A slow-releasing donor of hydrogen sulfide inhibits neuronal cell death via anti-PANoptosis in rats with spinal cord ischemia‒reperfusion injury.

BACKGROUND: Spinal cord ischemia‒reperfusion injury (SCIRI) can lead to paraplegia, which leads to permanent motor function loss. It is a disastrous complication of surgery and causes tremendous socioeconomic burden. However, effective treatments for SCIRI are still lacking. PANoptosis consists of three kinds of programmed cell death, pyroptosis, apoptosis, and necroptosis, and may contribute to ischemia‒reperfusion-induced neuron death. Previous studies have demonstrated that hydrogen sulfide (H2S) exerts a neuroprotective effect in many neurodegenerative diseases. However, whether H2S is anti-PANoptosis and neuroprotective in the progression of acute SCIRI remains unclear. Thus, in this study we aimed to explore the role of H2S in SCIRI and its underlying mechanisms. METHODS: Measurements of lower limb function, neuronal activity, microglia/macrophage function histopathological examinations, and biochemical levels were performed to examine the efficacy of H2S and to further demonstrate the mechanism and treatment of SCIRI. RESULTS: The results showed that GYY4137 (a slow-releasing H2S donor) treatment attenuated the loss of Nissl bodies after SCIRI and improved the BBB score. Additionally, the number of TUNEL-positive and cleaved caspase-3-positive cells was decreased, and the upregulation of expression of cleaved caspase-8, cleaved caspase-3, Bax, and Bad and downregulation of Bcl-2 expression were reversed after GYY4137 administration. Meanwhile, both the expression and activation of p-MLKL, p-RIP1, and p-RIP3, along with the number of PI-positive and RIP3-positive neurons, were decreased in GYY4137-treated rats. Furthermore, GYY4137 administration reduced the expression of NLRP3, cleaved caspase-1 and cleaved GSDMD, decreased the colocalization NeuN/NLRP3 and Iba1/interleukin-1ß-expressing cells, and inhibited proinflammatory factors and microglia/macrophage polarization. CONCLUSIONS: H2S ameliorated spinal cord neuron loss, prevented motor dysfunction after SCIRI, and exerted a neuroprotective effect via the inhibition of PANoptosis and overactivated microglia-mediated neuroinflammation in SCIRI.

Transcriptome sequencing and bioinformatics analysis of gastrocnemius muscle in type 2 diabetes mellitus rats.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is one of the high risk factors for sarcopenia. However, the pathogenesis of diabetic sarcopenia has not been fully elucidated. This study obtained transcriptome profiles of gastrocnemius muscle in normal and T2DM rats based on high-throughput sequencing technology, which may provide new ideas for exploring the pathogenesis of diabetic sarcopenia. METHODS: Twelve adult male Sprague-Dawley rats were randomly divided into Control group and T2DM group, and gastrocnemius muscle tissue was retained for transcriptome sequencing and real-time quantitative polymerase chain reaction (qRT-PCR) 6 months later. Screening differentially expressed genes (DEGs), Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Gnomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. Six DEGs related to apoptosis were selected for qTR-PCR verification. RESULTS: Transcriptomic analysis showed that there were 1016 DEGs between the gastrocnemius muscle of T2DM and normal rats, among which 665 DEGs were up-regulated and 351 DEGs were down-regulated. GO analysis showed that the extracellular matrix organization was the most enriched in biological processes, with 26 DEGs. The extracellular matrix with 35 DEGs was the most abundant cellular component. The extracellular matrix structural constituent, with 26 DEGs, was the most enriched in molecular functions. The highest number of DEGs enriched in biological processes, cellular components and molecular functions were positive regulation of transcription by RNA polymerase II, nucleus and metal ion binding, respectively. There were 78, 230 and 89 DEGs respectively. KEGG pathway enrichment analysis showed that ECM-receptor interaction, PI3K-Akt signaling pathway and TGF-ß signaling pathway(p < 0.001) had higher enrichment degree and number of DEGs. qRT-PCR results showed that the fold change of Map3k14, Atf4, Pik3r1, Il3ra, Gadd45b and Bid were 1.95, 3.25, 2.97, 2.38, 0.43 and 3.6, respectively. The fold change of transcriptome sequencing were 3.45, 2.21, 2.59, 5.39, 0.49 and 2.78, respectively. The transcriptional trends obtained by qRT-PCR were consistent with those obtained by transcriptome sequencing. CONCLUSIONS: Transcriptomic analysis was used to obtain the "gene profiles" of gastrocnemius muscle of T2DM and normal rats. qRT-PCR verification showed that the genes related to apoptosis were differentially expressed. These DEGs and enrichment pathways may provide new ideas for exploring the pathogenesis of diabetic sarcopenia.

Effect of body mass index on 30-day complication rate and implant survival rate after simultaneous bilateral unicompartmental knee arthroplasty: a multicentre retrospective study.

OBJECTIVE: The practice of simultaneous bilateral unicompartmental knee arthroplasty (SBUKA) remains a topic of debate, particularly in patients with obesity. Thus, the purpose of this study was to assess the impact of body mass index (BMI) on the 30-day complication rate and the survival rate of the implant following SBUKA. METHODS: We retrospectively examined the clinical records of 245 patients (490 knees) who underwent SBUKA at the Affiliated Hospital of Qingdao University and the Third Hospital of Hebei Medical University between January 2010 and December 2020. Patients were categorised based on their BMI at the time of surgery into four groups: normal weight (BMI 18.5 to 22.9 kg/m2), overweight (BMI 23.0 to 24.9 kg/m2), obese (BMI 25.0 to 29.9 kg/m2), and severely obese (BMI ≥30 kg/m2). Variables such as length of hospital stay, duration of surgery, and costs of hospitalisation were compared across all groups. Additionally, we recorded the 30-day postoperative complication rate and the time from surgery to any required revision. The Kaplan-Meier survival analysis was employed to evaluate and compare the implant survival rates. RESULTS: The follow-up period for the 245 patients ranged from 39 to 114 months, with an average of 77.05±18.71 months. The incidence of complications within 30 days post-surgery did not significantly differ across the groups (χ2 = 1.102, p = 0.777). The implant survival rates from the lowest to the highest BMI groups were 97.14%, 93.9%, 94.44%, and 96.43%, respectively. Both the rate of implant revision (χ2 =1.612, p = 0.657) and the survival curves of the implants (p = 0.639) showed no statistically significant differences among the groups. CONCLUSIONS: BMI did not influence the 30-day complication rate nor the survival rate of implants following SBUKA, suggesting that SBUKA should not be contraindicated based on BMI alone.

Bio-mechanical effects of femoral neck system versus cannulated screws on treating young patients with Pauwels type III femoral neck fractures: a finite element analysis.

INTRODUCTION: As a novel internal fixation for femoral neck fractures, the femoral neck system has some advantages for young Pauwels type III femoral neck fractures without clear biomechanical effects and mechanisms. Thus, the objection of the study is to realize the biomechanical effects and mechanism of FNS cannulated screws on treating young patients with Pauwels type III femoral neck fractures compared to cannulated screws which are commonly used for femoral neck fractures by finite element analysis. METHODS: Firstly, the model of young Pauwels type III femoral neck fractures, femoral neck system (FNS), and three cannulated screws (CS) arranged in an inverted triangle were established, and the internal fixations were set up to fix young Pauwels type III femoral neck fractures. Under 2100 N load, the finite element was performed, and the deformation, peak von Mises stress (VMS), and contact at fracture segments were recorded to analyze the biomechanical effects and mechanism of FNS and three-CS fixing young Pauwels type III femoral neck fractures. RESULTS: Compared to three-CS, the deformation of the whole model, internal fixation, and fracture segments after FNS fixation were lower, and the peak VMS of the whole model and the internal fixation after FNS were higher with lower peak VMS of the distal femur and the fracture segments. With a sticking contact status, the contact pressure at fracture segments after FNS fixation was lower than that of three-CS. CONCLUSIONS: FNS can provide better mechanical effects for young patients with Pauwels type III femoral neck fractures, which may be the mechanical mechanism of the clinical effects of FNS on femoral neck fracture. Although there is high stress on FNS, it is still an effective and safe internal fixation for young patients with Pauwels type III femoral neck fractures.

A formula for instability-related bone loss: estimating glenoid width and redefining bare spot.

PURPOSE: The aim of the study reveals a new intuitive method for preoperatively assessing defect ratio in glenoid deficiency based on the native glenoid width and the bare spot. METHODS: A linear relationship, i.e. the rh formula, between the native glenoid width (2r) and height (h) was revealed by a cadaver cohort (n = 204). To validate the reliability of the rh formula, 280 3D-CT images of intact glenoids were recruited. To evaluate the accuracy of rh formula in estimating glenoid defect, the 65 anterior-inferior defect models were artificially established based on the 3D-CT images of intact glenoids. Moreover, a clinically common anterior-posterior (AP) method was compared with the rh formula, to verify the technical superiority of rh formula. RESULTS: The regression analysis indicated a linear relationship between the width and height of intact glenoid: 2r = 0.768 × h - 1.222 mm (R2 = 0.820, p < 0.001). An excellent reliability was found between the formula prediction and model width (ICC = 0.911, p = 0.266). An excellent agreement was found between the predicted values and model parameters (glenoid width, ICCrh = 0.967, prh = 0.778; defect ratio, prh = 0.572, ICCrh = 0.997). And, it is of higher accuracy compared to the AP method (glenoid width, ICCAP = 0.933, pAP = 0.001; defect ratio, ICCAP = 0.911, pAP = 0.033). CONCLUSION: Applying the cadaver-based formula on 3D-CT scans accurately predicts native glenoid width and redefines bare spot for preoperatively determining glenoid bone loss.

Dysregulation of metalloproteinases in spinal ligament degeneration.

PURPOSE: Degenerative changes in the spinal ligaments, such as hypertrophy or ossification, are important pathophysiological mechanisms of secondary spinal stenosis and neurological compression. Extracellular matrix (ECM) remodeling is one of the major pathological changes in ligament degeneration, and in this remodeling, ECM proteinase-mediated degradation of elastin and collagen plays a vital role. Zinc-dependent endopeptidases, including matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs), and ADAMs with thrombospondin-1 motifs (ADAMTSs) are key factors in ECM remodeling. This review aims to elucidate the underlying mechanisms of these metalloproteinases in the initiation and progression of spinal ligament degeneration. METHODS: We clarify current literature on the dysregulation of MMPs/ADAMs/ADAMTS and their endogenous inhibitors in degenerative spinal ligament diseases. In addition, some instructive information was excavated from the raw data of the relevant high-throughput analysis. RESULTS AND CONCLUSIONS: The dysregulation of metalloproteinases and their endogenous inhibitors may affect ligament degeneration by involving several interrelated processes, represented by ECM degradation, fibroblast proliferation, and osteogenic differentiation. Antagonists of the key targets of the processes may in turn ease ligament degeneration.

Single-cell RNA sequencing reveals differences between force application and bearing in ankle cartilage.

Chondrocytes are the major functional elements of articular cartilage. Force has been demonstrated to influence the structure and function of articular cartilage and chondrocytes. Therefore, it is necessary to evaluate chondrocytes under different force conditions to gain deep insight into chondrocyte function. Six cartilage tissues from the distal tibia (referred to as the AT group) and five cartilage tissues from the trochlear surface of the talus (referred to as the ATa group) were obtained from 6 donors who had experienced fatal accidents. Single-cell RNA sequencing was used on these samples. A total of 149,816 cells were analyzed. Nine chondrocyte subsets were ultimately identified. Pseudotime analyses, enrichment analyses, cell-cell interaction studies, and single-cell regulatory network inference and clustering were performed for each cell type, and the differences between the AT and ATa groups were analyzed. Immunohistochemical staining was used to verify the existence of each chondrocyte subset and its distribution. The results suggested that reactive oxygen species related processes were active in the force-applied region, while tissue repair processes were common in the force-bearing region. Although the number of prehypertrophic chondrocytes was small, these chondrocytes seemed to play an important role in the ankle.

A Computed Tomography Radiomics Nomogram in Differentiating Chordoma From Giant Cell Tumor in the Axial Skeleton.

OBJECTIVE: The aim of the study is to develop and validate a computed tomography (CT) radiomics nomogram for preoperatively differentiating chordoma from giant cell tumor (GCT) in the axial skeleton. METHODS: Seventy-three chordomas and 38 GCTs in axial skeleton were retrospectively included and were divided into a training cohort (n = 63) and a test cohort (n = 48). The radiomics features were extracted from CT images. A radiomics signature was developed by using the least absolute shrinkage and selection operator model, and a radiomics score (Rad-score) was acquired. By combining the Rad-score with independent clinical risk factors using multivariate logistic regression model, a radiomics nomogram was established. Calibration and receiver operator characteristic curves were used to assess the performance of the nomogram. RESULTS: Five features were selected to construct the radiomics signature. The radiomics signature showed favorable discrimination in the training cohort (area under the curve [AUC], 0.860; 95% confidence interval [CI], 0.760-0.960) and the test cohort (AUC, 0.830; 95% CI, 0.710-0.950). Age and location were the independent clinical factors. The radiomics nomogram combining the Rad-score with independent clinical factors showed good discrimination capability in the training cohort (AUC, 0.930; 95% CI, 0.880-0.990) and the test cohort (AUC, 0.980; 95% CI, 0.940-1.000) and outperformed the radiomics signature ( z = 2.768, P = 0.006) in the test cohort. CONCLUSIONS: The CT radiomics nomogram shows good predictive efficacy in differentiating chordoma from GCT in the axial skeleton, which might facilitate clinical decision making.

Deep learning radiomic nomogram to predict recurrence in soft tissue sarcoma: a multi-institutional study.

OBJECTIVES: To evaluate the performance of a deep learning radiomic nomogram (DLRN) model at predicting tumor relapse in patients with soft tissue sarcomas (STS) who underwent surgical resection. METHODS: In total, 282 patients who underwent MRI and resection for STS at three independent centers were retrospectively enrolled. In addition, 113 of the 282 patients received additional contrast-enhanced MRI scans. We separated the participants into a development cohort and an external test cohort. The development cohort consisted of patients from one center and the external test cohort consisted of patients from two other centers. Two MRI-based DLRNs for prediction of tumor relapse after resection of STS were established. We universally tested the DLRNs and compared them with other prediction models constructed by using widespread adopted predictors (i.e., staging systems and Ki67) instead of radiomics features. RESULTS: The DLRN1 model incorporated plain MRI-based radiomics signature into the clinical data, and the DLRN2 model integrated radiomics signature extracted from plain and contrast-enhanced MRI with the clinical predictors. Across both study sets, the two MRI-based DLRNs had relatively better prognostic capability (C index ≥ 0.721 and median AUC ≥ 0.746; p < 0.05 compared with most other models and predictors) and less opportunity for prediction error (integrated Brier score ≤ 0.159). The decision curve analysis indicates that the DLRNs have greater benefits than staging systems, Ki67, and other models. We selected appropriate cutoff values for the DLRNs to divide STS recurrence into three risk strata (low, medium, and high) and calculated those groups' cumulative risk rates. CONCLUSION: The DLRNs were shown to be a reliable and externally validated tool for predicting STS recurrence by comparing with other prediction models. KEY POINTS: • The prediction of a high recurrence rate of STS before emergence of local recurrence can help to determine whether more active treatment should be implemented. • Two MRI-based DLRNs for prediction of tumor relapse were shown to be a reliable and externally validated tool for predicting STS recurrence. • We used the DLRNs to divide STS recurrence into three risk strata (low, medium, and high) to facilitate more targeted postoperative management in the clinic.

Strong and tough self-wrinkling polyelectrolyte hydrogels constructed via a diffusion-complexation strategy.

Self-wrinkling hydrogels enable various engineering and biomedical applications. The major challenge is to couple the self-wrinkling technologies and enhancement strategies, so as to get rid of the poor mechanical properties of existing self-wrinkling gels. Herein we present a facile diffusion-complexation strategy for constructing strong and ultratough self-wrinkling polyelectrolyte hydrogels with programmable wrinkled structures and customizable 3D configurations. Driven by the diffusion of low-molecular-weight chitosan polycations into the polyanion hydrogels, the high-modulus polyelectrolyte complexation shells can form directly on the hydrogel surface. Meanwhile, the polyanion hydrogels deswell/shrink due to the low osmotic pressure, which applies an isotropous surface compressive stress for inducing the formation of polygonal wrinkled structures. When the diffusion-complexation reaction occurs on a pre-stretched hydrogel sheet, the long-range ordered wrinkled structures can form during the springback/recovery of the hydrogel matrix. Moreover, through controlling the regions of diffusion-complexation reaction on the pre-stretched hydrogels, they can be spontaneously transformed into various 3D configurations with ordered wrinkled structures. Notably, because of the introduction of plenty of electrostatic binding (i.e., sacrificial bonds), the as-prepared self-wrinkling gels possess outstanding mechanical properties, far superior to the reported ones. This diffusion-complexation strategy paves the way for the on-demand design of high-performance self-wrinkling hydrogels.

Ghrelin infusion into the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways.

Ghrelin is a circulating orexigenic hormone that promotes feeding behavior and regulates metabolism in humans and rodents. We previously reported that local infusion of ghrelin into the basolateral amygdala (BLA) blocked memory acquisition for conditioned taste aversion (CTA) by activating growth hormone secretagogue receptor 1a. In this study, we further explored the underlying mechanism and signaling pathways mediating ghrelin modulation of CTA memory in rats. Pharmacological agents targeting distinct signaling pathways were infused into the BLA during conditioning. We showed that preadministration of the PI3K inhibitor LY294002 abolished the repressive effect of ghrelin on CTA memory. Moreover, LY294002 pretreatment prevented ghrelin from inhibiting Arc and zif268 mRNA expression in the BLA triggered by CTA memory retrieval. Preadministration of rapamycin eliminated the repressive effect of ghrelin, while Gsk3 inhibitors failed to mimic ghrelin's effect. In addition, PLC and PKC inhibitors microinfused in the BLA blocked ghrelin's repression of CTA acquisition. These results demonstrate that ghrelin signaling in the BLA shapes CTA memory via the PI3K/Akt/mTOR and PLC/PKC pathways. We conducted in vivo multichannel recordings from mouse BLA neurons and found that microinjection of ghrelin (20 µM) suppressed intrinsic excitability. By means of whole-cell recordings from rat brain slices, we showed that bath application of ghrelin (200 nM) had no effect on basal synaptic transmission or synaptic plasticity of BLA pyramidal neurons. Together, this study reveals the mechanism underlying ghrelin-induced interference with CTA memory acquisition in rats, i.e., suppression of intrinsic excitability of BLA principal neurons via the PI3K/Akt/mTOR and PLC/PKC pathways.

Effect of body mass index on symptomatic venous thromboembolism and prosthesis revision risk after total knee arthroplasty: a long-term study from China.

OBJECTIVE: To investigate the effect of body mass index (BMI) on the risk of symptomatic VTE and prosthesis revision after total knee arthroplasty (TKA). METHODS: Seven thousand one hundred eighty-two patients with primary unilateral TKA treated in our hospital from 2011 to 2020 were divided into four groups according to BMI: BMI < 25 kg/m2, BMI 25 kg/m2-29.9 kg/m2, BMI 30 kg/m2-34.9 kg/m2 and BMI ≥ 35 kg/m2. Incidence, Odds ratio and Kaplan-Meier survival analysis were used to evaluate the effects of BMI on symptomatic VTE and prosthesis revision risk after TKA. RESULTS: The incidence of VTE after TKA was 8.9‰(64/7182). There was no significant difference in the incidence of VTE among different BMI groups(P = 0.452). Deep vein thrombosis mainly occurred in the distal lower extremities, especially in intermuscular veins. Revision rate of prosthesis after TKA was 6.4‰(46/7182). There was no significant difference in revision rate among different BMI groups(P = 0.718). In the univariate analysis of TKA, compared with patients with normal BMI, the risk of postoperative VTE and prosthesis revision in patients with overweight, obesity class I and obesity class II did not increase. Higher prosthesis revision rate and lower prosthesis survival rate were observed in BMI ≥ 35 kg/m2 group, although the difference was not statistically significant. CONCLUSIONS: Through such a retrospective large sample data of long-term follow-up, we believe that the higher BMI was not associated with the increased risk of symptomatic VTE and prosthesis revision after TKA. When TKA was used for appropriate indications, high BMI should not be considered as a contraindication.

Qualitative and Quantitative Anatomy of the Deep Radioulnar Ligaments' Insertion on Ulna: Cadaveric, Histologic, and MRI Study.

PURPOSE: To qualitatively and quantitatively analyze the anatomic features of the insertion of deep radioulnar ligaments (RULs) and provide an anatomic basis for further studies. METHODS: The anatomic features of deep RUL insertion were observed macroscopically in 26 cadaveric wrists, after which the size of the deep RUL footprint and distance from the center of the footprint to the ulnar-sided margin of articular cartilage of the ulnar head were each measured. Five specimens were analyzed histologically to examine the attachment of the RUL on the ulna. In addition, we evaluated 21 asymptomatic wrists from healthy volunteers using 3.0 T magnetic resonance imaging. RESULTS: The insertion of the deep RUL was located mainly on the radial aspect of the ulnar fovea from the foveal center to the articular cartilage. The footprint of the deep RUL appeared in 3 different shapes. The maximal width, length, and area of the footprint of the deep RUL were 3.7 (95% confidence interval [CI], 3.3-4.0) mm, 8.4 (95% CI, 7.9-8.9) mm, and 26.3 (95% CI, 23.4-29.1) mm2, respectively. Histologic analyses showed the attachment of the deep RUL on the radial wall of the fovea exhibited a direct insertion with typical 4-layer structures. The deep RUL fibers formed an acute angle with the distal component of the triangular fibrocartilage complex. CONCLUSIONS: The deep RUL was inserted on the radial side of the ulnar fovea and not the foveal center; it had direct insertion on the radial wall continuous with articular cartilage, and the fibers in the direct insertion formed an acute angle with the distal component of the triangular fibrocartilage complex. CLINICAL RELEVANCE: Understanding the quantitative anatomy of the deep RUL insertion may help guide surgeons to perform an anatomic foveal repair of the triangular fibrocartilage complex in its native footprint.

Clavicular hook plate for acute high-grade acromioclavicular dislocation involving Rockwood type V: clinical and radiological outcomes and complications evaluation.

BACKGROUND: The surgical treatment of high-grade acromioclavicular joint dislocation remains a matter of debate. Clavicular hook plate internal fixation was widely used in the treatment of acromioclavicular dislocation because of its easy-to-master surgical technique. This study aimed to evaluate outcomes using hook plate fixation for acromioclavicular dislocation. METHODS: A consecutive series of 57 patients with acute acromioclavicular joint dislocation involving Rockwood type V were treated between November 2013 and September 2019 using hook plate fixation. The functional outcomes (using the visual analogue score, Constant-Murley score, and University of California Los Angeles score), the quality of surgical reduction (using the coracoclavicular distance), and post-operative complications were assessed with about 46 months of follow-up. RESULTS: The mean Constant-Murley score increased from 72.6 before surgery to 87.6 at final follow-up. The mean University of California Los Angeles score was 14.1 pre-operatively and 31.6 at final follow-up. Meanwhile, the visual analogue scores were significantly reduced from 3.4 pre-operatively to 1.3 post-operatively. The coracoclavicular distance decreased from 19.4 mm pre-operatively to 10.9 mm at the last follow-up. Post-operative functional and radiological outcomes were significantly improved compared with pre-operative outcomes (P < 0.01). The overall excellent and good result was 35.1% (20/57) and 54.1% (31/57), respectively. At follow-up, the overall complication rate was 15.8% (9/57) including subacromial impingement (three patients), acromial osteolysis (three patients), reduction loss (one patient), acromioclavicular joint osteoarthritis (one patient), and calcification (one patient). CONCLUSION: Hook plate fixation was a viable treatment approach, and achieved good clinical outcomes in the treatment of acute acromioclavicular dislocation involving V. But some complications of hook plate fixation should not be ignored.

Development and validation of an immune gene-set based prognostic signature for soft tissue sarcoma.

BACKGROUND: Sarcomas is a group of heterogeneous malignant tumors originated from mesenchymal tissue and different types of sarcomas have disparate outcomes. The present study aims to identify the prognostic value of immune-related genes (IRGs) in sarcoma and establish a prognostic signature based on IRGs. METHODS: We collected the expression profile and clinical information of 255 soft tissue sarcoma samples from The Cancer Genome Atlas (TCGA) database and 2498 IRGs from the ImmPort database. The LASSO algorithm and Cox regression analysis were used to identify the best candidate genes and construct a signature. The prognostic ability of the signature was evaluated by ROC curves and Kaplan-Meier survival curves and validated in an independent cohort. Besides, a nomogram based on the IRGs and independent prognostic clinical variables was developed. RESULTS: A total of 19 IRGs were incorporated into the signature. In the training cohort, the AUC values of signature at 1-, 2-, and 3-years were 0.938, 0.937 and 0.935, respectively. The Kaplan-Meier survival curve indicated that high-risk patients were significantly worse prognosis (P < 0.001). In the validation cohort, the AUC values of signature at 1-, 2-, and 3-years were 0.730, 0.717 and 0.647, respectively. The Kaplan-Meier survival curve also showed significant distinct survival outcome between two risk groups. Furthermore, a nomogram based on the signature and four prognostic variables showed great accuracy in whole sarcoma patients and subgroup analyses. More importantly, the results of the TF regulatory network and immune infiltration analysis revealed the potential molecular mechanism of IRGs. CONCLUSIONS: In general, we identified and validated an IRG-based signature, which can be used as an independent prognostic signature in evaluating the prognosis of sarcoma patients and provide potential novel immunotherapy targets.

Magnetic Resonance Imaging-Based Radiomics Nomogram for Prediction of the Histopathological Grade of Soft Tissue Sarcomas: A Two-Center Study.

BACKGROUND: Preoperative prediction of soft tissue sarcoma (STS) grade is important for treatment decisions. Therefore, formulation an STS grade model is strongly needed. PURPOSE: To develop and test an magnetic resonance imaging (MRI)-based radiomics nomogram for predicting the grade of STS (low-grade vs. high grade). STUDY TYPE: Retrospective POPULATION: One hundred and eighty patients with STS confirmed by pathologic results at two independent institutions were enrolled (training set, N = 109; external validation set, N = 71). FIELD STRENGTH/SEQUENCE: Unenhanced T1-weighted (T1WI) and fat-suppressed T2-weighted images (FS-T2WI) were acquired at 1.5 T and 3.0 T. ASSESSMENT: Clinical-MRI characteristics included age, gender, tumor-node-metastasis (TNM) stage, American Joint Committee on Cancer (AJCC) stage, progression-free survival (PFS), and MRI morphological features (ie, margin). Radiomics feature extraction were performed on T1WI and FS-T2WI images by minimum redundancy maximum relevance (MRMR) method and least absolute shrinkage and selection operator (LASSO) algorithm. The selected features constructed three radiomics signatures models (RS-T1， RS-FST2, and RS-Combined). Univariate and multivariate logistic regression analysis were applied for screening significant risk factors. Radiomics nomogram was constructed by incorporating the radiomics signature and risk factors. STATISTICAL TESTS: Clinical-MRI characteristics were performed by a univariate analysis. Model performances (discrimination, calibration, and clinical usefulness) were validated in the external validation set. The RS-T1 model, RS-FST2 model, and RS-Combined model had an area under curves (AUCs) of 0.645, 0.641, and 0.829, respectively, in the external validation set. The radiomics nomogram, incorporating significant risk factors and the RS-Combined model had AUCs of 0.916 (95%CI, 0.866-0.966, training set) and 0.879 (95%CI, 0.791-0.967, external validation set), and demonstrated good calibration and good clinical utility. DATA CONCLUSION: The proposed noninvasive MRI-based radiomics models showed good performance in differentiating low-grade from high-grade STSs. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Effects of Temperature and Volume of Intraoperative Normal Saline Irrigation on Postoperative Pain, Swelling, and Serum Markers of Inflammation in Patients After Elective, Arthroscopic, Single-Bundle Surgical Reconstruction of the Anterior Cruciate Ligament: A Retrospective, Single-Center Study.

BACKGROUND Arthroscopic single-bundle surgical reconstruction of the anterior cruciate ligament (ACL) is often performed electively after 3 weeks of mobilization therapy. The present single-center retrospective study aimed to investigate the effects of temperature and volume of intraoperative normal saline irrigation on postoperative pain and swelling and on serum markers of inflammation following elective, arthroscopic, single-bundle surgical reconstruction of the ACL. MATERIAL AND METHODS Clinical data from 716 patients with non-acute ACL injuries who met the criteria between March 2015 and May 2020 were retrospectively analyzed. The patients were broken into 5 groups, depending on the volume or temperature of intraoperative irrigation with normal saline. At specific times after surgery, pain, knee swelling, and skin temperature were assessed. Postoperative levels of serum C-reactive protein (CRP), interleukin (IL)-1, IL-6, and IL-10 also were measured. RESULTS Visual analog scale (VAS) scores for pain, rates of swelling, and skin temperature differed significantly among the 5 groups at all postoperative time points (P<0.001). The VAS scores(P=0.322) and ratings for swelling (P=0.245), and skin temperature (P=0.093) were not significantly different among the volume groups. There were no significant differences in the VAS scores (P=0.055), swelling ratings (P=0.570), or skin temperatures (P=0.321) among the groups that received irrigation with normal saline at different temperatures. There were no significant differences in postoperative serum levels of CRP, IL-1, IL-6, or IL-10 among the groups (P>0.05). CONCLUSIONS Irrigation with different volumes and temperatures of normal saline did not have a significant effect on postoperative pain, swelling, or serum markers of inflammation.

Comparison of clinical outcome of decompression of suprascapular nerve at spinoglenoid notch for patients with posterosuperior massive rotator cuff tears and suprascapular neuropathy.

PURPOSE: In the present study, we aimed to determine whether decompression of suprascapular nerve (SSN) at the spinoglenoid notch could lead to a better functional outcome for the patients who underwent repairment of rotator cuff due to posterosupeior massive rotator cuff tear (MRCT) and suprascapular neuropathy. METHODS: A total of 20 patients with posterosuperior MRCT and suprascapular neuropathy were analyzed in the present work. The preoperative magnetic resonance imaging (MRI) showed rotator cuff tear in supraspinatus and infraspinatus. All patients underwent arthroscopic rotator cuff repair. Patients were divided into two groups (group A: non-releasing, group B: releasing) according to whether the SSN at the spinoglenoid notch was decompressed. The modified University of California at Los Angeles shoulder rating scale (UCLA) and visual analog scale (VAS) questionnaire were adopted to assess the function of the affected shoulder preoperatively and 12 months after the operation. Electromyography (EMG) and nerve conduction study (NCS) were used to evaluate the nerve condition. Patients underwent MRI and EMG/NCS at 6 months after operation and last follow-up. RESULTS: All patients were satisfied with the treatment. MRI showed that it was well-healed in 19 patients at 6 months after the operation. However, the fatty infiltration of supraspinatus and infraspinatus was not reversed. Only one patient in the non-releasing group showed the retear. The retear rate of group A and group B were 30% (3/10) and 20% (2/10) respectively at 12 months after the operation. One patient undergoing SSN decompression complained of discomfort in the infraspinatus area. His follow-up EMG after 6 months showed fibrillation potentials (1+) and positive sharp waves (1+) in the infraspinatus. The other patients' EMG results showed no abnormality. The postoperative UCLA and VAS scores were improved in both groups, and there was no significant difference in the follow-up outcomes between the two groups. CONCLUSIONS: Patients with postersuperior MRCT and suprascapular neuropathy, decompression of suprascapular nerve at spinoglenoid notch didn't lead to a better functional outcome with the repairment of rotator cuff. Arthroscopic rotator cuff repair could reverse the suprascapular neuropathy. LEVEL OF EVIDENCE: Level III.

The influence of previous arthroscopic treatment on subsequent primary total knee arthroplasty: the comparison between bilateral knees of the same patient.

BACKGROUND: To explore whether previous arthroscopic knee surgery affects future total knee arthroplasty (TKA) results or not. METHODS: A total of 56 patients with the previous arthroscopic treatment on one knee underwent subsequent bilateral total knee arthroplasty in our hospital from September 2012 to July 2018. Data on each patient were collected in regards to changes in postoperative clinical and functional scores, various other scores, as well as postoperative functional recovery and complications. We defined the knees with a previous arthroscopic history as group A, and the counter side as group B. The Knee Society clinical score, functional scores, range of motion (ROM), finger joint size (FJS), visual analogue scale (VAS) scores were assessed before and after surgery. Using the Kolmogorov-Smirnov Test to test the normality of continuous variables, and the chi-square test to compare the rate of reoperation and complications between two groups. For all statistical comparisons, P < 0.05 was considered significant. RESULTS: There were no statistically significance differences found in postoperative Knee Society clinical scores and functional scores between group A and group B, as well as in ROM, FJS, VAS scores and local complications. CONCLUSION: There were no statistically significant differences found in postoperative functional recovery and complications in patients, who underwent total knee arthroplasty with previous knee arthroscopy.

Bilateral single-staged arthroscopic rotator cuff repair is comparable to staged procedures: a retrospective follow up study of 2 years.

BACKGROUND: Bilateral rotator cuff tears are not uncommon and the timing of the surgical treatment of both shoulders is debated. In the present study, we aimed to compare the clinical outcomes of patients who underwent single-stage or staged bilateral arthroscopic rotator cuff repair. METHODS: From March 2013 to May 2018, a retrospective review on all patients who underwent bilateral arthroscopic rotator cuff repair at our department was performed. Patients were separated into 2 groups: single-stage and staged. The minimum follow-up period was 2 years. The visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, University of California, Los Angeles (UCLA) score, Constant-Murley (Constant) score, the range of motion (ROM) of the shoulder and the hospitalization costs were evaluated for comparison between the two groups before and after the operation. Differences between groups were assessed using t-tests and ANOVA. RESULTS: All 51 patients completed follow-up of 2 years, single stage (n = 24) and staged group (n = 27). There was no significant difference in the VAS, ASES, UCLA and Constant scores between the single-stage group and the staged group before the operation. Postoperative clinical scores were significantly improved in both groups (P < 0.05). All outcome scores were significantly different between the two groups at 6 months postoperatively, and the staged scored better than the single-stage (P < 0.05). At 12, 18, and 24 months after the operation, the outcome scores were not significantly different between the two groups. At follow-up, the ROM of the shoulder was not significantly different between the two groups. In the single-stage group, the outcome scores and ROM were similar for both shoulders and comparable to the staged group. We also found significant cost savings in the single-stage group (4440.89 ± 130.55 USD) compared to the staged group (5065.73 ± 254.76 USD) (p < 0.05). CONCLUSIONS: Patients receiving single-stage or staged bilateral arthroscopic rotator cuff repair showed similarly good clinical outcomes at follow-ups longer than 6 months. Moreover, good outcomes were observed on both sides of the single-stage group.