CircFOXK2 Promotes the Progression of Osteoarthritis by Regulating the miR-4640-5p/NOTCH2 Axis.

OBJECTIVE: Osteoarthritis (OA) is the most common age-related chronic and disabling joint disease, frequently causing pain and disability in the adult population. Given that there are no proven disease-modifying drugs for OA, it is urgent to gain a deeper understanding of OA pathogenesis. This study intended to uncover the circFOXK2 regulation in OA. METHODS: Firstly, in vitro OA cell model was constructed by treating murine chondrocytes with interleukin (IL)-1ß. Then, a series of functional assays were conducted to evaluate the effect of circFOXK2 on OA progression in murine chondrocytes. Bioinformatics analysis and mechanism investigations were performed to investigate the competitive endogenous RNA (ceRNA) network of circFOXK2 in OA. RESULTS: CircFOXK2 is overexpressed in IL-1ß-treated chondrocyte. We confirmed the cyclic structure and cytoplasmic distribution of circFOXK2. Functionally, circFOXK2 promotes chondrocyte apoptosis and extracellular matrix (ECM) degradation but inhibiting chondrocyte proliferation. Mechanically, circFOXK2 competitively binds to microRNA-4640-5p (miR-4640-5p) to enhance NOTCH2 expression in OA, affecting OA progression. Besides, circFOXK2 could motivate the Notch pathway to accelerate OA progression. CONCLUSION: CircFOXK2/miR-4640-5p/NOTCH2 axis stimulates the Notch pathway to promote the transcription of inflammatory cytokines (IL33, IL17F and IL6), consequently facilitating OA progression in murine chondrocytes.

Numerical simulations on shear behaviour of rock joint network under constant normal stiffness conditions.

In this study, the numerical direct shear tests were conducted to investigate the shear mechanical properties of joint networks under constant normal stiffness (CNS) boundary conditions. The influence of random joint number on shear stress (τ), dilation (normal displacement, δv) and normal stress (σn) of rock mass were studied quantitatively with fixed main slip surface. At the same time, the internal stress evolution process and failure process were analyzed. The results reveal that the number of random joints (γ) has little effect on the shear and normal stresses. The normal displacement of the sample generally decreases as the number of random joints increases. In addition, the normal displacement of the specimen is absorbed by the random joints when the number of random joints in the specimen increases to a certain level: when γ is greater than 6 and the shear displacement (µ) reaching 10 mm, the specimen exhibits shear contraction. Therefore, the internal random joints mainly control the failure mode and dilatancy performance of the specimen, while the main joint of the rock controls the shear stress of the specimen.

Triaxial Creep Mechanical Behaviors and Creep Damage Model of Dolomitic Limestone Material under Multi-Stage Incremental Loading.

Dolomitic limestone is the main surrounding rock material in Yangzong tunnel engineering; the instantaneous mechanical properties and creep behaviors of limestone are significant for stability evaluation during the stages of tunnel excavation and long-term maintenance. Herein, four conventional triaxial compression tests were carried out to explore its instantaneous mechanical behavior and failure characteristics; subsequently, the creep behaviors of limestone subjected to multi-stage incremental axial loading at the confinements of 9 MPa and 15 MPa were studied by employing an advanced rock mechanics testing system (i.e., MTS815.04). The results reveal the following. (1) comparing the curves of axial strain-, radial strain-, and volumetric strain-stress under different confining pressures shows that these curves present a similar trend, whereas the stress drops during the post-peak stage decelerate with the increase in confining pressure, suggesting that the rock transits from brittleness to ductility. The confining pressure also has a certain role in controlling the cracking deformation during the pre-peak stage. Besides, the proportions of compaction- and dilatancy-dominated phases in the volumetric strain-stress curves differ obviously. Moreover, the failure mode of the dolomitic limestone is a shear-dominated fracture but is also affected by the confining pressure. (2) When the loading stress reaches a creep threshold stress, the primary and steady-state creep stages occur successively, and a higher deviatoric stress corresponds to a greater creep strain. When the deviatoric stress surpasses an accelerated creep threshold stress, a tertiary creep appears and then is followed by creep failure. Furthermore, the two threshold stresses at 15 MPa confinement are greater than that at 9 MPa confinement, suggesting that the confining pressure has an obvious impact on the threshold values and a higher confining pressure corresponds to a greater threshold value. Additionally, the specimen's creep failure mode is one of "abrupt" shear-dominated fracturing and is similar to that under a conventional triaxial compression test at high confining pressure. (3) A multi-element nonlinear creep damage model is developed by bonding a proposed visco-plastic model in series with the Hookean substance and Schiffman body, and can accurately describe the full-stage creep behaviors.

[Clinical observation of arthroscopic single channel treatment of carpal tunnel syndrome with self-made instruments].

OBJECTIVE: To investigate the efficacy of self-made arthroscopic single channel in the treatment of carpal tunnel syndrome. METHODS: Sixty patients with primary carpal tunnel syndrome treated from January 2014 to December 2019 were divided into arthroscopic group and traditional open operation group. There were 30 cases in arthroscopic group, including 12 males and 18 females, aged (47.5±4.5) years and the course of disease was (6.6±4.2) months. There were 30 cases in the traditional operation group, including 10 males and 20 females, aged (48.5±3.5) years, and the course of disease was (5.6±4.4) months. Both groups were unilateral. According to the anatomy of wrist joint and the characteristics of transverse carpal ligament and arthroscopy, the instruments including cannula, inner heart and hook knife were designed. The patients in two groups were treated with decompression of transverse carpal ligament using arthroscopy combined with self-made instruments and traditional open sergery. The incision length, operation time, intraoperative bleeding, hospitalization cost, hospitalization time and recovery time of the two groups were observed and compared. Boston Carpal Tunnel Questionnaire (BCTQ) score was used to evaluate the clinical efficacy of arthroscopy combined with self made instruments in the treatment of carpal tunnel syndrome. RESULTS: Compared with the traditional group, the arthroscopic group had significant advantages in incision length, operation time, intraoperative bleeding and hospital stay, but the total cost of hospitalization was increased. The Boston score was significantly higher in the arthroscopic group than that in the traditional group at 1 month after operation, but not at 3 and 6 months after operation. CONCLUSION: Arthroscopy combined with self-made instruments in the treatment of carpal tunnel syndrome is more reliable, minimally invasive and simplified than open surgery, but the patients should be clearly diagnosed and appropriately selected before operation to achieve satisfactory clinical effect.

Association between breastfeeding and osteoporotic hip fracture in women: a dose-response meta-analysis.

OBJECTIVE: Approximately 300 mg of calcium a day is provided into infants to maintain the physical development of infants, and 5 to 10% bone loss occurs in women during breastfeeding. Hip fractures are considered the most serious type of osteoporotic fracture. We performed this meta-analysis to investigate the association between breastfeeding and osteoporotic hip fractures. MATERIAL AND METHODS: PubMed and Embase were searched until May 1, 2019, for studies evaluating the relationship between breastfeeding and osteoporotic hip fracture in women. The quality of the included studies was evaluated by the methodological index for non-randomized studies (MINORS). For the dose-response meta-analysis, we used the "generalized least squares for trend estimation" method proposed by Greenland and Longnecker to take into account the correlation with the log RR estimates across the duration of breastfeeding. RESULTS: Seven studies were moderate or high quality, enrolling a total of 103,898 subjects. The pooled outcomes suggested that breastfeeding can decrease the incidence of osteoporotic hip fracture (RR = 0.64 (95% CI 0.43, 0.95), P = 0.027). Dose-response analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the increase of breastfeeding time. The RR and 95% CI for 3 months, 6 months, 12 months, and 24 months were RR = 0.93, 95% CI 0.88, 0.98; RR = 0.87, 95% CI 0.79, 0.96; RR = 0.79, 95% CI 0.67, 0.92; and RR = 0.76, 95% CI 0.59, 0.98, respectively, whereas no significant relationship was found between them when the duration of breastfeeding time was more than 25 months. CONCLUSIONS: Our meta-analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the extension of breastfeeding time. However, there is no significant relationship between them when the duration of breastfeeding time was more than 25 months.

Comparison of targeted percutaneous vertebroplasty and traditional percutaneous vertebroplasty for the treatment of osteoporotic vertebral compression fractures in the elderly.

OBJECTIVE: To investigate the clinical effect of precise puncture and low-dose bone cement in percutaneous vertebroplasty (PVP). METHODS: Sixty patients with osteoporotic vertebral compression fracture (OVCFs) who were treated with PVP in our hospital from July 2018 to June 2019. These included patients were divided into group A (N = 30) and group B (N = 30). Group A has punctured to the fracture area accurately and injected with a small dose of bone cement, the group B was injected with a conventional dose of bone cement. The operation time, the amount of bone cement injection, the number of X-rays, the VAS scores, the leakage rate of bone cement, and the incidence of adjacent vertebral fractures were compared between the two groups. RESULT: The operation time, fluoroscopic times, and bone cement volume in group A are less than that in group B (P < 0.05). Patients in group A had a lower incidence of cement leakage and adjacent vertebral fracture than that in patients in group B. There was no significant difference in postoperative pain relief between the two groups. CONCLUSIONS: Precise puncture and injection of small doses of bone cement can reduce the number of X-ray fluoroscopy, operation time, amount of bone cement injection, reduce the rate of bone cement leakage and the incidence of adjacent vertebral fractures, which is a safe and effective surgical approach for the treatment for the aged with OVCFs.

Aggregate gradation effects on dilatancy behavior and acoustic characteristic of cemented rockfill.

Investigating the effect of the aggregate gradation on the material properties of cemented rockfill is significant for the green mining, economic benefit and engineering safety. Consequently, the ultrasonic test, uniaxial compression experiment and acoustic emission (AE) monitor on cemented rockfill were carried out, for which the aggregate satisfied Talbot gradation. The dilatancy behavior and AE characteristic of cemented rockfill under load were investigated. The damage in the internal structure under compression was revealed by the deformation and AE signals of cemented rockfill. The effect of the Talbot index on the ultrasonic pulse velocity (UPV) and the strength parameters such as stress of dilatancy onset and uniaxial compressive strength (UCS) of cemented rockfill was analyzed. The mechanical properties of cemented rockfill materials were evaluated by the establishment of the relation between the UPV and the strength parameter. The results show that The difference between the stress of dilatancy onset and the UCS, the deformation performance and the activity of AE signals during dilatancy are positive correlated with the Talbot index of aggregate in cemented rockfill. The relation between the UPV and the strength parameters (stress of dilatancy onset and UCS) of cemented rockfill can be characterized by the positive linearity, and the UPV is also suitable for characterizing the stress of dilatancy onset of cemented rockfill material. The cubic polynomial is more suitable for describing the relations between the parameters of strength and UPV and the Talbot index of aggregate than the quadratic polynomial, and the Talbot index with optimal aggregate gradation reflected the maximum strength of cemented rockfill material should be around 0.45-0.47.

[Short term effect of total hip arthroplasty through direct anterior approach for the treatment of ankylosing spondylitis with hip flexion deformity].

OBJECTIVE: To investigate the short term clinical efficacy of direct anterior approach(DAA) total hip arthroplasty for the treatment of ankylosing spondylitis with hip flexion deformity. METHODS: From September 2014 to June 2017, 15 cases of ankylosing spondylitis with flexion deformity of the hip were treated with total hip arthroplasty through DAA approach including 12 males(17 hips) and 3 females(4 hips) with an average age of 34.4 years old ranging from 21 to 57 years old. Harris score system was used before and after operation to evaluate hip function, total hip activity and visual analogue scale (VAS) were used to evaluate the clinical efficacy. RESULTS: All 15 patients were followed up for an average of 26.2 months. In the operation, 1 case of great trochanter avulsion was given wire binding, and 1 case of linear split of the femur were given by wire binding. There were no hematoma, nerve injury and deep vein thrombosis of lower extremity. No prosthesis loosening and sinking were observed in the follow-up of X-ray film after operation. There was no heterotopic ossification after operation. After operation, 18 hips pain were relieved completely, and 3 hips pain were found when walking, which all satisfied with the daily life self-care requirements. Harris hip score, total hip motion and VAS score at 1 week after operation were significantly different from those before operation(P<0.05). There was no significant difference in the scores of HHS, total hip motion and VAS at 1, 6 months after operation(P>0.05). At the final follow-up, the Harris score was 91.2±5.3, the total hip mobility was (217.1±29.7)°, and the postoperative VAS pain score was 1.2±0.5, which was significantly different from the preoperative score(P<0.05). CONCLUSIONS: DAA approach THA has good effect in treating AS hip nonfunctional ankylosis with less trauma, less pain and quick recovery. It has a good short term effect, which can effectively improve the quality of life of patients.

[Comparison of the efficacy of total arthroscopy and traditional surgical treatment for the treatment of popliteal cyst].

OBJECTIVE: To compare the clinical efficacy of total arthroscopic surgery and traditional surgery for popliteal cyst. METHODS: From August 2014 to July 2017, 60 cases of popliteal cyst were treated with total arthroscopy or traditional surgery respectively. In total arthroscopy group, there were 30 patients including 7 males and 23 females with an average age of (55.81±8.53) years old; the duration of the disease was (3.52±1.12) years;according to Rauschning-Lingdgren grading, 7 cases were grade I, 19 cases were grade II, 4 cases were grade III. In traditional surgical group, there were 30 patients including 5 males and 25 females with an average age of (57.93±9.84) years old; the duration of the disease was (3.48±1.34) years; according to Rauschning-Lingdgren grading, 5 cases were grade I, 21 cases were grade II, 4 cases were grade III. Preoperative symptoms involved such as arthralgia and swelling after knee joint and limited mobility. MRI confirmed a popliteal cyst. Arthroscopic surgery and traditional surgical was used respectively. Incision length, operation time, average stay, total hospital cost and Lysholm score of two groups were compared. RESULTS: In the total arthroscopic group, 1 case suffered from nerve injury, and all cases' incision healed well. In the traditional surgical group, there was 1 case of incision infection, 2 cases of poor healing, 1 case of nerve injury and 1 case of recurrence. All 60 cases were followed up for 6 to 30 months with an average of (13.3±6.5) months. After operation, the symptoms of knee joint arthralgia and swelling, discomfort were significantly improved in the two groups. There were statistically significant differences in incision length, operation time, average stay, total hospitalcost and Lysholm score 6 months after surgery(P<0.05). CONCLUSIONS: The total arthroscopic resection of popliteal cyst, via anterior approach to having a knee joint cavity exploration and treatment of meniscus and bursa, while combined with posteromedial approach for cyst excision would promise a minimal surgery and less pain for patients. Patients will have a rapider recovery, lower recurrence rate and less complication. The total arthroscopic resection easy to accepting for the patient and having a better clinical curative effect is obviously superior to the traditional surgery.

The length of pre-existing fissures effects on the mechanical properties of cracked red sandstone and strength design in engineering.

It is important to study the mechanical properties of cracked rock to understand the engineering behavior of cracked rock mass. Consequently, the influence of the length of pre-existing fissures on the strength, deformation, acoustic emission (AE) and failure characteristics of cracked rock specimen was analyzed, and the optimal selection of strength parameter in engineering design was discussed. The results show that the strength parameters (stress of dilatancy onset and uniaxial compressive strength) and deformation parameters (axial strain and circumferential strain at dilatancy onset and peak point) of cracked rock specimen decrease with the increase of the number of pre-existing fissures, and the relations which can use the negative exponential function to fit. Compared with the intact rock specimens, the different degrees of stress drop phenomena were produced in the process of cracked rock specimens when the stress exceeds the dilatancy onset. At this moment, the cracked rock specimens with the existence of stress drop are not instantaneous failure, but the circumferential strain, volumetric strain and AE signals increase burstingly. And the yield platform was presented in the cracked rock specimen with the length of pre-existing fissure more than 23mm, the yield failure was gradually conducted around the inner tip of pre-existing fissure, the development of original fissures and new cracks was evolved fully in rock. However, the time of dilatancy onset is always ahead of the the time of that point with the existence of stress drop. It indicates that the stress of dilatancy onset can be as the parameter of strength design in rock engineering, which can effectively prevent the large deformation of rock.

Overexpression of miR­214 promotes the progression of human osteosarcoma by regulating the Wnt/ß­catenin signaling pathway.

The aberrant expression of microRNA (miR)­214 contributes to the regulation of normal and cancer cell biology, and is associated with human malignancies, however, it can operate in a contradictory manner. The role of miR­214 in osteosarcoma remains to be fully elucidated. The aim of the present study was to investigate the effects of miR­214 on osteosarcoma progression and tumor cell proliferation, and examine the molecular mechanism underlying osteosarcoma. The level of miR­214 was determined using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis in osteosarcoma and matched paracancerous tissues, and in human osteosarcoma cancer cell lines. The roles of miR­214 in cell proliferation, survival and cell cycle were analyzed using miR­214 lentivirus (LV­miR­214)­infected osteosarcoma cells. In addition, the downstream target proteins in the Wnt/ß­catenin signaling pathway were evaluated using western blot analysis in the LV­miR­214­infected cells. The LV­miR­214­infected MG63 cells were also treated with exogenous ß­catenin for 24, 48 and 72 h, respectively, following which the expression of ß­catenin was measured using western blot analysis and survival was determined using a 3­(4,5­cimethylthiazol­2­yl)­2,5­diphenyl tetrazolium bromide (MTT) assay. The results of the RT­qPCR analysis showed that the expression level of miR­214 was significantly higher in the osteosarcoma tissues, compared with that in the matched paracancerous tissues, and the same was observed in the osteosarcoma cell lines. The MG63, Saos­2 and U2OS cells were infected with the hsa­mir­214 lentivirus for 48 h, and the levels of miR­214 were significantly upregulated in the human osteosarcoma cancer cells. The overexpression of miR­214 in the MG­63 and Saos­2 cells promoted cell growth, and treatment of the cells with specific antisense­microRNA oligonucleotides (AMOs) for miR­214 for indicated durations reversed the effects of miR­214. Additionally, the AMO­treated MG63 cells showed G0/G1 phase arrest, suggesting that miR­214 contributed to regulation of the cell cycle. In addition, the results of western blot analysis showed that, in the miR­214 lentivirus­infected cells, the levels of cyclin­D1, c­myc and lymphoid enhancer­binding factor­1 were significantly increased, compared with those in the control lentivirus­infected cancer cells. Of note, infection with the miR­214 lentivirus did not affect the levels of Wnt1, Wnt2, Wnt4, Axin or glycogen synthase kinase ß in the U2OS cells, whereas the expression levels of ß­catenin in the MG63 cells and Saos­2 cells were significantly increased. The addition of exogenous ß­catenin effectively reversed the efficiency of miR­214­specific AMOs, which was detected using an MTT assay. These data suggested the critical role of miR­214 in human osteosarcoma via regulation of the Wnt/ß­catenin signaling pathway and demonstrated that miR­214 is as an oncogene for human osteosarcoma.

[EFFECTIVENESS OF ARTHROSCOPY FOR ANKLE IMPINGEMENT SYNDROME].

OBJECTIVE: To explore the effectiveness of arthroscopy for ankle impingement syndrome. METHODS: Between March 2009 and April 2013, 30 patients with ankle impingement syndrome were treated. Among them, there were 22 males and 8 females with an average age of 28.6 years (range, 16-55 years). Twenty-six patients had a history of obvious ankle sprains. The disease duration was 6-62 months (mean, 21.5 months). All cases had ankle pain, limitation of activity, and positive results of ankle impact test. According to Meislin scoring criteria, 5 cases were rated as good, 8 cases as medium, and 17 cases as poor; the excellent and good rate was 16.7%. American Orthopedic Foot and Ankle Society (AOFAS) score was 43.3 ± 5.1. Visual analogue scale (VAS) score was 6.7 ± 2.3. Preoperative X-ray film showed ankle loose bodies and hyperplasia osteophyte in 6 cases, and lateral malleolus old avulsion fracture in 4 cases. MRI showed soft tissue in the ankle joint in the 17 cases, and articular cartilage injury of tibiotalar joint and bone marrow edema in 7 cases. The location, degree, and organization of the impact were observed under arthroscopy. The joint debridement, removal of loose body and osteophyte, plasty of articular cartilage, and plasma radiofrequency ablation of lateral and medial ligaments were performed. RESULTS: All incisions healed primarily. No infection of skin and joint, or neurological and vascular injury was found. All patients were followed up 6-32 months (mean, 19.5 months). According to Meislin scoring criteria at last follow-up, 16 cases were rated as excellent, 11 cases as good, and 3 cases as medium; the excellent and good rate was 90.0%, showing significant difference when compared with preoperative value (Z = 6.045, P = 0.000). AOFAS score was 89.8 ± 4.3, showing significant difference when compared with preoperative score (t = 38.180, P = 0.000). VAS score was 2.8 ± 1.6, showing significant difference when compared with preoperative score (t = 7.624, P = 0.000). CONCLUSION: A clear understanding of impingement characteristics, pertinent joint debridement, and complication treatment are important to treat ankle impingement syndrome by simulating ankle impingement under arthroscopy, which have the advantages of strong pertinence, less injury, and fast recovery.