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.

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).

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.

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.

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.

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.

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.

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.

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.

Evaluation of the performance of Ca-deficient hydroxyapatite (CDHA)/MgF2 bilayer coating on biodegradable high-purity magnesium in a femoral condyle defect model in rabbits.

The two most critical factors in promoting the clinical translation of magnesium (Mg) are reducing its degradation rate and improving its osteogenesis. In this study, a Ca-deficient hydroxyapatite (CDHA)/MgF2 bilayer coating was prepared on high-purity magnesium (HP Mg) rods by fluorination and hydrothermal treatment. Scanning electron microscope showed that the thickness of the bilayer coating was 3.78 µm and that the surface morphology was nanoscale. In an in vivo experiment on femoral condyle defects in rabbits, the serum magnesium ion levels of rabbits were always in the normal range after surgery, and the liver and kidney functions were not abnormal, which indicated that the CDHA/MgF2 bilayer coating has good biosafety. Micro-CT showed that the CDHA/MgF2 bilayer coating significantly reduced the degradation rate of the HP Mg rods and enhanced the promotion of bone formation. Hard tissue sections showed that the CDHA/MgF2 bilayer coating gave the bone tissue a tight contact interface with the HP Mg rod and improved the bone mass. Immunohistochemistry showed that the expression of vascular endothelial growth factor and BMP-2 was more obvious. These results confirm that the CDHA/MgF2 bilayer coating can improve the properties of HP Mg and provide a basis for the further transformation of HP Mg in the future. It also provides a new reference for the surface modification of magnesium metal.

Modulation of Osteogenesis and Angiogenesis Activities Based on Ionic Release from Zn-Mg Alloys.

The enhancement of osteogenesis and angiogenesis remains a great challenge for the successful regeneration of engineered tissue. Biodegradable Mg and Zn alloys have received increasing interest as potential biodegradable metallic materials, partially due to the biological functions of Mg2+ and Zn2+ with regard to osteogenesis and angiogenesis, respectively. In the present study, novel biodegradable Zn-xMg (x = 0.2, 0.5, 1.0 wt.%) alloys were designed and fabricated, and the effects of adding different amounts of Mg to the Zn matrix were investigated. The osteogenesis and angiogenesis beneficial effects of Zn2+ and Mg2+ release during the biodegradation were characterized, demonstrating coordination with the bone regeneration process in a dose-dependent manner. The results show that increased Mg content leads to a higher amount of released Mg2+ while decreasing the Zn2+ concentration in the extract. The osteogenesis of pre-osteoblasts was promoted in Zn-0.5Mg and Zn-1Mg due to the higher concentration of Mg2+. Moreover, pure Zn extract presented the highest activity in angiogenesis, owing to the highest concentration of Zn2+ release (6.415 µg/mL); the proliferation of osteoblast cells was, however, inhibited under such a high Zn2+ concentration. Although the concentration of Zn ion was decreased in Zn-0.5Mg and Zn-1Mg compared with pure Zn, the angiogenesis was not influenced when the concentration of Mg in the extract was sufficiently increased. Hence, Mg2+ and Zn2+ in Zn-Mg alloys show a dual modulation effect. The Zn-0.5Mg alloy was indicated to be a promising implant candidate due to demonstrating the appropriate activity in regulating osteogenesis and angiogenesis. The present work evaluates the effect of the Mg content in Zn-based alloys on biological activities, and the results provide guidance regarding the Zn-Mg composition in designs for orthopedic application.

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.

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.

Prognostic value of post-discharge depression in patients recently hospitalized with acute heart failure.

Background: Depression is a prevalent comorbidity in patients with heart failure (HF). However, data regarding the prognostic significance of depression during the early post-discharge period in patients hospitalized with acute HF, regardless of left ventricular ejection fraction (LVEF), were scarce. Methods and results: The Heart Failure Registry of Patient Outcomes (HERO) study is a prospective, multicenter study of patients hospitalized with acute HF in China. At the first follow-up after discharge (median 4.0, interquartile range [IQR]: 2.4-6.1 weeks), depressive symptoms over the past 2 weeks were assessed using the Patient Health Questionnaire-9 (PHQ-9). Of 3,889 patients, 480 (12.3%) patients had depression (PHQ-9 score ≥ 10). A total of 3,456 patients (11.4% with depression) were included in the prospective analysis. After a median follow-up of 47.1 weeks (IQR: 43.9, 49.3) from the first follow-up, 508 (14.7%) patients died, and 1,479 (42.8%) patients experienced a composite event (death or HF rehospitalization). Cox proportional hazards models were used to assess the association of post-discharge depression with adverse events. After adjustment, post-discharge depression was associated with an increased risk of all-cause mortality (hazard ratio [HR] 2.38 [95% confidence interval (CI): 1.93-2.94]; p < 0.001) and the composite event (HR 1.78 [95% CI: 1.55-2.05]; p < 0.001). A per scale point increase in PHQ-9 score (ranging from 0 to 27 points) was associated with a 7.6% increase in all-cause mortality (HR 1.08 [95% CI: 1.06-1.09]; p < 0.001). In the subgroup analysis, the association between depression and the composite event was significantly stronger in relatively younger patients (< 75 vs. ≥ 75 years; p for interaction = 0.011), and the association between depression and all-cause mortality was significantly stronger in patients with preserved ejection fraction than in those with reduced ejection fraction (p for interaction = 0.036). Conclusion: Post-discharge depression in patients recently hospitalized with acute HF is associated with an increased risk of adverse events, regardless of LVEF. Screening for depressive symptoms during the early post-discharge period may help to better identify high-risk patients and tailor patient management. Further studies are needed to determine how regular depression screening can help improve patient management and clinical outcomes.

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.

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.

Experimental study of a 3D printed permanent implantable porous Ta-coated bone plate for fracture fixation.

Metal plates have always been the gold standard in the clinic for internal fracture fixation due to their high strength advantages. However, high elastic modulus can cause stress shielding and lead to bone embrittlement. This study used an electron beam melting method to prepare personalized porous Ti6Al4V (pTi) bone plates. Then, chemical vapor deposition (CVD) technology coats tantalum (Ta) metal on the pTi bone plates. The prepared porous Ta-coated bone plate has an elastic modulus similar to cortical bone, and no stress shielding occurred. In vitro experiments showed that compared with pTi plates, Ta coating significantly enhances the attachment and proliferation of cells on the surface of the scaffold. To better evaluate the function of the Ta-coated bone plate, animal experiments were conducted using a coat tibia fracture model. Our results showed that the Ta-coated bone plate could effectively fix the fracture. Both imaging and histological analysis showed that the Ta-coated bone plate had prominent indirect binding of callus formation. Histological results showed that new bone grew at the interface and formed good osseointegration with the host bone. Therefore, this study provides an alternative to bio-functional Ta-coated bone plates with improved osseointegration and osteogenic functions for orthopaedic applications.

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.

Advancing the Regulation of Traditional and Complementary Medicine Products: A Comparison of Five Regulatory Systems on Traditional Medicines with a Long History of Use.

BACKGROUND: An appropriate regulatory system to ensure and promote the quality, safety, and efficacy of the products of traditional medicine (TM) and complementary medicine (CM) is critical to not only public health but also economic growth. The regulatory approach and evaluation standards for TM/CM products featured with a long history of use are yet to be developed. This study aims to investigate and compare the existing regulatory approaches for TM/CM products with a long history of use. METHOD: A mixed approach of documentary analysis involving official and legal documents from official websites, as well as a scoping review of scholarly work in scientific databases about regulatory systems of TM/CM products in China, Hong Kong, Taiwan, Japan, and Korea, was employed in this study and used for comparison. RESULTS: For registration purposes, all five regulatory systems recognized the history of use as part of the totality of evidence when evaluating the safety and efficacy of TM/CM products with a long history of use. Generally, the list of classic formulas is predefined and bound to the formulas recommended in the prescribed list of ancient medical textbooks. Expedited pathways are usually in place and scientific data of nonclinical and clinical studies may be exempted. At the same time, additional restrictions with the scope of products constitute a comprehensive approach in the regulation. Quality assurance and postmarketing safety surveillance were found to be the major focus across the regulatory schemes investigated in this study. CONCLUSION: The regulatory systems investigated in this study allow less stringent registration requirements for TM/CM products featured with a long history of use, assuming safety and efficacy to be plausible based on historic use. Considering the safety and efficacy of these products, regulatory standards should emphasize the technical requirements for quality control and postmarket surveillance.