Exosomes derived from MSC as drug system in osteoarthritis therapy.

Osteoarthritis (OA) is the most common degenerative disease of the joint with irreversible cartilage damage as the main pathological feature. With the development of regenerative medicine, mesenchymal stem cells (MSCs) have been found to have strong therapeutic potential. However, intraarticular MSCs injection therapy is limited by economic costs and ethics. Exosomes derived from MSC (MSC-Exos), as the important intercellular communication mode of MSCs, contain nucleic acid, proteins, lipids, microRNAs, and other biologically active substances. With excellent editability and specificity, MSC-Exos function as a targeted delivery system for OA treatment, modulating immunity, inhibiting apoptosis, and promoting regeneration. This article reviews the mechanism of action of MSC-Exos in the treatment of osteoarthritis, the current research status of the preparation of MSC-Exos and its application of drug delivery in OA therapy.

Engineered Exosomes with ATF5-Modified mRNA Loaded in Injectable Thermogels Alleviate Osteoarthritis by Targeting the Mitochondrial Unfolded Protein Response.

Osteoarthritis (OA) progression is highly associated with chondrocyte mitochondrial dysfunction and disorders of catabolism and anabolism of the extracellular matrix (ECM) in the articular cartilage. The mitochondrial unfolded protein response (UPRmt), which is an integral component of the mitochondrial quality control (MQC) system, is essential for maintaining chondrocyte homeostasis. We successfully validated the pivotal role of activating transcription factor 5 (ATF5) in upregulating the UPRmt, mitigating IL-1ß-induced inflammation and mitochondrial dysfunction, and promoting balanced metabolism in articular cartilage ECM, proving its potential as a promising therapeutic target for OA. Modified mRNAs (modRNAs) have emerged as novel and efficient gene delivery vectors for nucleic acid therapeutic approaches. In this study, we combined Atf5-modRNA (modAtf5) with engineered exosomes derived from bone mesenchymal stem cells (ExmodAtf5) to exert cytoprotective effects on chondrocytes in articular cartilage via Atf5. However, the rapid localized metabolization of ExmodAtf5 limits its application. PLGA-PEG-PLGA (Gel), an injectable thermosensitive hydrogel, was used as a carrier of ExmodAtf5 (Gel@ExmodAtf5) to achieve a sustained release of ExmodAtf5. In vitro and in vivo, the use of Gel@ExmodAtf5 was shown to be a highly effective strategy for OA treatment. The in vivo therapeutic effect of Gel@ExmodAtf5 was evidenced by the preservation of the intact cartilage surface, low OARSI scores, fewer osteophytes, and mild subchondral bone sclerosis and cystic degeneration. Consequently, the combination of ExmodAtf5 and PLGA-PEG-PLGA could significantly enhance the therapeutic efficacy and prolong the exosome release. In addition, the mitochondrial protease ClpP enhanced chondrocyte autophagy by modulating the mTOR/Ulk1 pathway. As a result of our research, Gel@ExmodAtf5 can be considered to be effective at alleviating the progression of OA.

Treatment of old femoral neck fractures in young adults with a medial buttress plate combined with three cannulated screws and iliac autograft: Surgical technique and preliminary results.

OBJECTIVES: Whether the application of MBP plus cannulated screws works for old femoral neck fractures (OFNF) is unknown. The purpose of this study is to present a case series of OFNF in young adults using calcar buttress plate and three cannulated screws with autologous iliac bone grafts. METHODS: We conducted a retrospective study of eleven young patients (6 males and 5 females) with femoral neck fractures who were treated with open reduction and internal fixation at a single center between 2013 and 2021. The subjects had trauma-to-surgery intervals longer than 3weeks and all were fixed with a calcar buttress plate combined with three cannulated screws, which were supplemented by autologous iliac bone grafts. RESULTS: All eleven cases achieved radiological union under the surgery technique, which occurred on average at 4.46±1.29months after surgery. Complications included femoral neck shortening in all cases, heterotopic ossification in three cases, and osteonecrosis of the femoral head in two cases. One patient with osteonecrosis of the femoral head received total hip arthroplasty. In follow-ups of 24-52months, the median Harris hip score was 81.64±15.39. CONCLUSIONS: The medial buttress plate in combination with three cannulated screws and iliac autograft may be a good choice for treating old femoral neck fractures in young adults. LEVEL OF EVIDENCE: IV, case series.

Comparative analysis of pathogen distribution in patients with fracture-related infection and periprosthetic joint infection: a retrospective study.

BACKGROUND: The purpose of this study is to investigate the microbial patterns of periprosthetic joint infection (PJI) and fracture-related infection (FRI), and guide for the formulation of more accurate empirical antimicrobial regimens based on the differences in pathogen distribution. METHODS: A comparative analysis of pathogen distribution was conducted between 153 patients (76 with PJI and 77 with FRI). Predicted analyses against isolated pathogens from two cohorts were conducted to evaluate the best expected efficacy of empirical antimicrobial regimens (imipenem + vancomycin, ciprofloxacin + vancomycin, and piperacillin/tazobactam + vancomycin). RESULTS: Our study found significant differences in pathogen distribution between the PJI and FRI cohorts. Staphylococci (61.3% vs. 31.9%, p = 0.001) and Gram-negative bacilli (GNB, 26.7% vs. 56.4%, p < 0.001) were responsible for the majority of infections both in the PJI and FRI cohorts, and their distribution in the two cohorts showed a significant difference (p < 0.001). Multi-drug resistant organisms (MDRO) were more frequently detected in the FRI cohort (29.3% vs. 44.7%, p = 0.041), while methicillin-resistant coagulase-negative Staphylococci (MRCoNS, 26.7% vs. 8.5%, p = 0.002) and Canidia albicans (8.0% vs. 1.1%, p = 0.045) were more frequently detected in the PJI cohort. Enterobacter spp. and Acinetobacter baumannii were detected only in the FRI cohort (11.7% and 8.5%, respectively). CONCLUSIONS: Staphylococci and GNB were responsible for the majority of infections in both PJI and FRI. Empirical antimicrobial therapy should focus on the coverage of Staphylococci in PJI and GNB in FRI, and infections caused by MDROs should be more vigilant in FRI, while the high incidence of MRCoNS in PJI should be noted, which could guide for the formulation of more accurate empirical antimicrobial regimens. Targeted therapy for FRI caused by A. baumannii and PJI caused by C. albicans needs to be further investigated. Our study reports significant differences in pathogen distribution between the two infections and provides clinical evidence for studies on the mechanism of implant-associated infection.

Core decompression with ß-tri-calcium phosphate grafts in combination with platelet-rich plasma for the treatment of avascular necrosis of femoral head.

BACKGROUND: This study was aimed to investigate whether the application of platelet-rich plasma (PRP) combined with ß-tri-calcium phosphate (ß-TCP) grafts after core decompression (CD) could improve the clinical outcomes of early stage of avascular necrosis of femoral head. METHODS: Forty-five (54 hips) patients with Ficat-Arlet classification stage I-II treated by CD with ß-TCP grafts with or without the application of PRP from July 2015 to October 2020 were reviewed. Group A (CD + ß-TCP grafts) included 24 patients (29 hips), while group B (CD + ß-TCP grafts + PRP) included 21 patients (25 hips). Visual analogue scale (VAS) score, Harris hip score (HHS), change in modified Kerboul angle and the hip joint survival were evaluated and compared between the groups. Patients had a mean follow-up period of 62.1 ± 17.2 months and 59.3 ± 14.8 months in group A and group B, respectively. RESULTS: The mean VAS scores in group A was significantly higher than group B at the 6 months (2.9 ± 0.7 vs 1.9 ± 0.6, p < 0.01) and final follow up postoperative (2.8 ± 1.2 vs 2.2 ± 0.7, p = 0.04). The mean HHS in group A was significantly lower than group B at the 6 months (80.5 ± 13.8 vs 89.8 ± 12.8, p = 0.02). However, at the final follow up, there is no significant difference between the groups (77.0 ± 12.4 vs 83.1 ± 9.3, p = 0.07). The mean change in modified Kerboul angle was -7.4 ± 10.6 in group A and -19.9 ± 13.9 in group B which is statistically significant (p < 0.01). Survivorship from total hip arthroplasty were 86.2%/84% (p = 0.86) at the final follow up, which was not statistically significant. No serious complications were found in both groups. CONCLUSIONS: A single dose of PRP combined with CD and ß-TCP grafts provided significant pain relief, better functional outcomes, and delayed progression in the short term compared to CD combined with ß-TCP grafts. However, the prognosis of the femoral head did not improve significantly in the long term. In the future, designing new implants to achieve multiple PRP injections may improve the hip preservation rate.

Variations in lower limb alignments indicate pelvic tilt after total hip arthroplasty.

OBJECTIVE: We sought to correlate various spinopelvic and lower limb alignments, and to examine the current spinopelvic theories on a Chinese cohort. METHODS: We retrospectively reviewed 166 patients undergoing THA. Among them, 138 patients with unilateral THA met the inclusion criteria. Sagittal alignments and cup orientations were measured on standing and sitting lateral EOS images. Patients were categorized into two groups with a scoring system for lumbar spine degeneration. Patients' demographics including age, sex, lumbar spine degeneration and radiographic measurements were studied. RESULTS: PT, SS, LL and TK differed significantly between standing and sitting within each group except for TK in degenerative group (32.8 ± 13.9 vs. 32.9 ± 14.2, p = 0.905). Compared with degenerative spine group, non-degenerative spine patients have great pelvic mobility (ΔPT, -24.4 ± 12.5° vs. -17.6 ± 10.7, p = 0.0008), greater lumbar mobility (ΔLL, -34.8 ± 15.2 vs. -21.7 ± 12.2, p = < 0.0001) and compensatory cup orientation changes (ΔRA, -15.5 ± 11.1 vs. -12.0 ± 8.4, p = 0.00920; ΔRI, -10.8 ± 11.5 vs. -5.6 ± 7.5, p = 0.0055). Standing PT and ankle dorsiflexion angle correlated positively (R2 = 0.236, p = 0.005). CONCLUSION: THA patients in this cohort showed a spinopelvic motion paradigm similar to that from previous studies on Caucasians. Ankle dorsiflexion indicate greater posterior pelvic tilt on standing. Surgeons should beware of risks of instability in patients with lower limb compensations. ADVANCES IN KNOWLEDGE: This study provides new insights into the clinical relevance of lower limb alignments to spinopelvic motion after THA in a relatively young Chinese population.

Preoperative prognostic nutritional index is useful factor for predicting postoperative delirium after primary total joint arthroplasty.

BACKGROUND: Postoperative delirium (PD), as an acute brain failure, is widely reported as a very common postoperative complication, and it is closely associated with increased morbidity and mortality. Recently, malnutrition is reported as one of the risk factors for PD. The prognostic nutritional index (PNI) is a simple method for nutritional evaluation. However, few studies have discussed the effectiveness of PNI as a nutritional assessment in predicting PD after primary total joint arthroplasty (TJA). The aim of this study is to investigate potential risk factors including PNI for PD following primary TJA. METHODS: A retrospective analysis of 994 patients was performed to identify risk factors associated with PD after primary TJA by using univariate and multivariate analyses. A receiver operating characteristic curve and the area under the curve were applied to evaluate the significant results of the multivariate analysis and the optimal cutoff value (CV). RESULTS: Postoperatively, sixty-seven patients (67/994, 6.7 %) experienced PD. Univariate analysis demonstrated that operative time, duration of anesthesia, age, hypertension, serum albumin, and PNI differed between the PD and non-PD groups (P < 0.05). Multivariate logistic regression analysis showed that the preoperative PNI (odds ratio [OR]: 0.908; 95 % confidence interval [CI]: 0.840-0.983; CV: 47.05), age of patients (OR: 1.055; 95 % CI: 1.024-1.087; CV: 73.5 years), and hypertension (OR: 1.798; 95 % CI: 1.047-3.086), were independently associated with PD (P < 0.05). CONCLUSIONS: A low preoperative PNI associated with malnutrition was demonstrated to be an independent risk factor for PD following primary TJA. Patients with preoperative low PNI should be cautioned and provided with adequate nutritional intervention to reduce postoperative PD.

A modified anterior drawer test for anterior cruciate ligament ruptures.

OBJECTIVE: This study was aimed to utilize a modified anterior drawer test (MADT) to detect the anterior cruciate ligament (ACL) ruptures and investigate its accuracy compares with three traditional tests. METHODS: Four hundred patients were prospectively enrolled between January 2015 and September 2017 preoperatively to undergo knee arthroscopic surgeries. The MADT, anterior drawer test, Lachman test, and pivot shift test were used in the outpatient clinical setting and were compared statistically for their accuracy in terms of ACL ruptures, with arthroscopic findings as the gold standard. RESULTS: The prevalence of ACL ruptures in this study was 37.0%. The MADT demonstrated the highest sensitivity (0.89) and accuracy (0.92) among the four tests and had comparable specificity (0.94) and a positive predictive value (0.90) compared with the anterior drawer test, Lachman test, and pivot shift test. The diagnostic odds ratio (DOR) of MADT was 122.92, with other test values of no more than 55.45. The area under the receiver operating characteristic curve (AUC) for the MADT was 0.92 ± 0.01, with a significant difference compared with that for the anterior drawer test (z = 17.00, p < 0.001), Lachman test (z = 9.66, p = 0.002), and pivot shift test (z = 16.39, p < 0.001). The interobserver reproducibility of the MADT was good, with a kappa coefficient of 0.86. When diagnosing partial tears of ACL, the MADT was significantly more sensitive than the anterior drawer test (p < 0.001), Lachman test (p = 0.026), and pivot shift test (p = 0.013). The MADT showed similar sensitivity in detecting anteromedial and posterolateral bundle tears (p = 0.113) and no difference in diagnosing acute and chronic ACL ruptures (χ2 = 1.682, p = 0.195). CONCLUSIONS: The MADT is also an alternative diagnostic test to detect ACL tear, which is equally superior to the anterior drawer test, Lachman test, and pivot shifting test. It could improve the diagnosis of ACL ruptures combined with other clinical information including injury history, clinical examination, and radiological findings. LEVELS OF EVIDENCE: Level II/observational diagnostic studies TRIAL REGISTRATION: Chinese Clinical Trial Registry. ChiCTR1900022945 /retrospectively registered.

Tibial component coverage affects tibial bone resorption and patient-reported outcome measures for patients following total knee arthroplasty.

PURPOSE: The aim of this study is to investigate the prognostic value of tibial component coverage (over-hang and under-hang) and the alignment of total knee arthroplasty (TKA) components 1 week after surgery. We select patient-reported outcome measures (PROMS) (the Knee Society score (KSS score) and the Western Ontario and McMaster Universities Osteoarthritis Index-pain score (WOMAC pain score)) and tibial bone resorption (TBR) 2 years after surgery as the end points. METHODS: The study retrospectively analyzed 109 patients undergoing TKA (fixed-bearing prosthesis with asymmetrical tibial tray) from January 2014 to December 2017 in Huashan Hospital. By using standard long-leg X-rays, anteroposterior (AP) and lateral X-rays of the knee, tibial component coverage (under-hang or over-hang), AP tibial-femoral anatomical angle (AP-TFA), AP femoral angle (AP-FA), AP tibial angle (AP-TA), and lateral tibial angle (L-TA) were measured at 1 week after surgery, while TBR was measured through postoperative 1-week and 2-year AP and lateral radiographs of the knee on three sides (medial side, lateral side on AP radiograph, and anterior side on lateral radiograph). The Pearson correlation analysis, simple linear regression, multiple linear regression, the Student's t test, and one-way ANOVA together with Tukey's post hoc test (or Games-Howell post hoc test) were used in the analyses. RESULTS: Tibial under-hang was more likely to appear in our patients following TKA (42%, medially, 39%, laterally, and 25%, anteriorly). In multivariate linear regression analysis of TBR, tibial under-hang (negative value) 1 week after surgery was positively correlated with TBR 2 years later on the medial (p = 0.003) and lateral (p = 0.026) side. Tibial over-hang (positive value) 1 week after surgery on the medial side was found negatively related with KSS score (p = 0.004) and positively related with WOMAC pain score (p = 0.036) 2 years later in multivariate linear regression analysis of PROMS. Both scores were better in the anatomically sized group than in the mild over-hang group (or severe over-hang) (p < 0.001). However, no significant relationship was found between the alignment of TKA components at 1 week after surgery and the end points (TBR and PROMS) 2 years later. CONCLUSION: Under-hang of the tibial component on both the medial and lateral sides can increase the risk of TBR 2 years later. Over-hang of tibial component on the medial side decreases the PROMS (KSS score and WOMAC pain score) 2 years later. An appropriate size of tibial component during TKA is extremely important for patient's prognosis, while the alignment of components might not be as important.

Nonanatomical Reduction of Femoral Neck Fractures in Young Patients (≤65 Years Old) with Internal Fixation Using Three Parallel Cannulated Screws.

PURPOSE: The study is aimed at investigating the association between different reduction classifications (anatomic reduction, positive buttress position reduction, and negative buttress position reduction) and two end points (complications and reoperations). METHODS: The study retrospectively analyzed 110 patients undergoing internal fixation with three parallel cannulated screws from January 2012 to January 2019 in Huashan Hospital. Based on the principles of the "Gotfried reduction," all enrolled patients were divided into three groups: anatomic reduction, positive buttress position reduction, and negative buttress position reduction intraoperatively or immediately after surgery. Clinical characteristics including age, sex, side, Garden classification, Pauwels classification, fracture level, reduction classification, Garden alignment index angles, cortical thickness index (CTI), tip-caput distance (TCD), angle of the inferior screw, and the two ending points (complications and reoperations) were included in the statistical analysis. The Mann-Whitney U-test, the chi-square test, Fisher's exact test, and multiple logistic regression analysis were used in the study. RESULTS: Of the 110 patients included in our study, the mean ± standard deviation (SD) of age was 51.4 ± 10.4 years; 41 patients showed anatomic reduction, 35 patients showed positive buttress position reduction, and 34 patients showed negative buttress position reduction. For the outcomes, 24 patients (anatomic reduction: 6 [14.6%]; positive buttress position reduction: 5 [14.3%]; negative buttress position reduction: 13 [38.2%]) had complications, while 18 patients (anatomic reduction: 5 [12.2%]; positive buttress position reduction: 3 [8.6%]; negative buttress position reduction: 10 [29.4%]) underwent reoperations after surgery. In the multivariate logistic regression analysis of complications, negative buttress position reduction (negative buttress position reduction vs. anatomic reduction, OR = 4.309, 95%CI = 1.137 to 16.322, and p = 0.032) was found to be correlated with higher risk of complications. The same variable (negative buttress position reduction vs. anatomic reduction, OR = 5.744, 95%CI = 1.177 to 28.042, and p = 0.031) was also identified as risk factor in the multivariate logistic regression analysis of reoperations. However, no significant difference between positive reduction and anatomical reduction was investigated in the analysis of risk factors for complications, not reoperations. CONCLUSION: Positive buttress position reduction of femoral neck fractures in young patients showed a similar incidence of complications and reoperations compared with those of anatomic reduction. For irreversible femoral neck fractures, if positive buttress position reduction has been achieved intraoperatively, it is not necessary to pursue anatomical reduction; however, negative reduction needs to be avoided.

Predictive values of the postoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio for the diagnosis of early periprosthetic joint infections: a preliminary study.

BACKGROUND: Several studies have been conducted to report diagnostic values of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in the many diseases, such as oncological, inflammatory, and some infectious diseases. However, the predictive value of these laboratory parameters for early periprosthetic joint infections (PJIs) has not yet been reported. The aim of this study was to determine predictive values of the postoperative NLR, PLR, and LMR for the diagnosis of PJIs. METHODS: In this retrospective study, 104 patients (26 early PJI cases and 78 non-PJI cases) who underwent total joint arthroplasty were enrolled in this study. All the patients were then categorized into two groups: PJI group, patients with the diagnosis of PJI (26 patients; 14 males, 12 females; mean age = 65.47 ± 10.23 age range = 51-81 ) and non-PJI group, patients without PJI (78 patients; 40 males, 38 females; mean age = 62.15 ± 9.33, age range = 41-92). We defined "suspected time" as the time that any abnormal symptoms or signs occurred, including fever, local swelling, or redness around the surgical site between 2 and 4 weeks after surgery and before the diagnosis. Suspected time and laboratory parameters, including NLR, PLR, LMR, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), were compared between both groups. The trends of postoperative NLR, LMR, PLR, CRP, and ESR were also reviewed. The predictive ability of these parameters at the suspected time for early PJI was evaluated by multivariate analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: NLR, PLR, and LMR returned to preoperative levels within 2 weeks after surgery in the two groups. In the PJI group, NLR and PLR were significantly increased during the incubation period of infection or infection, and LMR was significantly reduced, although 61.5% (16/26) of the patients had normal white blood cells. Interestingly, ESR and CRP were still relatively high 2 weeks after surgery and were not different between the two groups before infection started (p = 0.12 and 0.4, respectively). NLR and PLR were significantly correlated with early PJI (Odds ratios for NLR and PLR = 88.36 and 1.12, respectively; p values for NLR and PLR = 0.005 and 0.01, respectively). NLR had great predictive ability for the diagnosis of early PJI, with a cut-off value of 2.77 (sensitivity = 84.6%, specificity = 89.7%, 95% CI = 0.86-0.97). CONCLUSIONS: ESR and CRP seem not to be sensitive for the diagnosis of early PJI due to their persistently high levels after arthroplasty. The postoperative NLR at the suspected time may have a great ability to predict early PJI.

Predictive value of adipose to muscle area ratio based on MRI at knee joint for postoperative functional outcomes in elderly osteoarthritis patients following total knee arthroplasty.

BACKGROUND: The current research used a new index-adipose to muscle area ratio (AMR)-to measure fatness compared with body mass index (BMI) in elderly osteoarthritis (OA) patients following total knee arthroplasty. Our study aimed to test the relationship between the two indexes (AMR and BMI) and to examine whether AMR was a predictive factor of patient-reported outcome measures (PROMS) for elderly OA patients following total knee arthroplasty (TKA). METHODS: The retrospective data of 78 OA patients (older than 60 years) following TKA was included in our study. Clinical features of patients included age, BMI, sex, AMR, side of the implant, time of follow-up, complications, the Knee Society Score (KSS score), and the Hospital for Special Surgery knee score (HSS score). The area of adipose tissue and muscle tissue was measured on the cross section (supra-patella, midline of the patella, joint line of the knee) of the knee magnetic resonance imaging (MRI). AMR was calculated as the average of adipose to muscle area ratio at the three levels. The Pearson correlation analysis, simple linear regression, and multiple linear regression were used to study the relationship between BMI, AMR, and PROMS (KSS total-post score and HSS-post score) in the study. RESULTS: Of all patients, the mean (± standard deviations (SD)) of age was 67.78 ± 4.91 years. For BMI and AMR, the mean (± SD) were 26.90 ± 2.11 and 2.36 ± 0.69, respectively. In Pearson correlation analysis, BMI had a good correlation with AMR (r = 0.56, p = 0.000), and AMR (r = - 0.37, p = 0.001, HSS-post score; r = - 0.43, p = 0.000, KSS total-post score) had better correlations with PROMS postoperatively compared with BMI (r = - 0.27, p = 0.019, HSS-post score; r = - 0.33, p = 0.003, KSS total-post score). In multivariate linear regression analysis, AMR was negatively correlated with KSS total-post score as well as HSS-post score, while BMI was not. As for patients with complications, AMR values were between the 3rd quartile and 4th quartile of the AMR value in the entire study cohort. CONCLUSIONS: In this study, the new obesity evaluation indicator-AMR, which was well related with BMI, was found to be a predictor of PROMS (KSS total-post score and HSS-post score) in elderly OA patients following TKA.

Combined culture experiment of mouse bone marrow mesenchymal stem cells and bioceramic scaffolds.

Articular cartilage injuries are common orthopedic conditions that severely affect the quality of life of patients. Tissue engineering can facilitate cartilage repair and the key points involve scaffolding and seed cell selection. Pre-experiments found a range of microstructures of bioceramic scaffolds suitable for chondrocyte adhesion and proliferation, and maintaining chondrocyte phenotype. Three-dimensional cultures of bone marrow mesenchymal stem cell (BMSC) scaffolds were implanted into mice. According to the shape of the bioceramic scaffolds and the implantation time in vivo, RNA sequencing was performed on the removed scaffolds to explore the molecular mechanism. The in vitro bone plate culture can induce differentiation of chondrocytes, making culture different to that produced in vitro. Implantation of scaffolds in vivo increases the expression of bone-related genes. The ceramic rod-like material was found to be superior to the disc shape, and the bone repair effect was more marked with longer implantation times. Gene Ontology analysis revealed that 'cell chemotaxis', 'negative regulation of ossification' and 'bone development' pathways were involved in recovery. It was further confirmed that BMSCs were suitable as seed cells for cartilage tissue engineering, and that the ß-tricalcium phosphate scaffold maybe ideal as cartilage tissue engineering scaffold material. The present research provided new insights into the molecular mechanism of cartilage repair by BMSCs and bioceramic scaffolds. Bioinformatics analysis revealed that AMMECR1L-like protein, tumor necrosis factor-induced protein 2, inhibitor of nuclear factor-B kinase subunit and protein kinase C type and 'negative regulation of ossification' and 'bone development' pathways may be involved in osteoblast maturation and bone regeneration.

Three-dimensional finite element analysis of silk protein rod implantation after core decompression for osteonecrosis of the femoral head.

BACKGROUND: Several methods are available for the treatment of early-stage osteonecrosis of the femoral head. Core decompression with implantation is a widely-used treatment. However, no single implant is recognized as the most effective way to prevent disease progression. Silk has high strength and resiliency. This study explored the possibility of a strong and resilient silk protein biomaterial as a new alternative implant. METHODS: We investigated the biomechanical properties of the silk protein material by regular compression, torsion, and three-point bending tests. We established three-dimensional finite element models of different degrees of femoral head osteonecrosis following simple core decompression, fibula implantation, porous tantalum rod implantation, and silk protein rod implantation. Finally, we compared the differences in displacement and surface stress under load at the femoral head weight-bearing areas between these models. RESULTS: The elastic modulus and shear modulus of the silk protein material was 0.49GPa and 0.66GPa, respectively. Three-dimensional finite element analyses demonstrated less displacement and surface stress at the femoral head weight-bearing areas following silk protein rod implantation compared to simple core decompression (p < 0.05), regardless of the extent of osteonecrosis. No differences were noted in the surface deformation or surface stress of the femoral head weight-bearing areas following silk protein rod, fibula or tantalum rod implantation (p > 0.05). CONCLUSIONS: When compared with simple core decompression, silk protein rod implantation demonstrated less displacement and surface stress at the femoral head weight-bearing area, but more than fibula or tantalum rod implantation. Similar effects on the surface stress of the femoral head between the silk rod, fibula and tantalum rod implantations, combined with additional modifiable properties support the use of silk protein as a suitable biomaterial in osteonecrosis surgery.

Association of hepatitis B infection with high-risk complications in total joint arthroplasty.

BACKGROUND: An increasing number of patients with hepatitis B virus (HBV) infection are undergoing total joint arthroplasty (TJA) surgery in China. Less attention is provided to the special populations and the purpose of this study is to assess the effect of HBV infection on the prognosis TJAs. METHODS: We retrospectively reviewed patients who underwent elective primary hip and knee arthroplasties in Shanghai Huashan Hospital from 2013 to 2016. Non-hepatitis B cohort was built to match the case cohort to identify whether HBV infection was a risk factor associated with postoperative complications. A total number of 196 patients who underwent primary TJAs were involved in the study, including 49 patients with hepatitis B and 147 non-hepatitis B subjects. RESULTS: Among all the patients with TJAs, 5.5% of patients were infected with HBV for the first time. The incidence rate of complications in patients after arthroplasty with hepatitis B infection was significantly higher than that in patients without hepatitis B (10.2% compared to 4.7%, P < 0.01). Surgical related complications (6.1% compared to 3.4%) and general medical complications (4.1% compared to 1.3%) were higher than those in non-B hepatitis group. Compared with non-B hepatitis group, the overall risk of hepatitis B infection increased by 25% (95% CI, 1.04-1.46; p < 0.01). Similar results were obtained for medical and surgical complications. HBV infection presented a 31% increased risk (95% CI, 1.02-1.62; p < 0.01) for medical complication and an 18% increased risk (95% CI, 1.10-1.26; p < 0.01) for surgical complication. No statistical difference was found between the surgical methods and sex. However, a significant difference of C-reactive protein (CRP) level was found between HBV infection group and the matched non-infected group (P < 0.01). CONCLUSION: This is the first study to investigate the risk of perioperative complications of hepatitis B in Chinese TJAs patients. In consideration of the large population of HBV infection in China, more attention and medical care should be provided to patients with HBV infection who need to undergo TJA operation.

How much does lumbar fusion change sagittal pelvic tilt in individuals receiving total hip arthroplasty?

BACKGROUND: This study primarily aims to examine the effect of lumbar fusion on changes in sagittal pelvic tilt (SPT) in total hip arthroplasty (THA) patients. METHODS: We reviewed 19 hip osteoarthritic patients undergoing THA with or without lumbar fusion. The gender, age, primary disease, Deyo comorbidity score, and year of surgery were sorted and matched. All patients were followed up for at least 12 months. They were compared in terms of the SPT angle, Harris hip score (HHS) and complications. RESULTS: On average, the patients receiving lumbar fusion had a - 3.9 (95% CI - 7.7 to - 1.5) degrees of SPT before THA and - 2.7 (95% CI - 6.5 to 1.1) degrees postoperatively, and the THA patients without lumbar fusion averaged 2.5 (95% CI - 0.1 to 5.0) degrees and 4.2 (95% CI 2.0 to 6.4) degrees, respectively. In the lumbar fusion patients, the mean SPT was - 3.9 (95% CI - 9.9 to 2.0) degrees with L5S1 fusion and - 4.0(95% CI - 10.0 to 2.1) degrees without L5S1 fusion on the standing radiograph before THA (t = 0.01, P = 0.99). The mean SPT was - 1.2 (95% CI - 4.9 to 2.6) degrees with one- and two-segment fusion and - 10.0 (95% CI - 18.5 to 1.5) degrees with three- and four-segment fusion before THA (t = 2.60, P = 0.02). There was no statistically significant difference in cup inclination and cup anteversion after THA between the lumbar fusion and control groups. These patients in the two groups achieved a similar HHS 12 months after THA despite the fact that they had different SPT and HHS before THA. CONCLUSION: Lumbar fusion appears to increase the posterior SPT by approximately 6 degrees in the patients undergoing THA. Lumbar fusion of more than two segments is a predictor of more posterior SPT changes, but fusion of L5S1 is not.

The predictive value of preoperative neutrophil-lymphocyte ratio (NLR) on the recurrence of the local pigmented villonodular synovitis of the knee joint.

BACKGROUND: To explore and evaluate the predictive value of preoperative Neutrophil-lymphocyte ratio (NLR) on the recurrence of pigmented villonodular synovitis (PVNS) of the knee joint treated by arthroscopic surgery combining local radiotherapy. METHODS: Sixty pathological-proven PVNS cases of the knee joint in our department from April 2006 to March 2017 were included. All of them are treated by arthroscopic synovectomy combined with adjuvant radiotherapy. The pre-operative hematological indexes such as c-reactive protein (CRP), erythrocyte sedimentation rate (ESR), NLR, Platelet-lymphocyte ratio (PLR) and Lymphocyte-monocyte ratio (LMR) were collected retrospectively and their relationship with postoperative recurrence was analyzed by using univariate and multivariate analysis, the receiver operating characteristic curves (ROC curve), the Kappa correspondence test and the Mc Nemar Chi-square test. RESULTS: All 60 patients were followed up for a median of 52.8 months (7-138 months) and the recurrence rate is about 23.3% (14/60). There is a significant difference in NLR between the recurrent and non-recurrent group (P = 0.002). It had a certain correlation with postoperative recurrence (correlation coefficient r = 0.438, P = 0.001). The optimal thresholds in ROC curve were 2.42 (sensitivity 71.4%, specificity 78.3% respectively). which had predictive ability for recurrence after arthroscopic treatment. CONCLUSION: The preoperative NLR is an easy and cost-effective predictor for relapse in PVNS of the knee joint after the arthroscopic surgery combined with local radiotherapy, which is of profound significance to guide clinical work.

Norcantharidin modulates the miR-30a/Metadherin/AKT signaling axis to suppress proliferation and metastasis of stromal tumor cells in giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is a benign but locally aggressive tumor, which can cause significant bone destruction at the epiphysis of long bones. Recent studies have demonstrated that norcantharidin (NCTD) can inhibit the proliferation and migration of various human cancer cells, but the role of NCTD in GCTB has not previously been evaluated. The aim of this study was to explore the nature of the anti-cancer effects of NCTD in GCTB and to elucidate the biomolecular mechanisms responsible for these effects. Primary stromal cell cultures, representing the main neoplastic component of GCTB, were used for cell-based experiments. Firstly, the anti-cancer effects of NCTD on GCTB stromal tumor cells were investigated by CCK-8 assay, flow cytometry and transwell invasion assay. Next, microRNA (miRNA) microarray and quantitative reverse transcription PCR (qRT-PCR) analyses were performed to examine and verify altered expression of miRNAs associated with NCTD treatment. Subsequently, the GCTB stromal cells were transfected with miR-30a inhibitor to confirm its involvement in the observed anti-cancer effects of NCTD. Luciferase reporter assays were carried out to identify the target gene of miR-30a. Moreover, changes in the expression of protein markers of AKT signaling were measured by Western Blot analysis. The results demonstrated that NCTD treatment could inhibit cell proliferation, block the cell cycle process and induce cell apoptosis in GCTB stromal cells. An inhibitory effect of NCTD on GCTB stromal cell invasion through inhibition of epithelial mesenchymal transition (EMT) was also observed. Expression of miR-30a was significantly upregulated by NCTD treatment and miR-30a knockdown significantly reversed the anti-tumor effects of NCTD against GCTB stromal cells. Of note, metadherin (MTDH), a novel oncogene which modulates the AKT pathway, was identified as a direct target of miR-30a in GCTB stromal cells. Further data showed that miR-30a could negatively regulate the expression of MTDH and the AKT pathway in GCTB stromal cells. Importantly, MTDH expression was found to be inversely correlated with miR-30a expression in clinical GCTB specimens. Moreover, NCTD treatment effectively suppressed the AKT signaling pathway as demonstrated by downregulation of phosphorylated-Akt S473 (p-Akt S473), p-Akt (T308), phosphorylated-glycogen synthase kinase (GSK)3ß (p-GSK3ß) and c-Myc, whilst miR-30a inhibition re-activated the AKT signaling pathway in GCTB stromal cells. Our findings demonstrate that NCTD can inhibit cell proliferation and metastasis of GCTB stromal cells in vitro, via modulating the miR-30a/MTDH/AKT signaling axis. This suggests that NCTD has potential as a novel therapeutic treatment for GCTB.

FGF2 and FAM201A affect the development of osteonecrosis of the femoral head after femoral neck fracture.

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease associated with high disability, and femoral neck fracture (FNF) is one of the most common reasons for traumatic ONFH. This study was designed to reveal the mechanisms underlying ONFH. Using fastx_toolkit and prinseq-lite tools, quality control was conducted for the sequencing data. The differentially expressed genes (DEGs, including both mRNAs and lncRNAs) between ONFH and FNF samples were identified using the edgeR package in R, and were then subjected to enrichment analysis using the BioCloud platform. Subsequently, protein-protein interaction (PPI) networks were constructed using Cytoscape software. After the target genes of DE-lncRNAs were predicted based on Spearman's rank correlation coefficient, lncRNA-gene coexpression network was visualized using the Cytoscape software. Furthermore, functional enrichment analysis was carried out for the target genes using the clusterprofiler package in R. Additionally, the key genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2965 DEGs were identified from the ONFH samples, including 602 DE-lncRNAs (such as downregulated FAM201A). In the PPI networks, eight upregulated genes (including FGF2, IGF1, SOX9, and COL2A1) and 11 downregulated genes were among the top 20 genes according to all of the scores, such as degree centrality, closeness centrality, and betweenness centrality scores. Functional enrichment analysis showed that IGF1, SOX9, and COL2A1 were significantly enriched during skeletal system development. Moreover, qRT-PCR experiments detected the upregulation of FGF2 and downregulation of FAM201A in ONFH samples. FGF2 and FAM201A were correlated with the development of ONFH. Besides, IGF1, SOX9, and COL2A1 might also affect the pathogenesis of ONFH.

Microarray­based screening of differentially expressed genes in glucocorticoid­induced avascular necrosis.

The underlying mechanisms of glucocorticoid (GC)­induced avascular necrosis of the femoral head (ANFH) have yet to be fully understood, in particular the mechanisms associated with the change of gene expression pattern. The present study aimed to identify key genes with a differential expression pattern in GC­induced ANFH. E­MEXP­2751 microarray data were downloaded from the ArrayExpress database. Differentially expressed genes (DEGs) were identified in 5 femoral head samples of steroid­induced ANFH rats compared with 5 placebo­treated rat samples. Gene Ontology (GO) and pathway enrichment analyses were performed upon these DEGs. A total 93 DEGs (46 upregulated and 47 downregulated genes) were identified in GC­induced ANFH samples. These DEGs were enriched in different GO terms and pathways, including chondrocyte differentiation and detection of chemical stimuli. The enrichment map revealed that skeletal system development was interconnected with several other GO terms by gene overlap. The literature mined network analysis revealed that 5 upregulated genes were associated with femoral necrosis, including parathyroid hormone receptor 1 (PTHR1), vitamin D (1,25­Dihydroxyvitamin D3) receptor (VDR), collagen, type II, α1, proprotein convertase subtilisin/kexin type 6 and zinc finger protein 354C (ZFP354C). In addition, ZFP354C and VDR were identified to transcription factors. Furthermore, PTHR1 was revealed to interact with VDR, and α­2­macroglobulin (A2M) interacted with fibronectin 1 (FN1) in the PPI network. PTHR1 may be involved in GC­induced ANFH via interacting with VDR. A2M may also be involved in the development of GC­induced ANFH through interacting with FN1. An improved understanding of the molecular mechanisms underlying GC­induced ANFH may provide novel targets for diagnostics and therapeutic treatment.