In vitro performance of a biodegradable zinc alloy adjustable-loop cortical suspension fixation for anterior cruciate ligament reconstruction

Anterior cruciate ligament(ACL)injuries of the knee are one of the most common and serious athletic injuries.The widely used cortical suspension fixation buttons for ligament reconstruction are permanent implants,particularly those made from conventional steel or titanium alloys.In this study,a biodegradable Zn-0.45Mn-0.2Mg(ZMM42)alloy with the yield strength of 300.4 MPa and tensile strength of 329.8 MPa was prepared through hot extrusion.The use of zinc alloys in the preparation of cortical suspension fixation buttons was proposed for the first time.After 35 d of immersion in simulated body fluids,the ZMM42 alloy fixation buttons were degraded at a rate of 44μm/a,and the fixation strength was retained(379.55 N)in the traction loops.Simultaneously,the ZMM42 alloy fixation buttons exhibited an increase in MC3T3-E1 cell viability and high antibacterial activity against Escherichia coli and Staphylococcus aureus.These results reveal the potential of biodegradable zinc alloys for use as ligament reconstruction materials and for developing diverse zinc alloy cortical suspension fixation devices.

Second phase refining induced optimization of Fe alloying in Zn:Significantly enhanced strengthening effect and corrosion uniformity

Many non-toxic alloying elements,such as Fe,Ca,and Sr,have negligible solid solubilities in Zn matrix,leading to formation of coarse second phase particles.They exhibit low strengthening effects but highly detrimental to ductility.So refining second phase is a common pursuit for Zn alloys.The present paper takes Zn-0.3Fe alloy suffered from coarse FeZn_(13) second phase particles as a touchstone to testify microstructure refining effect through solidification with an accelerated speed and multi-pass rolling.FeZn_(13) particles are refined from 24 to 2μm,and Zn grains are refined to 5μm.As a result,the strengthening effect of Fe is enhanced significantly,with yield strength and the ultimate tensile strength of the alloy increased from 132 to 218 MPa and from 159 to 264 MPa,respectively.Furthermore,corrosion non-uniformity and penetration are much alleviated.These results show that microstructure refinement,especially on coarse intermetallic second phases,has a great potential to improve mechanical and degradation properties of biodegradable Zn alloys.

Correlation between prion protein gene codon 129 polymorphism and late-onset Alzheimer's disease

BACKGROUND： Studies addressing the correlation between prion protein gene codon 129 polymorphism, Alzheimer＇s disease, and cognitive disorders have mainly focused on Caucasians. However, prion protein gene codon 129 polymorphism is thought to also affect the Chinese Han and Wei populations. OBJECTIVE： To analyze the differences of prion protein gene codon 129 distribution among the elderly Chinese Han, East Asian, and Caucasian populations, and to study the correlation between prion protein gene codon 129 distribution and late-onset Alzheimer＇s disease. DESIGN, TIME AND SETTING： A gene polymorphism analysis was performed in the Institute of Geriatrics, General Hospital of Chinese PLA between January 2006 and January 2007. PARTICIPANTS： A total of 152 elderly Chinese Han people were selected from the Beijing Troop Cadre＇s Sanitarium. Among them, 60 patients with late-onset Alzheimer＇s disease, with a mean age of （82 ± 7） years （range 67-94 years） and disease course of （5.9 ± 4.4） years, comprising 44 males with a mean age of （83 ± 7） years and 16 females with a mean age of （78 ±7） years, were selected for the case group. An additional 92 healthy elderly subjects, with a mean of （76 ± 9） years （range 60-94 years）, comprising 76 males with a mean age of （77 ± 9） years and 16 females with a mean age of （70 ± 8） years, were selected for the control group. There were no significant differences in age and gender between the two groups （P〉 0.05）. METHODS： DNA was extracted from peripheral blood leukocytes using routine phenol/chloroform methodology. Prion protein gene codon 129 potymorphism and ApoE polymorphism were measured using PCR-restriction fragment length polymorphism. The ApoEε allele was considered the standard for analyzing correlations between prion protein gene codon 129 polymorphism and late-onset Alzheimer＇s disease. MAIN OUTCOME MEASURES： Prion protein gene codon 129 distribution; correlation between genotypic frequency and allele frequency of prion protein gene codon 129 with Alzheimer＇s disease; relationship between methionine/methionine genotype of priori protein gene, ApoEε4 allele, gender, and age of Alzheimer＇s disease patients. RESULTS： Methionine/methionine genotypic frequency of prion protein gene codon 129 was 94.08% in the Chinese elderly population, and the methionine/valine genotypic frequency was 5.92%. However, valine/valine homozygotes were not determined. There was no significant difference in prion protein gene codon 129 polymorphism between the Chinese elderly and East Asian populations （P〉 0.05）. However, there was a significant difference between the Chinese elderly and the Caucasian population （P 〈 0.05）. The methionine/methionine genotype for the positive and negative ApoEε4 alleles was a risk factor for increased incidence of Alzheimer＇s disease, but there was no significant difference between the positives and the negatives （odds ratio = 1.33, 95% confidence interval = 0.32-6.49, P〉 0.05）. CONCLUSION： Prion protein gene codon 129 distribution in the Chinese elderly was different from the Caucasian population, which suggested that the methionine/methionine genotype of prion protein gene codon 129 negatively correlated with late-onset Alzheimer＇s disease.

Direct evidence of VEGF-mediated neuroregulation and afferent explanation of blood pressure dysregulation during angiogenic therapy

Objective:Oncocardiology is increasingly hot research field/topic in the clinical management of cancer with anti-angiogenic therapy of vascular endothelial growth factor(VEGF)that may cause cardiovascular toxicity,such as hypertension via vascular dysfunction and attenuation of eNOS/NO signaling in the baroreflex afferent pathway.The aim of the current study was to evaluate the potential roles of VEGF/VEGF receptors(VEGFRs)expressed in the baroreflex afferent pathway in autonomic control of blood pressure(BP)regulation.Methods:The distribution and expression of VEGF/VEGFRs were detected in the nodose ganglia(NG)and nucleus of tractus solitary(NTS)using immunostaining and molecular approaches.The direct role of VEGF was tested by NG microinjection under physiological and hypertensive conditions.Results:Immunostaining data showed that either VEGF or VEGFR2/VEGFR3 was clearly detected in the NG and NTS of adult male rats.Microinjection of VEGF directly into the NG reduced the mean blood pressure(MBP)dose-dependently,which was less dramatic in renovascular hypertension(RVH)rats,suggesting the VEGF-mediated depressor response by direct activation of the 1st-order baroreceptor neurons in the NG under both normal and disease conditions.Notably,this reduced depressor response in RVH rats was directly caused by the downregulation of VEGFR2,which compensated the up regulation of VEGF/VEGFR3 in the NG during the development of hypertension.Conclusion:It demonstrated for the first time that the BP-lowering property of VEGF/VEGFRs signaling via the activation of baroreflex afferent function may be a common target/pathway leading to BP dysregulation in anti-angiogenic therapy.

Grey-matter volume as a potential feature for the classification of Alzheimer's disease and mild cognitive impairment: an exploratory study

Specific patterns of brain atrophy may be helpful in the diagnosis of Alzheimer＇s disease （AD）. In the present study, we set out to evaluate the utility of grey-matter volume in the classification of AD and amnestic mild cognitive impairment （aMCI） compared to normal control （NC）individuals. Voxel-based morphometric analyses were performed on structural MRIs from 35 AD patients, 27 aMCI patients, and 27 NC participants. A two-sample two-tailed t-test was computed between the NC and AD groups to create a map of abnormal grey matter in AD. The brain areas with significant differences were extracted as regions of interest （ROIs）, and the grey-matter volumes in the ROIs of the aMCI patients were included to evaluate the patterns of change across different disease severities. Next, correlation analyses between the grey-matter volumes in the ROIs and all clinical variables were performed in aMCI and AD patients to determine whether they varied with disease progression. The results revealed significantly decreased grey matter in the bilateral hippocampus/ parahippocampus, the bilateral superior/middle temporal gyri, and the right precuneus in AD patients.The grey-matter volumes with clinical variables were positively correlated Finally, we performed exploratory linear discriminative analyses to assess the classifying capacity of grey-matter volumes in the bilateral hippocampus and parahippocampus among AD, aMCI, and NC. Leave-one-out cross- validation analyses demonstrated that grey-matter volumes in hippocampus and parahippocampus accurately distinguished AD from NC. These findings indicate that grey-matter volumes are useful in the classification of AD.

Microstructure, wear resistance, and corrosion performance of Ti35Zr28Nb alloy fabricated by powder metallurgy for orthopedic applications

A ternary Ti35Zr28Nb alloy was fabricated by powder metallurgy(PM)from pre-alloyed powder.The microstructure,hardness,corrosion behavior,and wear response of the produced alloy were investigated systematically.The results show that nearly full dense Ti35Zr28Nb alloy(relative density is 98.1±1.2%)can be fabricated by PM.The microstructure was dominated with uniform phase.The Ti35Zr28Nb alloy displayed spontaneous passivity in a naturally aerated simulated body fluid(SBF)solution at 37±0.5°C.The Ti35Zr28Nb alloy exhibited the highest corrosion resistance as compared to as-cast Ti6Al4V and pure Ti because of the formation of a protective passive film containing TiO2,Nb2O5,and ZrO2,including the highest corrosion potential(-0.22±0.01 V),the lowest corrosion current density(57.45±1.88 nA),the lowest passive potential(0.05±0.01 V)and the widest passivation range(1.29±0.09 V).Under the same wear condition,the wear rate of the Ti35Zr28Nb alloy(0.0021±0.0002 mm3/m·N)was lower than that of the CP Ti(0.0029±0.0004 mm3/m·N)and close to that of the Ti6Al4V(0.0020±0.0003 mm3/m·N).The wear mechanism of the Ti35Zr28Nb alloy was mainly dominated by abrasive wear,accompanied by adhesive wear.The highest corrosion resistance together with the adequate wear resistance makes the PM-fabricated Ti35Zr28Nb alloy an attractive candidate for orthopedic implant materials.

Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior

The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system.In this study,two kind of aqueous model drugs with different molecule weight,Congo red and albumin from bovine serum(BSA)were nanoencapsulated in poly(DL-lactic-co-glycolic acid)(PLGA)microspheres by emulsion electrospray.In the preparation process,the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution.The emulsion was then electrosprayed to fabricate drugnanoencapsulated PLGA microspheres.The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase(V_(w)/V_(o))and the molecule weight of model drugs.Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to V_(w)/V_(o).With the increase of the volume ratio of aqueous drug phase,the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate.Moreover,BSA showed a slower release rate from PLGA microspheres comparing to Congo red,which indicated the drug release rate could be affected by not only V_(w)/V_(o)but also the molecule weight of model drug.In brief,the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple systemto achieve controlled drug release at a desired rate satisfying the need of the practices.

Associations of particulate matter with dementia and mild cognitive impairment in China: A multicenter cross-sectional study

Ambient air pollution has been shown to be associated with the pathogenesis of dementia and mild cognitive impairment(MCI).However,few studies have examined these associations in well-characterized populations with low residential mobility,similar living habits,and a standardized assessment of both air pollution exposure and clinical outcome.This study examined the associations of long-term exposure to particulate matter(PM)air pollution with dementia and MCI,using data from the Chinese Veteran Clinical Research Platform.The cognitive function of elderly veterans from 277 communities in 18 Chinese cities was examined.Participants’daily exposures to aerodynamic diameters%2.5 mm(PM2.5)and%10 mm(PM10)during the 3 years prior to the survey were estimated using a satellite-based prediction.The adjusted odds ratios(ORs)and 95%confidence intervals of MCI associated with each 10 mg/m^(3) increase in PM2.5 and PM10 were 1.52(1.39,1.67)and 1.04(1.00,1.08),and those of dementia associated with PM2.5 and PM10 were 1.27(1.11,1.46)and 1.13(1.05,1.21),respectively.This demonstrates that long-term exposure to PM2.5 and PM10 can increase the prevalence of dementia/MCI among veterans in China.Higher ORs were observed for those with%9 years of educational attainment,those who actively attended physical activities,those who never smoked,former drinkers,and those who did not suffer from cerebral infarction.Improvement of ambient air quality,especially decreasing levels of PM2.5,may help to decrease the risk of dementia/MCI.Given the statistically significant association between PM and cognitive impairment demonstrated here,future studies should focus on examining the causal effect of PM pollution on dementia and MCI.