Beneficial Therapeutic Approach of Acellular PLGA Implants Coupled With Rehabilitation Exercise for Osteochondral Repair: A Proof of Concept Study in a Minipig Model.

BACKGROUND: Osteochondral (OC) repair presents a significant challenge to clinicians. However, whether the use of acellular spongy poly(lactic-co-glycolic acid) (PLGA) scaffolding plus treadmill exercise as a rehabilitation program regenerates OC defects in a large-animal model has yet to be determined. HYPOTHESIS: PLGA scaffolding plus treadmill exercise may offer improved OC repair for both high and low weightbearing regions in a minipig model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 9 mature minipigs (18 knees) were randomly divided into the treadmill exercise (TRE) group or sedentary (SED) group. All pigs received critically sized OC defects in a higher weightbearing region of the medial condyle and a lower weightbearing region of the trochlear groove. In each minipig, a PLGA scaffold was placed in the defect of the right knee (PLGA subgroup), and the defect of the left knee was untreated (empty defect [ED] subgroup). The TRE group performed exercises in 3 phases: warm-up, 3 km/h for 5 minutes; main exercise, 4 km/h for 20 minutes; and cool-down, 3 km/h for 5 minutes. The total duration was about 30 minutes whenever possible. The SED group was allowed free cage activity. RESULTS: At 6 months, the TRE-PLGA group showed the highest gross morphology scores and regenerated a smooth articular surface covered with new hyaline-like tissue, while the defects of the other groups remained and contained nontransparent tissue. Histologically, the TRE-PLGA group also revealed sound OC integration, chondrocyte-like cells embedded in lacunae, abundant glycosaminoglycans, a sound collagen structure, and modest inflammatory cells with an inflammatory response (ie, tumor necrosis factor-α, interleukin-6). In addition, in the medial condyle region, the TRE-PLGA group (31.80 ± 3.03) had the highest total histological scores (TRE-ED: 20.20 ± 5.76; SED-PLGA: 10.25 ± 6.24; SED-ED: 11.75 ± 6.50; P = .004). In the trochlear groove region, the TRE-PLGA group (30.20 ± 6.42) displayed significantly higher total histological scores (TRE-ED: 19.60 ± 7.00; SED-PLGA: 10.00 ± 5.42; SED-ED: 11.25 ± 5.25; P = .006). In contrast, the SED-PLGA and SED-ED groups revealed an irregular surface with abrasion, fibrotic tissue with an empty void and inflammatory cells, disorganized collagen fibers, and less glycosaminoglycan deposition. Micro-computed tomography analysis revealed that the TRE-PLGA group had integrated OC interfaces with continued remodeling in the subchondral bone. Furthermore, comparing the 2 defect regions, no statistically significant differences in cartilage regeneration were detected, indicating the suitability of this regenerative approach for both high and low weightbearing regions. CONCLUSION: Implanting an acellular PLGA scaffold plus treadmill exercise promoted articular cartilage regeneration for both high and low weightbearing regions in minipigs. CLINICAL RELEVANCE: This study suggests the use of a cell-free porous PLGA scaffold and treadmill exercise rehabilitation as an alternative therapeutic strategy for OC repair in a large-animal knee joint model. This combined effect may pave the way for biomaterials and exercise regimens in the application of OC repair.

Effect of a Six-Week Core Conditioning as a Warm-Up Exercise in Physical Education Classes on Physical Fitness, Movement Capability, and Balance in School-Aged Children.

Whether the implementation of feasible, equipment-free, and simple core exercises in warm-up routines in physical education classes for school-aged children is beneficial remains unclear. Therefore, this study investigated the effects of a core conditioning in the warm-up routine of physical education classes on trunk muscular endurance, movement capability, and flexibility in this population. In these pre- and post-test control group experiments, 52 healthy, school-aged children (aged 10-11 years) were cluster randomized allocated to either the dynamic core exercise (DCE) group or general physical education (GPE) group. The DCE group performed a 10-min core exercise routine twice per week for six consecutive weeks; the GPE group performed traditional physical education warm-up exercises regularly. The children were assessed by conducting the trunk muscular endurance test (i.e., dynamic curl-up, static curl-up, plank, and lateral plank), functional movement screen (FMS), and single-leg balance test before and after the intervention. At the end of the intervention, the DCE group demonstrated a significant effect on trunk muscular endurance, movement capability (i.e., FMS scores), flexibility, and balance (each p < 0.001, effect size: 0.38-1.3). Furthermore, the DCE group showed significant improvements in all outcome measurements compared with the GPE group (p < 0.05, effect size: 0.29-1.68). These data may provide a reference for incorporating additional core stability exercises in the warm-up routine of physical education classes in school-aged children in the future.

Effect of different concentrations of bortezomib on the expression of ERK, JNK and P38 in daunorubicin-resistant K562 cells / 中国实验血液学杂志

The aim of this study was to investigate the effect of proteasome inhibitor bortezomib on the expression of ERK, JNK, and P38 in daunorubicin (DNR)-resistant K562 cells and its mechanism. MTT method was used to determine the drug-resistant K562 cells and the cellular toxicity of bortezomib; Western blot was used to detect the expression of protein ERK, JNK and P38 in K562 cells after treatment with 100 nmol/L DNR alone or combined with 1 nmol/L and 10 nmol/L bortezomib for 36 hours. Flow cytometry assay was used to detect the apoptosis rate in each group cells. The results indicated that the expression of ERK and P38 were significantly suppressed (p < 0.05) and the expression of JNK was significantly enhanced (p < 0.05) in the cells treated by DNR combined with bortezomib. It is concluded that bortezomib can decrease the expressions of protein ERK and P38 and enhance the expression of JNK, the bortezomib reverses the cellular drug-resistance and promote cell apoptosis through MAPK pathway.

Efficacy, side effects and blood concentration monitoring of high-dose methotrexate in treatment of 180 children with acute lymphoblastic leukemia / 中国实验血液学杂志

This study was purposed to investigate the effects of high-dose methotrexate (HD-MTX)-CF + VDT protocol on pediatric acute lymphoblastic leukemia (ALL) by means of retrospective analysis. MTX plasma concentration was dynamically detected and evaluated so as to avoid or reduce the side effects of HD-MTX, and adjust the time and dosage of calcium folinate (CF) or carry out the plasma exchange as occasion requires. Totally 180 cases of ALL were enrolled in this study, and received 380 administration of HD-MTX-CF + VDT protocol, including 122 patients with induction therapy as well as 58 cases during maintenance therapy, among which 68 cases were defined as low risk, 80 cases as middle risk and 32 cases as high risk. 2.0 g/m(2) MTX, 3.0 g/m(2) MTX, and 5.0 g/m(2) MTX were individually used according to low risk, middle risk or T immunohistochemical expression. The results indicated that 36.3% cases showed the side-effects of HD-MTX including mucocutaneous lesions, gastrointestinal reaction, hepatic dysfunction, renal damage, fever, myelosuppression, cardiotoxicity, infection and allergic response. All of these side effects were reversible through treatment. The elimination delay of MTX occurred in 110 cases, out of which 3 cases got MTX concentration > 10 µmol/L at 24 hours, 50 cases > 1.0 µmol/L at 44 hours, the remaining 57 cases > 0.1 µmol/L at 68 hours. CF dosage was adjusted according to the concentration of MTX until it was less than 0.1 µmol/L. 1 case had renal interstitial inflammation and acute renal failure, but finally he was cured. No patients received plasma exchange or died. It is concluded that the extramedullary leukemia control protocol, in which MTX is main drug, is effective therapy for obtaining long-term remission and event-free survival rate in ALL patients, but the side effects and risks increase along with the increase of MTX dose. The metabolic level of HD-MTX has found to be obvious individual, so the dynamic monitoring of MTX concentration in plasma and administration of proper dosage of CF are important factors for HD-MTX protocol application in ALL patients.

Side effects of L-asparaginase during therapies for remission induction and maintenance in children with acute lymphocytic leukemia / 中国实验血液学杂志

This study was purposed to investigate the possible side effects of L-asparaginase (L-ASP) in the treatment of patients with acute lymphoblastic leukemia (ALL) and to explore the correlation of these side effects at different therapeutic stages by means of retrospective analysis, so as to reduce the incidence of side effects and improve the safety of chemotherapy and the long-term survival of patients. The probability and severity of side effects related to use of L-ASP in 38 cases of ALL during remission induction therapy (VDLDex regimen) and 40 cases of ALL during maintenance intensive therapy (VMLDex regimen) were compared. The results showed that allergic response, diabetes and drug-induced liver disease happened more frequently during maintenance therapy than during remission induction therapy, while defibrination, abnormal hemagglutinin, acute pancreatitis, hypoproteinemia, gastrointestinal reaction and infectious shock were observed more during remission induction therapy than those at maintenance therapy. In conclusion, the L-ASP showed some side effects especially for the patients during the remission induction therapy which should be paid enough attention. The regular and comprehensive monitoring can effectively reduce and avoid the side effects of L-ASP, to improve the safety of chemotherapy.