Uninduced adipose-derived stem cells repair the defect of full-thickness hyaline cartilage.

OBJECTIVE: To testify the effect of the stem cells derived from the widely distributed fat tissue on repairing full-thickness hyaline cartilage defects. METHODS: Adipose-derived stem cells (ADSCs) were derived from adipose tissue and cultured in vitro. Twenty-seven New Zealand white rabbits were divided into three groups randomly. The cultured ADSCs mixed with calcium alginate gel were used to fill the full-thickness hyaline cartilage defects created at the patellafemoral joint, and the defects repaired with gel or without treatment served as control groups. After 4, 8 and 12 weeks, the reconstructed tissue was evaluated macroscopically and microscopically. Histological analysis and qualitative scoring were also performed to detect the outcome. RESULTS: Full thickness hyaline cartilage defects were repaired completely with ADSCs-derived tissue. The result was better in ADSCs group than the control ones. The microstructure of reconstructed tissue with ADSCs was similar to that of hyaline cartilage and contained more cells and regular matrix fibers, being better than other groups. Plenty of collagen fibers around cells could be seen under transmission electron microscopy. Statistical analysis revealed a significant difference in comparison with other groups at each time point (t equal to 4.360, P less than 0.01). CONCLUSION: These results indicate that stem cells derived from mature adipose without induction possess the ability to repair cartilage defects.

Micrometer-Sized Titanium Particles Induce Aseptic Loosening in Rabbit Knee.

Wear debris induced aseptic loosening is the leading cause of total knee arthroplasty (TKA) failure. The complex mechanism of aseptic loosening has been a major issue for introducing effective prevention and treatment methods, so a simplified yet efficient rabbit model was established to address this concern with the use of micrometer-sized titanium particles. 20 New Zealand white rabbits were selected and divided into two groups (control = 10, study = 10). A TKA surgery was then performed for each of them, with implantation of a titanium rod prosthesis which was coated evenly with micrometer-sized titanium in the study group and nothing in the control group, into right femoral medullary cavity. After 12 weeks, all the animals were euthanized and X-ray analyses, H&E staining, Goldner Masson trichrome staining, Von Kossa staining, PCR, and Western blotting of some specific mRNAs and proteins in the interface membrane tissues around the prosthesis were carried out. The implantation of a titanium rod prosthesis coated with 20 µm titanium particles into the femoral medullary cavity of rabbits caused continuous titanium particle stimulation around the prosthesis, effectively inducing osteolysis and aseptic loosening. Titanium particle-induced macrophages produce multiple inflammatory factors able to activate osteoclast differentiation through the OPG/RANKL/RANK signaling pathway, resulting in osteolysis while suppressing the function of osteoblasts and reducing bone ingrowth around the prosthesis. This model simulated the implantation and loosening process of an artificial prosthesis, which is an ideal etiological model to study the aseptic prosthetic loosening.

Astragaloside IV suppresses inflammatory mediator production in synoviocytes and collagen­induced arthritic rats.

The aim of the current study was to investigate the effects of Astragaloside­IV (AS­IV) on inflammatory mediators in synoviocytes and collagen­induced arthritic rats. Synoviocytes were stimulated with lipopolysaccharides (LPS) and Sprague­Dawley rats were injected with type II collagen. AS­IV was administered to the LPS­stimulated synoviocytes and collagen­induced arthritis (CIA) rats. The inflammation of LPS­stimulated synoviocytes and CIA rats was assessed using enzyme­linked immunosorbent assays and western blotting. Using Cell Counting Kit­8 analysis, it was demonstrated that AS­IV (5, 20 and 50 mg/ml) inhibited the LPS­stimulated synoviocytes proliferation in a dose­dependent manner. AS­IV significantly inhibited the LPS­stimulated inflammatory response, as indicated by the expression levels of TNF­α, IL­1ß, IL­6 and IL­8. In addition, treatment with AS­IV significantly reduced the LPS­stimulated cyclooxygenase (COX)­1, COX­2, high mobility group box 1 protein (HMGB1) and intercellular adhesion molecule 1 overexpression, and intranuclear nuclear factor (NF)­κBp65 subunit accumulation and activation of c­Jun N­terminal kinase (JNK)1/2 and p38. Similar to the protective effects of AS­IV on LPS­stimulated synoviocytes, AS­IV treatment significantly reduced the expression levels of tumor necrosis factor α, interleukin (IL)­1ß, IL­6 and IL­8 expression levels, and attenuated intranuclear NF­κBp65 subunit accumulation and overexpression of COX­2 and inducible nitric oxide synthase in CIA rats. In conclusion, the results of the present study demonstrated for the first time, to the best of our knowledge, that AS­IV protects synoviocytes against LPS­ and collagen­induced inflammatory responses through inhibition of the HMGB1­dependent JNK1/2­ and p38­activated NF­κB/COX­2 pathway.

Significance of the preoperative neutrophil-to-lymphocyte ratio in the prognosis of patients with gastric cancer.

AIM: To investigate the significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) in the prognosis of patients with gastric cancer (GC). METHODS: The clinical data of 291 GC patients were analysed retrospectively; these patients were divided into two groups according to their preoperative NLR: a high-NLR group (NLR ≥ 3.5, 131 cases) and a low-NLR group (NLR < 3.5, 160 cases). The clinicopathological characteristics and five-year survival rates of the two groups were compared. The NLR and other clinicopathological factors were subjected to univariate and multivariate survival analysis to evaluate the effects of the NLR on the prognosis of GC patients. RESULTS: The lowest preoperative NLR among the 291 patients was 0.56, whereas the highest preoperative NLR was 74.5. The mean preoperative NLR was 5.99 ± 8.98. Age, tumour size, T staging, tumour-node-metastasis (TNM) staging and platelet count were significantly different between the high- and low-NLR groups (P < 0.05). The five-year survival rate of the high-NLR group was 17.0%, which was significantly lower than that of the low-NLR group (43.6%; 17.0% vs 43.6%, P < 0.05). The univariate analysis results showed that the five-year survival rate was related to age, tumour size, T staging, N staging, TNM staging, carcinoembryonic antigen value and NLR (P < 0.05). Multivariate analysis results showed that the NLR was an independent risk factor that likely affected the five-year survival rate of GC patients (P = 0.003, HR = 0.626, 95%CI: 0.460-0.852). CONCLUSION: The preoperative NLR could be used as a prognostic factor for GC patients; in particular, a high NLR corresponded to poor prognosis of GC patients.

Effect of the human insulin-like growth factor 1 gene transfection to human umbilical cord blood mesenchymal stem cells.

OBJECTIVE: To observe the effect of transfecting the gene human insulin-like growth factor (hIGF)-1 into human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) via non-viral vector. METHODS: This study was performed in the Affiliated Hospital of Qingdao University, Qingdao, China from June 2012 to May 2013. Twelve hUCB samples were harvested, and isolated in lymphocyte separation medium, and then cultured. Surface antigen expression in MSCs was detected by flow cytometry. Recombinant plasmid pIRES2-enhanced green fluorescent protein (EGFP)-hIGF-1 was transfected into MSCs by X-treme GENE HP DNA transfection reagent. Then, EGFP was observed with reverse fluorescent microscope at different time points. Enzyme-linked immunosorbent assay was used to determine the hIGF-1 protein concentration in supernatants. Immunofluorescence microscopy and reverse transcription polymerase chain reaction were used to detect the expression of hIGF-1 in the hUCB-MSCs. Expression of type II collagen was detected by immunohistochemistry staining. RESULTS: Transfection efficiency was 28.74 +/- 7.31%. The cluster of differentiation (CD)90, CD105, and CD146 expression increased CD34, CD45, and anti-HLA-DR expression decreased. Results of immunofluorescence microscopy and RT-PCR confirmed expression of the hIGF-1 gene. The hIGF-1 protein concentration in the supernatants showed a peak level at 34.63 +/- 1.61 ng/ml 48 hours after transfection. Immunohistochemical analysis of transfected hUCB-MSCs proved that type II collagen could be expressed positively. CONCLUSION: Human IGF-1 gene can be transfected into hUCB-MSCs, and expressed at a high level with subsequent expression of type II collagen.

Preliminary study correlating CX3CL1/CX3CR1 expression with gastric carcinoma and gastric carcinoma perineural invasion.

AIM: To study the relationship between the CX3CL1 chemokine, its receptor CX3CR1, and gastric carcinoma/gastric carcinoma perineural invasion (PNI). METHODS: Thirty cases of gastric carcinoma were surgically resected (radical resection or palliative resection) between February 2012 and July 2012. Tumour and tumour-adjacent tissues were evaluated for the presence of CX3CL1 (ELISA) and CX3CR1 (immunohistochemistry and Western blotting) in an effort to analyse the relationship between CX3CL1/CX3CR1 and gastric carcinoma/gastric carcinoma PNI. RESULTS: Of these 30 cases, 14 were PNI-positive (46.7%). No significant differences in CX3CL and CX3CR1 expression in tumour-adjacent tissues were found between the PNI positive and negative groups. Expression levels of CX3CL and CX3CR1 in tumour tissues were significantly higher than those in adjacent tissues (P < 0.01), and were significantly higher in tumour tissues from the PNI-positive group compared to the PNI-negative group (P < 0.01). CONCLUSION: CX3CL1/CX3CR1 expression may be associated with the occurrence and development of gastric carcinoma as well as gastric carcinoma PNI.

Comparison of long-term clinical outcome between patients with chronic versus acute type B aortic dissection treated by implantation of a stent graft: a single-center report.

BACKGROUND: Stent grafting for treatment of type B aortic dissection has been extensively used. However, the difference in the long-term clinical outcome between patients with chronic versus acute type B aortic dissection remains unknown. This study aimed to analyze the difference in long-term clinical outcome after endovascular repair for patients with chronic (≥2 weeks) versus acute (<2 weeks) type B aortic dissection. METHODS: Between May 2000 and June 2011, a total of 174 patients with type B aortic dissection (56 chronic, 118 acute) treated by endovascular repair were studied prospectively. Follow-up three-dimensional computed tomography scanning and aortoangiography were scheduled at 3-6 months after the index procedure. Propensity score matching was used to compare the difference in the endpoint between the two groups. RESULTS: The procedure-related event rate was 18.6% in the acute group and 5.4% in the chronic group (P = 0.021), but this difference became nonsignificant after propensity score matching. At the end of follow-up (mean 2.49 years), overall and aorta-related mortality was 11.0% and 7.6%, respectively, in the acute group, and was not significantly different from that in the chronic group (3.6% and 3.6%, P = 0.148 and P = 0.506, respectively). Both false and true lumina showed significant remodeling over time, with >93% complete false-lumen thrombosis. Untreated tear and type I endoleak were predictors of clinical events during follow-up. CONCLUSION: Comparable long-term clinical results were achieved in patients with chronic or acute type B aortic dissection after implantation of a stent graft.

[Analysis of clinical characteristics and prognosis of perineural invasion in patients with gastric carcinoma].

OBJECTIVE: To investigate the association between perineural invasion(PNI) and clinicopathological factors and the effect of PNI on overall survival in patients with gastric carcinoma. METHODS: A total of 178 patients with gastric carcinoma from January 2004 to May 2008 were analyzed retrospectively. Paraffin sections of surgical specimens from all the patients who underwent gastric resection were stained with laminin. PNI-positive was defined as infiltration of carcinoma cells into the perineurium or neural fascicles. The association of PNI with clinicopathologic features and prognosis of gastric carcinoma was studied. RESULTS: PNI was positive in 78 of 178 patients(43.8%). The proportions of T stage, lymph node metastasis and TNM stage were significantly higher in PNI-positive group than those in PNI-negative group(all P<0.01). The PNI positive rate was correlated with the depth of gastric mural invasion and clinical stage. The overall survival in PNI-positive group was significantly lower than that in PNI-negative group by univariate analysis(P<0.01). The mean survival of PNI-positive patients(28.6 months) was significantly shorter than that of PNI-negative patients (44.3 months, P<0.01), which was also influenced by pN stage, pT stage, and clinical stage(P<0.01). By multivariable Cox proportional hazards model of overall survival, the positivity of PNI appeared to be an independent prognostic factor (hazards ratio=2.257, 95% CI:1.268-4.019, P=0.006). CONCLUSIONS: PNI is associated with the degree of malignancy in gastric cancer. PNI can be a candidate of new prognostic factor.

Modified biplanar open-wedge high tibial osteotomy with rigid locking plate to treat varus knee.

OBJECTIVE: To introduce and characterize the modified biplanar opening high tibial osteotomy with rigid fixation to treat varus knee in young and active patients. METHODS: Between June 2001 to July 2008, 18 patients with monocompartmental degeneration of the knee combined with a varus malalignment of the leg had the modified biplanar opening high tibial osteotomy and the osteotomy was fixed with the locking plates (Locking Compression Plate System). The mean varus deformity before operation was 11.5 degrees (5 degrees approximately 19 degrees ) and no degenerative changes were found in other departments. Stability of the knee was normal in 15 patients, but ruptures in anterior cruciate ligaments or lateral collateral ligament were presented in the remaining 3 patients. Preoperative symptom was mainly limited in the pain of medial compartment. The preoperative and follow-up data for the range of motion and Lysholm score were determined. Subjective satisfactory examination was also applied to the patients for the operation they selected. RESULTS: All of the patients were followed up with an average of 32.5 months (12 approximately 82 months). There was no ununion or delayed union in this group during the follow-up period. No complications like broken plate, nerve injury, or blood vessel injury occurred. The postoperative average corrected degree was 9.5 degrees (5.5 degrees approximately18 degrees ). No degenerations developed in the three departments of the knee. The Lysholm scores before and after surgery were 42.5 and 77.5, respectively (P<0.01). The overall fineness rate was 83.3%. The subjective satisfactory survey demonstrated that about 83.3% patients showed satisfactory on the operation. There was no obvious difference in the range of motion before and after operation, but significant changes were found in the Lysholm score and varus degree from preoperative to follow-up. CONCLUSION: Proximal opening high tibial osteotomy performed in conjunction with the special rigid locking plate yielded good results for symptomatic genu varum. This new classic technique can be effectively applied to the medial compartment degeneration of the knee in active young patients.