The Nomogram Model and Factors for the Postoperative Mortality of Elderly Patients with Femoral Neck Fracture Undergoing Artificial Hip Arthroplasty: A Single-Institution 6-Year Experience.

OBJECTIVE: Artificial hip arthroplasty (AHA) is widely accepted in elderly patients with femoral neck fractures, but it is associated with high risk of death and various postoperative complications due to old age and accompanying chronic diseases. Therefore, this study aimed to explore the risk factors for death in elderly patients with femoral neck fractures after AHA and to establish a nomogram risk prediction model, which is expected to reveal high-risk patients and improve the postoperative quality of life and survival rate of patients. METHODS: Elderly patients who underwent AHA for femoral neck fractures in our hospital from September 2014 to May 2021were retrospectively analyzed. These patients were divided into a survival group and a death group according to their clinical outcomes. The following clinical data were recorded for the patients in the two groups: sex, age, underlying diseases, smoking and drinking history, preoperative nutritional risk score (NRS) and American Society of Anesthesiologists (ASA) score, as well as relevant indicators about the operation. These data were subject to univariate analysis and then logistic analysis to determine the risk factors of death. Subsequently, a nomogram risk prediction model was established and further validated with the receiver operating characteristic curve (ROC) and the Hosmer-Lemeshow test. Finally, the effects of predictive risk factors were analyzed using the Kaplan-Meier survival curve. RESULTS: Follow-up was completed by 260 patients, including 206 patients in the survival group and 54 patients in the death group; the overall death rate was 20.77%, and the follow-up time, age, postoperative 1, 3 and 5-year death rates were 3.47 ± 1.93 years, 75.32 ± 9.12 years, 5.77%, 12.51%, and 25.61%, respectively. The top three causes of death in 54 patients were respiratory disease, cerebrocardiovascular disease, and digestive disease, respectively. The logistic analysis indicated that elderly patients with femoral neck fractures, the risk factors for death after AHA were age ≥ 80 years, preoperative NRS ≥ 4, HB ≤ 90 g/L, CR ≥ 110 umol/L, and ASA score ≥ 3, as well as postoperative albumin ≤ 35 g/L, the nomogram was established, and then its predictive performance was successfully validated using the ROC curve (AUC = 0.814, 95% confidence interval = 0.749-0.879) and the Hosmer-Lemeshow test (p = 0.840). Furthermore, Kaplan-Meier survival curve analysis revealed that the abovementioned six indicators were correlated with the post-AHA survival time of elderly patients with femoral neck fractures (pLog Rank < 0.05). CONCLUSION: Old age, preoperatively high NRS and ASA score, anemia, poor renal function, and postoperative hypoproteinemia are the major risk factors for death in elderly patients with femoral neck fractures after AHA; they are also associated with postoperative survival. Early identification and effective interventions for optimization of modifiable risk factors are recommended to improve the postoperative quality of life and survival rates.

An Injectable Integration of Autologous Bioactive Concentrated Growth Factor and Gelatin Methacrylate Hydrogel with Efficient Growth Factor Release and 3D Spatial Structure for Accelerated Wound Healing.

Growth factors are essential for wound healing owing to their multiple reparative effects. Concentrated growth factor (CGF) is a third-generation platelet extract containing various endogenous growth factors. Herein, a CGF extract solution is combined with gelatin methacrylate (GM) by physical blending to produce GM@CGF hydrogels for wound repair. The GM@CGF hydrogels show no immune rejection during autologous transplantation. Compared to CGF, GM@CGF hydrogels not only exhibit excellent plasticity and adhesivity but also prevent rapid release and degradation of growth factors. The GM@CGF hydrogels display good injectability, self-healing, swelling, and degradability along with outstanding cytocompatibility, angiogenic functions, chemotactic functions, and cell migration-promoting capabilities in vitro. The GM@CGF hydrogel can release various effective molecules to rapidly initiate wound repair, stimulate the expressions of type I collagen, transform growth factor ß1, epidermal growth factor, and vascular endothelial growth factor, promote the production of granulation tissues, vascular regeneration and reconstruction, collagen deposition, and epidermal cell migration, as well as prevent excessive scar formation. In conclusion, the injectable GM@CGF hydrogel can release various growth factors and provide a 3D spatial structure to accelerate wound repair, thereby providing a foundation for the clinical application and translation of CGF.

Blockade of JAK2 retards cartilage degeneration and IL-6-induced pain amplification in osteoarthritis.

Osteoarthritis (OA) is a complex chronic inflammatory disease characterized by articular degeneration and pain. Recent studies have identified interleukin 6 (IL-6) as a potential mediator leading to OA, but the therapeutic effects of inhibiting IL-6 signaling in intreating OA need to be further clarified. Here, we identified the intracellular signal transduction induced by recombinant IL-6 and focused on the impact of tyrphostin AG490 (a JAK2 inhibitor) on cartilage degeneration and OA pain. We found that IL-6 increased the inflammatory cytokines production and hypertrophic markers expression of primary mouse chondrocytes by activating JAK2/STAT3. Meanwhile, tyrphostin AG490 significantly attenuated articular degeneration and osteophyte formation in experimental mice with anterior cruciate ligament transection (ACLT) surgery. In vivo electrophysiological experiments showed that articular stimulation of IL-6 induced spinal hyperexcitability, which was prevented by coinjection of tyrphostin AG490. Specifically, compared with DMSO-treated ACLT mice, tyrphostin AG490 improved ambulate activity of mice and abolished the enhancement of serum bradykinin induced by IL-6. Together, we suggest that tyrphostin AG490 protected against progression of OA and improved OA prognosis by reducing cartilage degeneration and arthritis pain. Our findings provide further evidence for targeting IL-6 signaling in the treatment of OA.

NIX Mediates Mitophagy in Spinal Cord Injury in Rats by Interacting with LC3.

Excessive mitophagy plays a role in neuronal death in spinal cord injury (SCI), its molecular regulation remains largely unknown. The present study aims to determine the role of NIX, a member of a unique subfamily of death-inducing mitochondrial proteins, in the regulation of mitophagy in SCI. Here we show that NIX is highly upregulated in SCI and hypoxia, and localized to mitochondria. The mitochondria-bound NIX interacts with autophagosome-localized LC3 (Microtubule-associated protein 1 light chain 3) to form a mitochondria-NIX-LC3-autophagosome complex, resulting in excessive mitophagy in SCI. Downregulation of NIX by RNA interference restores the function of mitochondria in spinal cord neurons under hypoxia. Importantly, inhibition of NIX improves recovery of locomotor function in rats after SCI. The present study demonstrates that NIX interacts with LC3 to activate excessive mitophagy in SCI. Inhibition of NIX is therefore likely a neuroprotective strategy.

Association of RDM1 with osteosarcoma progression via cell cycle and MEK/ERK signalling pathway regulation.

RAD52 motif-containing 1 (RDM1), a key regulator of DNA double-strand break repair and recombination, has been reported to play an important role in the development of various human cancers, such as papillary thyroid carcinoma, neuroblastoma and lung cancer. However, the effect of RDM1 on osteosarcoma (OS) progression remains unclear. Here, this study mainly explored the connection between RDM1 and OS progression, as well as the underlying mechanism. It was found that RDM1 was highly expressed in OS cells compared with human osteoblast cells. Knockdown of RDM1 caused OS cell proliferation inhibition, cell apoptosis promotion and cell cycle arrest at G1 stage, whereas RDM1 overexpression resulted in the opposite phenotypes. Furthermore, RDM1 silencing leads to a significant decrease in tumour growth in xenograft mouse model. RDM1 also increased the protein levels of MEK 1/2 and ERK 1/2. All these findings suggest that RDM1 plays an oncogenic role in OS via stimulating cell cycle transition from G1 to S stage, and regulating MEK/ERK signalling pathway, providing a promising therapeutic factor for the treatment of OS.

Bcl-2/E1B-19KD-Interacting Protein 3/Light Chain 3 Interaction Induces Mitophagy in Spinal Cord Injury in Rats Both In Vivo and In Vitro.

Autophagy and mitophagy have been shown to occur in spinal cord injury (SCI). Bcl-2/E1B-19KD-interacting protein 3 (BNIP3) and its homologue, NIX, have been implicated in the regulation of mitophagy. The aim of this work was to characterize the mechanisms and role of BNIP3 in SCI-associated mitophagy. Our data showed that BNIP3, targeted to mitochondria, interacted with microtubule-associated protein 1A/1B-light chain 3 (LC3), which is targeted to autophagosomes, thus forming a mitochondria-BNIP3-LC3-autophagosome complex and resulting in mitophagy. Downregulation of BNIP3 by RNA interference strengthened the mitochondrial function and decreased cell death in spinal cord neurons under hypoxia. Particularly, BNIP3 knockdown significantly improved neurological recovery and the number of neuronal nuclei-positive cells post-SCI in rats. The present study demonstrated that BNIP3 interacts with LC3 to induce mitophagy, whereas its inhibition provided protective neuronal effects in SCI rat models both in vivo and in vitro.