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Objective:To observe the occurrence of epithelial-mesenchymal transition (EMT) in cervical cancer cell line Siha irradiated by X-rays with clinical conventional fraction radiotherapy model and investigate the role of exosomes in this process.Methods:Siha cells were irradiated by 6 MV-X rays with 50 Gy in 25 fractions. EMT was evaluated by cell morphology, EMT biomarkers and cell migration and invasion ability. Exosomes released from cells were detected by transmission electron microscopy and nanoparticle tracking analysis (NTA), and its function in EMT was explored by using an exosome inhibitor GW4869 (10 μmol/L).Results:After irradiation, EMT phenomenon was induced in the survived Siha cells, including the incidence of mesenchymal phenotype, upregulation of epithelial marker E-cadherin ( t=9.66, P<0.05), downregulation of mesenchymal marker N-cadherin ( t=41.61, P<0.05), and increase of cell migration and invasion abilities ( t=6.11, 13.22; P<0.05). Meanwhile, the secretion of exosomes was also increased after irradiation ( t=7.51, P<0.05). When the cells were pre-treated with GW4869, radiation-induced exosome secretion was reduced ( t=7.28, P<0.05), so that radiation-induced EMT was reversed. Conclusions:Ionizing radiation with clinical conventional fraction radiotherapy model promotes EMT of cervical cancer cells through increasing the secretion of exosomes.
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In order to unveil ubiquitin pathway genes (UPGs) that are essential for non-small cell lung cancer (NSCLC) cell proliferation, we recently conducted a siRNA screening experiment to knockdown the expression of 696 UPGs found in the human genome in A549 and H1975 NSCLC cells. We found that silencing of one of the candidates, RFWD3 that encodes an E3 ubiquitin ligase essential for the repair of DNA interstrand cross-links in response to DNA damage, led to dramatic inhibition of NSCLC cell proliferation with significant Z-scores. Knockdown of RFWD3 suppressed colony forming activity of NSCLC cells.We further evaluated the significance of RFWD3 in NSCLCs and found that this gene was more elevated in tumor samples than in paired normal lung tissues and was inversely associated with the clinical outcome of patients with NSCLC. Moreover, RFWD3 expression was significantly higher in smokers than in non-smokers. These results show for the first time that RFWD3 is required for NSCLC cell proliferation and may have an important role in lung carcinogenesis.
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BACKGROUND@#Lung cancer is the most common neoplasmas with a poor prognosis and a low 5-year survival rate. Early screening is an important measure for the prevention and treatment of lung cancer. At present, different countries have issued corresponding lung cancer screening guidelines, but China still lacks guidelines based on Chinese population research. Therefore, the National Cancer Center launched a Multi-center Cancer Screening Program in Urban China. This study analyzed the evaluation of lung cancer risk assessment model and screening effect in urban China of Yunnan, so as to explore the evaluation model of high-risk lung cancer population suitable for China's national conditions and develop lung cancer screening guidelines for Chinese.@*METHODS@#A questionnaire survey and lung cancer risk assessment were conducted on 165,337 people in 36 street offices in 4 main urban areas of Kunming, Yunnan Province, using cluster sampling method from January 2015 to December 2019. People with high-risk of lung cancer conducted low-dose computed tomography (LDCT) screening of chest. What's more, all participants were followed up by active or passive follow-up.@*RESULTS@#There were 264 patients were diagnosed lung cancer by pathology, and the overall incidence of lung cancer was 0.16% (264/165,337). The high-risk group (0.31%, 116/37,914) was higher than the non-high-risk group (0.12%, 148/127,423), and the difference was statistically significant (P<0.001). The incidence of lung cancer in the high-risk group was higher than the non-high-risk group among the male, female, and lower 50-year-old or more than 50-year-old subgroups, with statistical differences (P<0.001), but there was no statistical difference in the group without LDCT screening (P=0.73). The sensitivity of the lung cancer high-risk population assessment model was 43.94% (116/264) and the specificity was 77.10% (127,275/165,073). The early diagnosis rate of the screening group was 72.97% (54/74), which was significantly higher than that of the non-screening group [28.48% (43/151)].@*CONCLUSIONS@#The lung cancer high-risk population assessment model of National Key Public Health Program: Cancer Screening Program in Urban China can detect high-risk populations and improve the early diagnosis rate of lung cancer effectively.
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Objective To investigate the efficacy of radiotherapy,as well as the prognostic factors of survival in patients with extracranial oligometastases. Methods A total of 164 patients who underwent intensity-modulated radiotherapy ( IMRT ) of the extracranial oligometastases, from January 2013 to December 2016, were enrolled in the study. The short-term efficacy, local control rate, overall survival, progression free survival and adverse effects of treatment were observed. Results Short-term efficacy was assessed within the first 1-3 months after the end of radiotherapy. The objective response rate (CR+PR) was 78. 7% and the short-term efficacy is mainly related to the T stage of primary tumor ( P＝0. 004).Until the last follow-up,all patients with 1-,2-and 3-year LC were 89. 8%,82. 5% and 74. 9% respectively.Univariate analysis showed that the influencing factors of LC include tumor size and gross tumor volume dose ( all P＜0. 05),multivariate analysis found no significant influence factors. The 1-,2- and 3-year OS were 83. 4%, 69. 6% and 54. 6% respectively. Univariate and multivariate analysis showed that the primary tumor sources, metastasis organs,whether synchronous or adjuvant chemotherapy and short-term efficacy were independent prognostic factors in patients of OS ( P＜0. 05 ).Main toxicity-associated events were grade 1-2 acute reactions,with only 6 patients experiencing grade 3 toxicity;no grade≥4 toxic reactions or treatment-related deaths occurred. Conclusions Radiation therapy for the treatment of extracranial oligometastases can achieve good curative effect,is well-tolerated and has low toxicity.
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Objective To investigate epidermal growth factor receptor(EGFR)gene T790M mutation in plasmatic ctDNA samples from 171 patients with non-small cell lung cancer and analyze the relationship between EGFR T790M mutation and the clinical factors. Methods The EGFR T790M mutation was detected in 171 cases by super amplification refractory mutation system(Super ARMS)in this paper. Rusults The EGFR gene T790M mutation was identified in 7.60%(13/171)plasmatic ctDNA samples which mostly came from patients withⅢb~Ⅳstages of lung cancer. The EGFR T790M mutation rate was identified in 2.05%(3/146)plasmatic samples of pa-tients who did not received treatment of EGFR-TKIs,which was lower than 40.00%(10/25,P<0.05)plasmatic samples of patients who received treatment of first generational EGFR-TKIs. The EGFR T790M mutation rate was identified in 75.00%(3/4) and 60.00%(6/10) plasmatic samples of patients who have received TKI for 6 to 10 months and more than 10 months,which was higher than 9.10%(1/11,P < 0.05)plasmatic samples of patients who have received TKIs for less than 6 months. Conclusions This article demonstrated that EGFRT790M muta-tion was more common in lately NSCLC patients who have received TKIs treatmentover 6 months,meanwhile the EGFR T790M mutation dynamical detective technology will effectively guide the clinic treatment.
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Objective To investigate epidermal growth factor receptor(EGFR)gene T790M mutation in plasmatic ctDNA samples from 171 patients with non-small cell lung cancer and analyze the relationship between EGFR T790M mutation and the clinical factors. Methods The EGFR T790M mutation was detected in 171 cases by super amplification refractory mutation system(Super ARMS)in this paper. Rusults The EGFR gene T790M mutation was identified in 7.60%(13/171)plasmatic ctDNA samples which mostly came from patients withⅢb~Ⅳstages of lung cancer. The EGFR T790M mutation rate was identified in 2.05%(3/146)plasmatic samples of pa-tients who did not received treatment of EGFR-TKIs,which was lower than 40.00%(10/25,P<0.05)plasmatic samples of patients who received treatment of first generational EGFR-TKIs. The EGFR T790M mutation rate was identified in 75.00%(3/4) and 60.00%(6/10) plasmatic samples of patients who have received TKI for 6 to 10 months and more than 10 months,which was higher than 9.10%(1/11,P < 0.05)plasmatic samples of patients who have received TKIs for less than 6 months. Conclusions This article demonstrated that EGFRT790M muta-tion was more common in lately NSCLC patients who have received TKIs treatmentover 6 months,meanwhile the EGFR T790M mutation dynamical detective technology will effectively guide the clinic treatment.
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Xuanwei district in Yunnan Province of China has pretty high incidence of lung cancer in China, even a- round the world. Studies have shown that there exists a close relationship between lung cancer and local indoor air pollution caused by Bituminous coal. Considering that the indoor air pollution in Xuanwei District is caused by "open fireplace", an indoor air pollution simulation system was designed, and an F344 rats lung damage model was estab- lished for this indoor air pollution fireplace. The model is based on indoor air pollution simulation system with signal multiplexer control and multi-channel acquisition, and mining PID algorithm was used for polynomial fitting to each test point, and a relatively constant PM2. 5 air pollution status was simulated. The results showed that the system could simulate a variety of states of air pollution, provide a new test method for evaluation of human injury caused by indoor air pollution and a new idea for the study of the incidence of lung cancer in Xuanwei district and other places.
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Animals , Humans , Rats , Air Pollution, Indoor , China , Coal , Incidence , Lung , Pathology , Lung Neoplasms , Epidemiology , Models, Biological , Particulate Matter , Rats, Inbred F344ABSTRACT
Objective To investigate the value of EBUS-TBNA (endobronchial ultrasound-guided trans-bronchial needle aspiration) in diagnosis of lung cancer and analyze its complications. Methods A retrospective study was carried out in our hospitalfrom March 2013 to March 2015. A total of 171patients received C-TBNA (Con-ventional transbronchial needle aspiration) first and got negative results. Therefore, they received EBUS-TBNA next. Weanalyzedthe sensitivity, specificity, accuracy of malignancy with EBUS-TBNA and positive (malignant) lymph node sites biopsied with EBUS-TBNAand the incidence of its complications. Results Lung cancer was proven in 107 patients who had received EBUS-TBNA, while 16 were benign cases. Thirty-onenegative patients received CT guided needle biopsy or surgeryfor finally pathology. Based on above statistical data , we calculated EBUS-TBNA′s sensitivity, specificity and accuracy in 88.42%, 100.00%and 94.21%respectively. A totalof 818 lymph nodes were punctured by EBUS-TBNA, 408 were malignancy. The rate of diagnosis for malignancy was 49.88%. The complica-tioncontained 1 in hemorrhage, 1 in infectionand no life-threatening conditionandno death. Conclusion The value ofdiagnosis in lung cancerisrelatively high with EBUS-TBNAin safety and efficient.
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Objective To summarize the experience of surgical techniques and prevention of postoperative complications of giant intracranial meningiomas.Methods The clinical data of 32 patients with giant intracranial meningiomas were analyzed retrospectively.The cause of operative complications was analyzed and the experience was summarized.Results The meningiomas Simpson grade Ⅰ resection was 16 is.cases,grade Ⅱ resection was 9 cases,grade Ⅲ resection was 5 cases,grade Ⅳ resection was 2 cases.The postoperative complications included anemia was 14 cases,intracranial hemorrhage was 2 cases,severe cerebral edema was 4 cases,epilepsy was 3 cases,cerebral infarction was 2 cases,and recovered well after treatment.Conclusion Good surgical technique,advanced prevention of surgical complications,early diagnosis and treatment can significantly improve the prognosis.
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<p><b>OBJECTIVE</b>To study the effect of targeted Sox4 gene-knock-down on the growth of xenografts of Xuanwei female lung cancer cell line XWLC-05 cells in nude mice.</p><p><b>METHODS</b>Recombinant plasmid pGFP-V-RS-Sox4 shRNA was constructed and transfected into XWLC-05 cells. Real-time quantitative PCR and Western blot were applied to confirm the effect of Sox4 gene-knock-down. XWLC-05 cells stably transfected with the plasmids were inoculated into nude mice to establish the xenograft model. The nude mouse status, tumor formation and tumor growth were observed, and the tumor inhibition rate was calculated. CT scan was performed to assess the metastasis of xenografts. Immunohistochemical staining was applied to detect Sox4 and ki-67 protein expression.</p><p><b>RESULTS</b>Recombinant plasmid pGFP-V-RS-A-Sox4 shRNA which can effectively knocking-down Sox4 gene was successfully constructed and the stable transfected cells were selected by puromycin-screening. The success rate of tumor cell inoculation was 100% in the mice of all groups except those inoculated with saline. The body weight of all mice inoculated with parental XWLC-05 cells (blank control), pGFP-V-RS-scram shRNA trsfected XWLC-05 cells (negative control), and pGFP-V-RS-Sox4 shRNA transfected XWLC-05 cells was increased to a varying degree, but there was no significant difference among the groups (P > 0.05 ). The growth of xenografts was significantly inhibited after silencing the Sox4 gene expression when compared with that of the blank and negative controls (P < 0.05) . The volume of removed tumors of the Sox4 gene-inhibited mice was (2.30 ± 0.34) cm(3) , significantly smaller than that of the negative control (3.99 ± 0.45) cm(3) and the blank control (4.03 ± 0.42) cm(3) (P < 0.05) . The weight of removed tumors of Sox4 gene-inhibited mice was (0.86 ± 0.14) g, significantly lower than that of the negative control (1.84 ± 0.27) g and blank control (1.86 ± 0.22) g, (P < 0.05). Immunohistochemical staining showed that Sox4 and ki-67 proteins mainly expressed in cell nuclei. The staining was significantly decreased in xenografts of Sox4-inhibited mice when compared with the negative and blank controls (P < 0.05). No distant metastasis was found in any mouse by CT imaging and pathological examination during the observation period.</p><p><b>CONCLUSIONS</b>The xenograft model of Xuanwei female lung cancer cell line XWLC-05 cells in nude mice is successfully established. Knocking-down of Sox4 gene can suppress the xenograft tumor growth.</p>
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Animals , Female , Humans , Mice , Gene Knockdown Techniques , Heterografts , Lung Neoplasms , Genetics , Pathology , Mice, Nude , SOXC Transcription Factors , MetabolismABSTRACT
Objective To evaluate laparoscopic D2 lymph node dissection gastrectomy in the treatment of advanced gastric cancer.Methods The clinical data of 239 cases of advanced gastric cancer admitted from January 2004 to June 2011 were respectively analyzed,patients were divided into laparoscopic resection group and open surgery group.Data analysis was performed by SPSS 19.0 statistical software.Results There were 102 cases in laparoscopic group,and 137 cases in open group.The length of incision,operative blood loss,recovery time of gastrointestinal function,food-taking time and postoperative hospital stay in laparoscopic operation group were (5.0 ± 1.1) cm,(70 ± 44) ml,(57 ± 14) h,(68 ± 12) h,(7.1 ± 1.4) d and in open operation group were (17.4 ± 2.1) cm,(107 ± 59) ml,(75 ± 12) h,(91 ±15) h,(9.9 ± 1.8) d respectively.There were significant differences between the two groups (t =-58.86,-5.50,-10.72,-12.58,-12.58,all P =0.00).There was no significant differences between the two groups in operative time (t =1.63,P =0.11),with operative time in laparoscopic operation group of (192 ± 32) min,and (185 ± 30) min in open group.Average proximal,distal cutting edge and the average number of lymph node harvested were (5.0 ± 1.0) cm,(4.7 ± 0.8) cm,(27.6 ± 7.2) in laparoscopic operation group,and (5.1 ±0.9) cm,(4.7 ±0.9) cm,(27.0 ±6.5) in open group (t =-0.61,0.10,0.68,P ＞ 0.05).The 3-,5-,7 d white blood cell counts in laparoscopic group was (11.1 ± 1.3) ×109/L,(9.5 ± 1.4) × 109/L,(7.0 ± 1.5) × 109/L,and (12.8 ± 1.3) × 109/L,(11.1 ± 1.5) × 109/L,(8.6 ± 1.3) × 109/L,in open group (t =-9.83,-8.88,-9.40,all P =0.00).Complications developed in 9.8 ％ (10/102) in laparoscopic operation group,and 17.5 ％ (24/137) in open group (x2 =0.285,P =0.09).The 1-year,3-year,5-year survival rate of patients in laparoscopic group were 96.1％,74.1％,47.2％,and 95.6％,70.0％,50.9％ in open group (x2=0,0.04,0.21,P ＞0.05).Conclusions In selected cases,laparoscopic D2 lymph node dissection gastrectomy for advanced gastric cancer is safe and effective,and long-term outcomes are satisfactory.
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Objcetive To investigate the protective effects of the nitroxides R-1 on human liver cells exposed to ionizing radiation.Methods Human liver cells L-02 were cultured and irradiated with 60Co γ-rays at the doses of 0,1,2,4,and 8 Gy,in order to screen the proper irradiation dose.WR2721 at the terminal concentration of 4 mmol/L was used as positive control.L-02 cells irradiated with 4 Gy were added with R-1 at the terminal concentration of 0.25 μmol/L at 30 min before irradiation or immediately after irradiation.MIT method was used to screen the proper conditions for follow-up experiment 72 h later.L-02 cell culture fluid was added with R-1 at the concentrations of 0,0.125,0.25,0.5,and 1 μmol/L,respectively for 30 min before irradiation at the doses of 0,1,2,4,and 8 Gy to ealculate clone formation rate at 10 d post-irradiation.L-02 cells were cultured and divided into 4 groups:control group without any treatment.drug group pretreated by 0.25 μmol/L R-1 only,irradiation group,irradiated at 4 Gy only,and drug + irradiation group with combination of 0.25 μmol/L R-01 and 4 Gy irradiation.The inverted microscopy and Hoechst 33258 staining and flow eytometry were used to observe the apoptosis of the cells at 24,48,and 72 h later.Results Nitroxides R-1 did not inhibit the viability of L-02 cell when its concentration was less than 1 μmol/L and it inhibited the L-02 cell growth when the concentration wu higher than 2 μmoL/L.The A value and colony formation rate of different concentration of R-1 groups were all higher than those of the irradiation group,and the effect of the 0.25 μmol/L drug concentration group was the most significant.Consequently,the concentration 0.25 μmoL/L was selected for follow-up experiment.Compared with the irradiation group,the L-02 cells of the pretreatment group showed solid adherence, increased refraction,clear outline,less apoptotic and dead cells at 4 Gy post-irradiation.Conclusions Nitroxides R-1 can protect the human liver cells from 60Coγ-ray induced injury effectively.The mechanism of its protective effect may be the reduction of apoptosis.
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Recent studies have revealed that sox4 gene expresses abnormally in many kinds of tumor tissues and it probably involves in tumorigenesis,development and metastasis of cancer.Regulating proliferation,differentiation,apoptosis and other process may participate in the work mechanisms of sox4 gene.Therefore,further studies about the relationship between sox4 gene and tumor would provide new ideas of exploring special diagnosis markers and novel targets for tumor therapy.
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<p><b>BACKGROUND AND OBJECTIVE</b>The mouse lung cancer orthotopic model includes spontaneous lung cancer model and endotracheal transplanted model, and etc. The spontaneous lung cancer needs longer time and does not ensure the rate of the generation of the tumor; as for endotracheal transplanted model, the position and size of the tumor are instable. In this study, the 3LL cell line was orthotopically transplanted into the lung of the C57BL/6 mice, compare to the heterotopic model, to discuss their stability and transfer-characteristics. And this study was also to optimize the method of establishing lung cancer orthotopic animal model.</p><p><b>METHODS</b>Different quantity of 3LL cells were inoculated into the left oxter of C57BL/6 mice to establish the heterotopic model; or suspended with Matrigel then inoculated into the left lung of C57BL/6 mice to establish orthotopic model. The survival-time of the mice was examined. The tissue was collected for the subsequent histology assay after euthanizing the mice. Microvessels density (MVD) was observed and counted by immunohistological chemistry. CD44v was detected by flow cytometry.</p><p><b>RESULTS</b>TTumor-form-rate of the heterotopic group were 100%, 66.7%, 16.7%, respectively, and had no macroscopic transfer. Tumor-form-rate of the orthotopic group were 100%, 100%, 83.3%, respectively, and had widespread transfer in contralateral chest and the lung. The median survival time of the orthotopic group (38, 35, 23 days) were less than the heterotopic group (82, 72, 50 days). MVD of the orthotopic group (120.2 +/- 9.73) was higher than the heterotopic group (92.6 +/- 7.12). The expression of CD44v of orthotopic (26.46 +/- 1.56)% was higher than the heterotopic group (23.13 +/- 1.02)%.</p><p><b>CONCLUSION</b>The lung cancer orthotopic model which established by 3LL cells transplanted into the lung of the mice is simple, dependable, repeatable and has stronger transfer characteristics than the heterotopic model.</p>
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Animals , Female , Male , Mice , Carcinoma, Lewis Lung , Cell Line, Tumor , Disease Models, Animal , Lung Neoplasms , Mice, Inbred C57BL , Neoplasm Transplantation , Random AllocationABSTRACT
Objective To study the clinical and prognostic value of CK19 mRNA-positive circulating tumor cells in early breast cancer patients. Methods We analyzed the peripheral blood in 50 patients with early breast cancer after surgery and before the initiation of any adjuvant treatment for the presence of CK19 mRNA-positive circulating tumor cells using a nest reverse polymerase chain reaction assay. All patients were followed up. Results CK19 mRNA-positive cells were detected in 40.0 %(20/50) of patients with early breast cancer, 12.5 %(3/24) of patients with breast benign lesions, but 5 %(1/20) in healthy individuals (P =0.017,P =0.004); 11 to 20 of them relapsed during the follow-up period (P =0.002). There was no significant association between the detection of CK19 mRNA-positive cell and the patients' menstrual status, tumor stage, tumor size, etc (P ＞0.05). Detection of peripheral-blood CK19 mRNA-positive cells was associated with reduced median relapse-free interval in early breast cancer patients (P =0.007). Conclusion CK19 mRNA is one of the molecular markers for the detection of circulating tumor cells in early breast cancer. Detection of peripheral blood CK19 mRNA-positive cells might be an important predictive value as a marker of relapse in early breast cancer patients.
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Objective To evaluate the safety and feasibility of laparoscopic hepatectomy for hepatocellular carcinoma(HCC). Methods From January 2002 through December 2007,86 HCC cases were divided into laparoscopic hepatectomy group and open hepatectomy group.Clinical data were analyzed. Results There were 36 cases in LH group,and 50 cases in OH group.Significant differences were noticed in the length of incision,operative blood loss,food-taking time,postoperative hospital stays,and analgesic usage between the two groups (respectively t =-37.608、-2.396、-13.073、-4.283 、x2 = 35.765,all P＜0.05),in which LH group was superior to OH group.Differences appeared in ALT,AST,ALP,r-GT and LDH on post-op day 1,and 3.APTT,ALB response on the fifth day after operation were different in the two groups (separately t =-3.465,-3.236,-3.470,-6.812,-4.837 and-3.998,-2.894,-4.286,-7.887,-5.388,6.131,7.292; all P ＜0.05);ALT,AST,ALP,r-GT value on the fifth day post-operation,and T-BIL on the day 1,5 post-operation were different in two groups (separately t =-4.795,-2.155,-3.442,-4.194,-2.712,-1.600,all P ＜0.05),Meanwhile,as the results all showed that,injuries were all less severe in LH than OH group.There were no significant differences between the two groups in operative time,resection method,overall complications,1-year,3-year survival rate,disease free survival (t =-0.893,separately x2 =0.066,0.026,0.468,0.156,0.106,2.732,all P ＞0.05) while 3-year survival rate in LH group and OH group were 50.0%,25% respectively (x2=2.732,P = 0.098). Conclusion Laparoscopic hepatectomy was safe and feasible for treatment of HCC,and its short-term efficacy was better than open hepatectomy.Furthermore,laparoscopic hepatectomy had promising long-term effectiveness.