Transformer-Based Multilabel Deep Learning Model Is Efficient for Detecting Ankle Lateral and Medial Ligament Injuries on Magnetic Resonance Imaging and Improving Clinicians' Diagnostic Accuracy for Rotational Chronic Ankle Instability.

PURPOSE: To develop a deep learning (DL) model that can simultaneously detect lateral and medial collateral ligament injuries of the ankle, aiding in the diagnosis of chronic ankle instability (CAI), and assess its impact on clinicians' diagnostic performance. METHODS: DL models were developed and externally validated on retrospectively collected ankle magnetic resonance imaging (MRI) between April 2016 and March 2022 respectively at 3 centers. Included patients had confirmed diagnoses of CAI through arthroscopy, as well as individuals who had undergone MRI and physical examinations that ruled out ligament injuries. DL models were constructed based on a multilabel paradigm. A transformer-based multilabel DL model (AnkleNet) was developed and compared with 4 convolution neural network (CNN) models. Subsequently, a reader study was conducted to evaluate the impact of model assistance on clinicians when diagnosing challenging cases: identifying rotational CAI (RCAI). Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS: Our transformer-based model achieved AUCs of 0.910 and 0.892 for detecting lateral and medial collateral ligament injury, respectively, both of which were significantly higher than those of CNN-based models (all P < .001). In terms of further CAI diagnosis, there was a macro-average AUC of 0.870 and a balanced accuracy of 0.805. The reader study indicated that incorporation with our model significantly enhanced the diagnostic accuracy of clinicians (P = .042), particularly junior clinicians, and led to a reduction in diagnostic variability. The code of the model can be accessed at https://github.com/ChiariRay/AnkleNet. CONCLUSIONS: Our transformer-based model was able to detect lateral and medial collateral ligament injuries based on MRI and outperformed CNN-based models, demonstrating a promising performance in diagnosing CAI, especially patients with RCAI. CLINICAL RELEVANCE: Developing such an algorithm can improve the diagnostic performance of clinicians, aiding in identifying patients who would benefit from arthroscopy, such as patients with RCAI.

Mortality Benefits of Cardiac Rehabilitation in Coronary Artery Disease Are Mediated by Comprehensive Risk Factor Modification: A Retrospective Cohort Study.

BACKGROUND: Cardiac rehabilitation (CR) is a multicomponent intervention to reduce adverse outcomes from coronary artery disease, but its mechanisms are not fully understood. The aims of this study were to examine the impact of CR on survival and cardiovascular risk factors, and to determine potential mediators between CR attendance and reduced mortality. METHODS AND RESULTS: A retrospective mediation analysis was conducted among 11 196 patients referred to a 12-week CR program following an acute coronary syndrome event between 2009 and 2019. A panel of cardiovascular risk factors was assessed at a CR intake visit and repeated on CR completion. All-cause and cardiovascular mortality were ascertained via health care administrative data sets at mean 4.2-year follow-up (SD, 2.81 years). CR completion was associated with reduced all-cause (adjusted hazard ratio [HR], 0.67 [95% CI, 0.54-0.83]) and cardiovascular (adjusted HR, 0.57 [95% CI, 0.40-0.81]) mortality, as well as improved cardiorespiratory fitness, lipid profile, body composition, psychological distress, and smoking rates (P<0.001). CR attendance had an indirect effect on all-cause mortality via improved cardiorespiratory fitness (ab=-0.006 [95% CI, -0.008 to -0.003]) and via low-density lipoprotein cholesterol (ab=-0.002 [95% CI, -0.003 to -0.0003]) and had an indirect effect on cardiovascular mortality via cardiorespiratory fitness (ab=-0.007 [95% CI, -0.012 to -0.003]). CONCLUSIONS: Cardiorespiratory fitness and lipid control partly explain the mortality benefits of CR and represent important secondary prevention targets.

Identification of molecular markers for predicting the severity of heart failure after AMI: An Olink precision proteomic study.

BACKGROUND: Acute myocardial infarction (AMI) still has a high incidence of varying degrees of heart failure (HF). The aim of this study is to identify new molecular markers for predicting the severity of HF after AMI. METHODS: We analyzed demographic indicators, past medical history, clinical indicators, major adverse cardiac events (MACEs) and molecular markers in patients with different Killip classifications after AMI. Olink proteomics was used to explore new molecular markers for predicting different severity of HF after AMI. RESULTS: Neutrophil count was the independent risk factors for in-hospital MACEs. Nineteen differentially expressed proteins (DEPs) increased significantly with increasing Killip classification. Five DEPs were also found to have an AUC (95 % CI) value greater than 0.8: GDF-15, NT-pro BNP, TNF-R2, TNF-R1 and TFF3. CONCLUSIONS: Neutrophil count, GDF-15, TNF-R2, TNF-R1 and TFF3 were closely related to the Killip classification of HF after AMI, which suggests that the inflammatory response plays an important role in the severity of HF after AMI and that regulating inflammation might become a new target for controlling HF.

A case of diffuse large B-cell lymphoma with interstitial pneumonia.

This report involves a 54-year-old female patient diagnosed with diffuse large B-cell lymphoma who developed interstitial pneumonia (IP) during treatment. The patient presented to the ward with enlarged lymph nodes in the neck and was treated with the standard regimen, which included rituximab, cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (R-CDOP regimen). After 3 cycles, the treatment was assessed as effective. However, following the 4th cycle, the patient experience shortness of breath after physical activity. A repeat lung computer tomography indicated IP, which completely recovered after receiving "full coverage" treatment. Subsequently, the patient underwent 2 cycles of cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (CDOP), followed by local radiotherapy. Currently, the patient is now being followed up with regular reviews.

Arthroscopic Direct Anterior-to-Posterior Suture Suspension Fixation for the Treatment of Posterior Cruciate Ligament Tibial Avulsion Fracture.

OBJECTIVES: A posterior cruciate ligament (PCL) avulsion fracture of the tibial attachment site is a specific type of PCL injury that is difficult and unpleasant to manage. The objective of this study is to report the preliminary results of a newly developed technique: arthroscopic endobutton-suture fixation using a single tibial tunnel. METHODS: From January 2016 to January 2018, 120 patients with PCL avulsion fracture who met our criteria were recruited. Sixty cases were treated by arthroscopic direct anterior-to-posterior suture suspension fixation (endobutton-suture group), and 60 cases were treated by arthroscopic screw-suture fixation (screw-suture group). All radiographic studies were recorded. The curative effect was evaluated by the range of motion (ROM), KT-2000, International Knee Documentation Committee (IKDC) scores, Tegner activity scale, and Lysholm scoring system. For statistical analysis the Student t-test was used. RESULTS: The average follow-up duration was 24 months. Findings and difficulties in surgery are the following. The lax anterior cruciate ligament is one of the diagnostic criteria. The anatomic location of PCL avulsion fractures is deep and surrounded by nerves and vessels; thus, operating through this region is difficult. After each tunnel drilling, the debris at the edge of opening needs to be cleaned to avoid obscuring the operator's vision or wearing the sutures. In endobutton-suture group, ROM improved from 0° preoperatively to 140.0° ± 5.6° at the last follow-up (P < 0.001). The postoperative KT-2000 arthrometric data at 90 N were available for all patients. The IKDC score was 23.6 ± 2.6 and 91.4 ± 4.1 pre- and postoperatively, respectively. The Tegner score improved from 1.2 ± 0.6 to 7.3 ± 2.3 (p < 0.001). The median Lysholm knee score increased from 40.4 ± 5.2 preoperatively to 90.1 ± 10.1 postoperatively (p < 0.001). The operative time was shorter in the endobutton-suture group (p < 0.001). The Lysholm knee score in the endobutton-suture group was lower than that in the endobutton-suture group (3.1 ± 1.2 vs. 4.2 ± 1.8, p < 0.01). No significant complications were noted in the study. CONCLUSIONS: The arthroscopic direct anterior-to-posterior suture suspension fixation is a simple and reliable method that not only provides better clinical outcomes, but also fixes avulsion fragments of any size.

Attenuation of the upregulation of NF­κB and AP­1 DNA­binding activities induced by tunicamycin or hypoxia/reoxygenation in neonatal rat cardiomyocytes by SERCA2a overexpression.

The present study aimed to investigate the effects of the overexpression of sarco/endoplasmic reticulum Ca2+­ATPase (SERCA2a) on endoplasmic reticulum (ER) stress (ERS)­associated inflammation in neonatal rat cardiomyocytes (NRCMs) induced by tunicamycin (TM) or hypoxia/reoxygenation (H/R). The optimal multiplicity of infection (MOI) was 2 pfu/cell. Neonatal Sprague­Dawley rat cardiomyocytes cultured in vitro were infected with adenoviral vectors carrying SERCA2a or enhanced green fluorescent protein genes, the latter used as a control. At 48 h following gene transfer, the NRCMs were treated with TM (10 µg/ml) or subjected to H/R to induce ERS. The results of electrophoretic mobility shift assay (EMSA) revealed that overexpression of SERCA2a attenuated the upregulation of nuclear factor (NF)­κB and activator protein­1 (AP­1) DNA­binding activities induced by TM or H/R. Western blot analysis and semi­quantitative RT­PCR revealed that the overexpression of SERCA2a attenuated the activation of the inositol­requiring 1α (IRE1α) signaling pathway and ERS­associated apoptosis induced by TM. The overexpression of SERCA2a also decreased the level of phospho­p65 (Ser536) in the nucleus, as assessed by western blot analysis. However, the overexpression of SERCA2a induced the further nuclear translocation of NF­κB p65 and higher levels of tumor necrosis factor (TNF)­α transcripts in the NRCMs, indicating the occurrence of the ER overload response (EOR). Therefore, the overexpression of SERCA2a has a 'double­edged sword' effect on ERS­associated inflammation. On the one hand, it attenuates ERS and the activation of the IRE1α signaling pathway induced by TM, resulting in the attenuation of the upregulation of NF­κB and AP­1 DNA­binding activities in the nucleus, and on the other hand, it induces EOR, leading to the further nuclear translocation of NF­κB and the transcription of TNF­α. The preceding EOR may precondition the NRCMs against subsequent ERS induced by TM. Further studies using adult rat cardiomyocytes are required to prevent the interference of EOR. The findings of the present study may enhance the current understanding of the role of SERCA2a in cardiomyocytes.

Endoscopic reconstruction for chronic Achilles tendon ruptures using a hamstring tendon autograft.

BACKGROUND: To determine the safety and efficacy of endoscopic reconstruction of chronic Achilles tendon ruptures using a hamstring tendon autograft at mid-term follow-up. METHODS: We reviewed the medical records of patients with chronic Achilles tendon rupture treated surgically by endoscopic reconstruction using a hamstring tendon autograft at our institution between March 2010 and October 2015. Radiologic outcomes were assessed using pre- and postoperative magnetic resonance imaging (MRI). Functional outcomes were evaluated with the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, the Plantar Flexion Strength (PFS), the Victorian Institute of Sport Assessment-Achilles (VISA-A) scale, the Visual Analogue Scale (VAS) pain score, and the Arner-Lindholm standard. All patients achieved primary healing with no lengthening of the Achilles tendon, skin necrosis, infection, deep vein thrombosis or other complications. RESULTS: Mean follow-up period was 15 ± 3 months (range, 12-18 months). There was no Achilles tendon re-rupture. MRI examination revealed that Achilles tendon continuity was restored. Patients' mean AOFAS, PFS, and VISA-A scores were significantly higher and mean VAS pain score was significantly lower after surgery compared to before (P < 0.05). According to Arner-Lindholm standards, there were twenty (76.9%) excellent, six (23.1%) good, and zero bad outcomes. CONCLUSION: Endoscopic reconstruction utilizing a hamstring tendon autograft is a safe and efficacious option for repair of chronic Achilles tendon ruptures. Studies with larger sample sizes and a longer follow-up are required to confirm the advantage of this technique compared to open surgery.

A modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction: medium-term clinical and radiologic results comparable with open reconstruction.

BACKGROUND: The aim of this study was to compare clinical and radiologic outcomes of a modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction with traditional open reconstruction. METHODS: From January 2012 and March 2016, 60 eligible patients with chronic lateral ankle instability (CLAI) received all arthroscopic remnant-preserving reconstruction or open reconstruction of the anterior talofibular ligament and calcaneofibular ligament using semitendinosus autograft. They were divided into the arthroscopic group (n = 28) and the open group (n = 32). The American Orthopaedic Foot and Ankle Society (AOFAS),visual analog scale (VAS), and Karlsson scores and ankle range of motion (ROM) were used to evaluate clinical outcomes pre-operatively and at six and 12 months and the final follow-up of at least 24 months post-operatively, with SF-36 physical component summary (PCS) and mental component summary (MCS) scores evaluated for quality of life, and the anterior talar translation and talar tilt measurements for radiologic outcomes. RESULTS: There was no difference in pre-operative demographics between two groups (P > 0.05). At the final follow-up, the AOFAS, VAS, Karlsson, SF-36 PCS, and MCS scores improved significantly in both groups (P < 0.05). However, no significant difference was found in AOFAS (91.9 ± 6.8 vs 91.1 ± 5.5), VAS (2.7 ± 1.7 vs 2.5 ± 1.6), Karlsson (95.3 ± 6.7 vs 94.8 ± 6.5), SF-36 PCS (53.2 ± 6.1 vs 52.9 ± 5.7), and MCS scores (55.7 ± 5.8 vs 54.2 ± 5.4) between the two groups (P > 0.05). There was no significant difference in post-operative operated/non-operated ankle ROM between two groups (P > 0.05). No significant difference was observed in talar tilt angle (7.6 ± 4.1° vs 6.8 ± 3.6°) and anterior talar translation (5.8 ± 1.7 mm vs 5.7 ± 1.5 mm) between the two groups at the final follow-up (P > 0.05), although these two variables improved significantly in both groups (P < 0.05). No severe complications were encountered in both groups during the follow-up period. CONCLUSIONS: The modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction could produce excellent clinical and radiologic outcomes comparable with open reconstruction.

[Clinical analysis of autogenous tendon reconstruction under total arthroscopy in treatment of chronic Achilles tendon rupture].

OBJECTIVE: To investigate the effectiveness of autogenous tendon reconstruction under total arthroscopy in the treatment of chronic Achilles tendon rupture. METHODS: Between June 2015 and June 2018, 16 patients with chronic Achilles tendon ruptures were treated by autogenous tendon reconstruction under total arthroscopy. Of the 16 patients, 11 were males and 5 were females. Their mean age was 40.7 years (range, 21-55 years). The disease duration was 14-20 months (mean, 16.4 months). Preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score was 41.2±2.2 and the pain visual analogue scale (VAS) score was 7.9±1.2. MRI and B-ultrasonography examinations showed that the Achilles tendon was not continuous. The length of Achilles tendon defect was 5.0-10.3 cm, with an average of 5.8 cm. The rupture of the Achilles tendon happened on top of the insertion of the tendon in 4 cases and at the tendon-muscle belly connection in 12 cases. The operation time, intraoperative blood loss, hospital stay, and related complications were recorded. The AOFAS score and VAS score were used to evaluate the improvement of ankle joint function and pain. RESULTS: The average operation time was 77.2 minutes (range, 60-90 minutes). The average intraoperative blood loss was 20.5 mL (range, 15-30 mL). The average hospital stay was 7.2 days (range, 5-10 days). All incisions healed by first intention. There was no skin necrosis, infection, or deep vein thrombosis. All the patients were followed up 8-18 months, with an average of 12 months; and 10 cases were followed up more than 12 months. During the follow-up, there was no Achilles tendon re-rupture, and the symptoms of pain and heel lifting failure significantly improved. MRI reexamination showed that the continuity of Achilles tendon recovered. At 1, 3, 6, and 12 months postoperatively, AOFAS scores significantly improved and VAS scores significantly reduced, except for 1 month postoperatively, the scores at other time points were superior to that before operation, the differences were significant ( P<0.05). CONCLUSION: Autogenous tendon reconstruction under total arthroscopy in the treatment of chronic Achilles tendon rupture has the advantages of small trauma, rapid functional recovery, and satisfactory surgical efficacy.

Surgery-induced cognitive dysfunction is alleviated through triggering receptor expressed on myeloid cells 2.

Neuroinflammation plays a key role in perioperative neurocognitive disorders (PND). Increased evidences indicate that triggering receptor expressed on myeloid cells 2 (TREM2) can mitigate inflammatory response in the brain, and the aim of this study is to investigate whether TREM2 is involved in surgery-induced cognitive dysfunction in adult mice. We used adult C57BL/6 mice subjected to intramedullary fixation surgery, and found that surgery did not impair the motor ability of mice, but worsened the learning and memory function, and reduced the expression of TREM2. Meanwhile, up-regulated TREM2 expression in the brain of mice, induced by selective TREM2 agonist HSP60, significantly improved the learning and memory, alleviated the neuroinflammation, and decreased the neuronal cell apoptosis in mice. Meanwhile, TREM2-siRNA abolished the increased expression of TREM2 induced by HSP60, and reversed all the HSP60-induced beneficial effects. Therefore, our study indicated that up-regulation of TREM2 alleviated neuroinflammation and improved learning and memory function after surgery in mice.

Non-Targeted Metabolomic Profiling of Coronary Heart Disease Patients With Taohong Siwu Decoction Treatment.

Traditional Chinese medicine is one of the complementary and alternative therapies to improve the prognosis of coronary heart disease (CHD). Taohong Siwu Decoction (THSWD), a classical traditional Chinese medication that promotes blood circulation, is clinically beneficial in CHD. However, the underlying mechanism of THSWD is still unclear. To comprehensively understand the material foundation of the "blood", it is significantly important to study the differential metabolites involved in the treatment of CHD with Chinese medicinal herb promoting blood circulation in TCM theory. Hence, this study investigated the metabolic profiles of the serum in CHD patients to determine the differential metabolites between the THSWD group and the placebo group. Eleven CHD patients were recruited and divided into two groups randomly and double-blindly. Serum samples were determined by performing non-targeted ultra-performance liquid chromatography with tandem mass spectrometry-based metabolomics. Pearson's correlation analysis was used to assess the association between identified metabolites and clinical serum indexes of CHD. Based on the result, a total of 513 metabolites were found in the serum of CHD patients, of which 27, involved in 29 metabolic pathways, were significantly different between the two groups. Among the differential metabolites, THSWD upregulated succinylcarnitine in fatty acid metabolism and 5'-methylthioadenosine in cysteine and methionine metabolism compared with the placebo group. However, THSWD downregulated pelargonic acid, involved in FA metabolism; succinate, involved in the tricarboxylic acid cycle; gluconic acid, gluconolactone, and d-glucose, involved in pentose phosphate pathway; glycerophosphocholine, involved in glycerophospholipid metabolism; 8,9-dihydroxyeicosatrienoic acid (8,9-DiHETrE), l-lysine, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, indoxyl sulfate, and 3-ureidopropionate involved in amino acid metabolism compared with the placebo group. Moreover, succinylcarnitine, pelargonic acid, succinate, d-glucose, gluconic acid, l-lysine, N-alpha-acetyl-l-asparagine, 5'-methylthioadenosine, indoxyl sulfate, 8,9-DiHETrE, and 3-ureidopropionate were associated with total cholesterol or low-density lipoprotein. Succinylcarnitine, pelargonic acid, gluconolactone, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, and 5'-methylthioadenosine were associated with activated partial thromboplastin time. Our findings indicated that glycerophosphocholine, 8,9-DiHETrE, 5'-methylthioadenosine, hippurate, indoxyl sulfate, and 3-ureidopropionate might constitute the partial material foundation of the "blood" in CHD patients treated with THSWD.

Postconditioning with Calreticulin Attenuates Myocardial Ischemia/Reperfusion Injury and Improves Autophagic Flux.

BACKGROUND: Impaired autophagic flux contributes to cardiomyocyte death in ischemia/reperfusion (I/R) injury. Restoring the impaired autophagic flux by using agents may be a promising strategy that alleviates myocardial I/R injury. The present study aimed to evaluate the effect of exogenous calreticulin (CRT) postconditioning on impaired autophagic flux induced by hypoxia/reoxygenation (H/R) injury in H9c2 cells. METHODS: Rat myocardial I/R injury model was prepared. CRT postconditionging was fulfilled by an intraperitoneal injection of CRT (0.5 mg/kg body weight) 5 min before reperfusion. Hemodynamics, serum lactate dehydrogenase (LDH) activity and Cardiac troponin T (TnT) content, and infarct size were measured. The H/R injury model of H9c2 cells was prepared. CRT postconditioning was performed by adding 25 pg/mL CRT to the medium at the onset of reoxygenation. Cell death rate, lactate dehydrogenase (LDH) leakage, intracellular reactive oxygen species (ROS), and malondialdehyde (MDA) were assessed. Autophagic flux was monitored by mRFP-GFP-LC3 adenovirus infection. The number of autophagosomes and autolysosomes in cells were determined by counting the fluorescence dots. Western blot assay was used to determine the expression of autophagy-related proteins. RESULTS: CRT postconditionging improved cardiac function, reduced serum LDH activity and TnT content, and limited myocardial infarct size after myocardial I/R injury in rat. H/R induced H9c2 cells injury and autophagosomes accumulation in cells. CRT postconditioning attenuated H/R-induced cell death, LDH leakage, and the increase of intracellular ROS and MDA. Meanwhile, CRT postconditioning suppressed H/R-induced excessive formation of autophagosomes, as shown by a decrease of autophagosomes and the ratio of LC3-II/LC3-I, LC3-II, and Beclin1. It also improved H/R-induced impaired autophagosomes clearance, as shown by an increase of autolysosomes and the level of LAMP-2, and a decrease of the level of p62. CONCLUSION: These findings suggested that CRT postconditioning reduced myocardial I/R injury. CRT postconditioning also inhibited the excessive formation of autophagosomes, promoted the clearance of autophagosomes, and resorted the autophagic flux, consequently reduced the H/R injury in H9c2 cells.

Calreticulin stabilizes F-actin by acetylating actin and protects microvascular endothelial cells against microwave radiation.

AIMS: Calreticulin (CRT) is a multifunctional protein that protects endothelial cells by alleviating actin cytoskeleton injury, but the underlying mechanism remains unclear. CRT was recently identified as a novel acyltransferase; acetylation at the N-terminus of actin monomers strengthens actin polymerization. This study was undertaken to determine whether CRT protects human microvascular endothelial cells (HMECs) against microwave radiation through actin acetylation. MATERIALS AND METHODS: We prepared a eukaryotic-derived recombinant CRT and incubated the HMECs with it prior to microwave exposure. We then assessed cell injury and endothelial function, detected actin polymerization and acetylation after HMECs exposure to S-band high-power microwaves. Coimmunoprecipitation, pull-down, and ex vitro acetylation reaction were performed to determine whether actin is a novel substrate of CRT acyltransferase. Finally, we employed the mutant experiments to demonstrate the acetylation sites contributing to CRT acetyltransferase activity. KEY FINDINGS: Microwave radiation induced severe cell injury and endothelial contact dysfunction, reduced the polymerization of actin filaments, and destroyed the actin arrangement, ultimately reducing acetylated actin expression. CRT treatment upregulated actin acetylation levels, promoted polymerization, and facilitated thicker and longer F-actin stress fibre formation. Pre-incubation with CRT rescued microwave-induced cell injury, decreased actin acetylation, and rendered the actin cytoskeleton radiation-retardant. The level of acetyl-actin was positively correlated with actin polymerization. Actin was identified as a novel substrate of CRT, being acetylated mainly through the CRT P-domain at lys-206 and -207. SIGNIFICANCE: This work provides a better understanding of the underlying mechanism of CRT-induced cytoprotection, and suggests a novel therapeutic target for microwave radiation-related diseases with endothelial dysfunction.

Relationship of vitamin D receptor gene polymorphisms with susceptibility, surgical outcome and prognosis of hallux valgus in a Chinese Han population.

BACKGROUND: This study aimed to identify the relationship between the vitamin D receptor (VDR) BsmI gene polymorphism and risk factors, surgical outcome and prognosis of hallux valgus (HV). METHODS: A case-control study was performed on a cohort of 236 HV patients and 236 controls in a Chinese Han population. Detection of the VDR BsmI/G2A polymorphism was performed using restriction fragment length polymorphism-polymerase chain reaction. RESULTS: We detected a statistically significant difference in the allele distribution of the BsmI polymorphism between cases and controls (p<0.01). Significant loss of hallux valgus angle (HVA) and intermetatarsal angle (IMA) correction was only noted in patients with the bb genotype during the 2-year follow-up period (p<0.01). The average American Orthopaedic Foot and Ankle Society (AOFAS) scores at the 2-year follow-up were decreased in both groups when compared with those at the 6 month follow-up, and 1.45 points more decrease in patients with the bb genotype was observed as compared to those with the BB and Bb genotypes (p<0.0001). The average visual analogue scales (VAS) also had the tendency with more pains in the bb genotype group (p<0.0001). Furthermore, larger numbers of transfer metatarsalgia were found in patients with the bb genotype upon 2-year follow-up (p=0.049). CONCLUSIONS: We report the first candidate gene polymorphism associated with susceptibility, surgical outcome and prognosis of HV in a Chinese Han population. Moreover, development of genetically-based method to predict the surgical outcome accurately and individualized therapy for HV are warranted.

All arthroscopic remnant-preserving reconstruction of the lateral ligaments of the ankle: A biomechanical study and clinical application.

Lateral ankle sprains are one of the most common injuries in sports. Recently, arthroscopic lateral ligament reconstruction has been recently advocated, however no biomechanical studies and clinical application of this technique are available. In this biomechanical study, eighteen fresh-frozen cadaveric ankles were randomized into three groups: (1) intact anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL), (2) arthroscopic anatomic reconstruction of ATFL and CFL, and (3) all arthroscopic remnant-preserving reconstruction of ATFL and CFL. The specimens were then tested for stiffness and load to ultimate failure using a customized jig. In biomechanical test, the all arthroscopic remnant-preserving reconstruction of ATFL and CFL produced a reconstruction that could withstand loads to failure and stiffness similar to the arthroscopic anatomic reconstruction. However, both two reconstruction groups were much weaker than the intact, uninjured ATFL and CFL. Moreover, we used the technique of all arthroscopic remnant-preserving reconstruction of ATFL and CFL on 20 patients from September 2016 to September 2017. American Orthopaedic Foot and Ankle Society (AOFAS) scores and Anterior Talar Translation (ATT) were applied for statistical collection at preoperative and postoperative 12 months to evaluate clinical efficacy. The differences of the preoperative and postoperative 12 months AOFAS scores and ATT of patients were both statistical significant (P < 0.01). We confirmed that all arthroscopic remnant-preserving reconstruction of ATFL and CFL exhibited positive effect, thus promoting the recovery of ankle function and had good short-term clinical effect.

Zedoarondiol Attenuates Endothelial Cells Injury Induced by Oxidized Low-Density Lipoprotein via Nrf2 Activation.

BACKGROUND/AIMS: Zedoarondiol, a sesquiterpene lactone compound, showed an anti-proliferative activity on vascular smooth muscle cells in our previous study. However, whether it has a beneficial effect on endothelial cells injury induced by oxidized low-density lipoprotein (ox-LDL) remains unclear. This study was designed to investigate the protective effect of zedoarondiol on ox-LDL-induced injury of endothelial cells and explored its underlying mechanism. METHODS: The protective effect of zedoarondiol on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) injury were evaluated by Cell Counting Kit-8 (CCK-8) assay and released lactic dehydrogenase (LDH) activity assay. Oxidative stress was determined by malonedialdehyde (MDA) content and superoxide dismutase (SOD) activity. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The culture supernatant was collected for enzyme linked immune-sorbent assays (ELISA) of interleukine-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Immunofluorescence staining was used to observe NF-E2-related factor 2 (Nrf2) translocation. Western blotting was performed to determine the expression of IL-1ß, TNF-α, MCP-1, Kelch-like ECH associated protein 1 (Keap1), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and Nrf2. RESULTS: Zedoarondiol attenuated HUVECs injury, up-regulated SOD activity, suppressed formation of MDA and ROS, and secretion and protein expression of IL-1ß, TNF-α, and MCP-1 in injured HUVECs induced by ox-LDL. Zedoarondiol induced nuclear Nrf2 translocation from cytoplasm into nucleus and up-regulated expression of HO-1, NQO1, and Nrf2 in nucleus. All-trans-retinoic acid (ATRA), an inhibitor of Nrf2, abolished zedoarondiol-mediated anti-oxidative effect. CONCLUSION: Zedoarondiol attenuates ox-LDL-induced endothelial cells injury by inhibiting oxidative stress and inflammation via Nrf2/HO-1 pathway, suggesting that zedoarondiol might be meaningful on prevention and treatment of atherosclerosis.

Association of Vitamin D Receptor Gene TaqI, BsmI, FokI, and ApaI Polymorphisms and Susceptibility to Hallux Valgus in the Chinese Population.

Previous studies have indicated that vitamin D receptor (VDR) TaqI, BsmI, FokI and ApaI gene polymorphisms are associated with the risk of skeletal malformations with inflammation. However, the potential association of VDR gene polymorphisms with the susceptibility to hallux valgus remains unclear. To clarify this association, we compared the genotypes of 228 patients with hallux valgus with those of 200 controls using the Multiplex SNaPshot system. The χ2 test was used to compare the allele and genotype frequencies between groups, and p ≤ .05 was considered statistically significant. The frequencies of the mutant allele C in TaqI (p= .036; odds ratio [OR] 1.57; 95% confidence interval [CI] 1.03-2.39) and mutant allele A in BsmI (p= .036; OR 1.33; 95% CI 1.02-1.74) were significantly greater in the patients than in the controls. In addition, after adjusting for sex and age, TaqI (p= .047; OR 1.61; 95% CI 1.00-2.58) and BsmI (p= .025; OR 1.67; 95% CI 1.06-2.61) were associated with the risk of hallux valgus through a dominant genetic model. A homozygous genetic model of BsmI was also significantly associated with the risk of hallux valgus (p= .033; OR 1.81; 95% CI 1.05-2.57). However, neither ApaI nor FokI were associated with increased susceptibility. To the best of our knowledge, we have reported for the first time that VDR gene TaqI and BsmI polymorphisms might contribute to the increased risk of hallux valgus in Chinese population.

Comparison of distraction arthroplasty alone versus combined with arthroscopic microfracture in treatment of post-traumatic ankle arthritis.

BACKGROUND: This study aims to compare clinical outcomes of distraction arthroplasty alone versus combined with arthroscopic microfracture in treating post-traumatic ankle arthritis. METHODS: The study cohort consisted of 96 patients (96 ankles) who underwent distraction arthroplasty alone or combined with arthroscopic microfracture between May 2005 and April 2012. Patients were divided into the distraction group (n = 46) and the combined group (n = 50). The American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analog scale (VAS), and ankle activity score (AAS) were used to compare the clinical outcomes between groups. Arthritis severity was assessed on the radiograph. RESULTS: At the mean follow-up period of 30.8 ± 3.1 and 31.4 ± 3.6 months, respectively, no severe complications occurred and no further surgical interventions for symptomatic arthritis were required in both groups. The AOFAS scores improved significantly in the combined group than in the distraction group (59.0 ± 4.7 and 58.0 ± 4.9 preoperatively versus 85.0 ± 4.9 and 88.9 ± 5.4 at final visit, P < 0.001). The AAS scores were also significantly higher in the combined group (3.6 ± 1.1 and 3.3 ± 1.0 preoperatively versus 6.5 ± 1.1 and 7.1 ± 1.3 at final visit, P = 0.009). Pain was significantly alleviated in the combined group by the VAS scores (6.4 ± 0.9 and 6.7 ± 0.9 preoperatively versus 2.3 ± 0.8 and 2.0 ± 0.7 at final visit, P = 0.040). The combined group achieved better radiographic arthritis severity decrease than the distraction group (P = 0.012). CONCLUSIONS: Compared to distraction arthroplasty alone, distraction arthroplasty combined with arthroscopic microfracture can offer better functional recovery, pain relief, and ankle arthritis resolution for treating post-traumatic ankle arthritis.

Calreticulin attenuated microwave radiation-induced human microvascular endothelial cell injury through promoting actin acetylation and polymerization.

Recent work reveals that actin acetylation modification has been linked to different normal and disease processes and the effects associated with metabolic and environmental stressors. Herein, we highlight the effects of calreticulin on actin acetylation and cell injury induced by microwave radiation in human microvascular endothelial cell (HMEC). HMEC injury was induced by high-power microwave of different power density (10, 30, 60, 100 mW/cm2, for 6 min) with or without exogenous recombinant calreticulin. The cell injury was assessed by lactate dehydrogenase (LDH) activity and Cell Counting Kit-8 in culture medium, migration ability, intercellular junction, and cytoskeleton staining in HMEC. Western blotting analysis was used to detected calreticulin expression in cytosol and nucleus and acetylation of globular actin (G-actin). We found that HMEC injury was induced by microwave radiation in a dose-dependent manner. Pretreatment HMEC with calreticulin suppressed microwave radiation-induced LDH leakage and increased cell viability and improved microwave radiation-induced decrease in migration, intercellular junction, and cytoskeleton. Meanwhile, pretreatment HMEC with exogenous calreticulin upregulated the histone acetyltransferase activity and the acetylation level of G-actin and increased the fibrous actin (F-actin)/G-actin ratio. We conclude that exogenous calreticulin protects HMEC against microwave radiation-induced injury through promoting actin acetylation and polymerization.

Zedoarondiol Inhibits Platelet-Derived Growth Factor-Induced Vascular Smooth Muscle Cells Proliferation via Regulating AMP-Activated Protein Kinase Signaling Pathway.

BACKGROUND/AIMS: Vascular smooth muscle cells (VSMCs) proliferation contributes significantly to atherosclerosis and in-stent restenosis. Platelet-derived growth factor-BB (PDGF-BB) plays a vital role in VSMCs proliferation. Zedoarondiol, a sesquiterpene lactone compound, has an anti-inflammatory activity. However, the role of zedoarondiol in PDGF-BB-mediated VSMCs proliferation remains unclear. In this study, we investigated the effects of zedoarondiol on PDGF-BB-induced VSMCs proliferation and explored the possible mechanisms. METHODS: The inhibitory effects of zedoarondiol on PDGF-BB-induced VSMCs proliferation were evaluated by direct cell counting and the Cell Counting Kit-8 (CCK-8) assay. DNA synthesis was examined by bromodeoxyuridine (BrdU) incorporation assay. Cell cycle was assessed by propidium iodide staining. Western blotting was performed to determine the expression of cyclin-dependent kinase 2 (CDK2), cyclin E, p53, p21, total and phosphorylated adenosine monophosphate-activated protein kinase (AMPK), acetyl CoA carboxylase (ACC), mammalian target of rapamycin (mTOR), and p70 ribosomal protein S6 kinase (p70S6K). RESULTS: Zedoarondiol suppressed PDGF-BB-induced VSMCs proliferation and DNA synthesis, and induced cell cycle arrest in G0/G1 phase. In addition, zedoarondiol activated AMPK and ACC, inhibited the phosphorylation of mTOR and p70S6K, increased the expression of p53 and p21, and decreased the expression of CDK2 and cyclin E. Compound C (an AMPK inhibitor) abrogated, whereas 5-aminoimidazole-4-carboxamide 1-ß-ribofuranoside (AICAR, an AMPK activator) enhanced zedoarondiol-mediated inhibition of VSMCs proliferation and DNA synthesis. CONCLUSION: Zedoarondiol inhibits PDGF-BB-induced VSMCs proliferation via AMPK-mediated down-regulation of the mTOR/p70S6K pathway and up-regulation of the p53/p21 pathway. These findings suggest that zedoarondiol might be a promising compound against atherosclerosis and in-stent restenosis.