Correlation of DNA Damage Repair Gene FANCI with Prognosis and Immune Infiltration of Hepatocellular Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4+ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

Establishment and clinical validation of an artificial intelligence YOLOv51 model for the detection of precancerous lesions and superficial esophageal cancer in endoscopic procedure / 中华肿瘤杂志

Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.

Endoscopic submucosal dissection for early hypopharyngeal carcinoma and precancerous lesions / 中华消化内镜杂志

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for early hypopharyngeal carcinoma and precancerous lesions.Methods:Clinical data of 41 patients who received ESD for early hypopharyngeal carcinoma and precancerous lesions from August 2013 to August 2019 in the Department of Endoscopy of Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were retrospectively analyzed. Main outcome measurements included operation completion rate, operation time, en bloc resection rate, R0 resection rate, complication rate and recurrence.Results:ESD was successfully completed in all 41 cases, with a success rate of 100.0% and a mean time of 49.1 min (ranged 10-110 min). Fifty-four lesions underwent en bloc resection, with an en bloc resection rate of 98.2% (54/55), of which 41 had negative horizontal and vertical margins, and the R0 resection rate was 74.5% (41/55). During the operation of 55 lesions, there was a small amount of blood oozing on the wound surface, and electrocoagulation with thermal biopsy forceps could successfully stop the bleeding. No perforation occurred, and 2 cases (4.3%) had delayed bleeding after ESD, and hemostasis was successful under emergency endoscopy. Postoperative endoscopy showed that 1 case (2.2%) had esophageal entrance stenosis, and the obstruction was relieved after repeated water balloon dilatation. The follow-up period ranged from 3 to 72 months, and the median time was 18 months. One case was found to have mucosal lesions in the same part of the hypopharynx and received ESD treatment again. Follow-up to October 2020, no residual lesions and recurrence were found.Conclusion:ESD is a safe and effective option for the treatment of early hypopharyngeal carcinoma and precancerous lesions, which is worthy of clinical application.

Clinical effect of different plastic biliary stent indwelling methods on managing obstructive jaundice in unresectable hilar cholangiocarcinoma / 中华消化内镜杂志

Objective:To compare the clinical effect of three indwelling methods of plastic biliary stent on relieving obstructive jaundice caused by unresectable hilar cholangiocarcinoma.Methods:A retrospective study was performed on data of 61 patients with obstructive jaundice caused by unresectable hilar cholangiocarcinoma from April 2014 to December 2020 in Cancer Hospital, Chinese Academy of Medical Sciences. Plastic biliary stent placement was used to relieve jaundice, including 18 cases of intragastric indwelling at the end of biliary stent, 31 cases of duodenal papilla indwelling at the end of biliary stent, and 12 cases of horizontal portion of duodenum indwelling at the end of biliary stent. Incidence of fever within 2 weeks, perioperative mortality, 90-day obstruction rate, and median stent patency period were followed up and the results were analyzed.Results:The incidence of fever within 2 weeks of the three groups were significantly different [66.7% (12/18), 58.1% (18/31) and 16.7% (2/12), χ2=7.30, P=0.026]. There were no statistically differences in the perioperative mortality [0 (0/16), 3.2% (1/31) and 0 (0/10), χ2=1.09, P=1.000], 90-day obstruction rate [52.9% (9/17), 48.3% (14/29) and 40.0% (4/10), χ2=1.91, P=0.589], or median stent patency period (66.0 d, 91.5 d and 94.0 d, Z=4.96, P=0.084) among three groups. Conclusion:Patients with biliary plastic stents with ends placed at the horizontal portion of the duodenum show lower incidence of fever within two weeks after implantation, and similar median stent patency period, 90-day obstruction rate and perioperative mortality compared with intragastric indwelling and duodenal papilla indwelling groups. Therefore, biliary plastic stents with ends placed at the horizontal portion of the duodenum should be recommended as the preferred procedure.

Clinicopathological features of the colorectal serrated adenoma and analysis on influencing factors of malignancy / 中华胃肠外科杂志

Objective: Serrated adenoma is recognized as a precancerous lesion of colorectal cancer, and the serrated pathway is considered as an important pathway that can independently develop into colorectal cancer. However, little is known about the related risk factors of carcinogenesis of serrated adenoma. The purpose of this study was to analyze the distribution characteristics and potential malignant factors of serrated adenoma in the colon and rectum. Methods: A retrospective case-control study was conducted to collect the clinical data of patients with serrated adenoma who underwent colonoscopy and were pathologically diagnosed in the Cancer Hospital of Chinese Academy of Medical Sciences from April 2017 to July 2019, and exclude patients with two or more pathological types of lesions. The clinical characteristics of serrated adenoma were summarized, and univariate and logistic multivariate regression analysis was conducted to explore the influencing factors for serrated adenoma to develop malignant transformation. Results: Among 28 730 patients undergoing colonoscopy, 311 (1.08%) were found with 372 serrated adenomas, among which 22 (5.9%) were sessile serrated adenomas/polyps, 84 (22.6%) were traditional serrated adenomas, and 266 (71.5%) were unclassified serrated adenomas according to WHO classification. The pathological results showed that 106 (28.5%) lesions were non-dysplasia, 228 (61.3%) lesions were low grade intraepithelial neoplasia, and 38 (10.2%) lesions were high grade intraepithelial neoplasia or cancer. There were 204 (54.8%) lesions with long-axis diameter <10 mm and 168 (45.2%) lesions with length long-axis ≥ 10 mm. 238 (64.0%) lesions were found in the left side colon and rectum and 134 (36.0%) lesions in the right side colon. Gross classification under endoscopy: 16 flat type lesions (4.3%), 174 sessile lesions (46.8%), 117 semi-pedunculated lesions (31.5%), 59 pedunculated lesions (15.9%). Narrow-band imaging international colorectal endoscopic (NICE) classification: 85 (22.8%) type I lesions, 280 (75.3%) type II lesions, 4 (1.1%) type III lesions. Univariate analysis showed that lesion size, lesion location, lesion site and different WHO classifications were associated with malignant transformation of colorectal serrated adenoma (all P<0.05). For the serrated adenomas with different NICE classifications, there were statistically significant differences in the distribution of malignant lesions among groups (P=0.001). Multivariate analysis showed that the long-axis diameter of the lesion ≥10 mm (OR=6.699, 95% CI: 2.843-15.786) and the lesion locating in the left side colorectum (OR=2.657, 95% CI: 1.042-6.775) were independent risk factors for malignant transformation. Conclusions: Serrated adenomas mainly locate in the left side colon and rectum, and are prone to malignant transformation when the lesions are ≥10 mm in long-axis diameter or left-sided.

Comparison of long-term outcomes between endoscopic submucosal dissection and surgical resection for early gastric cancer with undifferentiated histology / 中华胃肠外科杂志

Objective: Endoscopic submucosal dissection (ESD) of undifferentiated early gastric cancer (UD-EGC) remains controversial due to high positive rate of horizontal and vertical resection margins and the risk of lymph node metastasis. The purpose of this study was to compare long-term outcomes of patients with UD-EGC undergoing ESD versus surgery. Methods: This study was a retrospective cohort study. Inclusion criteria: (1) patients with early gastric cancer undergoing ESD or surgical resection; (2) histological types included poorly differentiated adenocarcinoma, poorly differentiated adenocarcima with signet ring cell carcinoma, and signet ring cell carcinoma; (3) no lymph node metastasis or distant metastasis was confirmed by preoperative CT and endoscopic ultrasonography. Exclusion criteria: (1) previous surgical treatment for gastric cancer; (2) synchronous tumors; (3) death with unknown cause; (4) additional surgical treatment was performed within 1 month after ESD. According to the above criteria, clinical data of patients with UD-EGC who received ESD or surgery treatment in Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2016 were collected. After further comparing the clinical outcomes between the two groups by 1:1 propensity score matching, 61 patients in the ESD group and 61 patients in the surgery group were finally included in this study. The disease-free and overall survivals were analyzed by Kaplan-Meier method. Results: All patients in the two groups completed operations successfully. In the ESD group, the median operation time was 46.3 (26.5, 102.3) minutes, 61 cases (100%) were en-bloc resection, and 57 cases (93.4%) were complete resection. Positive margin was found in 4 (6.6%) patients, of whom 2 were positive in horizontal margin and 2 were positive both in horizontal and vertical margins. In the surgery group, only 1 case had positive horizontal margin and no positive vertical margin was observed. There was no significant difference in the positive rate of margin between the two groups (P>0.05). Median follow-up time was 59.8 (3.0, 131.5) months. The follow-up rate of ESD group and surgery group was 82.0% (50/61) and 95.1% (58/61), respectively. The 5-year disease-free survival rate in ESD group and surgery group was 98.2% and 96.7%, respectively (P=0.641), and the 5-year overall survival rate was 98.2% and 96.6%, respectively (P=0.680). In the ESD group, 1 patient (1.6%) had lymph node recurrence, without local recurrence or distant metastasis. In the surgery group, 1 case (1.6%) had anastomotic recurrence and 1 (1.6%) had distant metastasis. Conclusion: ESD has a sinilar long-term efficacy to surgery in the treatment of UD-EGC.

Risk factors for esophageal refractory stenosis after large-scale endoscopic submucosal dissection of superficial esophageal neoplasms / 中华消化内镜杂志

Objective:To determine risk factors for postoperative esophageal refractory stenosis after endoscopic submucosal dissection (ESD) of large-scale early esophageal carcinomas and precancerous lesions.Methods:Two hundred and twelve early esophageal carcinomas or precancerous lesions in 186 patients who underwent ESD larger than 3/4 the total esophageal circumference in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, between July 2013 and December 2017 were divided into two groups according to session number of endoscopic balloon dilatation (EBD), the refractory stenosis group ( n=69, ≥6 EBD sessions) and non-refractory stenosis group ( n=117, ≤5 EBD sessions). Student′s t-test or Mann-Whitney U test was used for univariate analysis and χ2 test and Fisher exact test were used for comparison of categorical variables. Logistic regression was used for multivariate analysis. Results:Compared with the non-refractory stenosis group, the refractory stenosis group had statistically significant differences in the longitudinal diameter of lesions, the longitudinal diameter of artificial ulcer, lesion location, the circumferential range of lesions and the composition of the muscular layer injury (all P<0.05). After eliminating the factor of the vertical diameter of artificial ulcer (because there was significant correlation between the vertical diameter of artificial ulcer and the longitudinal diameter of lesion in clinical practice), multivariate logistic regression analysis showed that the longitudinal diameter of lesion>5 cm (VS ≤5 cm: P=0.003, OR=3.531, 95% CI:1.547-8.060), the location of lesion in the upper thoracic segment (VS lower thoracic segment: P=0.001, OR=36.720, 95% CI:4.233-318.551), in the cervical segment (VS lower thoracic segment: P=0.003, OR=24.959, 95% CI:2.927-212.795), the whole circumferential lesion (VS ≥3/4 but not the whole circumference: P<0.001, OR=10.082, 95% CI:4.196-24.226) and the presence of muscular layer injury ( P<0.001, OR=7.128, 95% CI:2.748-18.486) were more likely to lead to esophageal refractory stenosis after ESD. Conclusion:The longitudinal lesion diameter of more than 5 cm, the circumferential extent of esophageal ESD, cervical or upper-thoracic esophageal lesions, and muscular layer damage are independent risk factors for postoperative esophageal refractory stenosis after ESD for large-scale esophageal cancer and precancerous lesions.

Submucosal tunneling endoscopic resection for submucosal tumors originating from muscularis propria layer at esophagogastric junction / 中华肿瘤杂志

Objective@#To evaluate the short-term outcomes and safety of submucosal tunneling endoscopic resection (STER) for submucosal tumors (SMT) originating from muscularis propria (MP) layer at esophagogastric junction.@*Methods@#The clinical data of 31 patients with SMT originating from MP layer at esophagogastric junction underwent STER were collected and retrospectively analyzed.@*Results@#The success rate of STER of the thirty-one patients was 100%. The mean tumor size was (2.5±1.3) cm and the average operative time was (95.9±56.7) min. Perforation occurred in 3 patients and was successfully clipped by endo-clips during operation. One patient developed delayed bleeding and the bleeding was stopped by endoscopic hemostasis. Twenty-nine leiomyomas and two stromal tumors (GIST) were finally pathologically diagnosed. No local recurrence and distant metastasis were noted during the mean 15.4 months follow-up of 20 cases. According to the lesion size, 31 patients who received STER were divided into two groups. The operation time of maximum diameter ≥3.5 cm group was (134.0±70.6) min, significantly longer than (80.3±42.6) min of maximum diameter <3.5 cm group (P=0.014). However, the en bloc removal rate, postoperative hospital stay and the complication incidence between the two groups had no obvious differences (P>0.05). Univariate analysis showed that the piecemeal removal group had longer tumor diameter, higher incidence of irregular tumor morphology, and longer operative time than the en bloc removal group (all P<0.05). Stepwise logistic regression analysis showed that irregular shape was a risk factor for failure of en bloc removal (OR=18.000, 95% CI: 1.885~171.88, P=0.012).@*Conclusion@#As a new method of minimally invasive treatment, STER technology appears to be a safe and effective option for patients with SMT originating from MP layer at esophagogastric junction.

Diagnostic value of thin-slice CT navigation combined with cytology in preoperative bronchoscopy of peripheral pulmonary lesions / 中华肿瘤杂志

Objective@#To evaluate the diagnostic value of thin-slice CT navigation combined with cytology in routine preoperative bronchoscopy of peripheral pulmonary lesions and compare the diagnostic effects of different cytological sampling methods.@*Methods@#The clinical data of peripheral lung cancer patients with preoperative bronchoscopy and cytology sampling guided by thin-slice CT from May 2015 to July 2016 in Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. The diagnostic accuracy, sensitivity and specificity of different cytological sampling methods for peripheral pulmonary lesions guided by thin-slice CT were compared, the factors affected the diagnostic sensitivity were analyzed, and the complications induced by these methods were observed.@*Results@#The diagnostic sensitivity of thin-slice CT navigation combined with bronchoalveolar lavage for peripheral pulmonary lesions was 39.1%, and the positive diagnosis rate was 35.1%. The diagnostic sensitivity of thin-slice CT navigation combined with cell brush for peripheral pulmonary lesions was 51.7%, and the positive diagnosis rate was 46.4%. The diagnostic sensitivity of bronchoalveolar lavage combined with cell brush for peripheral pulmonary lesions was 57.5%, and the positive diagnosis rate was 51.5%. The positive diagnosis rate between brush sampling and bronchoalveolar lavage was statistically different (P=0.01). No significant difference was observed in the diagnostic rate between cell brush and cell brush combined with bronchoalveolar lavage (P=0.06). The factors affected diagnostic sensitivity of brush included the lesion location, size, and the relationship between the lesion and bronchial (all P<0.05). When the size of the peripheral lung lesion >2 cm, the diagnostic sensitivity of thin-slice CT navigation combined with cell brush for peripheral pulmonary lesions was 73.6%. Its positive diagnosis rate was 68% and the specificity was 100%, respectively. Two cases of mild bleeding were observed, and hemorrhage was terminated by conservative treatment.@*Conclusion@#Preoperative thin-slice CT navigation combined with cytological examination is an effective method for the diagnosis of peripheral pulmonary lesions, and the diagnostic efficiency of cell brush is higher than that of bronchoalveolar lavage, especially for the lesion size >2 cm.

EffectandMechanismof EZH1/2 InhibitorUNC1999onHepatocellularCarcinomaCell： aPreliminaryStudy / 中山大学学报(医学科学版)

@#The aim of this study was to detect the effect and mechanism of EZH1/2 inhibitor UNC1999 on hepatocellular carcinoma cell line SMMC- 7721.【Methods】Two groups including DMSO group（control group）and UNC1999 group were treated with different concentration of DMSO and UNC1999 for different time，respectively，then OD values were detected by using CCK- 8 kit to screen the appropriate action concentration and time of UNC1999. Cell proliferation rate was detected with EdU（5-ethynyl-2-deoxyuridine）Cell Proliferation Kit. The clone formation ability of cell was investigated by clone formation assay. Wound healing assay and transwell assay were used to detect the ability of migration and invasion. Annexin V-FITC/PI double staining assay was performed to detect cell apoptosis. Flow cytometry was used to detect cell cycle. RNA-seq was performed to detect the cell transcriptomics. qRT-PCR was conducted to investigate the related genes，including EZH1，EZH2 and NECTIN4. Western blot was conducted to detect the expression of EZH1 ，EZH2 and H3K27me3. 【Results】 Compared with the control group ，the UNC1999 group showed lower cell proliferation，inhibited ability of migration and invasion（P < 0.05）. In UNC1999 group，G0/1 block occurred in the cell cycle（P<0.05），while cell apoptosis had no significant change（P > 0.05）.【Conclusion】UNC1999 could inhibit HCC by suppressing the expression of EZH1 and EZH2 both in protein level，as well as their function of catalyzing histone methylation. EZH1 and EZH2 play important roles in HCC，which may be potential targets for HCC treatment. UNC1999 could significantly promote the expression of NECTIN4 isoform which has been reported to be associated with the response to anti-cancer drug ，suggesting that the combination of EZH1/2 inhibitor and anti-cancer drug may exert greater effect of inhibiting HCC. This can provide a new idea for clinical drug treatment of liver cancer.

Detection of Immune Cell Subsets of Peripheral Blood in Hepatocellular Carcinoma before Liver Transplantation / 中山大学学报(医学科学版)

[Objective]To investigate the characteristics of immunophenotypes in hepatocellular carcinoma(HCC) before liver transplantation.[Methods]The immunophenotypes of T-,B- cells,monocytes,dendritic cells(DC)and NK-cells in peripheral blood from 6 HCC patient who were ready to have liver transplantation and 6 healthy volunteers were analyzed by multicolor flow cytometry.[Results]In the patients,the proportions of CD4+PD-1+T cells,Treg cell (CD4+CD25+CD39+T cells),CD19+B cells,Plasmablasts(CD27highCD38highIgD-IgM-),classical monocytes(CD14high CD16-)and mature NK-cells(CD3-CD56high)were all higher than those in the healthy controls(all P<0.05).However, marginal zone B cell(CD27+IgD+),Non-switched B cells(CD27+CD38dimIgM+),intermediate monocytes(CD14high CD16+)and immature NK-cells(CD3-CD56+)were lower than those in the healthy controls(all P<0.05). And there wasn't any obvious difference in quantity being observed among other cell types.[Conclusion]There was difference in the immunophenotypes of immune cells in peripheral blood between HCC patients before liver transplantation and healthy people.And this finding exerts important effects on monitoring the immune status of the patients after liver transplantation and guiding the administrations of immunosuppressors.

Cloning and prokaryotic expression of LDH gene in Echinococcus multilocularis and immunogenicity research of the recombinant protein / 中国人兽共患病学报

The present study aimed to clone and express the EmLDH gene of Echinococcus multilocularis in Qinghai Province,identifying immunogenicity of EmLDH recombinant protein and evaluating its immune diagnostic value preliminarily.EmLDH genes were cloned by RT-PCR technology and linked into pET15b vector.Recombinant expression pET15b-EmLDH vectors were constructed and transformed into E.coli Rosetta (DE3) competent cells.Recombinant proteins were induced and expressed.Expression forms of recombinant proteins were detected by SDS-PAGE.Recombinant proteins were purified by affinity chromatography of Ni-IDA resin.Immunogenicity of recombinant proteins was identified by Western blotting.Serum samples from patients with alveolar echinococcosis (57 cases),cystic echinococcosis (33 cases),and healthy persons (50 cases) were examined by ELISA,which evaluated preliminarily immune diagnosis effect of EmLDH recombinant proteins.Results showed that EmLDH gene was cloned successfully and the recombinant proteins were expressed and purified.Results of Western blotting showed EmLDH recombinant proteins were recognised by serum samples from patients with alveolar echinococcosis and cystic echinococcosis,but not by serum samples from healthy persons.Results of ELISA showed that diagnostic sensitivities of EmLDH recombinant protein reacted with serum samples from patients with alveolar echinococcosis and cystic echinococcosis were 84.21％ and 84.85 ％ respectively.EmLDH recombinant proteins of Echinococcus multilocularis have high immunogenicity and good immune diagnostic value for echinococcosis.

Immunomagnetic Nanosphere-based Strategy for Rapid, Efficient and Accurate Detection of Lymphnode Metastatic Carcinoma Cells / 分析化学

A strategy based on immunomagnetic nanospheres ( IMNs ) for rapid, efficient and accurate detection of lymphnode metastasis carcinoma cells ( LNMCCs ) was developed in this study. First, IMNs processing magnetism and biological targeting were fabricated by the approach developed by our group previously. Then, LNMCCs in lymph node fine needle aspiration ( LNFNA) specimens were separated and enriched by the immunomagnetic isolation using IMNs. At last, the captured cells were identified with Wright's staining and immunocytochemistry ( ICC) . The separation and enrichment of LNMCCs with immunomagnetic isolation could reduce the background interference of LNFNA specimens effectively; the identification with Wright ' s staining and ICC offered more reliable information for accurate diagnosis, so the sensitivity, specificity and overall diagnostic accuracy had an obvious improvement compared with the conventional cytologic diagnosis. Besides, the simple and rapid incubation of LNFNA specimens with IMNs needed just 5 min, so the cytomorphology of captured LNMCCs could be intactly retained, which enabled to provide important basis for classifying lymphnode metastasis carcinoma ( LNMC ) and the subsequent pathological study. Moreover, the specific capture of epithelial carcinoma cells in LNFNA specimens with IMNs could make a definite diagnosis of the captured cells as LNMCCs, thus realizing the differentiated diagnosis of LNMC and malignant lymphoma. Additionally, this strategy exhibited successful LNMCCs detection in LNFNA specimens from 110 patients and had higher sensitivity ( 98 . 0%) , specificity ( 100 . 0%) , and overall diagnostic accuracy (98. 2%) than the conventional cytologic diagnosis. Therefore, it was a new attempt to use IMNs for detection of LNMCCs in LNFNA specimens from LNMC patients, and offered new ideas for LNMC diagnosis and study.

Comparative analysis for clinical efficacy and life quality between endoscopic submucosal dissection and surgical treatment of patients with early gastric cancer / 中华消化内镜杂志

Objective To compare the efficacy, safety, and the life quality of patients with early gastric cancer ( EGC) between endoscopic submucosal dissection ( ESD) and surgical treatment. Methods A total of 460 cases with EGC receiving endoscopic therapy or surgical treatment were collected from October 2009 to January 2015 in the Cancer Hospital, Chinese Academy of Medical Sciences. The clinical efficacy and life quality of ESD and surgical treatment for EGC patients were retrospectively analyzed. Results There were 434 cases collected in the study, including 208 cases ( 229 lesions) in the ESD group and 226 cases in the surgery group. For the short-term clinical outcomes of the ESD group, the hospitalization time ( 7. 85 ± 3. 18 d VS 16. 68±5. 89 d, P<0. 001), hospitalization cost (3782. 30±1898. 84 CNY VS 9685. 60± 3643. 97 CNY, P<0. 001 ) and complications [ 0 ( 0/208 ) VS 6. 2% ( 14/226 ) , P<0. 001 ] were statistically different compared with those of the surgery group. For the long-term clinical outcomes, there was no statistical significance on recurrence rate[0. 4%(1/229) VS 0. 9% (2/226), P=0. 622] between the two groups. The cumulative multiple hazard probability curve showed that the ESD group had a significantly higher risk of multiple primary lesions than the surgery group ( P=0. 004) after the same follow-up period. In order to exclude the influence of confounding factors, COX regression model was used to control the age and other factors, and multiple primary risks of the two groups were also statistically significant ( P=0. 013) . The health score of self-evaluation and life quality between the two groups were statistically significant ( P<0. 001) . Conclusion For the short-term clinical outcomes, the ESD group was better than the surgery group. For the long-term clinical outcomes, multiple primary risks were higher in the ESD group than those in the surgery group, but most of the multiple primary cases were successfully treated with a second ESD. The health score of self-evaluation and life quality were better in the ESD group than those in the surgery group.

Comparative analysis for clinical efficacy and life quality between endoscopic submucosal dissection and surgical treatment of patients with early gastric cancer / 中华消化内镜杂志

Objective To compare the efficacy, safety, and the life quality of patients with early gastric cancer ( EGC) between endoscopic submucosal dissection ( ESD) and surgical treatment. Methods A total of 460 cases with EGC receiving endoscopic therapy or surgical treatment were collected from October 2009 to January 2015 in the Cancer Hospital, Chinese Academy of Medical Sciences. The clinical efficacy and life quality of ESD and surgical treatment for EGC patients were retrospectively analyzed. Results There were 434 cases collected in the study, including 208 cases ( 229 lesions) in the ESD group and 226 cases in the surgery group. For the short-term clinical outcomes of the ESD group, the hospitalization time ( 7. 85 ± 3. 18 d VS 16. 68±5. 89 d, P<0. 001), hospitalization cost (3782. 30±1898. 84 CNY VS 9685. 60± 3643. 97 CNY, P<0. 001 ) and complications [ 0 ( 0/208 ) VS 6. 2% ( 14/226 ) , P<0. 001 ] were statistically different compared with those of the surgery group. For the long-term clinical outcomes, there was no statistical significance on recurrence rate[0. 4%(1/229) VS 0. 9% (2/226), P=0. 622] between the two groups. The cumulative multiple hazard probability curve showed that the ESD group had a significantly higher risk of multiple primary lesions than the surgery group ( P=0. 004) after the same follow-up period. In order to exclude the influence of confounding factors, COX regression model was used to control the age and other factors, and multiple primary risks of the two groups were also statistically significant ( P=0. 013) . The health score of self-evaluation and life quality between the two groups were statistically significant ( P<0. 001) . Conclusion For the short-term clinical outcomes, the ESD group was better than the surgery group. For the long-term clinical outcomes, multiple primary risks were higher in the ESD group than those in the surgery group, but most of the multiple primary cases were successfully treated with a second ESD. The health score of self-evaluation and life quality were better in the ESD group than those in the surgery group.

Risk factors and survival analysis for synchronous esophageal carcinoma in patients with hypopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective@#To investigate the risk factors and survival status of hypopharyngeal carcinoma with synchronous second primary carcinoma of the esophagus.@*Methods@#One hundred and sixty patients with newly diagnosed hypopharyngeal carcinoma from January 2009 to December 2012 were retrospectively reviewed. The clinical data, tumor-related information and follow-up results were collected and analyzed.@*Results@#Forty-three synchronous esophageal carcinomas (27%) were detected in 160 patients with hypopharyngeal carcinoma, and most patients (72%) were at an early stage. On univariate analysis, the median age of less than 55 years old (χ2=4.525, P=0.033), excessive alcohol consumption (χ2=6.942, P=0.008) and invasion site more than 3 anatomical regions (χ2=21.503, P=0.000) had a significant correlation with the occurrence of synchronous esophageal carcinomas. Multivariate analysis showed that excessive alcohol consumption (OR=4.787, P=0.029) and invasion site more than 3 anatomical regions (OR=14.391, P=0.000) were independent risk factors. The median survival time was 26 months in 43 patients with synchronous esophageal carcinomas, which was significantly lower than that (58 months) in patients without secondary primary esophageal carcinomas (χ2=11.981, P=0.001).@*Conclusions@#There is a high incidence of synchronous esophageal carcinoma in hypopharyngeal carcinoma patients, affecting the prognosis of hypopharyngeal carcinoma. Surveillance for esophageal carcinomas in patients with hypopharyngeal carcinoma, especially in excessive alcohol drinkers, is warranted.

Evaluation of a new closure technique of large defects after endoscopic full-thickness resection / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the security and efficacy of a new endoscopic closure method of large defects after endoscopic full-thickness resection (EFTR) double purse-string suture using two endoloops and metallic clips via single-channel endoscopy.</p><p><b>METHODS</b>Clinical data of 23 cases with submucosal tumors (SMT) who received endoscopic resection from June 2015 to July 2016 in our National Cancer Center were collected. For gastric and esophageal SMTs or the mucosa layer injured during submucosal tunneling endoscopic resection (STER), double purse-string suture was conducted after EFTR. The key steps of closure were as follows: the endoloop was installed onto the delivery system and inserted into the gastric cavity to the defect location with endoscopy and then opened; the clips were transported into the gastric cavity from the biopsy channel; the endoloop was fixed onto the full thickness of gastric wall along the edge of the defect by clips one by one between the interval of about 5 mm; the endoloop was tightened slowly till the entire circumference of the defect was sutured, thus, one purse-string suture was done; in accordance with the operation above, another endoloop was released, and the second endoloop was fixed at 5-10 mm to the outer edge of the original one, and tied the endoloop gently; this sequence was continued till there was no gap, thus, the double-purse string suture was finished. A total of 23 patients were enrolled in the study, including 18 with gastric tumor and 5 with esophageal tumor, 15 males and 8 females, with the average age of 56 (19 to 76) years.</p><p><b>RESULTS</b>Eighteen cases of gastric SMT were successfully treated by endoscopic EFTR and double purse-string suture. The esophageal mucosa layer of all the 5 cases of esophageal SMT, including tumors of 3 cases located in cervical esophagus at 15-20 cm from the fore-tooth, 1 esophageal leiomyoma case complicated with squamous cell carcinoma in situ, and 1 case of mucosal layer injury during submucosal tunneling endoscopic resection (STER), was successfully repaired by using double purse-string suture. The mean maximum diameter of tumor was 2.3 cm, and the average suture time was 22.8 min. Postoperative pathology showed that 13 cases were gastrointestinal stromal tumors (GIST), 7 cases were leiomyoma, 2 cases were neurilemmoma, and 1 case was leiomyoma complicated with early squamous cell carcinoma in situ. No severe complications occurred during or after the operation.</p><p><b>CONCLUSIONS</b>The double purse-string suture by using metallic clips and endoloops with single channel endoscope is a relatively safe, easy, and reliable technique for repairing large gastric defect after EFTR. For cervical esophageal SMT, or the SMT combined with superficial mucosal lesions, and for the mucosa layer injury during submucosal tunneling endoscopic resection(STER), double purse-string suture is helpful to perform the closure.</p>

Risk factors analysis of the early colorectal carcinoma after endoscopic non-curative resection: A retrospective clinical study of 56 cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the risk factors contributing to the progression-free survival rate of patients undergoing endoscopic non-curative resection.</p><p><b>METHODS</b>Clinicopathological data of patients with early colorectal carcinoma and intraepithelial neoplasia undergoing endoscopic resection in our department from January 2009 to January 2015 were collected. Associated factors affecting the progression-free survival rate of the early colorectal carcinoma after endoscopic non-curative resection were analyzed. Any of the following conditions was defined as endoscopic non-curative resection: (1) positive lateral or vertical cutting margin; (2) submucosa invasion depth ≥1 000 μm; (3) vascular or lymphatic invasion; (4) low differentiation, including signet ring cell carcinoma or mucinous adenocarcinoma; (5) high grade tumor budding.</p><p><b>RESULTS</b>Clinicopathological data of 840 cases were collected. According to China's Endoscopic Screening, Diagnosis and Treatment Guidelines for Early Colorectal Cancer, 56(56/840, 6.7%) cases were defined as the non-curative resection, the metastasis or recurrence rate was 14.3%(8/56), 3-year progression-free survival rate was 85.7%(48/56), and 3-year overall survival rate was 94.6%(53/56). Univariate prognostic analysis showed that 3-year progression-free survival rate in low and moderate-high differentiation adenocarcinoma was 25.0% and 90.4%(χ=6.711, P=0.010), in patients with submucosa invasion depth ≥2 000 μm and <2 000 μm was 75.0% and 93.8%(χ=6.745, P=0.009), and in patients with and without vascular or lymphatic invasion was 60.0% and 88.2%(χ=7.708, P=0.005), whose differences were all significant. Multivariate Cox regression analysis revealed that low differentiation adencarcinoma (P=0.015, HR=8.021, 95%CI: 1.499-42.921), invasion depth ≥2 000 μm (HR=6.823, 95%CI: 1.299-35.848) and vascular or lymphatic invasion (HR=18.143, 95%CI: 2.079-158.358) were independent risk factors for the progression-free survival rate of the early colorectal carcinoma after endoscopic non-curative resection.</p><p><b>CONCLUSION</b>Pathology after endoscopic non-curative resection for early colorectal carcinoma indicates that low differentiation adenocarcinoma, submucosa invasion depth ≥2 000 μm and vascular or lymphatic invasion are independent risk factors of poor prognosis.</p>

Preliminary study on efficacy of radiofrequency ablation combined with endoscopic resection for eradicating widespread early non-flat type esophageal squamous cell carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of radiofrequency ablation(RFA) combined with endoscopic resection(ER) for eradicating widespread early non-flat type esophageal squamous cell carcinoma (ESCC) and precancerous lesions.</p><p><b>METHODS</b>Retrospective analysis was performed on the clinical data of 4 patients with early non-flat type ESCC and precancerous lesions in January 2010 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Proportion of patients with histological complete response (CR) 3 months, 12 months to 5 years after operation and adverse events were observed.</p><p><b>RESULTS</b>These 4 patients were all male, aged from 47 to 71 (mean age 62) years, including 2 of ESCC, 1 of HGIN, 1 of MGIN confirmed by pathology. USL length was 6-12 (mean 8.5) cm. Treatment area (TA) length was 8-14 (mean 10.5) cm. Three cases were 0-II a (mean length 2 cm), and 1 case 0-II c (mean length 4 cm). Lesions of 2 cases were complete cycle, and other 2 cases occupied 3/4 circumference. Four patients completed their operations successfully. Total operation time was 42-105 (mean 66.8) min, RFA time was 3-12 (mean 8.25) min, and ER time was 6-20 (10.25) min, without bleeding and perforation. The mean hospital stay was 3 days. Pathology examination showed that 2 cases were ESCC G2 (lesion length 12, 8 cm; non-flat type lesion length 3, 4 cm), 1 was HGIN (lesion length 12 cm; non-flat type lesion length 1 cm) and 1 was MGIN (lesion length 6 cm; non-flat type lesion length 2 cm). Three cases were CR 3 months, 1 to 5 years after operation. One case had HGIN at 3-month and MGIN at 1-year and 3-year during follow up, and was CR after treatment with HALO. Postoperative esophageal stenosis occurred in 4 cases. Among them, 2 cases were mild without treatment, and 2 were severe, who were relieved by endoscopic water sac dilation for 5-8 (mean 6.5) times.</p><p><b>CONCLUSION</b>RFA combined with ER is effective and safe in the treatment of patients with early non-flat esophageal squamous cell carcinoma and precancerous lesions.</p>

Research of anti-aging mechanism of ginsenoside Rg1 on brain / 中国中药杂志

Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their spatial learning and memory capacities enhanced, SA-beta-Gal positive granules in section of brain tissue decreased, the activity of antioxidant enzyme SOD and the contents of GSH increased in hippocampus, the level of IL-1 and IL-6 in hippocampus decreased, the length contraction of telomere suppressed while the change of telomerase activity increased in hippocampus. Compared with that of normal group, the spatial learning and memory capacities were enhanced in Rg1 normal group, SA-beta-Gal positive granules in section of brain tissue decreased in Rg1 normal group, the level of IL-1 and IL-6 in hippocampus decreased in Rg1 normal group. The results indicated that improvement of antioxidant ability, regulating the level of proinflammatory cytokines and regulation of telomerase system may be the underlying anti-aging mechanism of Ginsenoside Rg1.