All-inside endoscopic semiautomatic running locked stitch technique shows favourable outcomes for acute Achilles tendon ruptures.

PURPOSE: The safety and reliability of endoscopic Achilles tendon rupture repair are still concerning aspects. This study's aim is to evaluate an all-inside endoscopic semiautomatic running locked stitch (Endo-SARLS) technique. METHODS: Forty cases with acute Achilles tendon rupture were treated with the all-inside Endo-SARLS technique between 2020 and 2021. Under endoscopic control, the proximal tendon stumps were stitched with the running locked method using a semiautomatic flexible suture passer. The threads of the high-strength suture were grasped through the paratenon subspace and then fixed into calcaneal insertion with a knotless anchor. Magnetic resonance imaging (MRI), surgical time and complications were assessed. Achilles Tendon Total Rupture Score (ATRS), Achilles Tendon Resting Angle (ATRA) and Heel Rise Height Scale (HRHS) were utilised to evaluate final outcomes. RESULTS: The average follow-up time was 25.4 ± 0.4 (range: 24-32) months. Appropriate tendon regeneration was observed on MRI after 12 months. At the final follow-up, the median value of ATRS score was 95 (interquartile range: 94, 98). Furthermore, there is no significant difference between the injured and contralateral side in the average ATRA (18.2 ± 1.8 vs. 18.3 ± 1.9°, ns) and median value of HRHS [14.5 (13.3, 15.5) vs. 14.8 (13.5, 15.6) cm, ns]. No infection and nerve injuries were encountered. Thirty-nine patients reported that they resumed casual sports activity after 6 months. One patient had a slight anchor cut-out, due to an addition injury, which was removed after 5 months. CONCLUSIONS: An all-inside Endo-SARLS technique showed promising clinical results for acute Achilles tendon ruptures. This procedure reduces the risk of sural nerve injuries while establishing a reliable connection between the tendon stumps. LEVEL OF EVIDENCE: Level IV.

Knee osteoarthritis pendulum therapy: In vivo evaluation and a randomised, single-blind feasibility clinical trial.

Background: Exercise is recommended as the first-line management for knee osteoarthritis (KOA); however, it is difficult to determine which specific exercises are more effective. This study aimed to explore the potential mechanism and effectiveness of a leg-swinging exercise practiced in China, called 'KOA pendulum therapy' (KOAPT). Intraarticular hydrostatic and dynamic pressure (IHDP) are suggested to partially explain the signs and symptoms of KOA. As such this paper set out to explore this mechanism in vivo in minipigs and in human volunteers alongside a feasibility clinical trial. The objective of this study is 1) to analyze the effect of KOAPT on local mechanical and circulation environment of the knee in experimental animals and healthy volunteers; and 2) to test if it is feasible to run a large sample, randomized/single blind clinical trial. Methods: IHDP of the knee was measured in ten minipigs and ten volunteers (five healthy and five KOA patients). The effect of leg swinging on synovial blood flow and synovial fluid content depletion in minipigs were also measured. Fifty KOA patients were randomly divided into two groups for a feasibility clinical trial. One group performed KOAPT (targeting 1000 swings/leg/day), and the other performed walking exercise (targeting 4000 steps/day) for 12 weeks with 12 weeks of follow-up. Results: The results showed dynamic intra-articular pressure changes in the knee joint, increases in local blood flow, and depletion of synovial fluid contents during pendulum leg swinging in minipigs. The intra-articular pressure in healthy human knee joints was -11.32 ± 0.21 (cmH2O), whereas in KOA patients, it was -3.52 ± 0.34 (cmH2O). Measures were completed by 100% of participants in all groups with 95-98% adherence to training in both groups in the feasibility clinical trial. There were significant decreases in the Oxford knee score in both KOAPT and walking groups after intervention (p < 0.01), but no significant differences between the two groups. Conclusion: We conclude that KOAPT exhibited potential as an intervention to improve symptoms of KOA possibly through a mechanism of normalising mechanical pressure in the knee; however, optimisation of the method, longer-term intervention and a large sample randomized-single blind clinical trial with a minimal 524 cases are needed to demonstrate whether there is any superior benefit over other exercises. The translational potential of this article: The research aimed to investigate the effect of an ancient leg-swinging exercise on knee osteoarthritis. A minipig animal model was used to establish the potential mechanism underlying the exercise of knee osteoarthritis pendulum therapy, followed by a randomised, single-blind feasibility clinical trial in comparison with a commonly-practised walking exercise regimen. Based on the results of the feasibility trial, a large sample clinical trial is proposed for future research, in order to develop an effective exercise therapy for KOA.

SMEK1 ablation promotes glucose uptake and improves obesity-related metabolic dysfunction via AMPK signaling pathway.

Obesity has become a major risk of global public health. SMEK1 is also known as a regulatory subunit of protein phosphatase 4 (PP4). Both PP4 and SMEK1 have been clarified in many metabolic functions, including the regulation of hepatic gluconeogenesis and glucose transporter gene expression in yeast. Whether SMEK1 participates in obesity and the broader metabolic role in mammals is unknown. Thus, we investigated the function of SMEK1 in white adipose tissue and glucose uptake. GWAS/GEPIA/GEO database was used to analyze the correlation between SMEK1 and metabolic phenotypes/lipid metabolism-related genes/obesity. Smek1 KO mice were generated to identify the role of SMEK1 in obesity and glucose homeostasis. Cell culture and differentiation of stromal-vascular fractions (SVFs) and 3T3-L1 were used to determine the mechanism. 2-NBDG was used to measure the glucose uptake. Compound C was used to confirm the role of AMPK. We elucidated that SMEK1 was correlated with obesity and adipogenesis. Smek1 deletion enhanced adipogenesis in both SVFs and 3T3-L1. Smek1 KO protected mice from obesity and had protective effects on metabolic disorders, including insulin resistance and inflammation. Smek1 KO mice had lower levels of fasting serum glucose. We found that SMEK1 ablation promoted glucose uptake by increasing p-AMPKα(T172) and the transcription of Glut4 when the effect on AMPK-regulated glucose uptake was due to the PP4 catalytic subunits (PPP4C). Our findings reveal a novel role of SMEK1 in obesity and glucose homeostasis, providing a potential new therapeutic target for obesity and metabolic dysfunction.NEW & NOTEWORTHY Our study clarified the relationship between SMEK1 and obesity for the first time and validated the conclusion in multiple ways by combining available data from public databases, human samples, and animal models. In addition, we clarified the role of SMEK1 in glucose uptake, providing an in-depth interpretation for the study of its function in glucose metabolism.

Retrograde Drilling and Bone Graft for Hepple Stage V Subchondral Bone Lesion of Talus Using 3D Image-Based Navigation-Assisted Endoscopic Technique.

BACKGROUND: Retrograde drilling remains technically challenging, because of the difficulty of identifying the accurate location of cysts during surgery. This study's aim was to evaluate the 3-dimensional (3D) image-based surgical navigation-assisted endoscopic retrograde drilling technique for subchondral bone lesions of the talus. METHODS: From March 2017 to June 2020, a total of 21 cases with Hepple stage V subchondral bone lesions of the talus were treated with 3D image-based surgical navigation-assisted endoscopic retrograde drilling and bone graft technique. Arthroscopic views were categorized per Pritsch classifications. The correlation between the drilled tunnel with preoperative cystic lesions were assessed under postoperative computer tomographic (CT) scans. The American Orthopaedic Foot & Ankle Society (AOFAS) scores, visual analog scale (VAS) scores, and Foot and Ankle Ability Measure (FAAM) sports scales were evaluated at the preoperative and final consultation. All complications were recorded. RESULTS: On postoperative CT scans, in 20 cases (95.2%), the drilled tunnel was judged to have been in the center of previous cysts. Only 9 cases (42.9%) showed intact normal cartilage (grade 0, group A); 12 cases (57.1%) had intact, but soft, cartilage (grade I, group B). The median follow-up time was 24 (24, 30) months, and at final follow-up, there were no significant differences between the mean AOFAS and VAS scores in both groups (89.0 ± 6.4 vs 88.3 ± 7.0 and 1 vs 0.5) or postoperative FAAM sports scales (28.2 ± 2.2 vs 26.6 ± 4.9, P = .363). Two patients had revision surgery in group B. CONCLUSION: The 3D image-based surgical navigation-assisted endoscopic retrograde drilling and bone graft technique for the subchondral bone lesions of the talus in this small case series showed encouraging results. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Correlation between the Coaptation and Regeneration of Tendon Stumps in Endoscopic Assisted Achilles Tendon Rupture Repair.

OBJECTIVE: When the endoscopic Achilles tendon repair technique is utilized, direct stitching of the ruptured site is challenging due to the frayed tendon stumps. To explore whether undesirable coaptation of the tendon stumps influences the generation of the tendons. METHODS: This study is a retrospective analysis of 46 patients who underwent a modified endoscopic Achilles tendon rupture repair from October 2018 to June 2020. Patients were divided into two groups according to the coaptation of tendon stumps on postoperative ultrasonography. Group 1 included 17 cases with undesirable coaptation (<50%), and Group 2 included 29 cases with appropriate coaptation (≥50%). Magnetic resonance imaging (MRI) was obtained postoperatively at 3, 6, and 12 months to evaluate the tendon morphological construction. Clinical evaluations were performed using the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hind foot score, the Achilles Tendon Total Rupture Score (ATRS), muscle power, and the Achilles tendon resting angle at the final follow-up. Complications were also encountered. The Student's t-test and the Mann-Whitney U-test were used to assess differences among both groups. RESULTS: The mean follow-up time was 37.5 ± 10.6 months in Group 1 and 39.0 ± 11.6 months in Group 2, respectively. The average age in Group 1 is slightly older than in Group 2 (37.3 ± 6.1 vs. 32.7 ± 6.3, p = 0.021). The tendon cross-section areas and thickness increased initially and decreased later on postoperative MRI evaluation. It also showed a significantly higher signal/noise quotient (SNQ) in Group 1 at postoperative 3 months. At postoperative 6 and 12 months, the SNQ between both groups was similar. The AOFAS score (95.9 ± 5.1 vs. 96.2 ± 4.9, p = 0.832), ATRS score (97.0 ± 3.6 vs. 97.7 ± 3.3, p = 0.527), and muscle power (21.38 vs. 24.74, p = 0.287) were not significantly different between both groups. However, the resting angle of Group 1 was significantly larger than that of Group 2 (4.6 ± 2.4 vs. 2.4 ± 2.3, p = 0.004). There was no difference in the complications (p = 0.628). CONCLUSION: Although complete regeneration can be finally achieved, the early stage of tendon stump regeneration can be prolonged due to undesirable coaptation when endoscopic Achilles tendon repair technique is applied. The prolonged high signal duration on MRI indicates the less-than-ideal regeneration of the tendon, which might lead to elongation of the tendon.

Modified classifications and surgical decision-making process for chronic anterior talofibular ligament injuries based on the correlation of imaging studies and arthroscopic findings.

PURPOSE: Surgical treatment of chronic ankle instability (CAI) typically includes ligament repair or reconstruction. Using preoperative ultrasonography or magnetic resonance imaging (MRI) to choose an appropriate arthroscopic procedure is still difficult. The aim of this study was to evaluate the correlation of imaging studies with arthroscopic findings and support the arthroscopic surgical decision-making process. METHODS: One hundred twelve patients with chronic anterior talofibular ligament (ATFL) injuries were treated using the arthroscopic surgical decision-making process from November 2018 to August 2020. Preoperative imaging assessments using dynamic ultrasonography, MRI, and combined methods were applied to categorize the ATFL remnants into three quality grades ("good," "fair," and "poor"). Arthroscopic findings were classified into 6 major types (7 subtypes) and used to select an appropriate surgical procedure. Correlations between imaging studies, arthroscopic findings, and surgical methods were evaluated. Diagnostic parameters, clinical outcomes, and complications were also assessed. RESULTS: There was a significant interobserver agreement in the evaluation of dynamic ultrasonography (0.954, P < 0.001), MRI (0.958, P < 0.001), and arthroscopy diagnosis (0.978, P < 0.001). There was a significant correlation between the modified imaging classifications, arthroscopic diagnostic types, and surgical procedures. The mean follow-up period was 33.58 ± 8.85 months. Significant improvements were documented in postoperative ankle functions when assessed with Karlson-Peterson scores and Cumberland Ankle Instability Tool scores. The risk of complications is also very low. CONCLUSION: The modified classifications and surgical decision-making process based on dynamic ultrasonography, MRI, and arthroscopic findings, as proposed in this study, might help in selecting an appropriate arthroscopic surgical procedure for chronic ATFL injuries.

Arthro-Broström with endoscopic retinaculum augmentation using all-inside lasso-loop stitch techniques.

BACKGROUND: There is still some controversy about the augmentation of the inferior extensor retinaculum after arthroscopic anterior talofibular ligament repair. The aim of this study was to evaluate the novel arthro-Broström procedure with endoscopic retinaculum augmentation using all-inside lasso-loop stitch techniques for chronic lateral ankle instability. METHODS: Thirty-four cases with grade-2 or grade-3 chronic anterior talofibular ligament lesions who underwent the novel arthro-Broström procedure with endoscopic retinaculum augmentation using all-inside lasso-loop stitch techniques were assessed retrospectively. A total of 30 cases (30 ankles) were followed up for a mean of 26.67 ± 4.19 months (range, 24-36 months). four cases were excluded due to insufficient medical records or loss of follow-up reports. The Cumberland Ankle Instability Tool scores, The Karlsson-Peterson scores and Visual Analogue Scale scores were evaluated before surgery and at the final follow-up time. Also, the results of stress fluoroscopic tests and complications were recorded. RESULTS: At the final follow-up, the average of the Cumberland Ankle Instability Tool scores, The Karlsson-Peterson scores and Visual Analogue Scale scores were 86.63 ± 6.69 (range, 77-100), 90.17 ± 4.64 (range, 85-100) and 0.53 ± 0.63 (range, 0-2), respectively. Moreover, the results of stress fluoroscopic tests were improved significantly after surgery. Mild keloid formation and/or knot irritation were observed in four cases. No wound infections, nerve injuries and recurrent instability were recorded. Also, no stiffness or arthritis of the subtalar joint was encountered. CONCLUSIONS: The arthro-Broström procedure combined with endoscopic retinaculum augmentation using all-inside lasso-loop techniques is reliable and safe due to the advantage of direct endoscopic visualization.

Ppp4r3a deficiency leads to depression-like behaviors in mice by modulating the synthesis of synaptic proteins.

Chronic stress is one of the main risk factors for the onset of major depressive disorder. Chronic unpredictable mild stress results in reduced expression of synaptic proteins and depression-like behaviors in rodent models. However, the upstream molecule that senses the demand for synaptic proteins and initiates their synthesis under chronic stress remains unknown. In this study, chronic unpredictable mild stress reduced the expression of PPP4R3A in the prefrontal cortex and hippocampus in mice. Selective knockout of Ppp4r3a in the cortex and hippocampus mimicked the depression- and anxiety-like behavioral effects of chronic stress in mice. Notably, Ppp4r3a deficiency led to downregulated mTORC1 signaling, which resulted in reduced synthesis of synaptic proteins and impaired synaptic functions. By contrast, overexpression of Ppp4r3a in the cortex and hippocampus protected against behavioral and synaptic deficits induced by chronic stress in a PPP4R3A-mTORC1-dependent manner. Rapamycin treatment of Ppp4r3a-overexpressing neurons blocked the regulatory effect of Ppp4r3a on the synthesis of synaptic proteins by directly inhibiting mTORC1. Overall, our results reveal a regulatory role of Ppp4r3a in driving synaptic protein synthesis in chronic stress.

Arthroscopic Suture-Bridge Repair Technique for an Avulsion of the Talar Insertion of the Anterior Talofibular Ligament.

There are several studies about arthroscopic repair techniques for the lesion of the anterior talofibular ligament. However, the research concentrating on the avulsion of the talar insertion of the anterior talofibular ligament is very rare. Among 122 patients who suffered from recurrent ankle sprain and underwent arthroscopic anterior talofibular ligament repair from October 2016 to January 2019 in our hospital, 11 patients with an avulsion of the talar insertion of this ligament were diagnosed and then treated with the arthroscopic suture-bridge repair technique in the present study. The clinical outcomes were assessed using the Karlsson-Peterson score, Ankle and hindfoot score by American Orthopedic of Foot and Ankle Society, Sefton articular stability scale and Visual Analogue Scale. The complications were recorded at the time of observation. The median value of the follow-up time was 30 (range 18-36) months. At the final follow-up, the median value of the Karlsson-Peterson score, American Orthopedic of Foot and Ankle Society ankle-hindfoot score, and Visual Analogue Scale score was 90, 90, 1, respectively. Based on the Sefton stability scale, 10 cases were in the excellent or good category. No wound infections and no neurovascular injuries were encountered, also no case required revision surgery. Only 1 patient complained about mild local irritation at the knotless anchor site. The arthroscopic suture-bridge technique could be suitable for treatment of an avulsion of the talar insertion of the anterior talofibular ligament due to satisfactory activity recovery and few complications.

Long non-coding RNA KCNQ1OT1 overexpression promotes osteogenic differentiation of staphylococcus aureus-infected human bone mesenchymal stem cells by sponging microRNA miR-29b-3p.

Osteomyelitis (OM) is an orthopedic disease caused by bone infections in the bone cortex, bone marrow, periosteum, and surrounding soft tissues. Recent studies have implicated non-coding RNAs (ncRNAs) in the development of OM. However, little is known about the role of ncRNAs in the osteogenic differentiation during bone infection. In the present study, we investigated the role of KCNQ1OT1/miR-29b-3p axis in osteogenic differentiation in staphylococcus aureus (SpA)-infected human bone mesenchymal stem cells (hBMSCs). We first examined the expression of lncRNA KCNQ1OT1 and miR-29b-3p in the serum samples of OM patients and healthy controls. We also infected hBMSCs with different concentrations of SpA and studied the osteogenic differentiation after infection. Our results revealed that KCNQ1OT1 was downregulated while miR-29b-3p was upregulated in the serum samples of OM patients, as well as in SpA-infected hBMSCs. Overexpression of KCNQ1OT1 ameliorated the damage in hBMSCs caused by SpA infection. KCNQ1OT1 could support hBMSCs osteogenic differentiation by enhancing ALP activity, alizarin red S accumulation, expressions of osteogenic markers, and attenuating inflammatory responses after SpA infection. We further showed that miR-29b-3p was a downstream target of KCNQ1OT1, mediating the osteogenic differentiation of hBMSCs during SpA infection. Our data suggest that KCNQ1OT1 could ameliorate the SpA-induced suppression of osteogenic differentiation in hBMSCs by sponging miR-29b-3p. Modulating KCNQ1OT1 expression may serve as a strategy to ameliorate osteomyelitis.

Absorbable suture anchor and knotless anchor techniques produced similar outcomes in arthroscopic anterior talofibular ligament repair.

PURPOSE: The purpose of this study is to compare absorbable suture anchor with knotless anchor techniques for arthroscopic anterior talofibular ligament (ATFL) repair. METHOD: A multicenter retrospective study was performed with 185 patients, who had undergone an arthroscopic ATFL repair procedure using absorbable suture anchor or knotless anchor between May 2017 and October 2019. The follow-up time was a minimum of 18 months. Karlsson-Peterson score, visual analogue scale (VAS), and Cumberland ankle instability tool (CAIT) were evaluated. The complications were also recorded. RESULTS: One hundred and seven patients underwent one absorbable suture anchor repair procedure (Group A [A]), and the other seventy-eight patients underwent one knotless anchor repair procedure (Group B [B]). At the final follow-up, both Karlsson-Peterson score (A, pre 61.0 ± 8.0 vs post 93.5 ± 5.3, P < 0.001; B, pre 59.5 ± 8.2 vs post 92.4 ± 6.3, P < 0.001), VAS score (A, pre 5.0 ± 1.3 vs post 0.5 ± 0.7, P < 0.001; B, pre 5.5 ± 1.2 vs post 0.9 ± 1.0, P < 0.001), and CAIT score (A, pre 53.1 ± 12.0 vs post 93.1 ± 6.6, P < 0.001; B, pre 51.6 ± 12.0 vs post 93.1 ± 6.5, P < 0.001) improved significantly in both groups. There was no significant difference between the two groups regarding the Karlsson-Peterson score (A, pre 61.0 ± 8.0 vs B, pre 59.5 ± 8.2, n.s; A, post 93.5 ± 5.3 vs B, post 92.4 ± 6.3, n.s), CAIT score (A, pre 53.1 ± 12.0 vs B, pre 51.6 ± 12.0, n.s; A, post 93.1 ± 6.6 vs B, post 93.1 ± 6.5, n.s) and the change ranges of VAS (A, 4.5 ± 1.0 vs B, 4.6 ± 1.2, n.s). Anchor complications were easier to occur in Group B (0/107 vs 6/78, P = 0.007). Knot irritation slightly increased in Group A (10/107 vs 0/78, P = 0.006). No significant difference was found regarding total complication rates (A, 10/107 vs B, 6/78, n.s). CONCLUSION: Absorbable suture anchor and knotless anchor for arthroscopic ATFL repair produced similar clinical outcomes. The ankle stability scores increased significantly in both groups. However, the knotless anchor has a higher risk to loosen, deviated direction or break, while the absorbable suture anchor still has a slim chance of knot irritation. LEVEL OF EVIDENCE: III.

Aerosol Analysis Using Handheld Raman Spectrometer: On-site Quantification of Trace Crystalline Silica in Workplace Atmospheres.

A method for aerosol chemical analysis using handheld Raman spectrometer has been developed and its application to measurement of crystalline silica concentration in workplace atmosphere is described. The approach involves collecting aerosol as a spot sample using a wearable optical aerosol monitor, followed by direct-on-filter quantitative analysis of the spot sample for crystalline silica using handheld Raman spectrometer. The filter cassette of a commercially available optical aerosol monitor (designed to collect aerosol for post-shift analysis) was modified to collect 1.5-mm-diameter spot sample, which provided adequate detection limits for short-term measurements over a few tens of minutes or hours. The method was calibrated using aerosolized α-quartz standard reference material in the laboratory. Two Raman spectrometers were evaluated, one a handheld unit (weighing less than 410 g) and the other a larger probe-based field-portable unit (weighing about 5 kg). The lowest limit of quantification for α-quartz of 16.6 µg m-3 was obtained using the handheld Raman unit at a sample collection time of 1 h at 0.4 l min-1. Short-term measurement capability and sensitivity of the Raman method were demonstrated using a transient simulated workplace aerosol. Workplace air and personal breathing zone concentrations of crystalline silica of workers at a hydraulic fracturing worksite were measured using the Raman method. The measurements showed good agreement with the co-located samples analyzed using the standard X-ray powder diffraction (XRD) method, agreeing within 0.15-23.2% of each other. This magnitude of difference was comparable to the inter- and intra-laboratory analytical precision of established XRD and infrared methods. The pilot study shows that for silica-containing materials studied in this work it is possible to obtain quantitative measurements with good analytical figures of merit using handheld or portable Raman spectrometers. Further studies will be needed to assess matrix interferences and measurement uncertainty for several other types of particle matrices to assess the broader applicability of the method.

Fully Intra-articular Lasso-Loop Stitch Technique for Arthroscopic Anterior Talofibular Ligament Repair.

BACKGROUND: Arthroscopic techniques have gradually become popular for anterior talofibular ligament (ATFL) repair. However, the reliability of the repair and the risk of nerve injuries are of concern. The aim of this study was to evaluate the fully intra-articular lasso-loop stitch technique for arthroscopic ATFL repair. METHODS: From October 2018 to December 2019, 43 cases with chronic lateral ankle instability were treated with this fully intra-articular lasso-loop stitch technique using the Arthro-Pierce instrument. The Karlsson-Peterson score, Cumberland Ankle Instability Tool (CAIT) score, visual analog scale (VAS) score, anterior drawer and talar tilt stress fluoroscopy were evaluated at the preoperative and final follow-up appointments, respectively. All surgical complications were also recorded. RESULTS: A total of 39 cases were followed up for a mean of 28.23 ± 3.64 months (range, 23-34 months). At the final follow-up, the averages of the Karlsson-Peterson, CAIT and VAS scores were 90.26 ± 6.58, 88.56 ± 7.21 and 0.79 ± 1.06, respectively. During surgery, 2 cases were modified with augmentation of the inferior extensor retinaculum. No nerve injuries were encountered. Only 1 female complained about mild knot irritation. A 25-year-old solider required revision surgery due to an accidental injury. CONCLUSION: We found the fully intra-articular lasso-loop stitch technique for ATFL repair using the Arthro-Pierce instrument to be reliable and safe with a sufficient and good-quality ligament remnant. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Deficiency in WDFY4 reduces the number of CD8+ T cells via reactive oxygen species-induced apoptosis.

WDFY4 (WD repeat and FYVE domain-containing 4) is a susceptibility gene involved in several autoimmune diseases and plays an important role in the immune system. However, it is not clear how WDFY4 affects T cells. We have generated a Wdfy4-knockout mouse and found that selective deficiency of Wdfy4 in T cells led to a reduction in the number of CD8+ T cells in the periphery, thus promoting tumor growth when mice were challenged with a transplantable tumor. Moreover, conditional ablation of Wdfy4 in T cells enhanced the apoptosis of CD8+ T cells and increased the intracellular levels of reactive oxygen species accompanied by the upregulation of Nox2. Mechanistically, the decrease in the CD8+ T-cell numbers in Wdfy4-knockout mice was associated with activation of the p53 pathway and inhibition of the extracellular signal-regulated kinase pathway. In addition, WDFY4 participated in cell proliferation. In conclusion, our results elucidate the biological role of WDFY4 in apoptosis and establish a link between WDFY4 and T cells.

Modified mini-incision "internal splinting" versus percutaneous repair technique of acute Achilles tendon rupture: five year retrospective case-controlled study.

PURPOSE: Several kinds of minimally invasive surgical techniques are applied to acute Achilles tendon rupture. The risks of sural never injury and re-ruptures are still major issues. The purpose of this study was to compare the middle-term results of two different minimally invasive repair techniques for acute Achille tendon rupture. METHODS: Twenty-four cases underwent the modified mini-incision "internal splinting" repair technique in group A, and 29 cases underwent a percutaneous repair technique in group B and were evaluated. The intra-operative data, complications, the time of recovery, and the post-operative magnetic resonance imaging were analyzed. At the final follow-up, the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Thermann score were evaluated. RESULTS: The mean follow-up time was 59.96 ± 4.16 months (range 48-67). At the final follow-up, the AOFAS score and Thermann score in both groups had similar feedback. No nerve injury, infection, or re-rupture was encountered in group A, except two cases with anchor irritation. One case with sural nerve injury and one with a re-rupture were recorded in group B, respectively. The final MRI showed thicker regeneration of the tendon in both groups. CONCLUSIONS: The middle-term results indicated the modified mini-incision "internal splinting" technique for acute Achilles tendon rupture is similar to the percutaneous repair technique. A lower risk of sural nerve injury and re-rupture may be advantages.

Lack of WDFY4 Aggravates Ovalbumin-Induced Asthma via Enhanced Th2 Cell Differentiation.

BACKGROUND: Asthma is a chronic inflammatory airway disease, and Th2 cells play an important role in asthma. WDFY4 (WDFY family member 4) is a susceptibility gene in several autoimmune diseases. OBJECTIVE: In this study, the roles of WDFY4 in Th2 cell differentiation and Th2-dependent asthma were investigated. METHODS: Naïve CD4+ T cells were isolated from wild-type and WDFY4-deficient mice and induced to differentiate in vitro. Subsequently, a mouse model of asthma was established by sensitization with ovalbumin. RESULTS: Study results showed that WDFY4 deficiency could promote the differentiation of Th2 cells and the production of Th2 cytokines. WDFY4-deficient asthmatic mice showed higher levels of Th2 cytokines in the lungs and bronchoalveolar lavage fluid than wild-type mice. Moreover, infiltration of inflammatory cells, hyperplasia of goblet cells, production of mucus, and deposition of collagen were enhanced in WDFY4-deficient asthmatic mice. CONCLUSIONS: Our study demonstrates the pivotal role of WDFY4 in the pathogenesis of asthma and in Th2 cell differentiation.

Using arthroscopy combined with fluoroscopic technique for accurate location of the bone tunnel entrance in chronic ankle instability treatment.

BACKGROUND: Minimally invasive reconstruction techniques are used for anatomical ligament construction of the lateral collateral ligament complex of the ankle, but the two key elements, the bone tunnel and the appropriate graft tension, for the identification of the anatomic location during the surgery are not clearly stated. METHODS: The patients with chronic ankle instability who received arthroscopic anatomic lateral ligament complex reconstruction were retrospectively analyzed. The anatomical location of the bone tunnel was performed under arthroscopy combined with fluoroscopy for accurate location of the bone tunnel entrance. The graft tension and routing were controlled under arthroscopic visualization. The clinical outcomes were assessed using the Karlsson-Peterson score, Sefton articular stability scale, and Visual Analogue Scale (VAS). The complications were recorded during the follow-up. RESULTS: A total of 18 patients were enrolled in this study. The mean follow-up was 33.33 ± 3.69 (range from 24 to 36) months. No patient had recurrence of ankle instability after the operation. According to the Sefton articular stability scale, 94.5% of the patients had excellent/good function. The mean value of the anterior drawer tests and the talar tilt angle examination were decreased. The mean of the Karlsson-Peterson score and the Visual Analogue Scale(VAS) score were both improved significantly. CONCLUSIONS: The anatomic reconstruction of the ankle lateral ligament complex to treat chronic ankle instability using the arthroscopy combined with the fluoroscopic technique could improve the clinical functions, satisfaction, and reduced pain of patients.

Nonoperative treatment of insertional Achilles tendinopathy: a systematic review.

BACKGROUND: Insertional Achilles tendinopathy is difficult to manage, and there is no definite consensus on which nonoperative treatment is superior over the others. We aim to provide a clear summary of the best available evidence for nonoperative treatment specific to insertional Achilles tendinopathy. METHODS: Literatures were searched in PubMed, Embase, and Web of Science databases from inception to October 2020. The results were evaluated independently by two reviewers and assessed against the inclusion/exclusion criteria. All included articles were assessed for methodological quality, and study characteristics were extracted. RESULTS: Twenty-three studies (containing 35 groups) were eligible for the final review. The treatments included eccentric training, extracorporeal shockwave therapy (ESWT), injections, and combined treatment. Visual analog scale (VAS), Victorian Institute of Sport Assessment-Achilles questionnaire, AOFAS, satisfaction rate, and other scales were used to assess the clinical outcome. CONCLUSION: Current evidence for nonoperative treatment specific for insertional Achilles tendinopathy favors ESWT or the combined treatment of ESWT plus eccentric exercises.

Endoscopic "internal splinting" repair technique for acute Achilles tendon rupture.

INTRODUCTION: Recently, endoscopically assisted Achilles tendon repair techniques have improved to overcome the surgical complications. However, the risk of sural nerve injury and the strength of repair are still the most concerning aspects. MATERIAL AND METHODS: Twenty three patients with acute Achilles tendon rupture were reviewed in the present study. We stitch the Achilles tendon above the ruptured site using the endoscopic locking loop suture technique, and the knotless anchor suture-bridge technique can be used to make the distal fixation of threads. The function was assessed using the muscle power (MRC0-5), ATRS scores, AOFAS ankle-hindfoot scores, and VAS scores at the final follow-up. RESULTS: The mean follow-up time was 15.74 ± 2.43 months (12-18). At the final follow-up, the average of the muscle power (MRC0-5), ATRS score, AOFAS ankle-hindfoot score, and VAS score are 4.74 ± 0.45, 97.83 ± 2.77, 96.52 ± 4.87, and 0.35 ± 0.49, respectively. Every patient returned to previous sports activity at 6 months postoperative. No wound infection and sural nerve injuries were encountered. Only one case suffers local irritation at the medial knotless anchor site. CONCLUSIONS: Endoscopic "internal splinting" repair for acute Achilles tendon rupture using locking loop stitch with suture-bridge technique leads to an expedited return to activity with a low risk of complications. LEVEL OF EVIDENCE: Level IV, case series.

A SMOC2 variant inhibits BMP signaling by competitively binding to BMPR1B and causes growth plate defects.

Endochondral ossification is the major process of long bone formation, and chondrogenesis is the final step of this process. Several studies have indicated that bone morphogenetic proteins (BMPs) are required for chondrogenesis and regulate multiple growth plate features. Abnormal BMP pathways lead to growth plate defects, resulting in osteochondrodysplasia. The SPARC-related modular calcium binding 2 (SMOC2) gene encodes an extracellular protein that is considered to be an antagonist of BMP signaling. In this study, we generated a mouse model by knocking-in the SMOC2 mutation (c.1076 T > G), which showed short-limbed dwarfism, reduced, disorganized, and hypocellular proliferative zones and expanded hypertrophic zones in tibial growth plates. To determine the underlying pathophysiological mechanism of SMOC2 mutation, we used knock-in mice to investigate the interaction between SMOC2 and the BMP-SMAD1/5/9 signaling pathway in vivo and in vitro. Eventually, we found that mutant SMOC2 could not bind to COL9A1 and HSPG. Furthermore, mutant SMOC2 inhibited BMP signaling by competitively binding to BMPR1B, which lead to defects in growth plates and short-limbed dwarfism in knock-in mice.