Effect of Posterior Cruciate Ligament Resection on Gap Balancing in Robot-assisted Total Knee Arthroplasty.

OBJECTIVE: Retention or sacrifice of the posterior cruciate ligament (PCL) is one of the most controversial issues while performing total knee arthroplasty (TKA). This study aimed to evaluate the impact of PCL resection on flexion-extension gaps, femoral component rotation, and bone resection amounts during robot-assisted TKA. METHODS: This prospective study included 40 patients with knee osteoarthritis who underwent robot-assisted posterior-stabilized (PS) TKA between September 2021 and February 2022. Of the patients, 75% were women (30/40) with a mean age and BMI of 72.6 years and 27.4 kg/m2, respectively. The guidance module and camera stand assembly were used to capture gaps before and after PCL resection. Measurements of femoral component rotation and bone resection amounts were made in cruciate-retaining (CR) TKA mode and PS-TKA mode. RESULTS: After PCL resection, the mean change in the medial and lateral compartments of flexion gaps increased by 2.0 and 0.6 mm, respectively (p < 0.001). Compared with the CR-TKA mode group, the bone resection amounts of the medial posterior condyle and the lateral posterior condyle in the PS-TKA mode group decreased by 2.0 ± 1.1 and 1.1 ± 1.1 mm, respectively, and the external rotation of the femoral prosthesis relative to the posterior condylar axis and trans-epicondylar line was reduced by 1.0° ± 1.3° and 1.2° ± 1.6°, respectively (p < 0.001). CONCLUSION: The release of the PCL did not affect the extension gap, but significantly increased the flexion gap. Moreover, the increases in the medial flexion gap were greater than those of the lateral flexion gap. After PCL resection, less external rotation of the femoral prosthesis and fewer bone cuts of the posterior femur were needed in PS-TKA.

ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity.

BACKGROUND: The role of Acyl-CoA dehydrogenase long chain (ACADL) in different tumor types had different inhibiting or promoting effect. However, its role in non-small cell lung cancer (NSCLC) carcinogenicity is not clear. METHOD: In this study, we utilized The Cancer Genome Atlas (TCGA) database to analyze ACADL expression in NSCLC and its correlation with overall survival. Furthermore, we investigated the function of ACADL on cellular proliferation, invasion, colony, apoptosis, cell cycle in vitro with NSCLC cells. Mechanistically, we evaluated the regulatory effect of ACADL expression on its downstream factor yes-associated protein (YAP) by assessing YAP phosphorylation levels and its cellular localization. Finally, we verified the tumorigenic effect of ACADL on NSCLC cells through xenograft experiments in vivo. RESULTS: Compared to adjacent non-cancerous samples, ACADL significantly down-regulated in NSCLC. Overexpression of ACADL, effectively reduced the proliferative, colony, and invasive capabilities of NSCLC cells, while promoting apoptosis and inducing cell cycle arrest. Moreover, ACADL overexpression significantly enhanced YAP phosphorylation and hindered its nuclear translocation. However, the inhibitory effect of the overexpression of ACADL in NSCLC cells mentioned above can be partially counteracted by YAP activator XMU-MP-1 application both in vitro and in vivo. CONCLUSION: The findings suggest that ACADL overexpression could suppress NSCLC development by modulating YAP phosphorylation and limiting its nuclear shift. This role of ACADL-YAP axis provided novel insights into NSCLC carcinogenicity and potential therapeutic strategies.

Mid- to Long-term Follow-up of Severe Acetabular Bone Defect after Revision Total Hip Arthroplasty Using Impaction Bone Grafting and Metal Mesh.

OBJECTIVE: In revision total hip arthroplasty (THA), reconstruction of severe acetabular bone defect continues to be problematic for orthopedic surgeons. This study reports the mid- to long-term survivorship, radiological outcomes, and complications of impaction bone grafting (IBG) and metal mesh with a cemented acetabular component in the reconstruction of severe acetabular bone defects in revision THA. METHODS: This retrospective consecutive study included 26 patients (29 hips: type II B, four; type II C, three; type III A, 10; and type III B, 12) who underwent revision THA, which was performed using IBG and metal mesh, between 2007 and 2014 in our institution. All patients were followed up regularly for clinical and radiographical assessments. Migration and loosening of prosthesis graft integration and complications were observed and analyzed. Survival analysis was performed using a Kaplan-Meier survival analysis. RESULTS: At the time of revision, 75.9% of the hips (22 hips) were classified as type III bone defects. The average follow-up period was 9.4 ± 2.8 (range, 2.4-14.0) years. Of the 29 hips, four hips (13.8%) were assessed as clinical failures; at the last follow-up, two had undergone re-revision THA, and two had not been scheduled for re-revision THA despite radiological failure of the acetabular component. Among them, three clinical failures (10.3%) were due to aseptic loosening, and one (3.4%) was due to infection. Radiographic evaluation showed bone graft integration in all hips during the follow-up. The Kaplan-Meier survivorship analysis revealed an acetabular reconstruction survival rate of 86.5% (95% confidence interval, 61.4%-95.7%) at 10 years. CONCLUSION: IBG and metal mesh with a cemented acetabular component for revision THA is an effective technique for treating severe acetabular bone defects, with effective mid- to long-term outcomes due to the solid reconstruction of the acetabular bone defect and restoration of the hip rotation center.

Patterns of care and prognostic evaluation for stage I-III upper esophageal squamous cell carcinoma: a population-based study.

Background: There is no strong evidence regarding the optimal treatment and specific prognosis prediction model for upper esophageal squamous cell carcinoma (UESCC). This study aimed to investigate the real-world treatment patterns and develop models to predict overall survival (OS) and esophageal cancer-specific survival (ECSS) in patients with stage I-III UESCC. Methods: Patients with T1-4N0-3M0 UESCC in the Surveillance, Epidemiology, and End Results (SEER) database were identified from 2010 to 2017, and randomized to a training cohort and a validation cohort. The effect of treatment patterns on survival were comprehensively analyzed. Nomograms were developed by incorporating independent prognostic factors analyzed by Cox regression in the training cohort and evaluated by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA) in two cohorts. Results: A total of 677 patients were identified, including 452 in the training cohort and 225 in the validation cohort. Among all populations, 71.9% (487) received chemoradiotherapy without surgery, and chemoradiotherapy or/and surgery showed better survival than other treatments. However, surgery was rarely carried out for patients with stage II-III. T stage, N stage, surgery, chemotherapy, and radiotherapy were independent risks for both OS and ECSS, while age was also an independent risk for OS. The C-indexes for nomograms to predict OS (0.71 and 0.72) and ECSS (0.70 and 0.73) were greater than 7th AJCC staging system to predict OS (0.61 and 0.64) and ECSS (0.64 and 0.64) in both the training cohort and the validation cohort. Time-dependent ROC curves and DCA also suggested that nomograms performed consistently better than 7th AJCC staging system. The calibration curves demonstrated good consistency in predicting survival. Conclusions: Chemoradiotherapy was a major treatment with preferable survival for patients with stage I-III UESCC. We have firstly developed and validated prognostic nomograms in patients with stage I-III UESCC, which would play a supplementary role in the current staging system.

Macrophage-biomimetic porous Se@SiO2 nanocomposites for dual modal immunotherapy against inflammatory osteolysis.

BACKGROUND: Inflammatory osteolysis, a major complication of total joint replacement surgery, can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of proinflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (porous Se@SiO2 nanospheres) to manage inflammatory osteolysis. RESULTS: Macrophage membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) attenuated lipopolysaccharide (LPS)-induced inflammatory osteolysis via a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduced endotoxin levels and neutralized proinflammatory cytokines. Moreover, the release of Se could induce macrophage polarization toward the anti-inflammatory M2-phenotype. These effects were mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase (ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduced the inhibition of osteogenic differentiation caused by proinflammation cytokines, as confirmed through in vitro and in vivo experiments. CONCLUSION: Our findings suggest that M-Se@SiO2 have an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 are a promising engineered nanoplatform for the treatment of osteolysis occurring after arthroplasty.

A novel mutation of COL2A1 in a large Chinese family with avascular necrosis of the femoral head.

Avascular necrosis of the femoral head (ANFH) is a debilitating bone disease, characterized by collapse of the femoral head and subsequent loss of hip joint function. Heterozygous mutations in COL2A1 have been identified to cause familial ANFH. Here we report on a large Chinese family with ANFH and a novel heterozygous mutation (c.3517 G > A, p.Gly1173Ser) in exon 50 of COL2A1 in the Gly-X-Y domain. Previously, only five different COL2A1 mutations have been described in patients with familial ANFH. Therefore, our findings provide significant clues to the phenotype-genotype relationships in familial ANFH and may be helpful in clinical diagnosis. Furthermore, these results should assist further studies of the mechanisms underlying collagen diseases.

TBX2 Identified as a Potential Predictor of Bone Metastasis in Lung Adenocarcinoma via Integrated Bioinformatics Analyses and Verification of Functional Assay.

Objective: Bone metastasis from patients with advanced lung adenocarcinoma (LAC) is a very serious complication. To better understand the molecular mechanism, our current study sheds light on identification of hub genes mediating bone metastatic spread by combining bioinformatic analysis with functional verification. Methods: First, we downloaded a lung adenocarcinoma dataset (GSE76194) from Gene Expression Omnibus, analyzed differentially expressed genes (DEGs) through Limma package in R software and constructed a protein-protein interaction network. Based on that preliminary data, we further performed modular and topological analysis using Cystoscope to obtain biological connected genes. Through literature searching and performing mRNA expression analysis on the other independent public dataset (GSE10799), we finally focused on TBX2. Functional effects of TBX2 were performed in tumorigenicity assays including migration and invasion assays, cell proliferation assay, and cell cycle assay. In addition, mechanically, we found enriched pathways related to bone metastasis using Gene Set Enrichment Analysis (GSEA) and validated our results by western blot. Result: A total of 1132 significant genes were sorted initially. We selected common significant genes (log FC>2; p<0.01) from both the biological network data and microarray data. In total, 44 such genes were identified. we found TBX2, along with 10 other genes, to be reported with relevance to bone metastasis in other cancer types. Moreover, TBX2 showed significantly higher expression levels in patients that were found positive for metastasis to bone marrow compared to patients that did not exhibit this type of metastasis in the other separated cohort (GSE10799). Thus, we finally focused on TBX2. We found that TBX2 had detectable expression in LAC cell lines and silencing endogenous TBX2 expression in A549 and H1299 cell lines markedly suppressed migration and invasion, cell proliferation and arrested cell-cycle. Pathway enrichment analyses suggested that TBX2 drove LAC oncogenesis and metastasis through various pathways with epithelial mesenchymal transition (EMT) figuring prominently in the bone metastatic group, which was evidenced by western blot. Conclusion: Collectively, TBX2 plays as a potential predictor of bone metastasis from LAC, yielding a better promise view towards "driver" gene responsible for bone metastasis.

Curcumin has immunomodulatory effects on RANKL-stimulated osteoclastogenesis in vitro and titanium nanoparticle-induced bone loss in vivo.

Wear particle-stimulated inflammatory bone destruction and the consequent aseptic loosening remain the primary causes of artificial prosthesis failure and revision. Previous studies have demonstrated that curcumin has a protective effect on bone disorders and inflammatory diseases and can ameliorate polymethylmethacrylate-induced osteolysis in vivo. However, the effect on immunomodulation and the definitive mechanism by which curcumin reduces the receptor activators of nuclear factor-kappa B ligand (RANKL)-stimulated osteoclast formation and prevents the activation of osteoclastic signalling pathways are unclear. In this work, the immunomodulation effect and anti-osteoclastogenesis capacities exerted by curcumin on titanium nanoparticle-stimulated macrophage polarization and on RANKL-mediated osteoclast activation and differentiation in osteoclastic precursor cells in vitro were investigated. As expected, curcumin inhibited RANKL-stimulated osteoclast maturation and formation and had an immunomodulatory effect on macrophage polarization in vitro. Furthermore, studies aimed to identify the potential molecular and cellular mechanisms revealed that this protective effect of curcumin on osteoclastogenesis occurred through the amelioration of the activation of Akt/NF-κB/NFATc1 pathways. Additionally, an in vivo mouse calvarial bone destruction model further confirmed that curcumin ameliorated the severity of titanium nanoparticle-stimulated bone loss and destruction. Our results conclusively indicated that curcumin, a major biologic component of Curcuma longa with anti-inflammatory and immunomodulatory properties, may serve as a potential therapeutic agent for osteoclastic diseases.

Puerarin Exerts Protective Effects on Wear Particle-Induced Inflammatory Osteolysis.

Wear particle-stimulated inflammatory bone destruction and the consequent aseptic loosening remain major postoperative problems for artificial joints. Studies have indicated that puerarin promotes osteogenesis and alleviates lipopolysaccharide-induced osteoclastogenesis in vitro. However, the underlying molecular mechanism by which puerarin interacts with receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclast formation in vitro and wear particle-stimulated osteolysis in vivo has not been reported. In this work, the protective effects exerted by puerarin on titanium particle-stimulated bone destruction in vivo and on RANKL-induced osteoclast activation in osteoclastic precursor cells in vitro were investigated. As expected, puerarin significantly inhibited wear particle-mediated bone resorption and proinflammatory cytokine productions in a calvarial resorption model. Additionally, puerarin inhibited RANKL-induced osteoclast activation, bone resorption ability, and F-actin ring formation in vitro as puerarin concentration increased. Furthermore, mechanistic investigation indicated that reduced RANKL-stimulated MEK/ERK/NFATc1 signaling cascades might regulate the protective effect of puerarin. Conclusively, these results indicate that puerarin, a type of polyphenol, might serve as a protective agent to prevent osteoclast-related osteolytic diseases.

Lithium chloride with immunomodulatory function for regulating titanium nanoparticle-stimulated inflammatory response and accelerating osteogenesis through suppression of MAPK signaling pathway.

BACKGROUND: Wear particle-induced inflammatory osteolysis and the consequent aseptic loosening constitute the leading reasons for prosthesis failure and revision surgery. Several studies have demonstrated that the macrophage polarization state and immune response play critical roles in periprosthetic osteolysis and tissue repair, but the immunomodulatory role of lithium chloride (LiCl), which has a protective effect on wear particle-induced osteolysis by suppressing osteoclasts and attenuating inflammatory responses, has never been investigated. METHODS: In this work, the immunomodulatory capability of LiCl on titanium (Ti) nanoparticle-stimulated transformation of macrophage phenotypes and the subsequent effect on osteogenic differentiation were investigated. We first speculated that LiCl attenuated Ti nanoparticle-stimulated inflammation responses by driving macrophage polarization and generating an immune micro-environment to improve osteogenesis. Furthermore, a metal nanoparticle-stimulated murine air pouch inflammatory model was applied to confirm this protective effect in vivo. RESULTS: The results revealed that metal nanoparticles significantly activate M1 phenotype (proinflammatory macrophage) expression and increase proinflammatory cytokines secretions in vitro and in vivo, whereas LiCl drives macrophages to the M2 phenotype (anti-inflammatory macrophage) and increases the release of anti-inflammatory and bone-related cytokines. This improved the osteogenic differentiation capability of rat bone marrow mesenchymal stem cells (rBMSCs). In addition, we also provided evidence that LiCl inhibits the phosphorylation of the p38 mitogen-activated protein kinase (p38) and extracellular signal-regulated kinase (ERK) pathways in wear particle-treated macrophages. CONCLUSION: LiCl has the immunomodulatory effects to alleviate Ti nanoparticle-mediated inflammatory reactions and enhance the osteogenic differentiation of rBMSCs by driving macrophage polarization. Thus, LiCl may be an effective therapeutic alternative for preventing and treating wear debris-induced inflammatory osteolysis.

Crocin inhibits titanium particle-induced inflammation and promotes osteogenesis by regulating macrophage polarization.

Wear particle-induced periprosthetic inflammatory osteolysis and resultant aseptic loosening are major causes of orthopedic implant failure, for which there are no effective treatments other than revision surgery. Crocin, a carotenoid compound derived from crocus flowers, has anti-inflammatory properties, but its immunomodulatory function and role in particle-induced osteolysis are not well characterized. Here we report the effect of crocin on titanium (Ti) particle-induced macrophage polarization and osteogenic differentiation. We found that crocin induced anti-inflammatory (M2) macrophage polarization and attenuated Ti particle-induced inflammation by promoting the expression of anti-inflammatory cytokines in vitro as well as in vivo in a mouse air-pouch model. Additionally, crocin pre-treated macrophages promoted osteogenic differentiation of co-cultured mouse bone mesenchymal stem cells (BMSCs). These effects were mediated via inhibition of p38 and c-Jun N-terminal kinase signaling. Our results indicate that crocin suppresses Ti particle-induced inflammation and enhances osteogenic differentiation of BMSCs by inducing M2 macrophage polarization, highlighting its therapeutic potential for preventing wear particle-induced osteolysis.

MicroRNA-34a suppresses invasion and metastatic in esophageal squamous cell carcinoma by regulating CD44.

In human esophageal squamous cell carcinoma (ESCC), miR-34a was downregulated and could inhibit in vitro cell proliferation and migration. However, the underlying mechanism was not clear yet. The expression levels of mRNA and protein were detected by quantitative real-time PCR or western blotting, respectively. MiR-34a was knocked down or overexpressed and transfected into human ESCC cell lines ECA109 and TE-13, respectively. Cell migration and wound healing assays were used to examine the effect on migration and invasion in vitro. Animal models were used to examine the role of miR-34a in metastasis in vivo. Luciferase assay was carried out to validate the potential target of miR-34a. CD44 was upregulated and miR-34a was downregulated in ESCC tissues and cell lines. The linear regression analysis showed that CD44 expression was negatively correlated with the level of miR-34a. Luciferase assay showed that miR-34a interacted with a putative binding site in the CD44 3'UTR. MiR-34a was found to negatively regulate the expression of CD44. In vitro experiment showed that miR-34a overexpression inhibited ESCC cell invasion and migration; whereas miR-34a knockdown showed reversed results. MiR-34a also inhibited esophagus tumor growth and metastasis in vivo; whereas miR-34a knockdown showed reversed results. Finally, we found that CD44 knockdown reversed the effects of miR-34a knockdown on ESCC cell invasion and migration in vitro. MiRNA-34a suppresses invasion and metastatic in ESCC by regulating CD44.

Pursestring stapled anastomotic technique for minimally invasive Ivor Lewis esophagectomy.

We describe a pursestring stapled anastomotic technique for minimally invasive Ivor Lewis esophagectomy, in which a pursestring is hand sewn through the muscular layer of the intact esophagus by using one piece of 3-0 Prolene suture. The anvil of a circular stapler is inserted through an esophageal incision, 2 to 3 cm distal to the pursestring, and secured by the pursestring. The esophagus is transected, and the mucosa of the proximal stump is retained 5 mm longer than the adjacent muscular layer. The gastroesophageal anastomosis is completed and embedded by using the previously reserved 2 cm of mediastinal pleura.