Bone-targeting delivery of platelet lysate exosomes ameliorates glucocorticoid-induced osteoporosis by enhancing bone-vessel coupling.

BACKGROUND: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. RESULTS: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. CONCLUSIONS: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP.

Long-term outcome of stereotactic aspiration, endoscopic evacuation, and open craniotomy for the treatment of spontaneous basal ganglia hemorrhage: a propensity score study of 703 cases.

BACKGROUND: To compare the long-term therapeutic effects of stereotactic aspiration (SA), endoscopic evacuation (EE), and open craniotomy (OC) in the surgical treatment of spontaneous basal ganglia hemorrhage and explore the appropriate clinical indications for each technique. METHODS: Multiple-treatment inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis was performed to evaluate the therapeutic effects of these techniques. The primary and secondary outcomes were 6-month modified Rankin Scale (mRS) and mortality rates, respectively. RESULTS: A total of 703 patients were ultimately enrolled. For the entire cohort, the 6-month mortality rate was significantly higher (OR 2.396, 95% CI: 1.865-3.080), and the 6-month functional outcome was significantly worse (OR 1.359, 95% CI: 1.091-1.692) for SA than that of EE. The 6-month mortality rate for OC was significantly higher (OR 1.395, 95% CI: 1.059-1.837) than that of EE. Further subgroup analysis was stratified by initial hematoma volume and Glasgow Coma Scale (GCS) score. The mortality rate for SA was significantly higher for patients with hematoma volume of 20-40 mL (OR 6.226, 95% CI: 3.848-10.075), 40-80 mL (OR 2.121, 95% CI: 1.492-3.016), and ≥80 mL (OR 5.544, 95% CI: 3.315-9.269) than in the same subgroups of EE. The functional outcomes for SA were significantly worse than that of EE for hematoma volume subgroups of 40-80 mL (OR 1.424, 95% CI: 1.039-1.951) and ≥80 mL (OR 4.224, 95% CI: 1.655-10.776). The mortality rate for SA was significantly higher than that of EE for the GCS score subgroups of 6-8 (OR 2.082, 95% CI: 1.410-3.076) and 3-5 (OR 2.985, 95% CI: 1.904-4.678). The mortality rate for OC was significantly higher for the GCS score of 3-5 subgroup (OR 1.718, 95% CI: 1.115-2.648), and a tendency for a higher mortality rate of 6-8 subgroup (OR 1.442, 95% CI: 0.965-2.156) than that of EE. CONCLUSIONS: EE can decrease the 6-month mortality rate and improve the 6-month functional outcomes of spontaneous basal ganglia hemorrhage in patients with a hematoma volume ≥40 mL. EE can decrease the 6-month mortality rate of spontaneous basal ganglia hemorrhage in patients with a GCS score of 3-8.

Theaflavin protects chondrocytes against apoptosis and senescence via regulating Nrf2 and ameliorates murine osteoarthritis.

Oxidative stress-mediated excessive apoptosis and senescence of chondrocytes are the main pathological alterations in the osteoarthritis (OA) development. The protective effects of theaflavin (TF), a common group of polyphenols in black tea, against many degenerative diseases by attenuating oxidative stress are well reported. Nevertheless, its role in the OA treatment is still scantily understood. In the current research, by applying enzyme-linked immunosorbent assay (ELISA) kits and immunofluorescent staining, TF treatment was found to inhibit tert-Butyl hydroperoxide (TBHP)-induced imbalance of anabolism and catabolism in primary mouse chondrocytes. Then, according to western blot, live-dead staining, and SA-ß-gal staining, the dramatically increased level of apoptosis and senescence of chondrocytes in response to TBHP was also found to be reduced by TF administration. With regard to upstream signaling investigation, the in vitro molecular binding analysis indicated that the beneficial effects of TF might be related to the regulation of the Keap1/Nrf2/HO-1 axis. Furthermore, the Silencing of Nrf2 resulted in the abolishment of the anti-apoptosis and anti-senescence effects of TF. In addition, the oral administration of TF was demonstrated to ameliorate osteoarthritis development in a surgically induced mouse OA model. Taken together, these results suggest that TF might be a promising therapeutic option for the treatment of OA.

Oroxylin A attenuates osteoarthritis progression by dual inhibition of cell inflammation and hypertrophy.

The imbalance between the anabolism and catabolism of the extracellular matrix (ECM) is of great importance to osteoarthritis (OA) development. Aberrant inflammatory responses and hypertrophic changes of chondrocytes are the main contributors to these metabolic disorders. In the present study, we found that Oroxylin A (ORA), a flavonoid compound derived from Oroxylum indicum, maintained ECM hemostasis of chondrocytes by Interleukin-1ß (IL-1ß) stimulation. Besides, it was demonstrated that IL-1ß induced over-production of inflammatory mediators was attenuated by ORA treatment. Moreover, ORA could rescue IL-1ß mediated hypertrophic alterations of chondrocytes. Mechanistically, ORA's protective effects were found to be associated with both NF-κB and Wnt/ß-catenin signaling inhibition. Meanwhile, molecular docking analysis revealed that ORA could strongly bind to the inhibitor kappa B kinaseß (IKKß) and dishevelled, Dsh Homolog 2 (Dvl2), the upstream molecules of the NF-κB axis and ß-catenin axis, respectively. In addition, ORA driven chondroprotective effects were also affirmed in a surgically induced OA mouse model. Taken together, the current study suggested that ORA might be a promising therapeutic option for the treatment of OA.

The acromion-greater tuberosity impingement index: A new radiographic measurement and its association with rotator cuff pathology.

PURPOSE: Several radiographic parameters describe humeral head coverage by the acromion. We describe a new radiographic measurement, the acromion-greater tuberosity impingement index (ATI), and its ability to predict rotator cuff pathology. METHODS: The ATI was measured with magnetic resonance imaging (MRI) and X-ray analysis in 83 patients with rotator cuff pathology and 76 patients with acute rotator cuff tears. The lateral acromial angle (LAA), acromion type, the acromion index (AI) and the critical shoulder angle (CSA) were measured to assess their correlations with the ATI. Receiver operating characteristic (ROC) curves were used to predict degenerative rotator cuff pathology. The change in the ATI after acromion surgery was evaluated in both groups. RESULTS: According to the ROC curves, the ATI is a good predictor of degenerative rotator cuff pathology on both X-ray (cut-off, 0.865) and MRI (cut-off, 0.965). Patients with degenerative rotator cuff pathology had a significantly higher average ATI compared to the trauma group (p = 0.001 for X-ray and MRI). The degenerative group had a significantly lower LAA (p = 0.001) and a higher ratio of type III acromion (p = 0.035) than the trauma group. The ATI on X-ray was negatively related to the LAA and positively related to the AI, the CSA and acromion type (each p < 0.05). The ATI on MRI was negatively related to the LAA and positively related to the AI and acromion type (each p <0.05). More patients in the degenerative group than the trauma group needed acromioplasty or acromion decompression (p < 0.05). The ATI on MRI was significantly lower after acromion surgery compared to before surgery in both groups (p < 0.05). CONCLUSION: The ATI is a good predictor of degenerative supraspinatus tendon tears or subacromial impingement syndrome. The ATI on MRI is more accurate and can precisely guide acromion surgery.

Enhancement of protein stability by an additional disulfide bond designed in human neuroglobin.

Human neuroglobin (Ngb) forms an intramolecular disulfide bond between Cys46 and Cys55, with a third Cys120 near the protein surface, which is a promising protein model for heme protein design. In order to protect the free Cys120 and to enhance the protein stability, we herein developed a strategy by designing an additional disulfide bond between Cys120 and Cys15 via A15C mutation. The design was supported by molecular modeling, and the formation of Cys15-Cys120 disulfide bond was confirmed experimentally by ESI-MS analysis. Molecular modeling, UV-Vis and CD spectroscopy showed that the additional disulfide bond caused minimal structural alterations of Ngb. Meanwhile, the disulfide bond of Cys15-Cys120 was found to enhance both Gdn·HCl-induced unfolding stability (increased by ∼0.64 M) and pH-induced unfolding stability (decreased by ∼0.69 pH unit), as compared to those of WT Ngb with a single native disulfide bond of Cys46-Cys55. Moreover, the half denaturation temperature (T m) of A15C Ngb was determined to be higher than 100 °C. In addition, the disulfide bond of Cys15-Cys120 has slight effects on protein function, such as an increase in the rate of O2 release by ∼1.4-fold. This study not only suggests a crucial role of the artificial disulfide in protein stabilization, but also lays the groundwork for further investigation of the structure and function of Ngb, as well as for the design of other functional heme proteins, based on the scaffold of A15C Ngb with an enhanced stability.

Association of osteoarthritis and circulating adiponectin levels: a systematic review and meta-analysis.

BACKGROUND: The objective of this study was to perform a meta-analysis to investigate the specific relationship between the expression level of circulating adiponectin and osteoarthritis (OA). METHOD: Multiple databases were searched to estimate the high quality of studies relevant to adiponectin and OA. We extracted the data from the eligible studies and included them in the meta-analysis using a random effects model. Subgroup analysis and meta-regression were further performed to explore the potential sources of heterogeneity. RESULTS: Ten articles consisting of thirteen case-control studies that contained a combined total of 1255 subjects. Our results revealed that the OA patients displayed higher adiponectin levels than the healthy controls (SMD = 0.327, 95% CI: 0.11-0.55, P = 0.003). The ethnicity-stratified subgroup analysis indicated that the adiponectin was a sensitive biomarker in both Caucasians (P = 0.021) and Asians (P = 0.037). Moreover, the meta-regression analysis suggested that the sample size (P = 0.03) and nationality (p = 0.01) could account for a part of heterogeneity in our study. CONCLUSION: Taken together, the current study indicated that the adiponectin expression levels were higher in the OA patients than in the healthy controls and might be associated with OA prevalence.

Neuroglobin is capable of self-oxidation of methionine64 introduced at the heme axial position.

Neuroglobin (Ngb), with its physiological role not fully understood, was found to be capable of self-oxidation of methionine64 introduced at the heme axial position (H64M Ngb), adopting a high-spin heme state and producing both methionine sulfoxide (SO-Met) and sulfone (SO2-Met), which represents the structure and function of cytochrome c in a non-native state.

No effectiveness of anticoagulants for thromboprophylaxis after non-major knee arthroscopy: a systemic review and meta-analysis of randomized controlled trials.

Arthroscopic knee surgery is the most commonly performed orthopedic procedure worldwide and whether thromboprophylaxis should be undertaken after knee arthroscopy is still controversial. To evaluate the efficacy of thromboprophylaxis for deep venous thrombosis (DVT) and venous thromboembolism (VTE) after knee arthroscopic surgery. A meta-analysis was conducted using data from eight randomized trials (4148 patients) to compare thromboprophylaxis with placebo or no prophylactic treatment in patients undergoing knee arthroscopy. The benefits and harms of thromboprophylaxis were evaluated, including the incidence of asymptomatic DVT, symptomatic VTE, pulmonary embolism and anti-coagulation related adverse events. Thromboprophylaxis significantly decreased the incidence of DVT (95% CI 0.07-0.64, P = 0.006) and symptomatic VTE in patients undergoing knee arthroscopy (95% CI 0.23-0.76, P = 0.004), but not significantly decreased the incidence of pulmonary embolism (n.s.). Regarding to non-major knee arthroscopy surgery (simple surgical procedures without ligament reconstruction), no significant difference of the incidence of DVT or symptomatic VTE was noted between thromboprophylactic group and control group (n.s.). Thromboprophylactic treatment showed higher incidence rate of anti-coagulation related adverse events compared with the control group (95% CI 1.12-1.90, P = 0.005). There was no significant difference of the incidence of clinically relevant major bleeding between the two groups (n.s.). This meta-analysis indicates no effectiveness of thromboprophylaxis for preventing DVT or symptomatic VTE in patients undergoing non-major knee arthroscopy. Regarding to patient undergoing knee ligament construction, the thromboprophylactic strategy should mainly take into account the patient's risk factors.

Selective medial soft tissue release combined with tibial reduction osteotomy in total knee arthroplasty.

BACKGROUND: To obtain the correct coronal alignment and balancing in flexion and extension, we established a selective medial release technique and investigated the effectiveness and safety of the technique during primary total knee arthroplasty (TKA). METHODS: Four hundred sixty-six primary TKAs with varus deformity were prospectively evaluated between June 2013 and June 2015. A knee joint position similar to Patrick's sign was used to release the medial structure. The medial release technique consisted of release of the capsule and the deep medial collateral ligament (dMCL) (step1), selective release of superficial medial collateral ligament (sMCL) or posterior oblique ligament (POL) (step 2), and selective tibial reduction osteotomy (step 3). Improvement of medial joint gap at each step and other clinical outcomes were evaluated. RESULTS: Among the 466 knees, symmetrical gaps could be achieved by the limited release of the capsule and the dMCcL in 276 (59%) knees. One hundred fifty-two (33%) required additional sMCL release with 2-5 cm from the joint line distally or POL release. Thirty-eight (8%) necessitated an additional tibial reduction osteotomy. Anterior-medial release and 4-mm medial osteotomy contributed to more improvement of medial gap in flexion than in extension (each p < 0.01). Posteromedial release and posteromedial osteotomy contributed to more improvement in extension than in flexion (each p < 0.01). No specific complication related to our technique was identified. CONCLUSION: The technique of the tibial reduction osteotomy combined with medial soft structure release using Patrick's sign is effective, safe, and minimally invasive to obtain balanced mediolateral and extension-flexion gaps in primary TKA.

Extramedullary versus intramedullary femoral alignment technique in total knee arthroplasty: a meta-analysis of randomized controlled trials.

BACKGROUND: There is no consensus whether the use of the extramedullary femoral cutting guide takes advantage over the intramedullary one in total knee arthroplasty. The aim of this study was to compare the extramedullary femoral alignment guide system with the conventional intramedullary alignment guide system for lower limb alignment, blood loss, and operative time during total knee arthroplasty. METHODS: The Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Chinese Periodical, Google, and reference lists of all the included studies were searched for randomized controlled trials. The following parameters were compared between the extramedullary technique and the intramedullary technique: (1) lower limb coronal alignment, (2) coronal alignment of femoral component, (3) sagittal alignment of femoral component, (4) blood loss, (5) and operation time. RESULTS: Four randomized controlled trials consisting of 358 knees were included in our study. There was no significant difference between the extramedullary and intramedullary groups for the lower limb coronal alignment (RR = 1.20, 95%CI 0.28~5.21, n.s.), coronal alignment of femoral component (RR = 0.65, 95%CI 0.19~2.22, n.s.), and sagittal alignment of femoral component (RR = 0.73, 95%CI 0.38~1.41, n.s.). A reduced blood loss was associated with the use of the extramedullary guide (MD = -120.34, 95%CI -210.08~-30.59, P = 0.009). No significant difference in operation time was noted between the two groups (MD = 1.41, 95%CI -1.82~4.64, n.s.). CONCLUSIONS: Neither extramedullary nor intramedullary femoral alignment is more accurate than the other in facilitating the femoral cut in total knee arthroplasty. Use of the extramedullary guide results in less blood loss and exhibits a similar operation time as compared with the intramedullary guide.

An ultrastructural study of chondroptosis: programmed cell death in degenerative intervertebral discs in vivo.

Apoptosis has been regarded to mediate intervertebral disc degeneration (IDD); however, the basic question of how the apoptotic bodies are cleared in the avascular intervertebral disc without phagocytes, which are essential to apoptosis, remains to be elucidated. Our goals were to investigate the ultrastructure of nucleus pulposus (NP) cells undergoing chondroptosis, a variant of apoptotic cell death, in a rabbit annular needle-puncture model of IDD. Experimental IDD was induced by puncturing discs with a 16-G needle in New Zealand rabbits. At 4 and 12 weeks after puncture, progressive degeneration was demonstrated by X-ray, magnetic resonance imaging and histological staining. TUNEL staining suggested a significant increase in the apoptosis index in the degenerated NP. However, the percentage of apoptotic cells with the classic ultrastructure morphology was much less than that with chondroptotic ultrastructure morphology under transmission electron microscopy (TEM). The chondroptotic cells from the early to late stage were visualized under TEM. In addition, the percentage of chondroptotic cells was significantly enhanced in the degenerated NP. Furthermore, 'paralyzed' cells were found in the herniated tissue. Western blotting revealed an increase in caspase3 expression in the degenerated NP. The expression of the Golgi protein (58K) was increased by the fourth week after puncture but decreased later. These findings indicate that chondroptosis is a major type of programmed cell death in the degenerated rabbit NP that may be related to the progressive development of IDD.

Pterostilbene inhibits inflammation and ROS production in chondrocytes by activating Nrf2 pathway.

Pterostilbene has been reported as a potential drug to inhibit oxidative stress and inflammation. However, the effect of pterostilbene on chondrocytes and osteoarthritis remains to be elucidated. We sought to investigate whether pterostilbene could protect chondrocytes from inflammation and ROS production through factor erythroid 2-related factor 2 (Nrf2) activation. The pterostilbene toxicity on chondrocytes collected from cartilages of Sprague-Dawley rats was assessed by CCK-8 test. Immunofluorescence and Western blotting explored the nuclear translocation of Nrf2. Nrf2 expression was silenced by siRNA to evaluate the involvement of Nrf2 in the effect of pterostilbene on chondrocytes. Finally, osteoarthritis model was established by the transection of anterior cruciate ligament and partial medial meniscectomy in rats, and then these rats received pterostilbene 30 mg/kg, daily, p.o. for 8 weeks. Histology and immunohistochemistry were used to assess histopathological change and Nrf2 expression in cartilage. Nuclear translocation of Nrf2 was stimulated by pterostilbene without cellular toxicity. Pterostilbene inhibited the level of COX-2, iNOS, PGE2, and NO, as well as the mitochondrial and total intracellular ROS production induced by IL-1ß in chondrocytes, partially reversed by the Nrf2 silencing. Pterostilbene prevented cartilage degeneration and promoted the nuclear translocation of Nrf2 in cartilage. These results suggest that pterostilbene could inhibit the IL-1ß-induced inflammation and ROS production in chondrocytes by stimulating the nuclear translocation of Nrf2.

A mini-invasive technique for severe arthrofibrosis of the knee: A technical note.

PURPOSE: In this article, a mini-invasive technique is described, which consists of arthroscopic adhesiolysis and quadriceps pie-crusting lengthening basing on pre-operative sonographic examination. Sonographic diagnostic value of quadriceps tendon fibrosis is also evaluated. METHODS: Pre-operative sonographic examination was performed to make an accurate location diagnosis of quadriceps fibrosis. After arthroscopic adhesiolysis, percutaneous pie-crusting release was performed basing on preoperative sonographic examination. An 18-gauge needle was used to puncture the stiff fibrous band of the distal and lateral quadriceps tendon under maximum knee flexion. The contractural quadriceps tendon is gradually released after 60-100 needle punctures. RESULTS: This technique was performed in five post-traumatic stiff knees and three stiff knees after previous infection. The contractural rectus femoris tendon is average 22% thinner than contralateral parts according to sonographic measurement. Mean maximum flexion increased from 35° preoperatively to 80° after arthroscopic adhesiolysis and 120° after pie-crusting. CONCLUSIONS: This technique is a simple, effective and mini-invasive method, allowing an immediate, aggressive rehabilitation postoperatively. Pre-operative sonographic location of quadriceps tendon fibrosis could potentially improve the efficacy and accuracy of percutaneous pie-crusting procedures.

Shorter survival rate in varus-aligned knees after total knee arthroplasty.

PURPOSE: One long-held tenet of total knee arthroplasty (TKA) is that post-operative neutral limb alignment promotes implant durability. Recently, the concept of generic safe zone (0° ± 3°) has been challenged. This meta-analysis aimed to evaluate whether neutral alignment was superior to malalignment in long-term survival of TKAs. METHODS: The MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Wan Fang Chinese Periodical, Google and reference lists of all the included studies were searched. Of the 1512 studies initially identified, ten met the eligibility criteria, including eight case-control studies and two cohort trials. Relative risks of implant failure were compared between post-operative neutrally aligned and malaligned knees. RESULTS: Post-operative malalignment showed higher failure rate of knee implants compared with neutral alignment (95 % CI 1.00-1.88, P = 0.05). Failure rate in knees with varus alignment was significantly higher than with neutral alignment (95 % CI 1.07-2.55, P = 0.02). There was no significant difference in the likelihood of implant failure between knees with valgus and neutral alignment (95 % CI 0.78-2.41, n.s.). No significant difference of failure rate was noted between neutral alignment and malalignment for fixed-bearing prothesis (95 % CI 0.94-1.95, n.s.) or rotating-platform prothesis (95 % CI 0.75-2.73, n.s.). There was no significant difference of failure rate between knees with neutral alignment and malalignment for studies with a mean follow-up of more than 10 years (95 % CI 0.81-2.01, n.s.) or studies using long-leg weight-bearing radiographs (95 % CI 0.79-1.79, n.s.). CONCLUSIONS: Post-operative varus alignment results in shorter survival rate after TKA. Not only neutral limb alignment but also the valgus alignment promotes implant durability. Neutral or valgus alignment rather than varus alignment is essential to achieve long-term survival of TKAs and patient satisfaction. LEVEL OF EVIDENCE: III.

Asymmetric Facet Joint Osteoarthritis and Its Relationships to Facet Orientation, Facet Tropism, and Ligamentum Flavum Thickening.

STUDY DESIGN: The degrees of osteoarthritis of the left and right facet joints were evaluated by using computerized tomography among elderly patients with low back or leg pain. OBJECTIVE: To reveal the phenomenon of asymmetry regarding facet joint osteoarthritis (FJOA) in old patients and establish its relationships to spinal level, facet orientation, facet tropism and ligamentum flavum (LF) thickening. SUMMARY OF BACKGROUND DATA: There were few reports regarding left-right asymmetry among severity of FJOA and its relationships to spinal level, facet orientation, facet tropism, and LF thickening remained unclear. METHODS: The grade of bilateral FJOA was evaluated using 4-grade scale on computerized tomography images at the L3-4, L4-5, and L5-S1 levels of patients with age ranging from 60 to 80 years. All subjects were divided into 2 groups: symmetric FJOA group (FJOA I-II on both sides or FJOA III-IV on both sides) and asymmetric FJOA group (FJOA I-II on one side and FJOA III-IV on the other side). The relationships of FJOA to spinal level, facet orientation, facet tropism, and LF hypertrophy were evaluated. RESULTS: No association between asymmetric FJOA and spinal level was noted (P>0.05). In asymmetric FJOA group, significant difference in facet orientation between 2 sides was observed at the L4-5 (P=0.018) and L5-S1 levels (P=0.033). Compared with symmetric FJOA, asymmetric FJOA showed significant difference in prevalence of facet tropism at the L5-S1 level (P<0.001). The LF showed significantly thicker on the side of FJOA III-IV than the side of FJOA I-II at each level in asymmetric FJOA group (P<0.05). However, no difference was found in thickness between 2 sides in symmetric FJOA group (P>0.05). CONCLUSIONS: Asymmetric FJOA is associated with facet orientation and tropism, but not with spinal level. There is a close relationship between severity of FJOA and LF thickness.

Absence of the Adenosine A2A Receptor Confers Pulmonary Arterial Hypertension Through RhoA/ROCK Signaling Pathway in Mice.

Numerous evidence suggests that RhoA/Rho kinase (ROCK) signaling pathway plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH), but little is known about its effects on the development of PAH in mice with absence of the adenosine A2A receptor (A2AR). Eight A2AR knockout (KO) and 8 wild-type mice were used. Morphometric analysis of pulmonary arterioles included right ventricle/left ventricle plus ventricular septum (Fulton index), vessel wall thickness/total vascular diameter (WT%), and vessel wall area/total vascular area (WA%). The expression of RhoA and ROCK1 mRNA was determined by real-time polymerase chain reaction. The expression of RhoA, ROCK1, and phosphorylation of myosin phosphatase target subunit 1 proteins in pulmonary tissue was tested by Western blot. The position of ROCK1 protein was evaluated by immunohistochemistry. Compared with wild-type mice, A2AR KO mice displayed (1) increased Fulton index, WT%, and WA% (P < 0.01); (2) increased mRNA expression of RhoA and ROCK1 (each P < 0.05); (3) increased protein expression of RhoA, ROCK1, and phosphorylation of myosin phosphatase target subunit 1 (each P < 0.01); (4) increased location of ROCK1 protein in endothelial and smooth muscle cells of pulmonary artery, bronchial, and alveolar epithelial cells. Activation of RhoA/ROCK signaling pathway may cause pulmonary vascular constriction, pulmonary artery remodeling, and PAH in adenosine A2A receptor KO mice.

Extramedullary versus intramedullary tibial alignment technique in total knee arthroplasty: A meta-analysis of randomized controlled trials.

The aim of this study was to establish whether the use of an extramedullary or intramedullary tibial cutting guide leads to superior mechanical leg axis and implant positioning. A meta-analysis of six randomized controlled trials including 350 knees was performed. For the mechanical axis, frontal tibial component angle and tibial slope, there were no significant differences in the mean values or the number of outliers (±3°) between the extramedullary and intramedullary groups. A reduced tourniquet time was associated with the intramedullary guide. No significant difference in the complication rate was noted between the two groups. Neither extramedullary nor intramedullary tibial alignment was more accurate in facilitating the tibial cut. Use of an intramedullary guide results in a shorter tourniquet time and exhibits a similar complication rate as the extramedullary guide.

Extramedullary versus intramedullary tibial alignment technique in total knee arthroplasty: A meta-analysis of randomized controlled trials

The aim of this study was to establish whether the use of an extramedullary or intramedullary tibial cutting guide leads to superior mechanical leg axis and implant positioning. A meta-analysis of six randomized controlled trials including 350 knees was performed. For the mechanical axis, frontal tibial component angle and tibial slope, there were no significant differences in the mean values or the number of outliers (±3°) between the extramedullary and intramedullary groups. A reduced tourniquet time was associated with the intramedullary guide. No significant difference in the complication rate was noted between the two groups. Neither extramedullary nor intramedullary tibial alignment was more accurate in facilitating the tibial cut. Use of an intramedullary guide results in a shorter tourniquet time and exhibits a similar complication rate as the extramedullary guide.

Quadriceps tendon pie-crusting release of stiff knees in total knee arthroplasty.

BACKGROUND: Traditional treatments for stiff knees, such as quadriceps snip and V-Y quadricepsplasty, require extensive soft tissue exposure and lead to recurrent poor arc of motion and a permanent extensor lag. In this study, we evaluated the effect of the quadriceps tendon pie-crusting release for treating limited knee flexion in total knee arthroplasty (TKA) and compared the outcomes of two surgical approaches. METHODS: Sixteen knees with severe osteoarthritis were treated with TKA using either a midvastus (eight knees) or parapatellar (eight knees) approach. Quadriceps tendon pie-crusting release was performed after fixation of the knee prosthesis. Maximum knee flexion, Knee Society Score (KSS), and quadriceps strength were recorded and compared between the two surgical approach groups at different time points. RESULTS: The average maximum flexion angle of the knee increased from 40.6 ± 11.8 preoperatively to 63.1 ± 8.4 after fixation of the knee prosthesis in the midvastus group and from 38.8 ± 10.3 to 65.6 ± 9.0 in the parapatellar group. TKA did not lead to adequate correction of extension contracture in these stiff knees. The quadriceps tendon pie-crusting release further improved knee flexion by 35.0 ± 4.6 and 25.6 ± 4.2 in the midvastus and parapatellar groups, respectively (p < 0.001). Patients in the midvastus group had higher mean KSS (88.2 ± 2.4) compared with the parapatellar group (84.1 ± 3.1) at the last follow-up (p = 0.048). CONCLUSIONS: The quadriceps tendon pie-crusting release technique was an effective procedure for improving knee flexion in cases of stiff knee. The midvastus approach maintained the integrity of the extensor mechanism and resulted in better outcomes than the parapatellar approach.