Effect of cyclophosphamide combined with glucocorticoid therapy on idiopathic membranous nephropathy: A multicenter open-label randomized controlled trial.

OBJECTIVE: We aimed to evaluate the effect of cyclophosphamide combined with glucocorticoid therapy on idiopathic membranous nephropathy through a multicenter open-label randomized controlled trial. MATERIALS AND METHODS: 92 patients with idiopathic membranous nephropathy admitted from March 2020 to September 2022 were included and assigned to a control group (n = 46) and a research group (n = 46) using a random number table. The control group was given glucocorticoid, and the research group was given cyclophosphamide combined with glucocorticoid. Clinical efficacy, renal function-related indicators (serum creatinine, blood urea nitrogen and albumin, and 24-hour urine protein quantification), inflammatory factors (interleukin (IL)-6, IL-18, transforming growth factor-ß, and tumor necrosis factor-α), immune function-related indicators (anti-phospholipase A2 receptor antibody, and T-lymphocyte subsets), oxidative stress-related indicators (heme oxygenase-1, superoxide dismutase, malondialdehyde, and nitric oxide), blood lipid-related indicators (total cholesterol, triacylglycerol, and low-density lipoprotein), and adverse reactions were compared. RESULTS: The overall remission rate of the research group was higher than that of the control group (93.48 vs. 78.26%, p < 0.05). After treatment, the research group had lower levels of 24-hour urine protein quantification, serum creatinine, blood urea nitrogen, IL-6, IL-18, transforming growth factor-ß, tumor necrosis factor-α, heme oxygenase-1, malondialdehyde, anti-phospholipase A2 receptor antibody, CD8+, total cholesterol, triacylglycerol and low-density lipoprotein, higher levels of albumin, superoxide dismutase, nitric oxide, and CD4+ and a higher CD4+/CD8+ ratio than the control group (p < 0.05). CONCLUSION: Cyclophosphamide combined with glucocorticoid therapy is effective for improving the overall remission rate and can suppress inflammatory responses and oxidative stress in patients with idiopathic membranous nephropathy.

Association between vacA genotypes and the risk of duodenal ulcer: a meta-analysis.

Epidemiological studies have reported the relationship between vacuolating cytotoxin A (vacA) s-/m- region genotypes and duodenal ulcer (DU), but the results remained inconclusive. We performed the present meta-analysis to investigate a more authentic association between vacA s-/m- region genotypes and DU. Literature search was performed by searching Embase, PubMed and ISI Web of Science databases as well as checking references from identified articles, reviews and the abstracts presented at related scientific societies meetings. The association was assessed by combined odds ratio (OR) with 95% confidence interval (CI). A total of 42 studies were included in our final meta-analysis. The combined ORs (95% CIs) showed that vacA s1 (OR = 2.96, 95% CI = 2.34-3.75), m1 (OR = 1.46, 95% CI = 1.05-2.04) and s1m1 (OR = 1.89, 95% CI = 1.47-2.42) were associated with increased DU risk significantly in the overall studied population. Subgroup analyses by ethnicity showed that vacA s1 increased the risk of DU in Asian countries (OR = 1.92, 95% CI = 1.30-2.83), European countries (OR = 3.58, 95% CI = 2.13-6.03) and Latin American countries (OR = 4.20, 95% CI = 2.21-7.98); vacA m1 increased the risk of DU in Latin American countries (OR = 2.98, 95% CI = 1.59-5.56); vacA s1m1 increased the risk of DU in Asian countries (OR = 2.04, 95% CI = 1.12-3.73) and Latin American countries (OR = 2.05, 95% CI = 1.20-3.48); vacA s2m1 increased the risk of DU in Latin American countries (OR = 2.30, 95% CI = 1.17-4.50). The data suggest that genotype testing of vacA s- and m- region will be useful in screening susceptible individuals for DU development.

Non-alcoholic fatty liver disease (NAFLD) fibrosis score predicts 6.6-year overall mortality of Chinese patients with NAFLD.

The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has emerged as a useful predictor of long-term outcome in NAFLD patients. We evaluated the predictive performance of the NFS for overall mortality in a Chinese population with NAFLD. All NAFLD patients diagnosed ultrasonographically at Xixi Hospital of Hangzhou between 1996 and 2011 were retrospectively recruited to the study. Outcome was determined by interview and causes of death were confirmed by medical records. The area under the receiver operating characteristic curve (AUCROC ) was used to determine the predictive accuracy of the NFS, BARD (body mass index, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, diabetes) score, FIB-4 index and the AST/platelet ratio index (APRI) for mortality. Data from a total of 180 eligible patients (median age 39 years; 96 men) were analysed, with 12 deaths over a median follow-up period of 6.6 years (range 0.5-14.8 years). Using Cox model analysis, the NFS as a continuous variable was identified as the only predictor for all-cause mortality (hazard ratio 2.743, 95% confidence interval (CI) 1.670-4.504). The NFS yielded the highest AUCROC of 0.828 (95% CI 0.728-0.928, P < 0.05), followed by the FIB-4 index, APRI and BARD score (AUCROC 0.806 (P < 0.05), 0.732 (P < 0.05) and 0.632, respectively). The data indicated that the NFS is a useful predictor of 6.6-year all-cause mortality for Chinese patients with NAFLD.

Toll-like receptor-4 signalling in the progression of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet in mice.

The aim of the present study was to investigate Toll-like receptor-4 (TLR4) signalling at different stages of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat, high-fructose (HFHFr) diet in mice. Both TLR4 wild-type (WT) and mutant (TLR4(mut) ) mice were fed either standard chow (SC) or the HFHFr diet for different periods of time from 4 to 16 weeks. Pathological characteristics and function of the liver were assessed. Simple steatosis, steatohepatitis and hepatic fibrosis occurred sequentially in Week 4, 8 and 16 in WT mice fed with the HFHFr. Expression of TLR4, myeloid differentiation factor 88 (MyD88), interferon regulatory factor (IRF) 3 and IRF7 started to increase at Week 4, peaked at Week 8 and then declined to basal levels at Week 16. This pattern was consistent with changes in inflammation in the liver revealed by haematoxylin and eosin staining. However, lipid accumulation, inflammation and fibrosis in livers of TLR4(mut) mice fed the HFHFr diet were significantly alleviated. In addition, the expression of activin A in WT mice fed the HFHFr diet increased at Week 16. The data suggest that TLR4 signalling mediates non-alcoholic steatohepatitis before fibrosis and that activin A is subsequently involved in NAFLD.

Heterlimnius luyashanensis sp. n. and Zaitzevia triangularis sp. n. from Shanxi Province, China (Coleoptera: Elmidae).

Two new species, Heterlimnius luyashanensis sp. n. and Zaitzevia triangularis sp. n. are described from Shanxi Province, China. The genus Heterlimnius Hinton, 1935 and Zaitzevia Champion, 1923 are reported from Shanxi Province for the first time. Heterlimnius luyashanensis sp. n. belonging to the Heterlimnius trachys species group has the following characteristics: 1. anterior margin of pronotum strongly produced anteriad; 2. median longitudinal sulcus of pronotum extends from basal 0.3 to 0.8. Zaitzevia triangularis sp. n. has a larger body size and a triangular apex of penis.

Modified Zhenwu Tang delays chronic renal failure progression by modulating oxidative stress and hypoxic responses in renal proximal tubular epithelial cells.

Background: Tubulointerstitial fibrosis (TIF) is a critical pathological feature of chronic renal failure (CRF), with oxidative stress (OS) and hypoxic responses in renal proximal tubular epithelial cells playing pivotal roles in disease progression. This study explores the effects of Modified Zhenwu Tang (MZWT) on these processes, aiming to uncover its potential mechanisms in slowing CRF progression. Methods: We used adenine (Ade) to induce CRF in rats, which were then treated with benazepril hydrochloride (Lotensin) and MZWT for 8 weeks. Assessments included liver and renal function, electrolytes, blood lipids, renal tissue pathology, OS levels, the hypoxia-inducible factor (HIF) pathway, inflammatory markers, and other relevant indicators. In vitro, human renal cortical proximal tubular epithelial cells were subjected to hypoxia and lipopolysaccharide for 72 h, with concurrent treatment using MZWT, FM19G11, and N-acetyl-l-cysteine. Measurements taken included reactive oxygen species (ROS), HIF pathway activity, inflammatory markers, and other relevant indicators. Results: Ade treatment induced significant disruptions in renal function, blood lipids, electrolytes, and tubulointerstitial architecture, alongside heightened OS, HIF pathway activation, and inflammatory responses in rats. In vivo, MZWT effectively ameliorated proteinuria, renal dysfunction, lipid and electrolyte imbalances, and renal tissue damage; it also suppressed OS, HIF pathway activation, epithelial-mesenchymal transition (EMT) in proximal tubular epithelial cells, and reduced the production of inflammatory cytokines and collagen fibers. In vitro findings demonstrated that MZWT decreased apoptosis, reduced ROS production, curbed OS, HIF pathway activation, and EMT in proximal tubular epithelial cells, and diminished the output of inflammatory cytokines and collagen. Conclusion: OS and hypoxic responses significantly contribute to TIF development. MZWT mitigates these responses in renal proximal tubular epithelial cells, thereby delaying the progression of CRF.

Additive Manufacturing of Biodegradable Molybdenum - From Powder to Vascular Stent.

Magnesium, iron, and zinc-based biodegradable metals are widely recognized as promising candidate materials for the next generation of bioresorbable stent (BVS). However, none of those metal BVSs are perfect at this stage. Here, a brand-new BVS based on a novel biodegradable metal (Molybdenum, Mo) through additive manufacturing is developed. Nearly full-dense and crack-free thin-wall Mo is directly manufactured through selective laser melting (SLM) with fine Mo powder. Systemic analyses considering the forming quality, wall-thickness, microstructure, mechanical properties, and in vitro degradation behaviors are performed. Then, Mo-based thin-strut (≤ 100 µm) stents are successfully obtained through an optimized single-track laser melting route. The SLMed thin-wall Mo owns comparable strength to its Mg and Zn based counterparts (as-drawn), while, it exhibits remarkable biocompatibility in vitro. Vessel related cells are well adhered and spread on SLMed Mo, and it exhibits a low risk of hemolysis and thrombus. The SLMed stent is compatible to vessel tissues in rat abdominal aorta, and it can provide sufficient support in an animal model as an extravascular stent. This work possibly opens a new era of manufacturing Mo-based stents through additive manufacturing.

Identifying optimal surgical approach among T1N2-3M0 non-small cell lung cancer patients: a population-based analysis.

Background: Whether stage T1N2-3M0 non-small cell lung cancer (NSCLC) patients could benefit from surgery and the optimal surgical procedure have remained controversial and unclear. This study aimed to investigate whether stage T1N2-3M0 NSCLC can benefit from different surgery types and develop a tool for survival prediction. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with stage T1N2-3M0 NSCLC between 2000 and 2015. A 1:1 propensity score-matched (PSM) analysis was used to balance the distribution of clinical characteristics. Survival analyses were performed by using the Kaplan-Meier (KM) curves and Cox proportional hazards regression. All patients were randomly split at a ratio of 7:3 into training and validation cohorts. The nomogram was constructed by integrating all independent predictors for overall survival (OS) and cancer-specific survival (CSS). The model's performance was evaluated by discrimination, calibration ability, and risk stratification ability. Results: A total of 4,671 patients were enrolled. After 1:1 PSM, the distribution proportions of clinical characteristics in 1,146 patients were balanced (all P>0.05). The non-surgical approach was associated with worse survival compared with sublobectomy and lobectomy in the unmatched and matched cohorts. The multivariate Cox analysis showed that sublobectomy and lobectomy were both related to better OS and CSS rates compared with no surgery (P<0.001). Moreover, the results of subgroup analyses based on age, N stage, and radiotherapy or chemotherapy strategy were consistent. A total of 801 patients were included in the training cohort and 345 cases constituted the validation cohort. The nomogram constructed for the 1-, 3-, and 5-year OS and CSS prediction showed good discrimination, performance, and calibration both in the training and validation sets. Significant distinctions in survival curves between different risk groups stratified by prognostic scores were also observed (all P<0.001). Conclusions: Stage T1N2-3M0 NSCLC patients could benefit from sublobectomy or lobectomy, and lobectomy provides better survival benefits. We developed and validated nomograms, which could offer clinicians instructions for strategy making.

Epileptic Seizure Prediction Using Attention Augmented Convolutional Network.

Early seizure prediction is crucial for epilepsy patients to reduce accidental injuries and improve their quality of life. Identifying pre-ictal EEG from the inter-ictal state is particularly challenging due to their nonictal nature and remarkable similarities. In this study, a novel epileptic seizure prediction method is proposed based on multi-head attention (MHA) augmented convolutional neural network (CNN) to address the issue of CNN's limit of capturing global information of input signals. First, data enhancement is performed on original EEG recordings to balance the pre-ictal and inter-ictal EEG data, and the EEG recordings are sliced into 6-second-long EEG segments. Subsequently, EEG time-frequency distribution is obtained using Stockwell transform (ST), and the attention augmented convolutional network is employed for feature extraction and classification. Finally, post-processing is utilized to reduce the false prediction rate (FPR). The CHB-MIT EEG database was used to evaluate the system. The validation results showed a segment-based sensitivity of 98.24% and an event-based sensitivity of 94.78% with a FPR of 0.05/h were yielded, respectively. The satisfying results of the proposed method demonstrate its possible potential for clinical applications.

Drug release and solubility properties of two zeolitic metal-organic frameworks influenced by their hydrophobicity/hydrophilicity.

Metal-organic frameworks (MOFs) have shown significant potential for drug delivery applications. However, there remains a scarcity of comprehensive research addressing the influence of surface properties of MOFs on drug release kinetics and drug solubility. This study focuses on examining the influence of MOFs hydrophilicity and hydrophobicity on the controlled release and solubility of drugs. To achieve this, we prepared drug-loaded nanoparticles through in situ synthesis and created a drug-MOF co-amorphous system using the ball milling technique. Under neutral conditions, the hydrophilic MOF-based drug delivery system demonstrated a comparatively slower drug release profile than its hydrophobic counterpart. This observation suggests that the hydrophilic system holds promise in mitigating drug side effects by enabling improved control over drug release. The implementation of hydrophobic MOFs in co-amorphous systems yields a more pronounced effect on enhancing solubility compared to hydrophilic MOFs. This study offers valuable insights for achieving optimal drug release kinetics and solubility by delicately manipulating surface properties of MOFs.

Design of single-phased magnesium alloys with typically high solubility rare earth elements for biomedical applications: Concept and proof.

Rare earth elements (REEs) have been long applied in magnesium alloys, among which the mischmetal-containing WE43 alloy has already got the CE mark approval for clinical application. A considerable amount of REEs (7 wt%) is needed in that multi-phased alloy to achieve a good combination of mechanical strength and corrosion resistance. However, the high complex RE addition accompanied with multiple second phases may bring the concern of biological hazards. Single-phased Mg-RE alloys with simpler compositions were proposed to improve the overall performance, i.e., "Simpler alloy, better performance". The single-phased microstructure can be successfully obtained with typical high-solubility REEs (Ho, Er or Lu) through traditional smelting, casting and extrusion in a wide compositional range. A good corrosion resistance with a macroscopically uniform corrosion mode was guaranteed by the homogeneously single-phased microstructure. The bimodal-grained structure with plenty of sub-grain microstructures allow us to minimize the RE addition to <1 wt%, without losing mechanical properties. The single-phased Mg-RE alloys show comparable mechanical properties to the clinically-proven Mg-based implants. They exhibited similar in-vitro and in-vivo performances (without local or systematic toxicity in SD-rats) compared to a high purity magnesium. In addition, metal elements in our single-phased alloys can be gradually excreted through the urinary system and digestive system, showing no consistent accumulation of RE in main organs, i.e., less burden on organs. The novel concept in this study focuses on the simplification of Mg-RE based alloys for biomedical purpose, and other biodegradable metals with single-phased microstructures are expected to be explored.

Fluorescent In Situ 3D Visualization of Dynamic Corrosion Processes of Magnesium Alloys.

Magnesium (Mg) alloys as implant materials with excellent biodegradation ability have promising clinical applications for tissue repair and restoration. Although the corrosion processes of Mg alloys in biophysiological media are closely related with their biodegradation ability, only limited methods have been developed for characterization of their corrosion processes, including electrochemical analysis, weight loss measurement, and hydrogen evolution analysis. Moreover, these methods suffer from drawbacks of poor spatiotemporal resolution, static observation, and tedious operation. To tackle these challenges, we herein developed a fluorescent probe PSPA for in situ 3D monitoring of the dynamic corrosion processes of Mg alloys on the basis of its selective turn-on detection ability toward magnesium hydroxide [Mg(OH)2], which is the main corrosion product of Mg alloys in biophysiological media. As far as we know, this is the first example of a fluorescent probe for the monitoring of corrosion processes of Mg alloys in biophysiological media. We believe this fluorescence analysis method with easy operation and high spatiotemporal resolution advantages will contribute greatly to the clinical applications of Mg alloy implants.

Recent advances on the mechanical behavior of zinc based biodegradable metals focusing on the strain softening phenomenon.

Zinc based biodegradable metals (BMs) show great potential to be used in various biomedical applications, owing to their superior biodegradability and biocompatibility. Some high-strength (ultimate tensile strength > 600 MPa) Zn based BMs have already been developed through alloying and plastic working, making their use in load-bearing environments becomes a reality. However, different from Mg and Fe based BMs, Zn based BMs exhibit significant "strain-softening" effect that leads to limited uniform deformation. Non-uniform deformation is detrimental to Zn based devices or implants, which will possibly lead to unexpected failure. People might be misled by the considerable fracture elongation of Zn based BMs. Thus, it is important to specify uniform elongation as a term of mechanical requirements for Zn based BMs. In this review, recent advances on the mechanical properties of Zn based BMs have been comprehensively summarized, especially focusing on the strain softening phenomenon. At first, the origin and evaluation criteria of strain softening were introduced. Secondly, the effects of alloying elements (including element type, single or multiple addition, and alloying content) and microstructural characteristics (grain size, constituent phase, phase distribution, etc.) on mechanical properties (especially for uniform elongation) of Zn based BMs were summarized. Finally, how to get a good balance between strength and uniform elongation was generally discussed based on the service environment. In addition, possible ways to minimize or eliminate the strain softening effect were also proposed, such as controlling of twins, solute clusters, and grain boundary characteristics. All these items above would be helpful to understand the mechanical instability of Zn based BMs, and to make the full usage of them in the future medical device design. STATEMENT OF SIGNIFICANCE: Biodegradable metals (BMs) is a hotspot in the field of metallic biomaterials. Fracture elongation is normally adopted to quantify the deformability of Mg and Fe based BMs owing to their negligible necking strain, yet the strain softening would occur in Zn based BMs, which is extremely detrimental to performance of their medical device. In this review paper, a better understanding the mechanical performance of Zn-based BMs with the term "uniform elongation" instead of "fracture elongation" was depicted, and possible ways to minimize or eliminate the strain softening effect were also proposed, such as twins, solute clusters, self-stable dislocation network, and grain boundary characteristics. It would be helpful to understand the mechanical instability of Zn based BMs and making full usage of it in the future medical device design.

Biomimetic Ti-6Al-4V alloy/gelatin methacrylate hybrid scaffold with enhanced osteogenic and angiogenic capabilities for large bone defect restoration.

Titanium-based scaffolds are widely used implant materials for bone defect treatment. However, the unmatched biomechanics and poor bioactivities of conventional titanium-based implants usually lead to insufficient bone integration. To tackle these challenges, it is critical to develop novel titanium-based scaffolds that meet the bioadaptive requirements for load-bearing critical bone defects. Herein, inspired by the microstructure and mechanical properties of natural bone tissue, we developed a Ti-6Al-4V alloy (TC4)/gelatin methacrylate (GelMA) hybrid scaffold with dual bionic features (GMPT) for bone defect repair. GMPT is composed of a hard 3D-printed porous TC4 metal scaffold (PT) backbone, which mimics the microstructure and mechanical properties of natural cancellous bone, and a soft GelMA hydrogel matrix infiltrated into the pores of PT that mimics the microenvironment of the extracellular matrix. Ascribed to the unique dual bionic design, the resultant GMPT demonstrates better osteogenic and angiogenic capabilities than PT, as confirmed by the in vitro and rabbit radius bone defect experimental results. Moreover, controlling the concentration of GelMA (10%) in GMPT can further improve the osteogenesis and angiogenesis of GMPT. The fundamental mechanisms were revealed by RNA-Seq analysis, which showed that the concentration of GelMA significantly influenced the expression of osteogenesis- and angiogenesis-related genes via the Pi3K/Akt/mTOR pathway. The results of this work indicate that our dual bionic implant design represents a promising strategy for the restoration of large bone defects.

Degradation behaviors and in-vivo biocompatibility of a rare earth- and aluminum-free magnesium-based stent.

Biodegradable stents can provide scaffolding and anti-restenosis benefits in the short term and then gradually disappear over time to free the vessel, among which the Mg-based biodegradable metal stents have been prosperously developed. In the present study, a Mg-8.5Li (wt.%) alloy (RE- and Al-free) with high ductility (> 40%) was processed into mini-tubes, and further fabricated into finished stent through laser cutting and electropolishing. In-vitro degradation test was performed to evaluate the durability of this stent before and after balloon dilation. The influence of plastic deformation and residual stress (derived from the dilation process) on the degradation was checked with the assistance of finite element analysis. In addition, in-vivo degradation behaviors and biocompatibility of the stent were evaluated by performing implantation in iliac artery of minipigs. The balloon dilation process did not lead to deteriorated degradation, and this stent exhibited a decent degradation rate (0.15 mm/y) in vitro, but divergent result (> 0.6 mm/y) was found in vivo. The stent was almost completely degraded in 3 months, revealing an insufficient scaffolding time. Meanwhile, it did not induce possible thrombus, and it was tolerable by surrounding tissues in pigs. Besides, endothelial coverage in 1 month was achieved even under the severe degradation condition. In the end, the feasibility of this stent for treatment of benign vascular stenosis was generally discussed, and perspectives on future improvement of Mg-Li-based stents were proposed.

Biomimicking Bone-Implant Interface Facilitates the Bioadaption of a New Degradable Magnesium Alloy to the Bone Tissue Microenvironment.

The most critical factor determining the success of biodegradable bone implants is the host tissue response, which greatly depends on their degradation behaviors. Here, a new magnesium-based implant, namely magnesium-silicon-calcium (Mg-0.2Si-1.0Ca) alloy, that coordinates its biodegradation along with the bone regenerative process via a self-assembled, multilayered bone-implant interface is designed. At first, its rapid biocorrosion contributes to a burst release of Mg2+ , leading to a pro-osteogenic immune microenvironment in bone. Meanwhile, with the simultaneous intervention of Ca and Si in the secondary phases of the new alloy, a hierarchical layered calcified matrix is rapidly formed at the degrading interface that favored the subsequent bone mineralization. In contrast, pure Mg or Mg-0.2Si alloy without the development of this interface at the beginning will unavoidably induce detrimental bone loss. Hence, it is believed this biomimicking interface justifies its bioadaptability in which it can modulate its degradation in vivo and accelerate bone mineralization.

PDLLA-Zn-nitrided Fe bioresorbable scaffold with 53-µm-thick metallic struts and tunable multistage biodegradation function.

Balancing the biodegradability and mechanical integrity of a bioresorbable scaffold (BRS) with time after implantation to match the remodeling of the scaffolded blood vessel is important, but a key challenge in doing so remains. This study presents a novel intercalated structure of a metallic BRS by introducing a nanoscale Zn sacrificial layer between the nitrided Fe platform and the sirolimus-carrying poly(d,l-lactide) drug coating. The PDLLA-Zn-FeN BRS shows a multistage biodegradation behavior, maintaining mechanical integrity at the initial stage and exhibiting accelerated biodegradation at the subsequent stage in both rabbit abdominal aortas and human coronary arteries, where complete biodegradation was observed about 2 years after implantation. The presence of the nanoscale Zn sacrificial layer with an adjustable thickness also contributes to the tunable biodegradation of BRS and allows the reduction of the metallic strut thickness to 53 µm, with radial strength as strong as that of the current permanent drug-eluting stents.

Comparative in vitro study on binary Mg-RE (Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu) alloy systems.

Correct selection of alloying elements is important for developing novel biodegradable magnesium alloys with superior mechanical and biological performances. In contrast to various reports on nutrient elements (Ca, Zn, Sr, etc.) as alloying elements of biomedical magnesium alloys, there is limited information about how to choose the right rare earth elements (REEs) as alloying elements of magnesium. In this work, 16 kinds of REEs were individually added into Mg, including Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Du, Ho, Er, Tm, Yb and Lu, to fabricate binary Mg-RE model alloys with different composition points. Under the same working history, comparative studies were undertaken and the impact of each kind of rare earth element on the microstructure, mechanical property, corrosion behavior and biocompatibility of Mg were investigated. The corresponding influence level for the 16 kinds of REEs were ranked. The results showed that the second phases were detected in some Mg-RE alloys, which were mainly composed of Mg12RE. By adding different REEs into Mg with proper contents, the mechanical properties of resulting Mg-RE binary alloys could be adjusted in wide range. The corrosion resistance of Mg-light REE alloys was generally better than Mg-heavy REE alloys. As for biocompatibility, Mg-RE model alloys showed no cytotoxic effect on MC3T3-E1 cells. The hemolysis rates of all experimental Mg-RE model alloys were lower than 5% except for Mg-Lu alloy model. In general, the addition of different REEs into Mg could improve its performance from different aspects. This work provides a better understanding on suitable REEs as alloying elements for magnesium, and the future R&D direction on biomedical Mg-RE alloys was proposed. STATEMENT OF SIGNIFICANCE: In contrast to various reports on nutrient elements (Ca, Zn, Sr, etc.) as alloying elements of biomedical magnesium alloys, until now there is limited information about how to choose the right rare earth elements (REEs) as alloying elements of magnesium. In this work, comparative studies were undertaken by individually adding 16 kinds of REEs, including Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Du, Ho, Er, Tm, Yb and Lu, into Mg to fabricate binary Mg-RE model alloys, with different composition points, then the impact of each kind of rare earth element on the microstructure, mechanical property, corrosion behavior and biocompatibility of Mg under the same working history were investigated, and the corresponding influence level for the 16 kinds of REEs were ranked. This work provides a better understanding on suitable REEs as alloying elements for magnesium, and the future R&D direction on biomedical Mg-RE alloys was proposed.

Magnetic resonance (MR) safety and compatibility of a novel iron bioresorbable scaffold.

Fully bioresorbable scaffolds have been designed to overcome the limitations of traditional drug-eluting stents (DESs), which permanently cage the native vessel wall and pose possible complications. The ultrathin-strut designed sirolimus-eluting iron bioresorbable coronary scaffold system (IBS) shows comparable mechanical properties to traditional DESs and exhibits an adaptive degradation profile during target vessel healing, which makes it a promising candidate in all-comers patient population. For implanted medical devices, magnetic resonance (MR) imaging properties, including MR safety and compatibility, should be evaluated before its clinical use, especially for devices with intrinsic ferromagnetism. In this study, MR safety and compatibility of the IBS scaffold were evaluated based on a series of well-designed in-vitro, ex-vivo and in-vivo experiments, considering possible risks, including scaffold movement, over-heating, image artifact, and possible vessel injury, under typical MR condition. Traditional ASTM standards for MR safety and compatibility evaluation of intravascular devices were referred, but not only limited to that. The unique time-relevant MR properties of bioresorbable scaffolds were also discussed. Possible forces imposed on the scaffold during MR scanning and MR image artifacts gradually decreased along with scaffold degradation/absorption. Rigorous experiments designed based on a scientifically based rationale revealed that the IBS scaffold is MR conditional, though not MR compatible before complete absorption. The methodology used in the present study can give insight into the MR evaluation of magnetic scaffolds (bioresorbable) or stents (permanent).

In vitro and in vivo studies of Mg-30Sc alloys with different phase structure for potential usage within bone.

Proper alloying magnesium with element scandium (Sc) could transform its microstructure from α phase with hexagonal closed-packed (hcp) structure into ß phase with body-cubic centered (bcc) structure. In the present work, the Mg-30 wt% Sc alloy with single α phase, dual phases (α + ß) or ß phase microstructure were developed by altering the heat-treatment routines and their suitability for usage within bone was comprehensively investigated. The ß phased Mg-30 wt% Sc alloy showed the best mechanical performance with ultimate compressive strength of 603 ±â€¯39 MPa and compressive strain of 31 ±â€¯3%. In vitro degradation test showed that element scandium could effectively incorporate into the surface corrosion product layer, form a double-layered structure, and further protect the alloy matrix. No cytotoxic effect was observed for both single α phased and ß phased Mg-30 wt% Sc alloys on MC3T3 cell line. Moreover, the ß phased Mg-30 wt%Sc alloy displayed acceptable corrosion resistance in vivo (0.06 mm y-1) and maintained mechanical integrity up to 24 weeks. The degradation process did not significantly influence the hematology indexes of inflammation, hepatic or renal functions. The bone-implant contact ratio of 75 ±â€¯10% after 24 weeks implied satisfactory integration between ß phased Mg-30 wt%Sc alloy and the surrounding bone. These findings indicate a potential usage of the bcc-structured Mg-Sc alloy within bone and might provide a new strategy for future biomedical magnesium alloy design. STATEMENT OF SIGNIFICANCE: Scandium is the only rare earth element that can transform the matrix of magnesium alloy into bcc structure, and Mg-30 wt%Sc alloy had been recently reported to exhibit shape memory effect. The aim of the present work is to study the feasibility of Mg-30 wt%Sc alloy with different constitutional phases (single α phase, single ß phase or dual phases (α + ß)) as biodegradable orthopedic implant by in vitro and in vivo testings. Our findings showed that ß phased Mg-30 wt%Sc alloy which is of bcc structure exhibited improved strength and superior in vivo degradation performance (0.06 mm y-1). No cytotoxicity and systematic toxicity were shown for ß phased Mg-30 wt%Sc alloy on MC3T3 cell model and rat organisms. Moreover, good osseointegration, limited hydrogen gas release and maintained mechanical integrity were observed after 24 weeks' implantation into the rat femur bone.