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Abstract Osteonecrosis of the femoral head (ONFH) is a common complication of glucocorticoid (GC) therapy. Recent advances demonstrate that sympathetic nerves regulate bone homeostasis, and GCs lower the sympathetic tone. Here, we show that the dramatically decreased sympathetic tone is closely associated with the pathogenesis of GC-induced ONFH. GCs activate the glucocorticoid receptor (GR) but hinder the activation of the mineralocorticoid receptor (MR) on neurons in the hypothalamic paraventricular nucleus (PVN). This disrupts the balance of corticosteroid receptors (GR/MR) and subsequently reduces the sympathetic outflow in the PVN. Vascular endothelial cells rapidly react to inhibition of sympathetic tone by provoking endothelial apoptosis in adult male mice treated with methylprednisolone (MPS) daily for 3 days, and we find substantially reduced H-type vessels in the femoral heads of MPS-treated ONFH mice. Importantly, treatment with a GR inhibitor (RU486) in the PVN promotes the activation of MR and rebalances the ratio of GR and MR, thus effectively boosting sympathetic outflow, as shown by an increase in tyrosine hydroxylase expression in both the PVN and the sympathetic postganglionic neurons and an increase in norepinephrine levels in both the serum and bone marrow of the femoral head of MPS-treated mice. Rebalancing the corticosteroid receptors mitigates GC-induced endothelial impairment and ONFH and promotes angiogenesis coupled with osteogenesis in the femoral head, while these effects are abolished by chemical sympathectomy with 6-OHDA or adrenergic receptor-β2 (Adrb2) knockout. Furthermore, activating Adrb2 signaling in vivo is sufficient to rescue the GC-induced ONFH phenotype. Mechanistically, norepinephrine increases the expression of the key glycolytic gene 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) via Adrb2-cyclic AMP response element-binding protein (CREB) signaling. Endothelial-specific overexpression of PFKFB3 attenuates endothelial impairment and prevents severe osteonecrosis in MPS-treated Adrb2 knockout mice. Thus, GC inhibits sympathetic tone via the hypothalamic descending pathway, which, in turn, acts as a mediator of GC-induced ONFH.

Abstract Wound healing is a complex process involving sequential stages of hemostasis, inflammation, proliferation, and remodeling. Multiple cell types and factors, including underlying conditions like diabetes and bacterial colonization, can influence healing outcomes and scar formation. N6-methyladenosine (m6A), a predominant RNA modification, plays crucial roles in gene expression regulation, impacting various biological processes and diseases. m6A regulates embryonic skin morphogenesis, wound repair, and pathophysiological processes like inflammation and angiogenesis. Recent studies have highlighted the role of m6A in wound healing, scar formation, and tissue remodeling. Additionally, m6A presents a unique expression pattern in pathological wounds and scars, potentially influencing wound healing and scar formation through modulating gene expression and cellular signaling, thereby serving as potential biomarkers or therapeutic targets. Targeting m6A modifications are potential strategies to enhance wound healing and reduce scar formation. This review aims to explore the roles and mechanisms of m6A RNA methylation in wound healing and scars, and discuss current challenges and perspectives. Continued research in this field will provide significant value for optimal wound repair and scar treatment.

Background: Osteonecrosis of the femoral head (ONFH) is a devastating disease affecting young adults, resulting in significant pain, articular surface collapse, and disabling dysfunction. ONFH can be divided into two broad categories: traumatic and non-traumatic. It has been established that ONFH results from an inadequate blood supply that causes the death of osteocytes and bone marrow cells. Nonetheless, the precise mechanism of ONFH remains to be elucidated. In this regard, preclinical animal and cell models to study ONFH have been established to assess the efficacy of various modalities for preventing and treating ONFH. Nevertheless, it should be borne in mind that many models do not share the same physiologic and metabolic characteristics as humans. Therefore, it is necessary to establish a reproducible model that better mimics human disease. Methods: We systematically reviewed the literatures in regard to ONFH experimental models over the past 30 years. The search was performed in PubMed and Web of Science. Original animal, cell studies with available full-text were included. This review summarizes different methods for developing animal and cell experimental models of ONFH. The advantages, disadvantages and success rates of ONFH models are also discussed. Finally, we provide experimental ONFH model schemes as a reference. Results: According to the recent literatures, animal models of ONFH include traumatic, non-traumatic and traumatic combined with non-traumatic models. Most researchers prefer to use small animals to establish non-traumatic ONFH models. Indeed, small animal-based non-traumatic ONFH modeling can more easily meet ethical requirements with large samples. Otherwise, gradient concentration or a particular concentration of steroids to induce MSCs or EPCs, through which researchers can develop cell models to study ONFH. Conclusions: Glucocorticoids in combination with LPS to induce ONFH animal models, which can guarantee a success rate of more than 60% in large samples. Traumatic vascular deprivation combines with non-traumatic steroids to induce ONFH, obtaining success rates ranging from 80% to 100%. However, animals that undergo vascular deprivation surgery may not survive the glucocorticoid induction process. As for cell models, 10-6mol/L Dexamethasone (Dex) to treat bone marrow stem cells, which is optimal for establishing cell models to study ONFH. The translational potential of this article: This review aims to summarize recent development in experimental models of ONFH and recommended the modeling schemes to verify new models, mechanisms, drugs, surgeries, and biomaterials of ONFH to contribute to the prevention and treatment of ONFH.

Osteonecrosis of the femoral head (ONFH) is a disabling disease characterized by the disruption of the blood supply to the femoral head, leading to the apoptosis and necrosis of bone cells and subsequent joint collapse. Total hip arthroplasty is not optimal since most patients are young. Multiple risk factors contribute to osteonecrosis, including glucocorticoid (GC) usage, excessive alcohol intake, hypercholesterolemia, and smoking. Continuous stimulation by many variables causes a chronic inflammatory milieu, with clinical repercussions including endothelial dysfunction, leading to thrombosis, coagulopathy, and poor angiogenesis. Immune cells are the primary regulators of inflammation. Innate and adaptive immune cells interact with endothelial cells to hinder the regeneration and repair of bone lesions. An in-depth examination of the pathological drivers of ONFH reveals that endothelial dysfunction may be a major cause of osteonecrosis. Understanding the involvement of endothelial dysfunction in the chronic inflammation of osteonecrosis could aid in the development of possible therapies. This review summarizes the role of endothelial cells in osteonecrosis and further explains the pathophysiological mechanism of endothelial dysfunction in this disease from the perspective of inflammation to provide new ideas for the treatment of osteonecrosis.

Abstract Background Malunion and nonunion of vertically displaced pelvic fractures result in lower limb length discrepancies, claudication, and pain. There have been few previous reports of this type of corrective surgery for these old pelvic fractures. We present a surgical technique of sacral osteotomy combined with triangular osteosynthesis in the treatment of malunion and nonunion of vertically displaced pelvic fractures and report on its short-term clinical results. Methods We retrospectively reviewed nine patients (five males and four females) with malunion or nonunion of vertically displaced pelvic fractures treated with sacral osteotomy and triangular osteosynthesis from April 2015 to January 2020. The age ranged from 14 to 45 years (average, 30.7 years). The time from injury to deformity correction surgery ranged from 3 months to 5 years (average, 12.8 months). The vertical displacement of a unilateral hemipelvis was 3.0–4.5 cm (average, 3.80 cm). According to AO/OTA classification at the initial fracture, there are eight cases in type C1.3 and one case in type C3.3. Sacral osteotomy and triangular osteosynthesis were used in all nine patients. The degree of unilateral hemipelvic reduction was assessed postoperatively based on measurements from the anteroposterior (AP) X-ray. Majeed score and pain visual analog scale (VAS) were used to assess the therapeutic effect of the patients during follow-up. Results In all nine patients, postoperative AP X-ray showed correction displacement of 1.7–3.9 cm (average, 3.20 cm). All the patients were followed up for 6–36 months (average, 12.7 months). At the last follow-up, the Majeed score of pelvic fracture increased from an average of 53.9 points (30–84 points) preoperatively to 87.0 points (72–94 points), and the VAS score for pain decreased from an average of 6.0 points (4–8 points) preoperatively to 1.2 points (0–3 points). None had complications like infection, implant broken, screw loosening, iatrogenic nerve, and blood vessel injury. Conclusion Sacral osteotomy combined with triangular osteosynthesis for the treatment of pelvic malunion and nonunion caused by sacral fractures can correct significantly vertical displacement of a unilateral pelvis, prolong limb length, and reconstruct the stability of a pelvic ring, achieving good clinical results.

IntroductionAlzheimer’s disease (AD) is a progressive neurodegenerative disease that results in cognitive impairment and is often accompanied by anxiety. In this study, we investigated whether the activation of VTAVgat neurons could reduce anxiety in APP/PS1 mice. We hypothesized that acute social defeat stress (SDS) would lead to anxiety in APP/PS1 mice, and that the activation of VTAVgat neurons would alleviate this anxiety.MethodsWe exposed APP/PS1 mice to acute SDS and assessed anxiety using the open field test and elevated plus-arm test. Activated VTAVgat neurons was tested by cfos staining. Sleep quality was detected using electroencephalogram after SDS or non-SDS procedure. Sleep duration, sleep latency, and non-rapid eye movement (NREM) percentage were analyzed. VTAVgat neurons were chemogenetically activated by deschloroclozapine.ResultsOur results showed that acute SDS led to anxiety in APP/PS1 mice, as evidenced by increased anxiety-related behaviors in the open field and elevated plus-arm tests. Activation of VTAVgat neurons by SDS led to an increase in sleep duration, primarily due to a decrease in sleep latency and an increase in NREMs. However, the quality of sleep was poor. Chemogenetical activation of VTAVgat neurons improved sleep quality and relieved SDS-induced anxiety. Furthermore, the anxiety state correlated negatively with sleep duration and NREM percentage and correlated positively with theta power density in APP/PS1 mice.DiscussionOur study provides evidence that the activation of VTAVgat neurons alleviates SDS-induced anxiety in APP/PS1 mice, suggesting that poor sleep quality may exacerbate anxiety in AD. These findings may have important implications for the treatment of anxiety in AD, as targeting VTAVgat neurons could be a potential therapeutic approach.

Objective The purpose of this study is to present a surgical technique that simultaneously reduces and fixates the transverse parts of U-shaped sacral fractures. Methods The sacral fracture was exposed through a posterior median approach. In a flexion injury, the rotation of the lower sacral segment is reduced by distraction along a pre-curved rod. Then, lordotic restoration is performed with a Weber clamp placed at the lower sacral segment through dragging. In an extension injury, longitudinal distraction is performed along the spinopelvic rod to reduce the vertical displacement. Next, the transverse displacement is reduced by a dissector placed between the upper and lower sacral segments through levering. The sagittal reduction on the lateral pelvic view was judged by PI. A regression analysis of Oswestry disability index (ODI) with Z-scores of PI, lumbar lordosis (LL), sacral slope (SS), and pelvic tilt (PT) was performed. Results At the 1-year follow-up, the average PI, LL, SS, and PT values were 51.6 (range: 43.1–76.0), 44.8 (34.6 – 60.1), 35.4 (18.1 – 48.0), and 16.7 (2.2–35.4) degrees, respectively. All patients were able to maintain an upright stance. The average ODI was 27.6% (2–72%). Surprisingly, the regression analysis demonstrated a significant linear relationship between ODI and LL ( R 2 = 0.367, p = .048) but not between ODI and PI (R 2 = 0.227, p = .138). Conclusions Using PI as guidance, the surgical procedures were helpful to reduce the PI of transverse sacral fractures into the normal range. However, the relationship between PI and the prognosis remains to be evaluated by future researches.

BackgroundThe purpose of this study was to compare total complications, complications stratified by type, readmissions, and reoperations at 30 and 90 days after outpatient and standard inpatient total knee and total hip arthroplasty (TKA, THA).MethodsA literature search was conducted from the PubMed, Cochrane Library, and Embase databases for articles published before 20 August 2021. The types of studies included prospective randomized controlled trials, prospective cohort studies, retrospective comparative studies, retrospective reviews of THA and TKA registration databases, and observational case-control studies. Comparisons of interest included total complications, complications stratified by type, readmissions, and reoperations at 30 and 90 days. The statistical analysis was performed using Review Manager 5.3.ResultsTwenty studies with 582,790 cases compared relevant postoperative indicators of outpatient and inpatient total joint arthroplasty (TJA) (TKA and THA). There was a significant difference in the total complications at 30 days between outpatient and inpatient THA (p = 0.001), readmissions following TJA (p = 0.03), readmissions following THA (p = 0.001), stroke/cerebrovascular incidents following TJA (p = 0.01), cardiac arrest following TJA (p = 0.007), and blood transfusions following TJA (p = 0.003). The outcomes showed an obvious difference in 90-day total complications between outpatient and inpatient TJA (p = 0.01), readmissions following THA (p = 0.002), and surgical-related pain following TJA (p

Endothelial impairment and dysfunction are closely related to the pathogenesis of steroid-associated osteonecrosis of the femoral head (SONFH). Recent studies have showed that hypoxia inducible factor-1α (HIF-1α) plays a crucial role in endothelial homeostasis maintenance. Dimethyloxalylglycine (DMOG) could suppress HIF-1 degradation and result in nucleus stabilization by repressing prolyl hydroxylase domain (PHD) enzymatic activity. Our results showed that methylprednisolone (MPS) remarkably undermined biological function of endothelial progenitor cells (EPC) by inhibiting colony formation, migration, angiogenesis, and stimulating senescence of EPCs, while DMOG treatment alleviated these effects by promoting HIF-1α signaling pathway, as evidenced by senescence-associated β-galactosidase (SA-β-Gal) staining, colony-forming unit, matrigel tube formation, and transwell assays. The levels of proteins related to angiogenesis were determined by ELISA and Western blotting. In addition, active HIF-1α bolstered the targeting and homing of endogenous EPCs to the injured endothelium in the femoral head. Histopathologically, our in vivo study showed that DMOG not only alleviated glucocorticoid-induced osteonecrosis but also promoted angiogenesis and osteogenesis in the femoral head as detected by microcomputed tomography (Micro-CT) analysis and histological staining of OCN, TRAP, and Factor Ⅷ. However, all of these effects were impaired by an HIF-1α inhibitor. These findings demonstrate that targeting HIF-1α in EPCs may constitute a novel therapeutic approach for the treatment of SONFH.

ObjectiveThe purpose of this study was to investigate the value of the lateral point of articular surface of distal tibia (LADT) for anatomical alignment in total knee arthroplasty.MethodsWe reconstructed 148 three-dimensional pre-arthritic tibias and measured the tibial component inclination angle corresponding to the distal landmark of LADT. A retrospective study included 81 TKA recipients divided into the AA group and MA group. Clinical assessments including ROM, HSS, WOMAC, satisfaction for surgery, and radiological assessment were evaluated at one-year follow-up.ResultsThe tibial component varus angle corresponding to the distal landmark of LADT in the male and female groups were 3.4 ± 0.3° (2.6~4.2°) and 3.2 ± 0.3° (2.3~4.0°), respectively (P

Background: There is controversy over whether use of new oral anticoagulants (NOACs) associates with increased hemorrhage risk compared with non-NOAC. Meanwhile, determining which NOAC to use remains unclear. We aimed to summarize the evidence about NOACs in venous thromboembolism (VTE) prevention for patients with total hip and knee arthroplasty (THA and TKA).Methods: We searched RCTs assessing NOACs for VTE prophylaxis in adults undergoing THA and TKA in Medline, Embase, and Cochrane up to May 2021. Primary outcomes were VTE [included deep vein thrombosis (DVT) and pulmonary embolism (PE)], major VTE, and major bleeding. The rank probabilities of each treatment were summarized by the surface under the cumulative ranking curve area (SUCRA).Results: 25 RCTs with 42,994 patients were included. Compared with non-NOAC, NOACs were associated with a decreased risk of VTE (RR 0.68; 95% CI 0.55–0.84) and major VTE (RR = 0.52; 95% CI 0.35–0.76). Additionally, rivaroxaban, apixaban, and edoxaban but not dabigatran and betrixaban, did confer a higher efficacy compared with non-NOAC. None of the individual NOACs increased the risk of bleeding, while apixaban and betrixaban were even associated with a decreased risk of bleeding. In the comparison of different NOACs, rivaroxaban was associated with the greatest benefits in VTE (SUCRA = 79.6), DVT (SUCRA = 88.8), and major VTE (SUCRA = 89.9) prevention. Furthermore, subgroup analysis confirmed that NOACs associated with a higher efficacy tendency in patients with follow-up duration

Abstract Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into several tissues, such as bone, cartilage, and fat. Glucocorticoids affect a variety of biological processes such as proliferation, differentiation, and apoptosis of various cell types, including osteoblasts, adipocytes, or chondrocytes. Glucocorticoids exert their function by binding to the glucocorticoid receptor (GR). Physiological concentrations of glucocorticoids stimulate osteoblast proliferation and promote osteogenic differentiation of MSCs. However, pharmacological concentrations of glucocorticoids can not only induce apoptosis of osteoblasts and osteocytes but can also reduce proliferation and inhibit the differentiation of osteoprogenitor cells. Several signaling pathways, including the Wnt, TGFβ/BMP superfamily and Notch signaling pathways, transcription factors, post-transcriptional regulators, and other regulators, regulate osteoblastogenesis and adipogenesis of MSCs mediated by GR. These signaling pathways target key transcription factors, such as Runx2 and TAZ for osteogenesis and PPARγ and C/EBPs for adipogenesis. Glucocorticoid-induced osteonecrosis and osteoporosis are caused by various factors including dysfunction of bone marrow MSCs. Transplantation of MSCs is valuable in regenerative medicine for the treatment of osteonecrosis of the femoral head, osteoporosis, osteogenesis imperfecta, and other skeletal disorders. However, the mechanism of inducing MSCs to differentiate toward the osteogenic lineage is the key to an efficient treatment. Thus, a better understanding of the molecular mechanisms behind the imbalance between GR-mediated osteoblastogenesis and adipogenesis of MSCs would not only help us to identify the pathogenic causes of glucocorticoid-induced osteonecrosis and osteoporosis but also promote future clinical applications for stem cell-based tissue engineering and regenerative medicine. Here, we primarily review the signaling mechanisms involved in adipogenesis and osteogenesis mediated by GR and discuss the factors that control the adipo-osteogenic balance.

Abstract Background As a pivotal regulator, cyclin D3 gives play to a crucial value in conversion from the G1 stage to the S stage of cell cycle, which is implicated in tumor progression, especially proliferation and migration. Recent literatures have reported that cyclin D3 could predict survival time of malignancy patients. But, its prognostic role of cyclin D3 in neoplasms remains controversial. Methods Databases involving EMBASE, PubMed and Web of Science were carefully searched, and literatures investigating the prognostic effect of aberrantly expressing cyclin D3 among human cancers were collected for further analysis. We used both hazards ratios and its corresponding 95% confidence intervals to evaluate the connection among the survival rate of malignancy patients and the expression of cyclin D3. Results There were 13 eligible researches involving 16 cohorts and 2395 participants which were included in this study. The outcomes suggested that highly expressing cyclin D3 was significantly correlated with worse clinical prognosis of overall survival (HR 1.88; 95% CI 1.31–2.69) and disease specific survival (HR 2.68; 95% CI 1.35–5.31). But there existed no significant connection between the elevated expression of cyclin D3 with disease free survival (HR 2.65; 95% CI 0.83–8.46), recurrence-free survival (HR 2.86; 95% CI 0.82–9.96) and progression-free survival (HR 5.24; 95% CI 0.46–60.25) of diffident kinds of malignancy patients. Moreover, we discovered that elevated cyclin D3 expression was significantly connected with decreased overall survival in lymphoma (HR 3.72; 95% CI 2.18–6.36) while no significant relevance between highly expressing cyclin D3 and the overall survival in breast cancer was obtained (HR 2.12; 95% CI 0.76–5.91). Conclusions This meta-analysis demonstrated that highly expressing cyclin D3 might be an unfavorable prognostic biomarker for various malignancy patients, which can make great contributions to the clinical diagnosis and treatment.

Abstract Background Total hip arthroplasty (THA) is considerably difficult to perform in patients with Crowe type IV developmental dysplasia of the hip (DDH). Some Crowe type IV DDH patients require a femoral subtrochanteric shortening osteotomy to equalize the length of the lower extremities and decrease the difficulty of intraoperative reduction. Subtrochanteric transverse osteotomy has been proven to have superior clinical efficacy, but some cases of nonunion occur. Case presentation We present the case of a 62-year-old male patient who underwent right THA with femoral subtrochanteric transverse osteotomy due to Crowe type IV DDH. Nonunion of the osteotomy occurred during the follow-up period. In July 2017, the patient underwent right THA and femoral subtrochanteric transverse osteotomy due to Crowe type IV DDH. In November 2017, a slight feeling of bone rubbing and slight pain in the hip were reported. The ends of the osteotomy had rotated and united poorly. However, the patient requested to undergo continued observation. In December 2017, the patient reported an obvious sensation of bone rubbing and aggravated hip pain. The ends of the osteotomy had rotated and continued to exhibit nonunion. On December 26, 2017, the patient was treated with plate and screw internal fixation with bone morphogenetic protein (BMP) following our suggestion. In August 2018, the ends of the osteotomy had united after internal fixation was applied. Conclusions THA with femoral subtrochanteric transverse osteotomy exhibits good efficacy for the treatment of patients with Crowe type IV DDH. However, postoperative nonunion occurs in a small number of cases. The causes of nonunion should be analysed, and effective measures should be taken to prevent this situation. Plate and screw internal fixation with BMP is an effective treatment for nonunion of the ends of an osteotomy.

Background: Ubiquinol-cytochrome C reductase core protein II (QCR2) is essential for mitochondrial functions, yet, its role in cancer development has remained elusive. Methods: The expression of QCR2 in cancer patients was assessed by immunohistochemistry. The proliferation of cancer cells was assessed by CCK-8 assay, EdU staining and Flow cytometry analysis. The biological function of QCR2 and PHB were determined using western blotting, RT-qPCR, microarray analysis and xenografts. The interactions between proteins and the ubiquitination of p53 were assessed by immunoprecipitation, mass spectrometry analysis and GST pull down. The subcellular location of PHB and QCR2 was assessed by immunoblotting and immunofluorescence. Finding: The expression of QCR2 is upregulated in multiple human tumors. Suppression of QCR2 inhibits cancer cell growth by activating p53 signaling and inducing p21-dependent cell cycle arrest and senescence. QCR2 directly interacts with PHB in the mitochondria. Overexpression of QCR2 inhibits PHB binding to p53 in the nucleus, and facilitates p53 ubiquitination and degradation, consequently leading to tumorigenesis. Also, increased QCR2 and decreased PHB protein levels are well correlated with decreased expression of p21 in cervical cancer tissues. Interpretation: These results identify a novel role for QCR2, together with PHB, in negative regulation of p53 stability and activity, thus promote cervical carcinogenesis. Fund: “973” Program of China, the National Science-technology Supporting Plan Projects, the National Natural Science Foundation of China, National Science and Technology Major Sub-Project and Technical Innovation Special Project of Hubei Province. Keywords: QCR2, Tumorigenesis, p53, Degradation, PHB, Senescence

Steroid-induced osteonecrosis of femoral head (SONFH) is a common and serious complication caused by long-term and/or excessive use of glucocorticoids (GCs). The decreased activity and abnormal differentiation of bone marrow mesenchymal stem cells (BMSCs) are considered to be one of the major reasons for the onset and progression of this disease. Periostin (POSTN) is a matricellular protein which plays an important role in regulating osteoblast function and bone formation. Sclerostin (SOST) is a secreted antagonist of Wnt signaling that is mainly expressed in osteocytes to inhibit bone formation. However, the exact role of POSTN and SOST in SONFH has not been reported yet. Therefore, we detected the differential expression of POSTN and SOST in BMSCs of SONFH Group patients, and Control Group was patients with traumatic ONFH (TONFH) and developmental dysplasia of the hip (DDH). Furthermore, we used lentiviral transfection to knockdown POSTN expression in BMSCs of patients with SONFH to study the effect of POSTN knockdown on the SOST expression and osteogenic differentiation of BMSCs. The results indicated that the endogenous expression of POSTN and SOST in BMSCs of SONFH Group was upregulated, compared with Control Group. POSTN was upregulated gradually while SOST was downregulated gradually at days 0, 3, and 7 of osteogenic differentiation of BMSCs in Control Group. Contrarily, POSTN was gradually downregulated while SOST was gradually upregulated during osteogenic differentiation of BMSCs in SONFH Group. This could be due to increased expression of SOST in BMSCs, which was caused by excessive GCs. In turn, the increased expression of POSTN in BMSCs may play a role in antagonizing the continuous rising of SOST during the osteogenic differentiation of BMSCs in patients with SONFH. POSTN knockdown significantly attenuated osteo-specific gene expression, alkaline phosphatase activity, and calcium nodule formation in vitro; thus inhibiting the osteogenic differentiation of BMSCs in patients with SONFH. Besides, POSTN knockdown upregulated SOST expression, increased GSK-3β activity, and downregulated β-catenin. These findings suggest that POSTN have an essential role in regulating the expression of SOST and osteogenic differentiation of BMSCs in patients with SONFH, and POSTN knockdown suppresses osteogenic differentiation by upregulating SOST and partially inactivating Wnt/β-catenin signaling pathway. Therefore, targeting POSTN and SOST may serve as a promising therapeutic target for the prevention and treatment of SONFH.

ObjectivePrecise hip cup positioning is essential for the prevention of component impingement and dislocation in robotic assisted total hip arthroplasty (THA). Currently, the robotic system uses a mechanical alignment guide (MAG) for cup placement, which is one-size-fits-all, and the optimal cup positioning is controversial. Robotic assisted THA has not used any personalized cup positioning guides. The goal of this study was to identify an optimal guide for cup placement in robotic assisted THA to improve prognosis and life quality after THA.Materials and MethodsPelvis and femoral CT data of 47 participants were retrospectively collected for preoperative planning of robotic THA. The universal MAG guide and three personalized guides, including acetabular rim labrum guide (ARLG), transverse acetabular ligament guide (TALG), and ischiatic-pubis line guide (IPLG), were used to pose cups in the acetabulum of each participant. The position of cups was evaluated by inclination and anteversion; the function of hip joints was evaluated by hip ranges of motion, including abduction, adduction, extension, flexion, internal rotation, and external rotation.ResultsIn terms of cup positioning, ARLG provided a bigger cup inclination (p < 0.0001), while IPLG and TALG provided smaller cup inclination (p < 0.001) than MAG; the three personalized guides provided larger cup anteversion (p < 0.0001) than MAG. In terms of HROMs, compared with the use of MAG, the use of three personalized guides significantly decreased abduction (p < 0.0001), extension (p < 0.0001), and external rotation (p < 0.0001), but increased significantly flexion (p < 0.0001) and internal rotation (p < 0.0001); the use of ARLG significantly reduced adduction (p < 0.0001), but the use of IPLG and TALG increased adduction (p < 0.0001).ConclusionCompared with MAG, personalized guides provided greater flexion and internal rotation, which may reduce the risk of posterior dislocation. Among the three personalized guides, IPLG is the most reliable one for the preoperative planning of robotic assisted THA.

Background: Long non-coding RNA PANDAR is an emerging non-coding RNA mapping to 6p21.2. It underlies metastatic progression and chromosomal instability in a variety of cancers. Despite the fact that recent studies have revealed that lncRNA PANDAR may be a potential prognostic biomarker for patients with cancer, there has still been controversy on the prognostic value of PANDAR.Methods: Databases of PubMed, Embase, SinoMed, and Web of Science were carefully searched and the literature which investigated the prognostic value of PANDAR expression among human cancers was collected for further analysis. Odds ratios (ORs) or hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled to estimate the relation between PANDAR expression and survival or clinicopathological characteristics of cancer patients.Results: There were 13 eligible studies in total, with 1,465 patients enlisted in this meta-analysis. All the eligible studies complied with the case-control study. The outcome showed that the elevated expression level of PANDAR was significantly related to poor overall survival (OS) (pooled HR 1.72, 95%CI 1.14–2.60). However, high or low expression of PANDAR did not differ in the prediction of event-free survival (EFS). Moreover, we discovered that high PANDAR expression was closely related to decreased OS in colorectal cancer (pooled HR 3.43, 95%CI 2.06–5.72) and reduced expression level of PANDAR was markedly related to poor OS (pooled HR 0.65, 95%CI 0.45–0.88) in non-small cell lung cancer. However, the expression level of PANDAR had no significant association with OS in renal cell carcinoma (pooled HR 1.19, 95%CI 0.56–2.50). Moreover, after analysis, we discovered that the high expression level of PANDAR was associated closely with the depth of invasion (pooled OR 3.95, 95%CI 2.36–6.63), lymph node metastasis (pooled OR 1.92, 95%CI 0.93–3.98), tumor stage (pooled OR 2.05, 95%CI 0.99–4.27), and distant metastasis (pooled OR 2.87, 95%CI 1.60–5.16).Conclusions: Our study revealed that increased PANDAR expression may serve as an adverse prognostic biomarker for cancer patients, thus helping the clinical decision-making process.