17例耳硬化症患者的临床与影像学分析

目的分析17例耳硬化症患者的临床特征、影像学表现及手术治疗效果。方法收集2020年5月~2023年5月在湖州市中心医院接受手术治疗的17例(17耳)耳硬化症患者临床、影像学资料,分析其临床表现、颞骨CT影像学表现及手术前后纯音测听结果变化。结果17例(17耳)患者中,11耳(64.71%)为前庭窗型,表现为进行性传导性听力损失,其中9耳有耳鸣,3耳有轻微平衡问题;混合型6耳(35.29%)显示混合性听力损失,5耳有耳鸣,3耳有偶发性平衡障碍。影像学上,前庭窗型显示镫骨底板区域骨质增厚、前庭窗密度增加;混合型则显示镫骨底板增厚及耳蜗周围密度减低,1耳可见“双环征”,两种类型耳硬化症患者骨密度差异无统计学意义(P>0.05)。术后均未见耳鸣加重或其他严重并发症,仅2例(11.76%)出现暂时性头晕,术后随访显示术区恢复良好,无感染或其他迟发性并发症;术后听力测试显示气导阈值、气骨导差较术前显著改善(P均<0.05)。结论前庭窗型和混合型耳硬化症的影像学和临床表现各有特点,镫骨成形术可显著改善听力,降低气导阈值和气骨导差,且手术安全、并发症少。

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.

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.

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.

Hydrogel loaded with bone marrow stromal cell-derived exosomes promotes bone regeneration by inhibiting inflammatory responses and angiogenesis

BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,necessitating the search for efficient healing methods.AIM To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells(BMSCs)facilitate the process of fracture healing.METHODS Hydrogels and loaded BMSC-derived exosome(BMSC-exo)gels were charac-terized to validate their properties.In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process.Hydrogels could recruit macrophages and inhibit inflammatory responses,enhance of human umbilical vein endothelial cell angiogenesis,and promote the osteogenic differen-tiation of primary cranial osteoblasts.Furthermore,the effect of hydrogel on fracture healing was confirmed using a mouse fracture model.RESULTS The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration,promoted the formation of large vessels,and enabled functional vascularization during bone repair.These effects were further validated in fracture models.CONCLUSION We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.

From liver to hormones:The endocrine consequences of cirrhosis

Hepatocrinology explores the intricate relationship between liver function and the endocrine system.Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption.Despite its importance,assessing endocrine issues in cirrhotic patients is frequently neglected.This article provides a comprehensive review of the epidemiology,pathophysiology,diagnosis,and treatment of endocrine disturbances in liver cirrhosis.The review was conducted using the PubMed/Medline,EMBASE,and Scielo databases,encompassing 172 articles.Liver cirrhosis is associated with endocrine disturbances,including diabetes,hypoglycemia,sarcopenia,thyroid dysfunction,hypogonadotropic hypogonadism,bone disease,adrenal insufficiency,growth hormone dysfunction,and secondary hyperaldosteronism.The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system,respectively.Sarcopenia can be assessed through imaging and functional tests,while other endocrine disorders are evaluated using hormonal assays and imaging studies.Treatment options include metformin,glucagon-like peptide-1 analogs,sodium-glucose co-transporter-2 inhibitors,and insulin,which are effective and safe for diabetes control.Established standards are followed for managing hypoglycemia,and hormone replacement therapy is often necessary for other endocrine dysfunctions.Liver transplantation can address some of these problems.

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.

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.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

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.

BMSC-derived Exosomes Ameliorate Peritoneal Dialysis-associated Peritoneal Fibrosis via the Mir-27a-3p/TP53 Pathway

Objective:Peritoneal fibrosis(PF)is the main cause of declining efficiency and ultrafiltration failure of the peritoneum,which restricts the long-term application of peritoneal dialysis(PD).This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes(BMSC-Exos)on PF in response to PD.Methods:Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing.C57BL/6J mice were infused with 4.25%glucose-based peritoneal dialysis fluid(PDF)for 6 consecutive weeks to establish a PF model.A total of 36 mice were randomly divided into 6 groups:control group,1.5%PDF group,2.5%PDF group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of PDF.HE and Masson staining were performed to evaluate the extent of PF.The therapeutic potential of BMSC-Exos for PF was examined through pathological examination,RT-qPCR,Western blotting,and peritoneal function analyses.Epithelial-mesenchymal transition(EMT)of HMrSV5 was induced with 4.25%PDF.Cells were divided into control group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Cell Counting Kit-8 assay was used to measure cell viability,and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 cells.Results:Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to BMSCs.The RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos,but decreased in PD mice.We found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD mice.Compared with the control mice,the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious fibroproliferative response,with markedly increased peritoneal thickness and higher expression ofα-SMA,collagen-I,fibronectin,and ECM1.The mice with PD showed decreased miR-27a-3p.Peritoneal structural and functional damage was significantly attenuated after BMSC-Exos treatment,while PF and mesothelial damage were significantly ameliorated.Additionally,markers of fibrosis(α-SMA,collagen-I,fibronectin,ECM1)and profibrotic cytokines(TGF-β1,PDGF)were downregulated at the mRNA and protein levels after BMSC-Exos treatment.In HMrSV5 cells,BMSC-Exos reversed the decrease in cell viability and the increase in cell migratory capacity caused by high-glucose PDF.Western blotting and RT-qPCR analysis revealed that BMSC-Exos treatment resulted in increased expression of E-cadherin(epithelial marker)and decreased expression ofα-SMA,Snail,and vimentin(mesenchymal markers)compared to those of the 4.25%PDF-treated cells.Importantly,a dual-luciferase reporter assay showed that TP53 was a target gene of miR-27a-3p.TP53 overexpression significantly reversed the decreases in PF and EMT progression induced by BMSC-Exos.Conclusion:The present results demonstrate that BMSC-Exos showed an obvious protective effect on PD-related PF and suggest that BMSC-derived exosomal miR-27a-3p may exert its inhibitory effect on PF and EMT progression by targeting TP53.

Small extracellular vesicles from hypoxia-preconditioned bone marrow mesenchymal stem cells attenuate spinal cord injury via miR-146a-5p-mediated regulation of macrophage polarization

Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.

Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage

BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.

Oral administration of egg white ovotransferrin prevents osteoporosis in ovariectomized rats

Ovotransferrin,an iron-binding glycoprotein,accounting for approximately 12%of egg white protein,is a member of transferrin fam ily.Our previous studies showed that ovotransferrin stimulates the proliferation and differentiation of osteoblasts,while inhibits osteoclastogenesis and resorption activity.The work aims to study the efficacy of orally administered ovotransferrin on the prevention of osteoporosis using ovariectomized(OVX)Sprague-Dawley rats.Oral administration of ovotransferrin showed no negative effect on body weight,food intake and organ weight.After 12-week treatment,feeding ovotransferrin at a dose of 1%(1 g ovotransferrin/100 g diet)prevented OVX-induced bone loss and maintained relatively high bone mineral density and integrated bone microarchitecture.The serum concentration of biomarkers indicating bone formation was increased in ovotransferrin administration groups,while the bone resorption biomarkers were decreased.Ovotransferrin feeding also decreased the production of serum cytokine TNF-αand IL-6,which are two stimulators for osteoclast differentiation.In addition to its direct regulatory role on bone turnover,ovotransferrin supplementation might benefit osteoporosis prevention by inhibiting adipogenesis,and regulating immune response.Our results suggested the potential application of ovotransferrin as a functional food ingredient on the prevention of osteoporosis.

The influence of yttrium and manganese additions on the degradation and biocompatibility of magnesium-zinc-based alloys:In vitro and in vivo studies

The repair and regeneration of bone defects are highly challenging orthopedic problems.Recently,Mg-based implants have gained popularity due to their unique biodegradation and elastic modulus similar to that of human bone.The aim of our study is to develop a magnesium alloy with a controllable degradation that can closely match bone tissue to help injuries heal in vivo and avoid cytotoxicity caused by a sudden increase in ion concentration.In this study,we prepared and modified Mg-3Zn,Mg-3Zn-1Y,and Mg-2Zn-1Mn by hot extrusion,and used Mg-2.5Y-2.5Nd was as a control.We then investigated the effect of additions of Y and Mn on alloys'properties.Our results show that Mn and Y can improve not only compression strength but also corrosion resistance.The alloy Mg-2Zn-1Mn demonstrated good cytocompatibility in vitro,and for this reason we selected it for implantation in vivo.The degraded Mg-2Zn-1Mn implanted a bone defect area did not cause obvious rejection and inflammatory reaction,and the degradation products left no signs of damage to the heart,liver,kidney,or brain.Furthermore,we find that Mg-2Zn-1Mn can promote an osteoinductive response in vivo and the formation of bone regeneration.

Hepatocellular carcinoma and musculoskeletal system: A narrative literature review

Musculoskeletal alterations in hepatocellular carcinoma(HCC)are less common than liver-related complications.However,they can significantly impact the quality of life and overall prognosis of patients with HCC.The main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asym-ptomatic and unapparent during routine clinical evaluations.This narrative literature review aimed to provide a comprehensive overview of the contem-porary literature related to the changes in the musculoskeletal system in patients with HCC,focusing on its clinical implications and underlying etiopathogenetic mechanisms.Osteolytic bone metastases are the most common skeletal alterations associated with HCC,which could be associated with an increased risk of low-trauma bone fracture.Moreover,previous studies reported that osteopenia,sarcopenia,and myosteatosis are associated with poor clinical outcomes in patients with HCC.Even though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients,these complications are frequently overlooked in the clinical management of patients with HCC.Taken together,contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient prognosis.Further research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.

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.

Understanding the eff ect of recreational drug use on bone health and musculoskeletal disease in the establishment of pain regimens

BACKGROUND:The widespread use of recreational drugs has raised concerns regarding their eff ects on various organ systems.The use of cannabis and opioids in chronic pain management increases their prevalence among patients with musculoskeletal conditions whose bone health may already be compromised.This article aims to review the pathophysiology and toxic eff ects of recreational drug use on musculoskeletal health to establish appropriate pain regimens for patients with substance use.METHODS:Medical literature published from 1970 until 2022 was identifi ed utilizing MEDLINE/PubMed and the Cochrane Library.In addition to the databases,references were obtained through the use of reference lists of published articles identifi ed by the aforementioned databases.The initial search terms included opioids,inhalants,hallucinogens,cannabis,stimulants,and bone health.There were no methodological limitations in relation to the initial acquisition and analysis of data.RESULTS:A total of 55 research articles were included in this review.Cannabis,stimulants,opioids,and inhalants impact bone maintenance,specifically osteoblast and osteoclast activity,as well as impede hormone production.These substances inhibit bone remodeling and development,manifesting as lower bone mineral density and increased fracture risk in chronic users.CONCLUSION:Although the current literature suggests a deleterious effect of recreational drugs on bone health and musculoskeletal disease,further research is warranted to evaluate the clinical effects of long-term substance use.The evaluation of such effects will aid in establishing appropriate pain regimens,as well as appropriate screening and treatment plans for recreational drug users.

Magnesium-incorporated biocomposite scaffolds:A novel frontier in bone tissue engineering

Nonunion represents a crucial challenge in orthopedic medicine,demanding innovative solutions beyond the scope of traditional bone grafting methods.Among the various strategies available,magnesium(Mg)implants have been recognized for their biocompatibility and biodegradability.However,their susceptibility to rapid corrosion and degradation has garnered notable research interest in bone tissue engineering(BTE),particularly in the development of Mg-incorporated biocomposite scaffolds.These scaffolds gradually release Mg2+,which enhances immunomodulation,osteogenesis,and angiogenesis,thus facilitating effective bone regeneration.This review presents myriad fabrication techniques used to create Mg-incorporated biocomposite scaffolds,including electrospinning,three-dimensional printing,and sol-gel synthesis.Despite these advancements,the application of Mg-incorporated biocomposite scaffolds faces challenges such as controlling the degradation rate of Mg and ensuring mechanical stability.These limitations highlight the necessity for ongoing research aimed at refining fabrication techniques to better regulate the physicochemical and osteogenic properties of scaffolds.This review provides insights into the potential of Mg-incorporated biocomposite scaffolds for BTE and the challenges that need to be addressed for their successful translation into clinical applications.

Self-reinforced Calcium Phosphate Cement Inspired by Sea Cucumber Dermis

A composite bone cement based onα-TCP with self-reinforcing characteristics is prepared by compounding cellulose whiskers and polyvinyl alcohol in different proportions.In this system,we are inspired by the sea cucumber,which can alter the stiffness of their inner dermis reversibly.Through the formation of hydrogen bonds between the hydroxyl groups on the cellulose whiskers and PVA,the bone cement matrix can be strengthened during the curing process of cement.In the process of bone cement blending,there is more water,the hydrogen bond connection is destroyed,so the slurry has better fluidity at this time.As the hydration of the bone cement progresses,the reduction of the water phase leads to the formation of a permeable network structure of hydrogen bond connections between the whiskers.The dual-phase action of PVA and whiskers greatly increases the mechanical strength of the bone cement system(5.5 to 23.8 MPa),while the presence of polyvinyl alcohol improves the toughness of the bone cement system.This work was supposed to explore whether the chemoresponsive materials can be adapted to biomedical materials,for example,bone repair.