Zinc finger BED-type containing 3 promotes hepatic steatosis by interacting with polypyrimidine tract-binding protein 1.

AIMS/HYPOTHESIS: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus, insulin resistance and the metabolic syndrome is well established. While zinc finger BED-type containing 3 (ZBED3) has been linked to type 2 diabetes mellitus and the metabolic syndrome, its role in MASLD remains unclear. In this study, we aimed to investigate the function of ZBED3 in the context of MASLD. METHODS: Expression levels of ZBED3 were assessed in individuals with MASLD, as well as in cellular and animal models of MASLD. In vitro and in vivo analyses were conducted using a cellular model of MASLD induced by NEFA and an animal model of MASLD induced by a high-fat diet (HFD), respectively, to investigate the role of ZBED3 in MASLD. ZBED3 expression was increased by lentiviral infection or tail-vein injection of adeno-associated virus. RNA-seq and bioinformatics analysis were employed to examine the pathways through which ZBED3 modulates lipid accumulation. Findings from these next-generation transcriptome sequencing studies indicated that ZBED3 controls SREBP1c (also known as SREBF1; a gene involved in fatty acid de novo synthesis); thus, co-immunoprecipitation and LC-MS/MS were utilised to investigate the molecular mechanisms by which ZBED3 regulates the sterol regulatory element binding protein 1c (SREBP1c). RESULTS: In this study, we found that ZBED3 was significantly upregulated in the liver of individuals with MASLD and in MASLD animal models. ZBED3 overexpression promoted NEFA-induced triglyceride accumulation in hepatocytes in vitro. Furthermore, the hepatocyte-specific overexpression of Zbed3 promoted hepatic steatosis. Conversely, the hepatocyte-specific knockout of Zbed3 resulted in resistance of HFD-induced hepatic steatosis. Mechanistically, ZBED3 interacts directly with polypyrimidine tract-binding protein 1 (PTBP1) and affects its binding to the SREBP1c mRNA precursor to regulate SREBP1c mRNA stability and alternative splicing. CONCLUSIONS/INTERPRETATION: This study indicates that ZBED3 promotes hepatic steatosis and serves as a critical regulator of the progression of MASLD. DATA AVAILABILITY: RNA-seq data have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231875 ). MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository ( https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD041743 ).

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.

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.

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.

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.

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.

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.

In Silico Prediction of the Dissociation Rate Constants of Small Chemical Ligands by 3D-Grid-Based VolSurf Method.

Accumulated evidence suggests that binding kinetic properties-especially dissociation rate constant or drug-target residence time-are crucial factors affecting drug potency. However, quantitative prediction of kinetic properties has always been a challenging task in drug discovery. In this study, the VolSurf method was successfully applied to quantitatively predict the koff values of the small ligands of heat shock protein 90α (HSP90α), adenosine receptor (AR) and p38 mitogen-activated protein kinase (p38 MAPK). The results showed that few VolSurf descriptors can efficiently capture the key ligand surface properties related to dissociation rate; the resulting models demonstrated to be extremely simple, robust and predictive in comparison with available prediction methods. Therefore, it can be concluded that the VolSurf-based prediction method can be widely applied in the ligand-receptor binding kinetics and de novo drug design researches.

Reattachment of the superior peroneal retinaculum versus the bone block procedure for the treatment of recurrent peroneal tendon dislocation: two safe and effective techniques.

PURPOSE: Clinical outcomes between reattachment of the superior peroneal retinaculum (SPR) and the bone block procedure were compared in this study to elucidate which procedure was safer and more effective. METHODS: From 2012 to 2016, 25 patients with recurrent peroneal tendon dislocation underwent the bone block procedure (group A), and another 22 patients underwent reattachment of the SPR (group B). American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Ankle Activity Score (AAS), time to return to sports activity, rate of return to sports level, range of motion (ROM) of the ankle, rate of recurrence, and overall patient satisfaction were collected to evaluate outcomes between the two groups. RESULTS: In group A, 24 patients followed up at a mean period of 42.5 ± 16.7 months. The mean postoperative AOFAS score was 92.9 ± 3.9. The median time to return to sports activity was 6.0 months (IQR 4.3-6.0 months) with 19 patients (79.2%) returning to their previous sports level. Two patients experienced recurrent dislocation, and 22 patients (91.7%) were satisfied with the procedure. In group B, 20 patients followed up at a mean period of 35.8 ± 15.3 months. The mean postoperative AOFAS score was 95.0 ± 4.2. The median time to return to sports activity was 5.0 months (IQR 4.0-5.0 months) with 18 patients (90.0%) returning to their previous sports level. No recurrence was reported, and 18 patients (90.0%) were satisfied with the procedure. The time to return to sports activity in group B was significantly shorter than that in group A. There was no significant difference in complications or clinical outcomes between the two procedures. CONCLUSION: Both procedures offered satisfactory results for recurrent peroneal tendon dislocation with low rates of recurrence and complications. However, the time to return to sports activity after the reattachment of the SPR was shorter than that after the bone block procedure. LEVEL OF EVIDENCE: Retrospective Comparative Study, Level III.

CaAlg hydrogel containing bone morphogenetic protein 4-enhanced adipose-derived stem cells combined with osteochondral mosaicplasty facilitated the repair of large osteochondral defects.

PURPOSE: Cartilage repair presents a challenge to clinicians and researchers. A more effective procedure that can produce hyaline-like cartilage is needed for articular cartilage repair. Mosaic osteochondral grafts for large osteochondral defects often show poor integration between the grafts and the surrounding normal cartilage, leading to defective cracks filled with fibrous tissue instead of hyaline-like cartilage. In the present study, we aimed to repair the defective cracks with a calcium alginate (CaAlg) hydrogel containing bone morphogenetic protein 4 (BMP4)-enhanced adipose-derived stem cells (ADSCs). METHODS: ADSCs were transduced with BMP4 (B-ADSCs). The expression of BMP4 and type II collagen was confirmed using an enzyme-linked immunosorbent assay (ELISA). Swine models of large cartilage defects of the knee were constructed and received one of the four treatments: mosaicplasty only, mosaicplasty with the CaAlg hydrogel, mosaicplasty with the CaAlg hydrogel containing ADSCs, or mosaicplasty with the CaAlg hydrogel containing B-ADSCs injected into the defective cracks. Outcomes were evaluated at 12 and 24 weeks after surgery. RESULTS: The in vitro study showed that the osteogenic and chondrogenic activities of the B-ADSCs were enhanced compared with those of the control. In vivo, in the group that received mosaicplasty-containing B-ADSCs, osteochondral tissue was completely integrated with an intact surface. Additionally, the histological scores of the mosaicplasty-containing B-ADSCs group were significantly higher than those of the other groups. Biomechanical examination confirmed that the neocartilage possessed properties similar to those of normal cartilage. CONCLUSIONS: Mosaicplasty and hydrogel containing B-ADSCs promoted the repair of large cartilage defects by regenerating hyaline cartilage and repairing dead spaces between osteochondral grafts and donor-site defects, thus improving the feasibility and success rate of one-stage complete repair surgery for large osteochondral defects. This proposed method provides a novel and effective means for the repair of large articular osteochondral defects.

Concurrent arthroscopic osteochondral lesion treatment and lateral ankle ligament repair has no substantial effect on the outcome of chronic lateral ankle instability.

PURPOSE: The purpose of the study was to evaluate the effect of concurrent arthroscopic osteochondral lesion (OCL) treatment and lateral ankle ligament repair on the outcome of chronic lateral ankle instability. It was hypothesized that the arthroscopic OCL treatment might have some negative effect on the outcome of chronic lateral ankle instability (CLAI) by compromising the rehabilitation program. METHODS: Ankle arthroscopy and anatomic lateral ankle ligament repair with suture anchors were performed for 70 patients with CLAI between 2010 and 2012. Thirty-four patients (group A), 20 males and 14 females with a median age of 30(14-54) years, received arthroscopic abrasion, curettage, drilling, or microfracture for OCLs. The splint was removed daily for joint motion exercises beginning at post-operative 2 weeks and full weight bearing was allowed between post-operative week 8 and 12. The other 36 patients (group B) with no combined OCL were followed up as controls. Pre-operative and post-operative visual analog scale (VAS) scores, American Orthopaedic Foot and Ankle Society (AOFAS) scores, Tegner scores, sprain recurrence, ankle stability, and range of motion (ROM) were evaluated and compared. RESULTS: The median follow-up was 46.5 (38-55) months and 44.5 (38-56) months for group A and group B, respectively. The median post-operative VAS score, AOFAS score, and Tegner score were improved from the pre-operative level for both groups with good-to-excellent results for more than 90% patients. No significant difference was found between the two groups for the subjective scores and satisfaction rate (n.s.). Recurrent sprain was found among nine patients(26.5%) of the group A and five patients (13.9%) of the group B (n.s.). The incidence of the ROM restriction of group A was significantly higher than in group B (23.5 vs 5.6%, P = 0.043). CONCLUSIONS: The concurrent arthroscopic treatment of OCL with lateral ankle ligament repair demonstrated no substantial negative effect on the overall mid-term outcome of the patients with CLAI except for a potential risk of ROM restriction. LEVEL OF EVIDENCE: III.

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.

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.

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.

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.

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.

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.

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.