CTGF regulates mineralization in human mature chondrocyte by controlling Pit-1 and modulating ANK via the BMP/Smad signalling.

OBJECTIVE: Connective tissue growth factor (CTGF) exhibits potent proliferative, differentiated, and mineralizing effects, and is believed to be contribute to cartilage mineralization in Osteoarthritis (OA). However, the underlying mechanism of chondrocyte mineralization induced by CTGF remains obscure. As a key regulator of mineral responses, type III phosphate transporter 1 (Pit-1) has been associated with the pathogenesis of articular mineralization. Therefore, the primary objective of this study was to investigate whether CTGF influences the development of mature chondrocyte mineralization and the underlying mechanisms governing such mineralization. METHODS: The effect of Connective tissue growth factor (CTGF) on human C-28/I2 chondrocytes were investigated. The chondrocytes were treated with CTGF or related inhibitors, and transfected with Overexpression and siRNA transfection of Type III Phosphate Transporter 1(Pit-1). Subsequently, the cells were subjected to Alizarin red S staining, PiPer Phosphate Assay Kit, Alkaline Phosphatase Diethanolamine Activity Kit, ELISA, RT-PCR or Western blot analysis. RESULTS: Stimulation with Connective tissue growth factor (CTGF) significantly upregulated the expression of the Type III Phosphate Transporter 1(Pit-1) and mineralization levels in chondrocytes through activation of α5ß1 integrin and BMP/Samd1/5/8 signaling pathways. Furthermore, treatment with overexpressed Pit-1 markedly increased the expression of Multipass Transmembrane Ankylosis (ANK) transporter in the cells. The inhibitory effect of CTGF receptor blockade using α5ß1 Integrin blocking antibody was demonstrated by significantly suppressed the expression of Pit-1 and ANK transporter, as well as chondrocyte mineralization. CONCLUSIONS: Our data indicate that Connective tissue growth factor (CTGF) plays a critical role inchondrocyte mineralization, which is dependent on the expression of the Type III Phosphate Transporter 1(Pit-1) and Multipass Transmembrane Ankylosis (ANK) transporter. Consequently, inhibition of CTGF activity may represent a novel therapeutic approach for the management of Osteoarthritis (OA).

Elevated lncRNA-UCA1 upregulates EZH2 to promote inflammatory response in sepsis-induced pneumonia via inhibiting HOXA1.

Sepsis is characterized by a dysregulated inflammatory response. We aimed to explore the role of the long noncoding RNA urothelial carcinoma associated 1 (lncRNA UCA1)/enhancer of zeste homolog 2 (EZH2)/homeobox A1 (HOXA1) axis in sepsis-induced pneumonia. The sepsis rat models and RLE-6TN cellular sepsis-induced pneumonia models were established using ligation and puncture (CLP) and lipopolysaccharide (LPS). The expression of UCA1, EZH2, and HOXA1 in rat lung tissues and RLE-6TN cells was detected. Then, the CLP rats were respectively treated with lentivirus to upregulate or downregulate the expression of UCA1 and EZH2 to measure their roles in the pathology, apoptosis, inflammation and phosphorylated NF-κB p65(p-p65) levels in CLP rat lung tissues. UCA1 and EZH2 expression was upregulated or downregulated in LPS-induced RLE-6TN cells to explore their effects on cell viability, apoptosis, inflammation and p-p65 levels. The interactions among UCA1, EZH2, and HOXA1 were identified. UCA1 and EZH2 were upregulated whereas HOXA1 was downregulated in CLP rat lung tissues and LPS-induced RLE-6TN cells. Elevated UCA1 or increased EZH2 aggravated pathology and promoted apoptosis, inflammation and phosphorylated NF-κB p-65 levels in CLP rat lung tissues, and inhibited viability while facilitated apoptosis, inflammation and phosphorylated NF-κB p-65 levels in LPS-induced RLE-6TN cells. Silenced EZH2 reversed the effects of UCA1 elevation on sepsis-induced pneumonia. UCA1 suppressed HOXA1 expression through physically interacting with EZH2. UCA1 overexpression upregulates EZH2 to repress HOXA1 expression, thus aggravating the progression of sepsis-induced pneumonia, which could be alleviated by EZH2 inhibition.

Cancer-associated fibroblasts subtypes and role in invasion and metastasis of gastric cancer.

Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Cancer-associated fibroblasts (CAFs), an important cell type in the tumor microenvironment, play an important role in GC development. In this review, we describe the current knowledge of CAFs' heterogeneity and their role in GC invasion and metastasis. Currently, CAF-targeted cancer therapies are being rapidly explored and developed. However, the heterogeneity of CAFs limits the application of this therapy, so it is urgent to find specific markers and divide them into different subpopulations. With the development of single-cell RNA sequencing technology, researchers have used this technology to classify CAFs in many tumors, but whether it is applicable to GC and other tumors needs further study. And we believe that this technology will be in the near future utilized to sort CAFs on the basis of different cell markers and functions, so as to target tumor-promoting CAFs and inhibit tumor progression. Targeting CAFs by cell surface markers or normalizing the activated CAFs subsets may be an effective therapy, alone or in combination with other therapeutic approaches for GC treatment. Therefore, in the coming decades, the interaction between CAFs and GC cells will be still the focus of our research.

Retrospective Study of 1255 Non-Anticoagulated Patients with Nonvalvular Atrial Fibrillation to Determine the Risk of Ischemic Stroke Associated with Left Atrial Spontaneous Echo Contrast on Transesophageal Echocardiography.

BACKGROUND Left atrial spontaneous echo contrast (LASEC) is associated with an increased risk of stroke in patients with nonvalvular atrial fibrillation (NVAF). Therefore, a tool that identifies the risk of LASEC in non-anticoagulated patients with NVAF may be helpful for stroke risk stratification and early stroke prevention in these patients. The aim of this retrospective study was to establish a novel risk score model to determine the risk of ischemic stroke associated with LASEC on transesophageal echocardiography (TEE). MATERIAL AND METHODS This study retrospectively and consecutively enrolled 1255 non-anticoagulated patients with NVAF who underwent TEE prior to catheter ablation or left atrial appendage occlusion. Most importantly, a novel nomogram was developed using a logistic regression model to predict the risk of LASEC. RESULTS A nomogram was established for LASEC prediction which included 5 independent risk factors determined by multivariable logistic regression analysis: increased age, non-paroxysmal atrial fibrillation, previous stroke/transient ischemic attack, congestive heart failure, and left atrial enlargement. The receiver operating characteristic curve analysis showed that the area under the curve (AUC) of the novel risk score model was 0.879 (95% confidence interval: 0.849-0.909, P<0.001). Compared with the CHA2DS2-VASc score, the novel risk score model had a better predictive power (AUC: 0.879 vs 0.617, P<0.001). CONCLUSIONS This novel risk score model effectively predicted the presence of LASEC in non-anticoagulated patients with NVAF.

Ruthenium Nanoparticles Anchored on Graphene Hollow Nanospheres Superior to Platinum for the Hydrogen Evolution Reaction in Alkaline Media.

The design and construction of highly efficient and stable Pt-free catalysts for the electrocatalytic hydrogen evolution reaction (HER) in alkaline media is extremely desirable. Herein, a novel hybrid of ruthenium (Ru) nanoparticles anchored on graphene hollow nanospheres (GHSs) is synthesized by a template-assisted strategy. The combination of ultrafine Ru nanoparticles and hollow spherical support endows the resultant Ru/GHSs an extraordinary catalytic performance with a low overpotential of 24.4 mV at a current density of 10 mA cm-2, a small Tafel slope of 34.8 mV dec-1, as well as long-term stability in 1.0 M KOH solution, which is, to our knowledge, superior to commercial 20% Pt-C catalyst and most of the state-of-the-art HER electrocatalysts reported. Remarkably, this work provides a new route for the development of other metal-based HER electrocatalysts for energy-related applications.

The imbalance in the aortic ceramide/sphingosine-1-phosphate rheostat in ovariectomized rats and the preventive effect of estrogen.

BACKGROUND: The prevalence of hypertension in young women is lower than that in age-matched men while the prevalence of hypertension in women is significantly increased after the age of 50 (menopause) and is greater than that in men. It is already known that sphingosine-1-phosphate (S1P) and ceramide regulate vascular tone with opposing effects. This study aimed to explore the effects of ovariectomy and estrogen supplementation on the ceramide/S1P rheostat of the aorta in rats, and to explore a potential mechanism for perimenopausal hypertension and a brand-new target for menopausal hormone therapy to protect vessels. METHODS: In total, 30 female adult SD rats were randomly divided into three groups: The sham operation group (SHAM), ovariectomy group (OVX) and ovariectomy plus estrogen group (OVX + E). After 4 weeks of treatment, the blood pressure (BP) of the rats was monitored by a noninvasive system; the sphingolipid content (e.g., ceramide and S1P) was detected by liquid chromatography-mass spectrometry (LC-MS); the expression of the key enzymes involved in ceramide anabolism and catabolism was measured by real-time fluorescence quantitative polymerase chain reaction (qPCR); and the expression of key enzymes and proteins in the sphingosine kinase 1/2 (SphK1/2)-S1P-S1P receptor 1/2/3 (S1P1/2/3) signaling pathway was detected by qPCR and western blotting. RESULTS: In the OVX group compared with the SHAM group, the systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) increased significantly, especially the SBP and PP (P < 0.001). For aortic ceramide metabolism, the mRNA level of key enzymes involved in anabolism and catabolism decreased in parallel 2-3 times, while the contents of total ceramide and certain long-chain subtypes increased significantly (P < 0.05). As for the S1P signaling pathway, SphK1/2, the key enzymes involved in S1P synthesis, decreased significantly, and the content of S1P decreased accordingly (P < 0.01). The S1P receptors showed various trends: S1P1 was significantly down-regulated, S1P2 was significantly up-regulated, and S1P3 showed no significant difference. No significant difference existed between the SHAM and OVX + E groups for most of the above parameters (P > 0.05). CONCLUSIONS: Ovariectomy resulted in the imbalance of the aortic ceramide/S1P rheostat in rats, which may be a potential mechanism underlying the increase in SBP and PP among perimenopausal women. Besides, the ceramide/S1P rheostat may be a novel mechanism by which estrogen protects vessels.

Identification of gene coexpression modules, hub genes, and pathways related to spinal cord injury using integrated bioinformatics methods.

Spinal cord injury (SCI) is characterized by dramatic neurons loss and axonal regeneration suppression. The underlying mechanism associated with SCI-induced immune suppression is still unclear. Weighted gene coexpression network analysis (WGCNA) is now widely applied for the identification of the coexpressed modules, hub genes, and pathways associated with clinic traits of diseases. We performed this study to identify hub genes associated with SCI development. Gene Expression Omnibus (GEO) data sets GSE45006 and GSE20907 were downloaded and the significant correlativity and connectivity between them were detected using WGCNA. Three significant consensus modules, including 567 eigengenes, were identified from the master GSE45006 data following the preconditions of approximate scale-free topology for WGCNA. Further bioinformatics analysis showed these eigengenes were involved in inflammatory and immune responses in SCI. Three hub genes Rac2, Itgb2, and Tyrobp and one pathway "natural killer cell-mediated cytotoxicity" were identified following short time-series expression miner, protein-protein interaction network, and functional enrichment analysis. Gradually upregulated expression patterns of Rac2, Itgb2, and Tyrobp genes at 0, 3, 7, and 14 days after SCI were confirmed based on GSE45006 and GSE20907 data set. Finally, we found that Rac2, Itgb2, and Tyrobp genes might take crucial roles in SCI development through the "natural killer cell-mediated cytotoxicity" pathway.

Effects of oestrogen and Cimicifuga racemosa on the cardiac noradrenaline pathway of ovariectomized rats.

NEW FINDINGS: What is the central question of this study? We investigated the effects of oestrogen and Cimicifuga racemosa on the stellate ganglion, cardiac noradrenaline pathway and Ca2+ -calmodulin-dependent protein kinase II in ovariectomized rats. What is the main finding and its importance? The right stellate ganglion, but not the left, may be associated with decreased left ventricular noradrenaline content in ovariectomized rats. Oestrogen can reverse all changes caused by ovariectomy. Cimicifuga racemosa did not affect left ventricular noradrenaline, but decreased protein expression of ß1 -adrenergic receptor and Ca2+ -calmodulin-dependent protein kinase II. The results might explain potential effects of C. racemosa on the cardiovascular system and provide new insights into cardiovascular protection. The aim of this study was to investigate the effects of oestrogen and Cimicifuga racemosa on the stellate ganglion, cardiac noradrenaline (NA) pathway and Ca2+ -calmodulin-dependent protein kinase II (CaMK II). Forty adult female Sprague-Dawley rats were randomly divided into the following four groups: sham operated (SHAM); ovariectomized (OVX); ovariectomized with oestrogen treatment (E2); and ovariectomized with C. racemosa treatment (iCR). After 4 weeks of treatment, the NA content was determined by high-performance liquid chromatography, and dopamine ß-hydroxylase (DBH) and noradrenaline transporter (NET) expression were detected by immunohistochemistry. Western blotting was used to determine NET, ß1 -adrenergic receptor (ß1 -AR) and CaMK II expression. Compared with the SHAM group, body weights, DBH and NET expression in the right stellate ganglia, and NET, ß1 -AR and CaMK II expression in the left ventricles of the OVX group were increased, whereas left ventricular NA content was decreased; DBH and NET expression in the left stellate ganglion was not significantly different. The indexes of the E2 group were similar to those of the SHAM group. Moreover, in the iCR group, DBH, NET, ß1 -AR and CaMK II expression was decreased; NET expression and NA content of the left ventricle remained unchanged. Our conclusions are as follows. First, the right stellate ganglion, but not the left, may be associated with decreased left ventricular NA content in OVX rats. Second, oestrogen increases the left ventricular NA content and adjusts the expression of DBH and NET in the right stellate ganglion and restores ß1 -AR and CaMK II protein expression to normal levels. Third, C. racemosa does not affect left ventricular NA, but decreases the protein expression of ß1 -AR and CaMK II.

3D printed osteochondral scaffolds: design strategies, present applications and future perspectives.

Articular osteochondral (OC) defects are a global clinical problem characterized by loss of full-thickness articular cartilage with underlying calcified cartilage through to the subchondral bone. While current surgical treatments can relieve pain, none of them can completely repair all components of the OC unit and restore its original function. With the rapid development of three-dimensional (3D) printing technology, admirable progress has been made in bone and cartilage reconstruction, providing new strategies for restoring joint function. 3D printing has the advantages of fast speed, high precision, and personalized customization to meet the requirements of irregular geometry, differentiated composition, and multi-layered boundary layer structures of joint OC scaffolds. This review captures the original published researches on the application of 3D printing technology to the repair of entire OC units and provides a comprehensive summary of the recent advances in 3D printed OC scaffolds. We first introduce the gradient structure and biological properties of articular OC tissue. The considerations for the development of 3D printed OC scaffolds are emphatically summarized, including material types, fabrication techniques, structural design and seed cells. Especially from the perspective of material composition and structural design, the classification, characteristics and latest research progress of discrete gradient scaffolds (biphasic, triphasic and multiphasic scaffolds) and continuous gradient scaffolds (gradient material and/or structure, and gradient interface) are summarized. Finally, we also describe the important progress and application prospect of 3D printing technology in OC interface regeneration. 3D printing technology for OC reconstruction should simulate the gradient structure of subchondral bone and cartilage. Therefore, we must not only strengthen the basic research on OC structure, but also continue to explore the role of 3D printing technology in OC tissue engineering. This will enable better structural and functional bionics of OC scaffolds, ultimately improving the repair of OC defects.

Selective Laser Melting of the Porous Ta Scaffold with Mg-Doped Calcium Phosphate Coating for Orthopedic Applications.

Addressing the repair of large-scale bone defects has become a hot research topic within the field of orthopedics. This study assessed the feasibility and effectiveness of using porous tantalum scaffolds to treat such defects. These scaffolds, manufactured using the selective laser melting (SLM) technology, possessed biomechanical properties compatible with natural bone tissue. To enhance the osteogenesis bioactivity of these porous Ta scaffolds, we applied calcium phosphate (CaP) and magnesium-doped calcium phosphate (Mg-CaP) coatings to the surface of SLM Ta scaffolds through a hydrothermal method. These degradable coatings released calcium and magnesium ions, demonstrating osteogenic bioactivity. Experimental results indicated that the Mg-CaP group exhibited biocompatibility comparable to that of the Ta group in vivo and in vitro. In terms of osteogenesis, both the CaP group and the Mg-CaP group showed improved outcomes compared to the control group, with the Mg-CaP group demonstrating superior performance. Therefore, both CaP and magnesium-CaP coatings can significantly enhance the osseointegration of three-dimensional-printed porous Ta, thereby increasing the surface bioactivity. Overall, the present study introduces an innovative approach for the biofunctionalization of SLM porous Ta, aiming to enhance its suitability as a bone implant material.

Design, fabrication and clinical characterization of additively manufactured tantalum hip joint prosthesis.

The joint prosthesis plays a vital role in the outcome of total hip arthroplasty. The key factors that determine the performance of joint prostheses are the materials used and the structural design of the prosthesis. This study aimed to fabricate a porous tantalum (Ta) hip prosthesis using selective laser melting (SLM) technology. The feasibility of SLM Ta use in hip prosthesis was verified by studying its chemical composition, metallographic structure and mechanical properties. In vitro experiments proved that SLM Ta exhibited better biological activities in promoting osteogenesis and inhibiting inflammation than SLM Ti6Al4V. Then, the topological optimization design of the femoral stem of the SLM Ta hip prosthesis was carried out by finite element simulation, and the fatigue performance of the optimized prosthesis was tested to verify the biomechanical safety of the prosthesis. A porous Ta acetabulum cup was also designed and fabricated using SLM. Its mechanical properties were then studied. Finally, clinical trials were conducted to verify the clinical efficacy of the SLM Ta hip prosthesis. The porous structure could reduce the weight of the prosthesis and stress shielding and avoid bone resorption around the prosthesis. In addition, anti-infection drugs can also be loaded into the pores for infection treatment. The acetabular cup can be custom-designed based on the severity of bone loss on the acetabular side, and the integrated acetabular cup can repair the acetabular bone defect while achieving the function of the acetabular cup.

Clinical characteristics and outcomes of patients with intracerebral hemorrhage after acute myocardial infarction.

Data regarding patients with intracranial hemorrhage (ICH) following acute myocardial infarction (AMI) is scarce. This study aims to investigate the incidence, clinical characteristics, prevention, treatment, and prognosis of ICH in patients with AMI. Among 5257 patients with AMI, 14 cases (0.27%) experienced ICH following AMI, including 11 males and three females. In-hospital mortality occurred in eight patients (57.1%), all of whom experienced sudden loss of consciousness. Six patients (42.6%) were classified as high or very high risk according to CRUSADE score, and seven patients (50.0%) were classified as high risk according to Academic Research Consortium for High Bleeding Risk (ARC-HBR). The CRUSADE and ARC-HBR scores can complement each other in risk assessment. All in-hospital deaths occurred within four days of ICH onset; The volume of ICH in patients who died in the hospital was significantly higher than in those who survived and were discharged, with 30 ml possibly serving as a threshold. The incidence of ICH following myocardial infarction is low; however, the mortality rate is extremely high, presenting considerable challenges for clinical treatment. Prevention, early detection, and prompt symptomatic management are essential for improving patient outcomes.

Acute myocardial infarction post-gastrointestinal bleeding: A clinical dilemma with poor prognosis.

Background: Gastrointestinal bleeding (GIB) complicating acute myocardial infarction (AMI) is a severe clinical condition with treatment contradiction and poor prognosis. This study aimed to evaluate the rate of in-hospital mortality in patients with GIB who subsequently suffered from AMI and to explore the potential risk factors for this condition. Methods: In this retrospective study, a total of 77 patients diagnosed with GIB, who subsequently suffered from AMI, were enrolled from January 2013 to March 2022. Demographic, laboratory, and clinical data were collected. The in-hospital mortality was the outcome of interest. Logistic regression analysis was used to investigate the potential risk factors of in-hospital mortality. Results: Among the 77 patients included in this study, 62 (80.52%) were males. The mean age of patients was 65.88 ± 12.15 years, and 48 patients (62.34%) were non-ST-segment elevation myocardial infarction (NSTEMI). There were 16 (20.78%) cases of in-hospital deaths. The subjects who died showed higher levels of white blood cell count (13.05 ± 5.76 vs. 9.31 ± 4.07 × 109/L, P = 0.003) and troponin I (TnI) (9.23 ± 9.17 vs. 4.12 ± 5.03 µg/L, P = 0.003). Besides, there were higher proportions of cardiogenic shock (81.25% vs. 26.23%, P < 0.001) and mechanical ventilator usage (75.0% vs. 11.48%, P < 0.001) among the patients who died. The multivariate logistic regression analysis showed that white blood cell count (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.02-1.39, P = 0.030), cardiogenic shock (OR 12.18, 95% CI 3.06-48.39, P = 0.017), and mechanical ventilator usage (OR 7.21, 95% CI 1.28-40.51, P = 0.025) were independently associated with in-hospital mortality. Conclusions: The in-hospital mortality of patients with GIB who subsequently develop AMI is high. White blood cell count, cardiogenic shock, and mechanical ventilator usage are independent predictors of in-hospital mortality.

Modelling 30-day hospital readmission after discharge for COPD patients based on electronic health records.

Chronic Obstructive Pulmonary Disease (COPD) is the third most common chronic disease in China with frequent exacerbations, resulting in increased hospitalization and readmission rate. COPD readmission within 30 days after discharge is an important indicator of care transitions, patient's quality of life and disease management. Identifying risk factors and improving 30-day readmission prediction help inform appropriate interventions, reducing readmissions and financial burden. This study aimed to develop a 30-day readmission prediction model using decision tree by learning from the data extracted from the electronic health record of COPD patients in Macao. Health records data of COPD inpatients from Kiang Wu Hospital, Macao, from January 1, 2018, to December 31, 2019 were reviewed and analyzed. A total of 782 hospitalizations for AECOPD were enrolled, where the 30-day readmission rate was 26.5% (207). A balanced dataset was randomly generated, where male accounted for 69.1% and mean age was 80.73 years old. Age, length of stay, history of tobacco smoking, hemoglobin, systemic steroids use, antibiotics use and number of hospital admission due to COPD in last 12 months were found to be significant risk factors for 30-day readmission of CODP patients (P < 0.01). A data-driven decision tree-based modelling approach with Bayesian hyperparameter optimization was developed. The mean precision-recall and AUC value for the classifier were 73.85, 73.7 and 0.7506, showing a satisfying prediction performance. The number of hospital admission due to AECOPD in last 12 months, smoke status and patients' age were the top factors for 30-day readmission in Macao population.

Adopting an electronic medication administration system in long-term care facilities: a key stakeholder interview study in Macao.

To improve medication safety for residents in long-term care facilities (LTCFs), electronic medication administration records (eMARs) are widely adopted in Macao. This study aimed to (1) develop a logic model for adopting eMAR in LTCFs and (2) explore the contextual factors relevant to the implementation. Semi-structured interviews were conducted with key stakeholders (managers, doctors, nurses, pharmacy staff and other frontline workers) experienced with eMAR in LTCFs in Macao between February and March 2021. Purposive sampling was used for recruitment and thematic analysis followed the theoretical framework of the logic model. All 57 participants were positive about eMAR. Financial and nonfinancial resources were critical to adopting eMAR. eMAR was mostly used for its functions in documentation, e-prescribing and monitoring. Immediate output included simplified working process, reduced errors, closer monitoring of residents' conditions, and timely communication among staff. The outcomes mainly related to efficiency, safety and quality of care, workload redundancy, and data unification. Key influencing factors included eMAR flexibility, stability, and technical support. Adopting eMARs is highly consuming and the benefits in improving quality of care can only be realized with appropriate implementation, precise execution, regular evaluation and responsive adjustment. The proposed logic model framework serves as a roadmap for LTCFs, both current and future users of eMAR.

Biomechanical analysis and clinical observation of 3D-printed acetabular prosthesis for the acetabular reconstruction of total hip arthroplasty in Crowe III hip dysplasia.

Objective: This study aimed to evaluate the biomechanical effectiveness of 3D-printed integrated acetabular prosthesis (IAP) and modular acetabular prosthesis (MAP) in reconstructing the acetabulum for patients with Crowe III developmental dysplasia of the hip (DDH). The results of this study can provide a theoretical foundation for the treatment of Crowe III DDH in total hip arthroplasty (THA). Methods: Finite element (FE) analysis models were created to reconstruct Crowe III DDH acetabular defects using IAP and MAP. The contact stress and relative micromotion between the acetabular prosthesis and the host bone were analyzed by gradually loading in three increments (210 N, 2100 N, and 4200 N). In addition, five patients with Crowe III DDH who underwent IAP acetabular reconstruction were observed. Results: At the same load, the peak values of IAP contact stress and relative micromotion were lower than those of MAP acetabular reconstruction. Under jogging load, the MAP metal augment's peak stress exceeded porous tantalum yield strength, and the risk of prosthesis fracture was higher. The peak stress in the bone interface in contact with the MAP during walking and jogging was higher than that in the cancellous bone, while that of IAP was higher than that of the cancellous bone only under jogging load, so the risk of MAP cancellous bone failure was greater. Under jogging load, the relative micromotion of the MAP reconstruction acetabular implant was 45.2 µm, which was not conducive to bone growth, while under three different loads, the relative micromotion of the IAP acetabular implant was 1.5-11.2 µm, all <40 µm, which was beneficial to bone growth. Five patients with IAP acetabular reconstruction were followed up for 11.8 ± 3.4 months, and the Harris score of the last follow-up was 85.4 ± 5.5. The imaging results showed good stability of all prostheses with no adverse conditions observed. Conclusion: Compared with acetabular reconstruction with MAP, IAP has a lower risk of loosening and fracture, as well as a better long-term stability. The application of IAP is an ideal acetabular reconstruction method for Crowe III DDH.

Research progress and clinical translation of three-dimensional printed porous tantalum in orthopaedics.

With continuous developments in additive manufacturing technology, tantalum (Ta) metal has been manufactured into orthopaedic implants with a variety of forms, properties and uses by three-dimensional printing. Based on extensive research in recent years, the design, processing and performance aspects of this new orthopaedic implant material have been greatly improved. Besides the bionic porous structure and mechanical characteristics that are similar to human bone tissue, porous tantalum is considered to be a viable bone repair material due to its outstanding corrosion resistance, biocompatibility, bone integration and bone conductivity. Numerous in vitro, in vivo, and clinical studies have been carried out in order to analyse the safety and efficacy of these implants in orthopaedic applications. This study reviews the most recent advances in manufacturing, characteristics and clinical application of porous tantalum materials.

Treatment of Acetabular Bone Defect in Revision of Total Hip Arthroplasty Using 3D Printed Tantalum Acetabular Augment.

OBJECTIVE: The treatment of acetabular defects is one of the most difficult challenges of revision of total hip arthroplasty (RTHA), and tantalum is regarded as a promising bone substitute material. This study aims to investigate the effectiveness of 3D printed acetabular augment used in RTHA for the treatment of acetabular bone defect. METHODS: A retrospective analysis of the clinical data of seven patients who had undergone RTHA was carried out using 3D printed acetabular augment from January 2017 to December 2018. The CT data of the patients were exported to Mimics 21.0 software (Materialise, Leuven, Belgium), and the acetabular bone defect augment were designed, printed and then implanted during operation. The postoperative Harris score, visual analogue scale (VAS) score and prosthesis position were observed to evaluate the clinical outcome. A I-test was used for preoperative and postoperative comparison of the paired-design dataset. RESULTS: A firm attachment of the bone augment to the acetabulum during operation without any complications was found during the follow-up time 2.8-4.3 years. The VAS score of all patients was found 6.9 ± 1.4 before operation and was 0.7 ± 0.7 at the last follow-up (P ≤ 0.001), and the Harris hip scores, were 31.9 ± 10.3 and 73.3 ± 12.8 before operation, and at the last follow-up (P ≤ 0.001), respectively. Moreover, no loosening sign between the bone defect augment and the acetabulum was observed during the entire implantation period. CONCLUSION: 3D printed acetabular augment is effective in reconstructing the acetabulum following an acetabular bone defect revision, which enhances the hip joint function and eventually makes a satisfactory stable prosthetic.

Association of On-Admission Anemia With 1-Year Mortality in Patients Hospitalized With Acute Heart Failure: Results From the HERO Study.

Background: Anemia is common in patients with chronic heart failure (HF) and is associated with adverse outcomes. However, data regarding the prognostic value of on-admission anemia on mortality in patients hospitalized with acute HF were relatively limited and conflicting. This study aimed to investigate the association of on-admission anemia with 1-year mortality and evaluate whether anemia is an independent predictor of mortality in patients hospitalized with acute HF. Methods: The present analysis included 4,244 patients hospitalized with acute HF from the HERO (Heart Failure Registry of Patient Outcomes) study. On-admission anemia was defined using the World Health Organization (WHO) criteria (hemoglobin <120 g/L in women and <130 g/L in men). Cox proportional hazards models were used to assess the association of anemia with 1-year all-cause and cardiovascular mortality. Results: Of 4,244 patients, 2,206 (52.0%) patients had no anemia, 1,106 (26.1%) patients had mild anemia (men 110 ≤ hemoglobin < 130 g/L; women 110 ≤ hemoglobin < 120g/L), and 932 (22.0%) patients had moderate-to-severe anemia (hemoglobin < 110 g/L). After a median follow-up of 12.4 months (interquartile range: 11.9, 12.6), 867 (20.4%) patients died. Among the 742 (85.6%) deaths with confirmed causes, 664 (89.5%) were due to cardiovascular diseases. The mortality rates in patients with no anemia, mild anemia, and moderate-to-severe anemia were 16.6%, 20.4%, and 29.4%, respectively (p < 0.001). The association of anemia with increased all-cause mortality was significant in the unadjusted model (hazard ratio [HR]: 1.54, 95% confidential interval [CI]: 1.35-1.77, p < 0.001), and remained statistically significant after adjustment for most potential confounders (HR: 1.20, 95%CI: 1.03-1.40, p = 0.020), but no longer significant after additional adjustment for natriuretic peptides (HR: 1.02, 95%CI: 0.86-1.21, p = 0.843). When considering the degree of anemia, moderate-to-severe anemia was an independent predictor of all-cause mortality after full adjustment (HR:1.26, 95%CI: 1.03-1.54, p = 0.028), whereas mild anemia was not (HR: 0.84, 95%CI: 0.69-1.04, p = 0.104). A similar relationship was also found between anemia and cardiovascular mortality. Conclusions: On-admission anemia, defined by the WHO criteria, is not an independent predictor of mortality in patients hospitalized with acute HF. Moderate-to-severe anemia in patients with acute HF is independently associated with increased mortality.

Exploring the implementation of an outreach specialist program for nursing home residents in Macao: A multisite, qualitative study.

Background: The "Specialist Medical Outreach Project (SMOP)" involving inter-disciplinary hospital-based healthcare professionals is a government initiative that aims to provide integrative specialist care to high-risk residents at the nursing homes. However, research exploring the implementation and impact of SMOP is lacking. This study aimed to evidence the impact of SMOP on the quality of care at the nursing home and the key contextual determinants influencing SMOP outcomes. Method: Semi-structured key informant audio-recorded face-to-face interviews were conducted with eight managers, six doctors, 28 nursing staff, and seven pharmacy staff at the nursing homes participating in the SMOP to collect insights about how SMOP was operated and performed, and the impact of SMOP as observed and expected. Participants were recruited with purposive sampling. A thematic analysis approach was employed and key themes were identified using open coding, grouping, and categorizing. Results: Forty-nine interviews were conducted. Thematic analysis identified three principal themes: the overall perception about SMOP, the benefits as observed; and the areas of improvement. Together with the 10 subthemes, the results highlighted the expectations for SMOP to address the unmet needs and promote patient-centered care, and the benefits of SMOP in supporting effective use of resources for the nursing home, reducing the risks of adverse events for the residents, promoting communication and capacity building for the healthcare providers and facilitating efficient use of healthcare resources for the health system. Requests for more frequent visits by a larger inter-disciplinary specialist team were raised. Careful staff and workflow planning, and mechanisms for data-sharing and communication across care settings were deemed the most important actions for improvement. Conclusion: It is a general perception that the SMOP is beneficial in enhancing the quality of care for high-risk residents in the nursing home in Macao. Cross-sector inter-disciplinary collaboration and efficient data-sharing and communication mechanism play a crucial role in ensuring the success of the program. A robust assessment framework to monitor and evaluate the cost-effectiveness of the program is yet to be developed.