Suppression of Overactive Insulin-Like Growth Factor 1 Attenuates Trauma-Induced Heterotopic Ossification in Mice.

Heterotopic ossification (HO) is the ectopic bone formation in soft tissues. Aside from hereditary HO, traumatic HO is common after orthopedic surgery, combat-related injuries, severe burns, or neurologic injuries. Recently, mammalian target of rapamycin (mTOR) was demonstrated to be involved in the chondrogenic and osteogenic processes of HO formation. However, its upstream signaling mechanism remains unknown. The current study used an Achilles tendon puncture-induced HO model to show that overactive insulin-like growth factor 1 (IGF-1) was involved in the progression of HO in mice. Micro-computed tomography imaging showed that IGF-1 not only accelerated the rate of osteogenesis and increased ectopic bone volume but also induced spontaneous ectopic bone formation in undamaged Achilles tendons. Blocking IGF-1 activity with IGF-1 antibody or IGF-1 receptor inhibitor picropodophyllin significantly inhibited HO formation. Mechanistically, IGF-1/IGF-1 receptor activates phosphatidylinositol 3-kinase (PI3K)/Akt signaling to promote the phosphorylation of mTOR, resulting in the chondrogenic and osteogenic differentiation of tendon-derived stem cells into chondrocytes and osteoblasts in vitro and in vivo. Inhibitors of PI3K (LY294002) and mTOR (rapamycin) both suppressed the IGF-1-stimulated mTOR signal and mitigated the formation of ectopic bones significantly. In conclusion, these results indicate that IGF-1 mediated the progression of traumatic HO through PI3K/Akt/mTOR signaling, and suppressing IGF-1 signaling cascades attenuated HO formation, providing a promising therapeutic strategy targeting HO.

Outcome evaluation of dye-assist arthroscopic inside-out ganglionectomy: a retrospective study of 29 patients.

OBJECTIVE: To evaluate the clinical outcomes of arthroscopic inside-out ganglionectomy of dominant dorsal wrist ganglion. METHODS: Patients with dominant wrist ganglion cyst treated in our hospital from January 1, 2014 to June 31, 2023 was enrolled in this retrospective analysis. All patients underwent dye-assist arthroscopic inside-out ganglionectomy. After discharge, the patients were followed for a minimum of 6 months. The primary outcomes were to assess patient wrist function using the Patient-Rated Wrist Evaluation (PRWE) and Mayo Modified Wrist Score (MMWS). The secondary outcomes were visual analog score (VAS), wrist active range of motion (ROM), grip strength, recurrence rate and complication. RESULTS: All ganglion were successfully resected after dye staining. Patients were followed for an average of 12.17 months. There were no significant changes between preoperative and postoperative wrist active ROM or grip strength, except for wrist flexion (which showed a slightly greater improvement after surgery, P = 0.049), there were notable improvements in VAS, MMWS, and PRWE postoperatively. Recurrence occurred in 3 patients. No major complications observed during the follow-up period. CONCLUSION: Dye-assist arthroscopic inside-out ganglionectomy is safe and uncomplicated, worth of clinical promotion.

Effect of different ulnar osteotomies on loading of the distal radioulnar joint: a finite element analysis.

BACKGROUND: Ulnar impingement syndrome is a prevalent source of ulnar carpal pain; however, there is ongoing debate regarding the specific location of shortening, the method of osteotomy, the extent of shortening, and the resulting biomechanical alterations. METHOD: To investigate the biomechanical changes in the distal radioulnar joint (DRUJ) resulting from different osteotomy methods, a cadaveric specimen was dissected, and the presence of a stable DRUJ structure was confirmed. Subsequently, three-dimensional data of the specimen were obtained using a CT scan, and finite element analysis was conducted after additional processing. RESULTS: The DRUJ stress did not change significantly at the metaphyseal osteotomy of 2-3 mm but increased significantly when the osteotomy length reached 5 mm. When the osteotomy was performed at the diaphysis, the DRUJ stress increased with the osteotomy length, and the increase was greater than that of metaphyseal osteotomy. Stress on the DRUJ significantly increases when the position is changed to pronation dorsi-extension. Similarly, the increase in stress in diaphyseal osteotomy was greater than that in metaphyseal osteotomy. When the model was subjected to a longitudinal load of 100 N, neither osteotomy showed a significant change in DRUJ stress at the neutral position. However, the 100 N load significantly increased stress on the DRUJ when the position was changed to pronation dorsi-extension, and the diaphyseal osteotomy significantly increased stress on the DRUJ. CONCLUSIONS: For patients with distal oblique bundle, metaphyseal osteotomy result in a lower increase in intra-articular pressure in the DRUJ compared to diaphyseal osteotomy. However, it is crucial to note that regardless of the specific type of osteotomy employed, it is advisable to avoid a shortening length exceeding 5 mm.

Clinical Efficacy of Arthroscopic Transplantation of Palmaris Longus Tendon Combined with Early Accelerated Motion Rehabilitation After Scapholunate Ligament Reconstruction for Geissler Type IV Scapholunate Instability.

Objective: The aim of this study is to investigate the clinical efficacy of early accelerated motion rehabilitation in treating wrist joint instability with Geissler IV scapholunate instability (SLI) using arthroscopic palmaris longus tendon transplantation in conjunction with scapholunate ligament reconstruction. Methods: From June 2019 to January 2022, seven patients with Geissler Type IV SLI underwent arthroscopic ligament reconstruction and repair surgery of the wrist joint, followed by early accelerated motion rehabilitation. Postoperative follow-up indicators included visual analogue scale (VAS) for pain assessment, DASH-CHINESE upper limb function score, Mayo wrist joint score, wrist joint range of motion, and grip strength. Surgical efficacy was evaluated based on these indicators. Results: All patients were followed up postoperatively, with a follow-up duration ranging from 6 to 20 months (mean: 15.3 months). No postoperative complications occurred, and significant improvements were observed in all measured parameters. Postoperative MRI results at one year indicated restoration of the anatomical structure of the scapholunate joint with good healing. Both VAS and DASH-CHINESE scores significantly decreased, and the differences between pre- and postoperative scores were statistically significant (P < .001). The preoperative Mayo wrist joint score was (47.857±21.380) points, with 2 cases rated as fair and 5 cases as poor. At the latest follow-up, the score was (84.286±6.726) points, with 2 cases rated as excellent, 2 cases as good, and 3 cases as fair. Wrist joint flexion-extension range, rotation range, and grip strength all significantly improved compared to the preoperative values, with statistically significant differences (P < .001). Conclusion: The combined approach of arthroscopic transplantation of the palmaris longus tendon and early accelerated motion rehabilitation shows satisfactory clinical outcomes in treating Geissler Type IV scapholunate instability of the wrist joint. This combined approach is of great significance in improving the patient's quality of life and wrist function and helps reduce pain symptoms. Furthermore, in future research, it is recommended to increase the sample size and prolong the observation period to further validate the efficacy.

Biomechanical Analysis of Transosseous Repair Versus Combined Transosseous With Capsular Repair for Triangular Fibrocartilage Complex Tears With Instability.

PURPOSE: This study compared the biomechanical stability of transosseous repair and transosseous combined with capsular repair techniques to reattach the triangular fibrocartilage complex (TFCC) for distal radioulnar joint instability. METHODS: Eight adult cadaveric upper-extremity specimens were studied. Each underwent peripheral ulnar-sided detachment of the deep and superficial TFCC fibers and repair. Four groups were prepared sequentially: intact TFCC, disrupted TFCC, transosseous repair, and combined transosseous with capsular repair. Forearm rotational torque was measured in three wrist positions: 60° flexion, neutral position, and 60° extension. Maximum dorsal and palmar ulnar translations in response to a 20-N traction load were measured at nine wrist positions after stabilizing the humerus and radius. Measurements were taken before and after TFCC disruption and following repair. RESULTS: Clear instability of the radius relative to the ulna was observed after sectioning the deep and superficial fibers of the TFCC, and stability was markedly improved after reconstruction in all positions. Compared with the normal group, rotational torque was similar between the two repair methods. In the pronation palmar flexion and supination dorsal extension positions, dorsal-palmar translation was smaller in the combined transosseous with capsular repair group than in the transosseous repair-alone group. CONCLUSIONS: Triangular fibrocartilage complex deep fibers are the primary stabilizing structure of the distal radioulnar joint. In this cadaveric study, the combined transosseous with capsular repair technique demonstrated less dorsal-palmar translation compared with the transosseous-alone repair technique. CLINICAL RELEVANCE: Combined transosseous with capsular repair is expected to provide improved postoperative stability for patients with peripheral TFCC tears and distal radioulnar joint instability.

Long Head of the Biceps Tendon Plays a Role in Stress Absorption and Humeral Head Restriction during the Late Cocking and Deceleration Phases of Overhead Throwing: A Finite Element Study.

BACKGROUND: Emerging evidence suggests that the long head of the biceps (LHBT) may play a role in stabilizing the glenohumeral joint, and this has led to controversy around the efficacy of biceps tenotomy for superior labral anterior and posterior (SLAP) lesions. Therefore, the aim of this finite element analysis (FEA) study was to determine the stress absorption and humeral head translation restriction effects of the LHBT within the glenohumeral joint during the late cocking and deceleration phases of overhead throwing with a view to resolving the controversy around tenotomy. METHODS: Eight FEA models were created using computed tomography and magnetic resonance imaging data from normal glenohumeral joints. The models represented four LHBT conditions: uninjured, subpectoral tenodesis, tenotomy, and type II SLAP lesions. The late cocking and deceleration phases of the overhead throwing were simulated for each model. The impacts of the four LHBT conditions on glenohumeral joint stress absorption and humeral head displacement restriction were studied based on 1) stress and related distributions on the cartilage, labrum, capsule, and LHBT and 2) humeral head translation variation. RESULTS: The FEA analysis showed that the magnitude of the contact stress on the articular cartilage, labrum, and capsule was the lowest in the uninjured models, followed by the subpectoral tenodesis, tenotomy, and type II SLAP lesion models. Humeral head translation was the most restricted in the subpectoral tenodesis models, followed by the tenotomy and type II SLAP lesion models. CONCLUSION: Finite element analysis demonstrated that the LHBT plays a significant role in stress absorption and displacement restriction in the late cocking and deceleration phases of overhead throwing. Subpectoral tenodesis of the LHBT exhibited lesser amount of stress and humeral head translation than those of tenotomy, thereby making it a better option for patients who engage in overhead throwing.

Investigating 3D-printed disk compressing against skin for pain relief in intradermal infiltration anesthesia: a randomized controlled trial.

BACKGROUND: Pain intensity may be varied during the needle advancing through different skin layers, injection into the intradermal layer may exclude mixed pain from deeper planes. This study aimed to investigate whether compressing a three-dimensional (3D)-printed disk against the skin may relieve pain associated with intradermal injection of local anesthetic which mimics the skin test procedure. METHODS: After institutional review board approval, 3D-printed disks with projections were designed for this study. Enrolled patients were randomized to receive either a disk compressing against the axillary skin during the intradermal injection of local anesthesia (compressing disk group) or an intradermal injection of local anesthesia without any compression (no compressing disk group). The primary outcomes were pain intensity (100-mm visual analog scale) and satisfaction (5-point Likert scale) as assessed by patients. RESULTS: Ninety patients with American Society of Anesthesiologists I-II physical status receiving intradermal local anesthesia prior to an ultrasound-guided axillary approach were included. Eighty-seven patients completed the study, with 44 and 43 patients in disk and no disk groups, respectively. Pain scores were significantly different (P < 0.001) in compressing disk (median, 10; IQR, 5-20) and no compressing disk (median, 30; IQR, 20-40) groups. The median satisfaction score was 5 in both groups. No complications occurred during follow-up. CONCLUSION: Compressing a 3D-printed disk against the skin may reduce intradermal needle pain and offers an effective alternative for nerve block induction.

Ibrutinib versus bendamustine plus rituximab for first-line treatment of 65 or older patients with untreated chronic lymphocytic leukemia without del(17p)/TP53 mutation in China: a lifetime economic research study.

BACKGROUND: The incidence and mortality rates of patients with chronic lymphocytic leukemia (CLL) in China have recently increased. This study performed a long-term economic evaluation of the first-line treatment strategies ibrutinib (IB) or bendamustine (BE) plus rituximab (RI) for previously untreated older patients with CLL without the del(17p)/TP53 mutation in China. METHODS: Based on clinical data from large, randomized trials, a Markov model including four disease states (event-free survival, treatment failure, post-treatment failure, and death) was used to estimate the incremental costs per quality adjusted-life year (QALY) gained from the first-line IB strategy versus the BE plus RI strategy over a 10-year period. All costs were adjusted to 2022 values based on the Chinese Consumer Price Index, and all costs and health outcomes were discounted at an annual rate of 5%. Sensitivity analysis was performed to confirm the robustness of base-case results. RESULTS: Compared to the first-line BE plus RI strategy, first-line IB treatment achieved 1.17 additional QALYs, but was accompanied by $88,046.78 (estimated in 2022 US dollars) in decremental costs per patient over 10 years. Thus, first-line treatment with IB appeared to have absolute dominance compared to the BE plus RI strategy. Sensitivity analysis confirmed the robustness of these results. CONCLUSIONS: The first-line treatment with IB is absolutely cost-effective compared to the first-line BE plus RI treatment strategy for 65 or older patients with CLL without the del (17p)/TP53 mutation from the Chinese payer perspective. Therefore, it is strongly recommended that Chinese health authorities select the former strategy for these CLL patients.

Comparison of diaphyseal and metaphyseal ulnar shortening osteotomies for the treatment of ulnar impaction syndrome.

BACKGROUND: Ulnar shortening osteotomy (USO) is a common surgical procedure for the treatment of ulnar impaction syndrome (UIS). The purpose of this study was to compare the results of metaphyseal and diaphyseal USO.  METHODS: This retrospective study compared the clinical outcomes and complications of 32 patients who underwent diaphyseal step-cut USO (n = 10), diaphyseal oblique USO (n = 12), or metaphyseal USO (n = 10). RESULTS: Patient characteristics, ulnar variance, wrist range of motion, preoperative pain, grip strength, and functional scores (quick disability of the arm, shoulder, and hand and patient-rated wrist evaluation) were comparable. Both operation time (79.5 vs. 138/139 min) and incision length (7.80 vs. 9.67/13.00 cm) were shorter in the metaphyseal USO than in the diaphyseal oblique/step-cut USO. Compared with diaphyseal oblique/step-cut USO, metaphyseal osteotomies were associated with greater improvement in the pain on postoperative day 3 and shorter bone healing time. The requirements for implant removal were the same among the three groups. No complications were observed in any group. CONCLUSION: Compared with diaphyseal USO, metaphyseal USO has advantages for operation time and incision length, early postoperative pain, bone healing in UIS management. The results suggested that metaphyseal USO could be widely applied to the surgical treatment of UIS. However, the long-term outcomes of these techniques still require further evaluation using more large-scale, randomized clinical trials.

Comparative study of trimming and resection of diseased finger superficial flexor tendons in gouty carpal tunnel syndrome.

BACKGROUND: Hyperuricemia can lead to synovial hyperplasia in the wrist. In severe cases, it can lead to the deposition of gouty stone in the carpal tunnel, resulting in increased pressure in the carpal tunnel and compression of the median nerve to cause carpal tunnel syndrome (CTS), which is called gouty carpal tunnel syndrome (GCTS). As for the surgical treatment of gouty carpal tunnel syndrome, scholars have different opinions on whether it is necessary to remove the superficial flexor tendon. The purpose of this study was to compare the clinical efficacy of trimming and resection of the diseased superficial flexor tendon in the treatment of gouty carpal tunnel syndrome. METHODS: Clinical data were collected from May 2016 to July 2021 from 10 patients (13 affected wrists) diagnosed with gouty carpal tunnel syndrome and classified into two groups according to the surgical modality: the diseased portion of the gout-eroded superficial finger tendon was trimmed in 9 wrists, and the diseased superficial finger flexor tendon was excised in 4 wrists. Values related to flexion and extension functions, 2-PD, DASH, BCTQ, VAS and recurrence in the affected fingers were compared between the two groups as well as before and after surgery in each group. RESULTS: All affected limbs used were cleared of gouty stones, finger numbness improved, no skin necrosis occurred, and all incisions healed at stage I. At follow-up (13.58 ± 5.53 months), there was no significant difference between groups in flexion and extension function, 2-PD, DASH, BCTQ, and VAS with respect to the affected fingers, and patients in both groups improved significantly before and after surgery. Treatment of only one wrist involved trimming to remove lesion-affected portions of tendon, which reappeared 1 year after surgery, and there was one case of poor recovery from greater piriformis muscle atrophy in both procedures. CONCLUSION: Regarding surgical treatment of patients with gouty carpal tunnel syndrome in which the gouty stone has invaded the superficial flexor tendons of the fingers, the diseased superficial flexor tendons can be selectively excised, and the postoperative mobility of the affected fingers may not be impaired.

Endoscopic-assisted locking block modified Krackow technique combined with a V-Y flap for chronic Achilles tendon rupture.

PURPOSE: The purpose of this study was to evaluate the clinical outcomes of the endoscopic-assisted locking block modified Krackow technique with a V-Y flap. The hypothesis was that the minimally invasive technique can reduce wound complications and facilitate early recovery. METHODS: In total, 29 men with chronic Achilles tendon rupture who underwent either minimally invasive technique (n = 13) or open repair (n = 16) at our department between 2013 and 2019 were retrospectively analyzed. The rate of complications, time to return to moderate-intensity exercise, American Orthopedic Foot and Ankle Society ankle hindfoot score, Achilles tendon Total Rupture Score, heel-rise repetitions in 1 min, heel-rise height, and bilateral calf circumference at 6 months, 1 year, and 2 years postoperatively were recorded. RESULTS: All incisions healed primarily in the minimally invasive technique group; however, three patients in the open repair group experienced wound complications. The time to return to moderate-intensity exercise, American Orthopedic Foot and Ankle Society score, Achilles tendon Total Rupture Score, heel-rise repetition ratio, and heel-rise height ratio at 6 months postoperatively in the minimally invasive technique group were significantly better than those in the open repair group. However, it was not significantly different between both groups at 2 years postoperatively. CONCLUSION: Endoscopy allowed scar tissue and adhesions to be removed, allowing the tendon ends to be mobilized out of the small proximal and distal incisions. Minimally invasive technique may result in a lower wound complication incidence and provide better early functional recovery and return to moderate-intensity exercise time than the conventional open procedure in treating chronic Achilles tendon ruptures. CLINICAL TRIAL REGISTRATION: Wuxi Ninth People's Hospital Medical Ethical Committee, LW2021026. LEVEL OF EVIDENCE: III.

Contralateral C7 nerve transfer via the prespinal route in treatment of spastic paralysis of upper limb after cerebral palsy.

BACKGROUND: Upper limb spasticity leads to different degrees of disabilities in cerebral palsy, which seriously affects the life of patients. Contralateral C7 nerve transfer has been shown to improve function and reduce spasticity in the affected upper limb with post-stroke hemiplegia. However, reports about the efficacy of this procedure in treating upper limb spasticity caused by hemiplegic cerebral palsy were limited. CASE DESCRIPTION: We reported two cases (a 23-year-old male and a 18-year-old female) who suffered from hemiplegic cerebral palsy with unilateral sustained upper limb spasticity and underwent contralateral C7 nerve transfer in adulthood. The scores of Fugel-Meyer and ROM of the affected upper limbs were observed before and after surgery. Compared with the preoperative, scores of the latest follow-up both were significantly improved. The muscle tension of the upper limbs decreased, and the symptoms of spasm were alleviated. CONCLUSIONS: Considering contralateral C7 nerve transfer could effectively relieve spasticity and improve upper limb activity, it can be recommended as one of the reliable methods to manage spasticity and dystonia of upper limbs in patients with hemiplegic cerebral palsy.

Radial arteriovenous fistula complicated with ischemic steal syndrome after transradial cardiac catheterization: a case report and literature review.

BACKGROUND: The radial arteriovenous fistula (AVF) is a rare complication occurring after transradial cardiac catheterization. Patients with AVF typically present with signs of venous dilation, such as swelling or palpable thrills. However, neurological complications secondary to radial AVFs are rare. This paper reported a rare case of ischemic steal syndrome that occurred 11 months after the transradial cardiac catheterization, most likely as a consequence of radial arteriovenous fistula. CASE PRESENTATION: This paper described a case of a 73-year-old female, who complained of right forearm swelling and radial 1-3 fingers numbness for several months after the catheterized stent surgery through radial approach. Upon Clinical examination, this patient presented with a slight bump and palpable thrill at the distal third of right forearm, and the sensory of radial 1-3 fingers and pinch force was compromised. The Ultrasonography and computed tomography angiography (CTA) of the upper extremity revealed AVF between the right radial artery and the adjacent vein. Microsurgery was performed successfully to ligate the fistula and reconstruct the radial artery. The numbness has gradually improved about 1 week after the surgery, with no recurred swelling. The two-point pinch force and digital sensitivity recovered at the 20-month follow-up. What's more, due to the scarcity of cases, the optimal therapy for iatrogenic radial AVF is controversial. Accordingly, we provided a literature review of previous reports of catheter-related radial AVFs and proposed an algorithm to manage them. CONCLUSIONS: We believe that once an AVF is diagnosed, early treatment options such as compression or surgery are necessary to relieve symptoms and prevent further complications. Otherwise, serious complications can occur, including the ischemic steal syndrome.

The optimal tension for the reconstruction of the distal radioulnar ligaments.

PURPOSE: This study aimed to investigate the optimal tension for the reconstruction of the distal radioulnar ligaments (DRULs) in the treatment of the distal radioulnar joint (DRUJ) instability. METHODS: A total of eight human cadaver upper extremities were used. First, the Tekscan sensor film system was used to measure the contact characteristics of the intact DRUJ. Following this, the DRULs were resected, and the measurement was repeated. The DRULs were then reconstructed according to Adams' procedure, and the contact forces under different initial tension were compared with that of the intact group to obtain the optimal tension. At that point, the contact force of the DRUJ was close to normal. The reliability of the obtained tension was verified by translational testing, which reflected the stability of the DRUJ. RESULTS: In the neutral position, the contact force, area, and pressure inside DRUJ were 0.51 ± 0.10 N, 64.08 ± 11.58 mm2, and 8.33 ± 2.42 kPa, respectively. After the DRULs were resected, they were 0.19 ± 0.02 N, 41.75 ± 5.01 mm2, and 4.86 ± 1.06 kPa, respectively. The relationship between the tension and contact force was linear regression (Y = 0.0496x + 0.229, R2 = 0.9575, P < 0.0001). According to the equation, when the tension was 3.64-7.68 N, the contact force was close to normal. There was no statistical difference in the stability of the reconstructed DRUJ under this tension compared with the intact group (P = 0.08). CONCLUSION: By comparing the contact forces under different reconstruction tensions with the normal value, we obtained the optimal tension, which can provide the theoretical basis for the clinical treatment of chronic DRUJ instability.

Biomechanical evaluation of interference screw fixation techniques for distal radioulnar ligament reconstruction: a cadaveric experimental study.

INTRODUCTION: In the reconstruction of distal radioulnar ligaments (DRULs), interference screws can be used for antegrade or retrograde fixation of grafts to the ulna. However, the biomechanics of interference screw fixation are currently unknown. This study aimed to determine the biomechanical effects of these two fixations on the distal radioulnar joint (DRUJ) in a cadaveric model and to investigate the appropriate initial tension. MATERIALS AND METHODS: A total of 30 human cadaver upper extremities were used, and the DRULs were reconstructed according to Adams' procedure. First, eight specimens were randomly divided into two groups: antegrade and retrograde, followed by translational testing and load testing. Then, the other eight specimens were divided into the two groups above, and the contact mechanics, including forces, areas, and pressures, were measured. Finally, to investigate the appropriate initial tension, the remaining 14 specimens were fixed with interference screws under different tensions in an antegrade way, and the translational testing was repeated as before. RESULTS: In the neutral position, antegrade fixation exhibited less translation than retrograde fixation (7.21 ± 0.17 mm versus 10.77 ± 1.68 mm, respectively). The maximum failure load was 70.45 ± 6.20 N in antegrade fixation, while that in retrograde fixation was 35.17 ± 2.95 N (P < 0.0001). Antegrade fixation exhibited a larger increase in contact force than retrograde fixation (99.72% ± 23.88% versus 28.18% ± 10.43%) (P = 0.001). The relationship between tension and displacement was nonlinear (Y = - 1.877 ln(x) + 7.94, R2 = 0.868, P < 0.0001). CONCLUSIONS: Compared with retrograde fixation, the antegrade fixation of interference screws may be a more reliable surgical technique, as it shows a higher failure load and stability. In addition, to avoid the risk of potential arthritis caused by anterograde fixation, we propose an equation to determine the appropriate initial tension in DRUL reconstruction.

Inhibition of heat shock protein family A member 8 attenuates spinal cord ischemia-reperfusion injury via astrocyte NF-κB/NLRP3 inflammasome pathway : HSPA8 inhibition protects spinal ischemia-reperfusion injury.

BACKGROUND: Astrocyte over-activation and extensive neuron loss are the main characteristic pathological features of spinal cord ischemia-reperfusion injury (SCII). Prior studies have placed substantial emphasis on the role of heat shock protein family A member 8 (HSPA8) on postischemic myocardial inflammation and cardiac dysfunction. However, it has never been determined whether HSPA8 participates in astrocyte activation and thus mediated neuroinflammation associated with SCII. METHODS: The left renal artery ligation-induced SCII rat models and oxygen-glucose deprivation and reoxygenation (OGD/R)-induced rat primary cultured astrocytes were established. The lentiviral vector encoding short hairpin RNA targeting HSPA8 was delivered to the spinal cord by intrathecal administration or to culture astrocytes. Then, the spinal neuron survival, gliosis, and nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and its related pro-inflammatory cytokines were analyzed. RESULTS: SCII significantly enhanced the GFAP and HSPA8 expression in the spinal cord, resulting in blood-brain barrier breakdown and the dramatical loss of spinal neuron and motor function. Moreover, injury also increased spinal nuclear factor-kappa B (NF-κB) p65 phosphorylation, NLRP3 inflammasome-mediated caspase-1 activation, and subsequent interleukin (IL)-1ß as well as IL-18 secretion. Silencing the HSPA8 expression efficiently ameliorated the spinal cord tissue damage and promoted motor function recovery after SCII, through blockade of the astrocyte activation and levels of phosphorylated NF-κB, NLRP3, caspase-1, IL-1ß, and IL-18. Further in vitro studies confirmed that HSPA8 knockdown protected astrocytes from OGD/R-induced injury via the blockade of NF-κB and NLRP3 inflammasome activation. CONCLUSION: Our findings indicate that knockdown of HSPA8 inhibits spinal astrocytic damage after SCII, which may provide a promising therapeutic strategy for SCII treatment.

Tamoxifen Inhibits the Progression of Trauma-Induced Heterotopic Ossification in Mice.

BACKGROUND Heterotopic ossification (HO) is a kind of abnormal mineralized bone which usually occurs in muscle, tendon, or ligament. There are currently no effective drugs for the treatment and prevention of HO. Developing effective drugs that can inhibit HO is of profound significance and would provide new strategies for clinical treatment of this disease. The present investigation evaluated the inhibitory effect of tamoxifen against HO. MATERIAL AND METHODS Using an Achilles tendon trauma-induced HO female mice model, we screened different doses of tamoxifen (1, 3, and 9 mg/kg) in mice to determine the optimal dosage on the inhibition of the HO formation. The curative effect of tamoxifen was also illustrated at different HO progression stages including inflammation, chondrogenesis, osteogenesis, and HO maturation. RESULTS Heterotopic bone was formed with typical endochondral ossification in Achilles tendons 6 weeks after surgery and continued to enlarge up to 12 weeks. The formation of HO was significantly inhibited with the treatment of tamoxifen at the dosage of 9 mg/kg, whereas 1 mg/kg and 3 mg/kg did not reduce HO bone volume remarkably. The progression of HO was both attenuated by tamoxifen from Day 1 and Week 4 post-surgery, whereas no inhibitory effect was shown at the osteogenesis and maturation stages treated with tamoxifen. CONCLUSIONS Tamoxifen exerts an inhibitory effect on the heterotopic bone progression at inflammation and chondrogenesis stages, with the TGF-ß signaling pathway suppressed following the increase in estrogen receptor alpha activity.

Celecoxib cannot inhibit the progression of initiated traumatic heterotopic ossification.

BACKGROUND AND HYPOTHESIS: Heterotopic ossification (HO) is a recognized sequela after trauma and arthroplasty. The purpose of this study was to evaluate the therapeutic effect of celecoxib on HO. We hypothesized that celecoxib may inhibit the progression of initiated HO. METHODS: We performed a retrospective review of 37 patients who underwent elbow joint surgery between January 2014 and June 2018. Seventeen patients were prescribed orally administered celecoxib (200 mg/dose, twice daily) for 2 months after the diagnosis of HO, whereas the remaining 20 patients were administered celecoxib for 1 month starting immediately after surgery. HO progression was evaluated by plain radiographs. By use of an Achilles tendon puncture-induced HO mouse model, the curative effect of celecoxib was illustrated at different HO progression stages. The mice were assigned to 1 of 4 groups: sham group, vehicle group, group receiving celecoxib on day 1, and group receiving celecoxib in week 6. Achilles tendons were analyzed by micro-computed tomography and histochemistry after 12 weeks. RESULTS: Celecoxib did not inhibit the progression of initiated HO in the patients in whom HO was diagnosed, whereas those who received celecoxib after surgery had lower morbidity. Achilles tendon puncture effectively induced typical HO in mice. The ectopic bone volume was significantly reduced in the day 1 celecoxib group compared with the vehicle group; however, the difference was not statistically significant in the week 6 celecoxib group. CONCLUSIONS: Administration of celecoxib starting immediately after surgery can significantly inhibit the formation of HO. Once HO is visible on plain radiographs or micro-computed tomography, celecoxib cannot effectively attenuate further progression of HO in humans and mice.

Muscle fiber types composition and type identified endplate morphology of forepaw intrinsic muscles in the rat.

The failure to accept reinnervation is considered to be one of the reasons for the poor motor functional recovery of intrinsic hand muscles (IHMs) after nerve injury. Rat could be a suitable model to be used in simulating motor function recovery of the IHMs after nerve injury as to the similarities in function and anatomy of the muscles between human and rat. However, few studies have reported the muscle fiber types composition and endplate morphologic characteristics of intrinsic forepaw muscles (IFMs) in the rat. In this study, the myosin heavy chain isoforms and acetylcholine receptors were stained by immunofluorescence to show the muscle fiber types composition and endplates on type-identified fibers of the lumbrical muscles (LMs), interosseus muscles (IMs), abductor digiti minimi (AM) and flexor pollicis brevis (FM) in rat forepaw. The majority of IFMs fibers were labeled positively for fast-switch fiber. However, the IMs were composed of only slow-switch fiber. With the exception of the IMs, the other IFMs had a part of hybrid fibers. Two-dimensional morphological characteristics of endplates on I and IIa muscle fiber had no significant differences among the IFMs. The LMs is the most suitable IFMs of rat to stimulate reinnervation of the IHMs after nerve injury. Gaining greater insight into the muscle fiber types composition and endplate morphology in the IFMs of rat may help understand the pathological and functional changes of IFMs in rat model stimulating reinnervation of IHMs after peripheral nerve injury.

Thumb fingertip reconstruction with palmar V-Y flaps combined with bone and nail bed grafts following amputation.

INTRODUCTION: The aim of treating thumb fingertip amputations with no indication for replantation is to reestablish functional and esthetic properties. MATERIALS AND METHODS: From March 2005 to October 2008, we treated 14 patients with thumb fingertip amputation using palmar V-Y flaps combined with bone and nail bed grafts. There were 10 men and 4 women, whose ages at surgery ranged from 19 to 63 years (mean 35.8 years). In all, 11 of the injuries occurred in the dominant hand. According to Allen's classification, two were type II, seven were type III, and five were type IV. All patients underwent emergency surgery, with a time delay after injury of 3-12 h (mean 6.4 h). In each case, the amputation was a crush or avulsion injury, making microsurgical replantation not feasible. RESULTS: All of the flaps survived. At 8-17 months (average 12.8 months) of follow-up, the average subjective satisfaction score was 8.64. All patients experienced cold intolerance, and none of the patients complained of dysesthesia. Favorable results (excellent or good) were found in 78.6%. Thin primary nails appeared on the grafted nail bed about 3 weeks after surgery, following which the newly formed nail thickened and developed a more natural appearance. In one case, the new nail plate showed abnormal thickening due to hyperkeratosis. The bone graft healed at 5 weeks. The mean two-point discrimination was 7.5 mm. Grip strength was 10% less than that in the unaffected hand. Metacarpophalangeal and proximal interphalangeal joint mobility losses were less than 10°. All patients returned to their jobs. No patients had postoperative complications. CONCLUSIONS: We believe that the combination of palmar V-Y flap and bone and nail bed grafts provides a distinct advantage over other choices. It improves function when replantation is not an option.