Objective To investigate the potential mechanism of tumor-derived exosome miR-3173-5p promoting the activation of cancer-associated fibroblasts(CAFs)and regulating the proliferation,invasion and apoptosis of non-small cell lung cancer(NSCLC)cells.Methods Exosome(Exo)of NSCLC cell A549 was extracted,the morphology of Exo was observed by transmission electron microscopy,and the expression of Exo marker protein was detected by Western blot.Real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the expression of miR-3173-5p in A549 cells and Exo.The binding of miR-3173-5p to F-box/WD-40 domain protein11(FBXW11)was predicted by Starbase database,and verified by luciferase reporter gene analysis.Human lung fibroblast cell line(MRC-5)was treated with Exo and Exo inhibitor GW4869 or NC inhibitor/mimic or miR-3173-5p inhibitor/mimic and/or FBXW11 overexpression/empty vector,NC group,Exo group,Exo+GW4869 group,Exo-NC inhibitor group,Exo-miR-3173-5p inhibitor group,Exo-NC mimic group,Exo-miR-3173-5p mimic group,Exo-miR-3173-5p mimic+Vector group and Exo-miR-3173-5p mimic+FBXW11 group were set up respectively.The level of CAFs marker protein[Matrix metalloproteinase-9(MMP-9),α-Smooth muscle aorta(α-SMA),Chemokine(C-X-C motif)ligand 12(CXCL12),Fibronectin,Vimentin,Interleukin-1β(IL-1β),Interleukin-6(IL-6),Interleukin-8(IL-8)]in cells of each group was detected by Western blot analysis,and the influence of exosome miR-3173-5p and FBXW11 expression on CAFs activation was analyzed.Exo and Exo-miR-3173-5P mimic were separated and the supernatant of MRC-5 cells incubated with Exo-FBXW11 was used as conditioned medium(CM)to culture A549 cells.The NC-CM group,Exo-CM group,Exo-miR-3173-5p mimic-CM group and Exo-FBXW11-CM group were set up respectively.MTT assay,Transwell assay and flow cytometry were used to detect the effects of CAFs activation on proliferation,invasion and apoptosis of NSCLC cells.Results Transmission electron microscopy showed that the diameter of exosomal vesicles derived from NSCLC cells was about 30～100 nm.Western blot analysis showed that all exosome labeled proteins were positive.The expression of miR-3173-5p(33.45±3.16)in NSCLC-derived exosomes was significantly higher than that in tumor cells(1.01±0.07),and the difference was statistically significant(t=1.263,P<0.001).MiR-3173-5p targets FBXW11 and inhibits its expression.Compared with NC group,CAFs marker protein levels in Exo group were significantly increased(t=12.214～24.908),the expression of CAFs marker protein in Exo+GW4869 group was significantly inhibited compared with Exo group(t=13.160～25.143),the differences were statistically significant(all P<0.01),respetively.Compared with Exo group,miR-3173-5p inhibitor inhibited EXO-induced CAFs marker protein expression(t=11.059～21.094),and miR-3173-5p mimic promoted the expression of CAFs marker protein(t=12.943～18.671),the differences were statistically significant(all P<0.01),respectively.Overexpression of FBXW11 reversed the induction of CAFs activation by miR-3173-5p mimic.Compared with the NC-CM group,the proliferation activity and invasion rate of A549 cells in the Exo-CM group were significantly enhanced,and the apoptosis rate was significantly inhibited(t=10.207,2.359,3.001),miR-3173-5p mimic enhanced the promoting effect of Exo-CM on proliferation and invasion of A549 cells and the inhibitory effect on apoptosis(t=9.399,3.438,3.208),while overexpression of FBXW11 can antagonize the promotion effect of Exo-CM on proliferation and invasion of A549 cells and the inhibition effect on apoptosis(t=18.868,7.070,9.813),the differences were statistically significant(all P<0.05),respectively.Conclusion Tumor-derived exosome miR-3173-5p promotes CAFs activation through targeted inhibition of FBXW11 expression,further promotes proliferation and invasion of NSCLC cells,inhibits cell apoptosis,and regulates the occurrence and development of NSCLC.

Objective To investigate the potential mechanism of tumor-derived exosome miR-3173-5p promoting the activation of cancer-associated fibroblasts(CAFs)and regulating the proliferation,invasion and apoptosis of non-small cell lung cancer(NSCLC)cells.Methods Exosome(Exo)of NSCLC cell A549 was extracted,the morphology of Exo was observed by transmission electron microscopy,and the expression of Exo marker protein was detected by Western blot.Real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the expression of miR-3173-5p in A549 cells and Exo.The binding of miR-3173-5p to F-box/WD-40 domain protein11(FBXW11)was predicted by Starbase database,and verified by luciferase reporter gene analysis.Human lung fibroblast cell line(MRC-5)was treated with Exo and Exo inhibitor GW4869 or NC inhibitor/mimic or miR-3173-5p inhibitor/mimic and/or FBXW11 overexpression/empty vector,NC group,Exo group,Exo+GW4869 group,Exo-NC inhibitor group,Exo-miR-3173-5p inhibitor group,Exo-NC mimic group,Exo-miR-3173-5p mimic group,Exo-miR-3173-5p mimic+Vector group and Exo-miR-3173-5p mimic+FBXW11 group were set up respectively.The level of CAFs marker protein[Matrix metalloproteinase-9(MMP-9),α-Smooth muscle aorta(α-SMA),Chemokine(C-X-C motif)ligand 12(CXCL12),Fibronectin,Vimentin,Interleukin-1β(IL-1β),Interleukin-6(IL-6),Interleukin-8(IL-8)]in cells of each group was detected by Western blot analysis,and the influence of exosome miR-3173-5p and FBXW11 expression on CAFs activation was analyzed.Exo and Exo-miR-3173-5P mimic were separated and the supernatant of MRC-5 cells incubated with Exo-FBXW11 was used as conditioned medium(CM)to culture A549 cells.The NC-CM group,Exo-CM group,Exo-miR-3173-5p mimic-CM group and Exo-FBXW11-CM group were set up respectively.MTT assay,Transwell assay and flow cytometry were used to detect the effects of CAFs activation on proliferation,invasion and apoptosis of NSCLC cells.Results Transmission electron microscopy showed that the diameter of exosomal vesicles derived from NSCLC cells was about 30～100 nm.Western blot analysis showed that all exosome labeled proteins were positive.The expression of miR-3173-5p(33.45±3.16)in NSCLC-derived exosomes was significantly higher than that in tumor cells(1.01±0.07),and the difference was statistically significant(t=1.263,P<0.001).MiR-3173-5p targets FBXW11 and inhibits its expression.Compared with NC group,CAFs marker protein levels in Exo group were significantly increased(t=12.214～24.908),the expression of CAFs marker protein in Exo+GW4869 group was significantly inhibited compared with Exo group(t=13.160～25.143),the differences were statistically significant(all P<0.01),respetively.Compared with Exo group,miR-3173-5p inhibitor inhibited EXO-induced CAFs marker protein expression(t=11.059～21.094),and miR-3173-5p mimic promoted the expression of CAFs marker protein(t=12.943～18.671),the differences were statistically significant(all P<0.01),respectively.Overexpression of FBXW11 reversed the induction of CAFs activation by miR-3173-5p mimic.Compared with the NC-CM group,the proliferation activity and invasion rate of A549 cells in the Exo-CM group were significantly enhanced,and the apoptosis rate was significantly inhibited(t=10.207,2.359,3.001),miR-3173-5p mimic enhanced the promoting effect of Exo-CM on proliferation and invasion of A549 cells and the inhibitory effect on apoptosis(t=9.399,3.438,3.208),while overexpression of FBXW11 can antagonize the promotion effect of Exo-CM on proliferation and invasion of A549 cells and the inhibition effect on apoptosis(t=18.868,7.070,9.813),the differences were statistically significant(all P<0.05),respectively.Conclusion Tumor-derived exosome miR-3173-5p promotes CAFs activation through targeted inhibition of FBXW11 expression,further promotes proliferation and invasion of NSCLC cells,inhibits cell apoptosis,and regulates the occurrence and development of NSCLC.

Objective:To examine the preliminary clinical efficacy of Chinese magnetic sphincter augmentation (MSA) in the treatment of gastroesophageal reflux disease (GERD).Methods:According to the enrollment criteria for the MSA developed by ShengJieKang Co. and Shanghai Chest Hospital (SS-MSA) clinical trial, a total of 19 GERD patients were treated with SS-MSA from August 2018 to January 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University. The majority of registered cases were male patients with age of (32.2±7.3) years (range: 22 to 50 years), height of (170.7±6.2) cm (range: 160 to 179 cm) and weight of (65.2±10.3) kg (range: 47.5 to 90.0 kg). SS-MSA was implanted via laparoscopy. The major evaluation indexs of postoperative efficacy were the total time of acid exposure within 24 hours and the total number of reflux. Secondary efficacy indicators included: (1) evaluation of the average daily dose of proton pump inhibitor medications; (2) the score of GERD health related quality of life questionnaire (GERD-Q) before and after MSA implantation. Paired design t-test was used to evaluate the efficacy of the SS-MSA. Results:A total of 19 patients underwent SS-MSA surgery successfully. The history of the GERD were 19 (54) months ( M( QR)). The operation time was 63 (22) minutes and the in-hospital stay was 3 (2) days. No obvious surgical complications occurred. Postoperative adverse events included 14 cases with mild to moderate dysphagia exited after surgery, gradually eased within 1 to 3 months, 1 case with the removal of the device after 1 month of severe swallowing difficulties, 1 case of diarrhea. No corrosion, perforation, displacement occurred. The GERD-Q score (11.0(4.5) vs. 6(1.0), t=4.274, P=0.013), 24-hour acid exposure time (6.2(4.8)% vs. 0.1(0.9)%, t=5.814, P=0.004), and Demeester score (23.72(16.20) vs. 0.96(3.10), t=6.678, P=0.003) were significantly decreased 1 year after surgery( n=5). Proton pump inhibitor reuse rates were 6/18, 5/15, 3/10, and 1/5 in 1, 3, 6 and 12 months after the operation, respectively. Conclusions:SS-MSA implantation is feasible and safe with short hospital stay and rare perioperative complications. The preliminary results is good after 1 year follow-up. It could be expected to be an ideal substitutive for future GERD treatment.

Objective:To examine the preliminary clinical efficacy of Chinese magnetic sphincter augmentation (MSA) in the treatment of gastroesophageal reflux disease (GERD).Methods:According to the enrollment criteria for the MSA developed by ShengJieKang Co. and Shanghai Chest Hospital (SS-MSA) clinical trial, a total of 19 GERD patients were treated with SS-MSA from August 2018 to January 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University. The majority of registered cases were male patients with age of (32.2±7.3) years (range: 22 to 50 years), height of (170.7±6.2) cm (range: 160 to 179 cm) and weight of (65.2±10.3) kg (range: 47.5 to 90.0 kg). SS-MSA was implanted via laparoscopy. The major evaluation indexs of postoperative efficacy were the total time of acid exposure within 24 hours and the total number of reflux. Secondary efficacy indicators included: (1) evaluation of the average daily dose of proton pump inhibitor medications; (2) the score of GERD health related quality of life questionnaire (GERD-Q) before and after MSA implantation. Paired design t-test was used to evaluate the efficacy of the SS-MSA. Results:A total of 19 patients underwent SS-MSA surgery successfully. The history of the GERD were 19 (54) months ( M( QR)). The operation time was 63 (22) minutes and the in-hospital stay was 3 (2) days. No obvious surgical complications occurred. Postoperative adverse events included 14 cases with mild to moderate dysphagia exited after surgery, gradually eased within 1 to 3 months, 1 case with the removal of the device after 1 month of severe swallowing difficulties, 1 case of diarrhea. No corrosion, perforation, displacement occurred. The GERD-Q score (11.0(4.5) vs. 6(1.0), t=4.274, P=0.013), 24-hour acid exposure time (6.2(4.8)% vs. 0.1(0.9)%, t=5.814, P=0.004), and Demeester score (23.72(16.20) vs. 0.96(3.10), t=6.678, P=0.003) were significantly decreased 1 year after surgery( n=5). Proton pump inhibitor reuse rates were 6/18, 5/15, 3/10, and 1/5 in 1, 3, 6 and 12 months after the operation, respectively. Conclusions:SS-MSA implantation is feasible and safe with short hospital stay and rare perioperative complications. The preliminary results is good after 1 year follow-up. It could be expected to be an ideal substitutive for future GERD treatment.

Objective: To evaluate the safety and effectiveness of esophageal replacement with ileocolon graft. Methods: Totally 34 cases of esophageal replacement with ileocolon graft from July 2015 to November 2017 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University were analyzed retrospectively, including 24 male and 10 female, aging from 7 to 72 years old. Esophageal replacement with ileocolon graft by right and/or middle colic artery as a blood supply using retrosternal route except one subcutaneous route. The primary esophageal disease, postoperative complication rate and quality of life were analyzed. Results: The overall postoperative complication rate was 23.5% (8/34), cervical anastomotic leakage rate of 5.9% (2/34), necrosis of colon graft of 5.9% (2/34). There were 3 patients experienced re-operation including 2 patients with colon graft necrosis and 1 patient with intestinal obstruction after ERC. One patient with colon graft necrosis died of septic shock after reoperation. Six cases of cervical esophago-jejunal anastomosis stenosis and 1 case of diarrhea occurred in the later time. All patients were followed up for a median time of 9 months (range: 1 to 28 months), 32 cases survived but 1 patient died until last follow-up by the end of December 2017. Conclusion Esophageal replacement with ileocolon graft by right and/or middle colic artery as a blood supply using retrosternal route was safe and effective.

Objective To assess the effectiveness of the clinical pathway for the treatment of advanced schistosomiasis he-patic fibrosis. Methods The duration of hospital stay,gross hospitalization expense,individual-paid expense,interior diame-ter of portal vein,levels of four serum hepatic fibrosis-related parameters(PIIIP,CIV,HA,and LN),and activities of ALT, AST andγ-GT were assessed and compared between the advanced schistosomiasis patients receiving the clinical pathway and ones receiving non-clinical pathway. Results There were 142 advanced schistosomiasis patients with hepatic fibrosis receiving the clinical pathway of anti-hepatic fibrosis. Compared with the patients receiving non-clinical pathway ,the gross hospitalization expenses reduced by 11.2％(t=6.310,P<0.05),and the individual-paid expenses reduced by 16.1％(t=4.326,P<0.05). The mean HA level was twice higher than the normal range,with a positive rising from 70.4％to 83.1％,and the abnormal rates of CIV andγ-GT were 64.1％and 28.9％respectively. Conclusions The clinical pathway can drastically reduce the treatment expenses in advanced schistosomiasis patients with hepatic fibrosis. However,the patients have a trend towards the persistent disease progression. Therefore,the researches of more effective therapeutic methods for advanced schistosomiasis hepatic fibro-sis are urgently needed.

Objective To investigate our early results of robot-assisted esophagectomy (RAE) and present our learning curve experience with the largest study from one-single institution of China.Methods Between November 2015 and April 2017,a series of consecutive patients undergoing RAE at Shanghai Chest Hospital were reviewed.The patients'demographics,operative and postoperative outcomes were demonstrated.Results A total of 154 patients underwent RAE during the study.All patients received Mckeown esophagectomy and extensive thoraco-abdominal two-field lymph node dissection.Of these,122 were male and 32 were female.The mean total operative duration was 179-445 (271.0 ±61.5) min and the operative duration of the thoracic phase was 51-142 (96.7 ± 27.0)min.The mean estimated blood loss was 100 -1 000 (230.4 ±74.4)ml.The pathological results showed that 150 had squamous cell carcinoma,2 had adenocarcinoma,and 2 had small cell carcinoma.The R0 resection was 92.2％.The mean number of lymph node dissection was 11-64 (20.4 ± 8.5) and the lymph node sampling rate along left and right recurrent laryngeal nerve (RLN) were 92.2％ and 88.3％.The morbidity was present in 64 of 154 patients (41.6％).The major complications rate was anastomotic leak (12.3％),and vocal cord paralysis (16.9％).Intensive care unit (ICU) hospital stay time was 0-27 (2.7 ± 3.6) d,the median length of hospital stay was 7-81 (15.8 ± 11.6)days.There was no 90-day mortality.Conclusions RAE is a safe and feasible alternative for treatment of esophageal cancer.RAE can improve the efficacy of lymph node dissection,especially for the lymphadenectomy along recurrent laryngeal nerve.

Objective To understand the current status of Toxoplasma gondii(TOX)infection among pregnant women and to explore the risk factors in some areas of Lhasa City,Tibet. Methods From 2015 to 2016,3 districts(counties)of Lhasa City were chosen as the investigation sites,and 200 pregnant women in each district(county)were selected as the investigation objectives. Meanwhile,450 pregnant women from Xuzhou,Yangzhou,Wuxi cities in Jiangsu Province were chosen as the con?trol. Then the blood samples of the pregnant women both in Lhasa and Jiangsu were detected by ELISA for TOX antibodies IgG , IgM,and the detection results were analyzed and compared. In addition,the individual information of the pregnant women in Lhasa City was surveyed by questionnaires,and the related risk factors of TOX infection were analyzed. Results Among 600 pregnant women investigated in Lhasa City,there were 99 pregnant women with positive TOX antibodies,and the positive rate was 16.50%,which was significantly higher than that(5.11%)of the pregnant women in Jiangsu Province(P<0.05). There was no statistically significant difference among the 3 districts(counties)of Lhasa City in the positive rates of pregnant women (P>0.05). The positive rates of the women who preferred raw meat or had the intimate contact with animal were high. Conclu?sions Compared with Jiangsu Province,the infection rate of TOX among pregnant women in Lhasa City is high. Therefore,the comprehensive measures including health education,early examination and treatment should be taken actively,so as to prevent and control TOX infection in this area.

Schistosomiasis hematobia is one major human schistosomiasis. The disease is endemic in Africa and Mediterra-nean region,and is the main cause of urogenital diseases. Although only Schistosoma japonicum is spreading across the Main-land China,now more schistosomiasis hematobia cases are reported among aid projects and migrant workers to Africa,with the economy development and the increasing degree of foreign exchanges. Meanwhile,the relevant clinical data of schistosomiasis hematobia are rare in China. This article reviews the clinical manifestations and progress in diagnosis and treatment of the dis-ease.

ObjectiveTo evaluate the efficacy and safety profiles of enteeavir (ETV) in patients with advanced schistosomiasis and hepatitis B virus (HBV) co-infection.Methods Totally sixty patients with advanced schistosomiasis and HBV co-infection were enrolled in this study.The patients were divided into ETV treatment group (n=30) and rhubarb treatment group who refused to receive antiviral treatment (n=30).The patients were treated with ETV or rhubarb thelepus ball on the basis of routine supportive therapy for 52 weeks.The hepatic fibrosis markers (e.g.hyaluronic acid,type Ⅲ procollagen,type Ⅳ collagen,laminin and fibronectin),alanine transaminase (ALT),HBV DNA,Child-Pugh score between two groups were compared.Intention to treat (ITT) population was used for analysis.The measurement data and the enumeration data were analyzed by t test and x2 test,respectively.ResultsAfter 52-week treatment,the hepatic fibrosis markers (hyaluronic acid,type Ⅲ procollagen,type Ⅳ collagen,laminin and fibronectin) were significantly improved in ETV treatment group compared to the rhubarb treatment group (t =3.952,3.765,3.857,3.122 and 3.735,respectively; all P＜0.05),and the fibrosis of liver tissue in ETV treatment group was significantly improved compared with rhubarb treatment group (x2 =11.207,P＜0.05).The ALT level,HBV DNA,Child-Pugh score after 52-weeks treatment in ETV treatment group were statistically reduced compared with rhubarb treatment group (t =3.287,4.382 and 3.872,respectively; all P＜0.05),meanwhile,the ALT normalization rate and HBV DNA undetectable rate were significantly increased in ETV treatment group (x2 =17.376 and 39.095,respectively; both P＜0.05).In addition,no obvious adverse reaction was observed during ETV treatment.Conclusion Entecavir is safe and effective in patients with advanced schistosomiasis and HBV co-infection.