ObjectiveTo explore the mechanisms of perineural invasion (PNI) in pancreatic cancer so as to find a new treatment for pancreatic cancer. MethodsThe literatures on PNI, neurotropism, nerve-tumor microenvironment and nerve growth factor in pancreatic cancer were reviewed and the mechanisms of PNI were summarized. ResultsThe rich innervation of pancreatic tissue itself and the minute slits within perineural structure were the anatomic basis of PNI. Tumor cells expressed neural antigens were the pathological basis of PNI. Tumor-nerve microenvironment and nerve growth factor family and themselves receptors might play an important molecular role in PNI. However, tumor cells expressed neural antigens were not only closely related to the PNI, but also the interaction between tumor cells and nerves played an important role in PNI. ConclusionsThe detailed mechanisms of PNI are extremely complex and controversial up to today. However, it is possible to search a new therapeutic target in pancreatic cancer according to the mechanisms of PNI.
Objective To evaluate the effects of indoor temperature and relative humidity on acute exacerbations of chronic obstructive pulmonary disease（AECOPD）.Methods A total of 70 moderate to very severe COPD patients were recruited.The data including indoor temperature and relative humidity twice daily，increase over their stable symptoms in "major" symptoms（dyspnea，sputum purulence，sputum amount） and "minor" symptoms（nasal discharge/congestion，sore throat，cough），and adjustment of medication were recorded on diary cards.All data were collected from Jan 2005 to Dec 2005 by telephone inquiring or home visiting.Furthermore，the corresponding median outdoor temperature，relative humidity and air pressure from atmosphere bureau were compared with indoors parameters to examine the different effects on AECOPD.Results Fifty-five cases completed the whole investigation.Indoor temperature and relative humidity were both risk factors when logistic regression was used to evaluate the effect.Our research showed that AECOPD was significantly related to indoor and ourdoor environment factors.The correlation coefficient of all factors were r=－0.686（indoor temperature），r=－0.671（outer temperature），r=0.105（indoor humidity），r=－0.115（outer humidity），r=0.545（atmospheric pressure） respectively.Conclusions The indoor temperature and relative humidity，especially low temperature and high relative humidity，had important effects on AECOPD of moderate to very severe patients.It may be helpful to prevent AECOPD by adjusting the indoor temperature and relative humidity.
Objective The bone marrow mesenchymal stem cells (BMSCs) have the capacity to differentiate into insul in-producing cells (IPCs) in vitro. However, low differentiation efficiency and poor maturity are the main obstacles. To investigate the feasibil ity of BMSCs differentiation into IPCs in diabetic pancreatic microenvironment of pigs. Methods BMSCs were isolated and purified from the bone marrow of a 4-week-old male pig. Fifteen female pigs (aged 8 to 10 weeks, weighing 8 to 10 kg) were randomly divided into 3 groups: normal control group (group A, n=5), diabetic control group (group B, n=5), and BMSCs transplanted group (group C, n=5). The pigs of groups B and C were treated by auris vein injections of styeptozocin and alloxan for 3 days to induce diabetes mell itus (DM) model, whose blood glucose level 2 days all greater than 17 mmol/L was successful DM model. A total of 1.1 mL of the 3rd passage BMSCs labeled with enhanced green fluorescent protein (EGFP), with cell density of 5 × 107/ mL, were injected into subcapsular pancreas of group C at multi ple points, normal saline at the same dosage into those of groups A and B. After 30 days of monitoring blood glucose, the histological analysis of islet number and size were done; the immunofluorescence staining was used to detect the protein expression of insul in in the new-formed islets. The EGFP+ cells were collected from the sections using laser-capture microdissection; RT-PCR was used to detect insulin mRNA and pancreatic and duodenal homeobox factor 1 (PDX1) mRNA expressions from EGFP+ cells, and the insul in and sexdetermining region of the Y chromosome (SRY) genes were detected by fluorescence in situ hybridization (FISH). Results The blood glucose level decreased significantly in group C when compared with that in group B from 18 days and gradually decreased with time (P lt; 0.05). The histological observation showed that the number of islets was increased significantly in group C when compared with that in group B (10.9 ± 2.2 vs. 4.6 ± 1.4, P lt; 0.05), and there was no significant difference when compared with that in group A (10.9 ± 2.2 vs.12.6 ± 2.6, P gt; 0.05). The size of new-formed islets in group C was significantly smaller than that in group A [(47.2 ± 19.6) μm vs. (119.6 ± 27.7) μm, P lt; 0.05]. The immunofluorescence staining showed that new-formed islets of group C expressed insulin protein. RT-PCR showed that the microdissected EGFP+ cells of group C expressed insulin mRNA and PDX-1 mRNA. FISH showed that the new-formed islet cells of group C contained SRY gene in Y chromosome and insulin double positive cells. Conclusion BMSCs can differentiate into IPCs in diabetic pancreatic microenvironment of pigs.
Objective To observe the anti-adhesion and repair effect of 3 composite patches which composed of polylactide-co-caprolactone (PLC), hyaluronic acid (HA), collagen, and polypropylene (PP) mesh repairing abdominal wall defectin rats under contaminated environment, and to investigate the characteristics of 3 composite patches and the feasibil ity of onestage repair. Methods Ninety-three adult male Wistar rats (weighing 150-250 g) were randomly divided into 3 groups (n=31): PP/PLC composite patches (group A), PP/HA/PLC composite patches (group B), and PP/collagen/PLC composite patches (group C). One rat was selected from each group to prepare the contaminated homogenate of the small intestine. The abdominal wall defect models (1 cm in diameter) were established in other rats, and the defects were repaired with 3 composite patches (1.5 cm in diameter) according to grouping method. At 30, 60, and 90 days postoperatively, the adhesions was observed, and the patch and adjacent tissue was harvested for histological observation. Results Six rats died at 10-70 days postoperatively (2 in group A, 3 in group B, and 1 in group C). No wound infection, intestinal obstruction, or hernia occurred in 3 groups. Adhesion was observed between abdominal viscera and the patch, especially intestine, epiploon, and l iver. According to the modified Katada criteria, no significant difference in the adhesion score was found among 3 groups at 30 and 60 days (P gt; 0.05); the adhesion score was significantly lower in group C than in groups A and B at 90 days (P lt; 0.05). The histological results showed that inflammatory cell infiltration, fibroblasts, secreted collagen, and the residual absorbable material were observed around the patch at 30 days in 3groups. Decreased inflammatory cell infiltration, increased fibroblasts and residual PLC were observed at 60 days in 3 groups. At 90 days, the fibroblasts became increasingly mature, collagen deposited, the mesothelium formed gradually, and the residual PLC decreased. Conclusion In contaminated environment, PP/collagen/PLC composite patch is superior to PP/PLC and PP/HA/ PLC composite patches in aspect of abdominal adhesion and inflammatory reaction, and it is more applicable to one-stage repair of rat abdominal wall defect. But it is necessary to further study in the long-term efficacy and the security of the composite patch.
Objective To explore the influence of different stress environmentson the growth of tissue engineering blood vessels in vivo． Methods The engineering vascular scaffolds were prepared with the porcine small intestinal submucosa(SIS) wrapping vascular endothelial cells and smooth muscle cells，which were implanted into the subcutaneous tissue(subcutaneous group), the femoral quadriceps(intramuscular group), and sheathed the femoral artery(perivascular group) respectively. Four weeks postoperatively, these cultured tissues were harvested, and evaluated by macroscopic observation and histology detection. Results The cultivated tissues in different stress environments had obvious difference in respectof the tubular configuration, cellular proliferation and tissue shape. In subcutaneous group, the wall structure integrity, seed cell proliferation and SIS scaffold decomposition were poor, lumen surface was covered without endothelial cells; in intramuscular group, integrity tubular structure had formed, seed cell proliferation was found to a certain extent, lumen surface was covered with sparseendothelial cells, and a little SIS scaffold was found, cellular and fiber structured arranged irregularly; in perivascular group, vascular-like structure formed, the seed cell growth and proliferation were good, the lumen surface was completely covered with endothelial cells, the smooth muscle cells were in good morphologicaldistribution, the antihydrostatic pressure was 247.0±35 kPa，showingsignificant differences when compared with subcutaneous group(67.0±5.8 kPa) and intramuscular group(104.0±7.6 kPa) (Plt;0.01).The total scoring of tissue engineering blood vessel formation in subcutaneous group, intramuscular group and perivascular group were 5.529±0.272，8.875±0.248 and 14.824±0.253 respectively, and the differences among them were significant (P lt; 0.05). Conclusion Stress excitation has a great influence on the cellular proliferation and the growth of tissue engineering blood vessel in vivo.
Objective To review the research progress of osteoblasts in the hematopoietic microenvironment of bone marrow and regulatory pathways and mechanisms. Methods The advances in the osteoblasts as crucial components for hematopoietic microenvironment in bone marrow, regulation to osteoblasts and hematopoietic stem cells(HSCs), and correlative singal pathways and mechanisms were introduced based on the recent related literature. Results Evidence indicates that osteoblasts are crucial components of the hematopoietic microenvironments in adult bone marrow. The osteoblasts maintainthe quiescence of primitive HSCs by the signaling receptorsligands, secreted cell factors and celladhesion molecules and by regulating other cells in the niche. The quiescent primitive HSCs persist stem cell characteristic which has unlimited selfrenewal and multipotent differentiation potential. Conclusion The further understanding of the relationship between osteoblasts and hematopoietic microenvironment should lead to development of new strategies directed toward clinical therapeutics of HSCs transplantation.
Objective To compare and research the process of woundhealing in occlusive moist environment and dry environment on the skin donor site. Methods The wound healing of adult skin donor site was studied by clinical observation, histological and electromicroscopical examinations on the operative day and the 1st, 2nd, 3rd, 4th, 7th days postoperatively, each skin donor site was divided into two parts: occlusive environment and dry environment. Results The wounds of occlusive moist environment healed faster than those of dry environment; thefibroblasts were more active and activated earlier, revascularization and re-epithelialization happened earlier and more quickly. Conclusion In occlusive environment, more active fibroblasts can accelerate granulation growth; quicker regenerative capillaries bring more nourishment; quicker re-epithelialization accelerates the wound healing.
Objective To study the influence of different mechanical environments on repair cartilage defect with marrow mesenchymal stem cells as seed cells. Methods The rabbit marrow mesenchymal stem cells were isolated and cultured. The cartilage defects were repaired by autologous tissue engineered cartilage with the marrow mesenchymal stem cells as seed cells. Fifteen rabbits with cartilage defect were divided into 3 groups: dislocation group with cell-free scaffold(controlgroup), dislocation group with cartilaginous construct and normal mechanical environment group with cartilaginous construct. The repaired tissue was harvested and examined 6 weeks postoperatively. Results The repair tissue in normal mechanical environment group with cartilaginous construct showed cartilage-like tissue in superficial layer and subchondral bone tissue in deep layer 6 weeks postoperatively. The defect was filled with bone tissue in dislocation group with cartilaginous construct 6 weeks postoperatively. The surrounding normal cartilage tissue showed vascular invasion from subchondral area and the concomitant thinningof the normal cartilage layer. The cartilaginous construct left in the femoral trochlea groove formed hyaline cartilage-like tissue. The defect was repaired byfibrous tissue in control group. Conclusion The repaired tissue by tissue engineered cartilage with marrow mesenchymal stem cells as seed cells showed the best result in normal mechanical environment group, which indicates that it will be essential for the formation and maintenance of tissue engineered cartilage to keep the normal mechanical stress stimulus.
Abstract To study the regulation of growth and proliferation of tissue-repair cell from wound microenvironment, the effects of wound fluid (WF) on the growth and proliferation of wound fibroblast were studied in vitro. Thirty rats were divided into 6 groups. On the back of every rat, an incision of 0.5～1.0cm was performed a subcutaneous sac was made by blunt dissection. A piece of sponge was put in, and the wound was sutured. After 1,3,7,9,11,15 days, one group of the rats were sacrificed respectively, and WF was collected from the sponge. Two kinds of medium were made with each WF: 1640+1%FCS+10%WF and1640+10%FCS+10%WF. After 48 hours incubation with newly prepared wound fibroblasts, the growth of the cells was observed. It was shown that (1) Under 1%FCS, WFfrom1,3,7 days stimulated cell proliferation, and WF from 9,11,15 days caused cell death. (2) Under 10%FCS, WF from 9,11,15 days inhibited cell growth. It was suggested that the wound microenvironment stimulated the fibroblasts to proliferate for one week after injury, and beyond that further growth seemed to be arrested, and that there might be some growth inhibitory factors present in the microenvironmentduring the late stage of wound healing.