Eccentrically widened bone tunnels after all-inside anterior cruciate ligament reconstruction: a computed tomography and three-dimensional model-based analysis.

PURPOSE: To evaluate the extent of tunnel widening after anterior cruciate ligament reconstruction (ACLR) using the all-inside technique and to establish its correlation with patient-reported clinical outcomes and femoral graft bending angle (GBA). METHODS: Tunnel widening was evaluated using computed tomography (CT)-based three-dimensional (3D) models, and the femoral GBA was directly measured on CT images using the Picture Archiving and Communication System (PACS) software. Clinical follow-up was routine procedure, and patient-reported clinical outcomes mainly included International Knee Documentation Committee (IKDC), Lysholm, and Knee Injury and Osteoarthritis Outcome Scores (KOOS) scores, and subjective knee stability assessment. RESULTS: Fifty-two patients received standard all-inside ACLR, with a median follow-up of 6 months. Reconstructed anterior cruciate ligaments (ACLs) were scanned during the first 3 days and 6 months after surgery. On both the femoral and tibial sides, bone tunnels were most significantly enlarged at the articular aperture segment; the femoral tunnel was 9.2 ± 1.3 mm postoperatively and was significantly enlarged by 32% to a mean tunnel diameter of 12.1 ± 2.0 mm at 6 months after surgery. Moreover, the extent of tunnel enlargement gradually decreased as the measured levels approached those of the bone cortex. The femoral tunnel center was shifted into the anterior and distal direction, and the tibial tunnel center was shifted into the posterior and lateral direction. Additionally, the mean femoral GBA was 105.9° ± 8.1° at the 6-month follow-up. Tunnel enlargement and GBA were not significantly correlated with patient-reported outcomes. CONCLUSIONS: Femoral and tibial tunnels were significantly greater and eccentrically shifted at the 6-month follow-up after all-side ACLR. However, the extent of tunnel widening does not markedly affect the short-term clinical outcomes. Meanwhile, the femoral GBA was not significantly correlated with femoral tunnel widening or patient-reported outcomes. Although the tunnel widening following all-inside ACLR was not associated with clinical outcomes, it potentially caused difficulties in revision ACLR. LEVEL OF EVIDENCE: Level IV.

All-Inside Anterior Cruciate Ligament Reconstruction: A Review of Advance and Trends.

Anterior cruciate ligament (ACL) injury is a common disease in orthopedics and mostly occurs as a noncontact injury in athletes. Patients' knee joint stability, which is crucial to their athletic ability, cannot be restored through conservative treatment; it can only be restored through ACLR (ACL reconstruction) surgery. The surgical techniques of ACLR are constantly evolving, from bone tendon bone (BTB) grafting combined with interface screw fixation to hamstring tendon autograft or allogeneic tendon and of suspension device constructs. In particular, the currently prevalent all-inside technique featuring good cosmetic results and quick recovery of early functions not only ensures the stable fixation of grafts but also reduces surgical trauma. This review compares the advantages and disadvantages of different aspects of all-inside ACLR, including graft selection and preparation, bone socket reconstruction, fixation methods, and surgical technique effects and limitations. It has been found that the all-inside technique excels both anatomically and clinically but still requires further development. Besides, it has some limitations, and high-quality randomized controlled trials are still required to compare the long-term effects of the all-inside technique and other ACLR techniques.

Effects of Platelet-Rich Plasma and Bone Marrow Mesenchymal Stem Cells on Meniscal Repair in the White-White Zone of the Meniscus.

OBJECTIVE: To investigate the role of autologous platelet-rich plasma (PRP) on the repair of meniscal white-white zone injury through promoting the proliferation of canine bone marrow-derived mesenchymal stem cells (BMSCs). METHODS: A total of 24 beagle dogs were selected to construct meniscal white-white zone injury models in both lateral knee joints. All subjects were divided into four groups: control, BMSCs, PRP, and PRP + BMSCs. Immunohistochemistry was applied in the expression detection of type I and type II collagens. HE staining and methylene blue staining were performed to observe the injury of cartilage of lateral femoral condyle in each group. ELISA was used to detect the osteopontin (OPN) content in cartilage of lateral femoral condyle. HE staining and magnetic resonance imaging (MRI) were used to observe the healing of meniscus in each group. Outcome measures include the expression of OPN in the synovial fluid of knee joint, the expression of type I collagen and type II collagen, the healing of meniscus injury, and the damage degree of lateral femoral condyle cartilage. RESULTS: Compared with the control group, the expressions of type I and type II collagens were enhanced in the PRP group and the PRP + BMSCs group. Compared with 1 week before modeling, the expression of OPN was elevated in the control group and the BMSCs group at 3 weeks after modeling. There were no significant differences in the above indicators between the PRP group and the PRP + BMSCs group. According to MRI and pathological section after HE staining, meniscal healing in the PRP group and the PRP + BMSCs group was significantly improved as compared to that of the control group and the BMSCs group (all P < 0.05), and there was no significant difference between the PRP group and the PRP + BMSCs group (P > 0.05). All subjects were divided into the non-healing group and the healing group in accordance with the HE staining results in previous experiment. The injury of cartilage of lateral femoral condyle was significantly heavier in the non-healing group than that in the healing group. CONCLUSION: The application of PRP alone or in combination with BMSCs could promote the clinical healing rate of meniscal white-white zone injury.

Circular RNA in osteoarthritis: an updated insight into the pathophysiology and therapeutics.

Osteoarthritis (OA) is a common joint disease that mainly results in chronic pain, stiffness and dysfunction in elderly individuals. The molecular mechanisms in the pathogenesis of OA are still unclear, and available treatments are unable to slowdown the development of OA or reverse the tissue damage. Circular RNAs (circRNAs), a novel type of non-coding RNA, are ubiquitous, stable, evolutionally conserved, tissue-specific and functional. An increasing number of studies have revealed that many circRNAs are differentially expressed in OA-affected joint tissues and engage in the pathogenesis of OA by functioning as miRNA sponges. In this review, we briefly introduce the biogenesis, characteristics and functions of circRNAs, and shed light on the important role of circRNAs in the occurrence and progression of OA and their potential diagnostic and therapeutic value in this disease based on the research over the last five years.

Functional role of hedgehog pathway in osteoarthritis.

The hedgehog signalling pathway is one of the key regulators of metazoan development, and it plays an important role in the regulation of a variety of developmental and physiological processes. But it is aberrantly activated in many human diseases, including osteoarthritis (OA). In this study, we have reviewed the association of hedgehog signalling pathway in the development and progression of OA and evaluated the efforts to target this pathway for the prevention of OA. Usually in OA, activation of hedgehog induces up-regulation of the expression of hypertrophic markers, including type X collagen, increases production of nitric oxide and prostaglandin E2, several matrix-degrading enzymes including matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motifs in human knee joint cartilage leading to cartilage degeneration, and thus contributes in OA. Targeting hedgehog signalling might be a viable strategy to prevent or treat OA. Chemical inhibitors of hedgehog signalling is promising, but they cause severe side effects. Knockdown of HH gene is not an option for OA treatment in humans because it is not possible to delete HH in larger animals. Efficient knockdown of HH achieved by local delivery of small interfering RNA in future studies utilizing large animal OA models might be a more efficient approach for the prevention of OA. However, it remains a major problem to develop one single scaffold due to the different physiological functions of cartilage and subchondral bones possess. More studies are necessary to identify selective inhibitors for efficiently targeting the hedgehog pathway in clinical conditions.

Combining covalent bonding and electrostatic attraction to achieve highly viable species with ultrashort beryllium-beryllium distances: a computational design.

Though ultrashort metal-metal distances (USMMD, dM-M < 1.900 Å) were primarily realized between transition metals, USMMDs between main group metal atoms such as beryllium atoms have also been designed previously using two strategies: (1) formation of multiple bonding orbitals or (2) having favourable electrostatic attraction. We recently turned our attention to the reported species IH → Be2H2 ← IH (where IH denotes imidazol-2-ylidene) because the orbital energy level of its π-type HOMO is noted to be very high, which may result in intrinsic instability. In the present study, we combined the abovementioned strategies to solve the high orbital energy level problem without losing the ultrashort Be-Be distances. It was found that breaking of such π-type HOMO by addition of a -CH2- group onto the bridging position of two beryllium atoms led to the formation of IH → Be2H2CH2 ← IH species, which not only possesses an ultrashort Be-Be distance in the -Be2H2CH2- moiety, but also has a relatively low HOMO energy level. Replacing the IH ligands with NH3 and PH3 resulted in the formation of NH3 → Be2H2CH2 ← NH3 and PH3 → Be2H2CH2 ← PH3 species with similar features. The electronic structure analyses suggest that the ultrashort Be-Be distances in these species are achieved by the combined effects of the formation of two Be-H-Be 3c-2e bonds and having favourable Coulombic attractions between the carbon atom of the -CH2- group and two beryllium atoms. Remarkably, when the IH, NH3, and PH3 ligands were replaced by large ligands with bulky groups, such as 1,3-bis(2,6-diisopropyl phenyl)imidazol-2-ylidene (IDip), triphenylamine (NPh3), and triphenylphoshpine (PPh3), respectively, the resultant species IDip → Be2H2CH2 ← IDip, NPh3 → Be2H2CH2 ← NPh3, and PPh3 → Be2H2CH2 ← PPh3 exhibit good steric protection around the -Be2H2CH2- core. These species are thus examples for the experimental realization of species with ultrashort metal-metal distances between main group metals.

[Inhibitory Effect of LY294002 on Proliferation of Multiple Myeloma Cells and Its Mechanism].

OBJECTIVE: To explore the inhibitory effect of 2- (4-morpholine) -8- phenyl -4 hydrogen -1- benzo -4 ketone (LY294002) on proliferation of multiple myeloma cell U266 and its mechanism. METHODS: U266 cells were cultured with 0, 5, 10, 20 µmol/L LY294002 for 24, 48 and 72 h, the cell viability was measured by MTT method, cell morphology was observed by acridine orange staining, cell cycle was measured by flow cytometry. The expressions of B-cell lymphoma-2 (BCL-2), BCL-2-associated X protein (BAX), Cyclin D1, Cyclin E and activation of phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (AKT) signal pathway were measured by Western blot. RESULTS: U266 cell viability was reduced in time- and dose-dependent manner after treatment with 5, 10, 20 µmol/L of LY294002 for 24, 48, 72 h. The 5, 10, 20 µmol/L LY294002 leaded to cell nucleus dense and thick, and the cell cycle arrested in the G1 phase (P<0.01). The expressions of BCL-2, Cyclin D1, Cyclin E, PI3K and p-AKT were down-regulated (P<0.01), and the expression of BAX up-regulated (P<0.01). CONCLUSION: LY294002 can inhibit U266 cell proliferation via suppresion of activation of PI3K/AKT signal pathway.