The C2 isthmus screw provided sufficient biomechanical stability in the setting of atlantoaxial dislocation-a finite element study.

BACKGROUND: The emerging of the C2 isthmus screw fixation technique is gaining popularity in the setting of atlantoaxial dislocation or other conditions requiring fixation of C2. However, the biomechanical stability of this fixation is poorly understood. PURPOSE: To compare and elucidate the biomechanical stability of C2 pedicle screw (C2PS), C2 isthmus screw (C2IS) and C2 short isthmus screw (C2SIS) fixation techniques in atlantoaxial dislocation (AAD). METHOD: A three-dimensional finite element model (FEM) from occiput to C3 was established and validated from a healthy male volunteer. Three FEMs, C1 pedicle screw (PS)-C2PS, C1PS-C2IS, C1PS-C2SIS were also constructed. The range of motion (ROM) and the maximum von Mises stress under flexion, extension, lateral bending and axial rotation loading were analyzed and compared. The pullout strength of the three fixations for C2 was also evaluated. RESULT: C1PS-C2IS model showed the greatest decrease in ROM with flexion, extension, lateral bending and axial rotation. C1PS-C2PS model showed the least ROM reduction under all loading conditions than both C2IS and C2SIS. The C1PS-C2PS model had the largest von Mises stress on the screw under all directions followed by C1PS-C2SIS, and lastly the C1PS-C2IS. Under axial rotation and lateral bending loading, the three models showed the maximum and minimum von Mises stress on the screw respectively. The stress of the three models was mainly located in the connection of the screw and rod. Overall, the maximum screw pullout strength for C2PS, C2IS and C2SIS were 729.41N, 816.62N, 640.54N respectively. CONCLUSION: In patients with atlantoaxial dislocations, the C2IS fixation provided comparable stability, with no significant stress concentration. Furthermore, the C2IS had sufficient pullout strength when compared with C2PS and C2SIS. C2 isthmus screw fixation may be a biomechanically favourable option in cases with AAD. However, future clinical trials are necessary for the evaluation of the clinical outcomes of this technique.

Integrin αVß3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVß3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVß3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVß3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL. METHODS: OPLL or control ligament samples were collected in surgery. For OPLL samples, RNA-sequencing results revealed activation of the integrin family, particularly integrin αVß3. Integrin αVß3 expression was detected by qPCR, Western blotting, and immunohistochemical analysis. Fluorescence microscopy was used to observe the targeted inhibition of integrin αVß3 by the c(RGDyk) peptide on ligaments fibroblasts (LFs) derived from patients with OPLL and endothelial cells (ECs). The effect of c(RGDyk) peptide on the ossification of pathogenic LFs was detected using qPCR, Western blotting. Alkaline phosphatase staining or alizarin red staining were used to test the osteogenic capability. The effect of the c(RGDyk) peptide on angiogenesis was determined by EC migration and tube formation assays. The effects of the c(RGDyk) peptide on heterotopic bone formation were evaluated by micro-CT, histological, immunohistochemical, and immunofluorescence analysis in vivo. RESULTS: The results indicated that after being treated with c(RGDyk), the osteogenic differentiation of LFs was significantly decreased. Moreover, the c(RGDyk) peptide inhibited the migration of ECs and thus prevented the nutritional support required for osteogenesis. Furthermore, the c(RGDyk) peptide inhibited ectopic bone formation in mice. Mechanistic analysis revealed that c(RGDyk) peptide could inhibit osteogenesis and angiogenesis in OPLL by targeting integrin αVß3 and regulating the FAK/ERK pathway. CONCLUSIONS: Therefore, the integrin αVß3 appears to be an emerging therapeutic target for OPLL, and the c(RGDyk) peptide has dual inhibitory effects that may be valuable for the new therapeutic strategy of OPLL.

MRI-based vertebral bone quality score in cervical ossification of the posterior longitudinal ligament: a comparison with cervical spondylotic myelopathy using propensity score matching.

BACKGROUND: Bone mineral density plays a key role in the assessment of operative instrumentation complications and clinical outcomes. The MRI-based vertebral bone quality (VBQ) score has been introduced as a novel marker of bone quality. However, few studies have investigated the relationship between VBQ score and patients associated with cervical ossification of the posterior longitudinal ligament (OPLL). PURPOSE: The aims of the study were (1) to reveal bone mineral density between cervical OPLL and cervical spondylotic myelopathy (CSM) group by VBQ score, (2) to compare the VBQ score of cervical OPLL between male and female group, (3) to explore the relationship between segmental VBQ scores associated with OPLL. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Consecutive series of 425 patients at a single academic institution. OUTCOME MEASURES: MRI based measurements of C2-C7 VBQ scores. METHODS: Preoperative noncontrast T1-weighted MRIs of the cervical spine was used to measure the VBQ score. The VBQ score was defined as the mean value of the signal intensity of the vertebrae divided by that of the cerebrospinal fluid (CSF) space at the cisterna magna. Patients with cervical OPLL and CSM were matched based on age, sex, body mass index (BMI), comorbidity, medication history, diet habit, smoking, alcohol consumption via propensity score matching (PSM). Normality of each VBQ score was tested by the Shapiro-Wilk test. Wilcoxon's rank-sum test was used to compare matched cohorts. Kruskal-Wallis test was performed to compare the VBQ scores between segments. Multivariate logistic regression analysis was used to evaluate factors associated with the development of cervical OPLL. RESULTS: A total of 425 patients were assessed. For final analysis, 135 paired patients were compared between the cervical OPLL and CSM groups, and 22 paired patients were compared between male and female group associated with cervical OPLL. There were no statistically significant differences in age, sex, BMI, comorbidity, medication history, diet habit, smoking, alcohol between the matched cohorts. OPLL group was associated with lower VBQ score compared with CSM group at C3, while there were no differences in VBQ score for the other levels between the two groups. There were no differences between male and female group associated with OPLL in C2-C7 VBQ scores. VBQ scores of cervical OPLL are variable between segments, with significantly lower scores at C6, C7 compared with C1-C5. Multivariate logistic regression analysis showed that BMI was correlated with the development of OPLL (regression coefficient, 0.162; 95% confidence interval, 0.010-0.037). Additional risk factors included hypertension, calcium supple history and smoking. CONCLUSIONS: This study demonstrates that cervical OPLL is associated with lower VBQ score at C3, with no differences for the other levels when compared with CSM derived from measurements on MRI. No differences were found between male and female group associated with OPLL in C2-C7 VBQ scores. Cervical OPLL were found to have smaller VBQ score at C6, C7 compared with C1-C5. Our findings provide new insight for bone density assessment in cervical OPLL patient.

Engineered Macrophage Membrane-Coated Nanoparticles with Enhanced CCR2 Expression Promote Spinal Cord Injury Repair by Suppressing Neuroinflammation and Neuronal death.

Spinal cord injury (SCI) is a severe neurological disorder characterized by significant disability and limited treatment options. Mitigating the secondary inflammatory response following the initial injury is the primary focus of current research in the treatment of SCI. CCL2 (C─C motif chemokine ligand 2) serves as the primary regulator responsible for inflammatory chemotaxis of the majority of peripheral immune cells, blocking the CCL2-CCR2 (C─C chemokine receptor type 2) axis has shown considerable therapeutic potential for inflammatory diseases, including SCI. In this study, it presents a multifunctional biomimetic nanoplatform (CCR2-MM@PLGA/Cur) specifically designed to target the CCL2-CCR2 axis, which consisted of an engineered macrophage membrane (MM) coating with enhanced CCR2 expression and a PLGA (poly (lactic-co-glycolic acid)) nanoparticle that encapsulated therapeutic drugs. CCR2 overexpression on MM not only enhanced drug-targeted delivery to the injury site, but also attenuated macrophage infiltration, microglia pro-inflammatory polarization, and neuronal apoptosis by trapping CCL2. Consequently, it facilitated neural regeneration and motor function recovery in SCI mice, enabling a comprehensive treatment approach for SCI. The feasibility and efficacy of this platform are confirmed through a series of in vitro and in vivo assays, offering new insights and potential avenues for further exploration in the treatment of SCI.

Engineering Copper-Containing Nanoparticles-Loaded Silicene Nanosheets with Triple Enzyme Mimicry Activities and Photothermal Effect for Promoting Bacteria-Infected Wound Healing.

Skin wounds accompanied by bacterial infections threaten human health, and conventional antibiotic treatments are ineffective for drug-resistant bacterial infections and chronically infected wounds. The development of non-antibiotic-dependent therapeutics is highly desired but remains a challenging issue. Recently, 2D silicene nanosheets with considerable biocompatibility, biodegradability, and photothermal-conversion performance have received increasing attention in biomedical fields. Herein, copper-containing nanoparticles-loaded silicene (Cu2.8O@silicene-BSA) nanosheets with triple enzyme mimicry catalytic (peroxidase, catalase, and oxidase-like) activities and photothermal function are rationally designed and fabricated for efficient bacterial elimination, angiogenesis promotion, and accelerated wound healing. Cu2.8O@silicene-BSA nanosheets display excellent antibacterial activity through synergistic effects of reactive oxygen species generated from multiple catalytic reactions, intrinsic bactericidal activity of released Cu2+ ions, and photothermal effects, achieving high antibacterial efficiencies on methicillin-resistant Staphylococcus aureus (MRSA) of 99.1 ± 0.7% in vitro and 97.2 ± 1.6% in vivo. In addition, Cu2.8O@silicene-BSA nanosheets exhibit high biocompatibility for promoting human umbilical vein endothelial cell (HUVEC) proliferation and angiogenic differentiation. In vivo experiments reveal that Cu2.8O@silicene-BSA nanosheets with synergistic photothermal/chemodynamic therapeutics effectively accelerate MRSA-infected wound healing by eliminating bacteria, alleviating inflammation, boosting collagen deposition, and promoting angiogenesis. This research presents a promising strategy to engineer photothermal-assisted nanozyme catalysis for bacteria-invaded wound healing.

TMEM135 maintains the equilibrium of osteogenesis and adipogenesis by regulating mitochondrial dynamics.

BACKGROUND: Disturbance in the differentiation process of bone marrow mesenchymal stem cells (BMSCs) leads to osteoporosis. Mitochondrial dynamics plays a pivotal role in the metabolism and differentiation of BMSCs. However, the mechanisms underlying mitochondrial dynamics and their impact on the differentiation equilibrium of BMSCs remain unclear. METHODS: We investigated the mitochondrial morphology and markers related to mitochondrial dynamics during BMSCs osteogenic and adipogenic differentiation. Bioinformatics was used to screen potential genes regulating BMSCs differentiation through mitochondrial dynamics. Subsequently, we evaluated the impact of Transmembrane protein 135 (TMEM135) deficiency on bone homeostasis by comparing Tmem135 knockout mice with their littermates. The mechanism of TMEM135 in mitochondrial dynamics and BMSCs differentiation was also investigated in vivo and in vitro. RESULTS: Distinct changes in mitochondrial morphology were observed between osteogenic and adipogenic differentiation of BMSCs, manifesting as fission in the late stage of osteogenesis and fusion in adipogenesis. Additionally, we revealed that TMEM135, a modulator of mitochondrial dynamics, played a functional role in regulating the equilibrium between adipogenesis and osteogenesis. The TMEM135 deficiency impaired mitochondrial fission and disrupted crucial mitochondrial energy metabolism during osteogenesis. Tmem135 knockout mice showed osteoporotic phenotype, characterized by reduced osteogenesis and increased adipogenesis. Mechanistically, TMEM135 maintained intracellular calcium ion homeostasis and facilitated the dephosphorylation of dynamic-related protein 1 at Serine 637 in BMSCs. CONCLUSIONS: Our findings underscore the significant role of TMEM135 as a modulator in orchestrating the differentiation trajectory of BMSCs and promoting a shift in mitochondrial dynamics toward fission. This ultimately contributes to the osteogenesis process. This work has provided promising biological targets for the treatment of osteoporosis.

2D silicene nanosheets-loaded coating for combating implant-associated infection.

Implant-associated infection (IAI) is an unsolved problem in orthopaedics. Current therapies, including antibiotics and surgical debridement, can lead severe clinical and financial burdens on patients. Therefore, there is an urgent need to reinforce the inherent antibacterial properties of implants. Recently, two-dimensional (2D) silicene nanosheets (SNs) have gained increasing attention in biomedical fields owing to their considerable biocompatibility, biodegradability and strong photothermal-conversion performance. Herein, a dual-functional photosensitive coating on a Ti substrate (denoted as TPSNs) was rationally fabricated for bacterial inhibition and osteogenesis promotion. For the first time, SNs were loaded onto the surface of implants. Hyperthermia generated by the SNs and polydopamine (PDA) coating under 808 nm laser irradiation achieved the in vitro anti-bacterial efficiency of 90.7 ± 2.4 % for S. aureus and 88.0 ± 5.8 % for E. coli, respectively. In addition, TPSNs exhibited promising biocompatibility for the promotion of BMSC (bone marrow mesenchymal stem cells) proliferation and spreading. The presence of silicon (Si) in TPSNs contributed to the improved osteogenic differentiation of BMSCs, elevating the expressions of RUNX2 and OCN. In animal experiments, the combination of TPSNs with photothermal therapy (PTT) achieved an anti-bacterial efficiency of 89.2 % ± 1.6 % against S. aureus. Furthermore, TPSNs significantly improved bone-implant osseointegration in vivo. Overall, the development of a dual-functional TPSNs coating provides a new strategy for combating IAI.

M2 macrophage-derived exosome-encapsulated microneedles with mild photothermal therapy for accelerated diabetic wound healing.

Due to local overactive inflammatory response and impaired angiogenesis, current treatments for diabetic wounds remain unsatisfactory. M2 macrophage-derived exosomes (MEs) have shown considerable potential in biomedical applications, especially since they have anti-inflammatory properties that modulate macrophage phenotypes. However, exosome-based strategies still have limitations, such as short half-lives and instability. Herein, we develop a double-layer microneedle-based wound dressing system (MEs@PMN) by encapsulating MEs in the needle tips and polydopamine (PDA) nanoparticles in backing layer to simultaneously suppress inflammation and improve angiogenesis at the wound site. In vitro, released MEs increased macrophage polarization towards the M2 phenotype. In addition, mild heat (40 â€‹°C) generated by the photosensitive PMN backing layer contributed to improved angiogenesis. More importantly, MEs@PMN also showed promising effects in diabetic rats. The uncontrolled inflammatory response at the wound site was inhibited by MEs@PMN during a 14-day period; in addition, MEs and the photothermal effects produced by PMN provided a combined proangiogenic effect by improving the expression of CD31 and vWF. Collectively, this study provides a simple and efficient cell-free strategy for suppressing inflammation and promoting vascular regeneration to treat diabetic wounds.

Combined photothermal and sonodynamic therapy using a 2D black phosphorus nanosheets loaded coating for efficient bacterial inhibition and bone-implant integration.

Surgical site infection (SSI) remains a major threat for implant failure in orthopedics. Herein, we report a dual-functional coating on Ti implants (named Ti/PDA/BP) with the integration of two-dimensional (2D) photo-sono sensitive black phosphorus nanosheets (BPNSs) and polydopamine (PDA) for efficient bacterial inhibition and bone-implant integration. For the first time, we employ BPNSs as generators of reactive radicals (ROS) under ultrasound (US) stimuli for implant associated infection. Additionally, the application of PDA improves the stability of BPNSs, the biocompatibility and photothermal performance of this hybrid coating. The as-prepared Ti/PDA/BP coating exhibits superior biocompatibility, bioactivity, photothermal and sonodynamic conversion abilities. Owing to the synergistic effect of hyperthermia and ·OH, Ti/PDA/BP damages the membrane and antioxidant system of Staphylococcus aureus, reaching a high antibacterial activity of 96.6% in vitro and 97.3% in vivo with rapid 10 min NIR irradiation and 20 min US treatment. In addition, we firstly unveil the significant effect of Ti/PDA/BP-based sonodynamic therapy (SDT) on bacterial membrane and oxidative stress at the transcriptome level. Moreover, the Ti/PDA/BP coating remarkably promotes osteogenesis in vitro and bone-implant osseointegration in vivo. Overall, development of Ti/PDA/BP bioactive coating provides a new strategy for combating the implant associated infection.

Remote ischemic preconditioning protects against spinal cord ischemia-reperfusion injury in mice by activating NMDAR/AMPK/PGC-1α/SIRT3 signaling.

BACKGROUND: To study the protective effects of delayed remote ischemic preconditioning (RIPC) against spinal cord ischemia-reperfusion injury (SCIRI) in mice and determine whether SIRT3 is involved in this protection and portrayed its upstream regulatory mechanisms. METHODS: In vivo, WT or SIRT3 global knockout (KO) mice were exposed to right upper and lower limbs RIPC or sham ischemia. After 24 h, the abdominal aorta was clamped for 20 min, then re-perfused for 3 days. The motor function of mice, number of Nissl bodies, apoptotic rate of neurons, and related indexes of oxidative stress in the spinal cord were measured to evaluate for neuroprotective effects. The expression and correlation of SIRT3 and NMDAR were detected by WB and immunofluorescence. In vitro, primary neurons were exacted and OGD/R was performed to simulate SCIRI in vivo. Neuronal damage was assessed by observing neuron morphology, detecting LDH release ratio, and flow cytometry to analyze the apoptosis. MnSOD and CAT enzyme activities, GSH and ROS level were also measured to assess neuronal antioxidant capacity. NMDAR-AMPK-PGC-1α signaling was detected by WB to portray upstream regulatory mechanisms of RIPC regulating SIRT3. RESULTS: Compared to the SCIRI mice without RIPC, mice with RIPC displayed improved motor function recovery, a reduced neuronal loss, and enhanced antioxidant capacity. To the contrary, the KO mice did not exhibit any effect of RIPC-induced neuroprotection. Similar results were observed in vitro. Further analyses with spinal cord tissues or primary neurons detected enhanced MnSOD and CAT activities, as well as increased GSH level but decreased MDA or ROS production in the RIPC + I/R mice or NMDA + OGD/R neurons. However, these changes were completely inhibited by the absence of SIRT3. Additionally, NMDAR-AMPK-PGC-1α signaling was activated to upregulate SIRT3 levels, which is essential for RIPC-mediated neuroprotection. CONCLUSIONS: RIPC enhances spinal cord ischemia tolerance in a SIRT3-dependent manner, and its induced elevated SIRT3 levels are mediated by the NMDAR-AMPK-PGC-1α signaling pathway. Combined therapy targeting SIRT3 is a promising direction for treating SCIRI.

Engineering of M2 Macrophages-Derived Exosomes via Click Chemistry for Spinal Cord Injury Repair.

Spinal cord injury (SCI) is one of the most common causes of death and disability. The effective modulation of complicated microenvironment, regeneration of injured spinal cord tissue, and the functional recovery after SCI are still clinical challenges. Recently, macrophages-derived exosomes have shown great potential for various diseases due to their inflammation-targeting property. However, further modifications are needed to endow exosomes with the neural regenerative potential for SCI recovery. In the current study, a novel nanoagent (MEXI) is designed for SCI treatment by conjugating bioactive IKVAV peptides to the surface of M2 macrophages-derived exosomes via an easy and rapid click chemistry method. In vitro, MEXI inhibits the inflammation by reprograming macrophages and promotes neuronal differentiation of neural stem cells. In vivo, engineered exosomes target the injured site of the spinal cord after tail vein injection. Furthermore, histological analysis reveals that MEXI improves motor functional recovery of SCI mice by reducing infiltration of macrophages, downregulating pro-inflammatory factors, and improving the regeneration of injured nervous tissues. Taken together, this study provides strong evidence for the significance of MEXI in SCI recovery.

High GNG13 expression is associated with poor survival in epithelial ovarian cancer and breast cancer.

Recently, change in the GNG13 expression has been shown to result in multiple congenital malformations and sexual reversal, and it was also found in the brain. The aim of this study was to measure the expression levels in epithelial ovarian cancer (EOC) and breast cancer (BC) and assess their value as a potential prognostic marker. The correlation of GNG13 protein expression was detected by immunohistochemistry (IHC) in 119 EOC and 125 BC tissues. Assessment of the associations between GNG13 levels and various clinicopathological features was identified, the relationship between GNG13 and prognosis in BC and EOC patients was analyzed using online resources of Oncomine and Kaplan-Meier plotter. Protein expression levels of GNG13 were both significantly lower in BC and EOC compared with normal tissues (p<0.0001 and p<0.001, respectively). Among the clinicopathological characteristics of BC, tumor grade (p=0.001) and TNM stage (p=0.001) were significantly associated with low expression of GNG13. While in EOC, low expression of GNG13 was significantly related to FIGO stage (p=0.001), presence of metastasis (p=0.001), and CA125 (p=0.001). Our data suggest that GNG13 expression maybe as a new inhibitor, which can strongly inhibit metastasis and partially attenuates tumor growth in EOC and BC.

EphA8 inhibits cell apoptosis via AKT signaling and is associated with poor prognosis in breast cancer.

Erythropoietin­producing hepatocellular receptors (Ephs) comprise the largest subfamily of receptor tyrosine kinases and have been reported to be involved in a variety of biological cellular processes, including tumorigenesis and cancer progression. The present study aimed to determine the expression levels and clinicopathological significance of EphA8 in breast cancer (BC) using immunohistochemistry analysis of tissue microarrays. The results of the present study revealed that EphA8 expression levels were upregulated in BC tissue and were associated with tumor size and TNM stage. In addition, upregulated expression levels of EphA8 were identified to be a poor prognostic biomarker for patients with BC. The knockdown of EphA8 expression using short hairpin RNA resulted in increased levels of apoptosis as well as decreased proliferation, migration and invasion of BC cells both in vivo and in vitro. The knockdown of EphA8 also decreased the phosphorylation of AKT, which was accompanied by downregulation of Bcl­2 expression levels and upregulation of p53, Caspase­3 and Bax expression levels. Moreover, knockdown of EphA8 expression increased the chemosensitivity of BC cells to paclitaxel. In conclusion, the results of the present study indicated that EphA8 may be a useful prognostic marker in BC and that knockdown of EphA8 may represent a novel strategy in adjuvant chemotherapy for the treatment of BC.

The lncRNA ADAMTS9-AS2 Regulates RPL22 to Modulate TNBC Progression via Controlling the TGF-ß Signaling Pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) are key regulators of triple-negative breast cancer (TNBC) progression, but further work is needed to fully understand the functional relevance of these non-coding RNAs in this cancer type. Herein, we explored the functional role of the lncRNA ADAMTS9-AS2 in TNBC. METHODS: Next-generation sequencing was conducted to compare the expression of different lncRNAs in TNBC tumor and paracancerous tissues, after which ADAMTS9-AS2differential expression in these tumor tissues was evaluated via qPCR. The functional role of this lncRNA was assessed by overexpressing it in vitro and in vivo. FISH and PCR were used to assess the localization of ADAMTS9-AS2within cells. Downstream targets of ADAMTS9-AS2 signaling were identified via RNA pulldown assays and transcriptomic sequencing. RESULTS: The expression ofADAMTS9-AS2 was decreased in TNBC tumor samples (P < 0.05), with such downregulation being correlated with TNM stage, age, and tumor size. Overexpressing ADAMTS9-AS2 promoted the apoptotic death and cell cycle arrest of tumor cells in vitro and inhibited tumor growth in vivo. From a mechanistic perspective, ADAMTS9-AS2 was found to control the expression of RPL22 and to thereby modulate TGF-ß signaling to control TNBC progression. CONCLUSION: ADAMTS9-AS2 controls the expression of RPL22 and thereby regulates TNBC malignancy via the TGF-ß signaling pathway.

Study of effects of anthracycline drugs on myocardial function in breast cancer patients by quantitative analysis of layer-specific strain via 2D-STI technology.

OBJECTIVE: This study aimed to explore the value of layer-specific strain analysis by two-dimensional speckle tracking imaging (2D-STI) in the assessment of myocardial toxicity in breast cancer patients receiving anthracycline chemotherapy. METHODS: Thirty-four breast cancer patients receiving anthracycline chemotherapy were prospectively enrolled. Conventional echocardiography and 2D-STI were evaluated at baseline after the third and sixth cycles of anthracycline chemotherapy. The strains of different layers of left ventricle (LV) including peak systolic longitudinal strain (endo-LS, mid-LS, epi-LS) and circumferential strain (endo-CS, mid-CS, epi-CS) were measured using EchoPAC analysis software. Peak systolic longitudinal strain (MV-LS, PM-LS, AP-LS), circumferential strain (MV-CS, PM-CS, AP-CS) and radial strain (MV-RS, PM-RS, AP-RS) were measured at mitral valve, papillary muscle and apex levels of LV respectively. Global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and left ventricular twist (LVtw) were also analyzed. RESULTS: There was no significant difference in the structural and functional parameters of conventional 2D echocardiography in different cycles of anthracycline chemotherapy (P>0.05); layer specific LS and CS in various cycles decreased layer by layer from inside to outside. LS and CS increased from basal segment to apical segment, while RS showed no obvious gradient characteristics; compared with baseline, GLS and LSs (endo-PM, endo-AP, mid-PM, mid-AP and epi-AP) of LV decreased significantly after the third cycle of chemotherapy (P<0.05); LSs (epi-MV and epi-AP) decreased significantly after the sixth cycle of chemotherapy (P<0.05). No significant changes were detected in layer specific CS, RS and LVtw (P>0.05). CONCLUSION: Layer-specific strain analysis by 2D-STI technology can quantitatively analyze global and regional functions of LV. The myocardial toxicity due to anthracycline chemotherapy can be detected by layer-specific LS of LV in early stage, which is great valuable to guiding clinical early intervention and improving prognosis.

Ultrasonographic characteristics of Killian-Jamieson diverticula.

PURPOSE: A Killian-Jamieson diverticulum (KJD) may be mistaken for a thyroid nodule on ultrasound (US). The purpose of this retrospective study was to search for specific US features that would help differentiate between KJD and thyroid nodules. METHODS: A total of 12 patients with KJD who had undergone an US examination of the neck were identified. The size, shape, boundary, echopattern, location, color flow signals on color Doppler US of KJD and the relationship between the lesion and esophageal wall were analyzed. The change of size, shape and internal echotexture were also observed when the lesion was compressed with the probe and when the patient was asked to drink water. RESULTS: All KJD were confirmed by barium esophagography. All KJD were posterior to the left thyroid lobe on US, and were associated with a semicircular hypoechoic anterior wall. The internal echotexture was heterogeneous. In eight cases, the connection to the esophageal wall was seen. When compressing with the US probe or when the patients swallowed water, the size, shape or internal echotexture of the lesion changed. CONCLUSION: The specific criteria for US diagnosis of KJD included the connection to the esophageal wall and the fact that the internal echotexture, shape and size of KJD changed in real-time when the patient swallowed water or when the lesion was compressed with the transducer.

A comparison of the bilateral decompression via unilateral approach versus conventional approach transforaminal lumbar interbody fusion for the treatment of lumbar degenerative disc disease in the elderly.

BACKGROUND: Bilateral decompression via unilateral approach (BDUA) is an effective surgical approach for treating lumbar degenerative diseases. However, no studies of prognosis, especially the recovery of the soft tissue, have reported using BDUA in an elderly population. The aims of these research were to investigate the early efficacy of the bilateral decompression via unilateral approach versus conventional approach transforaminal lumbar interbody fusion (TLIF) for the treatment of lumbar degenerative disc disease in the patients over 65 years of age, especially in the perioperative factors and the recovery of the soft tissue. METHODS: The clinical data from 61 aging patients with lumbar degenerative disease who received surgical treatment were retrospectively analyzed. 31 cases who received the lumbar interbody fusion surgery with bilateral decompression via unilateral approach (BDUA) were compared with 30 cases who received conventional approach transforaminal lumbar interbody fusion. The radiographic parameters were measured using X-ray including lumbar lordosis angle and fusion rate. Japanese Orthopedic Association (JOA), Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were used to evaluate the clinical outcomes at different time points. Fatty degeneration ratio and area of muscle/vertebral body were used to detect recovery of soft tissue. RESULTS: The BDUA approach group was found to have significantly less intraoperative blood loss(p < 0.05) and postoperative drainage(p < 0.05) compared to conventional approach transforaminal lumbar interbody fusion group. Symptoms of spinal canal stenosis and nerve compression were significantly relieved postoperatively, as compared with the preoperative state. However, the opposite side had a lower rate of fatty degeneration (9.42 ± 3.17%) comparing to decompression side (11.68 ± 3.08%) (P < 0.05) six months after surgery in the BDUA group. While there were no significant differences (P > 0.05) in two sides of conventional transforaminal lumbar interbody fusion approach group six months after surgery. CONCLUSIONS: Bilateral decompression via unilateral approach (BDUA) is able to reduce the intraoperative and postoperative body fluid loss in the elderly. The opposite side of decompression in BDUA shows less fatty degeneration in 6 months, which indicates better recovery of the soft tissue of the aging patients.

Salidroside Ameliorates Mitochondria-Dependent Neuronal Apoptosis after Spinal Cord Ischemia-Reperfusion Injury Partially through Inhibiting Oxidative Stress and Promoting Mitophagy.

Ischemia-reperfusion injury is the second most common injury of the spinal cord and has the risk of neurological dysfunction and paralysis, which can seriously affect patient quality of life. Salidroside (Sal) is an active ingredient extracted from Herba Cistanche with a variety of biological attributes such as antioxidant, antiapoptotic, and neuroprotective activities. Moreover, Sal has shown a protective effect in ischemia-reperfusion injury of the liver, heart, and brain, but its effect in ischemia-reperfusion injury of the spinal cord has not been elucidated. Here, we demonstrated for the first time that Sal pretreatment can significantly improve functional recovery in mice after spinal cord ischemia-reperfusion injury and significantly inhibit the apoptosis of neurons both in vivo and in vitro. Neurons have a high metabolic rate, and consequently, mitochondria, as the main energy-supplying suborganelles, become the main injury site of spinal cord ischemia-reperfusion injury. Mitochondrial pathway-dependent neuronal apoptosis is increasingly confirmed by researchers; therefore, Sal's effect on mitochondria naturally attracted our attention. By means of a range of experiments both in vivo and in vitro, we found that Sal can reduce reactive oxygen species production through antioxidant stress to reduce mitochondrial permeability and mitochondrial damage, and it can also enhance the PINK1-Parkin signaling pathway and promote mitophagy to eliminate damaged mitochondria. In conclusion, our results show that Sal is beneficial to the protection of spinal cord neurons after ischemia-reperfusion injury, mainly by reducing apoptosis associated with the mitochondrial-dependent pathway, among which Sal's antioxidant and autophagy-promoting properties play an important role.

Elevated Expression of RIOK1 Is Correlated with Breast Cancer Hormone Receptor Status and Promotes Cancer Progression.

PURPOSE: RIOK1 has been proved to play an important role in cancer cell proliferation and migration in various types of cancers-such as colorectal and gastric cancers. However, the expression of RIOK1 in breast cancer (BC) and the relationship between RIOK1 expression and the development of BC are not well characterized. In this study, we assessed the expression of RIOK1 in BC and evaluated the mechanisms underlying its biological function in this disease context. MATERIALS AND METHODS: We used immunohistochemistry, western blot and quantitative real-time polymerase chain reaction to evaluate the expression of RIOK1 in BC patients. Then, knockdown or overexpression of RIOK1 were used to evaluate the effect on BC cells in vitro and in vivo. Finally, we predicted miR-204-5p could be a potential regulator of RIOK1. RESULTS: We found that the expression levels of RIOK1 were significantly higher in hormone receptor (HR)-negative BC patients and was associated with tumor grades (p=0.010) and p53 expression (p=0.008) and survival duration (p=0.011). Kaplan-Meier analysis suggested a tendency for the poor prognosis. In vitro, knockdown of RIOK1 could inhibit proliferation, invasion, and induced apoptosis in HR-negative BC cells and inhibited tumorigenesis in vivo, while overexpression of RIOK1 promoted HR-positive tumor progression. MiR-204-5p could regulate RIOK1 expression and be involved in BC progression. CONCLUSION: These findings indicate that RIOK1 expression could be a biomarker of HR-negative BC, and it may serve as an effective prognostic indicator and promote BC progression.

Exosomal miRNA-128-3p from mesenchymal stem cells of aged rats regulates osteogenesis and bone fracture healing by targeting Smad5.

Transplantation of mesenchymal stem cells (MSCs) has been considered an effective therapeutic treatment for a variety of diseases including bone fracture. However, there are associated complications along with MSCs transplantation. There is evidence to show that exosomes (Exos) derived from MSCs exert a similar paracrine function. In addition, repair capabilities of MSCs decline with age. Hence, this study aims to confirm whether the Exos protective function on osteogenic differentiation and fracture healing from aged MSCs was attenuated. This information was used in order to investigate the underlying mechanism. MSCs were successfully isolated and identified from young and aged rats, and Exos were then obtained. Aged-Exos exhibited significantly attenuated effects on MSCs osteogenic differentiation in vitro and facture healing in vivo. Using miRNA array analysis, it was shown that miR-128-3p was markedly upregulated in Aged-Exos. In vitro experiments confirmed that Smad5 is a direct downstream target of miR-128-3p, and was inhibited by overexpressed miR-128-3p. A series gain- and loss- function experiment indicated that miR-128-3P serves a suppressor role in the process of fracture healing. Furthermore, effects caused by miR-128-3P mimic/inhibitor were reversed by the application of Smad5/siSmad5. Taken together, these results suggest that the therapeutic effects of MSCs-derived Exos may vary according to differential expression of miRNAs. Exosomal miR-128-3P antagomir may act as a promising therapeutic strategy for bone fracture healing, especially for the elderly.