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Abstract Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions.

Objective: Our study aims to develop a deep learning-based Ankylosing Spondylitis (AS) diagnostic model that achieves human expert-level performance using only a minimal amount of labeled samples for training, in regions with limited access to expert resources., Methods: Our semi-supervised diagnostic model for AS was developed using 5389 pelvic radiographs (PXRs) from a single medical center, collected from March 2014 to April 2022. The dataset was split into a training set and a validation set with an 8:2 ratio, allocating 431 labeled images and the remaining 3880 unlabeled images for semi-supervised learning. The model's performance was evaluated on 982 PXRs from the same center, assessing metrics such as AUC, accuracy, precision, recall, and F1 scores. Interpretability analysis was performed using explainable algorithms to validate the model's clinical applicability., Results: Our semi-supervised learning model achieved accuracy, recall, and precision values of 0.891, 0.865, and 0.859, respectively, using only 10% of labeled data from the entire training set, surpassing human expert performance. Extensive interpretability analysis demonstrated the reliability of our model's predictions, making the deep neural network no longer a black box., Conclusion: This study marks the first application of semi-supervised learning to diagnose AS using PXRs, achieving a 90% reduction in manual annotation costs. The model showcases robust generalization on an independent test set and delivers reliable diagnostic performance, supported by comprehensive interpretability analysis. This innovative approach paves the way for training high-performance diagnostic models on large datasets with minimal labeled data, heralding a cost-effective future for medical imaging research in big data analytics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To evaluate the difference of clinical outcomes and radiological outcomes through meta-analysis on the total hip arthroplasty (THA) between hydroxyapatite(HA) coating and non-HA coating femoral stems., Methods: We searched the MEDLINE, Embase, Cochrane library and CBM for published randomized controlled trial (RCT) comparing HA coating and non-HA coating femoral stems in primary THA clinical outcomes with Harris hip score and incidence postoperative thigh pain, radiological outcomes with presence of endosteal condensation and radioactive line on the prothesis, heterotopic ossification. Data analysis were performed using RevMan 5.0(the Cochrane Collaboration)., Results: Ten studies and 917 hips into our analysis, with 464 hips in HA groups and 453 hips in non-HA groups. The combined results of the meta-analysis indicated there was no statistical differences between the two groups on postoperative Harris hip score(WMD = 3.04, 95%CI:-4.47-10.54, P = 0.43) , there was statistical difference on incidence postoperative thigh pain (RR = 0.56, 95%CI:0.33-0.94, P = 0.03) . There were no significant differences between the two groups on presence of endosteal condensation (RR = 1.01, 95%CI:0.91-1.11, P = 0.91), presence of radioactive line (RR = 0.99, 95%CI:0.88-1.11, P = 0.83) and incidence of heterotopic ossification (RR = 0.97, 95%CI:0.77-1.21, P = 0.77)., Conclusions: There are no clinical and radiological benefits in the use of HA coating femoral stems in Primary THA, there is not enough evidence prove the HA can reduce the incidence postoperative thigh pain.

Objective: To evaluate the effect of associated ulnar styloid fracture on wrist function after distal radius fracture by comparing the clinical data between the cases of distal radius fracture with or without ulnar styloid fractures., Methods: The clinical data of 182 patients with distal radius fracture between February 2005 and May 2010 were retrospectively analyzed, including 75 with ulnar styloid fracture (group A), and 107 without ulnar styloid fracture (group B). There was no significant difference in sex, age, disease duration, and fracture classification between 2 groups (P > 0.05). In groups A and B, closed reduction and splintlet or cast fixation were performed in 42 and 63 cases respectively, and open reduction and internal fixation in 33 and 44 cases respectively. All ulnar styloid fractures were not treated., Results: The patients were followed up 21 months on average in group A and 20 months on average in group B. All incisions healed by first intention after operation. Ulnar wrist pain occurred in 4 patients (5.3%) of group A and 6 patients (5.6%) of group B, showing no significant difference (chi2=0.063, P=0.802). The fracture healing time was (10.9 +/- 2.7) weeks in group A and (11.6 +/- 2.3) weeks in group B, showing no significant difference (t=1.880, P=0.062). There was no significant difference in the palmar tilt angle, the ulnar inclination angle, and the radial length between groups A and B when fracture healing (P > 0.05). At last follow-up, there was no significant difference in wrist flexion-extension, radial-ulnar deviation, pronation-supination, and grip and pinch strength between 2 groups (P > 0.05). According to the Gartland-Werley score in groups A and B, the results were excellent in 24 and 35 cases, good in 43 and 57 cases, fair in 5 and 10 cases, and poor in 3 and 5 cases with execllent and good rate of 89.3% and 86.0%, respectively, showing no significant difference between 2 groups (Z=0.203, P=0.839). There were significant differences in the above indexes between patients undergoing closed reduction and open reduction in group A (P < 0.05)., Conclusion: Associated ulnar styloid fracture has no obvious effect on the wrist function after distal radius fracture. The anatomical reduction of distal radial fracture is the crucial importance in the treatment of distal radial fracture accompanying ulnar styloid fracture.