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Objective: In addition to the surface hemorrhage of cancellous bone after large‐area osteotomy, the intramedullary hemorrhage after the reamed knee joint is also a major cause of postoperative bleeding after total knee arthroplasty (TKA). This study evaluated the efficacy and safety of bone wax application at different time points of prone hemorrhage to reduce perioperative blood loss. Methods: From August 2023 to December 2023, 150 patients undergoing primary unilateral TKA were included in this prospective, randomized controlled trial, patients were randomly divided into three groups: group A, after autogenous osteotomy plug was used to fill the femoral medullary cavity, the residual space was sealed with bone wax and the exposed cancellous bone surface around the prosthesis was coated with bone wax after the prosthesis adhesion; group B, only the exposed cancellous bone surface around the prosthesis was coated with bone wax; and group C, no bone wax was used. The primary outcome was total perioperative blood loss. Secondary outcomes included occult blood loss, postoperative hemoglobin reduction, blood transfusion rate, lower limb diameter, and knee function, while length of hospital stay was recorded. Tertiary outcomes included the incidence of postoperative related adverse events. Results: The total blood loss in group A (551.5 ± 224.5 mL) and group B (656.3 ± 267.7 mL) was significantly lower than that in group C (755.3 ± 248.3 ml, p < 0.001), and the total blood loss in group A was also lower than that in group B (p < 0.05). There were also significant differences in the reduction of hemoglobin level and hidden blood loss among the three groups (p < 0.05). However, there was no significant improvement in postoperative lower limb swelling, knee joint activity and hospitalization time; there was no significant difference in the incidence of complications such as thromboembolism. Conclusion: The use of bone wax in TKA can safely and effectively reduce perioperative blood loss and hemoglobin drop rate, and multiple use at time points during the operation when blood loss is prone to occur can produce more significant hemostatic effect. [ABSTRACT FROM AUTHOR]

Author(s): Berk Aykut [sup.1] , Smruti Pushalkar [sup.2] , Ruonan Chen [sup.1] , Qianhao Li [sup.2] , Raquel Abengozar [sup.1] , Jacqueline I. Kim [sup.1] , Sorin A. Shadaloey [sup.1] [...], Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA).sup.1. However, the mycobiome has not been clearly implicated in tumorigenesis. Here we show that fungi migrate from the gut lumen to the pancreas, and that this is implicated in the pathogenesis of PDA. PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue. The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices. Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp. in both mice and humans. Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species--but not species in the genera Candida, Saccharomyces or Aspergillus--accelerated oncogenesis. We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment--or knockdown of C3aR in tumour cells--were both protective against tumour growth. In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice. Collectively, our work shows that pathogenic fungi promote PDA by driving the complement cascade through the activation of MBL. In humans and mouse models, the mycobiome of pancreatic ductal adenocarcinoma tumours is markedly enriched in Malassezia species compared to that of normal pancreas, which implicates these pathogenic fungi in oncogenesis.

Introduction Gut microbiota represent the most abundant and diverse collection of commensal organisms in the body (1). The intestinal microbiome plays a fundamental role in shaping the host immune system [...], The gut microbiome shapes local and systemic immunity. The liver is presumed to be a protected sterile site. As such, a hepatic microbiome has not been examined. Here, we showed a liver microbiome in mice and humans that is distinct from that of the gut and is enriched in Proteobacteria. It undergoes dynamic alterations with age and is influenced by the environment and host physiology. Fecal microbial transfer experiments revealed that the liver microbiome is populated from the gut in a highly selective manner. Hepatic immunity is dependent on the microbiome, specifically the bacteroidetes species. Targeting bacteroidetes with oral antibiotics reduced hepatic immune cells by approximately 90%, prevented antigen-presenting cell (APC) maturation, and mitigated adaptive immunity. Mechanistically, our findings are consistent with presentation of bacteroidetes-derived glycosphingolipids to NKT cells promoting CCL5 signaling, which drives hepatic leukocyte expansion and activation, among other possible host-microbe interactions. Collectively, we reveal a microbial/glycosphingolipid/NKT/CCL5 axis that underlies hepatic immunity.

Autophagy may play an important role in the occurrence and development of glucocorticoid‐induced osteonecrosis of the femoral head (GC‐ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC‐ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC‐ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC‐induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC‐ONFH was used for evaluating the therapeutic effect of oral lithium on GC‐ONFH and underlying mechanism. Findings demonstrated that GC over‐activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over‐activated autophagy of GC‐treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC‐ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over‐activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up‐regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC‐ONFH. Lithium may be a promising therapeutic agent for GC‐ONFH. However, the role of autophagy in the pathogenesis of GC‐ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC‐ONFH, and the efficacy of lithium in the treatment of GC‐ONFH and its underlying mechanisms. [ABSTRACT FROM AUTHOR]

A high prevalence of osteoarthritis (OA) has been observed among individuals living at high altitudes, and hypobaric hypoxia (HH) can cause bone mass and strength deterioration. However, the effect of HH on OA remains unclear. In this study, we aimed to explore the impact of HH on OA and its potential mechanisms. A rat knee OA model was established by surgery, and the rats were bred in an HH chamber simulating a high‐altitude environment. Micro‐computed tomography (Micro‐CT), histological analysis, and RNA sequencing were performed to evaluate the effects of HH on OA in vivo. A hypoxic co‐culture model of osteoclasts and osteoblasts was also established to determine their effects on chondrogenesis in vitro. Cartilage degeneration significantly worsened in the HH‐OA group compared to that in the normoxia‐OA (N‐OA) group, 4 weeks after surgery. Micro‐CT analysis revealed more deteriorated bone mass in the HH‐OA group than in the N‐OA group. Decreased hypoxia levels in the cartilage and enhanced hypoxia levels in the subchondral bone were observed in the HH‐OA group. Furthermore, chondrocytes cultured in a conditioned medium from the hypoxic co‐culture model showed decreased anabolism and extracellular matrix compared to those in the normoxic model. RNA sequencing analysis of the subchondral bone indicated that the glycolytic signaling pathway was highly activated in the HH‐OA group. HH‐related OA progression was associated with alterations in the oxygen environment and bone remodeling in the subchondral zone, which provided new insights into the pathogenesis of OA. [ABSTRACT FROM AUTHOR]

In this paper, the regulation performance limitation of networked time‐delay systems is studied. The communication network is mainly affected by parameters such as packet dropouts, encoding‐decoding, interference signal, and channel noises. Non‐minimum phase zeros, unstable poles, and time delay are all considered for a given plant. The corresponding regulation performance expression is derived using coprime factorization and spectral decomposition techniques in the frequency domain. The results indicate that the regulation performance of the system is related to the inherent characteristics of the given plant, including non‐minimum phase zeros, unstable poles, and time delay. Additionally, network communication parameters such as white Gaussian noise, packet dropouts, encoding‐decoding, and external interference signals all affect the regulation performance of networked time‐delay systems. Finally, some simulation examples are provided to demonstrate the effectiveness of the theory. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusion Both blood loss and lower extremity swelling after total knee arthroplasty (TKA) can affect a patient's postoperative recovery. The aim of this trial was to investigate whether different doses of intra‐articular tranexamic acid (TXA) can reduce blood loss and postoperative lower limb swelling.In a prospective, randomized‐controlled trial, a total of 225 patients were randomly assigned to three groups from September 2020 through January 2021: intra‐articular injections of 3 g, 1 g of TXA, or placebo (saline solution). The primary outcome indicators were perioperative blood loss and decreased hemoglobin levels. The secondary outcome indicators were lower extremity swelling, functional recovery indicators (hospital for special surgery [HSS] scores, range of motion), visual analog scale [VAS] scores, and transfusion rates and safety outcomes, including thromboembolic events, incidence of wound‐related complications, and length of hospital stay. One‐way analysis of variance (ANOVA), post hoc Bonferroni correction, Pearson chi‐square test and Fisher exact test were used for statistical analysis.Postoperative blood loss was lower in the 1 and 3 g TXA groups (754.00 ± 409.67 mL and 568.70 ± 408.27 mL, respectively) than in the placebo group (977.32 ± 418.69 mL) (p < 0.001). The maximum postoperative decrease in hemoglobin was lower in the 1 and 3 g TXA groups (2.4 ± 0.9 and 1.8 ± 0.9 g/dL, respectively) than in the placebo group (3.1 ± 1.2 g/dL) (p < 0.001). On postoperative Days 1, 2, and 3, the TXA group presented significantly reduced thigh, suprapatellar, and calf swelling and significantly reduced pain scores during exercise. Compared with that in the low‐dose group, perioperative blood loss was further reduced in the high‐dose TXA group (p = 0.006). However, while patients in the TXA group had improved pain scores, Hospital for Special Surgery scores, and joint range of motion at postoperative rest, these differences were not statistically significant. There were no significant differences in thromboembolic events or complication rates among the three groups.Topical TXA in total knee arthroplasty was effective in reducing postoperative blood loss by 24%–43% and in reducing postoperative lower extremity swelling and pain during exercise. Higher doses (3 g) of TXA further controlled perioperative blood loss without affecting postoperative lower extremity swelling, and there was no increase in the incidence of related complications during follow‐up.Trial Registration: This study was a single‐center, prospective, randomized controlled trial (RCT). The trial was approved by the Clinical Trials and Biomedical Ethics Committee at our institution (number: 2018.676), all participants provided written informed consent, and the trial was prospectively registered in the Chinese Clinical Trial Registry (ChiCTR2000035271) [ABSTRACT FROM AUTHOR]

Objective: To summarize research progress on application of Cup-cage reconstruction in revision of chronic pelvic discontinuity (CPD) in patients undergoing total hip arthroplasty (THA)., Methods: Relevant literature at home and abroad in recent years was reviewed to summarize the principles of the Cup-cage reconstruction, preoperative patient assessment, intraoperative skills, clinical and radiological effectiveness, limitations, and postoperative complications., Results: For the treatment of CPD, the Cup-cage reconstruction achieved long-term acetabular cup bone ingrowth, CPD healing, and biologic fixation of the prosthesis by restoring pelvic continuity. Preoperative evaluation of the surgical site and general condition is necessary. The main intraoperative objectives are to reconstruct pelvic continuity, restore the center of rotation of the hip, and avoid neurovascular injury. Current studies have demonstrated significant clinical and radiological effectiveness as well as acceptable prosthesis survival rates after operation. Nevertheless, there is a lack of evidence regarding the staging of CPD, the optimal surgical approach and internal fixation, and the factors influencing postoperative prosthesis survival remain undefined., Conclusion: Cup-cage reconstruction can be an effective treatment for CPD after THA, but there is still a need to explore CPD staging, Cup-cage approach and internal fixation, and influencing factors on prosthesis survival.

Identifying effective target-disease associations (TDAs) can alleviate the tremendous cost incurred by clinical failures of drug development. Although many machine learning models have been proposed to predict potential novel TDAs rapidly, their credibility is not guaranteed, thus requiring extensive experimental validation. In addition, it is generally challenging for current models to predict meaningful associations for entities with less information, hence limiting the application potential of these models in guiding future research. Based on recent advances in utilizing graph neural networks to extract features from heterogeneous biological data, we develop CreaTDA, an end-to-end deep learning-based framework that effectively learns latent feature representations of targets and diseases to facilitate TDA prediction. We also propose a novel way of encoding credibility information obtained from literature to enhance the performance of TDA prediction and predict more novel TDAs with real evidence support from previous studies. Compared with state-of-the-art baseline methods, CreaTDA achieves substantially better prediction performance on the whole TDA network and its sparse sub-networks containing the proteins associated with few known diseases. Our results demonstrate that CreaTDA can provide a powerful and helpful tool for identifying novel target-disease associations, thereby facilitating drug discovery.