Necroptosis, a form of programmed cell death, initiates a series of biological responses and further culminates in necroinflammatory processes, consequently limiting the efficacy of cytokine antagonists in treating inflammatory diseases. To address this issue, DNAzyme R3-Dz specifically targeting receptor-interacting protein kinase 3 (RIP3) mRNA, a necrosome component, has been successfully developed and studied to elucidate the mechanism in cleaving its target mRNA. Then a polyamidoamine (PAMAM) derivative was constructed through the modification of nucleobase analog (termed AP) to achieve the R3-Dz delivery to macrophages. The AP/R3-Dz nanoparticles effectively downregulated the RIP3 expression, leading to subsequent decrease in the levels of reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs), ultimately inhibiting the necroinflammatory processes mediated by the NOD-like receptor family pyrin domain-containing 3 (NLRP3). Finally, AP/R3-Dz nanoparticles and their combination with the NLRP3 inhibitor MCC950 suppressed the necrotic phenotype and ameliorated the disease progression in diverse models, including gouty arthritis, autoimmune hepatitis and rheumatoid arthritis. In summary, the AP/R3-Dz nanoparticles in combination with MCC950 have been demonstrated to achieve the intervention in necroptosis and inflammation by dual disruption of the intricate feedback loop of necroinflammation and thus have promising potential in the treatment of inflammatory diseases.

OBJECTIVETo investigate the feasibility and efficacy of laparoscopic subtotal colectomy and modified Duhamel procedure combined with transanal endoscopic microsurgery (TEM) in the treatment of severe functional constipation(SFC).

METHODSThe clinical data of 10 patients with SFC treated by laparoscopic surgery combined with TEM between May 2010 and October 2012 in Ruijin Hospital of Shanghai Jiaotong University School of Medicine were retrospectively analyzed. The gastrointestinal quality of life index(GIQLI), Wexner constipation scale and daily frequency of defecation postoperatively during follow-up were collected.

RESULTSAll the 10 operations were successfully accomplished laparoscopic subtotal colectomy combined with TEM without abdominal incision. There was no conversion to open procedure. One case had preventive terminal ileum stoma. The mean operative time was (256 ± 58) min. The mean blood loss was (178 ± 67) ml. The mean time to first flatus was (40 ± 11) h. There were no ureteric injury, anastomotic leak, pelvic sepsis and other complications postoperatively. There was one case of insufficient small bowel obstruction which was released by conservative treatments. The patients were discharged from the hospital in (9.0 ± 1.5) d postoperatively. The GIQLI in one year postoperatively was (112 ± 10) points, which indicated good results compared to (75 ± 12) points preoperatively (P=0.000). The Wexner constipation scale was 20.8 ± 2.2 preoperatively and decreased to 5.2 ± 1.8 at one year follow-up(P=0.000).

CONCLUSIONLaparoscopic subtotal colectomy and modified Duhamel procedure combined with TEM provides SFC patients a safe and feasible minimally invasive surgery.

China ; Colonic Diseases ; surgery ; Colorectal Surgery ; Constipation ; surgery ; Defecation ; Humans ; Laparoscopy ; Microsurgery ; Minimally Invasive Surgical Procedures ; Postoperative Complications ; Quality of Life ; Rectal Diseases ; surgery ; Retrospective Studies

Objective To investigate the feasibility and efficacy of laparoscopic subtotal colectomy and modified Duhamel procedure combined with transanal endoscopic microsurgery (TEM) in the treatment of severe functional constipation (SFC). Methods The clinical data of 10 patients with SFC treated by laparoscopic surgery combined with TEM between May 2010 and October 2012 in Ruijin Hospital of Shanghai Jiaotong University School of Medicine were retrospectively analyzed. The gastrointestinal quality of life index (GIQLI), Wexner constipation scale and daily frequency of defecation postoperatively during follow-up were collected. Results All the 10 operations were successfully accomplished laparoscopic subtotal colectomy combined with TEM without abdominal incision. There was no conversion to open procedure. One case had preventive terminal ileum stoma. The mean operative time was (256±58) min. The mean blood loss was (178±67) ml. The mean time to first flatus was (40 ±11) h. There were no ureteric injury, anastomotic leak, pelvic sepsis and other complications postoperatively. There was one case of insufficient small bowel obstruction which was released by conservative treatments. The patients were discharged from the hospital in (9.0 ±1.5) d postoperatively. The GIQLI in one year postoperatively was (112 ±10) points, which indicated good results compared to (75 ±12) points preoperatively (P=0.000). The Wexner constipation scale was 20.8 ±2.2 preoperatively and decreased to 5.2 ±1.8 at one year follow-up (P=0.000). Conclusion Laparoscopic subtotal colectomy and modified Duhamel procedure combined with TEM provides SFC patients a safe and feasible minimally invasive surgery.

Objective To investigate the feasibility and efficacy of laparoscopic subtotal colectomy and modified Duhamel procedure combined with transanal endoscopic microsurgery (TEM) in the treatment of severe functional constipation (SFC). Methods The clinical data of 10 patients with SFC treated by laparoscopic surgery combined with TEM between May 2010 and October 2012 in Ruijin Hospital of Shanghai Jiaotong University School of Medicine were retrospectively analyzed. The gastrointestinal quality of life index (GIQLI), Wexner constipation scale and daily frequency of defecation postoperatively during follow-up were collected. Results All the 10 operations were successfully accomplished laparoscopic subtotal colectomy combined with TEM without abdominal incision. There was no conversion to open procedure. One case had preventive terminal ileum stoma. The mean operative time was (256±58) min. The mean blood loss was (178±67) ml. The mean time to first flatus was (40 ±11) h. There were no ureteric injury, anastomotic leak, pelvic sepsis and other complications postoperatively. There was one case of insufficient small bowel obstruction which was released by conservative treatments. The patients were discharged from the hospital in (9.0 ±1.5) d postoperatively. The GIQLI in one year postoperatively was (112 ±10) points, which indicated good results compared to (75 ±12) points preoperatively (P=0.000). The Wexner constipation scale was 20.8 ±2.2 preoperatively and decreased to 5.2 ±1.8 at one year follow-up (P=0.000). Conclusion Laparoscopic subtotal colectomy and modified Duhamel procedure combined with TEM provides SFC patients a safe and feasible minimally invasive surgery.

Objective To investigate the apoptosis of rat glioma C 6 cells induced by defective in-terfering( DI) particles of Sendai virus strain Tianjin .Methods Rat glioma C6 cells were treated with dif-ferent titers of DI particles of Sendai virus strain Tianjin in vitro with culture media as negative control and intact virus as positive control .At different time point , cells were collected and their apoptosis was detected by DNA gel electrophorsis , TUNEL assay and AnnexinⅤ/PI double-labeled flow cytometry .The C6 glioma-bearing rat model was established and then treated with three intratumoral injections of DI particles , intact virus or saline three times at interval of two days .The antitumor effects of ID particles were evaluated through daily measuring of the tumor size .Hematoxylin-eosin( HE) staining was used to observe the patho-logical changes in tumor tissues .TUNEL assay was performed to detect the apoptosis of tumor tissues .Re-sults Rat glioma C6 cells treated with DI particles or intact virus in vitro showed typical DNA ladder pattern in agarose gel electrophoresis in a time-and dose-dependent manner .With the intervention of DI particles , the apoptosis rate of C6 cells showed a time-and dose-dependent manner and was significantly higher than that of the control group (P<0.01) as indicated by flow cytometry assay and TUNEL assay .In vivo, DI par-ticles could markedly inhibit the growth of the tumors in comparison with saline control group .There were fe-wer tumor cells in tumor nodules in DI particles group or intact virus group as shown by histological examina -tion.The TUNEL assay showed that the apoptosis rate of tumor tissues injected with DI particles or intact vi -rus was much higher than that of the saline group (P<0.01), but there was no significant difference between the DI particles group and the intact virus group (P>0.05).Conclusion The DI particles of Sendai virus strain Tianjin could induce apoptosis of rat glioma C 6 cells in a time-and dose-dependent manner both in vitro and in vivo, suggesting that the DI particles might be applicable for the treatment of neurogliocytoma in the future.

Objective To evaluate the long-term therapeutic results of intersphincteric resection (ISR) in the treatment of ultra-low rectal cancer.Methods Sixty cases of ultra-low rectal cancer with the inferior border of the tumor within 5 cm to the edge of anus underwent intersphincteric resection (ISR),and the clinical data were analyzed retrospectively.There were 39 males,21 females and their average age was 55 years old (range from 30 to 77 years old).The inferior border of the tumor were from 28 to 50 mm to the edge of anus,averaging 42 mm.Results Sixty patients underwent intersphincteric resection successfully with 3 cases developing anastomotic leakage and 2 cases anastomotic stenosis postoperatively.After a median follow-up period of 49 months (range from 18 to 90 months),local and distant recurrence were observed in 6 and 4 patients respectively.Five-year overall survival rate and disease-free survival rate were 88.3％ and 83.3％ respectively.The mean stool frequency were (3.8 ± 1.3) times in each day based on data from 53 patients,and the stool control function of 73.6％ of all patients was preserved satisfactorily according to Kirwan classification.Conclusions This study indicated that intersphincteric resection might be a candidate technique in the treatment of early stage ultra-low rectal cancer restricted within rectal wall and could achieve satisfactory long-term results in both oncologic and functional respects.

Objective To evaluate the long-term functional outcome after ileal pouch anal anastomosis with modified double-stapled technique.Methods From January 2002 to March 2011,forty-five patients underwent ileal pouch anal anastomosis with modified double-stapled technique.The clinical data of these patients were reviewed.The postoperative anal function was assessed by Kirwan classification and Oresland pouch-specific function score.Results During the median follow-up of 65 months,2 patients with malignant adenomatous polyps died,2 patients were diagnosed dysplasia by biopsy,4 patients developed mild to moderate anastomotic narrowing,1 patient developed persistent anastomotic stricture needing surgical intervention,16 patients developed at least 1 episode of pouchitis.There was no incontinence in these patients,and the median functional Oresland score was 6,3 and 2 after 1 year,2.5 years and 5 years respectively.Conclusion The functional results of ileal pouch anal anastomosis with modified double-stapled technique are promising,with no incontinence in our patients.

Objective To compare the application,safety and theraputic effect of local resection of early rectal tumours by transanal endoscopic microsurgery(TEM) and the conventional transanal excision(TAE).Methods The data of seventy-six patients who were treated by conventional transanal excision from January 2003 to July 2006 and fifty-three patients who were treated by transanal endoscopic microsurgery from September 2006 to February 2010 in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were reviewed.Results Age,sex,tumour size,blood loss,postoperative hospital stay were similar in the two groups(P＞0.05).The median distance from the anal verge was significantly higher in the TEM group ( TEM/TAE =7.0/5.0 cm,P ＜ 0.01 ).The operation time was significantly longer in the TEM group (TEM/TAE =70.00/30.00 min,P ＜ 0.01 ).There was no operation-related mortality in both groups (P ＞ 0.05 ).Two patients in the TEM group developed postoperative haemorrhage,and one patient developed pulmonary infection and retention of urine respectively.There were two secondary haemorrhage cases in the TAE group.On median follow-up of 30 months,there was 7.8％ recurrence rate in the TEM group,compared with 23.2％ the in TAE group.Conclusions Transanal endoscopic microsurgery is a safe and effective mininally invasive surgical technique for the treatment of early rectal neoplasm.It has broader indication,and better theraputic effect than the conventional transanal excision.

Objective To elucidate the evaluation of therapeutic effects and surgical treatments of 45 cases of inflammatory bowel disease. Methods Clinical data of 45 cases with inflammatory bowel disease by surgical treatment in recent 6 years were retrospectively analyzed. Results Patients received emergency operation in 16 cases, Crohn' s disease in 9 cases, Ulcerative Colitis( UC) in 7 cases. Among 13 cases of Crohn' s disease, partial enterectomy occured in 6 cases, partial enterectomy and colectomy and anastomosis in 1 patient because of internal fistula, repair of ileal perforation in 1 case, laparoscopic ileocolic resection in 5 cases. Among 32 cases of UC, 25 cases underwent ileal pouch-anal anastomosis operation, 3 cases underwent ileostomy with total colectomy, and 4 cases only underwent ileostomy. Twenty- seven cases were cured by operation, 14 cases were improved and 4 cases died. Conclusion It is the key point to achieve successful operation that the corresponding operative modes for varied manifestations of inflammatory bowel disease should be adopted.