Search

To introduce toe-to-hand transplantation performed with the assistance of both bone and soft tissue modeling using 3-dimensional printing technology.From May 2015 to October 2018, 31 patients (group A, 24 thumbs and 7 fingers) were included. Computed tomography scans were acquired using a spiral computed tomography scanner, and the data were processed with software. Bone, skin, and nail models were created for tailoring the flap taken from the great toe. The impact of foot pathology in terms of pain, disability, and activity restriction was assessed using the Foot Function Index. For comparison, we included 35 patients (group B) who underwent toe-to-hand transplantation without the assistance of 3-dimensional computer-aided modeling.The mean duration of follow-up of groups A and B was 26 months (range, 24-31 months) and 27 months (range, 24-33 months), respectively. The mean Foot Function Index of groups A and B was 5 (range: 0-15) and 17 (range, 0-39), respectively.Three-dimensional computer-aided modeling and printing provide geometric accuracy in toe-to-hand transplantation. It also may reduce the donor foot morbidity by accurate flap designing and harvesting.Therapeutic IV.

MicroRNAs (miRs) have been reported to be potential clinical biomarkers for sepsis. miR-1184 is a multifunctional microRNA that exerts roles in the development of various diseases. However, the role of miR-1184 in children with sepsis remain unknown. In the present study, THP-1 cells were stimulated with 1 µg/ml lipopolysaccharide (LPS) for 24 h to establish an in vitro sepsis model. Reverse transcription-quantitative PCR was used to evaluate the expression of miR-1184 in clinical specimens, and of IL-6, TNF-α, IL-1β, miR-1184 and TNF receptor type 1-associated DEATH domain protein (TRADD) in cells with and without LPS treatment. Cell apoptosis was assessed using flow cytometry. Binding between miR-1184 and TRADD was predicted using bioinformatics software, and a luciferase reporter assay was performed to verify the interaction between miR-1184 and TRADD in LPS-induced THP-1 cells. In addition, western blot analysis was performed to detect TRADD and proteins associated with the NF-κB pathway. The results showed that miR-1184 was downregulated in the blood of children with sepsis and LPS-induced THP-1 cells. Overexpression of miR-1184 alleviated the LPS-induced production of inflammatory cytokines and cell apoptosis. Moreover, TRADD was verified to be a direct target of miR-1184. Upregulation of TRADD reversed the effects of miR-1184 on the LPS-induced inflammatory response and apoptosis of THP-1 cells. Furthermore, the NF-κB pathway was shown to be associated with the regulatory role of miR-1184 in sepsis. The present study provides evidence that miR-1184 exerts inhibitory effects on inflammatory responses and apoptosis in sepsis by targeting TRADD, which suggests that miR-1184 may be a novel potential target for the therapy of children with sepsis.

Background and objective Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor but highly sensitive to chemotherapy and radiotherapy. At present, the standard first-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. In this study, we analyzed the survival among all extensive-stage SCLC and patients who received first-line chemotherapy and determined prognostic factors. Methods Total of 394 patients who were diagnosed as extensive-stage small cell lung cancer from February 2001 to December 2011 hospitalized in Peking Union Medical College Hospital were collected. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the influence factors of survival. Results The median OS of all extensive-stage small cell lung cancer was 14.8 months; 1-year, 2-year and 5-year survival rates were 58.9%, 27.2% and 7.8%, respectively. According to the results of univariate and Cox multivariate analysis, OS of extensive-stage SCLC was closely associated with age (P=0.006), ECOG PS (P=0.021), liver metastasis (P

Background and objective Nowadays, comprehensive treatment, including surgery, chemotherapy and radiotherapy is advocated for stage III non-small cell lung cancer (NSCLC). However, many researchers have questioned the effectiveness of surgery. The aim of this study is to evaluate the effect of surgery for stage III NSCLC. Methods Between March 2002 and October 2012, 310 cases that have completed followed-up data with stage III NSCLC were received in the Peking Union Medical College Hospital. They were divided into surgical and non-surgical groups according to whether received surgery when diagnosed. In TNM staging, stage III NSCLC includes stage IIIa and IIIb, and stage IIIa NSCLC can be grouped into stage T4N0/T3-4N1M0 and T1-3N2M0 according to different N stages. Analyzed the enumeration data by Chi-Square test. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to draw the survival curves. A P value less than 0.05 was evaluated as statistically significant. Results Three hundred and ten stage III NSCLC patients include surgical group 189 cases and non-surgical group 121 cases. One hundred and eighty-eight stage IIIa NSCLC patients include surgical group 152 cases and non-surgical group 36 cases. In stage IIIa, stage T4N0/T3-4N1M0 had 57 patients with 44 surgical and 13 non-surgical patients, and stage T1-3N2M0 had 131 patients with 108 surgical and 23 non-surgical patients. Thirty-seven out of 121 stage IIIb NSCLC patients received surgery. They had 22 stage T4N2M0 cases and 15 stage T1-4N3M0 cases. The patient whose performance status was 0 and staging was stage IIIa was more inclined to undergo surgery. For stage IIIa NSCLC patients, the median OS of surgical and non-surgical groups were 38.9 and 21.8 months, and the median PFS of them were 19.2 and 11.9 months respectively. The difference of OS between the two groups was significant (P=0.041), but the PFS of them had no significant difference (P=0.209). For stage T4N0/T3-4N1M0 which belongs to stage IIIa, the median OS of surgical and non-surgical groups were 48.7 and 20.1 months, and the median PFS of them were 14.6 and 10.5 months respectively. There were no significant differences of OS and PFS between the two groups (P>0.05). For stage T1-3N2M0 which also belongs to stage IIIa, the median OS of surgical and non-surgical groups were 38.9 and 30.8 months, and the median PFS of them were 19.8 and 12.7 months respectively. There were also no significant differences of OS and PFS between the two groups (P>0.05). The maximum diameter of tumor and auxillary chemotherapy had significant influences on OS and PFS of stage IIIa-N2 NSCLC patients, while the histology of tumor only influenced the OS of them (P

Background and objective At present, surgery is advocated for stage IIIa non-small cell lung cancer (NSCLC), and the survival of them is determined by many factors. The aim of this study is to analyze the influencing factors of prognosis for stage IIIa surgical patients. Methods Between March 2002 and October 2012, 151 surgical cases that have postoperative pathological finding of stage IIIa NSCLC with completed followed-up data were received in the Peking Union Medical College Hospital. According to different N stages, 151 patients were divided into T4N0/T3-4N1M0 and T1-3N2M0 stages. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to proceed univariate analysis of survival. Cox regression analysis was used to conduct multivariate analysis. A p-value less than 0.05 was evaluated as statistically significant. Results 151 stage IIIa NSCLC patients had 43 stage T4N0/T3-4N1M0 cases and 108 stage T1-3N2M0 cases. The median OS and PFS of the whole group were 38.9 and 12.9 months respectively. The median OS of stage T4N0/T3-4N1M0 and T1-3N2M0 were 48.7 and 38.9 months. The median PFS of them were 14.9 and 19.8 months respectively. There were no significant differences of OS and PFS between two groups. Univariate and multivariate analysis indicated that postoperative chemotherapy had a significant influence on OS of the surgical patients with stage IIIa NSCLC (P=0.001), and family history of tumor had a significant influence on PFS (P

Background and objective Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor and sensitive to chemotherapy and radiotherapy. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. Currently, the standard first-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen while the standard second-line chemotherapy regimen is open to debate. The aim of this study is to analysis the prognostic factors of second-line chemotherapy in extensive-stage SCLC and to compare the differences of objective response rate, side effects and survival among different second-line chemotherapy regimens. Methods 181 patients who were diagnosed as extensive-stage SCLC and received second-line chemotherapy were collected. χ2 test was used to analysis the differences of enumeration data and between different groups. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the prognostic factors. Objective response rate was evaluated by RECIST criteria and side effects were evaluated by WHO criteria. Results The patients who received second-line chemotherapy can be divided into 6 groups, namly group A (CE/EP regimen) 27 cases, group B (regimens containing TPT) 44 cases, group C (regimens containing CPT-11) 33 cases, group D (regimens containing TAX/DXL) 20 cases, group E (regimens containing IFO) 28 cases and group F (other regimens) 29 cases. The median OS in second-line chemotherapy as 7.0 months and was relevant with smoking history (P=0.004), ECOG PS (P

Nowadays, lung cancer is the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC) makes up about 80%. There is a great many NSCLC patients have been in advanced stage when diagnosed. As a result, people pay more attention to curing advanced NSCLC. The standard treatment to advanced NSCLC is platinum-based combined chemotherapy. However, chemotherapy drugs usually have limited effects on improving the survival of the patients. Then exploring new therapies is extremely urgent to us. Now, molecular targeted therapy has been the most promising research area for the treatment of NSCLC with researches going deep into pathogenesis and biological behavior of lung cancer. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved a great success in the treatment of advanced NSCLC. Their representatives are erlotinib and gefitinib. The two drugs have been widely used to treat advanced NSCLCs worldwide, especially for the patients with EGFR activating mutations. However, after a period of treatment (median time is 6 to 12 months), most patients will develop drug resistance to EGFR-TKIs. Intense research in these NSCLCs has identified two major mechanisms of resistance to TKIs: primary and acquired resistances. The research about resistance mechanism of NSCLC to EGFR-TKIs is a hot one because of their excellent effects on improving overall and progression-free survival. The aim of this article was to summarize the development of the resistance mechanisms.

Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor but highly sensitive to chemotherapy and radiotherapy. At present, the standard first-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. In this study, we analyzed the survival among all extensive-stage SCLC and patients who received first-line chemotherapy and determined prognostic factors.Total of 394 patients who were diagnosed as extensive-stage small cell lung cancer from February 2001 to December 2011 hospitalized in Peking Union Medical College Hospital were collected. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the influence factors of survival.The median OS of all extensive-stage small cell lung cancer was 14.8 months; 1-year, 2-year and 5-year survival rates were 58.9%, 27.2% and 7.8%, respectively. According to the results of univariate and Cox multivariate analysis, OS of extensive-stage SCLC was closely associated with age (P=0.006), ECOG PS (P=0.021), liver metastasis (P0.001), bone metastasis (P0.001) and chemotherapy (P0.001). The mortality risk of patients who didn't receive chemotherapy was 4.919 times higher than that who received; the mortality risk of patients without liver, bone metastasis was reduced by approximately 50 percent. The first-line chemotherapy was mainly EP (DDP+VP-16) or CE (CBP+VP-16) regimens (accounting for 82.8%) with 4-6 cycles. The median OS and PFS in first-line chemotherapy were 15.1 months and 7.5 months, respectively. The result of Cox regression analysis indicated that OS in first-line chemotherapy was remarkably related to smoking history (P=0.041), liver metastasis (P0.001), bone metastasis (P0.001), chemotherapy cycle number (P0.001); PFS was relevant with smoking history (P=0.003), liver metastasis (P=0.001), bone metastasis (P0.001), chemotherapy cycle number (P0.001). Thoracic radiotherapy was not an independent influence factor of OS and PFS in extensive-stage small cell lung cancer.The patients who were younger than 60-year old, with good KPS, absence of liver and bone metastasis had better prognosis. Patients should receive chemotherapy with first-line standard regimen (CE/EP regimen). It was beneficial to survival if the effect of first-line chemotherapy was SD or PR-CR and the proper chemotherapy cycle number was 4-6 cycles. The role of thoracic radiotherapy in extensive-stage small cell lung cancer needed to be investigated further.背景与目的 小细胞肺癌（small cell lung cancer, SCLC）是恶性程度极高的神经内分泌肿瘤，对放化疗敏感。目前，广泛期SCLC的一线标准化疗方案为铂类联合依托泊苷方案，但大多数接受一线化疗的患者在1年-2年内复发。一旦疾病复发，预后不良。本研究旨在研究广泛期SCLC总体和一线化疗的生存情况及其影响因素。方法 收集2001年2月-2011年12月经病理学或细胞学确诊为广泛期的SCLC患者394例，采用Kaplan-Meier法计算总生存时间（overall survival, OS）和无进展生存时间（progression-free survival, PFS）并绘制生存曲线，单因素及Cox回归多因素分析各种因素对生存期的影响。结果 全组中位OS为14.8个月，1年、2年、5年生存率分别为58.9%、27.2%、7.8%。全组OS与年龄（P=0.006）、ECOG评分（P=0.021）、肝转移（P0.001）、骨转移（P0.001）、是否化疗（P0.001）密切相关。一线化疗广泛期SCLC患者的中位OS为15.1个月，中位PFS为7.5个月。多因素分析结果显示一线化疗广泛期SCLC的OS与吸烟（P=0.041）、肝转移（P0.001）、骨转移（P0.001）、化疗疗程数（P0.001）相关；一线化疗PFS与吸烟（P=0.003）、肝转移（P=0.001）、骨转移（P0.001）、化疗疗程数（P0.001）相关。胸部放疗并非广泛期SCLC OS和PFS的独立影响因素。结论 年龄60岁、体能状况好、无肝、骨转移的广泛期SCLC患者预后更好。广泛期SCLC患者应积极进行化疗，一线化疗的化疗疗效达到部分缓解-完全缓解有益于生存；适合的化疗疗程数目是4-6疗程。胸部放疗在广泛期SCLC治疗中的作用需要进一步研究。

Nowadays, comprehensive treatment, including surgery, chemotherapy and radiotherapy is advocated for stage III non-small cell lung cancer (NSCLC). However, many researchers have questioned the effectiveness of surgery. The aim of this study is to evaluate the effect of surgery for stage III NSCLC.Between March 2002 and October 2012, 310 cases that have completed followed-up data with stage III NSCLC were received in the Peking Union Medical College Hospital. They were divided into surgical and non-surgical groups according to whether received surgery when diagnosed. In TNM staging, stage III NSCLC includes stage IIIa and IIIb, and stage IIIa NSCLC can be grouped into stage T4N0/T3-4N1M0 and T1-3N2M0 according to different N stages. Analyzed the enumeration data by Chi-Square test. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to draw the survival curves. A P value less than 0.05 was evaluated as statistically significant.Three hundred and ten stage III NSCLC patients include surgical group 189 cases and non-surgical group 121 cases. One hundred and eighty-eight stage IIIa NSCLC patients include surgical group 152 cases and non-surgical group 36 cases. In stage IIIa, stage T4N0/T3-4N1M0 had 57 patients with 44 surgical and 13 non-surgical patients, and stage T1-3N2M0 had 131 patients with 108 surgical and 23 non-surgical patients. Thirty-seven out of 121 stage IIIb NSCLC patients received surgery. They had 22 stage T4N2M0 cases and 15 stage T1-4N3M0 cases. The patient whose performance status was 0 and staging was stage IIIa was more inclined to undergo surgery. For stage IIIa NSCLC patients, the median OS of surgical and non-surgical groups were 38.9 and 21.8 months, and the median PFS of them were 19.2 and 11.9 months respectively. The difference of OS between the two groups was significant (P=0.041), but the PFS of them had no significant difference (P=0.209). For stage T4N0/T3-4N1M0 which belongs to stage IIIa, the median OS of surgical and non-surgical groups were 48.7 and 20.1 months, and the median PFS of them were 14.6 and 10.5 months respectively. There were no significant differences of OS and PFS between the two groups (P0.05). For stage T1-3N2M0 which also belongs to stage IIIa, the median OS of surgical and non-surgical groups were 38.9 and 30.8 months, and the median PFS of them were 19.8 and 12.7 months respectively. There were also no significant differences of OS and PFS between the two groups (P0.05). The maximum diameter of tumor and auxillary chemotherapy had significant influences on OS and PFS of stage IIIa-N2 NSCLC patients, while the histology of tumor only influenced the OS of them (P0.05).The patient whose performance status is 0 and staging is stage IIIa is more inclined to undergo surgery. Surgery can prolong OS of patients with stage IIIa, especially for stage T4N0/T3-4N1M0. However, it has no benefit on PFS. The maximum diameter of tumor and auxillary chemotherapy have significant influences on OS and PFS of stage IIIa-N2 NSCLC patients, while the histology of tumor only influence the OS of them.背景与目的 对于III期非小细胞肺癌（non-small cell lung cancer, NSCLC），目前普遍倡导手术、化疗、放疗的多学科综合治疗，但许多研究者对是否应该手术提出了质疑。该研究探讨了手术对于III期NSCLC患者的价值。 方法 回顾性分析2002年3月-2012年10月北京协和医院收治的经病理学确诊的III期NSCLC患者310例。根据最初确诊时是否手术可分为手术组和非手术组。IIIa期根据N分期的不同可分为T4N0/T3-4N1M0期和T1-3N2M0期。采用χ2检验比较计数资料，Kaplan-Meier方法比较总生存期（overall survival, OS）和无进展生存期（progression free survival, PFS），并绘制生存曲线。结果 ECOG评分0分和IIIa期NSCLC患者更倾向于手术治疗。IIIa期手术与非手术组的中位OS分别为38.9个月和21.8个月，中位PFS分别为19.2个月和11.9个月。两组OS的差异有统计学意义（P=0.041），PFS的差异无统计学意义（P=0.209）。IIIa期中的T4N0/T3-4N1M0期手术与非手术组的中位OS分别为48.7个月和20.1个月，中位PFS分别为14.6个月和10.5个月，两组OS和PFS的差异均无统计学意义（P0.05）；T1-3N2M0期手术与非手术组中位OS分别为38.9和30.8月，中位PFS分别为19.8个月和12.7个月，两组OS和PFS的差异亦无统计学意义（P0.05）。肿瘤最大径和辅助化疗对IIIa-N2期患者的OS和PFS的影响有统计学意义，而肿瘤的病理类型仅影响患者的OS（P0.05）。结论 ECOG评分0分和IIIa期NSCLC患者更适于手术治疗。手术可延长IIIa期尤其是T4N0/T3-4N1M0期NSCLC患者的OS，但对PFS无改善作用。肿瘤最大径和辅助化疗对IIIa-N2期患者的OS和PFS均有明显影响，而肿瘤的病理类型只影响其OS。

Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor and sensitive to chemotherapy and radiotherapy. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. Currently, the standard first-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen while the standard second-line chemotherapy regimen is open to debate. The aim of this study is to analysis the prognostic factors of second-line chemotherapy in extensive-stage SCLC and to compare the differences of objective response rate, side effects and survival among different second-line chemotherapy regimens.181 patients who were diagnosed as extensive-stage SCLC and received second-line chemotherapy were collected. χ(2) test was used to analysis the differences of enumeration data and between different groups. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the prognostic factors. Objective response rate was evaluated by RECIST criteria and side effects were evaluated by WHO criteria.The patients who received second-line chemotherapy can be divided into 6 groups, namly group A (CE/EP regimen) 27 cases, group B (regimens containing TPT) 44 cases, group C (regimens containing CPT-11) 33 cases, group D (regimens containing TAX/DXL) 20 cases, group E (regimens containing IFO) 28 cases and group F (other regimens) 29 cases. The median OS in second-line chemotherapy as 7.0 months and was relevant with smoking history (P=0.004), ECOG PS (P0.001), liver metastasis (P=0.019) and bone metastasis (P=0.028) independently. The median PFS in second-line chemotherapy as 3.0 months and was relevant with smoking history (P=0.034), ECOG PS (P=0.011) and bone metastasis (P=0.005). The response rate among six regimens was significantly different (P=0.017); There was not statistical significance between each group. As to side effects, the incidence of gastrointestinal reaction in group C was higher than any other group. The differences of OS and PFS between six regimens in second-line therapy were not statistically different (P=0.914, P=0.293).The most significant prognostic factor of extensive-stage small cell lung cancer patients who received second-line chemotherapy was ECOG PS. The most optimal second-line chemotherapy regimen with definite curatice effect was controversial.背景与目的 小细胞肺癌（small cell lung cancer, SCLC）是恶性程度极高的神经内分泌肿瘤，对放化疗敏感，但大多数接受一线化疗的患者在1年-2年内复发。一旦疾病复发，预后不良。目前，广泛期SCLC的一线标准化疗方案为铂类联合依托泊苷方案，二线化疗方案尚无定论。该研究分析二线化疗预后的影响因素；比较不同二线化疗方案的近期疗效、不良反应和远期生存情况的差异。方法 回顾性分析接受二线化疗的181例广泛期SCLC患者的临床资料。根据不同化疗方案分为6组，采用χ2检验比较计数资料和各组组成差异。采用Kaplan-Meier法分析总生存时间（overall survival, OS）和无进展生存时间（progression-free survival, PFS）。采用单因素和Cox回归多因素分析方法分析生存期的影响因素。结果 二线化疗的中位OS为7.0个月，单因素和多因素的分析结果表明吸烟情况（P=0.004）、ECOG评分（P0.001）、肝转移（P=0.019）和骨转移（P=0.028）是影响二线化疗OS的独立影响因素；二线化疗的中位PFS为3.0个月，吸烟（P=0.034）、ECOG评分（P=0.011）和骨转移（P=0.005）是二线化疗PFS的独立影响因素。6组有效率有明显差异（χ2=12.413, P=0.017），两两比较各组无明显差异；副反应方面，伊立替康组胃肠道反应的发生率明显高于其它组；6组的OS和PFS无统计学差异（χ2=1.491, P=0.914; χ2=6.133, P=0.293）。结论 ECOG评分是影响广泛期SCLC二线化疗预后的最重要因素。广泛期SCLC的二线化疗尚无疗效确切的最优方案。

At present, surgery is advocated for stage IIIa non-small cell lung cancer (NSCLC), and the survival of them is determined by many factors. The aim of this study is to analyze the influencing factors of prognosis for stage IIIa surgical patients.Between March 2002 and October 2012, 151 surgical cases that have postoperative pathological finding of stage IIIa NSCLC with completed followed-up data were received in the Peking Union Medical College Hospital. According to different N stages, 151 patients were divided into T4N0/T3-4N1M0 and T1-3N2M0 stages. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to proceed univariate analysis of survival. Cox regression analysis was used to conduct multivariate analysis. A p-value less than 0.05 was evaluated as statistically significant.151 stage IIIa NSCLC patients had 43 stage T4N0/T3-4N1M0 cases and 108 stage T1-3N2M0 cases. The median OS and PFS of the whole group were 38.9 and 12.9 months respectively. The median OS of stage T4N0/T3-4N1M0 and T1-3N2M0 were 48.7 and 38.9 months. The median PFS of them were 14.9 and 19.8 months respectively. There were no significant differences of OS and PFS between two groups. Univariate and multivariate analysis indicated that postoperative chemotherapy had a significant influence on OS of the surgical patients with stage IIIa NSCLC (P=0.001), and family history of tumor had a significant influence on PFS (P0.05). The maximum diameter of tumor had a significant influence on PFS only in univariate analysis.For stage IIIa NSCLC, postoperative chemotherapy can increase OS and PFS, but postoperative radiotherapy have no benefit on them.背景与目的 IIIa期非小细胞肺癌（non-small cell lung cancer, NSCLC）目前多提倡手术治疗，术后患者的生存情况则受多种因素的影响。该研究对IIIa期NSCLC手术患者的预后影响因素进行了统计分析。方法 回顾性分析2002年3月-2012年10月北京协和医院收治的术后病理确诊为IIIa期NSCLC的患者151例。按照N分期的不同分为T4N0/T3-4N1M0和T1-3N2M0期两组。采用Kaplan-Meier方法比较生存期（overall survival, OS）和无进展生存期（progression free survival, PFS），进行OS和PFS影响因素的单因素分析，并绘制生存曲线。采用Cox比例风险模型进行多因素分析。以P0.05认为差异有统计学意义。结果 151例IIIa期NSCLC患者中有T4N0/T3-4N1M0期43例和T1-3N2M0期108例。全组患者的中位OS和PFS分别为38.9月和19.2月。T4N0/T3-4N1M0和T1-3N2M0期的中位OS分别为48.7月和38.9月，中位PFS分别为14.9月和19.8月。两组OS和PFS的差异均无统计学意义（P0.05）。单因素和多因素分析均显示术后化疗对IIIa期手术患者OS的影响有统计学意义（P=0.001），肿瘤家族史对其PFS的影响有统计学意义（P0.05）。肿瘤最大径只在单因素分析中对PFS有影响。结论 术后化疗可以改善IIIa期NSCLC手术患者的生存期，术后放疗对生存期无改善作用。

Nowadays, lung cancer is the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC) makes up about 80%. There is a great many NSCLC patients have been in advanced stage when diagnosed. As a result, people pay more attention to curing advanced NSCLC. The standard treatment to advanced NSCLC is platinum-based combined chemotherapy. However, chemotherapy drugs usually have limited effects on improving the survival of the patients. Then exploring new therapies is extremely urgent to us. Now, molecular targeted therapy has been the most promising research area for the treatment of NSCLC with researches going deep into pathogenesis and biological behavior of lung cancer. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved a great success in the treatment of advanced NSCLC. Their representatives are erlotinib and gefitinib. The two drugs have been widely used to treat advanced NSCLCs worldwide, especially for the patients with EGFR activating mutations. However, after a period of treatment (median time is 6 to 12 months), most patients will develop drug resistance to EGFR-TKIs. Intense research in these NSCLCs has identified two major mechanisms of resistance to TKIs: primary and acquired resistances. The research about resistance mechanism of NSCLC to EGFR-TKIs is a hot one because of their excellent effects on improving overall and progression-free survival. The aim of this article was to summarize the development of the resistance mechanisms.目前，肺癌是全世界范围内发病率和死亡率最高的恶性肿瘤，其中非小细胞肺癌（non-small cell lung cancer, NSCLC）占全部肺癌的80%左右，而NSCLC患者中有很大一部分在确诊时已经处于晚期。因此，对于晚期NSCLC的治疗也越来越受到人们的重视。虽然晚期NSCLC的标准治疗为含铂双药联合化疗，但是化疗药物对改善晚期NSCLC患者的生存期方面作用十分有限，因此寻求新的治疗方式迫在眉睫。随着对肺癌发病机制及其生物学行为的深入研究，分子靶向治疗已成为治疗晚期NSCLC最具前景的研究领域。其中表皮生长因子受体-酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors, EGFR-TKIs）在晚期NSCLC治疗方面取得了突破性进展，其代表药物为吉非替尼和厄洛替尼，这两种EGFR-TKIs已在全世界范围内得到认可并被广泛用于晚期NSCLC的治疗，尤其是对于EGFR敏感突变者。然而，经过一段时间（中位时间为6个月-12个月）的治疗后，大部分患者会对EGFR-TKIs产生耐药，其耐药机制主要包括原发性和获得性耐药。由于EGFR-TKIs在改善晚期NSCLC患者总生存期和无进展生存期方面的突出作用，对于EGFR-TKIs耐药机制的探索已成为国内外研究的热点。该文章就EGFR-TKI耐药机制的研究进展进行了综述。