Autologous osteoperiosteal transplantation for cystic osteochondral lesions of the talus: Bone reconstruction is essential.

PURPOSE: Autologous osteoperiosteal transplantation (AOPT) is one of the most feasible and effective techniques for cystic osteochondral lesions of the talus (OLT). However, few reports have been reported about the process of graft-host bone healing and bone articular surface reconstruction, which help us to further understand the actual situation of bone healing and modify surgical methods. METHODS: We retrospectively evaluated 33 osteochondral lesions in 30 patients undertaking AOPT for OLT with subchondral cysts from December 2016 to October 2021. According to CT observation, we used 4 variables to describe the bony articular repair, including the integration of the articular surface, the height of the bone filling, the status of bone union, and the appearance of bone resorption or cystic change. We also analyzed the demographic data and clinical function. Descriptive statistics were used for demographic and clinical variables. Normally distributed data were presented as mean ± SD, and non-normally distributed data were presented as median (Q1, Q3). Associations between these variables and the primary clinical outcomes were examined using t-test or one-way ANOVA test for continuous variables. RESULTS: The patients' mean age was (41.7 ± 14.0) years old and the mean follow-up time was (29.6 ± 17.8) months. The chondral lesion size was (14.3 ± 4.1) mm. The cyst depth was (10.9 ± 3.7) mm. Significant improvements were observed in functional outcomes (according to the numeric rating scale for pain when walking and the American orthopedic foot and ankle society score) between the preoperative and latest follow-up evaluations, from 4.2 ± 2.1 to 2.2 ± 2.0 (p < 0.001), and from 66.8 ± 12.9 to 83.2 ± 10.4, respectively (p < 0.001). The overall satisfaction reached 8.3 of 10 points. All patients returned to sports and their median daily steps reached 8000 steps with 27 (81.8%) patients walking over 6000 steps daily. According to CT observation, "discontinuous bony articular surface and gap > 1 mm" was found in 27 grafts (81.8%), and "below the level of the adjacent articular surface, ≤ 1 mm" in a third of the grafts. Abnormal height of bone filling affected numeric rating scale score (p = 0.049) and American Orthopedic Foot and Ankle Society score (p = 0.027). Of note, bone resorption or cystic changes appeared in up to 13 autografts (39.4%). CONCLUSIONS: AOPT is an effective and acceptable technique for cystic OLT. Bone reconstruction is essential for large cystic OLT. How to get better bony articular reconstruction and avoid cyst recurrence should still be paid more attention.

Effects of Pathological Characteristics on Functional Scores and Surgical Satisfaction in Patients after Hallux Valgus Surgery.

OBJECTIVE: Few studies have explored the relationship between the pathological characteristics of hallux valgus and surgical outcomes. The aim of our study was to report the influence of pathological characteristics such as the tibial sesamoid position (TSP) and first metatarsal pronation on postoperative functional scores and patient satisfaction with hallux valgus surgery. METHODS: From June 2017 to December 2022, a retrospective analysis was conducted on patients who underwent hallux valgus surgery at our hospital. Anteroposterior (AP) x-ray parameters (hallux valgus angle [HVA], intermetatarsal angle [IMA], distal metatarsal articular angle [DMAA], TSP, first metatarsal pronation, and first metatarsophalangeal joint dislocation) (preoperative weight-bearing, immediate postoperative non-weight-bearing, and early postoperative weight-bearing), visual analog scale (VAS) scores, American Orthopaedic Foot and Ankle Society (AOFAS) forefoot scores, SAFE-Q self-administered foot evaluation questionnaire (excluding the Sports Activity subscale), complications, and patient satisfaction were used to describe the outcomes. Correlation analysis and multiple linear regression models were used to identify factors influencing postoperative functional scores and patient satisfaction after hallux valgus surgery. RESULTS: Eighty-one patients (92 feet) whose early radiographic parameters and latest follow-up scores improved significantly (p < 0.01) were included in the present study. The overall complication rate was 27.2%, with recurrence being the most common complication (20.7%). Functional scores and patient satisfaction were associated with age; preoperative, immediate postoperative, and early postoperative HVA; and immediate postoperative IMA (p < 0.05), but not with TSP, first metatarsal pronation, DMAA, callosities, toe deformities, or first metatarsophalangeal joint dislocation (p > 0.05). The R2 values of the multiple linear regression models predicting postoperative functional scores and patient satisfaction ranged from 0.042 to 0.351. CONCLUSION: TSP and first metatarsal pronation were unrelated to postoperative functional scores or patient satisfaction. This finding enhances surgeons' understanding of the functional prognosis of hallux valgus surgery, particularly aiding in explaining the condition and assessing surgical outcomes.

Exploration of the miR-187-3p/CNR2 pathway in modulating osteoblast differentiation and treating postmenopausal osteoporosis through mechanical stress.

This study aimed to explore how mechanical stress affects osteogenic differentiation via the miR-187-3p/CNR2 pathway. To conduct this study, 24 female C57BL/6 mice, aged 8 weeks, were used and divided into four groups. The Sham and OVX groups did not undergo treadmill exercise, while the Sham + EX and OVX + EX groups received a 8-week treadmill exercise. Post-training, bone marrow and fresh femur samples were collected for further analysis. Molecular biology analysis, histomorphology analysis, and micro-CT analysis were conducted on these samples. Moreover, primary osteoblasts were cultured under osteogenic conditions and divided into GM group and CTS group. The cells in the CTS group underwent a sinusoidal stretching regimen for either 3 or 7 days. The expression of early osteoblast markers (Runx2, OPN, and ALP) was measured to assess differentiation. The study findings revealed that mechanical stress has a regulatory impact on osteoblast differentiation. The expression of miR-187-3p was observed to decrease, facilitating osteogenic differentiation, while the expression of CNR2 increased significantly. These observations suggest that mechanical stress, miR-187-3p, and CNR2 play crucial roles in regulating osteogenic differentiation. Both in vivo and in vitro experiments have confirmed that mechanical stress downregulates miR-187-3p and upregulates CNR2, which leads to the restoration of distal femoral bone mass and enhancement of osteoblast differentiation. Therefore, mechanical stress promotes osteoblasts, resulting in improved osteoporosis through the miR-187-3p/CNR2 signaling pathway. These findings have broad prospect and provide molecular biology guidance for the basic research and clinical application of exercise in the prevention and treatment of PMOP.

Clinical Outcomes for Arthroscopic Anterior Talofibular Ligament Repair After Suture Anchor Insertion Through the Anterolateral Portal vs the Lateral Accessory Portal.

BACKGROUND: Two types of suture anchor insertion pathways (anterolateral portal vs lateral accessory portal) are used in arthroscopic anterior talofibular ligament (ATFL) repair. However, it is not clear which one is the better choice. This study aims to compare the clinical outcomes of these 2 suture anchor insertion pathways when performing arthroscopic ATFL lasso-loop repair for the treatment of chronic lateral ankle instability (CLAI). METHODS: From 2019 to 2021, patients with CLAI who underwent arthroscopic ATFL lasso-loop repair were retrospectively reviewed and divided into the anterolateral portal (ALP) group and the lateral accessory portal (LAP) group. A 1:1 propensity score matching was used to control confounding factors based on age, sex, body mass index, follow-up duration, preoperative visual analog scale (VAS) score, and Tegner score (ALP group, n = 26; LAP group, n = 26). Karlsson score, VAS score, Tegner score, operation time, anterior drawer test results, patient symptoms, and magnetic resonance (MR) evaluation of ATFL quality were used to describe the outcomes. RESULTS: The patient characteristics and follow-up durations were similar between the 2 groups. After a mean follow-up duration of 28.8 ± 2.3 months, the ALP group had significantly better Karlsson score, VAS score, and Tegner score improvement than the LAP group, with fewer symptoms. Seven patients in the LAP group still had a feeling of ankle instability, and 3 of them exhibited ankle laxity. CONCLUSION: In this study, we found that inserting the suture anchor through the anterolateral portal was associated with better outcomes compared to that through the lateral accessory portal when performing arthroscopic ATFL lasso-loop repair for CLAI patients. The improvement was greater for pain relief and function and was associated with a lower frequency of subjective ankle instability.

Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3.

Extracellular matrix (ECM) stiffening is a typical characteristic of cartilage aging, which is a quintessential feature of knee osteoarthritis (KOA). However, little is known about how ECM stiffening affects chondrocytes and other molecules downstream. This study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane (PDMS) substrates. It demonstrated that epigenetic Parkin regulation by histone deacetylase 3 (HDAC3) represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte physiology. We found that ECM stiffening accelerated cultured chondrocyte senescence in vitro, while the stiffness ECM downregulated HDAC3, prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis (OA) in mice. Contrarily, intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in mice. The findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals, promoted the Parkin acetylation and hyperactivated mitophagy, and damaged chondrocyte health. These results may provide new insights into chondrocyte regulation by the mechanical properties of ECM, suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.

Comparison of Arthroscopic Microfracture for Osteochondral Lesions of the Talus With and Without Small and Shallow Subchondral Cysts.

BACKGROUND: Whether arthroscopic microfracture is effective in treating cystic osteochondral lesions of the talus (OLTs) remains controversial. In this study, outcome parameters in patients with small and shallow subchondral cysts are compared to patients without cysts with the hypothesis that equivalent outcomes may be found after primary microfracture treatment. METHODS: From 2018 to 2021, all 50 OLTs treated with arthroscopic microfracture in the authors' hospital were retrospectively reviewed for eligibility. Single unilateral symptomatic lesions were included and divided into the cyst and noncyst groups, whereas kissing lesions and arthritic lesions were excluded. Numeric rating scale (NRS) scores, American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores, Tegner activity level scores, Foot and Ankle Ability Measure (FAAM) scores, and magnetic resonance (MR) imaging results were used to describe outcomes. RESULTS: A total of 35 patients were included, 16 in the cyst group and 19 in the noncyst group. The patient characteristics were similar between the 2 groups (P > .05). In the cyst group the average cysts depth was 5.0 ± 1.3 mm. After a mean follow-up duration of 36.2 ± 10.2 months, no significant differences were found between the 2 groups in NRS, AOFAS, FAAM, or Tegner score improvement (P > .05). Three patients (19%) in the cyst group had no NRS score improvement. CONCLUSION: OLTs with small and shallow subchondral cysts can be treated with arthroscopic microfracture and achieve similar outcomes as noncystic lesions. A few cystic lesions may not respond to microfracture treatment. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Aligned cryogel fibers incorporated 3D printed scaffold effectively facilitates bone regeneration by enhancing cell recruitment and function.

Reconstructing extensive cranial defects represents a persistent clinical challenge. Here, we reported a hybrid three-dimensional (3D) printed scaffold with modification of QK peptide and KP peptide for effectively promoting endogenous cranial bone regeneration. The hybrid 3D printed scaffold consists of vertically aligned cryogel fibers that guide and promote cell penetration into the defect area in the early stages of bone repair. Then, the conjugated QK peptide and KP peptide further regulate the function of the recruited cells to promote vascularization and osteogenic differentiation in the defect area. The regenerated bone volume and surface coverage of the dual peptide-modified hybrid scaffold were significantly higher than the positive control group. In addition, the dual peptide-modified hybrid scaffold demonstrated sustained enhancement of bone regeneration and avoidance of bone resorption compared to the collagen sponge group. We expect that the design of dual peptide-modified hybrid scaffold will provide a promising strategy for bone regeneration.

Autologous Costal Chondral/Osteochondral Transplantation and Costa-Derived Chondrocyte Implantation for Articular Cartilage Repair: Basic Science and Clinical Applications.

There has been increasing application of autologous costal chondral/osteochondral transplantation (ACCT/ACOT) and costa-derived chondrocyte implantation (ACCI) for articular cartilage repair over the past three decades. This review presents the major evidence on the properties of costal cartilage and bone and their qualifications as grafts for articular cartilage repair, the major clinical applications, and the risks and strategies for costal chondral/osteochondral graft(s) harvest. First, costal cartilage has many specific properties that help restore the articular surface. Costa, which can provide abundant cartilage and cylindrical corticocancellous bone, preserves permanent chondrocyte and is the largest source of hyaline cartilage. Second, in the past three decades, autologous costal cartilage-derived grafts, including cartilage, osteochondral graft(s), and chondrocyte, have expanded their indications in trauma and orthopaedic therapy from small to large joints, from the upper to lower limbs, and from non-weight-bearing to weight-bearing joints. Third, the rate of donor-site complications of ACCT or ACOT is low, acceptable, and controllable, and some skills and accumulated experience can help reduce the risks of ACCT and ACOT. Costal cartilage-derived autografting is a promising technique and could be an ideal option for articular chondral lesions with or without subchondral cysts. More high-quality clinical studies are urgently needed to help us further understand the clinical value of such technologies.

Hierarchically Assembled Nanofiber Scaffold Guides Long Bone Regeneration by Promoting Osteogenic/Chondrogenic Differentiation of Endogenous Mesenchymal Stem Cells.

Critical-sized segmental long bone defects represent a challenging clinical dilemma in the management of battlefield and trauma-related injuries. The residual bone marrow cavity of damaged long bones contains many bone marrow mesenchymal stem cells (BMSCs), which provide a substantial source of cells for bone repair. Thus, a three-dimensional (3D) vertically aligned nanofiber scaffold (VAS) is developed with long channels and large pore size. The pore of VAS toward the bone marrow cavity after transplantation, enables the scaffolds to recruit BMSCs from the bone marrow cavity to the defect area. In vivo, it is found that VAS can significantly shorten gap distance and promote new bone formation compared to the control and collagen groups after 4 and 8 weeks of implantation. The single-cell sequencing results discovered that the 3D nanotopography of VAS can promote BMSCs differentiation to chondrocytes and osteoblasts, and up-regulate related gene expression, resulting in enhancing the activities of bone regeneration, endochondral ossification, bone trabecula formation, bone mineralization, maturation, and remodeling. The Alcian blue and bone morphogenetic protein 2 (BMP-2) immunohistochemical staining verified significant cartilage formation and bone formation in the VAS group, corresponding to the single-cell sequencing results. The study can inspire the design of next-generation scaffolds for effective long-bone regeneration is expected by the authors.

Preoperative temporary fixation for fractures around the ankle using a simple extensible external fixator significantly improves patient comfort.

BACKGROUND: The authors developed a simple extensible external fixator, which has the advantages of easy application and inexpensiveness. The present study aimed to make a comparison between this external fixator and calcaneal traction in preoperative temporary fixation for malaligned ankle fractures and pilon fractures. METHODS: From May 2020 to February 2022, patients with malaligned ankle fractures or Rüedi-Allgöwer type 2 or 3 pilon fractures with obvious soft tissue swelling were retrospectively reviewed and divided into the calcaneal traction group and the external fixation group. The two groups of patients were matched 1:1 before making comparisons. RESULTS: A total of 38 patients were included. Higher General Comfort Questionnaire score and lower visual analog scale score were noticed in the external fixation group during hospitalization (p < 0.05), while the operation latency time, total cost, patient satisfaction, and functional outcomes one year after surgery were not significantly different between the two groups. No wound complications were observed. CONCLUSION: Preoperative temporary fixation for fractures around the ankle using this simple extensible external fixator significantly improves patient comfort when compared to calcaneal traction. LEVEL OF EVIDENCE: III, retrospective comparative study.

Autologous Costal Osteochondral Transplantation for Cystic Osteochondral Lesions of the Talus: Feasible and Effective.

OBJECTIVE: Osteochondral lesions of the talus (OLT) is a common and clinically challenging disease. The optimal management is still under debate. The purpose of this prospective study was to investigate the feasibility and clinical outcomes of autologous costal osteochondral transplantation (ACOT) for the treatment of cystic OLT. METHODS: From November 2021 to April 2023, five patients underwent autologous costal osteochondral transplantation (ACOT) for cystic OLT. The demographic data was described, including age, gender, lesion size and location. We prospectively evaluated their functional and imaging outcomes of the five patients for 12 months postoperatively, including numeric rating score (NRS) for pain when walking, Tegner score, American Orthopedic Foot & Ankle Society (AOFAS) score and Foot and Ankle Ability Measure (FAAM) score, and imaging results. A paired t-test was used for preoperative and postoperative comparison of the paired-design dataset. RESULTS: The average age was 36.6 ± 11.1 years. The average diameter of chondral lesions was 14.95 ± 2.71 mm, the average diameter of subchondral cysts was 10.66 ± 1.84 mm, and their average depth was 10.40 ± 1.86 mm. At 12 months postoperatively, the clinical function indexes improved significantly, including NRS (from 5.2 ± 2.3 to 0), Tegner score (from 3.2 ± 0.4 to 5.8 ± 0.4), AOFAS score (from 72.8 ± 10.0 to 98.2 ± 4.0), and FAAM score (FAAM/ADL from 61.2 ± 24.7 to 99.3 ± 1.6; FAAM/Sports from 32.5 ± 13.73 to 96.3 ± 8.4). Their magnetic resonance observation of cartilage repair tissue (MOCART) scores reached 78.0 ± 7.6 points. ICRS scores of three patients were nearly normal (10 or 11 points). The biopsy of the surviving grafts showed plenty of hyaline cartilage matrix and scattered chondrocytes histologically. No major severe complications were reported during the 12 months follow-up. CONCLUSION: ACOT could significantly relieve the symptoms of patients with OLT and improve their clinical function at short-term follow-up. ACOT might be a feasible and useful method for repairing OLT with subchondral cysts.

The Reliability and Accuracy of the Medial Malleolar Fracture Classification Based on 3D CT Reconstruction.

OBJECTIVE: There is a new medial malleolar fracture classification based on 3D CT reconstruction. However, there is no study assessing the reliability and accuracy of the new classification system and comparison between the new and the classic classification. This study aimed to compare the reliability and accuracy of the medial malleolar fracture classification based on 3D CT reconstruction and the Herscovici classification system. METHODS: We retrospectively analyzed the consecutive ankle fractures in our hospital from January 2013 to September 2020. Five inexperienced and five experienced orthopedic surgeons were included as observers to assess 68 cases with medial malleolar fractures. Ten evaluators classified the cases according to the two classification systems. The reference results of each case were made by the consensus of three senior trauma surgeons. The interobserver reliability, intraobserver reliability, and accuracy were evaluated at an interval of 6 weeks using Fleiss's kappa (κ) statistics. RESULTS: We found substantial interobserver and intraobserver reliability and 81.4% accuracy for the new classification, which was statistically superior to the Herscovici classification (P < 0.05). The reliability and accuracy of both classifications were similar in inexperienced and experienced groups, except for type III in the new classification. The interobserver reliability of type II was the best (P < 0.05), and the intraobserver reliability of IVc ranked the worst (P < 0.05) in the new classification. CONCLUSION: The reliability and accuracy of the new classification are superior to the Herscovici classification. Clinical experiences will not affect the assessment of both classification systems in most instances.

Leucine Repeat Rich Kinase 1 Controls Osteoclast Activity by Managing Lysosomal Trafficking and Secretion.

We previously demonstrated that mice with targeted deletion of the leucine repeat rich kinase 1 (Lrrk1) gene were osteopetrotic due to the failure of osteoclasts to resorb bone. To determine how LRRK1 regulates osteoclast activity, we examined the intracellular and extracellular acidification with an acidotropic probe, acridine orange, in live osteoclasts on bone slices. We examined lysosome distribution in osteoclasts by localization of LAMP-2, cathepsin K, and v-ATPase by immunofluorescent staining with specific antibodies. We found that both vertical and horizontal cross-sectional images of the wild-type (WT) osteoclasts showed orange-staining of the intracellular acidic vacuoles/lysosomes dispersed to the ruffled border. By contrast, the LRRK1 deficient osteoclasts exhibited fluorescent orange staining in the cytoplasm away from the extracellular lacunae because of an altered distribution of the acidic vacuoles/lysosomes. In addition, WT osteoclasts displayed a peripheral distribution of LAMP-2 positive lysosomes with a typical actin ring. The clustered F-actin constitutes a peripheral sealing zone and a ruffled border which was stretched out into a resorption pit. The LAMP-2 positive lysosomes were also distributed to the sealing zone, and the cell was associated with a resorption pit. By contrast, LRRK1-deficient osteoclasts showed diffused F-actin throughout the cytoplasm. The sealing zone was weak and not associated with a resorption pit. LAMP-2 positive lysosomes were also diffuse in the cytoplasm and were not distributed to the ruffled border. Although the LRRK1-deficient osteoclast expressed normal levels of cathepsin K and v-ATPase, the lysosomal-associated cathepsin K and v-ATPase were not accumulated at the ruffled border in Lrrk1 KO osteoclasts. Our data indicate that LRRK1 controls osteoclast activity by regulating lysosomal distribution, acid secretion, and protease exocytosis.

Recent Progress in the Classification and Operation of Sacral Fractures.

Most sacral fractures are caused by high-energy, violent injuries, often accompanied by lumbosacral plexus injuries, which can cause instability of the posterior pelvic ring or lumbosacral junction in severe cases. Currently, the most commonly used clinical classification methods are Denis classification, Tile classification, Isler classification, and Denis II classification. In recent years, lumbosacral vertebral injury classification and injury degree scoring systems have often been applied clinically as the choice of treatment methods. At present, the internal fixation and implantation methods of sacral fracture are developing in the direction of positive, efficient, safe, and minimally invasive. But different fixation methods have their own indications, which should be strictly followed. This article reviews the classification of sacral fractures and the latest progress in surgical treatment.

Autologous Osteoperiosteal Transplantation for the Treatment of Large Cystic Talar Osteochondral Lesions.

OBJECTIVE: The effectiveness of autologous osteoperiosteal transplantation (AOPT) for the treatment of large cystic talar osteochondral lesions (OCLs) should be further evaluated, and the postoperative cartilage coverage is questionable. The purpose of this retrospective observational study was to investigate the clinical outcomes of AOPT for the treatment of large cystic talar OCLs and to report second-look arthroscopic results. METHODS: From June 1, 2017, to June 1, 2021, all talar OCLs at our center were reviewed. Painful cystic lesions treated with AOPT were included in the study. The American Orthopaedic Foot and Ankle Society (AOFAS; 0-100 points) ankle-hindfoot score, Foot Function Index (FFI; 0-100 points), visual analog scale (VAS; 0-10 points) score, and Tegner score (0-10 points) were used to describe pain and functional outcomes. Furthermore, complications, patient-reported satisfaction degrees, imaging results (including computed tomography and magnetic resonance), and second-look arthroscopic evaluation data were also collected for analysis. RESULTS: A total of 29 cases were eligible for the study, and 26 responded to the latest follow-up request, with a mean follow-up duration of 30.2 (range, 12-57) months. The AOFAS score improved from 69.2 ± 10.9 preoperatively to 80.9 ± 10.0 at the latest follow-up (p = 0.000). The FFI score improved from 30.4 ± 18.4 preoperatively to 16.3 ± 14.0 at the latest follow-up (p = 0.000). The VAS pain score improved from 4.0 ± 2.1 preoperatively to 2.5 ± 2.0 at the latest follow-up (p = 0.001). No donor site morbidity was found. The mean postoperative MOCART score was 57.7 ± 9.5. Second-look arthroscopy showed a fibrillated cartilage-like surface at the lesion site in most cases, while two cases exhibited a nearly normal surface. CONCLUSION: The transplantation of osteoperiosteal cylinder autografts taken from the iliac crest for the treatment of large cystic talar OCLs yielded acceptable clinical results. Good integration of the bony part was observed, but cartilage regeneration remained uncertain.

Clinical Outcomes of Fusion in Type II Accessory Naviculars With or Without Asymptomatic Flatfeet.

BACKGROUND: Few studies have reported the clinical outcomes of fusion surgeries for type II accessory naviculars. Whether the combination of accessory naviculars and asymptomatic flatfoot will result in worse outcomes in accessory navicular surgeries remains to be elucidated. Our study aims to report the clinical outcomes of fusion for type II accessory naviculars and make a subgroup comparison among accessory navicular patients with or without asymptomatic flatfeet. METHODS: From May 2017 to June 2021, all painful type II accessory naviculars with or without asymptomatic flatfeet in our inpatient center were reviewed, and those who only underwent fusion surgeries were included in the retrospective study. Visual analog scale (VAS) scores, American Orthopaedic Foot & Ankle Society (AOFAS) midfoot scores, Tegner activity level scores, complications, patient-reported satisfaction, and imaging results (Meary angle in the weightbearing lateral view, talo-first metatarsal angle and talonavicular coverage angle in the weightbearing anteroposterior view) were used to describe outcomes. RESULTS: Thirty-two eligible patients responded to the latest follow-up request and were included in this study. The mean follow-up duration was 37.1 ± 16.0 months. The average VAS pain score improved from 4.7 ± 1.8 preoperatively to 0.9 ± 1.2 at the latest follow-up (P<.001). The average AOFAS midfoot score improved from 67.1 ± 8.5 preoperatively to 90.2 ± 10.7 at the latest follow-up (P<.001). The preoperative and postoperative Tegner activity level scores were similar (3.3 ± 1.5 vs 3.5 ± 1.6, P=.136). The overall complication rate was 37.5%. The most common complication was nonunion (31.3%). The overall satisfaction rate was 90.6%. Similar outcomes were observed between the flatfoot and the nonflatfoot subgroups. CONCLUSION: Fusion for painful type II accessory naviculars resulted in good symptom relief, function improvement, and patient satisfaction at midterm follow-up, but the nonunion rate was relatively high. Fusion for painful type II accessory naviculars with or without asymptomatic mild to moderate flatfoot brought about similar clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

The lasso-loop technique is equivalent to the simple suture technique in arthroscopic anterior talofibular ligament repair.

PURPOSE: To compare the clinical outcomes of the lasso-loop and simple suture techniques in arthroscopic anterior talofibular ligament (ATFL) repair for the treatment of chronic lateral ankle instability (CLAI). METHODS: From 2018 to 2020, patients with CLAI who underwent arthroscopic ATFL repair using the lasso-loop or simple suture technique were matched 1:1 (arthroscopic lasso-loop [AL] group, n = 29; simple arthroscopic suture [AS] group, n = 29) based on age, sex, affected side, body mass index, and follow-up duration using propensity score matching and retrospectively evaluated. Karlsson score, visual analogue scale (VAS) score, Tegner score, anterior drawer test (ADT) results, complications, patient-reported satisfaction, and magnetic resonance (MR) re-evaluation findings of ATFL quality were used to describe the outcomes. RESULTS: The patient characteristics or follow-up durations did not significantly differ between the two groups. The Karlsson score, VAS score, and Tegner score improved significantly in both groups after a mean follow-up duration of 29.6 ± 2.8 months. The postoperative clinical scores, ADT results, satisfaction rates, complication rates and MR re-evaluation findings were not significantly different between the two groups at the latest follow-up. CONCLUSION: The lasso-loop technique was equivalent to the simple suture technique in arthroscopic ATFL repair for the treatment of CLAI after a minimum follow-up of 2 years, suggesting that the simple suture technique is sufficient for arthroscopic ATFL repair in most patients without the need to add a lasso loop. LEVEL OF EVIDENCE: Level III.

Design, synthesis, and bioevaluation of imidazo [1,2-a] pyrazine derivatives as tubulin polymerization inhibitors with potent anticancer activities.

Through structural optimization and ring fusion strategy, we designed a series of novel imidazo[1,2-a]pyrazine derivatives as potential tubulin inhibitors. These compounds displayed potent anti-proliferative activities (micromolar to nanomolar) against a panel of cancer cell lines (including HepG-2, HCT-116, A549 and MDA-MB-231 cells). Among them, compound TB-25 exhibited the strongest inhibitory effects against HCT-116 cells with an IC50 of 23 nM. Mechanism studies revealed that TB-25 could effectively inhibit tubulin polymerization in vitro, and destroy the dynamic equilibrium of microtubules in HCT-116 cells. In addition, TB-25 dose-dependently induced G2/M phase cell cycle arrest and apoptosis in HCT-116 cells. Furthermore, TB-25 suppressed HCT-116 cell migration in a concentration-dependent manner. Finally, molecular docking showed that TB-25 fitted well in the colchicine binding site of tubulin and overlapped nicely with CA-4. Collectively, these results suggest that TB-25 represents a promising tubulin inhibitor deserving further investigation.

Circ0038632 modulates MiR-186/DNMT3A axis to promote proliferation and metastasis in osteosarcoma.

Osteosarcoma is a highly malignant solid tumor with poor prognosis, early metastasis, and rapid progression and has a high mortality rate, in which better therapeutic strategies are needed. Circ0038632, also known as circPLK1, is a tumor promotor in multiple cancers. However, its biological functions and molecular regulatory mechanisms in osteosarcoma remain unclear. To ascertain the function of circ0038632 in osteosarcoma, we checked its expression in cells and in tissues and tested its abilities of proliferation and migration. Expression experiment manifested that circ0038632 showed an enhanced expression in osteosarcoma. Functional studies revealed that circ0038632 inhibition reduced cell proliferation and metastasis abilities of osteosarcoma. Mechanism studies revealed that circ0038632 sponged miR-186 to upregulate the expression of DNA methyltransferase 3A (DNMT3A) to promote osteosarcoma progression. The circ0038632/miR-186/DNMT3A axis was involved in osteosarcoma progression. The results elucidated the potential application of circ0038632 as a novel diagnostic biomarker for progressive process of osteosarcoma.

Identification and validation of MicroRNA-mRNA Networks in Dorsal Root Ganglia after Peripheral Nerve Injury.

Changes in DRG after nerve injury involve neuronal damage, apoptosis, pain transmission, and activation of regenerative programs. It is unclear which genes and microRNAs may play a major role in this process. Therefore, this study performed a meta-analysis of previously published gene expression data to reveal the potential microRNA-mRNA network in dorsal root ganglia (DRG) after peripheral nerve injury. We searched 5 mRNA and 3 microRNA expression data sets, obtained 447 differentially expressed genes (DEGs) and 5 differentially expressed miRNAs, determined the biological pathways enriched by these DEGs, and further predicted new microRNA-mRNA interactions, such as miR-21/Hmg20a, miR-221/Ube2ql1, miR-30c-1/Rhoq, miR-500/Sema3c, and miR-551b/Cdc42se2. We verified these hub mRNA and miRNA in rats by qRT-PCR and found the results were consistent with the bioinformatics analysis. And we predicted transcription factors associated with these genes (gTFs) and TFs associated with these microRNAs (mTFs) and constructed the mTF-miRNA-gene-gTF regulatory network to further explore the molecular mechanism in DRG. Finally, we compared the DRG transcriptome after PNI to that of chronic constriction injury (CCI), and found that PNI caused greater damage to DRG compared to CCI. At the same time, the related mechanisms of pain caused by the two pathophysiological process may be different.