Burden of bone disease in chronic pancreatitis:A systematic review and meta-analysis

BACKGROUND Bone disease is an under-recognized cause of morbidity in chronic pancreatitis(CP).Over the past decade,publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the problem.AIM To quantify the prevalence of osteopenia,osteoporosis,and fragility fractures in CP patients and investigate the associated clinical features and outcomes.METHODS A systematic search identified studies investigating bone disease in CP patients from Cochrane Library,Embase,Google Scholar,Ovid Medline,PubMed,Scopus,and Web of Science,from inception until October 2022.The outcomes included prevalence of osteopenia,osteoporosis,and fragility fractures,which were metaanalyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical features.RESULTS Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis.The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2%(95%CI:35.2%-47.3%)and 20.9%(95%CI:14.9%-27.6%),respectively.The pooled prevalence of fragility fractures described among CP was 5.9%(95%CI:3.9%-8.4%).Metaregression revealed significant association of pancreatic enzyme replacement therapy(PERT)use with prevalence of osteoporosis[coefficient:1.7(95%CI:0.6-2.8);P<0.0001].We observed no associations with mean age,sex distribution,body mass index,alcohol or smoking exposure,diabetes with prevalence of osteopenia,osteoporosis or fragility fractures.Paucity of data on systemic inflammation,CP severity,and bone mineralization parameters precluded a formal metaanalysis.CONCLUSION This meta-analysis confirms significant bone disease in patients with CP.Other than PERT use,we observed no patient or study-specific factor to be significantly associated with CP-related bone disease.Further studies are needed to identify confounders,at-risk population,and to understand the mechanisms of CP-related bone disease and the implications of treatment response.

Amino acid and mineral digestibility,bone ash,and plasma inositol is increased by including microbial phytase in diets for growing pigs

Background The effect of microbial phytase on amino acid and energy digestibility is not consistent in pigs,which may be related to the phytase dosage or the adaptation length to the diet.Therefore,an experiment was conducted to test the hypotheses that increasing dietary phytase after an 18-day adaptation period:1)increases nutrient and energy digestibility;2)increases plasma P,plasma inositol,and bone ash of young pigs;and 3)demonstrates that maximum phytate degradation requires more phytase than maximum P digestibility.Results Data indicated that increasing inclusion of phytase[0,250,500,1,000,2,000,and 4,000 phytase units(FTU)/kg feed]in corn-soybean meal-based diets increased apparent ileal digestibility(AID)of Trp(quadratic;P<0.05),and of Lys and Thr(linear;P<0.05),and tended to increase AID of Met(linear;P<0.10).Increasing dietary phytase also increased AID and apparent total tract digestibility(ATTD)of Ca and P(quadratic;P<0.05)and increased ATTD of K and Na(linear;P<0.05),but phytase did not influence the ATTD of Mg or gross energy.Concentrations of plasma P and bone ash increased(quadratic;P<0.05),and plasma inositol also increased(linear;P<0.05)with increasing inclusion of phytase.Reduced concentrations of inositol phosphate(IP)6 and IP5(quadratic;P<0.05),reduced IP4 and IP3(linear;P<0.05),but increased inositol concentrations(linear;P<0.05)were observed in ileal digesta as dietary phytase increased.The ATTD of P was maximized if at least 1,200 FTU/kg were used,whereas more than 4,000 FTU/kg were needed to maximize inositol release.Conclusions Increasing dietary levels of phytase after an 18-day adaptation period increased phytate and IP ester degradation and inositol release in the small intestine.Consequently,increasing dietary phytase resulted in improved digestibility of Ca,P,K,Na,and the first 4 limiting amino acids,and in increased concentrations of bone ash and plasma P and inositol.In a corn-soybean meal diet,maximum inositol release requires approximately 3,200 FTU/kg more phytase than that required for maximum P digestibility.

Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors:The iBoneFIT project

Background Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of muscle strength with aBMD are unknown in this population.Therefore,this study aimed to investigate the prevalence of upper-and lower-body muscle strength deficits and to examine the associations of upper-and lower-body muscle strength with age-,sex,and race-specific aBMD Z-scores at the total body,total hip,femoral neck,and lumbar spine.Methods This cross-sectional study included 116 pediatric cancer survivors(12.1±3.3 years old,mean±SD;42.2%female).Upper-and lower-body muscle strength were assessed by handgrip and standing long jump test,respectively.Dual‑energy X‑ray absorptiometry was used to measure aBMD(g/cm2).Associations between muscle strength and aBMD were evaluated in multivariable linear regression models.Logistic regression was used to evaluate the contribution of muscle strength(1-decile lower)to the odds of having low aBMD(Z-score≤1.0).All analyses were adjusted for time from treatment completion,radiotherapy exposure,and body mass index.Results More than one-half of survivors were within the 2 lowest deciles for upper-(56.9%)and lower-body muscle strength(60.0%)in comparison to age-and sex-specific reference values.Muscle strength deficits were associated with lower aBMD Z-scores at all sites(B=0.133–0.258,p=0.001–0.032).Each 1-decile lower in upper-body muscle strength was associated with 30%–95%higher odds of having low aBMD Z-scores at all sites.Each 1-decile lower in lower-body muscle strength was associated with 35%–70%higher odds of having low aBMD Z-scores at total body,total hip,and femoral neck.Conclusion Muscle strength deficits are prevalent in young pediatric cancer survivors,and such deficits are associated with lower aBMD Z-scores at all sites.These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added benefit of improving aBMD.

3D-printed Mg-1Ca/polycaprolactone composite scaffolds with promoted bone regeneration

In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.

Systemic modulation of skeletal mineralization by magnesium implant promoting fracture healing: Radiological exploration enhanced with PCA-based machine learning in a rat femoral model

The clinical application of magnesium(Mg)and its alloys for bone fractures has been well supported by in vitro and in vivo trials.However,there were studies indicating negative effects of high dose Mg intake and sustained local release of Mg ions on bone metabolism or repair,which should not be ignored when developing Mg-based implants.Thus,it remains necessary to assess the biological effects of Mg implants in animal models relevant to clinical treatment modalities.The primary purpose of this study was to validate the beneficial effects of intramedullary Mg implants on the healing outcome of femoral fractures in a modified rat model.In addition,the mineralization parameters at multiple anatomical sites were evaluated,to investigate their association with healing outcome and potential clinical applications.Compared to the control group without Mg implantation,postoperative imaging at week 12 demonstrated better healing outcomes in the Mg group,with more stable unions in 3D analysis and high-mineralized bridging in 2D evaluation.The bone tissue mineral density(TMD)was higher in the Mg group at the non-operated femur and lumbar vertebra,while no differences between groups were identified regarding the bone tissue volume(TV),TMD and bone mineral content(BMC)in humerus.In the surgical femur,the Mg group presented higher TMD,but lower TV and BMC in the distal metaphyseal region,as well as reduced BMC at the osteotomy site.Principal component analysis(PCA)-based machine learning revealed that by selecting clinically relevant parameters,radiological markers could be constructed for differentiation of healing outcomes,with better performance than 2D scoring.The study provides insights and preclinical evidence for the rational investigation of bioactive materials,the identification of potential adverse effects,and the promotion of diagnostic capabilities for fracture healing.

Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

Autograft or metal implants are routinely used in skeletal repair.However,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering alternative.The use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor tissueregeneration.Thus,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic lineage.In this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based deposition.The inclusion of the nanofiller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon printing.The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)model.The inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven days.This study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

Surgical management of tegmen defects of the temporal bone and meningoencephalic herniation: our experience

1. Introduction The tegmental wall of the tympanic cavity is a thin plate of the temporal bone that separates the middle cranial fossa(MCF) from the ear. This anatomical region consists of two areas: an anterior one, comprised of the tegmen tympani(To′th et al., 2007), and a posterior one, formed by the tegmen antri and the tegmen mastoideum(Makki et al., 2011). In some patients, the tegmental region of the temporal bone can be interrupted, causing a tegmen defect(TD). A TD is sometimes associated with a meningoencephalic herniation(MEH), in which brain tissue herniates through a TD.

Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiati

Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development.Osteogenesis is the process by which new bones are formed;it also aids in bone remodeling.Wnt/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for life.Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body.Recent studies have indicated that these two signaling pathways contribute to osteogenic differen-tiation.Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway.Here,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical pathways.This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.

Customized scaffolds for large bone defects using 3D‑printed modular blocks from 2D‑medical images

Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering applications.The use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and scaffolds.However,these sophisticated techniques can be timeconsuming,labor-intensive,and expensive.Moreover,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma patients.In this study,a novel design and AM methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a patient.These modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during surgery.The proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or segmentation.This algorithm can generate both patient-specific and average bone models.Additionally,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or images.The algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM process.Guidelines and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone defects.

Histological Assessment of Bone Regeneration in the Maxilla with Homologous Bone Graft:A Feasible Option for Maxillary Bone Reconstruction

Bone biomaterials have been increasingly used to reconstruct maxillary atrophic ridges.Thus,the aim of this study was to evaluate bone reconstruction in the maxilla using a homologous cortico-cancellous FFB(lyophilized)graft and verify its reliability.Eight individuals were included from 2014 to 2018.The first surgery was performed to install homologous bone blocks in the maxilla.The period of the second intervention varied between 5 months and 15 days to 11 months(≈7.93 months).The biopsies were taken from the central region of the matured graft during the surgery for implant placement.All patients presented clinical and radiographic conditions for the installation of dental implants.There was a 100%of survival rate.The histological assessment showed that the homologous block bone graft was an osteoconductive biomaterial,with connective tissue present,and newly formed bone juxtaposed on its surface.There were bone trabeculae with osteocytes and active osteoblasts with connective tissue in the mineralization process;the remodeling process can be found through the reverse lines.A limited focus of necrosis with fibrosis was detected,with small resorption and areas of inflammatory infiltrate,but without clinical significance.The homologous block bone graft can be considered a feasible option to substitute the autogenous bone graft(gold standard),with predictable clinical and favorable histological results.The patients had a shorter surgical period,low morbidity,and an unlimited amount of biomaterial available at an accessible cost.

Calcium-fortified fresh milk ameliorates postmenopausal osteoporosis via regulation of bone metabolism and gut microbiota in ovariectomized rats

The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy.After 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical testing.The results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid biosynthesis.Furthermore,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and microarchitecture.Mechanistically,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.

Design and Implementation of a Control System to Mitigate Osteonecrosis in Orthopedic Bone Drilling Procedures

The drilling process in orthopedic surgery can sometimes lead to an undesired increase in temperature,which can cause serious damage to bones and soft tissues.This overheating is typically identified as a temperature above 47℃,known as the critical limit,and can result in the condition known as osteonecrosis.This study aims to develop a new control system,using a proportional-integral-derivative(PID)controller,to prevent overheating and the resulting osteonecrosis.The bone temperature is constantly measured using a thermocouple and,when it reaches the critical temperature of 47℃,the cooling device is activated by the PID-controlled system.This new control system makes the drill machine with cooling device more user-friendly and allows surgeons to set a desired temperature level manually.

Andrias davidianus bone peptides alleviates hyperuricemia-induced kidney damage in vitro and in vivo

Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.

Icariin accelerates bone regeneration by inducing osteogenesisangiogenesis coupling in rats with type 1 diabetes mellitus

BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells

BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.

Preparation,characterization and antioxidant activity analysis of three Maillard glycosylated bone collagen hydrolysates from chicken,porcine and bovine

Bone collagen hydrolysates(peptides)derived from byproduct of animal product processing have been used to produce commercially valuable products due to their potential antioxidant activity.Maillard glycosylated reaction is considered as a promising method to enhance the antioxidant activity of peptides.Hence,this research aims at investigating the Maillard glycosylation activity and antioxidant activity of bone collagen hydrolysates from different sources.In this study,3 glycosylated bone collagen hydrolysates were prepared and characterized,and cytotoxicity and antioxidant activity were analyzed and evaluated.The free amino groups loss,browning intensity,and fluorescence intensity of G-Cbcp(glycosylated chicken bone collagen hydrolysates(peptides))were the heaviest,followed by G-Pbcp(glycosylated porcine bone collagen hydrolysates(peptides))and G-Bbcp(glycosylated bovine bone collagen hydrolysates(peptides)).The results of amino acid analysis showed that amino acid composition of different bone collagen hydrolysates was significantly different and the amino acid decreased to different degrees after Maillard glycosylated reaction,which may lead to differences in Maillard glycosylated reaction activity.Furthermore,the 3 glycosylated hydrolysates showed no significant cytotoxicity.The results showed that glycosylation process significantly increased the antioxidant activity of bone collagen hydrolysates,and G-Cbcp showed the strongest antioxidant activity,followed by G-Pbcp and G-Bbcp.Therefore,compared with the bone collagen hydrolysates,3 glycosylated hydrolysates showed significant characteristic and structural changes,and higher antioxidant activity.

Calcium-chelating peptides from rabbit bone collagen:characterization,identification and mechanism elucidation

This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating mechanism.Collagen peptides and calcium were extracted from rabbit bone by instant ejection steam explosion(ICSE)combined with enzymatic hydrolysis,followed by chelation reaction to prepare rabbit bone peptide-calcium chelate(RBCP-Ca).The chelating sites were further analyzed by liquid chromatography-tandem mass(LC-MS/MS)spectrometry while the chelating mechanism and binding modes were investigated.The structural characterization revealed that RBCP successfully chelated with calcium ions.Furthermore,LC-MS/MS analysis indicated that the binding sites included both acidic amino acids(Asp and Glu)and basic amino acids(Lys and Arg),Interestingly,three binding modes,namely Inter-Linking,Loop-Linking and Mono-Linking were for the first time found,while Inter-Linking mode accounted for the highest proportion(75.1%),suggesting that chelation of calcium ions frequently occurred between two peptides.Overall,this study provides a theoretical basis for the elucidation of chelation mechanism of calcium-chelating peptides.

MSADCN:Multi-Scale Attentional Densely Connected Network for Automated Bone Age Assessment

Bone age assessment(BAA)helps doctors determine how a child’s bones grow and develop in clinical medicine.Traditional BAA methods rely on clinician expertise,leading to time-consuming predictions and inaccurate results.Most deep learning-based BAA methods feed the extracted critical points of images into the network by providing additional annotations.This operation is costly and subjective.To address these problems,we propose a multi-scale attentional densely connected network(MSADCN)in this paper.MSADCN constructs a multi-scale dense connectivity mechanism,which can avoid overfitting,obtain the local features effectively and prevent gradient vanishing even in limited training data.First,MSADCN designs multi-scale structures in the densely connected network to extract fine-grained features at different scales.Then,coordinate attention is embedded to focus on critical features and automatically locate the regions of interest(ROI)without additional annotation.In addition,to improve the model’s generalization,transfer learning is applied to train the proposed MSADCN on the public dataset IMDB-WIKI,and the obtained pre-trained weights are loaded onto the Radiological Society of North America(RSNA)dataset.Finally,label distribution learning(LDL)and expectation regression techniques are introduced into our model to exploit the correlation between hand bone images of different ages,which can obtain stable age estimates.Extensive experiments confirm that our model can converge more efficiently and obtain a mean absolute error(MAE)of 4.64 months,outperforming some state-of-the-art BAA methods.

Ag-doped CNT/HAP nanohybrids in a PLLA bone scaffold show significant antibacterial activity

Bacterial infection is a major problem following bone implant surgery.Moreover,poly-l-lactic acid/carbon nanotube/hydroxyapatite(PLLA/CNT/HAP)bone scaffolds possess enhanced mechanical properties and show good bioactiv-ityregardingbonedefectregeneration.Inthisstudy,wesynthesizedsilver(Ag)-dopedCNT/HAP(CNT/Ag-HAP)nanohybrids via the partial replacing of calcium ions(Ca2+)in the HAP lattice with silver ions(Ag+)using an ion doping technique under hydrothermal conditions.Specifically,the doping process was induced using the special lattice structure of HAP and the abundant surface oxygenic functional groups of CNT,and involved the partial replacement of Ca2+in the HAP lattice by doped Ag+as well as the in situ synthesis of Ag-HAP nanoparticles on CNT in a hydrothermal environment.The result-ing CNT/Ag-HAP nanohybrids were then introduced into a PLLA matrix via laser-based powder bed fusion(PBF-LB)to fabricate PLLA/CNT/Ag-HAP scaffolds that showed sustained antibacterial activity.We then found that Ag+,which pos-sesses broad-spectrum antibacterial activity,endowed PLLA/CNT/Ag-HAP scaffolds with this activity,with an antibacterial effectiveness of 92.65%.This antibacterial effect is due to the powerful effect of Ag+against bacterial structure and genetic material,as well as the physical destruction of bacterial structures due to the sharp edge structure of CNT.In addition,the scaffold possessed enhanced mechanical properties,showing tensile and compressive strengths of 8.49 MPa and 19.72 MPa,respectively.Finally,the scaffold also exhibited good bioactivity and cytocompatibility,including the ability to form apatite layers and to promote the adhesion and proliferation of human osteoblast-like cells(MG63 cells).

Simple bone cysts of the proximal humerus presented with limb length discrepancy:A case report

BACKGROUND Simple bone cysts(SBC)are benign tumor-like bone lesions typically identified in children.While SBC may lead to growth disturbances or growth arrest,such cases are uncommon.The mechanisms behind these observations remain unclear.Additionally,research on the etiology of SBC remains inconclusive,and there has been no consensus on the appropriate timing and methodology for treatment.CASE SUMMARY Here,we present our experience in the successful surgical management of a 10-year-old girl with SBC,who presented with a pathological fracture complicated by malunion of the displaced fracture,varus deformity,and limb length discrepancy.We hypothesized two possible etiologies for the patient’s growth arrest and subsequent humerus varus deformity:(1)Direct disruption of the physis by fluid from the cyst itself;and(2)damage to the epiphysis due to repetitive pathological fractures associated with SBC.In addressing this case,surgical intervention was undertaken to correct the proximal humerus varus deformity.This approach offered the advantages of simultaneously correcting angular abnormalities,achieving mild limb lengthening,providing definitive SBC treatment,and reducing the overall treatment duration.CONCLUSION As per current literature,acute correction of acute angular deformity in proximal humeral SBC is not well comprehended.However,in this specific case,acute correction was considered an optimal solution.