Human Parathyroid Hormone (1-34) accelerates skin wound healing through inducing cell migration via up-regulating the expression of Rac1.

Delayed wound healing is a public issue that imposes a significant burden on both society and the patients themselves. To date, although numerous methods have been developed to accelerate the speed of wound closure, the therapeutic effects are partially limited due to the complex procedures, high costs, potential side effects, and ethical concerns. While some studies have reported that the in-vivo application of Human Parathyroid Hormone (1-34) (hPTH(1-34)) promotes the wound-healing process, the definitive role and underlying mechanisms through which it regulates the behavior of fibroblasts and keratinocytes remains unclear. Herein, hPTH(1-34)'s role in cell migration is evaluated with a series of in-vitro and in-vivo studies, whereby hPTH(1-34)'s underlying mechanism in activating the two types of cells was detected. The in-vitro study revealed that hPTH(1-34) enhanced the migration of both fibroblasts and HaCaT cells. Ras-associated C3 botulinum toxin subunit 1 (Rac1), a classical member of the Rho family, was upregulated in hPTH(1-34)-treated fibroblasts and HaCaT cells. Further study by silencing the expression of Rac1 with siRNA reversed the hPTH(1-34)-enhanced cell migration, thus confirming that Rac1 was involved in hPTH(1-34)-induced cell behavior. In-vivo study on rat wound models confirmed the effects of hPTH(1-34) on fibroblasts and keratinocytes, with increased collagen deposition, fibroblasts accumulation, and Rac1 expression in the hPTH(1-34)-treated wounds. In summary, the present study demonstrated that hPTH(1-34) accelerated wound healing through enhancing the migration of cells through the up-regulation of Rac1 expression.

Subtype Classification and Prognosis Signature Construction of Osteosarcoma Based on Cellular Senescence-Related Genes.

Background: Cellular senescence (CS) is an alternative procedure that replaces or reinforces inadequate apoptotic responses and is used as an influencing factor for a variety of cancers. The value of CS gene in evaluating the immunotherapy response and clinical outcome of osteosarcoma (OS) has not been reported, and an accurate risk model based on CS gene has not been developed for OS patients. Methods: 279 CS genes were obtained from CellAge. Univariate Cox regression analysis was used to screen the CS gene which was significantly related to the prognosis of OS samples in TARGET data set. The prognosis, clinicopathological features, immune infiltration, gene expression at immune checkpoints, tumor immune dysfunction and exclusion (TIDE) score, and chemotherapy resistance of OS were analyzed among clusters. Least absolute shrinkage and selection operator (Lasso) Cox regression analysis to build cellular senescence-related gene signature (CSRS). Univariate and multivariate Cox regression analysis of CSRS and clinical parameters were carried out, and the parameters with independent prognostic value were used to construct nomogram. Results: Based on 30 CS genes related to OS prognosis, OS samples were divided into three clusters: C1, C2, and C3. C3 showed the lowest survival rate and metastasis rate and the highest immune score and stromal score and was more likely to respond to immune checkpoint blockade (ICB) treatment. A CSRS scoring system including four CS genes (MYC, DLX2, EPHA3, and LIMK1) was constructed, which could distinguish the survival outcome, tumor microenvironment (TME) status, and ICB treatment response of patients with different CSRS score. Nomogram constructed by CSRS score and metastatic has a high prognostic value for OS. Conclusions: Our study identified a molecular classification determined by CS-related genes and developed a new CSRS that has potential value in OS immunotherapy response and clinical outcome prediction.

[Progress on measurement of tibial posterior slope and its biomechanical relationship with posterior cruciate ligament].

The most reliable and convenient measurement method of tibial posterior slope(TPS) and its biomechanical relationship with posterior cruciate ligament (PCL) are still controversial. For X-ray measurement, it is recommended to use full-length lateral X-ray of the lower extremity in quatrous section, which has advantage of highly repeatable and common in the daily diagnosis and treatment process, but it is only applicable to patients with tibial rotation within 15°. When the rotation exceeds 30°, it is difficult to identify the inner contour of platform and is no applicable. If it is only used for daily diagnosis and treatment evaluation, when tibial rotation angle is less than 15°, lateral knee X-ray also has a certain reference significance, but the accuracy could not meet requirements of higher clinical research. For CT measurement method, it could correct tibial rotation, but using the fitting point to measure tibial posterior slope on three-dimensional CT reconstruction is only applicable to knee joint without degeneration, more osteophyte affects the way of using fitting point to determine the plane of tibia with real tibia platform conformity degree, have some limitations. For measurement of MRI, it could not only correct tibial rotation, but also minimize the effect of osteophytes by using tibial anatomical axis as the reference axis, which is a good measurement method. For the biomechanical relationship between tibial posterior slope and tibial posterior slope, increased tibial posterior slope indirectly alleviates tension of PCL through tibial anterior displacement or directly reduces load on posterior cruciate ligament in tibial osteotomies, suggesting a protective mechanism for tibial posterior slope;in total knee arthroplasty with cruciate ligament preserved, the size of tibial posterior slope will affect roll back mechanism of femur. When affected knee with PCL injury, it should be avoid to release then aggravate injury, and the stress could be alleviated by increasing tibial posterior slope appropriately. There has been no unified conclusion on the range of tibial posterior slope that is most beneficial to PCL. The natural tibial posterior slope is between 7 ° and 10°, which is considered to be the most beneficial to protection of PCL, but further studies are needed according to the differences in patients' bone status, surgical methods and so on.

[Debridement and bone grafting with internal fixation via anterior approach for the treatment of tuberculosis of lower cervical vertebrae].

OBJECTIVE: To evaluate the clinical effects of debridement and bone grafting with internal fixation via anterior approach in treatment of tuberculosis of lower cervical vertebrae. METHODS: The clinical data of 15 patients with tuberculosis of lower cervical vertebrae who accepted the treatment of one-stage debridement and bone grafting with internal fixation from June 2010 to December 2018 were retrospectively analyzed. There were 9 males and 6 females, aged from 39 to 72 years with an average of (54.67±10.75) years. The lesion segment was C4 to C6. Pre- and post-operative neurologic functions were evaluated by ASIA grade. All the patients underwent the X-ray films of positive and lateral of cervical spine before and after the operation and accepted the periodic review of CT to evaluate the bone grafting. RESULTS: All the 15 operations were successful, no neurological or vascular injury occurred during the operation, and all patients were followed up for 18 to 52 months. The clinical symptoms improved significantly during the follow-up period and CT showed good bone grafting fusion. One patient suffered a relapse of the illness 3 years later, but was healed during the follow-up visit by strengthening the anti tuberculosis therapy. CONCLUSION: For the patients with vertebral destruction and loss of cervical stability, one-stage debridement and bone grafting with internal fixation via anterior approach has definite curative effects. On the basis of standard anti tuberculosis treatment before operation, the long-term standard anti-tuberculosis treatment after operation is the key to healing the tuberculosis of lower cervical vertebrae.