Improving iPSC Differentiation Using a Nanodot Platform.

Differentiation of induced pluripotent stem cells (iPSCs) is an extremely complex process that has proven difficult to study. In this research, we utilized nanotopography to elucidate details regarding iPSC differentiation by developing a nanodot platform consisting of nanodot arrays of increasing diameter. Subjecting iPSCs cultured on the nanodot platform to a cardiomyocyte (CM) differentiation protocol revealed several significant gene expression profiles that were associated with poor differentiation. The observed expression trends were used to select existing small-molecule drugs capable of modulating differentiation efficiency. BRD K98 was repurposed to inhibit CM differentiation, while iPSCs treated with NSC-663284, carmofur, and KPT-330 all exhibited significant increases in not only CM marker expression but also spontaneous beating, suggesting improved CM differentiation. In addition, quantitative polymerase chain reaction was performed to determine the gene regulation responsible for modulating differentiation efficiency. Multiple genes involved in extracellular matrix remodeling were correlated with a CM differentiation efficiency, while genes involved in the cell cycle exhibited contrasting expression trends that warrant further studies. The results suggest that expression profiles determined via short time-series expression miner analysis of nanodot-cultured iPSC differentiation can not only reveal drugs capable of enhancing differentiation efficiency but also highlight crucial sets of genes related to processes such as extracellular matrix remodeling and the cell cycle that can be targeted for further investigation. Our findings confirm that the nanodot platform can be used to reveal complex mechanisms behind iPSC differentiation and could be an indispensable tool for optimizing iPSC technology for clinical applications.

Human platelet lysate-cultured adipose-derived stem cell sheets promote angiogenesis and accelerate wound healing via CCL5 modulation.

BACKGROUND: A rising population faces challenges with healing-impaired cutaneous wounds, often leading to physical disabilities. Adipose-derived stem cells (ASCs), specifically in the cell sheet format, have emerged as a promising remedy for impaired wound healing. Human platelet lysate (HPL) provides an attractive alternative to fetal bovine serum (FBS) for culturing clinical-grade ASCs. However, the potential of HPL sheets in promoting wound healing has not been fully investigated. This study aimed to explore the anti-fibrotic and pro-angiogenic capabilities of HPL-cultured ASC sheets and delve into the molecular mechanism. METHODS: A rat burn model was utilized to evaluate the efficacy of HPL-cultured ASC sheets in promoting wound healing. ASC sheets were fabricated with HPL, and those with FBS were included for comparison. Various analyses were conducted to assess the impact of HPL sheets on wound healing. Histological examination of wound tissues provided insights into aspects such as wound closure, collagen deposition, and overall tissue regeneration. Immunofluorescence was employed to assess the presence and distribution of transplanted ASCs after treatment. Further in vitro studies were conducted to decipher the specific factors in HPL sheets contributing to angiogenesis. RESULTS: HPL-cultured ASC sheets significantly accelerated wound closure, fostering ample and organized collagen deposition in the neo-dermis. Significantly more retained ASCs were observed in wound tissues treated with HPL sheets compared to the FBS counterparts. Moreover, HPL sheets mitigated macrophage recruitment and decreased subsequent wound tissue fibrosis in vivo. Immunohistochemistry also indicated enhanced angiogenesis in the HPL sheet group. The in vitro analyses showed upregulation of C-C motif chemokine ligand 5 (CCL5) and angiogenin in HPL sheets, including both gene expression and protein secretion. Culturing endothelial cells in the conditioned media compared to media supplemented with CCL5 or angiogenin suggested a correlation between CCL5 and the pro-angiogenic effect of HPL sheets. Additionally, through neutralizing antibody experiments, we further validated the crucial role of CCL5 in HPL sheet-mediated angiogenesis in vitro. CONCLUSIONS: The present study underscores CCL5 as an essential factor in the pro-angiogenic effect of HPL-cultured ASC sheets during the wound healing process. These findings highlight the potential of HPL-cultured ASC sheets as a promising therapeutic option for healing-impaired cutaneous wounds in clinical settings. Furthermore, the mechanism exploration yields valuable information for optimizing regenerative strategies with ASC products. BRIEF ACKNOWLEDGMENT: This research was supported by the National Science and Technology Council, Taiwan (NSTC112-2321-B-002-018), National Taiwan University Hospital (111C-007), and E-Da Hospital-National Taiwan University Hospital Joint Research Program (111-EDN0001, 112-EDN0002).

Dislodgment Effects of Different Cage Arrangements in Posterior Lumbar Interbody Fusion: A Finite Element Study.

The vertebral cage has been widely used in posterior lumbar interbody fusion. The risk of cage dislodgment is high for patients undergoing lumbar fusion surgery. Therefore, the main objective of this study was to use a lumbar fusion model to investigate the effects of cage dislodgment on different cage arrangements after PLIF. Finite element analysis was used to compare three PEEK cage placements, together with the fibula-type cage, with respect to the four kinds of lumbar movements. The results revealed that a horizontal cage arrangement could provide a better ability to resist cage dislodgment. Overall lumbar flexion movements were confirmed to produce a greater amount of cage slip than the other three lumbar movements. The lower part of the lumbar fusion segment could create a greater amount of cage dislodgment for all of the lumbar movements. Using an autograft with a fibula as a vertebral cage cannot effectively reduce cage dislodgment. Considering the maximum movement type in lumbar flexion, we suggest that a horizontal arrangement of the PEEK cage might be considered when a single PEEK cage is placed in the fusion segment, as doing so can effectively reduce the extent of cage dislodgment.

Assessment of Thermal Osteonecrosis during Bone Drilling Using a Three-Dimensional Finite Element Model.

Bone drilling is a common procedure used to create pilot holes for inserting screws to secure implants for fracture fixation. However, this process can increase bone temperature and the excessive heat can lead to cell death and thermal osteonecrosis, potentially causing early fixation failure or complications. We applied a three-dimensional dynamic elastoplastic finite element model to evaluate the propagation and distribution of heat during bone drilling and assess the thermally affected zone (TAZ) that may lead to thermal necrosis. This model investigates the parameters influencing bone temperature during bone drilling, including drill diameter, rotational speed, feed force, and predrilled hole. The results indicate that our FE model is sufficiently accurate in predicting the temperature rise effect during bone drilling. The maximum temperature decreases exponentially with radial distance. When the feed forces are 40 and 60 N, the maximum temperature does not exceed 45 °C. However, with feed forces of 10 and 20 N, both the maximum temperatures exceed 45 °C within a radial distance of 0.2 mm, indicating a high-risk zone for potential thermal osteonecrosis. With the two-stage drilling procedure, where a 2.5 mm pilot hole is predrilled, the maximum temperature can be reduced by 14 °C. This suggests that higher feed force and rotational speed and/or using a two-stage drilling process could mitigate bone temperature elevation and reduce the risk of thermal osteonecrosis during bone drilling.

Dorsal spanning plating for complex carpometacarpal fracture-dislocations: a retrospective case series.

We studied the outcome of dorsal spanning plate for complex carpometacarpal fracture-dislocation management as a feasible option in nine patients, even on delayed presentation with substantial metacarpal shortening. However, patients must be informed about the need for plate removal.

Nerve bypass surgery for spinal cord reconstruction.

OBJECTIVE: Spinal cord injury (SCI) is a devastating condition that significantly decreases the patient's quality of life. Therefore, treatments that can facilitate nerve regeneration, reduce complications, and increase quality of life are valuable for these patients. In this study, we aimed to assess nerve bypass surgery's feasibility and clinical outcomes by transferring the intercostal nerves (ICNs) into the spinal cord. METHODS: Eight patients with complete thoracic SCI and delayed presentation more than a year after the injury were analyzed retrospectively. All patients underwent nerve bypass surgery with the transfer of two pairs of ICNs from proximal to the injury site to the anterolateral spinal cord, followed by duraplasty with fascia grafting to close the dura. RESULTS: Six of the eight (75%) patients demonstrated motor and sensory improvements, based on the American Spinal Cord Injury Association score. Three patients demonstrated a limited recovery of motor function that could be independently triggered without ICN initiation. Five patients demonstrated evidence of cerebrospinal fluid (CSF) leakage after surgery; however, only one patient complained of a headache. CONCLUSION: Spinal cord bypass surgery is a potential reconstruction method to treat chronic complete thoracic SCI with functional improvements, and is worth further investigation.

Interim Use of Antibiotic-Loaded Cement Spacer for Patients with Infected Cervical Fusion.

OBJECTIVE: The management of postoperative deep infection after anterior cervical discectomy and fusion (ACDF) remains challenging for spine surgeons. Our institution uses handmade antibiotic-loaded cement spacers to treat these complex cases. This study aimed to determine the efficacy and feasibility of this treatment. METHODS: This study included 4 patients with deep cervical spine infections after ACDF who underwent our treatment between March 2012 and January 2022. Patients' laboratory data, visual analog scale scores, comorbidities, complications, and neurological status were recorded. Their clinical conditions were also evaluated based on the Neck Disability Index, Japanese Orthopaedic Association score, and Odom criteria. RESULTS: Infection eradication was achieved in all patients after treatment. The average preoperative visual analog scale score was 7.5 (range: 7-8); this decreased to 1.25 (range: 1-2) at 1 year postoperatively. None of the patients experienced severe complications, such as neurological deterioration or bone graft dislodgement. The Neck Disability Index improved from a preoperative value of 54% (range: 48-60%) to 6% (range: 4-8%) at 1 year postoperatively. The Japanese Orthopaedic Association score improved from a preoperative score of 10.25 (range: 10-11)-14.75 (range: 14-16) at 1 year postoperatively. All patients achieved excellent outcomes based on Odom criteria at 1 year postoperatively. CONCLUSIONS: Good clinical outcomes were achieved in this study. Although 2-stage surgery is required, this technique could be an alternative for patients with postoperative deep infection after ACDF.

Isoliquiritigenin inhibits apoptosis and ameliorates oxidative stress in rheumatoid arthritis chondrocytes through the Nrf2/HO-1-mediated pathway.

Rheumatoid arthritis (RA) is a chronic inflammatory condition known for its irreversible destructive impact on the joints. Chondrocytes play a pivotal role in the production and maintenance of the cartilage matrix. However, the presence of inflammatory cytokines can hinder chondrocyte proliferation and promote apoptosis. Isoliquiritigenin (ISL), a flavonoid, potentially exerts protective effects against various inflammatory diseases. However, its specific role in regulating the nuclear factor E2-associated factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in chondrocytes in RA remains unclear. To investigate this, this study used human chondrocytes and Sprague-Dawley rats to construct in vitro and in vivo RA models, respectively. The study findings reveal that cytokines markedly induced oxidative stress, the activation of matrix metalloproteinases, and apoptosis both in vitro and in vivo. Notably, ISL treatment significantly mitigated these effects. Moreover, Nrf2 or HO-1 inhibitors reversed the protective effects of ISL, attenuated the expression of Nrf2/HO-1 and peroxisome proliferator-activated receptor gamma-coactivator-1α, and promoted chondrocyte apoptosis. This finding indicates that ISL primarily targets the Nrf2/HO-1 pathway in RA chondrocytes. Moreover, ISL treatment led to improved behavior scores, reduced paw thickness, and mitigated joint damage as well as ameliorated oxidative stress in skeletal muscles in an RA rat model. In conclusion, this study highlights the pivotal role of the Nrf2/HO-1 pathway in the protective effects of ISL and demonstrates the potential of ISL as a treatment option for RA.

Surgical reconstructions for adult brachial plexus injuries. Part II: Treatments for total arm type.

Brachial plexus injuries (BPI) contribute not only to physical dysfunction but also to socioeconomic aspects and psychological disability. Patients with total arm-type BPI will lose not only the shoulder and elbow function but also the hand function, making reconstruction particularly challenging. Reconstructive procedures commonly include nerve repair, grafting, neurotization (nerve transfer), tendon transfer and free functional muscle transfer (FFMT). Although it is difficult to achieve prehensile hand function, most of patients with total arm-type BPI can be treated with satisfied outcomes. In addition to surgical techniques, comprehensive rehabilitation is another important factor for successful outcomes, and efficient communication can help to boost patient morale and eliminate uncertainty.

First 100 total hip arthroplasties performed by a young surgeon using the direct anterior approach: learning curve and complications.

INTRODUCTION: Most of the reported discussions about the learning curve for the direct anterior approach (DAA) in total hip arthroplasty (THA) have been by experienced surgeons. The study's aim was to describe the learning curve, short-term outcomes, complications, and adaptations to the DAA used in the first 100 THA cases experienced by a young surgeon who had received DAA training for trauma surgeries. MATERIALS AND METHODS: This retrospective study summarizes the first 100 consecutive cases experienced by a young surgeon who performed the unilateral DAA for THA between 2019 and 2021. Cumulative sum (CUSUM) analysis was performed to evaluate the learning curve on the basis of operative time and overall complications. The demographics data, short-term outcomes, and complications of the first 50 and second 50 cases were compared. RESULTS: The CUSUM curve declined after 49 and 55 cases, measured by operative time and overall complications, respectively. The median operative time (104 vs. 80 min) and intraoperative fluoroscopic time (38 vs. 12 s) increased significantly in the first 50 cases compared with the times in the second 50 cases. Complications tended to occur in the first 50 cases (12% vs. 6%), and the overall rate was 9%. Major complications all occurred in the first 50 cases, with a rate of 4%. Only one case, which involved a complicated periprosthetic fracture around the stem that extended to the tip, required the intervention of a senior surgeon. CONCLUSIONS: Even after receiving training on the DAA for trauma surgeries, the young surgeon experienced a steep learning curve and more complications in the first 50 cases. The DAA for THA is a technically demanding procedure and may require guidance from an experienced surgeon to manage unexpected complications.

Cyclic Stability of Locking Plate Augmented with Intramedullary Polymethyl Methacrylate (PMMA) Strut Fixation for Osteoporotic Humeral Fractures: A Biomechanical Study.

The locking plate may provide improved fixation in osteoporotic bone; however, it has been reported to fail due to varus collapse or screw perforation of the articular surface, especially in osteoporotic bone with medial cortex comminution. Using bone graft as an intramedullary strut together with plate fixation may result in a stronger construct. However, the drawbacks of bone grafts include limited supply, high cost, and infection risk. PMMA (so-called bone cement) has been widely used for implant fixation due to its good mechanical properties, fabricability, and biocompatibility. The risk of donor-site infection and the drawbacks of allografting may be overcome by considering PMMA struts as alternatives to fibular grafts for humeral intramedullary grafting surgeries. However, the potential effects of intramedullary PMMA strut on the dynamic behaviour of osteoporotic humerus fractures remain unclear. This study aimed to investigate the influence of an intramedullary PMMA strut on the stability of unstable proximal humeral fractures in an osteoporotic synthetic model. Two fixation techniques, a locking plate alone (non-strut group) and the same fixation augmented with an intramedullary PMMA strut (with-strut group), were cyclically tested in 20 artificial humeral models. Axially cyclic testing was performed to 450 N for 10,000 cycles, intercyclic motion, cumulated fragment migration, and residual deformation of the constructs were determined at periodic cyclic intervals, and the groups were compared. Results showed that adding an intramedullary PMMA strut could decrease 1.6 times intercyclic motion, 2 times cumulated fracture gap migration, and 1.8 times residual deformation from non-strut fixation. During cycling, neither screw pull-out, cut-through, nor implant failure was observed in the strut-augmented group. We concluded that the plate-strut mechanism could enhance the cyclic stability of the fixation and minimize the residual displacement of the fragment in treating osteoporotic proximal humeral unstable fractures. The PMMA strut has the potential to substitute donor bone and serve as an intramedullary support when used in combination with locking plate fixation. The intramedullary support with bone cement can be considered a solution in the treatment of osteoporotic proximal humeral fractures, especially when there is medial comminution.

Comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury in the rat.

Cervical spinal cord injury interrupts supraspinal pathways innervating thoracic sympathetic preganglionic neurons and results in cardiovascular dysfunction. Both respiratory and locomotor functions were also impaired due to damages of motoneuron pools controlling respiratory and forelimb muscles, respectively. However, no study has investigated autonomic and somatic motor functions in the same animal model. The present study aimed to establish a cervical spinal cord injury model to evaluate cardiorespiratory response and locomotor activity in unanesthetized rats. Cardiovascular response and respiratory behavior following laminectomy or cervical spinal contusion were measured using noninvasive blood pressure analyzer and plethysmography systems, respectively. Locomotor activity was evaluated by an open-field test and a locomotor rating scale. The results demonstrated that mean arterial blood pressure and heart rate were significantly reduced in contused rats compared with uninjured rats at the acute injured stage. Tidal volume was also significantly reduced during the acute and subchronic stages. Moreover, locomotor function was severely impaired, evidenced by decreasing moving ability and locomotor rating scores from the acute to chronic injured stages. Retrograde neurotracer results revealed that cervical spinal cord injury caused a reduction in number of phrenic and triceps motoneurons. Immunofluorescence staining revealed a significant attenuation of serotonergic, noradrenergic, glutamatergic, and GABAergic fibers innervating the thoracic sympathetic preganglionic neurons in chronically contused rats. These results revealed the pathological mechanism underlying the comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury. We proposed that this animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.NEW & NOTEWORTHY The present study establishes a preclinical rodent model to comprehensively investigate physiological functions under unanesthetized condition following cervical spinal cord contusion. The results demonstrated that cervical spinal cord contusion is associated with impairments in cardiovascular, respiratory, and locomotor function. Respiratory and forelimb motoneurons and neurochemical innervations of sympathetic preganglionic neurons were damaged following injury. This animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.

Long-Term Use of Immunosuppressive Agents Increased the Risk of Fractures in Patients with Autoimmune Diseases: An 18-Year Population-Based Cohort Study.

The risk of fractures is higher in patients with autoimmune diseases, but it is not clear whether the use of immunosuppressive agents can further increase this risk. To investigate this issue, a retrospective study was conducted using data from Taiwan's National Health Insurance Research Database. Patients diagnosed with autoimmune diseases between 2000 and 2014, including psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus, were included in the study. A control group of patients without autoimmune diseases was selected from the same database during the same period. Patients with autoimmune diseases were divided into two sub-cohorts based on their use of immunosuppressive agents. This study found the risk of fractures was 1.14 times higher in patients with autoimmune diseases than in those without. Moreover, we found that patients in the immunosuppressant sub-cohort had a higher risk of fractures compared to those in the non-immunosuppressant sub-cohort. The adjusted sub-distribution hazard ratio for shoulder fractures was 1.27 (95% CI = 1.01-1.58), for spine fractures was 1.43 (95% CI = 1.26-1.62), for wrist fractures was 0.95 (95% CI = 0.75-1.22), and for hip fractures was 1.67 (95% CI = 1.38-2.03). In conclusion, the long-term use of immunosuppressive agents in patients with autoimmune diseases may increase the risk of fractures.

Influence of Simulated State of Disc Degeneration and Axial Stiffness of Coupler in a Hybrid Performance Stabilisation System on the Biomechanics of a Spine Segment Model.

Spinal fusion surgery leads to the restriction of mobility in the vertebral segments postoperatively, thereby causing stress to rise at the adjacent levels, resulting in early degeneration and a high risk of adjacent vertebral fractures. Thus, to address this issue, non-fusion surgery applies some pedicle screw-based dynamic stabilisation systems to provide stability and micromotion, thereby reducing stress in the fusion segments. Among these systems, the hybrid performance stabilisation system (HPSS) combines a rigid rod, transfer screw, and coupler design to offer a semi-rigid fixation method that preserves some mobility near the fusion site and reduces the adjacent segment compensatory effects. However, further research and confirmation are needed regarding the biomechanical effects of the dynamic coupler stiffness of the HPSS on the intrinsic degenerated adjacent segment. Therefore, this study utilised the finite element method to investigate the impact of the coupler stiffness of the HPSS on the mobility of the lumbar vertebral segments and the stress distribution in the intervertebral discs under flexion, extension, and lateral bending, as well as the clinical applicability of the HPSS on the discs with intrinsic moderate and severe degeneration at the adjacent level. The analytical results indicated that, regardless of the degree of disc degeneration, the use of a dynamic coupler stiffness of 57 N/mm in the HPSS may reduce the stress concentrations at the adjacent levels. However, for severely degenerated discs, the postoperative stress on the adjacent segments with the HPSS was still higher compared with that of the discs with moderate degeneration. We conclude that, when the discs had moderate degeneration, increasing the coupler stiffness led to a decrease in disc mobility. In the case of severe disc degeneration, the effect on disc mobility by coupler stiffness was less pronounced. Increasing the coupler stiffness ked to higher stress on intervertebral discs with moderate degeneration, while its effect on stress was less pronounced for discs with severe degeneration. It is recommended that patients with severe degeneration who undergo spinal dynamic stabilisation should remain mindful of the risk of accelerated adjacent segment degeneration.

Prespinal Versus Conventional Hemicontralateral C7 Nerve Transfer in the Treatment of Total Brachial Plexus Roots Avulsion Injuries: A Retrospective Study With a Minimum Follow-Up Period of 4 Years.

PURPOSE: Contralateral C7 (CC7)-to-median nerve transfer has been commonly used to restore hand function in brachial plexus injury. To shorten the nerve graft, the prespinal route was described and achieved direct coaptation when combined with humeral shortening osteotomy. The limb was positioned at 0° shoulder abduction and neutral head position. Given our concern about donor-site morbidity when harvesting the whole CC7 nerve and tension across the neurorrhaphy site after mobilization, we aimed to describe our modified prespinal route and compare its outcomes and complications with the conventional hemi-CC7 transfer. METHODS: From 2004 to 2014, 39 patients with preganglionic total brachial plexus root avulsion injuries, with a minimum of 4 years of follow-up, were included. Overall, 20 and 19 patients underwent the conventional hemi-CC7-to-median nerve and hemi-CC7-to-lower trunk (LT) transfer through the modified prespinal route, respectively. The modified prespinal route was combined with bilateral clavicle shortening osteotomy to achieve direct coaptation to the LT at 45° shoulder abduction. RESULTS: The modified prespinal route showed the median period to achieve ≥M3 hand grip assessed in clinical follow-up was shorter (26.5 months vs 45.5 months), and a higher proportion of patients achieved ≥M3 hand grip recovery (63% vs 30%). One patient experienced symptomatic phrenic nerve injury; however, the hemidiaphragm fully recovered after 6 months. The long-term donor-site complication rate was 2.6%, including one sensory abnormality, and no permanent donor-site weakness after hemi-CC7 harvesting was observed. CONCLUSIONS: The modified prespinal route combined with clavicle osteotomy allowed direct coaptation to the LT and did not require head immobilization. It may allow a higher proportion of patients to achieve ≥M3 hand grip more quickly than conventional hemi-CC7 transfer. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Low-temperature molten salt synthesis and catalytic mechanism of CoS2/NC as an advanced bifunctional electrocatalyst.

The development of productive and sustainable bifunctional electrocatalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) plays an important role in the commercial evolution of metal-air batteries. In this paper, a low-temperature molten salt template method was adopted to synthesize the composite of CoS2 and nitrogen-doped carbon (CoS2/NC) without the protection of inert gas. The structural characterization studies show that the specific surface area (SSA) and crystal growth kinetics are increased and effectively improved, respectively, by the composite of CoS2 and NC. The as-synthesized CoS2/NC composite demonstrates outstanding bifunctional catalytic activity in alkaline electrolytes and exhibits a half-wave potential (E1/2) of 0.854 V (vs. RHE) and an overpotential of only 220 mV for the OER at a current density of 10 mA cm-2 (η10). Simultaneously, CoS2/NC also exhibits excellent electrochemical stability. Additionally, density functional theory (DFT) calculations have manifested that the synergistic effect of CoS2 and NC results in a remarkable enhancement in the bifunctional catalytic performance of the composite materials. This study offers a new pathway and theoretical guidance for the fabrication of efficient bifunctional electrocatalysts.

Cisplatin triggers oxidative stress, apoptosis and pro-inflammatory responses by inhibiting the SIRT1-mediated Nrf2 pathway in chondrocytes.

Although the height of the proliferating layer that was suppressed in the growth plate has been recognized as an adverse effect of cisplatin in pediatric cancer survivors, the detailed pathological mechanism has not been elucidated. Sirtuin-1 (SIRT1) has been reported as an essential modulator of cartilage homeostasis, but its role in cisplatin-induced damage of chondrocytes remains unclear. In this study, we examined how cisplatin affected the expression of SIRT1 and cell viability. Next, we showed downregulation of SIRT1 after cisplatin treatment resulted in suppression of Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), leading to inhibition of Nrf2 nuclear translocation and subsequently decreased Heme oxygenase-1(HO-1) and NAD(P)H Quinone Dehydrogenase 1(NQO-1) expression. Blockage of the SIRT1/ PGC-1α axis not only increased oxidative stress with lower antioxidant SOD and GSH, but also contributed to mitochondrial dysfunction evidenced by the collapse of membrane potential and repression of mitochondrial DNA copy number and ATP. We also found that Cisplatin up-regulated the p38 phosphorylation, pro-inflammatory events and matrix metalloproteinases (MMPs) in chondrocytes through the SIRT1-modulated antioxidant manner. Collectively, our findings suggest that preservation of SIRT1 in chondrocytes may be a potential target to ameliorate growth plate dysfunction for cisplatin-receiving pediatric cancer survivors.

Dumontier group 2 radiocarpal fracture-dislocation: The results of open reduction and fixation without volar ligament repair.

INTRODUCTION: The radiocarpal fracture-dislocations are a spectrum of severe injury involving both the bony and ligamentous structures that stabilise the wrist joint. The aim of this study was to analyse the outcome of open reduction and fixation without volar ligament repair for Dumontier group 2 radiocarpal fracture-dislocation and to evaluate the incidence and clinical relevance of ulnar translation and advanced osteoarthritis. PATIENTS AND METHODS: We retrospectively reviewed 22 patients with Dumontier group 2 radiocarpal fracture-dislocation treated in our institute. Clinical and radiological outcomes were recorded. Postoperative visual analogue scale (VAS) score for pain, Disabilities of the Arm, Shoulder and Hand Outcome Measure (DASH), and Mayo modified wrist scores (MMWS) were collected. Furthermore, extension‒flexion and supination‒pronation arcs were collected by reviewing chart, either. We divided the patients into two groups according to the presence or absence of advanced osteoarthritis, and presented the differences in the pain, disability, wrist performance, and range of motion between the two groups. We performed the same comparison between the patients with and those without the ulnar translation of the carpus. RESULTS: There were sixteen men and six women with a median age of 23 years (range, 20‒48 years). The median follow-up period was 33 months (range, 12-149 months). The median VAS, DASH and MMWS were 0 (range 0-2), 9.1 (range, 0-65.9) and 80 (range, 45-90), respectively. The median flexion‒extension and pronation‒supination arcs were 142.5° (range, 20°â€’170°) and 147.5° (range, 70°â€’175°), respectively. Ulnar translation was recognised in four patients and the development of advanced osteoarthritis was noted in 13 patients during the follow-up period. However, neither was highly correlated with functional outcomes. CONCLUSION: The current study postulated that ulnar translation might occur following treatment for Dumontier group 2 lesions, whereas injury was predominantly caused by rotational force. Therefore, radiocarpal instability should be recognized during the operation. However, the clinical relevance of ulnar translation and wrist osteoarthritis needs to be assessed in further comparison studies.