LRRK1 regulation of actin assembly in osteoclasts involves serine 5 phosphorylation of L-plastin

Mice with disruption of Lrrk1 and patients with nonfunctional mutant Lrrk1 exhibit severe osteopetrosis phenotypes because of osteoclast cytoskeletal dysfunction. To understand how Lrrk1 regulates osteoclast function by modulating cytoskeleton rearrangement, we examined the proteins that are differentially phosphorylated in wild-type mice and Lrrk1-deficient osteoclasts by metal affinity purification coupled liquid chromatography/mass spectrometry (LC/MS) analyses. One of the candidates that we identified by LC/MS is L-plastin, an actin bundling protein. We found that phosphorylation of L-plastin at serine (Ser) residues 5 was present in wild-type osteoclasts but not in Lrrk1-deficient cells. Western blot analyses with antibodies specific for Ser5 phosphorylated L-plastin confirmed the reduced L-plastin Ser5 phosphorylation in Lrrk1 knockout (KO) osteoclasts. micro computed tomography (Micro-CT) analyses revealed that the trabecular bone volume of the distal femur was increased by 27% in the 16 to 21-week-old L-plastin KO females as compared with the wild-type control mice. The ratio of bone volume to tissue volume and connectivity density were increased by 44% and 47% (both P \u3c 0.05), respectively, in L-plastin KO mice. Our data suggest that targeted disruption of L-plastin increases trabecular bone volume, and phosphorylation of Ser5 in L-plastin in the Lrrk1 signaling pathway may in part contribute to actin assembly in mature osteoclasts

Recent Progress in the Classification and Operation of Sacral Fractures

Most sacral fractures are caused by high-energy, violent injuries, often accompanied by lumbosacral plexus injuries, which can cause instability of the posterior pelvic ring or lumbosacral junction in severe cases. Currently, the most commonly used clinical classification methods are Denis classification, Tile classification, Isler classification, and Denis II classification. In recent years, lumbosacral vertebral injury classification and injury degree scoring systems have often been applied clinically as the choice of treatment methods. At present, the internal fixation and implantation methods of sacral fracture are developing in the direction of positive, efficient, safe, and minimally invasive. But different fixation methods have their own indications, which should be strictly followed. This article reviews the classification of sacral fractures and the latest progress in surgical treatment

Autologous Costal Osteochondral Transplantation for Cystic Osteochondral Lesions of the Talus: Feasible and Effective

Objective Osteochondral lesions of the talus (OLT) is a common and clinically challenging disease. The optimal management is still under debate. The purpose of this prospective study was to investigate the feasibility and clinical outcomes of autologous costal osteochondral transplantation (ACOT) for the treatment of cystic OLT. Methods From November 2021 to April 2023, five patients underwent autologous costal osteochondral transplantation (ACOT) for cystic OLT. The demographic data was described, including age, gender, lesion size and location. We prospectively evaluated their functional and imaging outcomes of the five patients for 12 months postoperatively, including numeric rating score (NRS) for pain when walking, Tegner score, American Orthopedic Foot & Ankle Society (AOFAS) score and Foot and Ankle Ability Measure (FAAM) score, and imaging results. A paired t‐test was used for preoperative and postoperative comparison of the paired‐design dataset. Results The average age was 36.6 ± 11.1 years. The average diameter of chondral lesions was 14.95 ± 2.71 mm, the average diameter of subchondral cysts was 10.66 ± 1.84 mm, and their average depth was 10.40 ± 1.86 mm. At 12 months postoperatively, the clinical function indexes improved significantly, including NRS (from 5.2 ± 2.3 to 0), Tegner score (from 3.2 ± 0.4 to 5.8 ± 0.4), AOFAS score (from 72.8 ± 10.0 to 98.2 ± 4.0), and FAAM score (FAAM/ADL from 61.2 ± 24.7 to 99.3 ± 1.6; FAAM/Sports from 32.5 ± 13.73 to 96.3 ± 8.4). Their magnetic resonance observation of cartilage repair tissue (MOCART) scores reached 78.0 ± 7.6 points. ICRS scores of three patients were nearly normal (10 or 11 points). The biopsy of the surviving grafts showed plenty of hyaline cartilage matrix and scattered chondrocytes histologically. No major severe complications were reported during the 12 months follow‐up. Conclusion ACOT could significantly relieve the symptoms of patients with OLT and improve their clinical function at short‐term follow‐up. ACOT might be a feasible and useful method for repairing OLT with subchondral cysts

Spatiotemporal Variation and Hot Spot Detection of Visceral Leishmaniasis Disease in Kashi Prefecture, China

Visceral leishmaniasis (VL) remains a serious public health problem in China. To explore the temporal, spatial, and spatiotemporal characteristics of visceral leishmaniasis (VL), the spatial and spatiotemporal clustering distribution and their relationships with the surrounding geographic environmental factors were analyzed. In this study, the average nearest-neighbor distance (ANN), Ripley’s K-function and Moran’s I statistics were used to evaluate spatial autocorrelation in the VL distribution of the existing case patterns. Getis⁻Ord Gi* was used to identify the hot-spot and cold-spot areas based on Geographic Information System (GIS), and spatiotemporal retrospective permutation scan statistics was used to detect the spatiotemporal clusters. The results indicated that VL continues to be a serious public health problem in Kashi Prefecture, China, particularly in the north-central region of Jiashi County, which is a relatively high-risk area in which hot spots are distributed. Autumn and winter months were the outbreak season for VL cases. The detection of spatial and spatiotemporal patterns can provide epidemiologists and local governments with significant information for prevention measures and control strategies

Tensile strain promotes osteogenic differentiation of bone marrow mesenchymal stem cells through upregulating lncRNA-MEG3

Background. With the aging of the population, osteoporosis is becoming more and more common. This progressive bone disease increases the risk of fractures and pain and causes serious harm to people's health and quality of life. Several studies, including our previous studies, confirmed that tensile strain can promote bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation in vitro. In this study, we further explored the mechanism by which tensile strain regulates BMSC differentiation. Methods. A device designed by our group was used to apply tensile strain to BMSCs to study the effects of tensile strain on their differentiation. LncRNA-MEG3 overexpression and silencing models of BMSCs were constructed by lentivirus transfection to study the involvement of lncRNA-MEG3. We assessed osteogenic differentiation of BMSCs by alkaline phosphatase (ALP) staining and the expression of Runx2 mRNA and BMP2 mRNA, while adipogenic differentiation was evaluated by oil red staining and the expression of PPARγ mRNA and C/EBPα mRNA. Results. We demonstrated that proper tensile strain can promote osteogenic differentiation of BMSCs while inhibiting differentiation into adipocytes, and simultaneously promote the expression of lncRNAMEG3. The overexpression of lncRNA-MEG3 further promotes osteogenic differentiation of stressed BMSCs and inhibits expression of miR-140-5p; the knockdown of lncRNA-MEG3 induces the opposite effects. Conclusion. Appropriate mechanical stimulation can inhibit the expression of miR-140-5p by promoting lncRNA-MEG3 expression, thereby promoting the osteogenic differentiation of BMSCs. Our results provide a theoretical basis for physical exercise to improve the prevention and treatment of osteoporosi

Numerical Simulation Study on Flow Heat Transfer and Stress Distribution of Shell-and-Tube Superheater in Molten Salt Solar Thermal Power Station

The flow heat transfer and stress distribution of the shell and tube superheater of the steam generation system in a 50 MW molten salt tank solar thermal power station are studied by numerical simulation, and the influence of the flow pattern of molten salt and water vapor in the shell-and-tube superheater on the heat transfer efficiency and stress distribution under the heat–fluid–solid coupling condition is deeply studied. When the water vapor is located on the tube side of the superheater, the molten salt is located on the shell side, and the counterflow is used in the superheater, the water vapor outlet meets the inlet temperature of the steam turbine, and the heat exchange efficiency of the superheater can reach 94.2%. The optimum inlet temperatures of molten salt and steam in the superheater are 563 and 345 °C, respectively, and the optimum flow rate of molten salt at the inlet of the superheater is 2.5 m/s. Compared with the stable condition, the heat exchange efficiency can be increased by 2.9%, the equivalent stress value is reduced from 335.63 to 312.60 MPa, and the deformation is reduced by 0.48 mm

The Reliability and Accuracy of the Medial Malleolar Fracture Classification Based on 3D CT Reconstruction

Objective There is a new medial malleolar fracture classification based on 3D CT reconstruction. However, there is no study assessing the reliability and accuracy of the new classification system and comparison between the new and the classic classification. This study aimed to compare the reliability and accuracy of the medial malleolar fracture classification based on 3D CT reconstruction and the Herscovici classification system. Methods We retrospectively analyzed the consecutive ankle fractures in our hospital from January 2013 to September 2020. Five inexperienced and five experienced orthopedic surgeons were included as observers to assess 68 cases with medial malleolar fractures. Ten evaluators classified the cases according to the two classification systems. The reference results of each case were made by the consensus of three senior trauma surgeons. The interobserver reliability, intraobserver reliability, and accuracy were evaluated at an interval of 6 weeks using Fleiss's kappa (κ) statistics. Results We found substantial interobserver and intraobserver reliability and 81.4% accuracy for the new classification, which was statistically superior to the Herscovici classification (P < 0.05). The reliability and accuracy of both classifications were similar in inexperienced and experienced groups, except for type III in the new classification. The interobserver reliability of type II was the best (P < 0.05), and the intraobserver reliability of IVc ranked the worst (P < 0.05) in the new classification. Conclusion The reliability and accuracy of the new classification are superior to the Herscovici classification. Clinical experiences will not affect the assessment of both classification systems in most instances

Mechanical Stress-Induced IGF-1 Facilitates col-I and col-III Synthesis via the IGF-1R/AKT/mTORC1 Signaling Pathway

Mechanical stress promotes human ligamentum flavum cells (LFCs) to synthesize multitype collagens, leading to ligamentum flavum hypertrophy (LFH). However, the mechanism of mechanical stress in the formation of collagen remains unclear. Therefore, we investigated the relationship between mechanical stress and collagen synthesis in the present study. First, LFCs were isolated from 9 patients and cultured with or without mechanical stress exposure for different times. IGF-1, collagen I (col-I), and collagen III (col-III) protein and mRNA levels were then detected via ELISA and qPCR, respectively. Moreover, the activation of pIGF-1R, pAKT, and pS6 was examined by Western blot analysis. To further explore the underlying mechanism, an IGF-1 neutralizing antibody, NVP-AEW541, and rapamycin were used. IGF-1, col-I, and col-III were significantly increased in stressed LFCs compared to nonstressed LFCs. In addition, the activation of pIGF-1R, pAKT, and pS6 was obviously enhanced in stressed LFCs. Interestingly, col-I protein, col-I mRNA, col-III protein, col-III mRNA, and IGF-1 protein, but not IGF-1 mRNA, were inhibited by IGF-1 neutralizing antibody. In addition, col-I and col-III protein and mRNA, but not IGF-1, were inhibited by both NVP-AEW541 and rapamycin. Moreover, the activation of pIGF-1R, pAKT, and pS6 was reduced by the IGF-1 neutralizing antibody and NVP-AEW541, and the activation of pS6 was reduced by rapamycin. In summary, these results suggested that mechanical stress promotes LFCs to produce IGF-1, which facilitates col-I and col-III synthesis via the IGF-1R/AKT/mTORC1 signaling pathway