Activation of the PPARγ/NF-κB pathway by A-MPDA@Fe3O4@PVP via scavenging reactive oxygen species to alleviate hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (IRI) is a common pathological process during hepatectomy and liver transplantation and the two primary reasons for hepatic IRI are reactive oxygen species (ROS)-mediated oxidative stress and excessive inflammatory responses. Herein, a novel antioxidant nanodrug (A-MPDA@Fe3O4@PVP) is prepared by employing L-arginine-doped mesoporous polydopamine (A-MPDA) nanoparticles as the carrier for deposition of ultra-small ferric oxide (Fe3O4) nanoparticles and further surface modification with polyvinylpyrrolidone (PVP). A-MPDA@Fe3O4@PVP not only effectively reduces the aggregation of ultra-small Fe3O4, but also simultaneously replicates the catalytic activity of catalase (CAT) and superoxide dismutase (SOD). A-MPDA@Fe3O4@PVP with good antioxidant activity can rapidly remove various toxic reactive oxygen species (ROS) and effectively regulate macrophage polarization in vitro. In the treatment of hepatic IRI, A-MPDA@Fe3O4@PVP effectively alleviates ROS-induced oxidative stress, reduces the expression of inflammatory factors, and prevents apoptosis of hepatocytes through immune regulation. A-MPDA@Fe3O4@PVP can further protect liver tissue by activating the PPARγ/NF-κB pathway. This multiplex antioxidant enzyme therapy can provide new references for the treatment of IRI in organ transplantation and other ROS-related injuries such as fibrosis, cirrhosis, and bacterial and hepatic viral infection.

Toward the Improvement of the Mechanical and Tribological Properties of Braided Ligament for ACL Reconstruction: A "Carrot and Stick" Strategy.

Bone tunnel enlargement has been troubling the clinical adoption of braided artificial ligaments for decades, to which mechanical and tribological performance promotion shall be an effective and promising approach. Herein, a "carrot and stick" strategy has been introduced with two types of polyethylene terephthalate (PET) fibers to fabricate hybrid textures, which is expected to advance fatigue and tribological performance without yielding essential mechanical strength and biocompatibility. Owing to advancements in such a "carrot and stick" strategy, the obtained grafts present three promising properties: i) enhancement of mechanical strength; ii) coefficient of friction (COF) reduction of 25% at the greatest extent, thus lowering the risk of bone tunnel enlargement; iii) final displacement shrinkage of graft length after cyclic loadings, favored in the clinic for isometric reconstruction. The results obtained in this study show that the "carrot and stick" strategy can be a creative and convenient method to optimize the service life, saving the complication rate of artificial ligaments for clinical applications.

AIBI Modified Mesoporous Copper Sulfide Nanocomposites for Efficient Non-Oxygen Dependent Free Radicals-Assisted Photothermal Therapy in Uveal Melanoma.

Uveal melanoma (UM) is an ocular cancer predominantly affecting adults, characterized by challenging diagnostic outcomes. This research endeavors to develop an innovative multifunctional nanocomposite system sensitive to near-infrared (NIR) radiation, serving as both a non-oxygen free-radical generator and a photothermal agent. The designed system combines azobis isobutyl imidazoline hydrochloride (AIBI) with mesoporous copper sulfide (MCuS) nanoparticles. MCuS harnesses NIR laser energy to induce photothermal therapy, converting light energy into heat to destroy cancer cells. Simultaneously, AIBI is activated by the NIR laser to produce alkyl radicals, which induce DNA damage in remaining cancer cells. This distinctive feature equips the designed system to selectively eliminate cancers in the hypoxic tumor microenvironment. MCuS is also beneficial to scavenge the overexpressed glutathione (GSH) in the tumor microenvironment. GSH generally consumes free radicals and hiders the PDT effect. To enhance control over AIBI release in cancer cells, 1-tetradecyl alcohol (TD), a phase-changing material, is introduced onto the surface of MCuS nanoparticles to create the final AMPT nanoparticle system. In vitro and in vivo experiments confirm the remarkable anti-tumor efficacy of AMPT. Notably, the study introduces an orthotopic tumor model for UM, demonstrating the feasibility of precise and effective targeted treatment within the ocular system.

Association of insulin resistance indicators with hepatic steatosis and fibrosis in patients with metabolic syndrome.

BACKGROUND: To investigate the association of four insulin resistance (IR) indicators with hepatic steatosis and fibrosis in patients with metabolic syndrome (MetS), as well as to compare the diagnostic value of these indicators in identifying hepatic steatosis and fibrosis in individuals with MetS. METHODS: This cross-sectional study used the data from the National Health and Nutrition Examination Survey 2017-2018. IR indicators included homeostasis model assessment of IR (HOMA-IR), triglyceride/glucose (TyG) index, triglyceride glucose-waist-to-height ratio (TyG-WHtR), and metabolic score for IR (METS-IR). The main endpoints of this study were hepatic steatosis and hepatic fibrosis. Weighted univariate and multivariate logistic regression models were employed to evaluate the association between four IR indicators and both hepatic steatosis, hepatic fibrosis. The efficacy of various IR indicators in the detection of hepatic steatosis and hepatic fibrosis were assessed using receiver operating characteristics curve (ROC). RESULTS: A total of 876 participants with MetS were enrolled. Among the participants, hepatic steatosis was observed in 587 MetS individuals, while hepatic fibrosis was identified in 151 MetS individuals. In multivariate logistic regression model, HOMA-IR, TyG, TyG-WHtR, and METS-IR were related to the increased odd of hepatic steatosis. Additionally, HOMA-IR, TyG-WHtR, and METS-IR were associated with increased odd of hepatic fibrosis. According to the ROC analysis, the area under the curve (AUC) of the TyG-WHtR (AUC = 0.705, 95%CI: 0.668-0.743) was higher than HOMA-IR (AUC = 0.693, 95%CI: 0.656-0.730), TyG (AUC = 0.627, 95%CI: 0.587-0.666), and METS-IR (AUC = 0.685, 95%CI: 0.648-0.722) for identifying hepatic steatosis of MetS patients. Likewise, TyG-WHtR was also higher than HOMA-IR, TyG, and METS-IR for identifying hepatic fibrosis of MetS patients. CONCLUSION: HOMA-IR, TyG-WHtR, and METS-IR may be associated with the risk of hepatic steatosis and fibrosis among the U.S. adult population with MetS. In addition, TyG-WHtR may have a good predictive value for hepatic steatosis and hepatic fibrosis.

Avulsion fracture is associated with more pain after anatomic repair procedure for ATFL injury at the talar side.

PURPOSE: To evaluate the clinical outcomes of anatomic repair procedure for chronic anterior talofibular ligament (ATFL) injury at the talar side, and to compare the outcomes between patients with and without concomitant avulsion fractures. It was hypothesized that anatomic repair procedure could produce similarly satisfactory outcomes for those two groups. METHODS: Thirty-nine consecutive patients with chronic ATFL injuries at the talar side who underwent anatomic repair procedure at the department of sports medicine at Peking University Third Hospital between 2013 and 2018, were retrospectively evaluated. The pain visual analogue scale (VAS), American Orthopaedic Foot & Ankle Society (AOFAS) score, Tegner score, and Foot & Ankle Outcome Score (FAOS) were recorded as the primary outcomes. Time to return to sports (RTS), surgical satisfaction, deficiency of ankle range of motion (ROM), recurrent sprain, and postoperative complications were recorded as the secondary outcomes. Outcomes were compared between patients with (Group A, 16 cases) and without (Group B, 23 cases) concomitant avulsion fractures. RESULTS: The mean follow-up time was 79.4 ± 17.0 and 76.6 ± 18.5 months for Group A and B, respectively. VAS, AOFAS, Tegner, FAOS, and all subscale scores of FAOS were significantly improved in both groups at the final follow up. Patients in group A had inferior postoperative VAS, AOFAS, FAOS, and pain score of FAOS compared to group B (1.1 ± 1.1 vs. 0.4 ± 0.5, 89.1 ± 10.1 vs. 95.2 ± 5.2, 87.2 ± 7.2 vs. 91.5 ± 4.1, and 88.4 ± 11.3 vs. 96.7 ± 3.5, respectively).The mean time to RTS, rate of satisfaction and recurrent sprain had no significant differences between group A and B (6.1 ± 2.8, 93.8%, and 18.8% vs. 5.2 ± 2.2, 100.0%, and 13.0%, respectively), and the rate of ROM deficiency was significantly higher in group A (37.5 vs. 8.7%). Avulsion fracture was identified as an independent risk factor for inferior pain score of FAOS. CONCLUSION: Anatomic repair procedure for chronic ATFL injuries at the talar side produces favourable results for patients with and without avulsion fractures at 5 to 10 years follow-up, however, avulsion fracture is associated with more pain. LEVEL OF EVIDENCE: III.

The lowest point of fibula (LPF) could be used as a reliable bony landmark for arthroscopic anchor placement of lateral ankle ligaments ----compared with open Broström procedure.

BACKGROUND: Arthroscopic technique procedures was wide accepted for the treatment of chronic ankle instability (CAI). But little acknowledge was involved to the bony landmarks and anatomic features of different bundles of lateral ligaments under arthroscopic view. METHODS: Sixty patients with acute or chronic lateral ankle ligaments injury (LAI) were collected prospectively, and divided randomly into two groups. In arthroscopic group, the bone tunnels were made on the LPF arthroscopically. And in open group, the bone tunnels were made on the Fibular obscure tubercle (FOT) in open procedure. The inferior bundle of ATFL and Arcuate fibre was also identified reference to the LPF and labeled by a PDS II suture penetration. Following that, The distances of the bone tunnels to the different bony markers were measured and compare between two groups. The penetrating locations of PDS II on the inferior bundle of ATFL and Arcuate fibre were also confirmed intraoperatively. And the safe angle of anchor implantation on the axial view was measured on postoperative CT scan. RESULTS: The distances of bone tunnel to the fibular tip, the fibular insertion of anterior-inferior tibiofibular ligament (AITFL), and the FOT in arthroscopic and open locating groups were 4.9 ± 2.2 and 6.3 ± 2.2 mm, 13.5 ± 2.7 and 12.4 ± 1.1 mm, 5.8 ± 2.2 and 5.6 ± 1.0 mm, respectively. The distances of bone tunnels to the FOT and fibular tip on 3d-CT view was 4.4 ± 1.5 and 4.6 ± 0.9 mm, 14.4 ± 3.2 and 13.2 ± 1.8 mm in arthroscopic and open group, and there were no significant differences between two groups. The safe angle of arthroscopic anchor placement on the axial plan was ranged from 24.9 ± 6.3o to 58.1 ± 8.0o. The PDS II sutures penetrating on the inferior bundles of ATFL and the arciform fibres were also comfirmed successfully by open visualizaion.The average distance of penetration point to the horizontal line cross the fibular tip was 2.3 ± 2.7 mm (ranged from - 3.1 to 6.0 mm), and to the vertical line cross the FOT was 2.7 ± 2.7 mm (ranged from - 2.5 to 7.5 mm). CONCLUSION: Take the lowest point of fibula under arthroscopy (LPF) as a bony reference, we could identify the iATFL under arthroscopic visualization. By this way, we could place the suture anchors properly to the fibular footprint and suture the iATFL fibres successfully.

CPVL suppresses metastasis of nasopharyngeal carcinoma through inhibiting epithelial-mesenchymal transition.

PURPOSE: Distant metastasis is the main obstacle to treating nasopharyngeal carcinoma (NPC). Tumor distance metastasis is a complex process involving the jointly participation of multiple oncogenes, tumor suppressor genes, and metastasis-associated genes. Enough accurate prognostic genes for evaluating metastasis risk are lacking. We aimed to identify more precise biomarkers for NPC metastasis. METHODS: We performed weighted gene co-expression network analysis, differentially expressed gene analysis, univariate and multivariate stepwise Cox regression, and Kaplan-Meier (K-M) survival analyses, on data obtained from RNA sequencing of 10 NPC samples and the public database, to identify key genes correlated with NPC metastasis. Wound healing assays, transwell assays, and immunohistochemistry were conducted to validate our bioinformatic conclusions. Western blotting was performed to evaluate and quantify the effect of identified EMT genes on epithelial-mesenchymal transition (EMT) of NPC. RESULTS: Combined our own RNA sequencing data and public data, we determined carboxypeptidase vitellogenic-like protein (CPVL) as a tumor suppressor for NPC. Pathway enrichment analyses indicated that genes associated with CPVL are involved in EMT. NPC with low CPVL expression had high tumor purity and low levels of immune cells. Experimental results showed that CPVL protein predominantly expressed in cytoplasmic and membranous and it exhibited higher expression levels in NPC tissues without distant metastasis than those with distant metastasis. CPVL inhibits the migration and invasive capability of NPC cells. Overexpression of CPVL upregulates E-cadherin and ZO-1, whereas it downregulates vimentin, suggesting that CPVL suppresses tumor metastasis by inhibiting EMT. CONCLUSION: CPVL inhibits migration and invasion of NPC cells and is associated with tumor metastasis suppression through upregulating epithelial marker and inhibiting mesenchymal marker expression and could be a prognostic biomarker for metastasis risk evaluation in NPC.

Arthroscopic and Open Procedures Result in Similar Calcaneal Tunnels for Anatomical Reconstruction of Lateral Ankle Ligaments.

Purpose: The purpose of this study was to validate the accuracy and reliability of arthroscopic markers of distal insertion of the calcaneofibular ligament (CFL), and to compare the calcaneus bone tunnels of the CFL that were made under arthroscopy and open procedures. Methods: Fifty-seven patients who underwent lateral ankle ligament reconstruction procedures were enrolled and divided into open (n = 24) and arthroscopic groups (n = 33). Lateral ankle radiography was performed postoperatively, and the calcaneus bone tunnels referenced to several landmarks, including the subtalar joint, calcaneus superior edge, fibular tip, angulation with fibula axis, cross point of the fibular and tangential line of the fibular obscure tubercle cross point of the tangential lines of the talar posterior edge and deepest point of the subtalar joint, and cross point of the fibular axis and perpendicular line across fibular tip. These results were compared between the two groups. Results: No significant intergroup differences were observed between the parameters. When the bone tunnels of the CFL were referenced to the cross point of tangential lines of the talar posterior edge and deepest point of the subtalar joint, and the cross point of the fibular axis and perpendicular line across fibular tip, the coefficient variations were very high, which indicated that the locations of the bone tunnels were scattered over a large area in both groups. Conclusions: Arthroscopic and open procedures achieved similar results for calcaneus bone tunnel making of the CFL. However, large variations were observed in both groups. Level of Evidence: Level III, retrospective cohort study.

Favourable clinical, arthroscopic and radiographic outcomes after autologous osteoperiosteal transplantation for massive medial cystic osteochondral defects of the talus.

PURPOSE: The purpose of this study was to retrospectively evaluate the clinical, arthroscopic and radiological outcomes of autologous osteoperiosteal transplantation for massive cystic osteochondral defects of the talus. METHODS: Cases of autologous osteoperiosteal transplantation for medial massive cystic defects of the talus between 2014 and 2018 were reviewed. The visual analogue scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) score, Foot and Ankle Outcome Score (FAOS), and Ankle Activity Scale (AAS) were assessed preoperatively and postoperatively. The Magnetic Resonance Observation of Cartilage Tissue (MOCART) system and the International Cartilage Repair Society (ICRS) score were evaluated after surgery. The ability to return to daily activity and sport, as well as complications, were recorded. RESULTS: Twenty-one patients were available for follow-up, with a mean follow-up of 60.1 ± 11.7 months. All subscales of preoperative FAOS had significant (P < 0.001) improvement at the final follow-up. The mean AOFAS and VAS scores significantly (P < 0.001) improved from 52.4 ± 12.4 preoperatively to 90.9 ± 5.2 at the last follow-up and from 7.9 ± 0.8 to 1.5 ± 0.9, respectively. The mean AAS decreased from 6.0 ± 1.4 preinjury to 1.4 ± 0.9 postinjury and then increased to 4.6 ± 1.4 at the final follow-up (P < 0.001). All 21 patients resumed daily activities after a mean of 3.1 ± 1.0 months. Fifteen patients (71.4%) returned to sports after a mean of 12.9 ± 4.1 months. All patients underwent follow-up MRI with a mean MOCART score of 68.6 ± 5.9. Eleven patients underwent second-look arthroscopy, and the average ICRS was 9.4 ± 0.8. No donor site morbidity was found in any patient during the follow-up. CONCLUSION: Autologous osteoperiosteal transplantation provided favourable clinical, arthroscopic and radiographic outcomes in patients with massive cystic osteochondral defects of the talus during a minimum 3-year follow-up. LEVEL OF EVIDENCE: IV.

Acute Distal Rupture of the Calcaneus-Fibular Ligament Near the Calcaneus Insertion: Magnetic Resonance Imaging for Diagnostic Value and Comparison to Surgical Findings-A Retrospective Case Series Study.

Distal rupture of the calcaneus-fibular ligament (CFL) was unique and important, because it is crucial to diagnose this type of injury before surgical intervention. In the present study, we collected several imaging characteristics based on MRI and tried to determine whether those clues can be used to diagnose distal rupture of CFL specifically and sensitively. Several imaging characteristics based on MRI were collected and used to diagnose and determine the location of CFL injury. All these clues on preoperative MRI were verified by operative findings and postoperative roentgenography. The interobserver agreement for the quality of the MRI images had a p value of .6 (McNemar test) and a Cohen's kappa of 65.2% (confidence interval, 50.5%-79.9%), and the agreement of the 2 observers was categorized as substantial. The sensitivity and specificity of distal rupture of CFL between 2 observers were 76.3%, 91.4% and 72.2%, 85.55%, respectively. The sensitivity and specificity of MRI clues were calculated as follows: hyperintense signal changes (86.1%, 38.6%), peroneal sheath fluid (63.9%, 74.7%), wave or laxity of the ligament (80.6%, 51.8%), fluid exudation around the ligament (80.6%, 51.8%), bone marrow edema on the calcaneus insertion (2.8%, 91.6%), avulsion fracture of the calcaneus (0%, 96.4%), incongruency or disruption of the ligament (69.4%, 77.1%), and exudation on the subtalar joint (52.8%, 71.1%). Preoperative MRI scans are a useful tool to diagnose distal injury of the CFL.

Treatment of Symptomatic Subfibular Ossicle by Excision and Modified Broström Procedure for Skeletally Immature Patients.

BACKGROUND: Ossicle resection combined with ligament repair using the modified Broström procedure (MBP) is generally associated with favorable results in adults with symptomatic subfibular ossicles; however, the surgical results of this approach in skeletally immature patients remain unclear. The purpose of this study was to investigate the midterm clinical outcomes and radiographic outcomes including leg length and physeal growth of skeletally immature patients after this procedure. METHODS: Twenty-six consecutive skeletally immature patients who underwent ossicle resection combined with the MBP were retrospectively evaluated. Clinical scores were evaluated using the visual analog scale (VAS), American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, Karlsson-Peterson score, and Tegner score. The talocrural angle, fibular length on radiographs, and tape-measured leg length between the 2 ankles were also measured at the final follow-up. Time of return to sports and postoperative complications were also evaluated. RESULTS: Fourteen girls (53.8%) and 12 boys (46.2%) had surgery at a mean age of 12.7±2.4 years. Mean postoperative follow-up time was 40.0±10.8 months. Mean VAS pain score improved from 4.1 preoperatively to 0.5 at final follow-up (P < .05). Mean AOFAS score, Karlsson score, and Tegner score all improved from 62.0, 54.0, and 2.8 preoperatively to 95.5, 94.0, and 5.4 (P < .05), respectively, at final follow-up. Median time of return to sports was 17.0 weeks. Mean talocrural angle, fibular length, and tape-measured leg length of the injured ankle were not significantly different from those of the contra-side at the final follow-up. All patients were satisfied with the results; repeat ligamentous injury occurred in 2 patients (7.7%). We had no cases of wound infection, nerve injury, compartment syndrome, or any other complications. CONCLUSION: Ossicle resection combined with the MBP performed in skeletally immature patients with symptomatic subfibular ossicles resulted in improved clinical outcomes without disruption of fibular physeal growth by an average of 3.3-year follow-up. LEVEL OF EVIDENCE: Level IV, case series.

Predicting prognosis and immune responses in hepatocellular carcinoma based on N7-methylguanosine-related long noncoding RNAs.

Background: Hepatocellular carcinoma (HCC), which has high rates of recurrence and metastasis and is the main reason and the most common tumor for cancer mortality worldwide, has an unfavorable prognosis. N7-methylguanosine (m7G) modification can affect the formation and development of tumors by affecting gene expression and other biological processes. In addition, many previous studies have confirmed the unique function of long noncoding RNAs (lncRNAs) in tumor progression; however, studies exploring the functions of m7G-related lncRNAs in HCC patients has been limited. Methods: Relevant RNA expression information was acquired from The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov), and m7G-related lncRNAs were identified via gene coexpression analysis. Afterward, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate regression analyses were implemented to construct an ideal risk model whose validity was verified using Kaplan-Meier survival, principal component, receiver operating characteristic (ROC) curve, and nomogram analyses. In addition, the potential functions of lncRNAs in the novel signature were explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA). At last, in both risk groups and subtypes classified based on the expression of the risk-related lncRNAs, we analyzed the immune characteristics and drug sensitivity of patients. Results: After rigorous screening processes, we built a model based on 11 m7G-related lncRNAs for predicting patient overall survival (OS). The results suggested that the survival status of patients with high-risk scores was lower than that of patients with low-risk scores, and a high-risk score was related to malignant clinical features. Cox regression analysis showed that the m7G risk score was an independent prognostic parameter. Moreover, immune cell infiltration and immunotherapy sensitivity differed between the risk groups. Conclusion: The m7G risk score model constructed based on 11 m7G-related lncRNAs can effectively assess the OS of HCC patients and may offer support for making individualized treatment and immunotherapy decisions for HCC patients.

Sensitivity of the Dorsal-Central Retinal Pigment Epithelium to Sodium Iodate-Induced Damage Is Associated With Overlying M-Cone Photoreceptors in Mice.

Purpose: Retinal pigment epithelium (RPE) degeneration is a leading cause of blindness in retinal degenerative diseases, but the mechanism of RPE regional degeneration remains largely unknown. This study aims to investigate the sensitivity of RPE to sodium iodate (SI) injury in the dorsal and ventral visual fields in mice and analyze whether overlaying cone photoreceptors regulate the sensitivity of RPE to SI-induced damage. Methods: SI was used to induce RPE degeneration in mice. Hematoxylin-eosin staining, immunostaining, and TUNEL assay were used to evaluate retinal degeneration along the dorsal-ventral axis. Flat-mounted and sectional retinal immunostaining were used to analyze the distribution of cones along the dorsoventral axis in C57BL/6, albino, and 129 mice. Electroretinography was used to examine the retinal function. Results: Dorsal-central RPE was more sensitive to SI-mediated injury along the dorsal-ventral axis in C57BL/6 mice. Compared with the ventral RPE, the dorsal-central RPE was dominantly covered by M cone photoreceptors in these mice. Interestingly, M cone photoreceptor degeneration was followed by dorsal RPE degeneration under a low dose of SI. Furthermore, the sensitivity of dorsal RPE to a low dose of SI was reduced in both albino and 129 mouse strains with dominant mixed cones instead of M cones in the dorsal visual field. Conclusions: These findings suggest that dorsal-central RPE is more sensitive to SI injury and that SI-induced RPE degeneration could be controlled by modifying the dominant overlying cone population in the mouse dorsal retina, thereby highlighting a potential role of M cones in RPE regional degeneration.

Midterm Outcomes of Talocalcaneal Coalition Arthroscopic Resection in Adults.

BACKGROUND: Arthroscopic resection of the talocalcaneal coalition (TCC) has been reported to be associated with good short-term outcomes. However, the midterm outcomes of this approach remain uncertain. METHODS: We performed a retrospective study of patients who underwent arthroscopic resection for symptomatic TCC. The patients were divided into 2 groups (group P, patients with isolated posterior facet coalition; and group MP, patients with both middle and posterior facet coalition). The preoperative and postoperative visual analog scale (VAS) scores for pain and American Orthopaedic Foot & Ankle Society (AOFAS) scale scores were calculated. The postoperative AOFAS and VAS scores between the 2 groups were analyzed. Patient satisfaction was also assessed. RESULTS: Thirty-two patients were included in this study. The mean age at the time of surgery was 26.0±8.5 years, and the mean follow-up period was 56.9±18.0 months. Thirteen (41%) patients were in group P, whereas 19 (59%) patients were in group MP. Postoperative VAS and AOFAS scores improved more significantly than preoperative scores. At the final follow-up, excellent and good subjective outcomes were attained in 26 patients (81%), fair and poor outcomes in 6 patients (19%). There were no statistical differences in the postoperative AOFAS (91.0±7.0 vs 85.8±10.8, P = .532) and VAS score (2.1±1.7 vs 4.0±2.6, P = .537) between patients with the ratio of coalition/posterior facet more than or less than 50%. There were no statistical differences in postoperative VAS score (1.8±1.3 vs 2.6±2.2, P = .236) and AOFAS score (92.5±5.6 vs 89.2±8.7, P = .297) between group P (n=13) and group MP (n=19), either. Three patients (9.4%) had complications, including these notable findings: 1 patient complained of restricted dorsal flexion, 1 with computed tomography-proven coalition recurrence, and 1 with partial tibial nerve injury. CONCLUSION: We found that TCC arthroscopic resection was generally associated with reasonable outcomes at midterm follow-up. LEVEL OF EVIDENCE: Level IV, case series.

Comparison of Autologous Osteoperiosteal and Osteochondral Transplantation for the Treatment of Large, Medial Cystic Osteochondral Lesions of the Talus.

BACKGROUND: Autologous osteoperiosteal transplantation (AOPT) using graft harvested from the iliac crest is used to treat large cystic osteochondral lesions of the talus (OLTs). However, no studies have compared clinical and radiologic outcomes between AOPT and autologous osteochondral transplantation (AOCT) using graft harvested from the nonweightbearing zone of the femoral condyle of the ipsilateral knee in patients with large cystic OLTs. PURPOSE: To compare clinical and radiologic outcomes between patients undergoing AOPT and those undergoing AOCT for large cystic OLTs. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Between March 2015 and March 2018, patients who underwent AOCT and AOPT to treat medial large cystic OLTs (>10 mm) were retrospectively evaluated. For comparability, the 2 groups were matched 1:1 based on their characteristics, including sex, age, body mass index, side of injury, follow-up period, and the preoperative cyst volume. After propensity score matching, 23 patients were enrolled in each group for the analysis. Clinical outcomes were assessed using the visual analog scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) score, and the Tegner score. Donor-site morbidity was recorded according to the symptoms, including pain, stiffness, swelling, and discomfort. In addition, the Lysholm score was used to assess the most common knee donor-site morbidity. Radiologic outcomes were evaluated using the magnetic resonance observation of cartilage repair tissue (MOCART) score, and the International Cartilage Regeneration & Joint Preservation Society (ICRS) score was obtained during second-look surgery. RESULTS: The mean follow-up period was about 48 months. There were no significant differences in patient characteristics and lesion volumes between groups. Postoperative ankle pain VAS score, AOFAS score, and Tegner score were not significantly different between groups at final follow-up. Total donor-site morbidity (P = .004) and discomfort morbidity (P = .009) were significantly lower in the AOPT group than in the AOCT group. However, the Lysholm score showed no significant difference between the donor knee and the opposite knee (P = .503) in the AOCT group. The MOCART and ICRS scores were not significantly different between groups. CONCLUSION: Clinical and radiologic outcomes of patients who underwent AOPT from the iliac crest were found to be comparable with those of patients who underwent AOCT from the ipsilateral knee for the treatment of medial large cystic OLTs. These results may be helpful for orthopaedic surgeons to decide appropriate treatments for patients with large cystic OLTs.

A simple pan-specific RNN model for predicting HLA-II binding peptides.

The prediction of human leukocyte antigen (HLA) class II binding peptides plays important roles in understanding the mechanism of immune recognition and developing effective epitope-based vaccines. In this work, gated recurrent unit (GRU)-based recurrent neural network (RNN) was successfully employed to establish a pan-specific prediction model of HLA-II-binding peptides by using only the HLA and peptide sequence information. In comparison with the existing pan-specific models of HLA-II-binding peptides, the GRU-based RNN model covered a broad spectrum of HLA-II molecules including 50 HLA-DR, 47 HLA-DQ, and 19 HLA-DP molecules with peptide lengths varying from 8 to 43 mers. The results demonstrated strong discriminant capabilities of the GRU-based RNN model, of which the AUC values were 0.92, 0.88, and 0.88 for the training, validation, and test sets, respectively. Also, the GRU-based model showed state-of-the-art performances in predicting the binding peptides with the length ranging from 8-32 mers, which provides an efficient method for predicting HLA-II-binding peptides of longer lengths in comparison with the available methods. Overall, taking the advantages of the RNN architecture, the established pan-specific GRU model can be used for predicting accurately the HLA-II-binding peptides in a simple and direct manner.

A new classification of talocalcaneal coalitions based on computed tomography for operative planning.

BACKGROUND: Current classifications emphasize the morphology of the coalition, however, subtalar joint facets involved should also be emphasized. OBJECTIVE: The objective of this study was to develop a new classification system based on the articular facets involved to cover all coalitions and guide operative planning. METHODS: Patients were diagnosed with talocalcaneal coalition using a CT scan, between January 2009 and February 2021. The coalition was classified into four main types according to the shape and nature of the coalition: I, inferiorly overgrown talus or superiorly overgrown calcaneus; II, both talus and calcaneus overgrew; III, coalition with an accessory ossicle; IV, complete osseous coalition (I-III types are non-osseous coalition). Then each type was further divided into three subtypes according to the articular facets involved. A, the coalition involving the anterior facets; M, the coalition involving the middle facets, and P, the coalition involving the posterior facets. Interobserver reliability was measured at the main type (based on nature and shape) and subtype (articular facet involved) using weighted Kappa. Results There were 106 patients (108 ft) included in this study. Overall, 8 ft (7.5%) were classified as type I, 75 ft (69.4%) as type II, 7 ft (6.5%) as type III, and 18 ft (16.7%) as type IV. Twenty-nine coalitions (26.9%) involved the posterior facets only (subtype-P), 74 coalitions (68.5%) involved both the middle and posterior facets (subtype-MP), and five coalitions (4.6%) simultaneously involved the anterior, middle, and posterior facets (subtype-AMP). Type II-MP coalition was the most common. The value of weighted Kappa for the main type was 0.93 (95%CI 0.86-0.99) (p<0.001), and the value for the subtype was 0.78 (95%CI 0.66-0.91) (p<0.001). CONCLUSION: A new classification system of the talocalcaneal coalition to facilitate operative planning was developed.

Open Versus Endoscopic Osteotomy of Posterosuperior Calcaneal Tuberosity for Haglund Syndrome: A Retrospective Cohort Study.

BACKGROUND: Although endoscopic calcaneoplasty and retrocalcaneal debridement have been extensively applied to treat Haglund syndrome, evidence of the value of the endoscopic procedure remains to be fully established. PURPOSE/HYPOTHESIS: The purpose of this study was to compare the postoperative outcomes and the amount of osteotomy between open and endoscopic surgery for the treatment of Haglund syndrome. It was hypothesized that endoscopic calcaneoplasty would lead to higher patient satisfaction and lower complication rates compared with open surgical techniques. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The following postoperative outcomes were compared between the open surgery group (n = 20) and the endoscopic surgery group (n = 27): visual analog scale for pain, American Orthopaedic Foot & Ankle Society ankle-hindfoot scale, Foot Function Index, Tegner score, Ankle Activity Score, and 36-Item Short Form Health Survey; postoperative complications; and duration of surgery. To determine the extent of resection, the authors compared the calcaneal height ratio, calcaneal resection ratio, calcaneal resection angle, pitch line, and Haglund deformity height between groups. The learning curve for endoscopic calcaneoplasty was also calculated. RESULTS: There were no significant differences between the open and endoscopic groups on any outcome score. Two patients in the open group reported temporary paresthesia around the incisional site, indicating sural nerve injuries; no complication was reported in the endoscopy group. None of the parameters for extent of resection were statistically significant between the groups. The duration of surgery was 44.90 ± 10.52 and 65.39 ± 11.12 minutes in the open and endoscopy groups, respectively (P = .001). Regarding the learning curve for endoscopic calcaneoplasty (6 surgeons; 27 follow-up patients; 9 patients lost to follow-up), the duration of surgery reached a steady point of 55.68 ± 4.19 minutes after the fourth operation. CONCLUSION: The results of this study indicated that the endoscopy procedure was as effective as the open procedure. The endoscopic procedure required significantly more time than the open procedure, and the duration of the endoscopic procedure was shortened only after the fourth operation, suggesting that it requires high technical skills and familiarity with the anatomic relationships.

Hierarchical and heterogeneous hydrogel system as a promising strategy for diversified interfacial tissue regeneration.

Despite breakthroughs in tissue engineering, a tremendous problem still lies in repairing the interfacial tissue which connects soft tissue to hard tissue, particularly cartilage-bone, tendon/ligament-bone, and cementum-ligament-bone interfaces. The challenge comes from the complicated biophysical and biochemical characteristics of interfacial tissues, involving a graded variation of chemical components, structures, and mechanical properties as well as a heterogeneous cell distribution from the soft end to the hard end. Accordingly, significant progress has been made in the design of hierarchical and heterogeneous hydrogel systems in order to solve this problem. Advanced programmable technologies, such as 3D printing and microfluidic platforms, have shown potential in constructing templates or scaffolds with tissue-specific characteristics. The structural specialty of the three aforementioned interfacial tissues is summarized in this review. Then the text concentrates on how to utilize different scale hydrogels (from chemical variation, nanoscale, microscale to cellular regulation) to fabricate gradient constructions for regenerating interfacial tissues, together with in vitro and in vivo outcomes. In particular, the fabrication of continuous gradients is highlighted in this review. Promisingly, the versatile designs involved in fabricating hierarchical and heterogeneous hydrogel systems are predicted to tackle the unsolved problems, and this interfacial tissue engineering methodology is expected to expand its use in therapeutic applications.

Roles of oxygen level and hypoxia-inducible factor signaling pathway in cartilage, bone and osteochondral tissue engineering.

The repair and treatment of articular cartilage injury is a huge challenge of orthopedics. Currently, most of the clinical methods applied in treating cartilage injuries are mainly to relieve pains rather than to cure them, while the strategy of tissue engineering is highly expected to achieve the successful repair of osteochondral defects. Clear understandings of the physiological structures and mechanical properties of cartilage, bone and osteochondral tissues have been established, but the understanding of their physiological heterogeneity still needs further investigation. Apart from the gradients in the micromorphology and composition of cartilage-to-bone extracellular matrixes, an oxygen gradient also exists in natural osteochondral tissue. The response of hypoxia-inducible factor (HIF)-mediated cells to oxygen would affect the differentiation of stem cells and the maturation of osteochondral tissue. This article reviews the roles of oxygen level and HIF signaling pathway in the development of articular cartilage tissue, and their prospective applications in bone and cartilage tissue engineering. The strategies for regulating HIF signaling pathway and how these strategies finding their potential applications in the regeneration of integrated osteochondral tissue are also discussed.