Cellular senescence plays an important role in human diseases, including osteoporosis and osteoarthritis. Senescent cells (SCs) produce the senescence-associated secretory phenotype to affect the function of neighboring cells and SCs themselves. Delayed fracture healing is common in the elderly and is accompanied by reduced mesenchymal progenitor cells (MPCs). However, the contribution of cellular senescence to fracture healing in the aged has not to our knowledge been studied. Here, we used C57BL/6J 4-month-old young and 20-month-old aged mice and demonstrated a rapid increase in SCs in the fracture callus of aged mice. The senolytic drugs dasatinib plus quercetin enhanced fracture healing in aged mice. Aged callus SCs inhibited the growth and proliferation of callus-derived MPCs (CaMPCs) and expressed high levels of TGF-β1. TGF-β–neutralizing Ab prevented the inhibitory effects of aged callus SCs on CaMPCs and promoted fracture healing in aged mice, which was associated with increased CaMPCs and proliferating cells. Thus, fracture triggered a significant cellular senescence in the callus cells of aged mice, which inhibited MPCs by expressing TGF-β1. Short-term administration of dasatinib plus quercetin depleted callus SCs and accelerated fracture healing in aged mice. Senolytic drugs represent a promising therapy, while TGF-β1 signaling is a molecular mechanism for fractures in the elderly via SCs.

Intervertebral disc degeneration (IVDD) refers to the aging and degenerative diseases of intervertebral disc components such as nucleus pulposus, annulus fibrosus, and cartilage endplate, and is the main cause of chronic low back pain. Over the past few years, many researchers around the world concerned that the degeneration of nucleus pulposus (NP) cells plays the main role in IVDD. The degeneration of NP cells is caused by a series of pathological processes, including oxidative stress, inflammatory response, apoptosis, abnormal proliferation, and autophagy. Interestingly, many studies have found a close relationship between the senescence of NP cells and the progression of NP degeneration. The classical aging pathways also have been confirmed to be involved in the pathological process of IVDD. Moreover, several anti-aging drugs have been used to treat IVDD by inhibiting NP cells senescence, such as proanthocyanidins, resveratrol and bone morphogenetic protein 2. Therefore, this article will systematically list and discuss aging, cell senescence, the pathogenesis and targeted therapies of IVDD, in order to provide new ideas for the treatment of IVDD in the future.

Platelets are blood cells that are primarily produced by the shedding of megakaryocytes in the bone marrow. Platelets participate in a variety of physiological and pathological processesin vivo, including hemostasis, thrombosis, immune-inflammation, tumor progression, and metastasis. Platelets have been widely used for targeted drug delivery therapies for treating various inflammatory and tumor-related diseases. Compared to other drug-loaded treatments, drug-loaded platelets have better targeting, superior biocompatibility, and lower immunogenicity. Drug-loaded platelet therapies include platelet membrane coating, platelet engineering, and biomimetic platelets. Recent studies have indicated that platelet extracellular vesicles (PEVs) may have more advantages compared with traditional drug-loaded platelets. PEVs are the most abundant vesicles in the blood and exhibit many of the functional characteristics of platelets. Notably, PEVs have excellent biological efficacy, which facilitates the therapeutic benefits of targeted drug delivery. This article provides a summary of platelet and PEVs biology and discusses their relationships with diseases. In addition, we describe the preparation, drug-loaded methods, and specific advantages of platelets and PEVs targeted drug delivery therapies for treating inflammation and tumors. We summarize the hot spots analysis of scientific articles on PEVs and provide a research trend, which aims to give a unique insight into the development of PEVs research focus.

Mitochondrial dysfunction causes the production of reactive oxygen species (ROS) and oxidative damage, and oxidative stress and inflammation are considered key factors causing intervertebral disc degeneration (IVDD). Thus, restoring the mitochondrial dysfunction is an attractive strategy for treating IVDD. Platelet-derived extracellular vesicles (PEVs) are nanoparticles that target inflammation. Moreover, the vesicles produced by platelets (PLTs) have considerable anti-inflammatory effects. We investigate the use of PEVs as a therapeutic strategy for IVDD in this study. We extract PEVs and evaluate their properties; test their effects on H₂O₂-induced oxidative damage of nucleus pulposus (NP) cells; verify the role of PEVs in repairing H₂O₂-induced cellular mitochondrial dysfunction; and demonstrate the therapeutic effects of PEVs in a rat IVDD model. The results confirm that PEVs can restore impaired mitochondrial function, reduce oxidative stress, and restore cell metabolism by regulating the sirtuin 1 (SIRT1)-peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α)-mitochondrial transcription factor A (TFAM) pathway; in rat models, PEVs retard the progression of IVDD. Our results demonstrate that the injection of PEVs can be a promising strategy for treating patients with IVDD.

Background: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. Methods: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. Results: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P<0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) (P0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. Conclusions: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

Intra-operative cell salvage (CS) was reported to have no impairment on blood coagulation in low-bleeding-risk cardiac surgery with cardiopulmonary bypass (CPB), but studies in high-bleeding-risk cardiac surgery are limited. The objective of this study is to evaluate the impact of CS on blood coagulation in high-bleeding-risk cardiac surgery with CPB. One hundred and ten patients were randomly assigned to either with intra-operative CS group (Group CS) or without intra-operative CS group (Group C). Study endpoints included the incidence of impairment of blood coagulation during perioperative period (peri-op) and the incidence of adverse events during postoperative period (post-op). Peri-op was defined as the period from beginning of anesthesia (anesthesia induction) to 24 h after end of surgery. Post-op was defined as the period from the end of surgery to 24 h after end of surgery. The types of impairment of blood coagulation included heparin residual, coagulopathy due to low PLT, coagulopathy due to low FIB, coagulopathy due to low coagulation factors, hyperfibrinolytic. The sum of above five types was total impairment of blood coagulation. Adverse events included excessive bleeding, resternotomy, etc. The incidence of heparin residual measured both at the end of surgery and during post-op were significantly higher in Group CS than in Group C (15.09 vs 4.00, 13.21 vs 2.00 %; p = 0.024, 0.010, respectively). Similarly, the incidence of total impairment of blood coagulation at the end of surgery and during post-op were significantly higher in Group CS than in Group C (32.08 vs 18.00, 26.42 vs 12.00 %; p = 0.043, 0.040, respectively). The incidence of excessive bleeding during post-op was 32.08 % in Group CS compared with 16.00 % in Group C (p = 0.038). Intriguingly, CS was associated with a significantly increase in the relative risk ratios for heparin residual and excessive bleeding (p = 0.034, 0.049, respectively). Intra-operative CS could impair blood coagulation in the scenario of high-risk-bleeding cardiac surgery with CPB.