Human adipose-derived mesenchymal stem cells and synovial-derived mesenchymal stem cells synergistically inhibit the degeneration of inflammatory chondrocytes / 中国组织工程研究

BACKGROUND: Intra-articular injection of cells targeting to change the microenvironment in lesions can act on early osteoarthritis of inflammatory chondrocytes. Implanted cells affect the progress of the disease by the cell characteristics. OBJECTIVE: To explore the synergistic effect of mesenchymal stem cells from human knee adipose (ADMSCs) and synovial tissues (SDMSCs) to inhibit the degeneration of inflammatory chondrocytes. METHODS: ADMSCs, SDMSCs and inflammatory chondrocytes were primary cultured. Under in vitro two-dimensional culture conditions, cell proliferation assay (MTS) was performed to detect the proliferation of three kinds of cells. Differences in chondrogenic markers at mRNA and protein levels between three kinds of adherent cells were detected by quantitative PCR and immunofluorescence. Under in vitro three-dimensional mixed culture conditions, three groups were set up: (1) ADMSCs+inflammatory chondrocytes (A+C group), (2) SDMSCs+inflammatory chondrocytes (S+C group), and (3) ADMSCs-SDMSCs+inflammatory chondrocytes (A+S+C group). Alcian blue staining, safranin O staining and type Ⅱ collagen immunohistochemistry staining were performed on the mixed-cultured cell mass paraffin sections followed by quantitative analysis. Chondrogenic differentiation in each group was detected by quantitative PCR. Culture supernatants were collected to detect the secretion of pro-inflammatory and anti-inflammatory factors by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION: Under the two-dimensional culture, the proliferative rate of ADMSCs was significantly higher than that of inflammatory chondrocytes and SDMSCs (P < 0.05). The expression of type Ⅱ collagen mRNA and protein and proteoglycan protein in inflammatory chondrocytes was significantly higher than that in the other two kinds of cells (P < 0.01). Under the three-dimensional culture, the percentage of chondrogenic area per total area was significantly higher in the A+S+C group than the S+C and A+C groups (P < 0.05). The expression of type Ⅱ collagen and proteoglycan was significantly higher in the A+S+C group than the S+C and A+C groups (P < 0.05). Compared with the other two groups, the S+C group showed higher levels of interleukin 1, interleukin 6, and tumor necrosis factor α, but lower level of interleukin 10 (P < 0.05). To conclude, the combined use of ADMSCs and SDMSCs synergistically inhibits the degeneration of inflammatory chondrocytes.

Research Progress of Anti-allergy Natural Products / 中国药学杂志

Based on overseas and domestic data bank mainly as Scifinder, ACS publication, CNKI, and CQVIP. The relationships between the types of natural products and their anti-allergic activities have been summarized. The advances of anti-allergic natural products over the past ten years have been reviewed. The pathogenesis of allergic diseases and the diversity of anti-allergy components and natural products were summarized, together with their origins and mechanisms of anti-allergy activities. Many natural products show multiple anti-allergy targets and few side effects, while the research is still far from enough. Several suggestions were proposed for further research on anti-allergy natural medicines on the basis of our review.

Risk factors of early surgical intervention in Crohn's disease patients with spontaneous intra-abdominal abscess / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the risk factors of early surgical intervention in Crohn's disease (CD) patients with spontaneous intra-abdominal abscess.</p><p><b>METHODS</b>Clinical data of 94 CD patients with spontaneous intra-abdominal abscess admitted to The Sixth Affiliated Hospital of Sun Yat-sen University between May 2008 and Dec 2015 were analyzed retrospectively. Univariate and multivariate analysis were applied to evaluate the early surgery risk of CD patients with spontaneous intra-abdominal abscess using logistic regression model.</p><p><b>RESULTS</b>A total of 94 eligible patients were identified from our registry, including 70 males and 24 females. The mean age at the diagnosis of CD and at development of abscess was 28.4 years and 30.4 years old, respectively. The median duration of CD between the diagnosis and development of an abscess was 3 years. According to the Montreal classification, L3 (ileocolonic) was the most common disease location (81.9%) in these patients. Most of the patients(76.6%) developed a single abscess, while multiple abscesses were detected in 22 patients(23.4%). Forty-four patients(46.8%) underwent surgery within 60 days after hospitalization due to spontaneous intra-abdominal abscess complicating CD. Multivariate logistic regression analysis revealed that history of abdominal surgery(OR=3.23, 95%CI:1.12 to 9.31, P=0.030), concomitant intestinal stenosis (OR=3.52, 95%CI:1.26 to 9.85, P=0.017) and concomitant intestinal fistula (OR=4.31, 95%CI:1.25 to 14.80, P=0.020) were the independent risk factors of early surgical intervention, while enteral nutrition (OR=0.18, 95%CI:0.05 to 0.62, P=0.007) was the independent protective factor.</p><p><b>CONCLUSIONS</b>Nearly half of CD patients with spontaneous intra-abdominal abscess will undergo early surgical intervention. Patients with history of abdominal surgery, concomitant intestinal stenosis and concomitant intestinal fistula have higher risk of early surgical intervention, and appropriate application of enteral nutrition may reduce the risk.</p>

Historical evolution and current concepts of surgical treatment for inflammatory bowel diseases / 中华胃肠外科杂志

Patients with inflammatory bowel disease (IBD) may require surgical intervention for refractory disease or complications. Prompt surgery and appropriate surgical procedures are critical when surgery is indicatedd. With continuous optimization and innovation of surgical procedures, there have been significant changes in the concepts and operations of IBD in the past century. Learning the evolution of surgical treatment for IBD could help us understand the rationale, indications, and pertinent techniques of surgical procedures. Innovations are emerging in IBD management including the advent of biological agents, laparoscopy, and multi-disciplinary team approach, it is imperative for IBD specialist to learn the state-of-the-art knowledge.

Surgical management of inflammatory bowel disease in China: a systematic review of two decades

BACKGROUND/AIMS: The past decades have seen increasing incidence and prevalence of inflammatory bowel disease (IBD) in China. This article aimed to summarize the current status and characteristics of surgical management for IBD in China. METHODS: We searched PubMed, Embase, and Chinese databases from January 1, 1990 to July 1, 2014 for all relevant studies on the surgical treatment IBD in China. Eligible studies with sufficient defined variables were further reviewed for primary and secondary outcome measures. RESULTS: A total of 74 studies comprising 2,007 subjects with Crohn's disease (CD) and 1,085 subjects with ulcerative colitis (UC) were included. The percentage of CD patients misdiagnosed before surgery, including misdiagnosis as appendicitis or UC, was 50.8%±30.9% (578/1,268). The overall postoperative complication rate was 22.3%±13.0% (267/1,501). For studies of UC, the overall postoperative complication rate was 22.2%±27.9% (176/725). In large research centers (n>50 surgical cases), the rates of emergency operations for CD (P=0.032) and in-hospital mortalities resulting from both CD and UC were much lower than those in smaller research centers (n≤50 surgical cases) (P=0.026 and P <0.001, respectively). Regarding the changes in CD and UC surgery over time, postoperative complications (P=0.045 for CD; P=0.020 for UC) and postoperative in-hospital mortality (P=0.0002 for CD; P=0.0160 for UC) both significantly improved after the year 2010. CONCLUSIONS: The surgical management of IBD in China has improved over time. However, the rates of misdiagnosis and postoperative complications over the past two decades have remained high. Large research centers were found to have relatively better capacity for surgical management than the smaller ones. Higher quality prospective studies are needed in China.

Surgical management of inflammatory bowel disease in China: a systematic review of two decades

BACKGROUND/AIMS: The past decades have seen increasing incidence and prevalence of inflammatory bowel disease (IBD) in China. This article aimed to summarize the current status and characteristics of surgical management for IBD in China. METHODS: We searched PubMed, Embase, and Chinese databases from January 1, 1990 to July 1, 2014 for all relevant studies on the surgical treatment IBD in China. Eligible studies with sufficient defined variables were further reviewed for primary and secondary outcome measures. RESULTS: A total of 74 studies comprising 2,007 subjects with Crohn's disease (CD) and 1,085 subjects with ulcerative colitis (UC) were included. The percentage of CD patients misdiagnosed before surgery, including misdiagnosis as appendicitis or UC, was 50.8%±30.9% (578/1,268). The overall postoperative complication rate was 22.3%±13.0% (267/1,501). For studies of UC, the overall postoperative complication rate was 22.2%±27.9% (176/725). In large research centers (n>50 surgical cases), the rates of emergency operations for CD (P=0.032) and in-hospital mortalities resulting from both CD and UC were much lower than those in smaller research centers (n≤50 surgical cases) (P=0.026 and P <0.001, respectively). Regarding the changes in CD and UC surgery over time, postoperative complications (P=0.045 for CD; P=0.020 for UC) and postoperative in-hospital mortality (P=0.0002 for CD; P=0.0160 for UC) both significantly improved after the year 2010. CONCLUSIONS: The surgical management of IBD in China has improved over time. However, the rates of misdiagnosis and postoperative complications over the past two decades have remained high. Large research centers were found to have relatively better capacity for surgical management than the smaller ones. Higher quality prospective studies are needed in China.

Contemplation on the application of big data in clinical medicine / 中华胃肠外科杂志

Medicine is another area where big data is being used. The link between clinical treatment and outcome is the key step when applying big data in medicine. In the era of big data, it is critical to collect complete outcome data. Patient follow-up, comprehensive integration of data resources, quality control and standardized data management are the predominant approaches to avoid missing data and data island. Therefore, establishment of systemic patients follow-up protocol and prospective data management strategy are the important aspects of big data in medicine.

Experimental study of adipose-derived mesenchymal stem cells in the treatment of Crohn's disease / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the efficacy of adipose-derived mesenchymal stem cells (ADMSCs) in a murine model of inflammatory bowel disease, and its potential mechanism.</p><p><b>METHODS</b>Murine colitis mouse model of Crohn's disease(CD) was created by trinitrobenzene sulfonic acid(TNBS)-induced colitis. Seventy-five 6-8 weeks female BALB/c mice were randomly divided into 3 groups: control group, TNBS group and ADMSC group. To verify the therapeutic effect of ADMSC, real-time PCR and immunohistochemical staining were performed to measure inflammatory cytokines levels in colon tissues. The 10-day survival statuses were recorded after the infusion of ADMSCs.</p><p><b>RESULTS</b>Intraperitoneal injection of ADMSCs alleviated the clinical and histopathologic severity of intestinal inflammation, and increased survival(60% vs. 30%, P<0.05) in the TNBS-induced mouse model of CD. Compared with TNBS group, proinflammatory cytokines, including TNF-α, IL-12 and VEGF of ADMSC group were significantly reduced, with significant increase of IL-10 expression.</p><p><b>CONCLUSION</b>ADMSCs can effectively repair the injury of colonitis through down-regulation of proinflammatory cytokines TNF-α, IL-12 and VEGF expression, and up-regulation of anti-inflammatory cytokine IL-10 expression, which may be a potential new alternative of cell-based therapy for CD.</p>

Inflammation promotes the development of colitis-associated colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To confirm that the severity of inflammation can promote the colitis-associated colorectal cancer(CAC) and explore the function of STAT3 signal pathway in CAC.</p><p><b>METHODS</b>Mutagenic agent azoxymethane(AOM) and pro-inflammatory agent dextran sodium sulfate salt (DSS) were used to develop a mouse model of CAC. By changing the concentration of DSS (0, 1% and 2% respectively), the mouse model with different extent of severity of inflammation was developed and the risk of carcinogenesis among these groups was compared. The expression of STAT3 signal pathway was detected by immunohistochemistry staining.</p><p><b>RESULTS</b>In the evaluation of inflammatory severity, disease activity index, histopathological inflammation scores and the expression of pro-inflammation chemokines such as TNF-α, IL-6 and IL-12 in the higher inflammatory response group were higher than that in the lower inflammatory response group. The incidence of colorectal tumor was 100%(12/12) in the higher inflammatory response group and the incidence of colorectal tumor was 58.3%(7/12) in the lower inflammatory response group, and the difference between these two group was statistically significant (P<0.05). The multiplicity(number of tumors/colon) was 12.5±0.5 in the higher inflammatory response group and the multiplicity was 6.6±1.0 in the lower inflammatory response group, and the difference between these two groups was statistically significant (P<0.001). The tumor load(sum of tumor diameters per mouse) in the higher inflammatory response group was 44.2±2.4 mm and that in the lower inflammatory response group was only 18.7±2.7 mm, and the difference between these two groups was statistically significant (P<0.0001). Moreover, the expression of p-STAT3 (Tyr705) was higher in colitis tissue of the higher inflammatory response group than that of the lower inflammatory response group.</p><p><b>CONCLUSIONS</b>Inflammation can promote the colitis-associated CAC. And the activation of STAT3 signal pathway may promote the development of CAC.</p>

Efficacy and oncological safety of bone marrow mesenchymal stem cell transplantation for colitis in inflammatory bowel disease models in mice / 中国组织工程研究

BACKGROUND:Transfusion of bone marrow mesenchymal stem cells may become a novel and effective biological therapy for inflammatory bowel disease in clinical practice. Nevertheless, the oncological safety of the treatment is worrisome, and is a key to determine whether mesenchymal stem cells can be widely used in treatment of inflammatory bowel disease, and deserves further investigation. OBJECTIVE:To evaluate the therapeutic effect of bone marrow mesenchymal stem celltransfusion against inflammatory bowel disease in mouse models, and to clarify the effects of mesenchymal stem cells on tumorigenesis of inflammatory bowel disease. METHODS:Mouse model of colitis was established using Balb/c (H-2d) mice exposed to dextran sulfate sodium. Syngeneic bone marrow mesenchymal stem cells were transfused into mouse model through caudal vein. The therapeutic effect of mesenchymal stem cells was compared and observed, and pathological remission of colitis was evaluated. Mouse model of colitis-driven colon carcinogenesis was established using Balb/c (H-2d) mice exposed to dextran sulfate sodium and azoxymethane. Tumor formation within the murine colon was compared and observed after transfusion of mesenchymal stem cells. RESULTS AND CONCLUSION:In models of dextran sulfate sodium-induced colitis, weight loss and fecal occult blood were lessened in the bone marrow mesenchymal stem cellgroup compared with the phosphate buffered saline group. Histological damage score of colitis was less in the bone marrow mesenchymal stem cellgroup:mucosal structure of distal colon was almost intact under microscope, and there was smal area of epithelial defects and cryptal defects. Inflammatory cellinfiltration, proliferation of capil ary and smal vessels could be observed in mucosa and submucosa. Homing and colonization of mesenchymal stem cells in submucosa of inflamed colon could also be observed by in vivo tracing. In the dextran sulfate sodium/azoxymethane model of colitis-driven colon carcinogenesis, the number of intestinal tumors and tumor load were obviously less in the bone marrow mesenchymal stem cellgroup than in the control group. Results indicated that transfusion of bone marrow mesenchymal stem cells can apparently improve colitis lesions of mice with inflammatory bowel disease and inhibit carcinogenesis of colitis, which may provide theoretical support for the biological safety of mesenchymal stem cells transplantation for inflammatory bowel disease.

Comprehensive treatment of Crohn's disease complicated with anal fistula / 中华消化外科杂志

Objective To investigate the comprehensive treatment of Crohn's disease complicated with anal fistula.Methods The clinical data of 33 patients with Crohn's disease complicated with anal fistula who were admitted to the Sixth Hospital of Sun Yat-Sen University from June 2007 to April 2011 were retrospectively analyzed.According to the range of the disease,surgical,medical and combined treatment were applied.Surgical treatment included thread-drawing drainage,fistulectomy,incision and drainage of the perianal abscess and enterostomy.Medical treatment include 5-aminosalicylic acid,immunosuppressive therapy,glucocorticoid,tumor necrosis factor monoclonal antibodies.All the patients were followed up till August 2012.The Crohn's disease activity index (CDAI) and perianal Crohn's disease activity index (PDAI) before and after treatment were analyzed using the independent sample t test.Results Of the 33 patients,22 received surgical and medical treatment,7 received surgical treatment,and 4 received medical treatment.The anal fistula was healed in 18 patients after the initial treatment (3 of them did not receive surgical treatment),and the mean closure time of the fistula was (3.2 ± 2.6) months (range,1-12 months) ; the condition of 8 patients was improved ; 4 patients suffered from fistula persistence ; anal fistula recurrence was observed in 6 patients,and the time for anal fistula recurrence was (35 ±56)months (range,5-148 months).The preoperative CDAI and PDAI of the 33 patients were 166 ± 100 (range,7-361) and 9.2 ± 2.6 (range,5-16),and the postoperative CDAI and PDAI of the 33 patients were 83 ± 53 (range,0-212) and 2.7 ± 3.1 (range,0-11).There were significant differences between the pre-and postoperative CDAI and PDAI (t =4.20,8.92,P ＜0.05).Of the 12 patients who were failed in the initial treatment,the anal fistula was healed in 3 patients after the treatment,and the condition of the other 9 patients remained the same.Of the 6 patients with anal fistula recurrence,5 received reoperation (4 were healed and 1 remained the same after the treatment) and the fistula of 1 patient who received medical treatment was not healed.At the end of the follow up,the anal fistulas of 20 patients were healed,and 10 remained the same.Conclusions There is no standard treatment for Crohn's disease complicated with anal fistula,surgical treatment combined with medical treatment is important for the treatment of Crohn's disease complicated with anal fistula.Surgical procedures should be chosen carefully according to the condition of the patients.

Curative effect analysis of radical surgery for colon cancer invading duodenum / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the clinicopathological characteristics and access the immediate- and long-term outcome of radical surgery in patients with colon cancer invading duodenum.</p><p><b>METHODS</b>A retrospective review of 19 patients with colon cancer invading duodenum underwent radical surgery between 1995 and 2010 was performed. There were 7 male and 12 female, age ranged from 36 to 73 years with an average of 56 years. The main manifestations were abdominal pain, loss of weight, change of stool frequency and so on. The tumors located at the hepatic flexure in 15 patients. All of the patients underwent radical surgery, and none of the patients had positive resection margins. One patient underwent pancreaticoduodenectomy combined with right hemicolectomy (RH). Two patients underwent pylorus preserving pancreaticoduodenectomy combined with RH. One patient underwent duodenectomy combined with RH. Four patients underwent RH. And the other 11 patients underwent lateral duodenectomy combined with RH.</p><p><b>RESULTS</b>There was no postoperative morbidity and mortality, and the 30-day mortality rate was 0. The median overall survival was 5.3 years. Overall 1 and 5 years survival rate were 94.4% and 70.4%, respectively. And 3 patients developed recurrence in 3 years.</p><p><b>CONCLUSIONS</b>The patients with colon cancer invading duodenum are lack of specific clinical manifestations. And the radical surgical procedure is safe, which could prolong the survival and improves the prognosis in these patients.</p>

Laparoscopic colorectomy versus open colorectomy for elderly patients over 80 years old: a meta-analysis of safety and efficacy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the clinical safety and efficacy of laparoscopic versus open colorectal resection in octogenarians. Methods Studies comparing laparoscopic colorectal resection with open colorectal resection in octogenarians were identified from the Medline, Embase, Ovid, and Cochrane databases from 1990 to 2012. The methodological quality of the selected studies was assessed to determine studies suitable for inclusion. Meta-analysis was performed by fixed or random effects model.</p><p><b>RESULTS</b>Five observational studies with a total of 685 patients (330 laparoscopic colorectal resections and 355 open colorectal resections) were identified. Laparoscopic colorectal resection was associated with a prolonged operative time (WMD=27.89, P<0.01) and a lower rate of overall complications (OR=0.58, P<0.01), wound infection (OR=0.50, P<0.05), cardiovascular complication(OR=0.53, P<0.05), quicker bowel function return (WMD=-0.83, P<0.01), and shorter length of hospital stay (WMD=-3.60, P<0.05). No differences were found with regard to anastomotic leak (OR=1.13, P>0.05), prolonged ileus (OR=0.71, P>0.05), respiratory complication (OR=0.59, P>0.05),mortality (OR=0.67, P>0.05), and reoperation (OR=0.85, P>0.05).</p><p><b>CONCLUSION</b>Laparoscopic colorectal resection is as safe as open colorectal resection, and is more favorable in terms of length of hospital stay and bowel function return in octogenarians.</p>

Enterostomy and associated problems / 中华胃肠外科杂志

Stoma has been used in colorectal surgery for various indications. Stoma type and stoma location are associated with stoma complications and quality of life with a stoma. The question regarding how to avoid stoma complication and improve quality of life should be considered when stoma creation is planned. The benefit of stoma should be balanced with complications brought about by stoma creation.

Diagnosis and treatment of pouchitis and pouch dysfunction / 中华胃肠外科杂志

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC with dysplasia and for the majority of patients with familial adenomatous polyposis. However, UC patients with IPAA are susceptible to a number of inflammatory and non-inflammatory sequelae, such as pouchitis, Crohn disease(CD) of the pouch, cuffitis, and irritable pouch syndrome, in addition to common surgery-associated complications, which adversely affect the surgical outcome and compromise patient's health-related quality of life. Pouchitis is the most frequent long-term complication of IPAA in patients with UC, with a cumulative prevalence of up to 50%. Pouchitis may be classified based on the etiopathogenesis into "idiopathic" and "secondary" types and the management is often different. Pouchoscopy is the most important tool for the diagnosis and differential diagnosis in patients with pouch dysfunction. Antibiotic therapy is the main stay of treatment for active pouchitis. Some patients may develop dependency on antibiotics, requiring long-term maintenance therapy. While management of antibiotic-dependent or antibiotic-refractory pouchitis has been challenging, secondary etiology for pouchitis should be evaluated and modified, if possible.

Surgical treatment for ulcerative colitis / 中华胃肠外科杂志

Despite significant progress in medical therapy for ulcerative colitis, surgical intervention is still required in a portion of patients with ulcerative colitis. Ileal pouch-anal anastomosis has been commonly used in western countries, while ileorectal anastomosis may be appropriate in specific scenarios. The surgical decision should be made based upon the clinical situation and sufficient patient consent.

Increased rate change over time of a sphincter-saving procedure for lower rectal cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Total mesorectal excision (TME) has increased the rate of sphincter-preservation (SP) for more patients with low-lying rectal cancer. Here, we analyze the change of sphincter preserving rates in lower rectal cancer and their related factors.</p><p><b>METHODS</b>We reviewed retrospectively the medical records of 316 patients with lower rectal cancers, 1 to 5 cm from the anorectal line, who had surgical resections from August 1994 to November 2005. The 12-year span was divided into 2 periods: period I (August 1994-December 1998) and period II (January 1999-November 2005), based on the date (January 1999) when standard total mesorectal excision (TME) was introduced. The patients were divided into two groups based on the operation: abdominoperineal resection (APR) or SP surgery. SP rates, leakage and other clinico-pathological characteristics were compared between the two time periods and between the two different groups.</p><p><b>RESULTS</b>The SP rate increased significantly over the 12 years, from 44.9% in period I to 76.2% in period II (P = 0.000). The factors significantly influencing SP included the distance of the tumor from the anorectal line, gender, time period, circumference of intramural spread and histological differentiation (P < 0.05). Significant differences were detected between the two time periods in gender, blood transfusion volume and Dukes' stage (P < 0.05). The leakage rate was 2.7% in period I and 1.3% in period II (P > 0.05).</p><p><b>CONCLUSIONS</b>Over the 12-year period of the study the SP rate in rectal cancers 1 - 5 cm from the anorectal line has increased significantly while the blood transfusion volume has decreased due to the introduction of TME. However, TME had no effect on operating time and leakage rates.</p>