Regeneration of an injured meniscus continues to be a scientific challenge due to its poor self-healing potential. Tissue engineering provides an avenue for regenerating a severely damaged meniscus. In this study, we first investigated the superiority of five concentrations (0%, 0.5%, 1%, 2%, and 4%) of meniscus extracellular matrix (MECM)-based hydrogel in promoting cell proliferation and the matrix-forming phenotype of meniscal fibrochondrocytes (MFCs). We found that the 2% group strongly enhanced chondrogenic marker mRNA expression and cell proliferation compared to the other groups. Moreover, the 2% group showed the highest glycosaminoglycan (GAG) and collagen production by day 14. We then constructed a hybrid scaffold by 3D printing a wedge-shaped poly(ε-caprolactone) (PCL) scaffold as a backbone, followed by injection with the optimized MECM-based hydrogel (2%), which served as a cell delivery system. The hybrid scaffold (PCL-hydrogel) clearly yielded favorable biomechanical properties close to those of the native meniscus. Finally, PCL scaffold, PCL-hydrogel, and MFCs-loaded hybrid scaffold (PCL-hydrogel-MFCs) were implanted into the knee joints of New Zealand rabbits that underwent total medial meniscectomy. Six months postimplantation we found that the PCL-hydrogel-MFCs group exhibited markedly better gross appearance and cartilage protection than the PCL scaffold and PCL-hydrogel groups. Moreover, the regenerated menisci in the PCL-hydrogel-MFCs group had similar histological structures, biochemical contents, and biomechanical properties as the native menisci in the sham operation group. In conclusion, PCL-MECM-based hydrogel hybrid scaffold seeded with MFCs can successfully promote whole meniscus regeneration, and cell-loaded PCL-MECM-based hydrogel hybrid scaffold may be a promising strategy for meniscus regeneration in the future.
Decellularized meniscus extracellular matrix (DMECM) and polycaprolactone (PCL) were electrospun into nanofibers to make meniscus scaffolds with good mechanical properties.
ObjectiveTo reveal the familial prevalence and molecular variation of α- and β-globin gene mutations in Guangdong Province.MethodsA total of 40,808 blood samples from 14,332 families were obtained and analyzed for both hematological and molecular parameters.ResultsA high prevalence of α- and β-globin gene mutations was found. Overall, 17.70% of pregnant women, 15.94% of their husbands, 16.03% of neonates, and 16.83% of couples (pregnant women and their husbands) were heterozygous carriers of α- or β-thalassemia. The regions with the highest prevalence were the mountainous and western regions, followed by the Pearl River Delta; the region with the lowest prevalence was Chaoshan. The total familial carrier rate (both spouses were α- or β-thalassemia carriers) was 1.87%, and the individual carrier rates of α- and β-thalassemia were 1.68% and 0.20%, respectively. The total rate of moderate-to-severe fetal thalassemia was 12.78% among couples in which both parents were carriers.ConclusionsThere was a high prevalence of α- and β-thalassemia in Guangdong Province. This study will contribute to the development of thalassemia prevention and control strategies in Guangdong Province.
Tissue-engineered meniscus regeneration is a very promising treatment strategy for meniscus lesions. However, generating the scaffold presents a huge challenge for meniscus engineering as this has to meet particular biomechanical and biocompatibility requirements. In this study, we utilized acellular meniscus extracellular matrix (AMECM) and demineralized cancellous bone (DCB) to construct three different types of three-dimensional porous meniscus scaffold: AMECM, DCB, and AMECM/DCB, respectively. We tested the scaffolds' physicochemical characteristics and observed their interactions with meniscus fibrochondrocytes to evaluate their cytocompatibility. We implanted the three different types of scaffold into the medial knee menisci of New Zealand rabbits that had undergone total meniscectomy; negative control rabbits received no implants. The reconstructed menisci and corresponding femoral condyle and tibial plateau cartilage were all evaluated at 3 and 6 months (n = 8). The in vitro study demonstrated that the AMECM/DCB scaffold had the most suitable biomechanical properties, as this produced the greatest compressive and tensile strength scores. The AMECM/DCB and AMECM scaffolds facilitated fibrochondrocyte proliferation and the secretion of collagen and glycosaminoglycans (GAGs) more effectively than did the DCB scaffold. The in vivo experiments demonstrated that both the AMECM/DCB and DCB groups had generated neomeniscus at both 3 and 6 months post-implantation, but there was no obvious meniscus regeneration in the AMECM or control groups, so the neomeniscus analysis could not perform on AMECM and control group. At both 3 and 6 months, histological scores were better for regenerated menisci in the AMECM/DCB than in the DCB group, and significantly better for articular cartilage in the AMECM/DCB group compared with the other three groups. Knee MRI scores (Whole-Organ Magnetic Resonance Imaging Scores (WORMS)) were better in the AMECM/DCB group than in the other three groups at both 3 and 6 months. At both 3 and 6 months, RT-PCR demonstrated that aggrecan, Sox9, and collagen II content was significantly higher, and mechanical testing demonstrated greater tensile strength, in the AMECM/DCB group neomenisci compared with the DCB group.
BackgroundThe effect of neoadjuvant chemotherapy (NAC) on Gastric carcinoma (GC) has been extensively studied, while its survival and surgical benefits remain controversial. This study aims to perform a meta-analysis of high-quality randomized controlled trials (RCTs), comparing efficacy, safety and other outcomes of NAC followed by surgery with surgery alone (SA) for GC.MethodsWe systematically searched databases of MEDLINE, EMBASE, The Cochrane Library and Springer for RCTs comparing NAC with SA when treating GC. Reference lists of relevant articles and reviews, conference proceedings and ongoing trial databases were also searched. Primary outcomes were 3-year and 5-year survival rates, survival time, and total and perioperative mortalities. Secondary outcomes included down-staging effects, R0 resection rate, and postoperative complications. Meta-analysis was conducted where possible comparing items using relative risks (RRs) and weighted mean differences (WMDs) according to type of data. NAC-related objective response, safety and toxicity were also specifically analyzed.ResultsA total of 9 RCTs comparing NAC (n = 511) with SA (n = 545) published from 1995 to 2010 were identified. SA tended to be accompanied with higher overall mortality rate than NAC (46.03% vs 40.61%, RR: 0.83, 95% CI: 0.65–1.06, P = 0.14). Significantly, higher incidence of cases without regional lymph node metastasis observed upon resection were achieved among patients receiving NAC than those undergoing SA (25.68% vs 16.95%, RR: 1.92, 95% CI: 1.20–3.06, P = 0.006). All other parameters were comparable. Of the evaluable patients, 43.0% demonstrated either complete or partial response. The comprehensive NAC-related side-effect rate was 18.2% among patients available for safety assessment.ConclusionsNAC contributes to lowering nodal stages, and potentially reduces overall mortality. Response rate may be an important influential factor impacting advantages, with chemotherapy-related adverse effects as a drawback. This level 1a evidence doesn't support NAC to outweigh SA in terms of survival and surgical benefits when dealing with GC.
The hWJMSCs-ACECM scaffold complex achieved better quality repair and regeneration of hyaline cartilage without cartilage-inducing factor, while retaining the structure and functional integrity of the subchondral bone, compared with MF.
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