1.Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities.
Youtao XU ; Qinhong SUN ; Siwei WANG ; Hongyu ZHU ; Guozhang DONG ; Fanchen MENG ; Zhijun XIA ; Jing YOU ; Xiangru KONG ; Jintao WU ; Peng CHEN ; Fangwei YUAN ; Xinyu YU ; Jinfu JI ; Zhitong LI ; Pengcheng ZHU ; Yuxiang SUN ; Tongyan LIU ; Rong YIN ; Lin XU
Chinese Journal of Lung Cancer 2024;26(12):889-900
BACKGROUND:
In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.
METHODS:
A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.
RESULTS:
MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).
CONCLUSIONS
The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans
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Lung Neoplasms/genetics*
;
Adenocarcinoma of Lung/genetics*
;
China
;
Prognosis
;
Transcription Factors
2.Comparison of complications and analysis of factors affecting renal function decline after laparoscopic radical cystectomy with different urinary diversion methods
Bin JIN ; Zhengtong LYU ; Jibo JING ; Pengjie WU ; Yuan YUAN ; Hong MA ; Xin CHEN ; Jinfu WANG ; Yaoguang ZHANG ; Ming LIU
Chinese Journal of Geriatrics 2023;42(7):815-820
Objective:To compare the complications associated with various urinary flow diversion methods and identify the factors that contribute to the decline in renal function after radical total cystectomy for myoinfiltrating urothelial carcinoma.Methods:This study conducted a retrospective analysis on the clinical data of 46 patients with pathologically confirmed muscle-invasive bladder cancer.The patients underwent laparoscopic radical cystectomy with either ileal conduit diversion(n=21)or ureterocutaneous diversion(n=25)between January 2017 and December 2021.Perioperative data, postoperative pathology, postoperative complications, and follow-up results were compared between the two groups.Results:The study found significant differences between the two groups in terms of age[(67±6)years vs.(73±8)years, t=3.132, P=0.003], Charlson comorbidity index adjusted for age[(3.80±1.15) vs.(4.52±1.03), t=2.223, P=0.031], prognostic nutritional index[(48.81±5.74) vs.(43.64±4.74), t=3.347, P=0.002], operation time[(449±108)minutes vs.(326±130)minutes, P=0.001]], hospital stay[(20.1±11.1)days vs.(13.3±5.2)days, t=2.762, P=0.008], proportion of Clavien grade 3 or higher complications within 3 months after surgery(4/21 vs 0/25, χ2=2.105, P<0.05), and proportion of stoma-free patients(18/21 vs.5/25, χ2=6.373, P<0.01). According to Logistic multivariate analysis, perioperative blood transfusion and urinary tract infection were identified as independent risk factors for renal function decline 12 months after surgery.Escherichia coli was found to be the most common bacteria cultured from urinary tract infections in both groups after surgery. Conclusions:Laparoscopic radical cystectomy with ureterocutaneous diversion offers benefits such as shorter hospital stays and fewer perioperative complications for older and frail patients.However, a higher proportion of patients may require ureteral stenting.It is important to note that perioperative blood transfusion and urinary tract infection are major risk factors for renal function decline following radical cystectomy.
3.Efficacy and safety of flurbiprofen cataplasms versus loxoprofen sodium cataplasms in knee osteoarthritis: a randomized controlled trial.
Dong LI ; Yinchu CHENG ; Ping YUAN ; Ziyang WU ; Jiabang LIU ; Jinfu KAN ; Kun ZHANG ; Zhanguo WANG ; Hui ZHANG ; Guangwu ZHANG ; Tao XUE ; Junxiu JIA ; Suodi ZHAI ; Zhenpeng GUAN
Chinese Medical Journal 2023;136(18):2187-2194
BACKGROUND:
Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA.
METHODS:
This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events.
RESULTS:
Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain.
CONCLUSIONS
This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.
Humans
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Female
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Middle Aged
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Aged
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Osteoarthritis, Knee/drug therapy*
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Flurbiprofen/therapeutic use*
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Anti-Inflammatory Agents, Non-Steroidal/therapeutic use*
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Pain/drug therapy*
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Treatment Outcome
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Double-Blind Method
4.Clinical characteristics of the 2019 novel coronavirus Omicron variant infected cases
Ying LYU ; Wei YUAN ; Dongling SHI ; Yixin LIAO ; Yingchuan LI ; Ming ZHONG ; Feng LI ; Enqiang MAO ; Yinzhong SHEN ; Jinfu XU ; Yuanlin SONG ; Bijie HU ; Wenhong ZHANG ; Yun LING
Chinese Journal of Infectious Diseases 2022;40(5):257-263
Objective:To investigate the clinical characteristics and prognostic factors of 2019 novel coronavirus (2019-nCoV) Omicron variant infected cases.Methods:A total of 987 coronavirus disease 2019 (COVID-19) adult imported cases admitted to Shanghai Public Health Clinical Center, Fudan University from July 1, 2021 to January 6, 2022 were recruited. The cases were divided into Omicron group (193 cases) and non-Omicron group (794 cases) according to the genotype of the virus. The clinical data, imaging examination and laboratory results of two groups were collected and compared. Chi-square test and Mann-Whitney U test were used as statistical methods. Multiple linear regression analysis was used for multiple linear regression analysis. Results:The majority of patients in Omicron group were 18 to 30 years old, accounting for 51.3%(99/193), which was higher than 31.4%(249/794) in non-Omicron group. The difference was statistically significant ( χ2=52.75, P<0.001). The proportion of mild cases in Omicron group was 88.6%(171/193), which was higher than 81.6%(648/794) in non-Omicron group. The difference was statistically significant ( χ2=5.37, P=0.021). Cases with symptoms were more common in Omicron group than those in non-Omicron group (60.1%(116/193) vs 29.1%(231/794)), and the difference was statistically significant ( χ2=65.49, P<0.001), with the main clinical manifestations of sore/itchy throat, fever and cough/expectoration. The proportion of cases with pulmonary computed tomography (CT) imaging manifestations at admission in Omicron group was 13.0%(25/193), which was lower than that in non-Omicron group (215/794, 27.1%). The difference was statistically significant ( χ2=16.83, P<0.001). The proportion of cases with 2019-nCoV IgG positive at admission was 47.7%(92/193) in Omicron group, which was lower than 61.1%(485/794) in non-Omicron group, and the difference was statistically significant ( χ2=11.51, P<0.001). The hospitalization time of Omicron group was 20.0 (16.0, 23.0) d, which was longer than that of non-Omicron group (14.0 (10.0, 22.0) d), and the difference was statistically significant ( Z=-7.42, P<0.001). Multiple linear regression analysis showed that the time of hospitalization of cases with 2019-nCoV IgG positive at admission was shorter, while that of the cases with fever in Omicron group was longer (both P<0.050). Conclusions:The main clinical characteristics of cases with Omicron variant are fever and upper respiratory symptoms. Their pulmonary CT imaging manifestations are less, and the time of hospitalization is slightly longer. The time of hospitalization and the virus clearance time in Omicron variant infected cases with 2019-nCoV IgG positive at admission and not presented with fever are both shorter.
5.Efficacy analysis of porcine small intestine submucosa-derived mesh and polypropylene mesh applied in anterior abdominal wall incisional hernia repair
Weigang DAI ; Zhihui CHEN ; Jinfu TAN ; Yujie YUAN ; Jidong ZUO ; Qiongyun ZHAO ; Min TAN
Chinese Journal of Digestive Surgery 2018;17(11):1095-1100
Objective To investigate the clinical efficacy of porcine small intestine submucosa-derived (SIS) mesh and polypropylene (PP) mesh applied in anterior abdominal wall incisional hernia repair.Methods The retrospective cohort study was conducted.The clinical data of 59 patients who underwent anterior abdominal wall incisional hernia repair in the First Affiliated Hospital of Sun Yat-Sen University between January 2012 and December 2017 were collected.Of 59 patients,22 undergoing anterior abdominal wall incisional hernia repair with SIS mesh and 37 undergoing anterior abdominal wall incisional hernia repair with PP mesh were respectively allocated into the SIS group and PP group.Surgeons selected surgical procedures according to hernia ring situations of patients.Observation indicators:(l) intra-and post-operative recovery situations;(2) follow-up.Follow-up using outpatient examination and telephone interview was performed to detect long-term complications of patients including foreign body sensation or pain in abdominal wall and hernia recurrence up to May 2018.Measurement data with normal distribution were represented as (x)±s,and comparison between groups was done using t test.Measurement data with skewed distribution were described as M (range),and comparison between groups was done using Mann-Whitney U test.Comparison of count data was analyzed using the chi-square test or Fisher exact probability.Results (1) Intra-and post-operative recovery situations:patients of the SIS group and PP group underwent successfully anterior abdominal wall incisional hernia repair.There were 2,3,3,14 and 5,26,1,5 patients undergoing open Onlay repair,open Sublay repair,laparoscopic intraperitoneal onlay mesh repair,laparoscopic combined with open mesh repair in the SIS group and PP group respectively.The volume of intraoperative blood loss,cases of postoperative incisional seroma and surgical site infection were (23± 11)mL,7,5 in the SIS group and (30± 13)mL,3,1 in the PP group respectively,with statistically significant differences between groups (t=-2.238,P<0.05).(2) Follow-up:patients of the SIS group and PP group were respectively followed up for 29.3 months (6.0-66.0 months) and 31.0 months (7.0-76.0 months),with no statistically significant difference between groups (Z =-1.388,P>0.05).During the follow-up,foreign body sensation or pain in abdominal wall and hernia recurrence were detected in 6,6 patients in the SIS group and 4,2 patients in the PP group respectively,with a statistically significant difference in hernia recurrence between groups (P<0.05) and with no statistically significant difference in foreign body sensation or pain in abdominal wall between groups (P>0.05).Conclusion Compared with polypropylene mesh,anterior abdominal wall incisional hernia repair using SIS mesh has higher incidence rate of postoperative incisional seroma,surgical site infection and hernia recurrence,but fewer volume of intraoperative blood loss.
6.Observation of the efficacy of biological patch in hybrid technique for incisional herniorrhaphy: 5-year follow-up results from a single center.
Weigang DAI ; Yujie YUAN ; Jidong ZUO ; Jinfu TAN ; Weidong FENG ; Kaitao YUAN ; Qiongyun ZHAO ; Min TAN
Chinese Journal of Gastrointestinal Surgery 2018;21(7):766-771
OBJECTIVETo observe the safety and efficacy of biological patch (Biodesign Surgisis mesh, SIS) in hybrid technique for incisional herniorrhaphy.
METHODSClinical and follow-up data of 14 incisional hernia patients who underwent incisional herniorrhaphy with hybrid technique, using porcine small intestinal submucosa acellular matrix patch, at the First Affiliated Hospital of Sun Yat-sen University from January 1, 2012 to June 31, 2016 were analyzed retrospectively. This Biodesign Surgisis patch for incisional hernia is produced by the Cook company in the United States. The size of patch ranged from 9 cm × 15 cm to 20 cm × 25 cm. During operation, according to abdominal wall defect, the patch was cut to ensure the distance from its edge to the border of abdominal wall defect more than 5 cm.
RESULTSThere were four male and tenfemale patients with average age of (67.7±11.6) years and average body mass index(BMI) of (25.5±1.7) kg/m². As for operative history of these 14 cases, 7 cases had gastrointestinal tumor surgery, 2 had appendectomy, 1 had upper abdominal white line hernia repair, 1 had hysterectomy, 1 had cholecystectomy, 1 had splenectomy plus portal vein dissection, and 1 had right kidney and right ureter total resection plus partial excision of bladder wall. Ten casesdeveloped incisional infection after previous surgery. The duration of incisional hernia ranged 1 to 180 months (median, 8 months). Two cases were refractory hernia, 1 was incarcerated hernia, and 11 were reversible hernia. The locations of incisional hernia included 4 cases of right ventral wall, 1 case of left ventral wall, 2 cases of supra-umbilical incision, 4 cases of infra-umbilical midline incision, and 3 cases of peri-umbilical midline incision. There were 3 cases of middle incisional hernia, 5 cases of large incisional hernia and 6 cases of huge incisional hernia. All the patients completed operations eventlessly. The average operative time was (202.5±72.9) minutes. The average length and width of hernia ring were (10.9±4.3) cm and (9.3±3.9) cm, respectively. Clean operation was performed in 11 cases, potential contaminative operation in 2 cases and contaminative operation in 1 case. The amount of operative bleeding was (15.0±4.8) ml. The NRS pain scores within 24 hours after the operation, at POD3 and at POD7 were 5.1±0.9, 4.2±0.7 and 3.7±0.9, respectively. The time to flatus after operation was (2.5±0.9) days and the time to liquid diet was (3.8±1.2) days. No patient died during the perioperative period. The average hospitalization time was (21.5±12.0) days. Postoperative complications occurred in 8 cases, including 4 cases of fever, 8 cases of incision complications, 4 cases of abdominal infection, 4 cases of intestinal obstruction, 5 cases of effusion under patch, 2 cases of pneumonia, and 1 case of acute myocardial infarction. According to the Clavien-Dindo classification, 3 cases were grade zero, 3 cases were grade I(, 6 cases were grade II(, 1 case was grade III(, and 1 case was grade IIII(. Thirteen patients received follow-up and the average follow-up time was (33.2±12.3) (18.2-61.0) months. One patient died of cerebral infarction 38 months after operation. The chronic abdominal pain or discomfort was found in 4 cases. The recurrent incisional hernia developed in 5 cases and the average time of recurrence was (11.0±8.3) months.
CONCLUSIONSBiological patch can be used safely and effectively in hybrid technique for incisional herniorrhaphy. However, the morbidity of postoperative complication and the risk of recurrence are high. Terefore, the long-term outcome is still subject to observation.
Aged ; Animals ; Bioprosthesis ; Female ; Follow-Up Studies ; Hernia, Ventral ; surgery ; Herniorrhaphy ; Humans ; Male ; Middle Aged ; Postoperative Complications ; Recurrence ; Retrospective Studies ; Surgical Mesh ; Swine
7.Laparoscopic breast-conserving surgery combined with radiofrequency ablation to treat the early-stage breast cancer
Huiming ZHANG ; Hairui WU ; Zihan WANG ; Changsheng TENG ; Zhicheng GE ; Zhu YUAN ; Yinguang GAO ; Guoxuan GAO ; Jinfu WANG ; Xiang QU
International Journal of Surgery 2017;44(6):392-396,封3
Objective To analyze the clinical efficacy of the laparoscopic breast-conserving surgery combined with radiofrequency ablation to treat the early-stage breast cancer.Methods We collected 55 patients diagnosed early-stage breast cancer in retrospect,which started from January 2014 to December 2016.Twenty-seven of them were performed the laparoscopic breast-conserving surgery combined with radiofrequency ablation while others went through laparoscopic breast-conserving surgery without radiofrequency ablation.Meanwhile,we adopted the student t-test and the chi-square test to compare results of two groups.More specific,the main indexes of this study are including the post-operative local recurrence,the incidence of fat liquefaction or the incision-infection,operation time,post-operative hospital stay and the hospitalization expense.Results The laparoscopic breast-conserving surgery combined with radiofrequency ablation group had low local-recurrence than the laparoscopic breastconserving surgery group (0 and 7.69%).Additionally,there were no statistical differences between two groups in the incidence of fat liquefaction.However,The laparoscopic breast-conserving surgery combined with radiofrequency ablation group had more hospitalization expense than the laparoscopic breast-conserving surgery group [(4.1 ± 0.7) ten thousand yuan and (2.3 ± 0.6) ten thousand yuan,P < 0.05].Conclusions Although the laparoscopic breast-conserving surgery combined with radiofrequency ablation group remarkably increased the hospitalization expense because of the utility of the radiofrequency ablation related apparatus,it may provide the probability of shaving more residual tumor cell and may low down the recurrence,especially not rising up the incidence of the post-operative fat liquefaction.Therefore,this surgery method might be one of the potential developments in the minimal-invasive of early stage breast cancer.
8.Study on femoral 3D reconstruction and computer aid low-temperature deposition manufacturing.
Meijuan YUAN ; Mingen XU ; Jinfu HU ; Min YANG
Journal of Biomedical Engineering 2012;29(3):546-587
Serious femoral damages are a common human bone disease. Rebuilding the femur and studying its mechanical properties are a continuous medical research topic, but traditional femoral prosthesis often cause some problems such as prosthesis loosening. In this work, we selected a healthy male, took his femur scanning by CT, and rebuilt high-precision femur prototypes by Mimics10.0 software, then chose the material having good biocompatibility and biodegradable, utilizing low-temperature deposition manufacturing (LDM) technology for the femoral manufacturing. This approach, fabricating the femur via LDM technology, laid a foundation for the later research on the femoral implantation in the human body.
Adult
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Biocompatible Materials
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Cold Temperature
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Computer-Aided Design
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Femur
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diagnostic imaging
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injuries
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Humans
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Imaging, Three-Dimensional
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methods
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Male
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Prostheses and Implants
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Prosthesis Design
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Software
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Tomography, X-Ray Computed
9.Design of a three-dimensionally controlled multi-cell-assembly system based on the control of a mixer nozzle.
Qiujun WANG ; Mingen XU ; Yanlei LI ; Meijuan YUAN ; Jinfu HU
Journal of Biomedical Engineering 2011;28(5):1030-1034
Three-dimensionally controlled cell-assembly technique makes fabricating tissues and organs in vitro to be possible. However, for real tissues and organs with complex structure and various cells, fabricating tissues and organs in vitro need a technique that could assemble and locate multi cells and materials precisely in the space. Facing the needs of multi-cell assembly, we designed a mixer nozzle and the matching pulse switching circuit which based on the single-nozzle cell assembly system, and developed a multi-cell-assembly system. We also carried out some assembly experiments with this system using materials that were similar to the multi-component extracellular matrix materials. The results demonstrated that the system could assemble various cells and materials into three-dimensional inhomogeneous structures precisely.
Bioartificial Organs
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Cell Culture Techniques
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instrumentation
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Cell Physiological Phenomena
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Equipment Design
;
methods
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Extracellular Matrix
;
chemistry
;
Humans
;
Tissue Engineering
;
methods
10.Study on computer-aided deposition manufacturing of vascular tissue engineering scaffolds at low temperature.
Yanlei LI ; Ming'en XU ; Qinjun WANG ; Meijuan YUAN ; Jinfu HU
Journal of Biomedical Engineering 2011;28(4):804-809
Since there is a clinical need for the tissue-engineered vascular graft (TEVG), fabricating the vascular scaffold individually appears to be necessary. In this work, we have developed the traditional tubular scaffold and branch vascular scaffold utilizing low-temperature deposition manufacturing (LDM) technology. Then different tubular scaffolds were fabricated by changing the processing parameters, and the morphological properties of the scaffolds were assessed. The scaffolds reproduced the structure of 3D vascular model accurately. Wall thickness of the scaffold increased with the increase of velocity ratio (V(L)/V(s)) and nozzle temperature, and both the micropore size and wall roughness were positively correlated with the nozzle temperature. However, the porosity was barely affected by the nozzle temperature. This approach, fabricating vascular scaffold with special structure and appearance features via LDM technology, is potential for the individual fabrication of vascular scaffold.
Biocompatible Materials
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chemistry
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Blood Vessel Prosthesis
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Cold Temperature
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Computer-Aided Design
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Humans
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Lactic Acid
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chemistry
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Polyesters
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Polymers
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chemistry
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Tissue Engineering
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methods
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Tissue Scaffolds

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