Bioprinting-Enabled Biomaterials: A Cutting-Edge Strategy for Future Osteoarthritis Therapy.

Bioprinting is an advanced technology that allows for the precise placement of cells and biomaterials in a controlled manner, making significant contributions in regenerative medicine. Notably, bioprinting-enabled biomaterials have found extensive application as drug delivery systems (DDS) in the treatment of osteoarthritis (OA). Despite the widespread utilization of these biomaterials, there has been limited comprehensive research summarizing the recent advances in this area. Therefore, this review aims to explore the noteworthy developments and challenges associated with utilizing bioprinting-enabled biomaterials as effective DDS for the treatment of OA. To begin, we provide an overview of the complex pathophysiology of OA, highlighting the shortcomings of current treatment modalities. Following this, we conduct a detailed examination of various bioprinting technologies and discuss the wide range of biomaterials employed in DDS applications for OA therapy. Finally, by placing emphasis on their transformative potential, we discuss the incorporation of crucial cellular components such as chondrocytes and mesenchymal stem cells into bioprinted constructs, which play a pivotal role in promoting tissue regeneration and repair.

[Effectiveness analysis of percutaneous parallel screw fixation via posterolateral "safe zone" for Hawkins type â - â ¢ talar neck fractures].

Objective: To explore the effectiveness of the percutaneous parallel screw fixation via the posterolateral "safe zone" for Hawkins type Ⅰ-Ⅲ talar neck fractures. Methods: A retrospective analysis was conducted on the clinical data from 35 patients who met the selection criteria of talar neck fractures between January 2019 and June 2021. According to the surgical method, they were divided into a study group (14 cases, using percutaneous posterolateral "safe zone" parallel screw fixation) and a control group (21 cases, using traditional open reduction and anterior cross screw internal fixation). There was no significant difference in gender, age, affected side, Hawkins classification, and time from injury to operation between the two groups ( P>0.05). The operation time, bone healing time, complications, and Hawkins sign were recorded, and the improvement of pain and ankle-foot function were evaluated by visual analogue scale (VAS) score and American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score at last follow-up. The overall quality of life was assessed by the short form of 12-item health survey (SF-12), which was divided into physical and psychological scores; and the satisfaction of patients was evaluated by the 5-point Likert scale. Results: The operation time in the study group was significantly shorter than that in the control group ( P<0.05). All patients werefollowed up 13-35 months, with an average of 20.6 months; there was no significant difference in the follow-up time between the two groups ( P>0.05). The time of bone healing in the study group was shorter than that in the control group, and the positive rate of Hawkins sign (83.33%) was higher than that in the control group (33.33%), and the differences were significant ( P<0.05). In the control group, there were 2 cases of incision delayed healing, 7 cases of avascular necrosis of bone, 3 cases of joint degeneration, 1 case of bone nonunion, and 3 cases of internal fixation irritation; while in the study group, there were only 2 cases of joint degeneration, and there was a significant difference in the incidence of complications between the two groups ( P<0.05). At last follow-up, there was no significant difference in VAS score between the two groups ( P>0.05), but the SF-12 physical and psychological scores, AOFAS ankle and hindfoot scores, and patients' satisfaction in the study group were significantly better than those in the control group ( P<0.05). Conclusion: The treatment of Hawkins type Ⅰ-Ⅲ talar neck fractures with percutaneous parallel screw fixation via the posterolateral "safe zone" can achieve better effectiveness than traditional open surgery, with the advantages of less trauma, fewer complications, faster recovery, and higher patient satisfaction.

[Progress in clinical diagnosis and treatment of diabetic Charcot neuroarthropathy of foot and ankle].

Objective: To summarize the progress of clinical diagnosis and treatment of diabetic Charcot neuroarthropathy (CNO) of foot and ankle to provide reference for clinical treatment. Methods: The research literature on diabetic CNO of foot and ankle at home and abroad was widely reviewed, and the stages and classification criteria of CNO were summarized, and the treatment methods at different stages of the disease course were summarized. Results: CNO is a rapidly destructive disease of bone and joint caused by peripheral neuropathy, which leads to the formation of local deformities and stress ulcers due to bone and joint destruction and protective sensory loss, which eventually leads to disability and even life-threatening. At present, the modified Eichenholtz stage is a commonly used staging criteria for CNO of foot and ankle, which is divided into 4 stages by clinical and imaging manifestations. The classification mainly adopts the modified Brodsky classification, which is divided into 6 types according to the anatomical structure. The treatment of diabetic CNO of foot and ankle needs to be considered in combination with disease stage, blood glucose, comorbidities, local soft tissue conditions, degree of bone and joint destruction, and whether ulcers and infections are present. Conservative treatment is mainly used in the active phase and surgery in the stable phase. Conclusion: The formulation of individualized and stepped treatment regimens can help improve the effectiveness of diabetic CNO of foot and ankle. However, there is still a lack of definitive clinical evidence to guide the treatment of active and stable phases, and further research is needed.

Therapeutics of osteoarthritis and pharmacological mechanisms: A focus on RANK/RANKL signaling.

Osteoarthritis (OA) is a chronic degenerative disease afflicting millions globally. Despite the development of numerous pharmacological treatments for OA, a substantial unmet need for effective therapies persists. The RANK/RANKL signaling pathway has emerged as a promising therapeutic target for OA, owing to its pivotal role in regulating osteoclast differentiation and activity. In this comprehensive review, we aim to elucidate the relevant mechanisms of OA mediated by RANK/RANKL signaling, including bone remodeling, inflammation, cartilage degradation, osteophyte formation, and pain sensitization. Furthermore, we discuss and summarize the cutting-edge strategies targeting RANK/RANKL signaling for OA therapy, encompassing approaches such as gene-based interventions and biomaterials-aided pharmacotherapy. In addition, we highlight the prevailing challenges associated with pharmacological OA treatments and explore potential future directions, approached through a clinical-translational lens.

[Effectiveness and risk factors of supramalleolar osteotomy in treatment of varus-type ankle arthritis].

Objective: To assess the effectiveness of supramalleolar osteotomy (SMOT) as a therapeutic intervention for varus-type ankle arthritis, while also examining the associated risk factors that may contribute to treatment failure. Methods: The clinical data of 82 patients (89 feet) diagnosed with varus-type ankle arthritis and treated with SMOT between January 2016 and December 2020 were retrospectively analyzed. The patient cohort consisted of 34 males with 38 feet and 48 females with 51 feet, with the mean age of 54.3 years (range, 43-72 years). The average body mass index was 24.43 kg/m 2 (range, 20.43-30.15 kg/m 2). The preoperative tibial anterior surface angle (TAS) ranged from 77.6° to 88.4°, with a mean of 84.4°. The modified Takakura stage was used to classify the severity of the condition, with 9 feet in stage Ⅱ, 41 feet in stage Ⅲa, and 39 feet in stage Ⅲb. Clinical functional assessment was conducted using the Maryland sore, visual analogue scale (VAS) score, and psychological and physical scores in Health Survey 12-item Short From (SF-12). Radiology evaluations include TAS, talar tilt (TT), tibiocrural angle (TC), tibial medial malleolars (TMM), tibiocrural distance (TCD), tibial lateral surface angle (TLS), and hindfoot alignment angle (HAA). The results of clinical failure, functional failure, and radiology failure were statistically analyzed, and the related risk factors were analyzed. Results: The operation time ranged from 45 to 88 minutes, with an average of 62.2 minutes. No complication such as fractures and neurovascular injuries was found during operation. There were 7 feet of poor healing of the medial incision; 9 pin tract infections occurred in 6 feet using external fixator; there were 20 cases of allograft and 3 cases of autograft with radiographic bone resorption. Except for 1 foot of severe infection treated with bone cement, the remaining 88 feet were primary healing, and the healing area was more than 80%. All patients were followed up 24-82 months, with an average of 50.2 months. Maryland score, VAS score, SF-12 psychological and physiological scores, and TAS, TC, TLS, TCD, TT, TMM, HAA, and Takakura stage were significantly improved at last follow-up ( P<0.05). Postoperative clinical failure occurred in 13 feet, functional failure in 15 feet, and radiology failure in 23 feet. Univariate analysis showed that obesity, TT>10°, and Takakura stage Ⅲb were risk factors for clinical failure, HAA≥15° and Takakura stage Ⅲb were risk factors for functional failure, and TT>10° was risk factor for radiographic failure ( P<0.05). Further logistic regression analysis showed that TT>10°, HAA≥15°, and TT>10° were risk factors for clinical failure, functional failure, and radiographic failure, respectively ( P<0.05). Conclusion: SMOT is effective in the mid- and long-term in the treatment of varus-type ankle arthritis, but it should be used with caution in patients with obesity, severe hindfoot varus, severe talus tilt, and preoperative Takakura stage Ⅲb.

Changes in the subtalar joint alignment after supramalleolar osteotomy for varus ankle arthritis.

BACKGROUND: The subtalar joint may compensate for tibio-talar deformity, but what would happen to the joint after the deformity was corrected is not well known. Supramalleolar osteotomy (SMOT) is an effective procedure for the treatment of varus deformity of ankle arthritis. The objective of this study was to investigate the subtalar joint alignment pre and postoperatively following SMOT, and the factors which influenced the alignment of the subtalar joint. METHODS: Thirty-one patients with varus ankle arthritis (Takakura stage 2, 3a and 3b) who were treated using SMOT were retrospectively reviewed. The subtalar and ankle joint alignment was measured on weightbearing radiograph and weightbearing computerized tomography (WBCT). RESULTS: The foot and ankle offset (FAO), tibial articular surface angle (TAS), tibio-talar surface angle (TTS), and subtalar vertical angle (SVA) were significantly corrected (P＜0.05). The subtalar inclination angle (SIA) decreased in 19 patients and increased in the other 12 cases after the SMOT (P＜0.001). The shift of subtalar joint (ΔSIA) showed an inverse correlation with the preoperative FAO (P＜0.001, r = -0.621). CONCLUSIONS: The shift of subtalar joint after SMOT could maintain the neutral position of the hindfoot and showed a negative correlation with the preoperative FAO. The ΔSIA was greater in the severer preoperative hindfoot deformity. LEVEL OF EVIDENCE: Level IV, case series.

Cartilage Damage Pathological Characteristics of Diabetic Neuropathic Osteoarthropathy.

Background: Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients. Methods: The articular cartilages of eight patients with DNOAP and eight normal controls were included. Masson staining and safranine O/fixed green staining (S-O) were used to observe the histopathological characteristics of cartilage. The ultrastructure and morphology of chondrocytes were detected by electron microscopy and toluidine blue staining. Chondrocytes were isolated from DNOAP group and control group. The expression of receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and Aggrecan protein was evaluated by western blot. Reactive oxygen species (ROS) levels were measured using a 2',7'-dichlorofluorescin diacetate (DCFH-DA) probe. The percentage of apoptotic cells was determined by flow cytometry (FCM). The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG. Results: Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia, and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swellings were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1 ± 2.3 vs. 11.9 ± 0.7; P < 0.05). The expression of RANKL, TNF-α, IL-1ß, and IL-6 protein in DNOAP group was higher than that in normal control group, whereas OPG and Aggrecan protein were lower than that in normal control group (both P < 0.05). FCM showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group (P < 0.05). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15 mM. Conclusions: DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL and OPG) and inflammatory cytokines (IL-1ß, IL-6, and TNF-α) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15 mM made the RANKL/OPG ratio change rapidly.

[Calcaneal V-shaped osteotomy combined with subtalar arthrodesis for Stephens â ¡ and â ¢ calcaneal fractures malunion].

Objective: To investigate the effectiveness of calcaneal V-shaped osteotomy combined with subtalar arthrodesis in the treatment of Stephens Ⅱand Ⅲ calcaneal fracture malunion. Methods: The clinical data of 24 patients with severe calcaneal fracture malunion treated by calcaneal V-shaped osteotomy combined with subtalar arthrodesis between January 2017 and December 2021 were retrospectively analyzed. There were 20 males and 4 females with an average age of 42.8 years (range, 33-60 years). Conservative treatment of calcaneal fracture failed in 19 cases and operation failed in 5 cases. Stephens classification of calcaneal fracture malunion was type Ⅱ in 14 cases, and type Ⅲ in 10 cases. Preoperative Böhler angle of calcaneus was 4.0°-13.5° (mean, 8.6°), Gissane angle was 100°-152° (mean, 119.3°). The time from injury to operation was 6-14 months (mean, 9.7 months). American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score and visual analogue scale (VAS) score were used to evaluate the effectiveness before operation and at last follow-up. Bone healing was observed and the healing time was recorded. The talocalcaneal height, talus inclination angle, Pitch angle, calcaneal width, and hindfoot alignment angle were measured. Results: Necrosis of the cuticle edge of the incision occurred in 3 cases, which were cured by dressing change and oral administration of antibiotic therapy. The other incisions healed by first intention. All the 24 patients were followed up 12-23 months, with an average of 17.1 months. The foot shape of the patients recovered well, the shoes were restored to the size before injury, and there was no anterior ankle impingement. Bone union was achieved in all patients, and the healing time ranged from 12 to 18 weeks, with an average of 14.1 weeks. At last follow-up, no adjacent joint degeneration occurred in all patients; 5 patients had mild foot pain during walking, which had no significant impact on daily life and work; no patient needed revision surgery. The AOFAS ankle and hindfoot score was significantly higher than that before operation ( P<0.001), the results were excellent in 16 cases, good in 4 cases, and poor in 4 cases, and the excellent and good rate was 83.3%. The VAS score, talocalcaneal height, talus inclination angle, Pitch angle, calcaneal width, and hindfoot alignment angle were significantly improved after operation ( P<0.001). Conclusion: Calcaneal V-shaped osteotomy combined with subtalar arthrodesis can effectively relieve hindfoot pain, correct talocalcaneal height, restore talus inclination angle, and reduce the risk of nonunion after subtalar arthrodesis.

Supramalleolar Osteotomy vs Arthrodesis for the Treatment of Takakura 3B Ankle Osteoarthritis.

BACKGROUND: To compare the clinical/functional outcomes of supramalleolar osteotomy (SMOT) and ankle arthrodesis (AA) for the treatment of modified Takakura stage 3B ankle osteoarthritis. METHODS: Outcomes of 28 SMOT patients and 30 AA patients were reviewed at an average of 50 and 51 months, respectively. The baseline characteristics of the 2 groups were similar. The preoperative tibial articular surface angle and talar tilt angle in the SMOT group were 82.6 and 10 degrees and in the AA group, 83.9 and 9.1 degrees, respectively. The American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, visual analog scale (VAS) score, 12-item Short-Form Health Survey (SF-12) mental component summary (MCS) and physical component summary (PCS) scores, range of motion (ROM), radiologic parameters, and complications were compared. RESULTS: The AOFAS, VAS, and SF-12 MCS and PCS scores improved significantly postoperatively in both groups (P < .001). The VAS and SF-12 PCS scores indicate marginally better improvement in the AA group (P < .05). The patient satisfaction value (P = .028) and the possibility of repeated surgery value (P = .012) were also significantly higher in the AA group. The early (P = .905) and late (P = .181) complications did not significantly differ between the 2 groups. The reoperation rate was significantly higher in the SMOT group (P = .038). CONCLUSION: Both SMOT and AA showed improvements in function, pain, alignment, and quality of life after surgery. Patients in the AA group reported better pain relief, had a lower reoperation rate, and better hindfoot alignment during a short- to mid-term follow-up time. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

[Progress in diagnosis and treatment of fibular fracture in ankle fracture].

OBJECTIVE: To summarize the diagnosis and treatment of fibular fracture in ankle fracture. METHODS: Relevant literature at home and abroad in recent years was widely consulted, and various types of fractures were discussed and summarized according to Danis-Weber classification. RESULTS: Conservative treatment is not an ideal treatment for type A avulsion fracture. The operation method should be determined according to the position and size of bone mass. For simple type B fracture, both conservative treatment and surgical treatment can achieve good results. When the position of type C fracture is high and does not affect the stability of ankle joint, it can be treated conservatively, while when the position is low and affects the stability of ankle joint, it needs surgical treatment. CONCLUSION: First of all, whether the fibular fracture in the ankle fracture is stable or not should be determined. Whether it is treated surgically or not, the purpose is to restore the tibiofibular syndesmosis and restore the motor function of the ankle.

The RANK/RANKL/OPG system and tumor bone metastasis: Potential mechanisms and therapeutic strategies.

With the markedly increased diagnosis and incidence of cancer in the population, tumor bone metastasis has become a frequent event in tumor patients. Healthy bone integrity is maintained by a delicate balance between bone formation and bone resorption. Unfortunately, many tumors, such as prostate and breast, often metastasize to the bone, and the alterations to the bone homeostasis can particularly favor tumor homing and consequent osteolytic or osteoblastic lesions. Receptor activator of NF-κB ligand (RANKL), its receptor RANK, and osteoprotegerin (OPG) are involved in the regulation of the activation, differentiation, and survival of osteoclasts, which play critical roles in bone metastasis formation. High rates of osteoclastic bone resorption significantly increase fracture risk, cause severe bone pain, and contribute to homing tumor cells in bone and bone marrow. Consequently, suppression of the RANK/RANKL/OPG system and osteoclastic activity can not only ameliorate bone resorption but may also prevent tumor bone metastases. This review summarizes the important role of the RANK/RANKL/OPG system and osteoclasts in bone homeostasis and its effect on tumor bone metastasis and discusses therapeutic strategies based on RANKL inhibition.

Treatment of Early to Intermediate Stage Ankle Osteoarthritis With Nonosteotomy Approaches: Intermediate-Term Efficacy.

This study aimed to investigate the intermediate-term efficacy of nonosteotomy approaches in the treatment of early to intermediate stage ankle osteoarthritis (OA). Forty-two patients received treatment for early to intermediate stage ankle osteoarthritis with nonosteotomy approaches were reviewed. The surgical satisfaction was evaluated at 1 year after surgery and the last follow-up period; the American Orthopaedic Foot and Ankle Society (AOFAS) scale and Visual Analog Scale (VAS) were employed for the evaluation of function and pain, respectively, and the stage of ankle osteoarthritis was determined. At 1 year surgery and the last follow-up period, the surgical satisfaction was 37 (88.1%) and 35 (83.3%), respectively, and the favorable function was noted in 34 (80.9%) and 32 (76.2%), respectively. The AOFAS score significantly increased from 50.62 ± 10.81 (range 30-60) before surgery to 81.43 ± 12.00 (range 75-95) at 1 year after surgery (p < .0001) and 79.67 ± 10.34 (range 70-96) at the last follow-up period (p < .0001 vs before surgery; p = .107 vs 1 year). The VAS score reduced from 5.07 ± 1.57 (range 4-7) before surgery to 1.97 ± 1.41 (range 0-3) at 1 year (p < .0001) and 1.80 ± 1.15 (range 0-3) at the last follow-up period (p < .0001 vs before surgery; p = .265 vs 1 year). Moreover, the AOFAS score and VAS score in patients with ankle osteoarthritis at different stages were improved significantly after surgery (p < .0001). Intermediate-term follow-up period shows that nonosteotomy approaches are able to relieve pain and improve postoperative function in the treatment of early to intermediate stage ankle osteoarthritis; the improvement determined according to imaging examination is not completely consistent with that determined based on clinical function.

The first human induced pluripotent stem cell line of Kashin-Beck disease reveals involvement of heparan sulfate proteoglycan biosynthesis and PPAR pathway.

Kashin-Beck disease (KBD) is an endemic osteochondropathy. Due to a lack of suitable animal or cellular disease models, the research progress on KBD has been limited. Our goal was to establish the first disease-specific human induced pluripotent stem cell (hiPSC) cellular disease model of KBD, and to explore its etiology and pathogenesis exploiting transcriptome sequencing. HiPSCs were reprogrammed from dermal fibroblasts of two KBD and one healthy control donor via integration-free vectors. Subsequently, hiPSCs were differentiated into chondrocytes through three-week culture. Gene expression profiles in KBD, normal primary chondrocytes, and hiPSC-derived chondrocytes were defined by RNA sequencing. A Venn diagram was constructed to show the number of shared differentially expressed genes (DEGs) between KBD and normal. Gene oncology and Kyoto Encyclopedia of Genes and Genomes annotations were performed, and six DEGs were further validated in other individuals by RT-qPCR. KBD cellular disease models were successfully established by generation of hiPSC lines. Seventeen consistent and significant DEGs present in all compared groups (KBD and normal) were identified. RT-qPCR validation gave consistent results with the sequencing data. Glycosaminoglycan biosynthesis-heparan sulfate/heparin; PPAR signaling pathway; and cell adhesion molecules (CAMs) were identified to be significantly altered in KBD. Differentiated chondrocytes derived from KBD-origin hiPSCs provide the first cellular disease model for etiological studies of KBD. This study also provides new sights into the pathogenesis and etiology of KBD and is likely to inform the development of targeted therapeutics for its treatment.

Fibular osteotomy is helpful for talar reduction in the treatment of varus ankle osteoarthritis with supramalleolar osteotomy.

BACKGROUND: There have been debates on the necessity of fibular osteotomy (FO) in supramalleolar osteotomy (SMOT) for the treatment of varus ankle osteoarthritis. The purpose of the current study was to compare the clinical and radiological outcomes between SMOT with and without FO in the treatment of varus ankle osteoarthritis. METHODS: The SMOT group included 39 patients, and the SMOT with FO group included 24 patients. The basic information reached no significant difference between groups. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Ankle Osteoarthritis Scale (AOS), modified Takakura stage and range of motion (ROM) were used for the functional evaluation. The radiologic parameters were assessed at the last follow-up to compare the degree of talar reduction between the two groups. RESULTS: Both groups achieved significant improvements in AOFAS scores, modified Takakura stage, as well as AOS pain and functional scores (P < 0.001). The ROM of the ankle joint in the SMOT group was significantly decreased (P = 0.022). In both groups, all of the radiological parameters were significantly improved (P < 0.01). The tibiofibular clear space (TFCS) was significantly widened in the SMOT group (P < 0.001). No significant difference was found between the two groups according to the functional outcomes. However, the talar tilt angle (TT) and hindfoot alignment angle (HFA) in the SMOT with FO group were significantly smaller than those in the SMOT group (P < 0.05). The TFCS was significantly widened in the SMOT group (P = 0.001). The medial displacement of the talus (MDT) was better reduced in the SMOT with FO group (P = 0.006). CONCLUSION: SMOT is a promising procedure for functional improvement and malalignment correction in varus ankle osteoarthritis but reduces ankle range of motion. If SMOT is combined with FO, talar tilt and medial displacement will be better reduced.

Rosmarinic acid ameliorated cardiac dysfunction and mitochondrial injury in diabetic cardiomyopathy mice via activation of the SIRT1/PGC-1α pathway.

Mitochondrial injury plays an essential role in the pathogenesis of diabetic cardiomyopathy (DCM). Previous studies demonstrated that rosmarinic acid (RA) treatment prevented high glucose-induced mitochondrial injury in vitro. However, whether RA can ameliorate cardiac function by preventing mitochondrial injury in DCM is unknown. The SIRT1/PGC-1α pathway has emerged as an important regulator of metabolic control and other mitochondrial functions. The present study was undertaken to determine the effects of RA on mitochondrial and cardiac function in DCM as well as the involvement of the SIRT1/PGC-1α pathway. Our results revealed that RA improved cardiac systolic and diastolic function and prevented mitochondrial injury in DCM, as shown by the reduced blood glucose and lipid levels, increased mitochondrial membrane potential levels, improved adenosine triphosphate synthesis, and inhibited apoptosis (P < 0.05). Moreover, RA upregulated the expression of SIRT1 and PGC-1α in DCM mice and high glucose-treated H9c2 cardiomyocytes (P < 0.05). Further mechanistic studies in H9c2 cardiomyocytes revealed that suppression of SIRT1 by Sh-SIRT1 counteracted the effects of RA on high glucose-induced abnormal metabolism of glucose and lipids, oxidative stress and apoptosis (P < 0.05). Taken together, these data indicate that RA prevented mitochondrial injury and cardiac dysfunction in DCM mice, and the SIRT1/PGC-1α pathway mediated the protective effects of RA.

Downregulation of LncRNA OIP5-AS1 Induced by IL-1ß Aggravates Osteoarthritis via Regulating miR-29b-3p/PGRN.

BACKGROUND: Long noncoding RNA (lncRNA) OIP5 antisense RNA 1 (OIP5-AS1) is an oncogenic lncRNA; however, its role in osteoarthritis (OA) pathology still remains unknown. MATERIALS AND METHODS: qRT-PCR was performed to measure the expressions of OIP5-AS1, miR-29b-3p and progranulin (PGRN) mRNA in OA cartilage tissues and normal cartilage tissues. Chondrocyte cell lines, CHON-001 and ATDC5, were treated with different doses of interleukin-1ß (IL-1ß) to induce the inflammatory response. Overexpression plasmids, microRNA mimics, microRNA inhibitors and small interfering RNAs were constructed and transfected into CHON-001 and ATDC5 cells. CCK-8 assay was used for determining the cell viability and Transwell assay was used for monitoring cell migration. Western blot was applied to measure the expressions of apoptosis-related proteins. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the contents of inflammatory factors. StarBase and TargetScan were used to predict the binding sites between OIP5-AS1 and miR-29b-3p, miR-29b-3p and 3'-UTR of PGRN respectively, which were verified by dual luciferase reporter assay. RESULTS: OIP5-AS1 and PGRN mRNA were downregulated while miR-29b-3p was upregulated in OA tissues and models. The up-regulated OIP5-AS1 facilitated the proliferation and migration of CHON-001 and ATDC5 cells, while ameliorated the apoptosis and inflammatory response. However, miR-29b-3p had opposite effects. PGRN was identified as a target gene of miR-29b-3p, which could be indirectly suppressed by OIP5-AS1 knockdown. CONCLUSION: Downregulation of OIP5-AS1 induced by IL-1ß could inhibit the proliferation and migration abilities of CHON-001 and ATDC5 cells and facilitate the apoptosis and inflammation response via regulating miR-29b-3p/PGRN axis.

Ilizarov Gradual Distraction Correction for Distal Tibial Severe Varus Deformity Resulting from Epiphyseal Fracture: Case Report and Literature Review.

We present a case of a 13-year-old female with severe varus deformity and limb discrepancy resulting from epiphyseal fracture. The preoperative tibial articular surface angle was 64.1°, and the affected tibia was 14 mm shorter than the contralateral tibia. She underwent a medial open osteotomy and fibular osteotomy with gradual distraction correction using Ilizarov fixator. The deformity was corrected at 3 months, and the external fixator was removed when bony union was achieved 6 months postoperatively. At 9 months after surgery, the patient could play basketball without feeling pain. At the last follow-up, namely 36 months after the operation, the American Orthopaedic Foot and Ankle Society hindfoot-ankle score was improved from 58 to 90, the patient was pain free, and the radiological measurements were nearly normal. Ilizarov fixator gradual distraction correction for distal tibial severe varus deformity is a safe and cost-effective method that can yield excellent radiological and clinical outcomes.

[Research progress in Achilles tendinopathy].

OBJECTIVE: To explore the classification, diagnosis, and clinical treatment of Achilles tendinopathy. METHODS: The literature about Achilles tendinopathy at home and abroad was reviewed. The research results of classification and terms, imaging diagnosis, and clinical treatment of Achilles tendinopathy were summarized. RESULTS: The classification and name of Achilles tendinopathy are not completely unified, and the concept is vague, the cause of disease is not clear. There are many treatment plans, but there is no effective evidence-based medicine research. CONCLUSION: The diagnosis and treatment of Achilles tendinopathy is complicated. According to the characteristics of Achilles tendon anatomy and etiology, the classification and definition of Achilles tendinopathy need to be further studied in order to guide clinical treatment more effectively and facilitate experience exchange and learning.

Osteotomies combined with soft tissue procedures for symptomatic flexible flatfoot deformity in children.

BACKGROUND: The indications for surgery, timing, and procedure in children with flexible flatfoot deformity remain controversial. This study aims to evaluate the efficacy of osteotomies combined with soft tissue procedures in children with flexible flatfoot aged 9-14 years. METHODS: Twenty-eight children (47 feet) with flexible flatfoot who underwent osteotomy combined with soft tissue surgery between July 2014 and October 2017 were included in this study. The main observational indexes included the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Foot and Ankle Outcome Score (FAOS), talo-navicular coverage angle (TNCA), talar-first metatarsal angle (T1MA) on the foot anteroposterior (AP) view, calcaneal pitch angle and Meary's angle on the foot lateral view, and calcaneus valgus angle (CVA) on the Saltzman view. Intra- and interobserver reliabilities were assessed using intra-class correlation coefficient (ICC). Patient's satisfaction was assessed. RESULTS: All patients were followed up for an average duration of 29.7±8.6 months. The results showed that the mean AOFAS and FAOS had improved significantly from 56.6±8.0 and 47.4±9.5 preoperatively to 88.4±3.9 and 83.2±6.8 at final follow-up (P<0.001), respectively. There were statistically significant differences between preoperative and postoperative scores in all FAOS subscales (P<0.001). Radiographic parameters, such as TNCA (P<0.001) and T1MT (P<0.001) on foot AP views, calcaneal pitch angle (P=0.014) and Meary's angle (P<0.001) on foot lateral views, and CVA (P<0.001) on Saltzman views, had improved significantly. We observed overall substantial to perfect intra- and inter-observer agreements for all radiographic measurements preoperatively and final follow-up. All patients and their parents were satisfied with the functional outcomes. CONCLUSION: Osteotomies combined with soft tissue procedures is an effective strategy for flexible flatfoot deformity in children, as it results in favorable radiographic and functional outcomes.

Comparison of Minimally Invasive and Traditionally Open Surgeries in Correction of Hallux Valgus: A Meta-Analysis.

This meta-analysis aimed to compare the clinical outcomes of minimally invasive surgery (MIS) and traditional open surgery for the correction of symptomatic hallux valgus. A literature search was conducted, and a total of 11 studies with 1166 (52.98%, cases) patients treated with MIS and 1035 (47.02%, cases) patients treated with traditionally open surgery were included in the meta-analyses. The pooled data (odds ratio [OR] 6.28, 95% confidence interval [CI] 3.20 to 12.32, Z = 5.35, p < .01) indicated that patients treated with MIS had a significantly higher rate of excellent-good radiographic angular results than did patients treated with open surgery. However, the incidences of complications (OR 0.67, 95% CI 0.24 to 1.91, Z = 0.75, p = .45), recovery time (standard mean difference ‒3.09, 95% CI ‒7.98 to 1.80, Z = 1.24, p = .22), and patient-reported satisfaction (OR 2.76, 95% CI 0.72 to 10.65, Z = 1.48, p = .14) were similar between patients with hallux valgus treated with MIS and patients treated with open surgery. Heterogeneity between the sources of the pooled data threatened the validity of our observations, and we used statistical methods that aimed to limit such biases. At this time, more high-quality studies are needed to confirm or refute the results of this investigation.