Chrono-Aerobic Exercise Optimizes Metabolic State in DB/DB Mice through CLOCK-Mitophagy-Apoptosis.

Although the benefits of aerobic exercise on obesity and type 2 diabetes are well-documented, the pathogenesis of type 2 diabetes and the intervention mechanism of exercise remain ambiguous. The correlation between mitochondrial quality and metabolic diseases has been identified. Disruption of the central or peripheral molecular clock can also induce chronic metabolic diseases. In addition, the interactive effects of the molecular clock and mitochondrial quality have attracted extensive attention in recent years. Exercise and a high-fat diet have been considered external factors that may change the molecular clock and metabolic state. Therefore, we utilized a DB/DB (BSK.Cg-Dock7m +/+ Leprdb/JNju) mouse model to explore the effect of chrono-aerobic exercise on the metabolic state of type 2 diabetic mice and the effect of timing exercise as an external rhythm cue on liver molecular clock-mitochondrial quality. We found that two differently timed exercises reduced the blood glucose and serum cholesterol levels in DB/DB mice, and compared with night exercise (8:00 p.m., the active period of mice), morning exercise (8:00 a.m., the sleeping period of mice) significantly improved the insulin sensitivity in DB/DB mice. In contrast, type 2 diabetes mellitus (T2DM) increased the expression of CLOCK and impaired the mitochondrial quality (mitochondrial networks, OPA1, Fis1, and mitophagy), as well as induced apoptosis. Both morning and night exercise ameliorated impaired mitochondrial quality and apoptosis induced by diabetes. However, compared with morning exercise, night exercise not only decreased the protein expression of CLOCK but also decreased excessive apoptosis. In addition, the expression of CLOCK was negatively correlated with the expression of OPA1 and Fis1. In summary, our research suggests that morning exercise is more beneficial for increasing insulin sensitivity and promoting glucose transport in T2DM, whereas night exercise may improve lipid infiltration and mitochondrial abnormalities through CLOCK-mitophagy-apoptosis in the liver, thereby downregulating glucose and lipid disorders. In addition, CLOCK-OPA1/Fis1-mitophagy might be novel targets for T2DM treatment.

Mechanism of tumor cells escaping from immune surveillance of NK cells.

Natural killer (NK) cells play an important role in anti-tumor and anti-infection, and perform their immune surveillance function in various ways. However, no matter what kind of cancer, the functional activity of NK cells in the tumor microenvironment (TME) is suppressed. Understanding the relationship between tumor cells and NK cells is very critical for tumor immunotherapy. This review discusses the mechanism of tumor cells escaping the immune surveillance of NK cells. These include a variety of factors that inhibit the activity of NK cells, an imbalance of activating receptors and inhibiting receptors on NK cells, abnormal binding of receptors and ligands, cross-talk of surrounding cell groups and NK cells in the TME, and other factors that affect NK cell activity. An understanding of these factors is necessary to provide new treatment strategies for tumor immunotherapy.

Targeted salinomycin delivery with EGFR and CD133 aptamers based dual-ligand lipid-polymer nanoparticles to both osteosarcoma cells and cancer stem cells.

We previously developed salinomycin (sali)-entrapped nanoparticles labeled with CD133 aptamers which could efficiently eliminate CD133+ osteosarcoma cancer stem cells (CSCs). However, sufficient evidences suggest that the simultaneous targeting both CSCs and cancer cells is pivotal in achieving preferable cancer therapeutic efficacy, due to the spontaneous conversion between cancer cells and CSCs. We hereby constructed sali-entrapped lipid-polymer nanoparticles labeled with CD133 and EGFR aptamers (CESP) to target both osteosarcoma cells and CSCs. The cytotoxicity of CESP in osteosarcoma cells and CSCs was superior to that of single targeting or nontargeted sali-loaded nanoparticles. Administration of CESP in vivo showed the best efficacy in inhibiting tumor growth than other controls in osteosarcoma-bearing mice. Thus, CESP was demonstrated to be capable of efficiently targeting both osteosarcoma CSCs and cancer cells, and it represents an effective potential approach to treat osteosarcoma.

The Efficacy of Anterior Cruciate Ligament Reconstruction with Peroneus Longus Tendon and its Impact on Ankle Joint Function.

OBJECTIVE: Peroneus Longus Tendon (PLT), a viable anterior cruciate ligament (ACL) graft, shares similar biomechanics, making it suitable for reconstruction. Controversy exists over whether PLT transplants affects the donor ankle joint. The purpose of this study was to examine the recovery of knee joint function following arthroscopic ACL restoration using autologous PLT and its influence on the donor ankle joint. METHODS: A retrospective analysis was conducted on 65 patients with ACL rupture who underwent PLT graft reconstruction in our hospital from January 2016 to December 2021. A three-dimensional gait analysis of the bilateral knee and ankle joints was performed postoperatively using an Opti_Knee three-dimensional motion measurement and analysis system-Yidong Medical Infrared Motion Gait Analyzer. Knee function scores and changes in the range of motion of the bilateral knee and ankle joints were collected. The analysis of preoperative and postoperative joint function scores, bilateral knee and ankle mobility was performed by t-tests. RESULTS: One year after surgery, the patients' International Knee Documentation Committee (IKDC) scores, Knee Injury and Osteoarthritis Outcome Scores (KOOSs), and Lysholm scores were significantly improved compared to preoperative scores, with statistically significant differences (p < 0.05). There was no statistical difference in the American Orthopedic Foot and Ankle Society (AOFAS) score of the donor ankle joint before and after surgery (p > 0.05). During different gait cycles, there was no statistical difference in knee joint mobility between the affected and healthy sides (p > 0.05), but there was a statistical difference in the inversion and eversion angle of the donor ankle joint during the support phase (p < 0.05). CONCLUSION: ACL reconstruction using the PLT can yield satisfactory knee joint function. However, it does affect inversion and eversion in the donor ankle joint, necessitating postoperative exercises. Similar subjective function ratings for both operated and non-operated feet, despite increased inversion-eversion motion in the operated foot, may be influenced by the subjective nature and margin of error in the AOFAS Ankle-hindfoot score, along with the relatively small variation in ankle inversion-eversion angles.

Investigating the differential therapeutic efficacy and mechanisms of human umbilical cord mesenchymal stem cells at various passages in osteoarthritis treatment.

This study aimed to assess the clinical efficacy of umbilical cord mesenchymal stem cells (hUC-MSCs) from different passages (P3, P8, and P13) in the treatment of knee osteoarthritis (OA) and explore the underlying mechanisms. The hUC-MSCs from each passage were characterized and evaluated for their stemness, migration, proliferation, and marker expression. Rats with OA were treated with hUC-MSCs from each passage, and the therapeutic effects were assessed based on knee swelling, discomfort, and pathological examination of the knee joint. Co-culture experiments were conducted to examine the ability of hUC-MSCs to stimulate type II collagen synthesis and inhibit MMP13 expression in chondrocytes. Telomere length and telomerase activity of hUC-MSCs from each passage were measured to investigate the reasons for the observed differences in clinical efficacy. The results revealed that P3 and P8 hUC-MSCs exhibited superior osteogenic and chondrogenic differentiation potential compared to P13, while P13 demonstrated stronger adipogenic differentiation. The wound healing rate was significantly higher in the P3 and P8 groups compared to P13. All hUC-MSC groups expressed high levels of CD90 and CD105, indicating their mesenchymal stem cell characteristics, while CD31 and CD45 were not expressed. CD105 expression was significantly reduced in the P13 group. In the treatment of rat osteoarthritis, there were no significant differences in knee swelling, discomfort, Mankin scores, and pathological findings between P3 and P8 hUC-MSC treatments. However, there was a significant difference between the 8th and 13th passages. Co-culture experiments showed that hUC-MSCs from P3 and P8 enhanced type II collagen synthesis and reduced MMP13 expression in chondrocytes. Although no significant difference was observed between the P3 and P8 groups, a significant difference was found between the P13 and P8 groups. Telomere length analysis revealed that P13 samples had significantly shorter telomeres compared to both P3 and P8. The telomerase activity was positive in P3 and P8 hUC-MSCs, indicating no significant difference between these passages, while it was negative in P13 hUC-MSCs. In conclusion, P3 and P8 hUC-MSCs exhibited superior therapeutic potential for knee osteoarthritis compared to P13, possibly due to their enhanced differentiation capacity and telomerase activity.

PC 18:1/18:1 mediates the anti-inflammatory effects of exercise and remodels tumor microenvironment of hepatocellular carcinoma.

AIM: Phosphatidylcholine (PC) is essential for membrane structural integrity and lipid-dependent signaling pathways, and is an essential component required for cancer cell growth. Using hepatocellular carcinoma (HCC) as a tumor model, this study aims to further screen phospholipid biomarkers of the tumor microenvironment and explore the anti-tumor effects and mechanisms of aerobic exercise. MAIN METHODS: The HCC of C57BL/6J mice was induced by the injection of the carcinogen diethylnitrosamine (DEN). Exercise was performed on an ungraded treadmill for weeks. The inflammation-related markers were detected by ELISA, PCR and immunohistochemistry, hepatic metabolic profile was analyzed by GC/MS, and lipid metabolism profile was further detected by lipid-targeted LC/MS. Cell culture was used to verify the anti-inflammatory effect of PC. KEY FINDINGS: Exercise reduced hepatic inflammation, tumor incidence and volume. Metabolomics analysis showed that palmitic acid is a key metabolic marker for exercise to improve tumor microenvironment. Injection of exogenous palmitic acid following exercise impaired the anti-inflammatory and anti-tumor effects of exercise. Lipid metabolomics analysis further showed that metabolites for exercise were enriched in glycerol phospholipid metabolism, including 14 phosphatidylcholines (PCs), 18 phosphatidylethanolamines (PEs), and 6 triglycerides (TGs). These biomarkers contain different lengths of fatty acid chains and different numbers of unsaturated bonds, respectively. Cell culture verified that PC (18:1/18:1) mediated lipopolysaccharide (LPS)-induced inflammation in HepG2 cell. SIGNIFICANCE: Our results suggest that exercise remodels glycerophospholipid metabolism and reduces hepatic palmitic acid loading and PC (18:1/18:1) level, thereby reconstructing a microenvironment that is hostile to HCC.

Wrist autonomy based on upper-limb synergy: a pilot study.

Incorporating an electrically powered wrist can largely improve the dexterity of a prosthetic hand when grasping various objects; however, it also intensifies the difficulty of the hand's operation due to the introduction of extra degrees of freedom (DOFs). The mechanism of multi-joint synergy in human body movements provides a new sight to solve this problem. In this paper, focusing on four typical manipulation activities of daily life (ADLs), 10 upper-limb joint angles were collected and analyzed first to verify the existence of synergy. Then, a linear regression model was established to predict the wrist rotation angle from the shoulder and elbow joints, which can be directly used as a control reference for achieving wrist autonomy. For both healthy and amputee subjects, experimental platforms were established and control tests were conducted, wherein the task completion time and compensatory movement during the four ADLs were evaluated. The results show that our synergy-based wrist autonomy method can effectively improve the completion efficiency of multiple ADLs without increasing the control complexity. Also, it can significantly reduce the compensatory movements of multiple joints compared to traditional prostheses using an idle wrist.

Regulation of cGAS/STING signaling and corresponding immune escape strategies of viruses.

Innate immunity is the first line of defense against invading external pathogens, and pattern recognition receptors (PRRs) are the key receptors that mediate the innate immune response. Nowadays, there are various PRRs in cells that can activate the innate immune response by recognizing pathogen-related molecular patterns (PAMPs). The DNA sensor cGAS, which belongs to the PRRs, plays a crucial role in innate immunity. cGAS detects both foreign and host DNA and generates a second-messenger cGAMP to mediate stimulator of interferon gene (STING)-dependent antiviral responses, thereby exerting an antiviral immune response. However, the process of cGAS/STING signaling is regulated by a wide range of factors. Multiple studies have shown that viruses directly target signal transduction proteins in the cGAS/STING signaling through viral surface proteins to impede innate immunity. It is noteworthy that the virus utilizes these cGAS/STING signaling regulators to evade immune surveillance. Thus, this paper mainly summarized the regulatory mechanism of the cGAS/STING signaling pathway and the immune escape mechanism of the corresponding virus, intending to provide targeted immunotherapy ideas for dealing with specific viral infections in the future.

Compared with High-intensity Interval Exercise, Moderate Intensity Constant Load Exercise is more effective in curbing the Growth and Metastasis of Lung Cancer.

The morbidity and mortality of lung cancer are among the forefront of various cancers, and it is one of the major cancers that seriously threaten human life and health. It is well known that the abundant angiogenesis and lymphangiogenesis in tumor tissues play an important role in tumor growth and metastasis. In addition, The epithelial-mesenchymal transition (EMT), which facilitates the tumor cell metastasis and invasion, is triggered by many stimuli, such as matrix metalloproteinases 2 (MMP2), MMP9, and transforming growth factor-ß1 (TGF-ß1). At present, various studies have confirmed that both moderate intensity constant load exercise (MICE) and high-intensity interval exercise (HIIE) have a positive therapeutic effect on the treatment of lung cancer, delaying the progression of lung cancer. However, little is currently known regarding whether its specific treatment mechanism is related to blood vessels, lymphatic vessels, and EMT. Indeed, we found an increase in angiogenesis and lymphangiogenesis in lung cancer tissues. However, compared to high-intensity interval exercise, moderate intensity constant load exercise can significantly reduce tumor growth in the lung independent of blood vessels and lymphatic vessels. It is worth noting that moderate intensity constant load exercise can also reduce the level of MMP9 in lung cancer tissues, which may control tumor metastasis to a certain extent. In addition, high-intensity interval exercise reduces the expression of MMP2, but it tends to enhance EMT and activate TGF-ß1. Taken together, our findings suggest that, whether it is tumor growth or metastasis, moderate intensity constant load exercise has a better therapeutic effect on lung cancer than high-intensity interval exercise.

Exercise modulates polarization of TAMs and expression of related immune checkpoints in mice with lung cancer.

Purpose: Many studies have found that both endurance exercise (EX) and high-intensity interval training (HIIT) have a positive therapeutic effect on the treatment of lung cancer patients, but the specific mechanism is unclear. Therefore, we investigated whether EX and HIIT could delay the progression of lung cancer by affecting the infiltration of tumor-associated macrophages (TAMs) and restoring the tumor phagocytic activity of TAMs in lung cancer tissue. Methods: BALB/c mice were divided into 4 groups. The mice were given saline as the saline group (Saline), and the mice were given urethane as the lung cancer mice. The lung cancer mice were randomly divided into the control group (CON), EX group, and HIIT group. After exercise, the cancer tissues were collected for RT-PCR, immunofluorescence staining, and Wes automated western blotting system analysis. Results: Compared with the Saline group, the mRNA levels of TAMs M1 markers IL-6, TNF-α, iNOS, and M2 markers CD206, IL-10, and Arg-1 in the CON group were significantly increased (P<0.05). There was no significant difference in the percentage of F4/80 positive cells among the groups. Compared with the CON group, the percentage of CD86-positive cells in TAMs in the EX group was significantly decreased (P<0.05). From the protein expression level, compared with the CON group, the expression of SIRPα in the EX group was significantly increased (P<0.0001) and the expression of PD-L1 had a tendency to increase (P=0.06). Compared with the CON group, the expressions of IL-10, IL-12, CD47, and CD24 in the HIIT group were significantly increased (P<0.05). In addition, compared with the CON group, plasma IFN-γ in the EX group and HIIT group was significantly increased (P<0.05). Conclusion: Lung cancer tissue presents an inflammatory tumor microenvironment. The therapeutic effect of exercise on lung cancer is independent of the infiltration of TAMs in lung cancer tissue. In addition, endurance exercise can reduce the proportion of M1-type TAMs in lung cancer tissues, while HIIT antagonistically regulates M1 and M2 polarization of TAMs by increasing the levels of IL-10 and IL-12 in lung cancer tissues and circulating IFN-γ. Finally, endurance exercise and HIIT can modulate the expression of some immune checkpoints in lung cancer tissues.

miR-26a-5p Suppresses Wnt/ß-Catenin Signaling Pathway by Inhibiting DNMT3A-Mediated SFRP1 Methylation and Inhibits Cancer Stem Cell-Like Properties of NSCLC.

Background: Lung cancer is a malignant cancer which results in the most cancer incidence and mortality worldwide. There is increasing evidence that the pattern of DNA methylation affects tumorigenesis and progression. However, the molecules and mechanisms regulating DNA methylation remain unclear. Methods: The expression of miR-26a-5p in NSCLC cell lines was detected by qPCR and verified in NSCLC tissues from TCGA using Limma R package. CCK-8 assay, plate clone formation assay, flow cytometry, and sphere formation assay were used to detect the cell proliferation, colony formation, cell cycle, and cancer stem cell- (CSC-) like property in NSCLC cell lines. The immunoblotting was used to detect the protein levels of DNMT3A, SFRP1, and Ki67. Global DNA methylation levels and DNA methylation levels of SFRP1 promoter were examined using ELISA and MSP-PCR assay, respectively. The distribution of ß-catenin was examined using immunofluorescence (IF). Besides, xenograft mouse model was used to investigate the antitumor effects of miR-26a-5p in vivo. The pathology and protein levels were, respectively, detected by hematoxylin and eosin (H&E) and immunocytochemistry (IHC). Results: The expression of miR-26a-5p was downregulated in the tumor tissues comparted to adjacent normal tissues as well as NSCLC cell lines compared to normal lung epithelial cell (BEAS2B). The overexpression of miR-26a-5p inhibited cell proliferation, colony formation, CSC-like property, and arrested cell cycle at G1 phase. DNMT3A was a target of miR-26a-5p and upregulated DNA methylation on SFRP1 promoter. Mechanistically, miR-26a-5p repressed cell proliferation, colony formation, CSC-like property, and arrested cell cycle at G1 phase by binding DNMT3A to reduce DNA methylation levels of SFRP1 then upregulated SFRP1 expression. Moreover, miR-26a-5p exerted antitumor effects in vivo. Conclusion: Our results revealed that miR-26a-5p acted as a tumor suppressor through targeting DNMT3A to upregulate SFRP1 via reducing DNMT3A-dependent DNA methylation.

TUDCA protects against tunicamycin-induced apoptosis of dorsal root ganglion neurons by suppressing activation of ER stress.

The existence of endoplasmic reticulum (ER) stress in neurodegenerative diseases has been well established. Tauroursodeoxycholic acid (TUDCA) is a bile acid taurine conjugate derived from ursodeoxycholic acid, which has been reported to exert cytoprotective effects on several types of cells by inhibiting ER stress. The present study explored the effects of TUDCA on primary cultured rat dorsal root ganglion (DRG) neurons. Cell viability and apoptosis of DRG neurons treated with TUDCA and tunicamycin were detected by CellTiter-Blue assay and TUNEL staining, respectively. The protein levels and phosphorylation of apoptosis and ERS-related signaling pathway molecules were detected by western blot, and the mRNA levels of related genes were assessed by reverse transcription-quantitative PCR. Notably, TUDCA had no significant cytotoxic effect on DRG neurons at concentrations ≤250 µM. In addition, the apoptosis induced by tunicamycin exposure was markedly suppressed by TUDCA, as indicated by the percentage of TUNEL-positive cells, the activities of caspases and the changes in expression levels of critical apoptosis factors. Furthermore, the cytotoxicity of tunicamycin in DRG neurons was accompanied by an increase in malondialdehyde (MDA) content, reactive oxygen species (ROS) and lactate dehydrogenase (LDH) production, and a decrease in glutathione (GSH) levels. The changes in oxidative stress-related factors (ROS, LDH, MDA and GSH) were reversed by TUDCA. Furthermore, as determined by western blotting, the increase in C/EBP homologous protein, glucose-regulated protein 78 and cleaved caspase-12 expression following tunicamycin treatment suggested the activation of ER stress. Downregulation of ER stress components and unfolded protein response sensors by TUDCA confirmed the implication of ER stress in the effects of TUDCA on DRG neurons. In conclusion, the present study indicated that TUDCA may protect against tunicamycin-induced DRG apoptosis by suppressing the activation of ER stress. The protective effect and the therapeutic value of TUDCA in nervous system injury require further study in animal models.

PHILOS Plate Plus Oblique Insertion of Autologous Fibula for 2-Part Proximal Humerus Fractures With Medial Column Disruption: A Retrospective Study.

INTRODUCTION: The aim of this retrospective study was to evaluate the outcomes of older patients with 2-part proximal humerus fractures (PHFs) with medial column disruption stabilized using a proximal humeral internal locking system (PHILOS) plate plus oblique insertion of autologous fibula as a primary procedure. MATERIALS AND METHODS: Data involving 112 patients (112 shoulders) sustaining 2-part PHFs with medial column disruption treated with PHILOS plate plus oblique insertion of autologous fibula as a primary procedure during 2012-2019 were identified. The median follow-up was 36 months (range: 11.2-43.5 months). The primary endpoint was the Constant scores and American Shoulder and Elbow Surgeons (ASES) scores. The secondary endpoint was the main orthopedic complication rate. RESULTS: The median Constant and ASES scores were 78 (range, 52-95) and 77 (range, 62-96) at the final follow-up, respectively. The main orthopedic complication rate was 10.7% (12/112). Twelve orthopedic complications in 8 patients were detected, and they involved loss of reduction, varus collapse, aseptic loosening, mal-union, revision, and intolerable shoulder pain. Of these complications, 3 (2.6%) involved loss of reduction, 2 (1.7%) involved varus collapse, 3 (2.6%) involved aseptic loosening, 1 (0.8%) involved mal-union, 2 (1.7%) required revision surgery, and 1 (0.8%) presented intolerable shoulder pain. CONCLUSION: PHILOS plate plus oblique insertion of autologous fibula as a primary procedure may yield good functional outcomes and a low rate of the main orthopedic complications.

The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy.

Tumor microenvironment (TME) is composed of tumor cells and surrounding non-tumor stromal cells, mainly including tumor associated macrophages (TAMs), endothelial cells, and carcinoma-associated fibroblasts (CAFs). The TAMs are the major components of non-tumor stromal cells, and play an important role in promoting the occurrence and development of tumors. Macrophages originate from bone marrow hematopoietic stem cells and embryonic yolk sacs. There is close crosstalk between TAMs and tumor cells. With the occurrence of tumors, tumor cells secrete various chemokines to recruit monocytes to infiltrate tumor tissues and further promote their M2-type polarization. Importantly, M2-like TAMs can in turn accelerate tumor growth, promote tumor cell invasion and metastasis, and inhibit immune killing to promote tumor progression. Therefore, targeting TAMs in tumor tissues has become one of the principal strategies in current tumor immunotherapy. Current treatment strategies focus on reducing macrophage infiltration in tumor tissues and reprogramming TAMs to M1-like to kill tumors. Although these treatments have had some success, their effects are still limited. This paper mainly summarized the recruitment and polarization of macrophages by tumors, the support of TAMs for the growth of tumors, and the research progress of TAMs targeting tumors, to provide new treatment strategies for tumor immunotherapy.

Lipid-polymer nanoparticles with CD133 aptamers for targeted delivery of all-trans retinoic acid to osteosarcoma initiating cells.

Osteosarcoma, a common type of bone cancer in children, and represents an aggressive and fetal cancer worldwide. Osteosarcoma initiating cells are considered to be a subpopulation of cancer cells which contribute to the progression, recurrence, metastasis and multi-drug resistance of osteosarcoma. CD133 is considered to be one marker for osteosarcoma initiating cells. All-trans retinoic acid (ATRA), an active metabolite of vitamin A under the family retinoid, is an up-and-coming drug which was able to effectively treat various cancer initiating cells. Nevertheless, there have been no research that reported the activity of ATRA against osteosarcoma initiating cells. In this research, we hereby examined the potential activity of ATRA in osteosarcoma initiating cells, and developed lipid-polymer nanoparticles with CD133 aptamers for targeted ATRA delivery to osteosarcoma initiating cells. Using the cytotoxicity assay, colony formation assay, tumorsphere formation assay and flow cytometry, the therapeutic effect of ATRA and ATRA-loaded lipid-polymer nanoparticles conjugated with CD133 aptamers (ATRA-PLNP-CD133) against osteosarcoma initiating cells were investigated. The results showed that ATRA exerted potent activity towards osteosarcoma initiating cells. ATRA-PLNP-CD133, which showed a size of 129.9 nm and a sustained release of ATRA during 144 h, was demonstrated to efficiently and specifically promote the ATRA delivery to osteosarcoma initiating cells, and achieve superior therapeutic efficacy in osteosarcoma compared with ATRA and non-targeted nanoparticles. This is the first report of the therapeutic efficacy of ATRA towards osteosarcoma initiating cells, and the increased ATRA delivery by nanoparticles to osteosarcoma initiating cells using CD133 aptamers. ATRA-PLNP-CD133 represent an up-and coming approach for the therapy of osteosarcoma initiating cells.

Association of OPG gene polymorphisms with the risk of knee osteoarthritis among Chinese people.

BACKGROUND: Osteoarthritis (OA) is usually recognized to have a genetic factor, and in our study, we performed a case-control study to analyze the association between 14 single nucleotide polymorphisms (SNPs) in OPG and the risk of knee OA in a Chinese Han population. METHODS: Fourteen OPG SNPs were assayed using MassARRAY in 393 patients clinically and radiographically diagnosed with knee OA and in 500 controls. Allelic and genotypic frequencies were compared between the groups. Logistic regression adjusting for age and gender was used to estimate risk associations between specific genotypes and knee OA by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: We found that the minor alleles of six SNPs in OPG were associated with an increased or decreased risk of knee OA in the allelic model analysis. In the genetic model analysis, we found that rs1905786, rs1032128, rs3134058, rs11573828, rs11573849, rs3134056, and rs1564861 were associated with an increased or decreased risk of knee OA before adjusted by sex and age. And after adjustment, three SNPs (rs1485286, rs1905786, and rs1032128) were identified to have a negative effect on knee OA. CONCLUSION: Our results verify that genetic variants of OPG contribute to knee OA susceptibility in the population of northern China. These genetic associations may identify individuals at a particularly high risk of developing knee OA.

Optimizing stability in AO/OTA 31-A2 intertrochanteric fracture fixation in older patients with osteoporosis.

Objectives To compare the functional and radiographic outcomes of InterTAN nail (IT) and proximal femoral nail anti-rotation (PFNA) for managing primary AO/OTA 31-A2 intertrochanteric hip fractures (IHFs) in older osteoporotic patients. Methods Patients aged 60 years or older who received surgical treatment for IHFs (AO/OTA 3.1A2.1-A2.3) with IT or PFNA were retrospectively evaluated. The primary outcome was the postoperative treatment failure rate. The secondary outcome was the Harris Hip Score (HHS). Results A total of 326 osteoporotic cases (326 hips: IT, n = 162; PFNA, n = 164) were assessed with a mean follow-up of 43.5 months (range, 38-48 months). For the entire cohort, the incidence of postoperative treatment failure (periprosthetic fracture and reoperation) was 29/326 (8.9%); the IT-treated cohort (7/162, 4.3%) had a significantly lower rate compared with the PFNA-treated cohort (22/165, 13.3%). The incidence of postoperative periprosthetic fractures was significantly lower in the IT-treated cohort than in the PFNA-treated cohort (2.5% vs 7.9%). The postoperative HHS at the final follow-up was not significantly different between the groups. Conclusion IT might show a better outcome in managing osteoporotic AO/OTA 31-A2 IHFs in terms of periprosthetic fracture and reoperation compared with PFNA.

Epidermal growth factor receptor aptamer-conjugated polymer-lipid hybrid nanoparticles enhance salinomycin delivery to osteosarcoma and cancer stem cells.

Osteosarcoma is a common childhood bone cancer with a poor survival rate. Osteosarcoma cancer stem cells (CSCs) contribute to the recurrence, drug resistance and metastasis of this disease. Previous evidence suggested that cancer cells are able to spontaneously turn into CSCs, thus it is crucial to simultaneously target osteosarcoma cells and CSCs. Our previous studies have demonstrated that salinomycin preferably eliminated osteosarcoma CSCs. In addition, amplification of the epidermal growth factor receptor (EGFR) is a common genetic aberration in osteosarcoma, and thus EGFR is a promising target in osteosarcoma. The present study aimed to develop EGFR aptamer-conjugated salinomycin-loaded polymer-lipid hybrid nanoparticles (EGFR-SNPs) to target both osteosarcoma cells and CSCs. The results revealed that EGFR was overexpressed in these cells, and that EGFR-SNPs possessed a small size of 95 nm, suitable drug encapsulation efficiency (63%) and sustained drug release over 120 h. EGFR-SNPs targeted EGFR-overexpressing osteosarcoma cells and CSCs, resulting in an enhanced cytotoxic effect compared with non-targeted SNPs and salinomycin. Notably, EGFR-SNPs was able to reduce the osteosarcoma tumorsphere formation rate and proportion of CD133+ osteosarcoma CSCs in the osteosarcoma cell lines more effectively compared with SNPs and salinomycin, suggesting that EGFR-SNPs effectively reduced the proportion of osteosarcoma CSCs. In conclusion, the interaction of EGFR aptamers and EGFR is a potential approach to promote the effective delivery of salinomycin to osteosarcoma. The study results suggested that EGFR-SNPs represents a promising approach to target osteosarcoma cells and CSCs.

Scaphoid instability caused by a giant cell tumour of the tendon sheath: A case report.

Giant-cell tumour of the tendon sheath (GCTTS) is a soft tissue tumour that may invade bone, causing an intrinsic osseous lesion or instability on radiographs. A case with scaphoid instability caused by a histologically-confirmed neighbouring GCTTS has rarely been described in the literature. No definite and radical method is available for the treatment of GCTTS. This report describes an unusual case of a 22-year-old woman who previously experienced a GCTTS in her right elbow, which was removed 10 years earlier. Currently, she presented with an enlarged painless right wrist mass with focal swelling. The mass has been present for 5 years. During the previous 6 months, she felt something pop and experienced pain with limited motion in her right wrist. Magnetic resonance imaging demonstrated a well-circumscribed soft tissue mass. Under general anaesthesia, complete surgical resection of the mass was undertaken. Histopathological examination revealed that the mass was a GCTTS. Less invasive leverage reduction with external fixator support and iliac crest bone autologous graft for treatment of carpal instability were performed. Radical resection combined with external fixator support and bone grafting can provide a new option for the treatment of carpal instability.

Rivaroxaban versus nadroparin for preventing deep venous thrombosis after total hip arthroplasty following femoral neck fractures: A retrospective comparative study.

Objective This study was performed to evaluate the efficacy of rivaroxaban versus nadroparin for preventing deep venous thrombosis (DVT) in elderly patients with osteoporosis undergoing initial total hip arthroplasty (THA) for femoral neck fractures. Methods Prospectively maintained databases were reviewed to retrospectively compare elderly patients with osteoporosis who underwent initial THA for femoral neck fractures from 2007 to 2015. The patients received peroral rivaroxaban at 10 mg/day for 2 weeks or subcutaneous injections of nadroparin at 0.3 mL/day for 2 weeks until the primary analysis cut-off date. The time to first on-study DVT was the primary endpoint. Results In total, 399 patients were included (rivaroxaban group: n=200; mean age, 70.20 ± 9.16 years and nadroparin group: n = 199; mean age, 69.90 ± 8.87 years), with a mean 3-year follow-up. The time to first on-study DVT was significantly longer in the rivaroxaban than nadroparin group (12 and 5 days, respectively). The incidence of DVT within the 2-week follow-up was significantly higher in the nadroparin than rivaroxaban group (6.8% and 19.7%, respectively), but this difference was no longer present at the final follow-up. Conclusion Rivaroxaban was associated with a significant reduction in the occurrence of first on-study DVT compared with nadroparin.