[Synthesis of colon-specific prodrug of indomethacin and its inhibitory effect on liver metastasis from colon cancer].

OBJECTIVE: To develop a colon-specific prodrug of Indomethacin microbially triggered, carry out in vitro/in vivo evaluation of drug release, and appraise its inhibitory effect on liver metastasis from colon cancer. METHODS: Indomethacin prodrugs were synthesized and characterized by FTIR and NMR, and dissolution test simulating gastrointestinal tract was employed to screen the colon-specific prodrug. Then, the pharmacokinetic profile of portal vein and peripheral blood in Sprague-Dawley rats was studied. Lastly, the inhibitory effect on liver metastasis from colon cancer in nude mice was observed. RESULTS: The chemical structure characterized by FTIR and NMR demonstrated that six kinds of indomethacin-block-amylose with different drug loading (IDM-AM-1-6) were synthesized, among which IDM-AM-3 was degraded 1.3%, 9.3% and 95.3%, respectively, in simulated gastric fluid for 4 h, small intestine for 6 h, and colon for 36 h. The pharmacokinetic test of IDM-AM-3 showed that absorption was delayed significantly (P < 0.01), peak time [(11.35 + or - 2.45) h], elimination half-life [(16.74 + or - 4.04) h] and mean residence time [(22.27 + or - 0.52) h] were significantly prolonged (P < 0.01), as well as peak serum concentrations [(9.69 + or - 2.40) mg/L] and AUC(0-t) [(236.7 + or - 13.1) mg x L(-1) x h] were decreased markedly (P < 0.01) as compared with those of IDM regarding to portal vein. Additionally, its AUC(0-t) in peripheral blood was remarkably lower than that in Portal vein (P < 0.01). The tumor suppression observation showed that it could remarkably reduce the number of liver metastases in contrast to IDM (P < 0.05). CONCLUSION: Colon-specific IDM-AM-3 possesses advantage of sustained release in portal vein providing some experimental basis for colon-specific delivery system applied to sustained release in the portal vein.

[Meta-analysis of suture techniques for midline abdominal incisions].

OBJECTIVE: To evaluate the safety and efficacy of suture techniques for midline abdominal incisions with systematic review and meta-analysis. METHODS: The articles about suture techniques for midline abdominal incisions published from year of 1981 to 2009 in MedLine and Embase databases were retrieved. All the trials with a minimal follow-up of one year that randomized patients for midline laparotomy with different suture techniques and/or suture materials were subjected to meta-analysis. The outcomes included incisional hernia, wound dehiscence, wound infection and suture sinus formation. RESULTS: Total of 13 articles were collected in this analysis. Compared with continuous sutures, interrupted sutures had significantly more incisional hernias (OR = 0.80, 95%CI: 0.66 - 1.00;P = 0.05). Continuous rapidly absorbable suture was associated with significantly more incisional hernias than continuous slowly absorbable suture or continuous non-absorbable suture (15.8%, 10.0% and 8.3%, respectively; P < 0.05). More suture sinuses occurred in patients with continuous non-absorbable suture than in those with continuous rapidly absorbable suture (5.6% vs. 1.0%, P < 0.05); And more suture sinuses occurred in patients with interrupted non-absorbable suture than in those with interrupted rapidly absorbable suture (8.8% vs. 0, P < 0.05). Compared with continuous slowly absorbable suture, more suture sinuses occurred in patients with continuous non-absorbable suture (OR = 0.47, 95%CI: 0.24 - 0.92; P < 0.05). Less incisional hernias occurred in patients with a suture length/wound length ratio (SL/WL) of ≥ 4:1 than those with the ratio less than 4:1 (P < 0.05). CONCLUSION: To reduce the incidence of incisional hernia without increasing wound infection frequency, the ideal suture technique is mass closure using a continuous suture, with an adequate suture length/wound length ratio no less than 4:1, the suture materials should be slowly absorbable.

[Open total extraperitoneal herniorrhaphy for inguinal hernia via a ventral midline incision].

OBJECTIVE: To discuss the operation skills and evaluate the effects of open total extraperitoneal herniorrhaphy for inguinal hernia via a ventral midline incision. METHODS: From June 2008 to December 2009, 106 patients with inguinal hernia received open total extraperitoneal herniorrhaphy via a ventral midline incision, the clinical data were analyzed retrospectively. RESULTS: Of the patients, 86 cases were male, 20 were female, the mean age was 60.2 years (range, 21 - 86 years). The mean operation time was (32.6 ± 10.5) minutes. The postoperative hospital stay was (2.3 ± 0.7) days. Intra-operative peritoneal perforation occurred in 2 cases. Four cases experienced urine retention and seroma happened in 2 cases, 6 cases suffered early surgical-site pain, and all of the complications were cured with conservative treatment. Three cases developed scrotal hydrocele. No neuralgia or incisional infection occurred in this group. During a 3- to 22-months follow-up period (mean, 10.2 months), no patient complained of discomfort or foreign body sensation in the inguinal area. Two cases recurred 2 and 11 months after the surgery, respectively; the recurrence rate was 1.9%, the two patients healed after reoperation. CONCLUSIONS: Open total extraperitoneal herniorrhaphy operation via a ventral midline incision is a safe, effective and convenient technique for inguinal hernia with few postoperative complications. This method is worth popularizing.

A study on the design methodology of TAC3 for edge computing.

The following scenarios, such as complex application requirements, ZB (Zettabyte) order of magnitude of network data, and tens of billions of connected devices, pose serious challenges to the capabilities and security of the three pillars of ICT: Computing, network, and storage. Edge computing came into being. Following the design methodology of "description-synthesis-simulation-optimization", TAC3 (Tile-Architecture Cluster Computing Core) was proposed as the lightweight accelerated ECN (Edge Computing Node). ECN with a Tile-Architecture be designed and simulated through the method of executable description specification and polymorphous parallelism DSE (Design Space Exploration). By reasonable configuration of the edge computing environment and constant optimization of typical application scenarios, such as convolutional neural network and processing of image and graphic, we can meet the challenges of network bandwidth, end-cloud delay and privacy security brought by massive data of the IoE. The philosophy of "Edge-Cloud complements each other, and Edge-AI energizes each other" will become a new generation of IoE behavior principle.

Preoperative evaluation with T-staging system for hilar cholangiocarcinoma.

AIM: To investigate the clinical value of T-staging system in the preoperative assessment of hilar cholangiocarcinoma. METHODS: From March 1993 to January 2006, 85 patients who had cholangiocarcinoma diagnosed by operative tissue-biopsy were placed into one of three stages based on the new T-staging system, and it was evaluated the resectability and survival correlated with T-staging. RESULTS: The likelihood of resection and achieving tumor-free margin decreased progressively with increasing T stage (P < 0.05). The cumulative 1-year survival rates of T1, T2 and T3 patients were 71.8%, 50.8% and 12.9% respectively, and the cumulative 3-year survival rate was 34.4%, 18.2% and 0% respectively; the survival of different stage patients differed markedly (P < 0.001). Median survival in the hepatic resection group was greater than in the group that did not undergo hepatic resection (28 mo vs 18 mo; P < 0.05). The overall accuracy for combined MRCP and color Doppler Ultrasonagraphy detecting disease was higher than that of combined using CT and color Doppler Ultrasonagraphy (91.4% vs 68%; P < 0.05 ). And it was also higher in detecting port vein involvement (90% vs 54.5%; P < 0.05). CONCLUSION: The proposed staging system for hilar cholangiocarcinoma can accurately predict resectability, the likelihood of metastatic disease, and survival. A concomitant partial hepatectomy would help to attain curative resection and the possibility of long-term survival. MRCP/MRA coupled with color Doppler Ultrasonagraphy was necessary for preoperative evaluation of hilar cholangiocarcinoma.

MicroRNA-520c enhances cell proliferation, migration, and invasion by suppressing IRF2 in gastric cancer.

Dysregulation of microRNA (miRNA) is actively involved in the development and progression of gastric cancer (GC). MiR-520c was previously found to be overexpressed in GC specimens and cells. However, the clinical significance of miR-520c and its biological function in GC remain largely unknown. Here, we found that miR-520c expression in GC tissues was significantly increased compared to normal adjacent gastric tissues. Its increased level was prominently correlated with poor clinical parameters and prognosis of GC patients. Accordingly, the expression of miR-520c was obviously elevated in GC cell lines as compared with gastric epithelial cells. Overexpression of miR-520c in N-87 cells significantly increased the proliferative ability, migration, and invasion of cancer cells, while miR-520c silencing suppressed MKN-45 cell proliferation, migration, and invasion in vitro. Mechanically, miR-520c inversely regulated interferon regulatory factor 2 (IRF2) abundance in GC cells. Herein, IRF2 was found to be a downstream target of miR-520c in GC. Furthermore, IRF2 was down-regulated in GC tissues compared to nontumor tissues. An inverse correlation between IRF2 and miR-520c expression was observed in GC cases. Taken together, miR-520c may serve as a prognostic predictor and a therapeutic target for GC patients.

Functional and morphological changes of the gut barrier during the restitution process after hemorrhagic shock.

AIM: To investigate the functional, morphological changes of the gut barrier during the restitution process after hemorrhagic shock, and the regional differences of the large intestine and small intestine in response to ischemia/reperfusion injury. METHODS: Forty-seven Sprague-Dawley rats with body weight of 250-300 g were divided into two groups: control group (sham shock n = 5) and experimental group (n = 42). Experimental group was further divided into six groups (n = 7 each) according to different time points after the hemorrhagic shock, including 0(th) h group, 1st h group, 3rd h group, 6th h group, 12th h group and 24th h group. All the rats were gavaged with 2 mL of suspension of lactulose (L) (100 mg/2 mL) and mannitol (M) (50 mg/each) at the beginning and then an experimental rat model of hemorrhagic shock was set up. The specimens from jejunum, ileum and colon tissues and the blood samples from the portal vein were taken at 0, 1, 3, 6, 12 and 24 h after shock resuscitation, respectively. The morphological changes of the intestinal mucosa, including the histology of intestinal mucosa, the thickness of mucosa, the height of villi, the index of mucosal damage and the numbers of goblet cells, were determined by light microscope and/or electron microscope. The concentrations of the bacterial endotoxin lipopolysaccharides (LPS) from the portal vein blood, which reflected the gut barrier function, were examined by using Limulus test. At the same time point, to evaluate intestinal permeability, all urine was collected and the concentrations of the metabolically inactive markers such as L and M in urine were measured by using GC-9A gas chromatographic instrument. RESULTS: After the hemorrhagic shock, the mucosal epithelial injury was obvious in small intestine even at the 0(th) h, and it became more serious at the 1st and the 3rd h. The tissue restitution was also found after 3 h, though the injury was still serious. Most of the injured mucosal restitution was established after 6 h and completed in 24 h. Two distinct models of cell death-apoptosis and necrosis-were involved in the destruction of rat intestinal epithelial cells. The number of goblet cells on intestinal mucosa was reduced significantly from 0 to 24 h (the number from 243+/-13 to 157+/-9 for ileum, 310+/-19 to 248+/-18 for colon; r = -0.910 and -0.437 respectively, all P<0.001), which was the same with the large intestine, but the grade of injury was lighter with the values of mucosal damage index in 3 h for jejunum, ileum, and colon being 2.8, 2.6, 1.2, respectively. The mucosal thickness and the height of villi in jejunum and ileum diminished in 1 h (the average height decreased from 309+/-24 to 204+/-23 microm and 271+/-31 to 231+/-28 microm, r = -0.758 and -0.659, all P<0.001; the thickness from 547+/-23 to 418+/-28 microm and 483+/-45 to 364+/-35 microm, r = -0.898 and -0.829, all P<0.001), but there was no statistical difference in the colon (F = 0.296, P = 0.934). Compared with control group, the urine L/M ratio and the blood LPS concentration in the experimental groups raised significantly, reaching the peak in 3-6 h (L/M: control vs 3 h vs 6 h was 0.029+/-0.09 vs 0.063+/-0.012 vs 0.078+/-0.021, r = -0.786, P<0.001; LPS: control vs 3 h vs 6 h was 0.09+/-0.021 vs 0.063+/-0.012 vs 0.25+/-0.023, r = -0.623, P<0.001), and it kept increasing in 24 h. CONCLUSION: The gut barrier of the rats was seriously damaged at the early phase of ischemic reperfusion injury after hemorrhagic shock, which included the injury and atrophy in intestinal mucosa and the increasing of intestinal permeability. Simultaneously, the intestinal mucosa also showed its great repairing potentiality, such as the improvement of the intestinal permeability and the recovery of the morphology at different phases after ischemic reperfusion injury. The restitution of gut barrier function was obviously slower than that of the morphology and there was no direct correlation between them. Compared with the small intestine, the large intestine had stronger potentiality against injury. The reduction of the amount of intestinal goblet cells by injury did not influence the ability of intestinal mucosal restitution at a certain extent and it appeared to be intimately involved in the restitution of the epithelium.

Long-term outcome for open preperitoneal mesh repair of recurrent inguinal hernia.

AIM: Recurrent inguinal hernia represents a major challenge for surgeons with high risks of re-recurrence and complications, especially when an anterior approach is adopted. The aim of this study was to evaluate the long-term results of the open preperitoneal mesh repair for recurrent inguinal hernia. METHODS: We performed a prospective clinical study of 107 consecutive patients having recurrent inguinal hernias between April 2006 and November 2010. All patients were operated on using open preperitoneal mesh repair. The demographics, perioperative variables, complications and recurrences were evaluated with all patients. RESULTS: There were no major intraoperative complications. The average operative time was 42.1 min (range 28-83 min) for unilateral and 62.7 min (range 38-106 min) for bilateral hernias. The mean postoperative hospital stay was 1.6 days (range 1-9 days). The overall complication rate was 8.4%. There were two superficial wound infections, two groin seroma and three urinary retention. The mean follow-up time was 42.3 months (range 28-73 months), three patients developed hernia recurrence. No testicular, chronic pain or mesh-related complications were noted in these series. CONCLUSION: Open posterior preperitoneal mesh repair offers a viable option for recurrent inguinal hernias and achieves equally effective results to laparoscopic approaches with acceptable complication and recurrence rates. It is safer and easier to learn than laparoscopic repair and has become the preferred approach for treatment of the majority of recurrent inguinal hernias at our institution, especially useful for complex multirecurrent hernias and patients with cardiopulmonary insufficiency.

Reconstruction of abdominal wall defects using small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor.

PURPOSE: To construct a new biomaterial-small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor, and to evaluate the new biomaterials for the reconstruction of abdominal wall defects. METHODS: Thirty six Sprague-Dawley rats were used in the animal experiments and randomly divided into three groups. The new biomaterial was constructed by combining small intestinal submucosa with gelatin hydrogel for basic fibroblast growth factor release. Abdominal wall defects were created in rats, and repaired using the new biomaterials (group B), compared with small intestinal submucosa (group S) and ULTRAPROTM mesh (group P). Six rats in each group were sacrificed at three and eight weeks postoperatively to examine the gross effects, inflammatory responses, collagen deposition and neovascularization. RESULTS: After implantation, mild adhesion was caused in groups B and S. Group B promoted more neovascularization than group S at three weeks after implantation, and induced significantly more amount of collagen deposition and better collagen organization than groups S and P at eight weeks after implantation. CONCLUSION: Small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor could promote better regeneration and remodeling of host tissues for the reconstruction of abdominal wall defects.

Variations of urinary bladder and the urogenital fatty fascial compartment with different filling of the bladder are notable factors relevant to hernia repair-related bladder injury.

The present study investigated bladder and urogenital fatty fascial compartment (UFFC) variations during bladder filling in an attempt to identify other possible causes of hernia repair-related bladder injury besides mesh migration. The study included 30 patients scheduled for abdominal computed tomography (CT) scan for nonhernia diseases. Sixty-four-slice CT scan was performed immediately after urination and no more than 30 minutes later. Three-dimensional images were constructed by two independent experienced readers. The empty bladder was triangular in shape, narrow in the front and broad in the rear. Its vertex deviated from midline of the abdominal wall in 11 cases (36.7%).With normal filling, it appeared as an irregular oval shape. Only two cases (6.7%) of empty bladder extended inside Hesselbach's triangle. However, this area was occupied to some extent in all cases during bladder filling (P = 0.003). The UFFC formed a molar-like structure in cross-section. In three dimensions, it appeared as an inverted V-shaped structure from the front. In the lateral view it appeared as a spoon that contained the bladder. UFFC volume increased from 61.85 ± 6.23 to 139.23 ± 5.29 cm(3) with bladder filling (P < 0.0001). The UFFC can be clearly identified by CT scanning or three-dimensional reconstruction. The considerable spatial variation of the UFFC and movement and deformation of the mesh within this area may be related to bladder injury.

Repair of damaged intestinal mucosa in a mouse model of sepsis.

BACKGROUND: The intestine is not only the main target attacked by sepsis but also the vital organ which mediated sepsis. The recovery of the damaged intestinal barrier structure and function is related to the occurrence and outcome of multiple organ dysfunction syndrome (MODS). How to protect and reduce the damage of the intestinal mucosa and how to promote the reconstruction of the intestinal mucosa have been the important topics in sepsis for many years. This study aimed to investigate the influential factors of intestinal mucosal reconstruction after intestinal epithelial injury in vivo in a mouse model of sepsis. METHODS: Mice were subjected to cecal ligation and puncture (CLP) for induction of sepsis to assess intestinal mucosal damage, epithelial cell apoptosis, and transformed number of goblet cells, and to detect the concentration of TNF-α, IL-1 and TGF-ß1 and TFF3 (trefoil factor 3) expression in the small intestinal mucosa. All above were performed by HE staining, western blot, ELISA and immunohistochemistry respectively. The experimental animals were divided into a sepsis group and a sham-operation group. The animals with sepsis were separately killed at 6 (7 animals), 24 (7 animals) and 48 hours (7 animals) after CLP. RESULTS: Injured intestinal mucosa was observed in the 3 groups under a light microscope, in which damage scores in the 24-hour and 48-hour groups were higher than in the 6-hour group and no difference was found between the two groups. Moreover, less of goblet cells or other epithelial cells adjacent to the injured surface migrated into the wound to cover the denuded area. The number of goblet cells was substantially decreased in the three CLP groups compared with the sham-operation group. Protein levels of IL-1 and TNF-α were significantly increased by 3-4 fold at all time points when compared with the sham-operation group, and cleaved caspase-3 by 4 fold. Although TFF3 expression was modestly increased for 6 hours after the onset of CLP, it appeared to decline at 24 hours and 48 hours as shown by Western blot. A similar tendency was observed upon TGF-ß1, i.e. the protein level was not elevated at 24 hours and 48 hours, but increased modestly at 6 hours. CONCLUSIONS: Sepsis from CLP shows less restitution on the surface of injured intestinal mucosa. There is evidence that both constant inflammatory reaction and epithelial cell apoptosis may affect mucosal reestablishment of the intestine at the onset of sepsis. Mucosa after severe sepsis showed the state of high inflammation, and declined goblet cell function and mucosal reconstruction, which affected the repair of damaged intestinal barrier. Constant inflammatory reaction, and declined goblet cell function and mucosal reconstruction ability may affect the reestablishment of intestinal mucosa at the onset of sepsis.

Reconstruction of abdominal wall defects using small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor

To construct a new biomaterial-small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor, and to evaluate the new biomaterials for the reconstruction of abdominal wall defects. Thirty six Sprague-Dawley rats were used in the animal experiments and randomly divided into three groups. The new biomaterial was constructed by combining small intestinal submucosa with gelatin hydrogel for basic fibroblast growth factor release. Abdominal wall defects were created in rats, and repaired using the new biomaterials (group B), compared with small intestinal submucosa (group S) and ULTRAPROTM mesh (group P). Six rats in each group were sacrificed at three and eight weeks postoperatively to examine the gross effects, inflammatory responses, collagen deposition and neovascularization. After implantation, mild adhesion was caused in groups B and S. Group B promoted more neovascularization than group S at three weeks after implantation, and induced significantly more amount of collagen deposition and better collagen organization than groups S and P at eight weeks after implantation. Small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor could promote better regeneration and remodeling of host tissues for the reconstruction of abdominal wall defects.