ObjectiveTo clarify whether epigallocatechin gallate （EGCG） is involved in the clearance of amyloid β-protein （Aβ） and autophagy induction by microglia， so as to explore the potential mechanisms of EGCG in the prevention and treatment of Alzheimer's disease （AD）. MethodsSix-month-old APP/PS1 mice were randomly divided into model and EGCG groups， with some additional wild type （WT） mice as the control group， each group consisting of 15 mice. The EGCG group received continuous gavage administration［5 mg/（kg·d）］ for 8 weeks， followed by the open field test and Y-maze to assess the learning and memory abilities of the mice. Thioflavin-S staining was used to evaluate the content and distribution of amyloid β-protein （Aβ）in the brain parenchyma of the mice， and immunofluorescence was employed to detect the expression levels of Aβ_1-42， glial fibrillary acidic protein （GFAP）， and ionized calcium-binding adapter molecule 1 （Iba1） in the hippocampal tissue of the mice. Additionally， N9 mouse microglial cells were induced with 20 µmol/L Aβ_1-42， and the cell viability was measured after treatment with different concentrations of EGCG （5 µmol/L， 10 µmol/L， 20 µmol/L）. Western blotting was used to detect the levels of Aβ_1-42， low density lipoprotein receptor-related protein 1（LRP1）， receptor for advanced glycation endproducts （RAGE）， amyloid precursor protein （APP）， insulin degrading enzyme （IDE）， neprilysin （NEP）， microtubule associated protein 1 hydrogen chain 3（LC3）-Ⅱ/LC3-Ⅰ， phosphatidylinositol 3-hydroxy kinase（PI3K）， p-PI3K， protein kinase B （AKT）， p-AKT， mammalian target of rapamycin （mTOR）， p-mTOR， and histone deacetylase 6（HDAC6）. Finally， through the co-culture of microglial cells and neuronal SH-SY5Y cells， cell viability and Caspase-3 levels were measured to verify the protective effect of EGCG-mediated Aβ clearance on neurons. ResultsEGCG increased the activity time and frequency of APP/PS1 mice in the central area of the open field （P<0.05）， and enhanced the percentage of alternation in the Y-maze test （P<0.01）； EGCG reduced Aβ deposition in the hippocampal tissue of APP/PS1 mice and increased the number of microglia； in vitro experiments showed that EGCG improved the survival rate of Aβ-induced N9 cells （P<0.01）， upregulated RAGE activity （P<0.05）， and promoted the internalization and phagocytosis of Aβ （P<0.01）. ECGC activated microglial autophagy by downregulating the level of HDAC6 （P<0.05）， inhibiting the phosphorylation of PI3K， AKT， mTOR （P<0.001）， and increasing the LC3-Ⅱ/LC3-I ratio （P<0.001）； EGCG improved the survival rate of SH-SY5Y cells （P<0.05） and reduced the activity of Caspase-3 （P<0.01） by clearing Aβ_1-42 through microglia， and had a protective effect on neurons. ConclusionEGCG activates microglial autophagy to clear Aβ by targeting and inhibiting the HDAC6-PI3K/AKT/mTOR axis.

Objective:To assess the effectiveness and feasibility of carrier detection for Spinal muscular atrophy (SMA) by using digital PCR assay.Methods:Peripheral blood samples were collected from 214 pregnant women who were routinely screened for SMA carriers, of which 204 were randomly selected samples and 10 were samples with known copy numbers of SMN1 exons 7 and 8. Samples with known copy numbers of SMN1 exons 7 and 8 were randomly mixed into the experiment to validate the performance of the digital PCR assay. The copy numbers of SMN1 exons 7 and 8 and SMN2 exons 7 and 8 in peripheral blood samples were detected by digital PCR assay. The results of SMN1 exons 7 and 8 were compared with those of the quantitative PCR method to assess the reliability and clinical performance of the digital PCR assay. Results:Among the 204 random samples, digital PCR has detected five samples with simultaneous heterozygous deletion of SMN1 exons 7 and 8, three samples with heterozygous deletion of SMN1 exon 8 only, and 196 samples with no deletion of SMN1 exons 7 and 8. Ten samples with known SMN1 exons 7 and 8 copy numbers were detected with the expected values. The digital PCR test results were fully consistent with that of the quantitative PCR. Conclusion:The results of digital PCR for the detection of copy number variation of SMN1 exons 7 and 8 were consistent with qPCR. Digital PCR assay was able to clearly distinguish the copy number of the target genes, therefore can be used for SMA carrier screening. Moreover, it can also detect copy number of SMN2 exons 7 and 8, which can provide more information for genetic counseling.

Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

Objective: The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non-radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods: We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy (33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single-institution database.The survival rates were calculated by Kaplan-Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results: The median follow-up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease-free survival (DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3-year OS were 75.5%, 57.4%, 27.3% (P<0.001) and 3-year DFS were 72.0%, 44.7%, 17.6% (P<0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3-year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7% of the negative group (both P<0.001). The 3-year OS and DFS of pathologic stage Ⅰ, Ⅱ, ⅢA, ⅢB and Ⅵ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3% (P<0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3% (P<0.001), respectively.The operation-related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS (P<0.05 for all). Conclusions The planned neoadjuvant radiotherapy or chemoradiotherapy for the non-radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

Objective The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non?radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy ( 33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single?institution database.The survival rates were calculated by Kaplan?Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results The median follow?up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease?free survival ( DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3?year OS were 75.5%, 57.4%, 27.3%( P＜0.001) and 3?year DFS were 72.0%, 44.7%, 17.6%(P＜0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3?year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7%of the negative group (both P＜0.001).The 3?year OS and DFS of pathologic stage Ⅰ,Ⅱ,ⅢA,ⅢB andⅥ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3%( P＜0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3%(P＜0.001), respectively.The operation?related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS ( P＜0.05 for all). Conclusions The planned neoadjuvant radiotherapy or chemoradiotherapy for the non?radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

Objective The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non?radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy ( 33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single?institution database.The survival rates were calculated by Kaplan?Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results The median follow?up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease?free survival ( DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3?year OS were 75.5%, 57.4%, 27.3%( P＜0.001) and 3?year DFS were 72.0%, 44.7%, 17.6%(P＜0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3?year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7%of the negative group (both P＜0.001).The 3?year OS and DFS of pathologic stage Ⅰ,Ⅱ,ⅢA,ⅢB andⅥ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3%( P＜0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3%(P＜0.001), respectively.The operation?related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS ( P＜0.05 for all). Conclusions The planned neoadjuvant radiotherapy or chemoradiotherapy for the non?radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

Objective: To analyze risk factors of anastomotic leakage after McKeown'sesophagectomy. Methods: The clinical data of 635 esophageal cancer patients, who underwent McKeown's esophagectomy at Cancer Hospital of Chinese Academy of Medical Sciences from January 2012 to December 2015, were retrospectively analyzed. The risk factors of cervical anastomotic leakage were identified through analysis of medical history, surgical procedure, tumor characteristics and vascular calcification. Results: Among all the 635 patients, anastomotic leakage occurred in 111 (17.5%)patients. Univariate analysis showed that the American Society of Anesthesiologists (ASA) risk class, prior thoracic surgery, upper digestive tract ulcer, COPD, hypertension, peripheral vascular disease, renal insufficiency, FEV1% predicted, DLCO% predicted, duration of surgery and calcification of descending aorta, celiac trunk and left postceliac arteries were associated with a statistically significant increase in risk of cervical anastomotic leakage (P<0.05 for all). Logistic regression analysis showed that ASA risk class, peripheral vascular disease, renal insufficiency and calcification of descending aorta and celiac trunk were independent risk factors of cervical anastomotic leakage after McKeown's esophagectomy (P<0.05 for all). Conclusions ASA risk class, peripheral vascular disease, renal insufficiency, calcification of descending aorta and celiac trunk are independent risk factors of cervical esophageal anastomotic leakage after McKeown's esophagectomy.

[ Abstract] Objective To investigate the clinical efficacy of preoperative three-dimensional radiotherapy (3DRT) with or without concurrent chemotherapy for esophageal carcinoma.Methods We retrospectively analyzed 103 esophageal carcinoma patients who received preoperative 3DRT with or without concurrent chemotherapy from 2004 to 2014 in Cancer Hospital CAMS.The median radiation dose was 40 Gy, and the TP or PF regimen was adopted for concurrent chemotherapy if needed.The overall survival (OS) and disease-free survival ( DFS) were calculated by the Kaplan-Meier method, and the survival difference and univariate prognostic analyses were performed by the log-rank test.The Cox proportional hazards model was used for multivariate prognostic analysis.Results The number of patients followed at 3-years was 54.The 3-year OS and DFS rates were 61.1% and 54.9%, respectively, for all patients.There were no significant differences between the 3DRT and concurrent chemoradiotherapy (CCRT) groups as to OS (P=0.876) and DFS (P=0.521).The rates of complete, partial, and minimal pathologic responses of the primary tumor were 48.0%, 40.2%, and 11.8%, respectively.There were significant differences in OS and DFS between the complete, partial, and minimal pathologic response groups (P=0.037 and 0.003). No significant difference in pathologic response rate was found between the 3DRT and CCRT groups (P=0.953).The lymph node metastasis rate was 26.5%, and this rate for the complete, partial, and minimal pathologic response groups was 14%, 30%, and 67%, respectively, with a significant difference between the three groups (P=0.001).The OS and DFS were significantly higher in patients without lymph node metastasis than in those with lymph node metastasis (P=0.034 and 0.020).The surgery-related mortality was 7.8% in all patients.Compared with the 3DRT group, the CCRT group had significantly higher incidence rates of leukopenia (P=0.002), neutropenia (P=0.023), radiation esophagitis (P=0.008), and radiation esophagitis ( P=0.023).Pathologic response of the primary tumor and weight loss before treatment were independent prognostic factors for OS and DFS (P=0.030,0.024 and P=0.003,0.042). Conclusions Preoperative 3DRT alone or with concurrent chemotherapy can result in a relatively high complete pathologic response rate, hence increasing the survival rate.Further randomized clinical trials are needed to confirm whether preoperative CCRT is better than 3DRT in improving survival without increasing the incidence of adverse reactions.

OBJECTIVETo compare the short-term outcomes and pulmonary function loss between thoracoscopic anatomical partial-lobectomy and thoracoscopic lobectomy on the patients with pT1aN0M0 peripheral non-small cell lung cancer.

METHODSThe clinical data of 191 patients with pT1aN0M0 peripheral non-small cell lung cancer received thoracoscopic anatomical pneumonectomy between January 2013 and July 2013 in Department of Thoracic Surgery, Cancer Hospital Chinese Academy of Medical Sciences was analyze retrospectively. There were 71 patients underwent thoracoscopic anatomical partial-lobectomy and 120 patients underwent thoracoscopic lobectomy. Demographic features, operation time, blood loss, number of dissected lymph nodes, chest tube duration, drainage volume, postoperative hospital stay, postoperative complications, two-year progress and pulmonary function loss of FEV1% (percentage of the predicted forced expiratory volume in 1 second) at 6 months were retrospectively reviewed and compared by t test, rank-sum test, χ² test and Fisher exact test.

RESULTSThere were no significant differences in operation time, blood loss, number of dissected lymph nodes, chest tube duration, drainage volume, postoperative hospital stay, and postoperative complication rate (P > 0.05). The two-year progress rate between two groups did not differ significantly either (1.4% vs. 1.7%, χ² = 0.000, P = 1.000). Pulmonary function loss of FEV1% at 6 months was significantly smaller in thoracoscopic anatomical partial lobectomy group than thoracoscopic lobectomy group (14% ± 4% vs. 16% ± 4%, t = 2.408, P = 0.017).

CONCLUSIONSThoracoscopic anatomical partial-lobectomy is safe and feasible for patients with pT1aN0M0 peripheral non-small cell lung cancer. It could achieve equal short-term effect and reserve more pulmonary function compared with thoracoscopic lobectomy.

Carcinoma, Non-Small-Cell Lung ; surgery ; Chest Tubes ; Drainage ; Humans ; Length of Stay ; Lung Neoplasms ; surgery ; Lymph Node Excision ; Operative Time ; Pneumonectomy ; methods ; Postoperative Complications ; Retrospective Studies ; Thoracic Surgery, Video-Assisted