Objective To improve the detection rate of early esophageal cancer during endoscopy by construction of artificial intelligence assistant diagnosis system. Methods A total of 2400 esophageal images were collected from Zhongshan Hospital of Fudan University from January 2016 to December 2017, including 1200 images of early esophageal cancer and 1200 images of normal esophageal mucosa. The lesions in pictures were marked with rectangular box by using computer program. Among them, 2000 pictures were divided into the training set and 400 pictures into the test set. An assistant diagnostic model of early esophageal cancer was established by back propagation algorithm in computer deep learning. The training model was tested and the sensitivity and specificity of the system at different cut-off points in the test set was calculated. Receiver operating characteristic ( ROC) curve was used to evaluate the performance of the diagnostic model. Results The area under ROC curve ( AUC) of the auxiliary diagnostic model was 0. 9961. The sensitivity and specificity were satisfactory. Conclusion The deep learning model constructed in this study has good specificity, sensitivity and AUC value in the diagnosis of early esophageal cancer, and can assist endoscopists in real-time diagnosis in clinical examination.

The small ubiquitin-like modified protein (SUMO) is a protein structurally similar to ubiquitin which is involved in post-translational modification of proteins. SUMOylation refers to the process that SUMO molecule covalently binding to the specific lysine site of target proteins through maturation, activation, binding and ligation by ubiquitin-like specific protease 1 (Ulp1), E1 activating enzyme, E2 binding enzyme, and E3 ligase. SUMOylation alters the activity of target proteins, which is involved in the regulation of various cellular functions such as transcriptional regulation, regulation of embryonic development, cellular stress, maintenance of chromatin structure and genomic stability. In recent years, it has been found that SUMOylation modification is also widely involved in DNA damage repair, especially DNA double-strand breaks (DSBs), which are the most serious types of DNA damage. SUMOylation is involved in almost all processes of DSBs repair, so its role in DNA damage repair has become a research hotspot. In this paper, the research progress of the regulation of SUMOylation in DSBs repair was reviewed.

Objective To describe the characteristics of dysphagia in patients with head and neck cancer during radiotherapy,and analyze the cause of dysphagia and the relationship between dysphagia and weight change.Methods Patients with head and neck cancer treated with radiotherapy in Beijing Cancer Hospital from November 2017 to June 2018 were recruited.The M.D.Anderson Dysphagia Inventory (MDADI) was used to assess the dysphagia of patients before (T1),during (T2) and at the end (T3) of the radiotherapy.Meanwhile,the weight,dietary intake and radiation adverse effects were investigated.Generalized estimating equations were used to analyze the impact factors of dysphagia and the relationship among dysphagia,dietary intake and weight change.Results Ninety-six patients were completely investigated and the incidence of dysphagia were 6.3％ (6/ 96),80.2％ (77/96) and 85.4％ (82/96) in T1,T2 and T3.With the progress of radiotherapy,the total score and the scores of 4 dimensions of MDADI dropped and the dietary intake declined.The average weight loss was (5.09±3.31) kg,and 76.1％ of the patients had weight loss over 5％ at the end of radiotherapy.The occurrence of dysphagia was associated with the radiotherapy-related oral and laryngeal mucositis and the weight loss was closely associated with the site of radiation,dysphagia,and dietary intake decline.Conclusions The dysphagia of patients with head and neck cancer is affected by radiation adverse effects,and is most severe at the end of radiotherapy.Dysphagia might result in dietary intake decline and weight loss.Clinicians should pay close attention to the swallowing function of the patients and take measures earlier accordingly.

Objective: To study on the genomic stability of male workers engaged in e-waste dismantling area in Tianjin. Methods: In 2016, an e-waste dismantling area in Tianjin and an area 50 km away from the e-waste dismantling area (no e-waste or other chemical, industrial and agricultural pollution nearby) were selected as the study area and the reference area. Male residents of the study area and male farmers who planted vegetables, fruits, and crops in the reference area were selected as the exposed and reference group by using the convenient sampling method. The exposed group included 146 workers who engaged in e-waste recycling work more than 1 year. The reference group included 121 farmers who never engaged in e-waste recycling work. Questionnaires were used to collect information of all subjects. The semen and peripheral blood were also collected. Trace elements and polychlorinated biphenyl concentration in blood were detected. DNA damage in peripheral blood and sperm was detected, and gene expression was analyzed. DNA damage was assessed using tail DNA% (TDNA%), tail moment (TM) and olive tail moment (OTM) of comet assay. Results: The ages of the exposed group and the reference group were (33.6±12.1) and (33.9±11.9) years old, respectively. The proportions of subjects with exposure time of ≤3, 4-6, ≥7 years were 43% (63 cases), 26% (53 cases) and 21% (30 cases), respectively. The Pb and polychlorinated biphenyl(PCB) concentrations in the exposed group [(90.4±15.3) μg/ml and (101±30) ng/ml, respectively] were higher than those in the reference group [Pb and PCB concentrations were (60.2±8.9) μg/ml, and (2.5±1.4) ng/ml, respectively (both P values <0.05)]. The TDNA%, TM and OTM of peripheral blood and sperm in the exposed group were 5.9%±0.3% and 2.6%±0.90%, 0.93±0.16 and 0.51±0.20, 0.82±0.09 and 0.56±0.07, respectively, which were all higher than those in the reference group [TDNA%, TM and OTM of peripheral blood and sperm were 1.8%±0.2% and 1.9%±0.2%, 0.21±0.04 and 0.32±0.10, 0.19±0.03 and 0.20±0.08, respectively (all P values <0.001)]. The results of gene expression showed that 20 differentially expressed genes, including 13 up-regulated genes and 7 down-regulated genes, were detected in the exposed group compared with the reference group. Conclusion There are obvious DNA damage and DNA repair gene disorder in male workers of an e-waste dismantling area in Tianjin. The current operation mode brings potential health risks to workers.

Objective: To study on the exposure of polychlorinated biphenyl (PCB) contamination and DNA methylation in male employees in an e-waste dismantling area in Tianjin. Methods: In 2016, an e-waste dismantling area in Tianjin and an area 50 km away from the e-waste dismantling area (no e-waste or other chemical, industrial and agricultural pollution nearby) were selected as the study area and the reference area. Male residents of the study area and male farmers who planted vegetables, fruits, and crops in the reference area were selected as the exposed and reference group by using the convenient sampling method. A total of 60 subjects (30 in each of the exposed group and the reference group) were included. The peripheral blood (5 ml) of the study subject was collected, and the PCB concentration was detected. Eight independent subjects in the exposed group and the reference group were randomly selected by random number table method to detect the methylation level of the promoter region of all gene loci, and the mRNA transcript levels. Results: The PCB concentration in peripheral blood of the exposed group was higher than that of the reference group, and the difference was statistically significant (allP values <0.001). The methylation levels of the promoter region of the exposed group and the reference group showed obvious clustering, and 994 gene loci had different degrees of methylation. Compared with the reference group, there were 391 hypomethylation sites and 553 hypermethylation sites in the exposed group. The proportion of methylation sites in the high CpG-rich region was 59.2% and 48.1%, respectively. The mRNA level of the hypomethylated gene in the exposed group was higher (FAM131A, HBM), and the transcription level of the hypermethylated gene was lower (CAPN15, NFIC, SHISA5, FGF13, GRAMD1A, CLEC3B, LILRB2, DCAF7). The mRNA transcription levels of 10 genes above in the exposed group and the reference group were statistically significant (all P values <0.001). Conclusion The PCB concentration of peripheral blood in the exposed population of e-waste is high. PCB exposure changes the methylation level of specific genes and affects the mRNA transcription level of some genes.

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10⁷/kg on day 0) and (4.0-6.8) ×10⁷/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.

OBJECTIVETo analyze the risk factors of carcinogenesis of large colorectal polyps (diameter ≥ 10 mm) found by colonoscopy.

METHODSClinicopathological and follow-up data of 418 consecutive patients who were diagnosed as colorectal polyps with diameter≥10 mm by colonoscopy at two endoscopy centers of the Affiliated Wuxi Second People's Hospital, Nanjing Medical University (n=207) and Zhongshan Hospital, Fudan University (n=211) from January 2015 to December 2016 were retrospectively collected. High-grade intraepithelial neoplasia and cancer were defined as malignancy in this study. Chi square test was used for univariate analysis, and logistic regression was used for multivariate analysis (in patients with multiple polyps, if the pathological findings were all low grade intraepithelial neoplasia, one polyp with the largest diameter was selected to enter the model; in patients with high grade intraepithelial neoplasia, one polyp of high grade intraepithelial neoplasia with the largest diameter was selected to enter the model). Associated risk factors of malignancy were analyzed.

RESULTSAmong the 418 patients, 278(66.5%) were male and 140(33.5%) were female, with mean age of (58.7±10.2) (range 15-87) years old. Of 398 patients undergoing endoscopic treatment with resected 456 polyps, 142 cases with 150 polyps were malignant, including 134 polyps of high-grade intraepithelial neoplasia and 16 polyps of intra-mucosal cancer. The other 20 patients showed negative elevation signs after endoscopic submucosal injection and were transferred to surgery, of whom 20 polyps were resected. Histological examination of these 20 polyps indicated invasive cancer. Univariate analysis showed that age ≥ 50 years [40.5% (150/370) vs. 25.0% (12/48), χ² =4.323, P=0.041], multiple polyps [77.5%(31/40) vs. 34.7%(131/378), χ² =12.900, P=0.001], polyp locating at rectum [59.0%(36/61) vs. 32.3%(134/415), χ² =22.736, P=0.000], polyp diameter ≥31 mm [74.1%(20/27) vs. 33.4%(150/449), χ² =36.493, P=0.000] and tubular villous adenoma [67.4%(120/178) vs. 16.8%(50/298), χ² =71.810, P=0.000] were associated with malignancy. Multivariate analysis showed that age ≥ 50 years(OR=2.473, 95%CI:1.209-5.058, P=0.013), multiple polyps (OR=2.472, 95%CI: 1.300-4.702, P=0.006), polyp locating at rectum (OR=1.253, 95%CI: 1.091-1.439, P=0.001) and the polyp diameter ≥31 mm (OR=1.500, 95%CI:1.196-1.881, P=0.000) were independent risk factors for malignancy of large colorectal polyps. The mean follow-up time was (9.6±4.2) months. During the follow-up period, 86 patients (20.5%) who received endoscopic resection developed recurrent adenoma which all were successfully removed by colonoscopic polypectomy. Two patients(0.5%) developed colon cancer 6 months after endoscopic resection and both underwent radical surgery and chemotherapy. Their previous pathology from endoscopic resection was tubular villous adenoma and high grade intraepithelial neoplasia. All the patients were alive during the follow-up period.

CONCLUSIONSAge ≥50 years old, multiple polyps, polyps locating at rectum and polyps with diameter ≥ 31 mm are the risk factors of malignancy. Emphasized examination should be recommended for those with the above mentioned risk factors to avoid missed diagnosis and misdiagnosis. The choice of endoscopic treatment must be reasonable for curative resection.

Objective To study the effect of human umbilical cord mesenchymal stem cells (hMSCs) on the survival rate of mice with radiation-induced intestinal injury and its effect on the repair of intestinal damage.Methods Adult C57BL/6J mice were selected and divided into control group and abdomen irradiation + PBS(IR + PBS) group and abdominal irradiation+hMSCs transplantation treatment (IR+hMSCs)group.Intestinal injury model was induced by abdominal irradiation at 13 Gy of T ray and the 30-day survival rate was recorded.On the 3.5th and 5.0th day after irradiation,HE staining was used to observe changes in the villus structure and thc number of intestinal crypts in each segment of the small intestine (duodenum,jejunum,and ileum).Results The survival rate of IR+hMSCs group was significantly higher than that of IR+PBS group (P＜0.05).On the 3.5th day after 13 Gy of abdomen irradiation,the duodenum,cavities and ileum villus in IR+PBS group were all fractured,the length was shortened,and the numbers were sparse when compared with the control group,while the hMSCs reduced the intestinal damage.On the 5.0th day after irradiation,the structural integrity of the small intestine in IR+PBS group was repaired slightly,but it still more serious than that of IR+hMSCs group (P＜0.01).The amount of intestine crypts were significantly higher in IR+hMSCs group than that of IR+PBS group,but were significantly lower than that of control group (P＜0.01) at 3.5th day and 5.0th day after radiation.Conclusion Transplantation of hMSCs can improve the survival rate and promote the repairation of intestinal injury induced by radiation in mice.MSCs are hopeful to be used on the treatment of radiation-induced intestinal injury.

Objective To investigate the role and possible mechanisms of paracrine in radiation tolerance of non-small cell lung cancer (NSCLC) by observing the effects of radiation-resistant NSCLC H460R cell secretion on the radiosensitivity of parental H460 cells. Methods H460 cells were inoculated and cultured, and then divided into control group, conditional culturing group, irradiation group and irradiation combined conditional culturing group. One-time irradiation with 137Cs γ-rays was conducted with a dose rate of 1.02 Gy/min. Effect of H460R conditioned media on the radiation sensitivity of H460 cells was observed by clonogenic assay. The percentage of phospho-histone histone H2AX (γH2AX) positive cells was detected by immunofluorescence staining. The cyclical changes of the cells were detected by flow cytometry. The expression of DNA damage-associated proteinsγH2AX and Rad51 were detected by Western Blot. Results The results showed that compared with the singleγ-rays irradiation, the number of cell clones was significantly increased in the H460R cells after γ-rays irradiation combined with conditional culturing treatment at different doses of 2, 4, and 6 Gy, and the differences were statistically significant (2,4 Gy:all P<0.05;6 Gy:P<0.01). The results of immunofluorescence staining showed that the percentage ofγH2AX positive cells in the conditional culturing group was higher than that in the control group [(39.40±2.51)％vs. (25.21± 2.05)％], and the difference was statistically significant (P<0.01). This value in the irradiation combined conditional culturing group was lower than that in irradiated group [(60.48±2.79)％vs. (80.65±2.05)％], and the difference was statistically significant (P<0.001). The flow cytometry analysis showed that the percentage of cells in G2/M phase for the irradiation (4 Gy) combined conditional culturing group was higher than that of irradiated group [(26.83± 1.42)％ vs. (15.73±1.29)％], and the difference was statistically significant (P<0.001). The Western Blot results showed that γH2AX and Rad51 protein expression in the irradiation (4 Gy) combined conditional culturing group respectively was lower and higher than that in irradiated group. Conclusion In the tumor microenvironment, radiation-resistant H460R cells can enhance the radioresistance of H460 cells by paracrine, which may be related to the promotion of DNA repair ability after irradiation

In order to effectively improve the radiation sensitivity of tumors and reduce the side effects during radiotherapy,people have been working on the development of radiation sensitizers.In recent years,many researches focused on the nanoparticles with high atomic number elements as radiosensitizers.Researchers have recently developed a kind of new gadolinium-based radiation-sensitizing nanoparticles,i.e.AGUIX,which have low toxicity,low quality,and radiation-activated drug activity.These nanoparticles are consisted by a polysiloxane core and a network of covalently attached gadolinium chelates.They have a hydrodynamic diameter of less than 5 nm,and can be administered intravenously due to the preferential accumulation in tumor sites and elimination by kidney.Studies have proved that AGUIX can be used as a safe and effective radiation sensitizer under various irradiation conditions.In addition,due to the presence of strontium,AGUIX itself can also be used as a MRI contrast agent to monitor the biodistribution of drugs and tumor evolution,and then guide the development of radiotherapy.In this paper,the research progress of AGUIX in recent years was reviewed.