Intracellular Staphylococcus aureus infection in human osteoblasts: circRNA expression analysis.

Staphylococcus aureus (S. aureus) has the ability to invade human cortical bones and cause intracellular infections in osteoblasts, which may lead to a long-term infection that is difficult to eliminate. It is critical to identify the underlying mechanisms of the osteoblast response to the intracellular S. aureus. More recently, multiple circular RNA (circRNA) functions have been identified, including serving as protein scaffolds or miRNA sponges and being translated into polypeptides. The role that circRNAs play in intracellular S. aureus infection of osteoblasts has not, to our knowledge, been investigated. Here, we established an intracellular infection model of S. aureus in osteoblasts and compared the circRNA expression of osteoblasts between the infected and control groups using RNA sequencing technology, by which a significant difference was found. In total, 117 upregulated and 125 down-regulated differentially expressed circRNAs (DEcircRNAs) were identified, and reverse transcription-quantitative PCR was employed to validate the results of RNA sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that DEcircRNAs were enriched in processes associated with macromolecule modification, cellular component organization or biogenesis, and intracellular non-membrane-bound organelles. Finally, a potentially important network of circRNA-miRNA-mRNA based on the DEcircRNAs was constructed. Overall, this study revealed the circRNA expression profile of human osteoblasts infected by intracellular S. aureus for the first time, and identified the circRNAs that may contribute to the pathogenesis of infectious diseases caused by intracellular S. aureus infection in human osteoblasts.

P7C3 Ameliorates Bone Loss by Inhibiting Osteoclast Differentiation and Promoting Osteogenesis.

Bone homeostasis, the equilibrium between bone resorption and formation, is essential for maintaining healthy bone tissue in adult humans. Disruptions of this process can lead to pathological conditions such as osteoporosis. Dual-targeted agents, capable of inhibiting excessive bone resorption and stimulating bone formation, are being explored as a promising strategy for developing new treatments to address osteoporosis. In this study, we investigated the effects of P7C3 on bone remodeling and its potential therapeutic role in osteoporosis treatment in mice. Specifically, P7C3 can remarkably suppress receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages via the Akt-NF-κB-NFATc1 signaling pathway. Additionally, RNA sequencing (RNAseq) analysis revealed that P7C3 promoted osteoblast differentiation and function through the Wnt/ß-catenin signaling pathway, thereby enhancing bone formation. Furthermore, µCT analysis and histological examination of bone tissues from P7C3-treated mice showed attenuation of both Ti-induced bone erosion and ovariectomy (OVX)-induced bone loss. These findings suggest that P7C3 may have a novel function in bone remodeling and may be a promising therapeutic agent for the treatment of osteoporosis. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Macrophage Membrane-Reversibly Cloaked Nanotherapeutics for the Anti-Inflammatory and Antioxidant Treatment of Rheumatoid Arthritis.

During rheumatoid arthritis (RA) development, over-produced proinflammatory cytokines represented by tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) represented by H2 O2 form a self-promoted cycle to exacerbate the synovial inflammation and tissue damage. Herein, biomimetic nanocomplexes (NCs) reversibly cloaked with macrophage membrane (RM) are developed for effective RA management via dual scavenging of TNF-α and ROS. To construct the NCs, membrane-penetrating, helical polypeptide first condenses TNF-α siRNA (siTNF-α) and forms the cationic inner core, which further adsorbs catalase (CAT) via electrostatic interaction followed by surface coating with RM. The membrane-coated NCs enable prolonged blood circulation and active joint accumulation after systemic administration in Zymosan A-induced arthritis mice. In the oxidative microenvironment of joints, CAT degrades H2 O2 to produce O2 bubbles, which shed off the outer membrane layer to expose the positively charged inner core, thus facilitating effective intracellular delivery into macrophages. siRNA-mediated TNF-α silencing and CAT-mediated H2 O2 scavenging then cooperate to inhibit inflammation and alleviate oxidative stress, remodeling the osteomicroenvironment and fostering tissue repair. This study provides an enlightened strategy to resolve the blood circulation/cell internalization dilemma of cell membrane-coated nanosystems, and it renders a promising modality for RA treatment.

Analysis of Isokinetic Strength Test in Arthroscopic Meniscus Suture to Improve Knee Joint Strength and Function.

Objective: This study is aimed to examine the correlation between the transitions in the muscular strength pre and post arthroscopic meniscus suture surgery. Methods: A total of 87 patients records were collected from the electronic medical records of the Second Affiliated Hospital of Soochow University from 2020 to 2021. Patients in the operative group underwent arthroscopic meniscus sutures. The isokinetic muscular strength test system (ISOMED2000) tool was utilized to examine the isokinetic intensity of the knee joins on both sides and the balance was marked and adjusted to the training methods before the test. The HSS score was used to assess the transitions in the knee activity. Results: There was a significant variation in the extensor muscle strength found on the affected portion where F value was observed at 3747.845 (P < .01). The extensor knee joint strength of the affected side was less than the healthy side when compared with pre-operation, one month, three months, and six months post-surgery where F values were found to be 5287.41, 5510.517, and 1947.91 respectively (P < .001). After six months of the surgery, there was an improvement in the isokinetic muscular strength of patients, where the measurement of the damaged side and the healthier side was observed as 89.11 ± 6.78 and 93.45 ± 5.59, respectively. Conclusion: Arthroscopic meniscus suture surgery is observed to have a superior influence on the treatments. After 6 months of surgery, the muscular force of the knee extensor on the affected joint portion enhanced remarkably in contrast to the other durations.

Comparison of Arthroscopic-Assisted Percutaneous Internal Fixation With a Modified Reducer Versus Open Reduction and Internal Fixation for Schatzker Type II and III Tibial Plateau Fractures.

Background: Tibial plateau fractures require anatomical reduction and stable fixation to achieve satisfactory results. In addition, addressing any related injuries is of paramount importance. Arthroscopic reduction and internal fixation (ARIF) has been promoted as a possible technique to treat tibial plateau fractures. Purpose: To compare the effectiveness of ARIF with this modified reducer and open reduction and internal fixation (ORIF) for Schatzker types II and III tibial plateau fractures. Study Design: Cohort study; Level of evidence, 3. Methods: We retrospectively reviewed 68 patients who were treated for Schatzker type II or III tibial plateau fractures between August 1, 2014, and October 31, 2018. Patients were categorized into the ARIF (n = 33) and ORIF groups (n = 35). The groups were compared regarding intra-articular injuries, duration of hospital stay, complications, and clinical outcomes-including the International Knee Documentation Committee (IKDC) score, the Hospital for Special Surgery (HSS) score, and range of motion (ROM). The paired t test was used to compare preoperative and postoperative data, and the chi-square test was used to compare the IKDC and HSS scores. Results: The median follow-up period was 36 months (26-40 months). Additional intra-articular lesions were found in 29 patients-21 in the ARIF group and 8 in the ORIF group (P = .02). A significant difference was observed in the duration of hospital stay-3.58 ± 1.46 days for the ARIF group and 4.57 ± 1.12 days for the ORIF group (t = -3.169; P = .002). All fractures healed within 3 months after surgery. The complication rate for all patients was 11%, with no significant difference between the ARIF and ORIF groups (t = 1.244; P = .265). At the final follow-up, there were no significant differences between the 2 groups in the IKDC score, HSS score, and ROM (P > .05 for all). Conclusion: ARIF with a modified reducer was found to be an effective, reliable, and safe procedure for the treatment of Schatzker types II and III tibial plateau fractures. Both ARIF and ORIF provided equally good results, while ARIF offered a more precise evaluation and reduced the duration of hospital stay.

MiR-760 targets HBEGF to control cartilage extracellular matrix degradation in osteoarthritis.

The present study was developed to explore whether microRNA (miR)-760 targets heparin-binding EGF-like growth factor (HBEGF) to control cartilage extracellular matrix degradation in osteoarthritis. Both miR-760 and HBEGF expression levels were analysed in human degenerative cartilage tissues and in interleukin (IL)-1ß/tumour necrosis factor (TNF)-α-treated chondrocytes in vitro. A series of knockdown and overexpression assays were then used to gauge the functional importance of miR-760 and HBEGF in OA, with qPCR and western immunoblotting analyses. Bioinformatics assays were used to identify putative miR-760 target genes, with these predictions then being validated through RNA pulldown and luciferase reporter assays. A murine anterior cruciate ligament transection model of OA was then established to prove the in vivo relevance of these findings. These experiments revealed that human degenerative cartilage tissues exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF levels. IL-1ß/TNF-α-treated chondrocytes also exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF expression. When chondrocytes were transfected with either miR-760 inhibitor or HBEGF overexpression constructs, this was sufficient to interfere with degradation of the extracellular matrix (ECM). Moreover, miR-760 was confirmed to control chondrocyte matrix homeostasis by targeting HBEGF, and the overexpression of HBEGF partially reversed the effects of miR-760 mimic treatment on the degradation of the cartilage ECM. When OA model mice were administered an intra-articular knee injection of an adenoviral vector encoding a miR-760 mimic construct, cartilage ECM degradation was aggravated. Conversely, the overexpression of HBEGF in OA model mice partially reversed the effects of miR-760 overexpression, restoring appropriate ECM homeostasis. In summary, these data indicated that the miR-760/HBEGF axis plays a central role in orchestrating the pathogenesis of OA, making it a candidate target for therapeutic efforts in OA.

Multiplex Surface-Enhanced Raman Scattering: An Emerging Tool for Multicomponent Detection of Food Contaminants.

For survival and quality of human life, the search for better ways to ensure food safety is constant. However, food contaminants still threaten human health throughout the food chain. In particular, food systems are often polluted with multiple contaminants simultaneously, which can cause synergistic effects and greatly increase food toxicity. Therefore, the establishment of multiple food contaminant detection methods is significant in food safety control. The surface-enhanced Raman scattering (SERS) technique has emerged as a potent candidate for the detection of multicomponents simultaneously. The current review focuses on the SERS-based strategies in multicomponent detection, including the combination of chromatography methods, chemometrics, and microfluidic engineering with the SERS technique. Furthermore, recent applications of SERS in the detection of multiple foodborne bacteria, pesticides, veterinary drugs, food adulterants, mycotoxins and polycyclic aromatic hydrocarbons are summarized. Finally, challenges and future prospects for the SERS-based detection of multiple food contaminants are discussed to provide research orientation for further.

Synthesis of recyclable SERS platform based on MoS2@TiO2@Au heterojunction for photodegradation and identification of fungicides.

Surface-enhanced Raman spectroscopy (SERS) substrates based on metal/semiconductors have attracted much attention due to their excellent photocatalytic activity and SERS performance. However, they generally exhibit low light utilization and photocatalytic efficiencies. Herein, molybdenum disulfide coated titanium dioxide modified with gold nanoparticles (MoS2@TiO2@Au) as a heterojunction-based recyclable SERS platform was fabricated for the efficient determination of fungicides. Results showed that the MoS2@TiO2@Au platform could rapidly degrade 90.7% crystal violet in 120 min under solar light irradiation and enable reproducible and sensitive SERS analysis of three fungicides (methylene blue, malachite green, and crystal violet) and in-situ monitor of the photodegradation process. The platform could also be reused five times due to the unique integrated merits of the MoS2@TiO2@Au heterojunction. Meanwhile, experiments in determining methylene blue in prawn protein solution achieved a limit of detection of 1.509 µg/L. Therefore, it is hoped that this work could expand detection applications of photocatalytic materials.

Mid-term study on the effects of arthroscopic discoid lateral meniscus plasty on patellofemoral joint: An observational study.

In the present study, we aimed to investigate the clinical outcomes of arthroscopic discoid lateral meniscus (DLM) plasty and the adaptive changes in the patellofemoral joint after surgery. From September 2010 to March 2012, 25 patients with DLM injuries who underwent arthroscopic meniscus plasty were enrolled in the prospective study. All patients underwent clinical evaluation before the operation and at the last follow-up, and imaging evaluation was performed by upright magnetic resonance imaging before and 1 month after the operation as well as at the last follow-up. Clinical evaluation included Lysholm score, Kujala score, McMurray's sign, patellar mobility, patella grind test, and quadriceps atrophy. Imaging evaluation included bisect offset index, patella tilt angle (PTA), and cartilage damage. Lysholm score, Kujala score, McMurray's sign, and quadriceps atrophy at the last follow-up were significantly improved compared with the preoperative levels (P < .05). At the last follow-up, there were no statistical differences in patella mobility and patella grind test compared with the preoperative levels. In addition, bisect offset index and PTA showed a dynamic trend of rising and then falling over time (P < .05). At 1 month after the operation, bisect offset index and PTA were significantly increased compared with the preoperative levels or the values at the last follow-up (P < .05), while there were no differences between the preoperation and the last follow-up. Cartilage damage became worse with time (P < 0.05), and the 2 were positively correlated (Spearman = 0.368). At the last follow-up, the degree of cartilage damage was significantly increased compared with the preoperative level (P < .017), while there was no significant difference between the 1-month postoperative grade and the preoperational grade or the last follow-up grade. The effect of arthroscopic DLM plasty on the patellofemoral joint was dynamic, with the position of the patella deviating in the early stages and recovering in the mid-term, especially when the knee was in the biomechanical standing position. In addition, the patellofemoral joint cartilage might undergo accelerated degeneration after the operation, while the mid-term effect of the operation was positive, and the patellofemoral joint function was acceptable.

Structural Mapping of BMP Conformational Epitopes and Bioengineering Design of Osteogenic Peptides to Specifically Target the Epitope-Binding Sites.

Introduction: Human bone morphogenetic proteins (BMPs) constitute a large family of cytokines related to members of the transforming growth factor-ß superfamily, which fulfill biological functions by specificity binding to their cognate type I (BRI) and type II (BRII) receptors through conformational wrist and linear knuckle epitopes, respectively. Methods and Results: We systematically examined the intermolecular recognition and interaction between the BMP proteins and BRI receptor at structural, energetic and dynamic levels. The BRI-binding site consists of three hotspot regions on BMP surface, which totally contribute ~70% potency to the BMP-BRI binding events and represent the core sections of BMP conformational wrist epitope; the contribution increases in the order: hotspot 2 (~ 8%) < hotspot 3 (~ 20%) < hotspot 1 (~ 40%). Multiple sequence alignment and structural superposition revealed a consensus sequence pattern and a similar binding mode of the three hotspots shared by most BMP members, indicating a high conservation of wrist epitope in BMP family. The three hotspots are natively folded into wellstructured U-shaped,, loop and double-stranded conformations in BMP proteins, which, however, would become largely disordered when splitting from the protein context to derive osteogenic peptides in free state, thus largely impairing their rebinding capability to BRI receptor. In this respect, cyclization strategy was employed to constrain hotspot 1/3-derived peptides into a native-like conformation, which was conducted by adding a disulfide bond across the ending arms of linear peptides based on their native conformations. Fluorescence-based assays substantiated that the cyclization can effectively improve the binding affinities of osteogenic peptides to BRI receptor by 3-6-fold. The cyclic peptides also exhibit a good selectivity for BRI over BRII (> 5-fold), confirming that they can specifically target the wrist epitope-binding site of BRI receptor. Conclusion: The rationally designed cyclic peptides can be regarded as the promising lead entities that should be further chemically modified to enhance their in vivo biological stability for further bioengineering therapeutic osteogenic peptides against chondrocyte senescence and bone disorder.

Proteomics Reveals the Key Molecules Involved in Curcumin-induced Protection Against Sciatic Nerve Injury in Rats.

We generated a rat model of sciatic nerve crush injury and characterized the effects of curcumin on sciatic nerve recovery by using behavioral experiments, hematoxylin-eosin staining, toluidine blue staining, and immunohistochemical. Proteomic analysis using tandem mass tagging was performed to determine differentially expressed proteins (DEPs), and GO and KEGG pathway analyses of overlapping DEPs was conducted, following which, qPCR, western blotting, and immunofluorescence were further performed to validate the proteins of interest. Finally, a Schwann cell injury model was used to verify the effect of curcumin on potential targets. The rat model was successfully established and curcumin improved the sciatic nerve function index of rats with sciatic nerve injury (SNI) and increased the number and diameter of myelinated axons in the sciatic nerve. In the Sham group versus the Injured group and in the Injured group versus the Curcumin group, we identified a total of 4,175 proteins, of which 953 were DEPs, and 218 were known overlapping DEPs. Ten associated pathways, such as calcium signaling pathway, biosynthesis of antibiotics, and long-term potentiation, were identified. The 218 overlapping DEPs were primarily involved in negative regulation of apoptotic process, biological processes, cytoplasm cellular component, and protein binding molecular function based on GO annotation. Curcumin promoted increased expression of ApoD and inhibited the expression of Cyba in vivo and in vitro. These results indicated that curcumin promoted sciatic nerve repair through regulation of various proteins, targets, and pathways. Cyba and ApoD may be potential targets of curcumin in the treatment of SNI.

Clinical efficacy of arthroscopic treatment in ischial tuberosity cyst: A retrospective comparison study.

ABSTRACT: Ischial tuberosity cyst is a common disease, and the conventional incision procedure is associated with several disadvantages, leading to unsatisfactory therapeutic outcomes. The aim of the study was to evaluate the clinical outcomes of arthroscopic treatment for ischial tuberosity cyst and compared it with conventional incision surgery.The clinical data of 57 patients with ischial tuberosity cyst from May 2016 to September 2018 were retrospectively analyzed. According to the inclusion and exclusion criteria, a total of 49 patients were included. Of these patients, 24 patients received arthroscopic procedure (N = 24) and 25 patients received conventional incision procedure (N = 25). The operation time, intraoperative blood loss, postoperative drainage, postoperative hospital stay, and postoperative complications were compared between the 2 groups. Visual analogue scale scores was used to evaluate pain at 1 day, 1 week, and 1 month after the surgery.All 49 patients were followed up for (11.3 ±â€Š3.3) months. All patients in the arthroscopy group achieved phase I healing while 3 patients in conventional incision group developed complications. The operation time, intraoperative blood loss, postoperative drainage, and hospital stay in the arthroscopy group were (54.7 ±â€Š7.7) minutes, (20.8 ±â€Š3.5) mL, (20.3 ±â€Š5.6) mL, and (2.8 ±â€Š0.6) days, and were significantly better than those of (71.8 ±â€Š8.8) minutes, (67.3 ±â€Š12.0) mL, (103.6 ±â€Š20.3) mL, and (7.8 ±â€Š2.9) days in the conventional incision group, respectively. In the arthroscopy group, the visual analogue scale scores at 1 day, 1 week, and 1 month after the surgery [(2.6 ±â€Š0.7), (0.5 ±â€Š0.6), (0.3 ±â€Š0.5) points] were significantly lower than those in the conventional incision group [(6.0 ±â€Š0.7), (3.0 ±â€Š1.0), and (1.1 ±â€Š1.0) points], and the differences were statistically significant (P < .05). Finally, no significant difference was observed in the incidence of postoperative complications between the 2 groups (P > .05).In the treatment of ischial tuberosity cysts, arthroscopy has advantages of minimal invasion, less blood loss during perioperative period, milder postoperative pain, and rapid recovery when compared with conventional incision surgery.

Comparison between infrapatellar and suprapatellar approaches for intramedullary nailing for the fractures of the tibial shaft.

INTRODUCTION: This study aimed to compare the outcomes at the clinical and functional levels of suprapatellar (SP) and infrapatellar (IP) approaches for intramedullary nailing in treating tibial shaft fracture. METHODS: Patients who underwent tibial shaft fracture intramedullary nailing by the SP approach or IP approach in a trauma center were retrospectively reviewed. The demographics, intraoperative fluoroscopy time, operation time, blood loss, irrigation volume, postoperative X-ray alignment, and complications of patients were compared between the two groups under different approaches. Lysholm knee score, visual analog score (VAS), and incidence of anterior knee pain (AKP) were assessed 1 year after surgery. RESULTS: The study finally included well-documented 81 patients (38 SP versus 43 IP). The SP group exhibited significantly shorter intraoperative fluoroscopy time than that of the IP group (81.7 ± 14.5 s vs. 122.0 ± 24.3 s, P < 0.001). Both aspects recorded a precise reduction of the fracture: angulation (2.1 ± 1.2° vs 3.1 ± 1.5°, P < 0.05) and translation (0.6 ± 0.8 mm vs 1.4 ± 1.5 mm, P < 0.05) in the coronal plane in the SP group. However, the sagittal plane recorded no such change (P > 0.05). The Lysholm knee score was higher in the SP group than that of the IP group (87 ± 8 vs. 80 ± 15, P < 0.05). The SP group displayed an evidently lower average VAS score than that of the IP approach group (0.3 ± 0.8 vs 1.3 ± 1.4, P < 0.001). Six cases (16%) in the SP group and 16 cases (37%) in the IP group experienced AKP 1-year post-operation (P < 0.05). As far as complications are concerned, neither group showed any significant difference (P > 0.05). CONCLUSION: Compared with the IP approach, the application of intramedullary nailing through the SP approach in treating tibial shaft fractures can effectively shorten the intraoperative fluoroscopy time, correct coronal plane angulation and translation deformity, reduce the incidence of AKP and improve postoperative function.

Posterior Locking Plate Fixation of Bartonícek Type IV Posterior Malleolar Fracture: A Focus on Die-Punch Fragment Size.

Die-punch fragments refer to articular cartilage and subchondral bone embedded in cancellous bone as part of an intra-articular fracture. Bartonícek type IV posterior malleolar fractures with associated die-punch fragments are rare, and the appropriate surgical approach remains unclear. We determined outcomes, and the effect of die-punch fragment size on outcomes, for 32 patients with Bartonícek type IV posterior malleolar fractures with die-punch fragments between January 2015 and December 2017. Mean follow-up for all patients was 23.8 (range 20.0-30.0) months. At the final follow-up visit, mean ankle dorsal extension was 24.6° and plantar flexion was 40.0°; American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 88.6 ± 4.3; visual analog scale weightbearing pain score was 1.5 ± 0.6; and Bargon traumatic arthritis score was 0.8 ± 0.4. There were no severe complications. We divided patients into a small-fragment (≤3 mm) group (n = 12) and large-fragment (>3 mm) group (n = 20). The Bargon scores at final follow-up were 0.5 and 1, respectively (P=.02). There were no statistically significant differences between the 2 groups for the other outcome scores at various time intervals. The posterolateral approach with distal locking plate internal fixation for Bartonícek type IV posterior malleolar fractures with die-punch fragments can result in excellent anatomical reduction of the collapsed articular surface and the displaced fragment from the tibial plafond, recovery of articular surface congruity, and maintenance of joint stability. Die-punch fragment size may not impact clinical and functional outcomes but may contribute to post-traumatic arthritis.

Injectable Erythrocyte Gel Loaded with Bulleyaconitine A for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with clinical manifestations including joint cartilage, synovitis, and bone damage. Here we developed an injectable erythrocyte gel loaded with Bulleyaconitine A (BLA) for the treatment of RA and demonstrated its anti-inflammatory effects in vivo and in vitro. In vitro experiments showed that BLA could effectively down-regulate the expression of pro-inflammatory factor in activated macrophages through the nuclear factor-κB (NF-κB) pathway. In vivo experiments have shown that the injection of BLA@RBCs in the inflammatory joints of CIA mice increases the local concentration of BLA in a long time. Improved therapeutic outcomes and reduced toxicity of BLA are demonstrated in our work. Together, the developed BLA@RBCs drug delivery system provides an alternative strategy to treat RA joints and shows high potential in clinical RA treatment.

LncRNA SNHG16 promotes Schwann cell proliferation and migration to repair sciatic nerve injury.

BACKGROUND: To investigate the expression of long non-coding RNA (lncRNA) Snorna hostgene16 (SNHG16) in sciatic nerve injury tissues and cells. The molecular mechanism of SNHG16 regulating signal activator of transcription 3 (STAT3) expression through "sponge" adsorption of miR-93-5p was also studied. METHODS: A rat model of sciatic nerve injury was established, and primary Schwann cells (SCs) were extracted. The expression of SNHG16 in animal tissues with sciatic nerve injury and SCs treated with ischemia and hypoxia was detected by qPCR, and CCK-8 assay, cell scratch assay, and Transwell chamber assay were used to detect cell proliferation, migration, and invasion. The targeted binding of SNHG16 to miR-93-5p was verified by double luciferase reporter gene assay and miRNA immunoprecipitation assay. MiR-93-5p mimic, SNHG16 overexpression vector, and sh-STAT3 plasmid were transfected into cells, respectively, and the mRNA expressions of SNHG16, miR-93-5p, and STAT3 in the cells were detected by qPCR. RESULTS: The expression of lncRNA SNHG16 was decreased after sciatic nerve injury, while overexpression of SNHG16 promoted the proliferation, migration, and invasion of SCs. The results of dual luciferase reporter gene assay and miRNA immunoprecipitation reaction showed miR-93-5p interacted with SNHG16, and the overexpression of miR-93-5p reversed the promoting effects of SNHG16 on the proliferation and invasion of SCs. At the same time, the knockdown of STAT3, which is the target gene of miR-93-5p, reversed the proliferation and invasion promotion effect of SNHG16 on SCs. SNHG16 affected the expression of its downstream target gene STAT3 by adsorbing miR-93-5p via endogenous competitive sponge. CONCLUSIONS: SNHG16 can regulate STAT3 expression by sponge adsorption of miR-93-5p in SCs, and SNHG16 and miR-93-5p can be used as potential targets for the diagnosis and treatment of sciatic nerve injury.

Capsular Healing in Interportal and Periportal Capsulotomy Methods of Hip Arthroscopy.

OBJECTIVE: To evaluate the midterm outcomes and the capsular healing in patients who had interportal capsulotomy versus periportal capsulotomy of hip arthroscopy. METHODS: Retrospectively reviewed 33 patients with labral tear received hip arthroscopy, with an average age of 41 (27-67) years, including 13 cases of Cam deformity and three cases of Pincer deformity. All patients had positive sign of flexion adduction internal rotation or flexion abduction external rotation. With MRI and radiographic (CT, X plain) imageological examination. MRI showed that all patients had labral tear. Radiographic finding (CT, X plain) showed the pathological changes of acetabular and femoral neck osteophyte. One group with 23 patients were treated with periportal capsulotomy. Another group with 10 patients were treated with interportal capsulotomy. All patients did not close the capsule. Clinical outcomes were measured with the Hip Outcome Score Activities of Daily Living (HOS-ADL) and the modified Harris Hip Score (mHHS), patient satisfaction measured with visual analogue scale (VAS). The healing of the capsule was evaluated by MRI. MRI showed continuous capsular indicated healing, discontinuous capsular indicated unhealing. Postoperatively 6 months, mHHS and HOS-ADL were obtained. Randomized controlled trials were used in this study for analysis. RESULTS: All patients were followed up with average time of 9.3 months(3-29 months). The postoperative symptoms were obviously relieved, the VAS decreased from (4.9 ± 0.6) to (1.2 ± 0.2) after 3 months postoperative. Follow up 6 months post-operation, patients in the interportal group, the mHHS and HOS-ADL scores improvement were respectively 69.4 ± 9.3 & 70 ± 8.8 pre-operation, and 92.5 ± 5.0 & 86.6 ± 5.4 post-operation (P < 0.05); Patients in the periportal group, the mHHS and HOS-ADL scores improvement were respectively 69.9 ± 15.8, 68.1 ± 15.0 pre-operation, and 90.1 ± 9.3 & 86.7 ± 7.9 post-operation (P < 0.05).The differences were statistically significant. Six months after operation, MRI showed that 23 patients with periportal capsulotomy, the capsule have healed, without other complications. Three of the ten patients with interportal capsulotomy were healed and seven were not. CONCLUSION: Interportal and periportal capsulotomy had good outcomes. The technique of periportal capsulotomy had little damage to the joint capsule. Although the capsule did not close, the capsule healed well in postoperative follow-up. The nonunion rate of the joint capsule was high in the interportal capsulotomy without close the capsule.

The CT morphological characteristics and the clinical management strategy of posterior malleolar fractures with talar subluxation.

BACKGROUND: The optimal clinical treatment and the computed tomography (CT) morphological characteristics of posterior malleolar fractures (PMF) with talar subluxation remain inconclusive. Clinically, both plate screws and lag screws are widely used to fix posterior malleolar fragments using a direct or indirect approach. We sought to summarize the morphological characteristics and modified classification on the basis of CT and the intraoperative strategy for posterior talar subluxation in PMF. METHODS: Retrospectively, 46 adult PMF patients with subluxations of the talus were recruited as the study cohort. According to its morphological features, PMF with subluxation of the talus can be divided mainly into two types using this modified classification: a complete fracture (the single-fragment type) and PMF with two-angled fracture fragments (the double-fragment type). The cohort's demographic information, classifications, fracture morphology, fixation methods, pain levels, and functional scores were recorded for both fracture types. RESULTS: The average values of the depths and heights of the posterior malleolar fragments were (29.1±7.3) mm for the single-fragment type and (17.9±4.2) mm for the double-fragment type. There was a significant difference in the mean values between the two types (P < 0.05). Posterior plate fixation was suitable for the single-fragment type, while antero-posterior and postero-anterior (AP-PA) lag screws fixations were made available for the double-fragment type. Both methods achieved good results. No significant differences were found in terms of sex, age, body mass index (BMI), side, Haraguchi classification, Bartonícek and Rammelt classification, Visual Analog Scale (VAS) scores, or American Orthopedic Foot & Ankle Society scores (AOFAS) when comparing the single-/double-fragment type groups after the mid-term follow-up (P > 0.05). CONCLUSION: According to the injury mechanism and the morphological characteristics of the fractures, the proposed improved classification system for PMF with subluxation of the talus based on the injury mechanism and the fracture morphology can provide guidance for surgical management strategies and achieve optimal outcomes.

Sulforaphane protects against oxidative stress­induced apoptosis via activating SIRT1 in mouse osteoarthritis.

Osteoarthritis (OA), the most common form of human joint disease, is characterized by progressive degeneration of the articular cartilage, synovitis and subchondral osteoporosis. Chondrocyte apoptosis is the primary pathogenic mechanism of OA and is considered to be a potential therapeutic target. Sulforaphane (SFN), a dietary isothiocyanate obtained from cruciferous vegetables, has been reported to exert an anti­apoptotic effect by activating sirtuin 1 (SIRT1). To the best of our knowledge, however, the effects of SFN on apoptotic responses in OA have not been reported. In the present study, SFN was shown to significantly inhibit chondrocyte apoptosis while enhancing expression levels of SIRT1 in a H2O2­induced OA mouse model. The anti­apoptotic effect of SFN was reversed by SIRT1 small interfering RNA, implying that SIRT1 exerted a protective role against the effect of SFN on chondrocytes. The expression levels of C/EBP homologous protein, 78­kDa glucose regulated protein, Bax, Bcl­2 and cleaved caspase 3 were found to be downregulated in SFN­treated mice. Furthermore, SFN ameliorated cartilage degradation in the OA mouse model. These findings indicate that SFN exerted an anti­apoptotic effect on chondrocytes and ameliorated OA in vivo by activating the SIRT1 signaling pathway.

Activation of the extracellular-signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK) signal pathway and osteogenic factors in subchondral bone of patients with knee osteoarthritis.

BACKGROUND: The objectives of this study was to explore the activation of the extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathway and osteogenesis-related factors in the subchondral bone of patients with knee osteoarthritis (OA). METHODS: Ten patients with primary OA who underwent total knee arthroplasty in the Department of Arthritis Surgery of our hospital were enrolled, and subchondral bone tissue samples were obtained during the operation. He staining and saffron staining were used to observe the arrangement of chondrocytes in the patient tissues. The protein expression levels of JNK, p-JNK, ERK, p-ERK, Runx2 and OMD in subchondral bone were detected by Western Blot. Knee osteoarthritis mice were established. He staining was used to observe the arrangement of subchondral bone cells in the knee joint of mice. Cellular mineralized nodules were determined by alizarin red staining. RESULTS: Firstly, in general and staining, it was observed that the subchondral bone lesions of knee OA participants were obvious. Compared with normal knee joints, the levels of phosphorylation-c-Jun N-terminal kinase (P-JNK) and phosphorylation-extracellular-signal-regulated kinase (P-ERK) in the subchondral bone of knee arthritis participants were significantly increased (P<0.05). The level of osteomodulin (OMD) was significantly reduced (P<0.05). Secondly, compared with normal mice, the levels of JNK, P-JNK, OMD, ERK, and P-ERK in the model group were significantly different (P<0.05). At 2-8 weeks, the JNK and P-JNK levels in the mice model group increased significantly over time (P<0.05), and the OMD level decreased significantly over time (P<0.05). The levels of ERK and P-ERK fluctuated over time. Thirdly, osteoblasts were treated with different concentrations of anisomycin, and stained with alizarin red after continuous culture for 24 and 48 h, respectively. It was found that all the cells were stained with orange-red mineralized nodules. As the concentration of anisomycin was increased, the number of cell mineralization nodules was significantly larger, and the positive rate of chemical nodules increased. Different concentrations of anisomycin were given to interfere with the osteoblasts of mice. When anisomycin was administered at a dose of 25 ng, the OMD level reached the highest level. When the concentration of anisomycin was increased, the osteocalcin (OCN) level also showed an upward trend. CONCLUSIONS: The process by which the JNK signaling pathway regulates OMD may be closely related to the pathological changes of subchondral bone in patients with knee OA, and is involved in the occurrence and development of knee arthritis.