Serum microRNA-195 is down-regulated in breast cancer: a potential marker for the diagnosis of breast cancer.

MicroRNA-195 (miR-195) is a tumor suppressor that plays an important role in tumorigenesis. There are few studies on miR-195 expression in breast cancer patients and the results have been inconsistent; therefore, this study examined miR-195 expression in the serum of BC patients. Samples from 102 normal subjects and 210 subjects with BC who had detailed clinical follow-up information available were selected. An internal reference (miR-16) and serum miR-195 were amplified and quantitatively detected by SYBR green-based real-time RT-PCR. We analyzed the differences in miR-195 levels between BC and healthy cases and the relationships between the miR-195 level and TNM stage and other clinicopathological parameters. In addition, changes in miR-195 levels were examined for 21 BC cases using paired samples before and after neoadjuvant chemotherapy. miR-195 was downregulated in BC compared with control samples (P = 0.000, Mann-Whitney U test). The sensitivity and specificity of miR-195 in the diagnosis of BC were 69.0 and 89.2 %, respectively; whereas, the sensitivities of carcinoembryonic antigen (CEA) and carbohydrate antigen 153 (CA153) were only 15.08 and 21.1 %, respectively. Remarkably, serum miR-195 had higher sensitivity, 73.97 % (108/146), as a tumor marker in the diagnosis of early stage BC [ductal carcinoma in situ, tumor-node-metastasis (TNM) I, II] compared with the conventional tumor markers CA153 and CEA (12.41 and 7.59 %). Moreover, compared with CEA and CA153, miR-195 had a higher sensitivity for detecting the response to neoadjuvant chemotherapy and significantly increased, more than twofold, after neoadjuvant chemotherapy (P = 0.025, paired t test) in 52.381 % (11/21) of BC cases. However, there were no significant relationships between miR-195 expression and other clinicopathological parameters (TNM stage/pathotype/ER/PR/lymph node status). Our data indicate serum miR-195 is a promising tumor marker for BC diagnosis and general screening, especially for early stage BC. The high sensitivity of miR-195 to neoadjuvant chemotherapy may lay the foundation for future studies on the use of miRNA-based methods for monitoring BC treatment and therapy.

Mitochondrial protection and anti-aging activity of Astragalus polysaccharides and their potential mechanism.

The current study was performed to investigate mitochondrial protection and anti-aging activity of Astragalus polysaccharides (APS) and the potential underlying mechanism. Lipid peroxidation of liver and brain mitochondria was induced by Fe(2+)-Vit C in vitro. Thiobarbituric acid (TBA) colorimetry was used to measure the content of thiobarbituric acid reactive substances (TBARS). Mouse liver mitochondrial permeability transition (PT) was induced by calcium overload in vitro and spectrophotometry was used to measure it. The scavenging activities of APS on superoxide anion (O(2) (•-)) and hydroxyl radical (•OH), which were produced by reduced nicotinamide adenine dinucleotide (NADH)-N-Methylphenazonium methyl sulfate (PMS) and hydrogen peroxide (H(2)O(2))-Fe(2+) system respectively, were measured by 4-nitrobluetetrazolium chloride (NBT) reduction and Fenton reaction colorimetry respectively. The Na(2)S(2)O(3) titration method was used to measure the scavenging activities of APS on H(2)O(2). APS could inhibit TBARS production, protect mitochondria from PT, and scavenge O(2) (•-), •OH and H(2)O(2) significantly in a concentration-dependent manner respectively. The back of the neck of mice was injected subcutaneously with D-galactose to induce aging at a dose of 100 mg/kg/d for seven weeks. Moreover, the activities of catalase (CAT), surperoxide dismutase (SOD) and glutathione peroxidase (GPx) and anti-hydroxyl radical which were assayed by using commercial monitoring kits were increased significantly in vivo by APS. According to this research, APS protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting mitochondrial PT and increasing the activities of antioxidases. Therefore, APS has the effect of promoting health.

Finite element analysis of new headless compression supporting screw for the treatment of unstable femoral neck fracture.

BACKGROUND: Femoral neck fracture is an unsolved challenge in orthopedics. The complication rate in particular is high. There remains a lack of consensus on the optimal choice of internal fixation for unstable femoral neck fracture. OBJECTIVE: The study aimed to develop a new headless compression supporting screw (HCSS) for the treatment of unstable foemoral neck fracture. METHODS: We designed a new HCSS and used a femoral neck fracture (Pauwels III fracture) model (left, fourth-generation composite, Sawbones) and three-dimensional finite element analysis to compare the biomechanical performance of HCSSs with that of cannulated compression screws (CCSs) for treatment of unstable femoral neck fracture. RESULTS: Maximum displacement, peak von Mises stress, peak strain, and rotation for the HCSS were smaller than those for the CCS. The stress was more widely distributed for the HCSS, whereas the stress was concentrated for the CCS. CONCLUSIONS: The HCSS resulted in better biomechanical stability than that from the CCS. For Pauwels III fractures the HCSS exhibits better resistance to shear forces and better support, providing a new clinical treatment.

Effect of Capsular Closure on Outcomes of Hip Arthroscopy for Femoracetabular Impingement: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effect of hip arthroscopy with or without capsular closure in femoracetabular impingement (FAI) by meta-analysis. METHODS: Pertinent studies were identified by searching Pubmed, EMBASE databases with the last search update on 16 February 2020. Studies that reported hip arthroscopy for FAI were collected. Meta-analysis was performed by the use of Review Manager 5.3 software. The odds ratios (OR) and mean differences (MD) were used to compare dichotomous and continuous variables. Additionally, the I2 was used to assess heterogeneity among studies, and the fixed-effects model or the random-effects model was selected for the quantitative analysis. Outcomes were evaluated by forest plots. For statistical analysis, P < 0.05 was considered significant. RESULTS: There was no significant difference among the preoperative mHHS (MD = -2.66，95% CI [-7.25, 1.92], I2 = 80%, P = 0.25), preoperative (MD = -4.94, 95% CI [-11.56, 1.67], I2 = 50%, P = 0.14) and postoperative HOS-SSS (MD = -1.00, 95% CI [-6.98, 4.98], I2 = 66%, P = 0.74), patient satisfaction (MD = 0.03, 95% CI [-0.25, 0.31], I2 = 19%, P = 0.84; OR = 0.94, 95% CI [0.59, 1.50], I2 = 0%, P = 0.78), complications (OR = 1.23, 95%CI [0.56, 2.67], I2 = 0%, P = 0.61), revisions (OR = 1.77, 95% CI [0.87, 3.60], I2 = 36%, P = 0.11), and surgery time (SMD = -0.38, 95% CI [-1.16, 0.40], I2 = 92%, P = 0.34) between the capsule closure group and the non-closure group. For the comparison of postoperative mHHS (MD = -2.66, 95% CI [-7.25, 1.92], I2 = 80%, P = 0.25) and HOS-ADL (MD = -4.20, 95% CI [-5.75, -2.65], I2 = 24%, P < 0.00001), the score of the non-closure group was significantly better than that of the closure group. CONCLUSIONS: Remain capsule unclosed after hip arthroscopy for FAI may, to some extent, has a better postoperative functional score than the non-closure treatment.

(5R)-5-hydroxytriptolide (LLDT-8) prevents collagen-induced arthritis through OPG/RANK/RANKL signaling in a rat model of rheumatoid arthritis.

(5R)-5-hydroxytriptolide (LLDT-8) extracts from Tripterygium have anti-inflammatory, antineoplastic and immunity adjustment functions. The present study used a collagen-induced arthritis (CIA) model to evaluate whether LLDT-8 prevents collagen-induced arthritis, and investigated the signaling underlying this. Male Sprague-Dawley rats were induced to generate CIA, mimicking rheumatoid arthritis (RA). The presence of arthritis was determined using RA progression scores. The inflammatory cytokines interleukin (IL)-1ß, IL-6 and nuclear factor-κB were detected using enzyme-linked immunosorbent assay kits. Induced nitric oxide synthase (iNOS) and matrix metalloprotease (MMP)-13 protein expression were measured using western blot analysis. Lastly, reverse transcription-quantitative polymerase chain reaction was used to evaluate osteoprotegerin (OPG) and receptor activator of nuclear factor κB (RANK) gene expression. LLDT-8 improved RA progression scores and reduced the incidence and severity of CIA. Furthermore, LLDT-8 administration inhibited collagen-induced inflammation and iNOS protein expression in arthritic rats. The current data indicated that MMP-13 production was suppressed and OPG/RANKL expression was increased by LLDT-8 treatment in the arthritic rat. The present results suggest that LLDT-8 attenuates CIA through OPG/RANK/RANK ligand signaling in a rat model of RA.

Increased receptor activator of nuclear factor κß ligand/osteoprotegerin ratio exacerbates cartilage destruction in osteoarthritis in vitro.

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage destruction, matrix degradation and bony changes. Subchondral bone alterations in osteoarthritis are associated with cartilage destruction. It has previously been demonstrated that osteoprotegerin (OPG) and receptor activator of nuclear factor κß ligand (RANKL) mediate this process. The RANKL/OPG ratio is altered in OA chondrocytes compared with normal chondrocytes. In the pathogenesis of OA, abnormal expression levels of matrix metalloproteinase-13 (MMP-13) are secreted by chondrocytes has a vital role in the progression of cartilage erosion. In the present study, the effect of various RANKL/OPG ratios on MMP-13 expression levels was investigated in interleukin-1ß-stimulated SW1353 human chondrosarcoma cells. Cell viability was assessed by MTT assay and MMP-13 mRNA and protein expression levels were analyzed by quantitative reverse-transcription-quantitative polymerase chain reaction, ELISA and western blot analyses, respectively. The results demonstrated that an increase in MMP-13 mRNA and protein expression levels was observed with increasing RANKL/OPG ratio. These findings suggest that this mechanism may be used as a novel therapeutic strategy against OA.

Biomechanical effect of the configuration of screw hole style on locking plate fixation in proximal humerus fracture with a simulated gap: A finite element analysis.

BACKGROUND: Locking plate fixation for proximal humeral fractures is a commonly used device. Recently, plate breakages were continuously reported that the implants all have a mixture of holes allowing placement of both locking and non-locking screws (so-called combi plates). In commercialized proximal humeral plates, there still are two screw hole styles included "locking and dynamic holes separated" and "locking hole only" configurations. It is important to understand the biomechanical effect of different screw hole style on the stress distribution in bone plate. METHODS: Finite element method was employed to conduct a computational investigation. Three proximal humeral plate models with different screw hole configurations were reconstructed depended upon an identical commercialized implant. A three-dimensional model of a humerus was created using process of thresholding based on the grayscale values of the CT scanning of an intact humerus. A "virtual" subcapital osteotomy was performed. Simulations were performed under an increasing axial load. The von Mises stresses around the screw holes of the plate shaft, the construct stiffness and the directional displacement within the fracture gap were calculated for comparison. RESULTS: The mean value of the peak von Mises stresses around the screw holes in the plate shaft was the highest for combi hole design while it was smallest for the locking and dynamic holes separated design. The stiffness of the plate-bone construct was 15% higher in the locking screw only design (132.6N/mm) compared with the combi design (115.0N/mm), and it was 4% higher than the combi design for the locking and dynamic holes separated design (119.5N/mm). The displacement within the fracture gap was greatest in the combi hole design, whereas it was smallest for the locking hole only design. CONCLUSIONS: The computed results provide a possible explanation for the breakages of combi plates revealed in clinical reports. The locking and dynamic holes separated design may be a better configuration to reduce the risk of plate fracture.

The role of the serum RANKL/OPG ratio in the healing of intertrochanteric fractures in elderly patients.

Intertrochanteric fractures occur most commonly in elderly patients. Osteoblasts and osteoclasts have been reported to be regulated by the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), during bone modeling and remodeling, respectively. Based on these observations, we hypothesized that the serum levels of RANKL, OPG and the RANKL/OPG ratio are important in the healing of intertrochanteric fractures in elderly patients. Enzyme-linked immunosorbent assays were used to measure the serum concentrations of RANKL and OPG in 36 elderly patients with intertrochanteric fractures and 30 age-matched healthy control subjects, at baseline and 4, 8 and 12 weeks following injury. The RANKL/OPG ratio in the two groups was also evaluated. Similar trends in RANKL and OPG levels were detected during the fracture healing process. The serum levels of RANKL and OPG were higher in the fracture group than in the controls, and were significantly higher at baseline and 4 weeks following injury (P<0.05). Notably, although the RANKL/OPG ratio gradually increased during healing, it was lower in the fracture group than in the control group. The RANKL/OPG ratio was significantly lower immediately after and 4 weeks after injury in the fracture group (P<0.05). Our data suggest a close correlation between higher serum levels of RANKL and OPG and the fracture healing process, indicating that RANKL and OPG are involved in fracture healing. The serum RANKL/OPG ratio also appears to be significant in the healing of intertrochanteric fractures in elderly patients.