Inhibition of PI3K/Akt/NF-κB signaling with leonurine for ameliorating the progression of osteoarthritis: In vitro and in vivo studies.

Osteoarthritis (OA) is characterized as the degeneration and destruction of articular cartilage. In recent decades, leonurine (LN), the main active component in medical and edible dual purpose plant Herba Leonuri, has been shown associated with potent anti-inflammatory effects in several diseases. In the current study, we examined the protective effects of LN in the inhibition of OA development as well as its underlying mechanism both in vitro and in vivo experiments. In vitro, interleukin-1 beta (IL-1ß) induced over-production of prostaglandin E2, nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6 and tumor necrosis factor alpha were all inhibited significantly by the pretreatment of LN at a dose-dependent manner (5, 10, and 20 µM). Moreover, the expression of thrombospondin motifs 5 (ADAMTS5) and metalloproteinase 13 (MMP13) was downregulated by LN. All these changes led to the IL-1ß induced degradation of extracellular matrix. Mechanistically, the LN suppressed IL-1ß induced activation of the PI3K/Akt/NF-κB signaling pathway cascades. Meanwhile, it was also demonstrated in our molecular docking studies that LN had strong binding abilities to PI3K. In addition, LN was observed exerting protective effects in a surgical induced model of OA. To sum up, this study indicated LN could be applied as a promising therapeutic agent in the treatment of OA.

A novel oleanolic acid derivative HA-19 ameliorates muscle atrophy via promoting protein synthesis and preventing protein degradation.

Muscle atrophy refers to a decrease in the size of muscles in the body, occurs in certain muscles with inactivity in many diseases and lacks effective therapies up to date. Natural products still play an important role in drug discovery. In the present study, derivatives of a natural product, oleanolic acid, were screened with myoblast differentiation and myotube atrophy assays, respectively. Results revealed that one of the derivatives, HA-19 showed the most potent anti-muscle atrophy activity, and was used for further studies. We demonstrated that HA-19 led to the increase of the protein synthesis by activating mechanistic target of rapamycin complex 1 (mTORC1)/p70 S6K pathways, and also enhanced myoblast proliferation and terminal differentiation via up-regulating of the myogenic transcription factors Pax7, MyoD and Myogenin. The interesting thing was that HA-19 also suppressed protein degradation to prevent myotube atrophy by down-regulating negative growth factors, FoxO1, MuRF1 and Atrogin-1. The results were also supported by puromycin labelling and protein ubiquitination assays. These data revealed that HA-19 possessed a "dual effect" on inhibition of muscle atrophy. In disuse-induced muscle atrophy mice model, HA-19 treatment significantly increased the weights of bilateral tibialis anterior (TA), gastrocnemius (Gastroc.), quadriceps (Quad.), suggesting the effectiveness of HA-19 to remit disuse-induced muscle atrophy. Our finding demonstrated that HA-19 has a great potential as an inhibitor or lead compound for the anti-muscle atrophy drug discovery.

Effects of combined human parathyroid hormone (1-34) and menaquinone-4 treatment on the interface of hydroxyapatite-coated titanium implants in the femur of osteoporotic rats.

The objective of this study was to investigate the effects of human parathyroid hormone (1-34) (PTH1-34; PTH) plus menaquinone-4 (vitamin K2; MK) on the osseous integration of hydroxyapatite (HA)-coated implants in osteoporotic rats. Ovariectomized female Sprague-Dawley rats were used for the study. Twelve weeks after bilateral ovariectomy, HA-coated titanium implants were inserted bilaterally in the femoral medullary canal of the remaining 40 ovariectomized rats. All animals were then randomly assigned to four groups: Control, MK, PTH and PTH + MK. The rats from groups MK, PTH and PTH + MK received vitamin K2 (30 mg/kg/day), PTH1-34 (60 µg/kg, three times a week), or both for 12 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA and the bilateral femurs of rats were harvested for evaluation. The combination of PTH and MK clearly increased the serum levels of Gla-OC (a specific marker for bone formation) compared to PTH or MK alone. The results of our study indicated that all treated groups had increased new bone formation around the surface of implants and increased push-out force compared to Control. In addition, PTH + MK treatment showed the strongest effects in histological, micro-computed tomography and biomechanical tests. In summary, our results confirm that treatment with PTH1-34 and MK together may have a therapeutic advantage over PTH or MK monotherapy on bone healing around HA-coated implants in osteoporotic rats.

Hidden blood loss and the influential factors after percutaneous kyphoplasty surgery.

PURPOSE: Percutaneous kyphoplasty (PKP) is a minimally invasive procedure for the treatment of osteoporotic vertebral compression fractures (OVCFs). It is generally considered that there is little blood loss during the surgery. However, a significant perioperative hidden blood loss (HBL) is neglected. This study was to examine the amount of HBL and determine the influential factors during PKP. METHODS: From January 2015 to January 2016, 115 patients with OVCFs who were scheduled to have a PKP were enrolled in this study. The factors analyzed included gender, age, body mass index (BMI), percentage of vertebral height loss, percentage of vertebral height restoration, number of fracture levels, bone mineral density (BMD), duration of symptom, cement leakage, and other internal diseases (hypertension, diabetes mellitus). According to Gross's formula, each patient's height, weight, and pre-operative and post-operative hematocrit were recorded and used for calculating the blood loss. Influential factors were further analyzed by multivariate linear regression analysis and t test. RESULTS: The mean HBL was 282 ± 162 mL (mL) and the post-operative Hb loss was 8.7 ± 5.4 g per liter (g/L). According to multivariate linear regression analysis, patients with severe vertebral height loss (P = 0.016), better vertebral height restoration (P = 0.038), and multi-segmental vertebral fractures (P = 0.000) had a higher amount of HBL. Fresh fractures (P = 0.008) and cement leakage (P = 0.004) were also important factors to increase HBL, whereas gender (P = 0.642), age (P = 0.203), BMI (P = 0.075), hypertension (P = 0.099), diabetes mellitus (P = 0.905), and BMD (P = 0.521) were not correlate with HBL. When we compared the incidence of anemia between pre-operative and post-operative, we found that the incidence of anemia was significantly associated with HBL (P = 0.000). CONCLUSIONS: HBL cannot be ignored in perioperative period, especially for poor physical condition and multiple fractures patients. Having a correct understanding of HBL can help improve clinical assessment capabilities, ensuring patients' safety.

NPT-Loss: Demystifying Face Recognition Losses With Nearest Proxies Triplet.

Face recognition (FR) using deep convolutional neural networks (DCNNs) has seen remarkable success in recent years. One key ingredient of DCNN-based FR is the design of a loss function that ensures discrimination between various identities. The state-of-the-art (SOTA) solutions utilise normalised Softmax loss with additive and/or multiplicative margins. Despite being popular and effective, these losses are justified only intuitively with little theoretical explanations. In this work, we show that under the LogSumExp (LSE) approximation, the SOTA Softmax losses become equivalent to a proxy-triplet loss that focuses on nearest-neighbour negative proxies only. This motivates us to propose a variant of the proxy-triplet loss, entitled Nearest Proxies Triplet (NPT) loss, which unlike SOTA solutions, converges for a wider range of hyper-parameters and offers flexibility in proxy selection and thus outperforms SOTA techniques. We generalise many SOTA losses into a single framework and give theoretical justifications for the assertion that minimising the proposed loss ensures a minimum separability between all identities. We also show that the proposed loss has an implicit mechanism of hard-sample mining. We conduct extensive experiments using various DCNN architectures on a number of FR benchmarks to demonstrate the efficacy of the proposed scheme over SOTA methods.

Distribution Cognisant Loss for Cross-Database Facial Age Estimation With Sensitivity Analysis.

Existing facial age estimation studies have mostly focused on intra-database protocols that assume training and test images are captured under similar conditions. This is rarely valid in practical applications, where we typically encounter training and test sets with different characteristics. In this article, we deal with such situations, namely subjective-exclusive cross-database age estimation. We formulate the age estimation problem as the distribution learning framework, where the age labels are encoded as a probability distribution. To improve the cross-database age estimation performance, we propose a new loss function which provides a more robust measure of the difference between ground-truth and predicted distributions. The desirable properties of the proposed loss function are theoretically analysed and compared with the state-of-the-art approaches. In addition, we compile a new balanced large-scale age estimation database. Last, we introduce a novel evaluation protocol, called subject-exclusive cross-database age estimation protocol, which provides meaningful information of a method in terms of the generalisation capability. The experimental results demonstrate that the proposed approach outperforms the state-of-the-art age estimation methods under both intra-database and subject-exclusive cross-database evaluation protocols. In addition, in this article, we provide a comparative sensitivity analysis of various algorithms to identify trends and issues inherent to their performance. This analysis introduces some open problems to the community which might be considered when designing a robust age estimation system.

Urolithin A Promotes Angiogenesis and Tissue Regeneration in a Full-Thickness Cutaneous Wound Model.

The treatment of chronic wound is an important topic of current clinical issue. Neovascularization plays a crucial role in skin wound healing by delivering fresh nutrients and oxygen to the wound area. The aim of this study was to investigate the mechanisms of urolithin A (UA) in angiogenesis during wound healing. The results of in vitro experiments showed that treatment with UA (5-20 µM) promoted the proliferation, migration, and angiogenic capacity of HUVECs. Furthermore, we investigated the effect of UA in vivo using a full-thickness skin wound model. Subsequently, we found that UA promoted the regeneration of new blood vessels, which is consistent with the results of accelerated angiogenesis in vitro experiments. After UA treatment, the blood vessels in the wound are rapidly formed, and the deposition and remodeling process of the collagen matrix is also accelerated, which ultimately promotes the effective wound healing. Mechanistic studies have shown that UA promotes angiogenesis by inhibiting the PI3K/AKT pathway. Our study provides evidence that UA can promote angiogenesis and skin regeneration in chronic wounds, especially ischemic wounds.

SP-GAN: Self-Growing and Pruning Generative Adversarial Networks.

This article presents a new Self-growing and Pruning Generative Adversarial Network (SP-GAN) for realistic image generation. In contrast to traditional GAN models, our SP-GAN is able to dynamically adjust the size and architecture of a network in the training stage by using the proposed self-growing and pruning mechanisms. To be more specific, we first train two seed networks as the generator and discriminator; each contains a small number of convolution kernels. Such small-scale networks are much easier and faster to train than large-capacity networks. Second, in the self-growing step, we replicate the convolution kernels of each seed network to augment the scale of the network, followed by fine-tuning the augmented/expanded network. More importantly, to prevent the excessive growth of each seed network in the self-growing stage, we propose a pruning strategy that reduces the redundancy of an augmented network, yielding the optimal scale of the network. Finally, we design a new adaptive loss function that is treated as a variable loss computational process for the training of the proposed SP-GAN model. By design, the hyperparameters of the loss function can dynamically adapt to different training stages. Experimental results obtained on a set of data sets demonstrate the merits of the proposed method, especially in terms of the stability and efficiency of network training. The source code of the proposed SP-GAN method is publicly available at https://github.com/Lambert-chen/SPGAN.git.

EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression.

Emerging evidence indicates that circRNAs are broadly expressed in osteosarcoma (OS) cells and play a crucial role in OS progression. Recently, cancer-specific circRNA circPRKAR1B has been identified by high-throughput sequencing and is recorded in publicly available databases. Nevertheless, the detailed functions and underlying mechanisms of circPRKAR1B in OS remains poorly understood. By functional experiments, we found that circPRKAR1B enhanced OS cell proliferation, migration, and promotes OS epithelial-mesenchymal transition (EMT). Mechanistic investigations suggested that circPRKAR1B promotes OS progression through sponging miR-361-3p to modulate the expression of FZD4. Subsequently, we identified that EIF4A3 promoted cirPRKAR1B formation through binding to the downstream target of circPRKAR1B on PRKAR1B mRNA. Further rescue study revealed that overexpression of the Wnt signalling could impair the onco-suppressor activities of the silencing of circPRKAR1B. Interestingly, further experiments indicated that circPRKAR1B is involved in the sensitivity of chemoresistance in OS. On the whole, our results demonstrated that circPRKAR1B exerted oncogenic roles in OS and suggested the circPRKAR1B/miR-361-3p/FZD4 axis plays an important role in OS progression and might be a potential therapeutic target.

Using high competent shoot apical meristems of cockscomb as explants for studying function of ASYMMETRIC LEAVES2-LIKE11 (ASL11) gene of Arabidopsis.

Though shoot apical meristems (SAMs) commonly exhibit low or no competence for transformation, the potent regeneration of this tissue merits further research. Especially, when shoot regeneration is recalcitrant using other tissues as explants, SAM probably is an excellent selection. In cockscomb plants, using SAMs from seedlings obtained from MS medium with 0.5 mg l(-1) 6-BA as explants, high frequency of transformation (approximate 20%) is obtained; whereas control SAMs performed poorly for transformation (approximate 3%). These SAMs are malformed in morphology compared to control SAMs. Further observation found that, in these SAMs, cell proliferation and/or TE formation are seen; which are not found in control SAMs. GUS assays indicated that GUS-positive blue spots at TE zones are obvious; whereas the case was contrary in control SAMs. All these data suggest that cell proliferation and/or TE formation might cause high effective transformation. This transformation system should facilitate the use of this species for studies on gene manipulation and expression. Therefore, we introduced 35S:ASL11-GFP to cockscomb via Agrobacterium tumefaciens. ASYMMETRIC LEAVES2-LIKE11 (ASL11) gene of Arabidopsis is a member of the ASYMMETRIC LEAVES2 (AS2)/LATERAL ORGAN BOUNDARIES (LOB) domain gene family, and its function is largely unclear. By confocal laser scanning microscopy, we found that in most over 35S:ASL11-GFP cockscomb plants, ASL11-GFP fusion protein was in discrete nuclear location. These results indicate that the T-DNA contains within the construct inserted into the host chromosomes in an integral form, and also suggest that ASL11 might be a nuclear protein and function as a potential transcription factor. Moreover, SAMs of the over 35S:ASL11-GFP plants show needle-like patterns that lack organ primordial; suggesting ASL11 might be involved in sustaining indeterminate cell fate of SAMs.

Hsa_circ_0088233 Alleviates Proliferation, Migration, and Invasion of Prostate Cancer by Targeting hsa-miR-185-3p.

Prostate cancer is the most common malignant tumor of the urinary system. The mechanisms of the initiation and progression of prostate cancer have not been fully elucidated. Increasing evidence suggests that circular RNAs (circRNAs) are involved in cancer pathogenesis. In this study, we aimed to identify differentially expressed circRNAs in prostate cancer tissues and explored the role of circRNAs in the pathogenesis of prostate cancer. By screening a circRNA microarray assay, we found that circ_0088233 was upregulated in prostate cancer tissues compared to adjacent normal tissues, and this upregulation can be verified in 46 pairs of prostate cancer and adjacent normal tissues examined using quantitative reverse transcription-PCR. The level of circ_0088233 correlated with the TNM stage. Knockdown of circ_0088233 reduced cell proliferation, migration, invasion, and induced G1 phase arrest and apoptosis. In addition, miR-185-3p was identified as the downstream target of circ_0088233 using luciferase reporter assays and a biotinylated circ_0088233 probe pull-down assay. The miR-185-3p level showed a negative correlation with the circ_0088233 level in prostate cancer tissues. Overexpression of circ_0088233 blocked the effects of miR-185-3p on cell proliferation, migration, invasion, cell cycle, and apoptosis. In conclusion, circ_0088233 may function as an oncogene and play an oncogenic role by sponging hsa-miR-185-3p. This study increases the understanding of circRNAs in the progression of prostate cancer. These results implicate circ_0088233 as a potential therapeutic target for prostate cancer.

Rs145204276 and rs4759314 affect the prognosis of prostate cancer by modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

Non-coding RNAs play an important role in the pathogenesis of prostate cancer (PC). This study aims to characterize the role of GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms in the pathogenesis of PC. Both INS allele of GAS5 rs145204276 and A allele of HOTAIR rs4759314 were identified to increase the survival of PC patients. And patients carrying DEL/DEL + AG genotypes tend to present higher levels of HMGB1, GAS5, HOTAIR and lower levels of miR-1284 and miR-22. In addition, the transcription activity of GAS5 promoter was increased by the deletion allele of rs145204276 polymorphism, while the G allele of rs4759314 polymorphism increased the transcription activity of HOTAIR promoter. GAS5 and HOTAIR could bind to miR-1284 and miR-22, respectively, while miR-1284 and miR-22 could bind to the 3'UTR of HMGB1. Compared with the control group, the expressions of miR-1284 or miR-22 were decreased with the presence of GAS5 or HOTAIR, and the expression of HMGB1 was the highest in the GAS5 + HOTAIR group. In summary, the findings of this study demonstrated that both GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms could affect the prognosis of PC by modulating the expression of HMGB1 via modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

Learning Adaptive Discriminative Correlation Filters via Temporal Consistency Preserving Spatial Feature Selection for Robust Visual Object Tracking.

With efficient appearance learning models, discriminative correlation filter (DCF) has been proven to be very successful in recent video object tracking benchmarks and competitions. However, the existing DCF paradigm suffers from two major issues, i.e., spatial boundary effect and temporal filter degradation. To mitigate these challenges, we propose a new DCF-based tracking method. The key innovations of the proposed method include adaptive spatial feature selection and temporal consistent constraints, with which the new tracker enables joint spatial-temporal filter learning in a lower dimensional discriminative manifold. More specifically, we apply structured spatial sparsity constraints to multi-channel filters. Consequently, the process of learning spatial filters can be approximated by the lasso regularization. To encourage temporal consistency, the filter model is restricted to lie around its historical value and updated locally to preserve the global structure in the manifold. Last, a unified optimization framework is proposed to jointly select temporal consistency preserving spatial features and learn discriminative filters with the augmented Lagrangian method. Qualitative and quantitative evaluations have been conducted on a number of well-known benchmarking datasets such as OTB2013, OTB50, OTB100, Temple-Colour, UAV123, and VOT2018. The experimental results demonstrate the superiority of the proposed method over the state-of-the-art approaches.

An oleanolic acid derivative reduces denervation-induced muscle atrophy via activation of CNTF-mediated JAK2/STAT3 signaling pathway.

Denervation caused by sciatic nerve injury has brought great harm to the patients, especially denervation-induced muscle atrophy. The body stress produces a large number of Schwann cells when the sciatic nerve is injured, and the cells secrete some cytokines including ciliary neurotrophic factor (CNTF) that not only play a role in promoting the repair of sciatic nerve, but also maintain the normal physiological function of the muscles surrounding the damaged nerves. CNTF upregulates janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) signals in myoblasts, and consequently accelerates the proliferation and differentiation of myoblasts. This effect on myoblasts is the most effective way to relieve muscle atrophy. Therefore, increasing CNTF is a promising direction to improve muscle atrophy. In the present study, an oleanolic acid derivative, HA-19, increased the proliferation of Schwann cells, and elevated CNTF production of the cells. HA-19 up-regulated the phosphorylation of JAK2 and STAT3 not only by directly acting on myoblasts, but also by increasing the secretion of CNTF of Schwann cells; and consequently, promoted the proliferation and differentiation of myoblasts. In denervation-induced muscle atrophy mice model, treatment with HA-19 significantly increased the weights of tibialis anterior (TA), gastrocnemius (Gastroc.), extensor digitorum longus (EDL), soleus and quadriceps (Quad.) under atrophied state. And, very interestingly, these muscles under normal condition were also strengthened by HA-19. Our finding demonstrated that HA-19 has a great potential as a lead compound for the drug discovery of anti-denervation-induced muscle atrophy.

Modified pedicle screw placement at the fracture level for treatment of thoracolumbar burst fractures: a study protocol of a randomised controlled trial.

INTRODUCTION: The optimal treatment for burst fractures of the thoracolumbar spine is controversial. The addition of screws in the fractured segment has been shown to improve construct stiffness, but can aggravate the trauma to the fractured vertebra. Therefore, optimised placement of two pedicle screws at the fracture level is required for the treatment of thoracolumbar burst fractures. This randomised controlled study is the first to examine the efficacy of diverse orders of pedicle screw placement and will provide recommendations for the treatment of patients with thoracolumbar burst fractures. METHODS AND ANALYSIS: A randomised controlled trial with blinding of patients and the statistician, but not the clinicians and researchers, will be conducted. A total of 70 patients with single AO type A3 or A4 thoracolumbar fractures who are candidates for application of short-segment pedicle screws at the fractured vertebral level will be allocated randomly to the distraction-screw and screw-distraction groups at a ratio of 1:1. The primary clinical outcome measures will be the percentage loss of vertebral body height, screw depth in the injured vertebrae and kyphosis (Cobb angle). Secondary clinical outcome measures will be complications, Visual Analogue Scale scores for back and leg pain, neurological function, operation time, intraoperative blood loss, Japanese Orthopaedic Association score and Oswestry Disability Index. These parameters will be evaluated preoperatively, intraoperatively, on postoperative day 3, and at 1, 3, 6, 12 and 24 months postoperatively. ETHICS AND DISSEMINATION: The Institutional Review Board of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University have reviewed and approved this study (batch: LCKY2018-05). The results will be presented in peer-reviewed journals and at an international spine-related meeting after completion of the study. TRIAL REGISTRATION NUMBER: NCT03384368; Pre-results.

An enhanced recovery after surgery program in orthopedic surgery: a systematic review and meta-analysis.

OBJECTIVES: There is an increased interest in enhanced recovery after surgery (ERAS) minimizing adverse events after orthopedic surgery. Little consensus supports the effectiveness of these interventions. The purpose of present systematic review and meta-analysis is to comprehensively analyze and evaluate the significance of ERAS interventions for postoperative outcomes after orthopedic surgery. METHODS: PubMed, EMBASE, and Cochrane databases were totally searched from the inception dates to May 31, 2018. Two reviewers independently extracted the data from the selected articles using a standardized form and assessed the risk of bias. The analysis was performed using STATA 12.0. RESULTS: A total of 15 published studies fulfilled the requirements of inclusion criteria. We found that the ERAS group showed a significant association with lower incidence of postoperative complications (OR, 0.70; 95% CI, 0.64 to 0.78). Meanwhile, ERAS was also associated with the decline in 30-day mortality rate and Oswestry Disability Index (ODI). However, no significant differences were identified between the two groups regarding the 30-day readmission rate (P = 0.397). CONCLUSIONS: Our meta-analysis suggested that the ERAS group had more advantages in reducing incidence of postoperative complications, 30-day mortality rate, and ODI after orthopedic surgery, but not of 30-day readmission rate. However, further research with standardized, unbiased methods and larger sample sizes is required for deeper analysis.

Comparison of fracture risk using different supplemental doses of vitamin D, calcium or their combination: a network meta-analysis of randomised controlled trials.

OBJECTIVE: Inconsistent findings in regard to association between different concentrations of vitamin D, calcium or their combination and the risk of fracture have been reported during the past decade in community-dwelling older people. This study was designed to compare the fracture risk using different concentrations of vitamin D, calcium or their combination. DESIGN: A systematic review and network meta-analysis. DATA SOURCES: Randomised controlled trials in PubMed, Cochrane library and Embase databases were systematically searched from the inception dates to 31 December 2017. OUTCOMES: Total fracture was defined as the primary outcome. Secondary outcomes were hip fracture and vertebral fracture. Due to the consistency of the original studies, a consistency model was adopted. RESULTS: A total of 25 randomised controlled trials involving 43 510 participants fulfilled the inclusion criteria. There was no evidence that the risk of total fracture was reduced using different concentrations of vitamin D, calcium or their combination compared with placebo or no treatment. No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of hip or vertebral fractures. CONCLUSIONS: The use of supplements that included calcium, vitamin D or both was not found to be better than placebo or no treatment in terms of risk of fractures among community-dwelling older adults. It means the routine use of these supplements in community-dwelling older people should be treated more carefully. PROSPERO REGISTRATION NUMBER: CRD42017079624.

Salidroside inhibits steroid-induced avascular necrosis of the femoral head via the PI3K/Akt signaling pathway: In vitro and in vivo studies.

Dexamethasone (Dex) and other glucocorticoids are widely used to treat serious infections and immunological diseases, however they may cause steroid­induced avascular necrosis of the femoral head (SANFH). Salidroside (Sal) has demonstrated an anti­apoptotic effect on neurocytes by activating the phosphoinositide 3­kinase (PI3K)/protein kinase B (Akt) signaling pathway. In the present study, primary osteoblasts were used in vitro and in rats in vivo to determine the anti-apoptotic effect of Sal on SANFH. The result of the present study demonstrated that pretreatment with Sal increased the cell survival rate while decreasing the cell apoptosis and lactate dehydrogenase release rate. Additionally, Sal also caused the reduction of TUNEL positive cells in TUNEL staining assay. Sal decreased the expression of cleaved caspase-3, cleaved caspase­9, apoptosis regulator BAX and cytochrome C, while it increased the expression of B cell lymphoma­2 and phosphorylated­Akt in Dex­induced osteoblasts. In vivo Sal protected against SANFH in rats by decreasing the percentage of empty lacunae. The present study demonstrated that Sal alleviated Dex­induced osteoblast apoptosis by activating the PI3K/Akt signaling pathway and downregulating caspase­3 expression in osteoblasts. Sal also protected against SANFH in a rat model of SANFH by decreasing the percentage of empty lacunae. The inhibition of the mitochondrial apoptosis pathway was also involved. Further research is required to determine the full underlying mechanisms by which Sal has an effect.

Calcifying tendinitis of the long head of the biceps brachii and superior labrum: a report of one case and literature review.

Calcifying tendinitis of the shoulder is characterized with the formation of the calcium deposits in tendon, which mostly involves supraspinatus. The formation of the calcium deposits may be related to the excessive mechanical stimulation and non-tenocytes generation from tendon stem cell. The disease is usually associated with pain, especially when activating the shoulder. We describe one case of calcifying tendinitis involving the long head of the biceps brachii and superior labrum. The related literature and researches are also reviewed. After reviewing the past articles, there are no similar cases of calcification involving the long head of the biceps brachii and superior labrum. The diagnosis and treatment scheme may be similar with Calcifying tendinitis of the supraspinatus. The differential diagnosis of calcification involving the long head of the biceps brachii and superior labrum and glenoid cavity fracture is very important. Calcifying tendinitis involving the long head of the biceps brachii and superior labrum is rare and the diagnosis need to rule out fractures. The surgical treatment of arthroscopy is effective and relieves the symptoms quickly, but may not be the first choice.

Design of a 3D navigation template to guide the screw trajectory in spine: a step-by-step approach using Mimics and 3-Matic software.

Rapid development of 3D printing techniques has led to the design of navigation templates to assist with accurate insertion of pedicle screws in last decades. However, there are still without the precise step-by-step methods to design 3D navigation templates from computed tomography (CT) images. Our present article provides a detailed protocol to allow the readers or researchers to obtain the 3D navigation template easily, and assist with pedicle screw insertion in their future research and surgery. Using 3D navigation template-assisted pedicle screw fixation in spine surgery is low cost and can decrease the radiation exposure to both patients and surgeons.