similar to those in human umbilical vein endothelial cells.
CONCLUSIONSEPCs isolated from the human umbilical cord blood can differentiate into endothelial cells in vitro and form a functional endothelium atop decellularized heart valve scaffolds. Thus, EPCs may be a promising cell source for constructing tissue-engineered heart valves.
Animals ; Cell Proliferation ; Endothelial Cells ; cytology ; metabolism ; Heart Valve Prosthesis ; Heart Valves ; cytology ; metabolism ; ultrastructure ; Humans ; Immunohistochemistry ; Microscopy, Electron, Scanning ; Nitric Oxide Synthase Type III ; genetics ; metabolism ; Platelet Aggregation ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells ; cytology ; metabolism ; Swine ; Tissue Engineering ; methods ; Tissue Plasminogen Activator ; genetics ; metabolism ; Umbilical Cord ; cytology
9.Surgical treatment of hypopharyngeal cancer with cervical esophageal invasion.
Da-Peng LEI ; Xin-Liang PAN ; Feng-Lei XU ; Da-Yu LIU ; Li-Qiang ZHANG ; Xue-Zhong LI ; Guang XIE ; Xin-Yong LUAN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2005;40(9):691-695
OBJECTIVETo review the experience of different surgical construction methods for hypopharyngeal cancer with cervical esophageal invasion.
METHODSFrom 1989 to 2000,forty-eight patients with advanced hypopharyngeal cancer and cervical esophageal invasion were retrospectively reviewed, including 38 males and 10 females. The median age was 54. 3 years old, ranged from 26 to 71 years old. According to UICC 1997 criteria, all the tumors were T4 stage and originated from the pyriform sinus (33), posterior pharyngeal wall (14), postcricoid area (1), there were 28 patients in cN0, 15 in cN1, 5 in cN2 and no distant metastasis. Precise preoperative evaluation was performed with computed tomography scan, barium swallow perspective and biopsy. All the patients received modified neck dissection, including both unilateral (38 patients) and bilateral (10 patients). Pharyngoesophageal defect reconstruction methods were: laryngotracheal flap in 11 patients, pectoralis major musculocutaneous flap in 13, laryngotracheal flap combined with pectoralis major musculocutaneous flap in 6, pectoralis major musculocutaneous flap combined with the split graft in 10, stomach pulling-up in 3, colon interposition in 5 patients. Total laryngectomy was carried out in 8 patients. All patients received radiotherapy postoperatively (dose 55 - 75 Gy).
RESULTSThe cervical lymph node metastasis was found in 20 patients. Pathologic findings showed that well, moderately and lower differentiated squamous cell carcinomas were 18, 24, 6 cases, respectively. The overall 3 and 5 year survival rates were 52.1% (25/48) and 27.3% (12/44), respectively. The 3 and 5 year survival rates in functionally preserved group were 65.2% (15/23) and 33.3% (7/21), while in non functionally preserved group were 40.0% (10/25) and 21.7% (5/23), respectively. Fifteen patients laryngeal functions (voice, respiration and deglutition) were completely restored and 8 patients partially restored (voice and deglutition). The decannulation rate was 65% (15/23). The complication included pharyngeal fistulas in 10 cases and splitting of chest wall in 1 cases.
CONCLUSIONSCombined therapy was the best choice for hypopharyngeal cancer with cervical esophageal invasion. The laryngeal function is preserved as far as possible. The continuity of the pharyngoesophagus was restored by pectoralis major musculocutaneous flap, laryngotracheal flap, or combined with the split graft. Stomach transposition or colon interposition was used while the defect of the esophagus was greater.
Adult ; Aged ; Carcinoma, Squamous Cell ; mortality ; pathology ; surgery ; Esophageal Neoplasms ; mortality ; secondary ; surgery ; Esophagus ; pathology ; Female ; Humans ; Hypopharyngeal Neoplasms ; mortality ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate
10.Molecular cloning and expression of anti-tumor adhesion peptide (beta3).
Song-Mei WANG ; Jun ZHU ; Yan LI ; Luan-Feng PAN ; Xi-Liang ZHA ; Yin-Kun LIU
Chinese Journal of Biotechnology 2005;21(4):558-562
To block tumor cell adhesion, inhibit tumor metastasis and recurrence, the anti-adhesion peptide-trimeric beta peptide (DLYYLMDLSYSMKGGDLYYLMDLSYSMKGGDLYYLMDLSYSMK, beta3) was designed. The DNA fragment of beta3 was cloned into expression vector pET-His and the fusion protein His-beta3 was expressed in E. coli. BL21(DE3)plysS. After 1.5 hours' induction with IPTG, His-beta3 peptide was expressed significantly amounting to 10% of the insoluble proteins and 4% of the total proteins. 20mg of beta3 peptide was obtained from one litter culture medium after purification by using metal-chelating sepharose 6B FF. The purity of beta3 is 92.2% according to Gel-Pro analysis. The anti-adhesion effects of beta3 peptide, beta1 peptide (DLYYLMDLSYSMK) and GRGDS on the hepatocellular carcinoma cell line SMMC-7721 and the high metastasis hepatocellular carcinoma cell line HCCLM6 were studied. The result showed the beta3 blocked the adhesion of HCCLM6 cells and SMMC-7721 cells to fibronectin (FN) specifically. The inhibition effect was dose-dependent and time-dependent and the inhibition rate of beta3 was higher than three times concentration of beta1 and GRGDS. This suggested that pET-His-beta3/BL21(DE3)plysS was a suitable expression system for beta3, and the expressed beta3 specially inhibited the adhesion of cancer cells.
Amino Acid Sequence
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Antineoplastic Agents
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pharmacology
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Cell Adhesion
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drug effects
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Cloning, Molecular
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Escherichia coli
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genetics
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metabolism
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Molecular Sequence Data
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Peptide Fragments
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pharmacology
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Peptides
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genetics
;
metabolism
;
pharmacology
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Recombinant Proteins
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biosynthesis
;
genetics
;
Tumor Cells, Cultured

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