Osteogenic effect of magnesium oxychloride cement modified with phytic acid and loaded with strontium ranelate.

BACKGROUND: Magnesium oxychloride cement has good mechanical properties, but poor water resistance. METHODS: Phytic acid, which can form chelate with Mg2+, was used to modify magnesium oxychloride cement, and the effects of phytic acid on the strength, in vitro degradation and biological activity of magnesium oxychloride cement were studied. Based on the preparation of phytic acid modified magnesium oxychloride cement with good water resistance and biological activity, osteoporosis treatment strontium ranelate was loaded on phytic acid- magnesium oxychloride cement, strontium ranelate/phytic acid-magnesium oxychloride cement was prepared. RESULTS: It was found that the compressive strength of 1.25 wt% phytic acid-magnesium oxychloride cement after soaking in SBF for 28 d could reach 40.5 ± 2.0 MPa, 13.33% higher than that of the control group (when phytic acid was 0 wt%), and the mass loss rate of all ages was lower than that of the control group. The water resistance of magnesium oxychloride cement was effectively improved by phytic acid. After loading with strontium ranelate, the water resistance of 1.25 wt% phytic acid-magnesium oxychloride cement was improved. Cell experiments showed that strontium ranelate could effectively promote cell proliferation and improve the expression of osteoblast-related proteins. When strontium ranelate/phytic acid-magnesium oxychloride cement samples were implanted subcutaneously in rats for 4 w, no obvious inflammatory response was observed, and the material was tightly bound to the surrounding tissues. When bone cement was implanted into rat femur for 4 w, the bone cement was gradually wrapped and absorbed by new bone tissue, which grew from the outside to the inside, indicating that the bone cement containing strontium ranelate/phytic acid-magnesium oxychloride cement had excellent bone-forming ability. CONCLUSIONS: In conclusion, the results indicated that strontium ranelate/phytic acid-magnesium oxychloride cement composite bone cement had a potential application prospect in clinical bone repair.

Safety and Survival Outcomes of Liver Resection following Triple Combination Conversion Therapy for Initially Unresectable Hepatocellular Carcinoma.

Triple combination conversion therapy, involving transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), has shown an encouraging objective response rate (ORR) and successful conversion surgery rate in initially unresectable hepatocellular carcinoma (HCC). However, the safety and long-term survival outcomes of subsequent liver resection after successful conversion still remain to be validated. From February 2019 to February 2023, 726 patients were enrolled in this retrospective study (75 patients received hepatectomy after conversion therapy [CLR group], and 651 patients underwent pure hepatectomy [LR group]). Propensity score matching (PSM) was used to balance the preoperative baseline characteristics. After PSM, 68 patients in the CLR group and 124 patients in the LR group were analyzed, and all the matching variables were well-balanced. Compared with the LR group, the CLR group experienced longer Pringle maneuver time, longer operation time, and longer hospital stays. In addition, the CLR group had significantly higher incidence rates of intra-abdominal bleeding, biliary leakage, post-hepatectomy liver failure (PHLF), and Clavien-Dindo grade IIIa complications than the LR group. There were no significant statistical differences in overall survival (OS) (hazard ratio [HR] 0.724; 95% confidence interval [CI] 0.356-1.474; p = 0.374) and recurrence-free survival (RFS) (HR 1.249; 95% CI 0.807-1.934; p = 0.374) between the two groups. Liver resection following triple combination conversion therapy in initially unresectable HCC may achieve favorable survival outcomes with manageable safety profiles; presenting as a promising treatment option for initially unresectable HCC.

Strontium hydroxyapatite/magnesium oxychloride cement with high strength and high osteogenic activity for bone defect repair.

Strontium is a kind of element which can promote the increase of bone density and benefit the growth of bone tissue. This study combined strontium hydroxyapatite (Sr-HAp) with magnesium oxychloride cement (MOC) to prepare a bioactive material with good osteogenic activity and degradability. The results revealed that the incorporation of 10 wt.% Sr-HAp densified the structure of MOC, slowed down the degradation rate of hydration product phase 5 in water, and enhanced the water resistance of MOC. After soaking for 28 days, the compressive strength of Sr-HAp/MOC decreased by 53%, which was lower than that of MOC (93%) and HAp/MOC (61%) without adding Sr-HAp. During the degradation processin vitro, Sr-HAp/MOC continuously released Sr2+and the cumulative concentration of Sr2+releasedin vitroafter seven days of immersion was 1.27 ± 0.15 ppm. When Sr-HAp/MOC was soaking in simulated body fluid, Sr-HAp induced the growth and deposition of bone-like component hydroxyapatite crystals on MOC's surface, improving MOC's bioactivity. After implantation of femur defect in rats, the new bone tissue grew from outside to inside around Sr-HAp/MOC, which showed Sr-HAp/MOC had better osteogenic activity. MOC was containing 10 wt.% Sr-HAp can not only provide strong support for bone defects but also have the potential to promote bone regeneration.

NIR-excited upconversion nanoparticles used for targeted inhibition of Aß42 monomers and disassembly of Aß42 fibrils.

Much attention has been paid to oxidising amyloid-ß peptides (Aß) for inhibiting their aggregation using photosensitive materials. However, the low penetration of ultraviolet/visible light into biological tissues and low targeting properties of the materials hinder their application. Here, we constructed a novel platform for attenuating the neurotoxicity of Aß through functional upconversion nanoparticles (UCNPs@SiO2-ThS). UCNPs@SiO2-ThS can not only inhibit the aggregation of Aß42 monomers, but also disassemble Aß42 fibrils by its selective photooxidative capacity under the irradiation of near-infrared (NIR) light. Moreover, based on the enhancement of ThS fluorescence after attaching to Aß42 fibrils, only Aß42 fibrils exposed to both UCNPs@SiO2-ThS and light can be oxidized rather than other normal proteins. To further enhance Aß-target photooxygenation, we introduced the Aß-target peptide (KLVFF) on the surface. Compared to traditional chemotherapies and radiotherapies, this novel PDT strategy shows remarkably reduced side effects and improved targeting.

Chain structure and ß conformation of poly(9,9-dioctylfluorene) (PFO) with different molecular weights delivering from the solution to the film in a drop-casting process.

Over the last decade, considerable attention has been paid to the formation mechanism of the ordered ß conformation for PFO both in the solution and film to prepare high-efficiency optoelectronic devices. However, the process of solvent evaporation and aggregates transferred from the solution to the film also play key roles in forming ordered structures, which have been neglected. In this study, the influence of molecular weight on the above process was systematically studied using techniques such as SLS/DLS, UV-Vis, PL, and TEM. Five samples with different Mw ranging from 25 100 Da to 117 000 Da were obtained by the precipitation fractionation method. In dilute THF solution, the molecular chains were in α conformation without aggregates. In films, as the molecular weight increased, the content of ß conformation and ordered structure increased first and then decreased. By studying the solvent evaporation process, for the first time, we propose a possible mechanism for the transformation process of chain structure and ß conformation from the solution to the film, which involves three stages. This study reveals the transformation process of the chain structure and ß conformation of PFO from the solution to the film and its relationship with the molecular weight, which provides theoretical and practical versions for in-depth understanding and control of the formation of the ordered structure in high-efficiency films.

Preparation and properties of nano silica-based bioactive glass/apatite/sodium alginate composite hydrogel.

In this paper, given the lack of osteogenic activity of sodium alginate (SA) hydrogel and to simulate the composition of natural bone, ionic-crosslinking NBG/n-HA/SA hydrogel scaffolds were prepared by using nano bioactive glass (NBG) and nano hydroxyapatite (n-HA) with high bioactivity as composite calcium sources and reinforcement phases, and D-gluconic acid δ-lactone (GDL) as the coagulant. The results showed that the mixture of the precursor forming the network had good injectability and plasticity. When the dosage of GDL was 0.75 g, the gelling time of the composite hydrogel could be regulated within 4-8 min, and the hydrogel had high compressive strength (170-220 kPa), as well. When the mass ratio of calcium source to SA was 1:1, the crosslinking network was relatively uniform with a considerable number of large pores around 40 µm in the structure. In the immersion experiment in vitro, it was found that the composite hydrogel could promote the deposition of bone-like apatite on the material's surface. Meanwhile, the cell experiments in vitro verified that the NBG/n-HA/SA composite hydrogel had good cytocompatibility without cytotoxicity. Moreover, the composite hydrogel could enhance the activity of ALP of mouse bone marrow mesenchymal stem cells, and thus, it had good osteogenic activity.

High-throughput optimization of the chemically defined synthetic medium for the production of erythromycin A.

Erythromycin A is an important antibiotic. A chemically defined synthetic medium for erythromycin production was systematically optimized in this study. A high-throughput method was employed to reduce the number of components and optimize the concentration of each component. After two round single composition deletion experiment, only 19 components were remained in the medium, and then the concentration of each component was optimized through PB experiment. The optimal medium from the PB experiment was further optimized according to the nitrogen and phosphate metabolic consumption in 5 L bioreactor. It was observed that among the 8 amino acids concluded in the media, 4 amino acids were first consumed, when they are almost depleted, the other 4 amino acids were initiated their consumption afterwards in 5 L bioreactor. The decrease of phosphate concentration would increase qglc and qery. However, when phosphate concentration was too low, the production of erythromycin was hindered. The positive correlation between intracellular metabolite pools and Yery/glc indicated that low phosphate concentration in the medium can promote cell metabolism especially secondary metabolism during the stationary phase; however, if it was too low (5 mmol/L), the cell metabolism and secondary metabolism would both slow down. The erythromycin titer in the optimized medium (medium V) reached 1380 mg/L, which was 17 times higher than the previously used synthetic medium in our lab. The optimized medium can facilitate the metabolomics study or metabolic flux analysis of the erythromycin fermentation process, which laid a solid foundation for further study of erythromycin fermentation process.

Blood lead levels of children in urban and suburban areas in China (1997-2015): Temporal and spatial variations and influencing factors.

Blood lead (Pb) poisoning is a worldwide heath problem, especially in developing countries. As the largest developing country in the world, China faces severe health challenges, in particular the threat of blood Pb poisoning. In this study, the temporal trend of Chinese children's blood lead levels (BLLs) and blood lead poisoning incidence (BLPI) (percentage of BLL>100µg/L) and its influencing factors were investigated. We collected articles on children's BLLs published from 1997 to 2017 with sampling time from 1997 to 2015 by searching the databases of VIP Medical Information System (VMIS), China National Knowledge Infrastructure (CNKI) and Wanfang Data. After a rigorous investigation, 259 articles with eligible inclusion criteria were reviewed. Meanwhile, the data of Pb concentrations in the soil of 23 cities and the annual mean PM10 (particulate matter<10µm) concentrations of 24 provincial cities were collected. The temporal trend of children's BLLs and BLPIs could be divided into three stages: upward trend from 1997 to 2000, downward trend from 2001 to 2013, and upward trend from 2014 to 2015. The decline of BLLs from 2001 was primarily due to the phasing out of leaded gasoline since 2000 in China, while the descending air quality could explain the upward trend of BLLs in the period from 2014 to 2015. The correlation and regression analysis indicated that soil and air were two major pathways of Pb exposure for children in China. Although a noticeable decrease has been shown, the Chinese children's BLLs were still significantly higher than the levels of developed countries. We highly recommended that the critical value of blood Pb poisoning should be lowered to 50µg/L in China. Guidelines on the prevention and management of blood Pb poisoning are needed in China.

Preparation, bioactivity and mechanism of nano-hydroxyapatite/sodium alginate/chitosan bone repair material.

BACKGROUND: As the major inorganic component of natural bone, nano-hydroxyapatite (n-HA) on its own is limited in its use in bone repair, due to its brittleness. Chitosan (CS) and sodium alginate (SAL) are used to reduce its brittleness and tendency to degradation. However, the compressive strength of the composite is still low, and its biological performance needs further study. METHODS: Nano-hydroxyapatite/sodium alginate/chitosan (n-HA/SAL/CS) composite was prepared via an in situ synthesis method. Further, we prepared the n-HA/SAL/CS self-setting bone repair material by mixing n-HA/SAL/CS powder with a curing liquid (20 wt.% citric acid). In addition, the in vitro bioactivity and cell cytotoxicity were also explored. RESULTS: Transmission electron microscopy photos revealed that the n-HA crystals were uniformly distributed throughout the polymer matrix. Infrared IR spectroscopy indicated that the HA interacted with the COO- of SAL and NH2- of CS. The compressive strength of the n-HA/SAL/CS bone cement was 34.3 MPa and matched the demands of weight-bearing bones. Soaking in vitro in simulated body fluid demonstrated that the composite material had reasonably good bioactivity, while cytotoxicity tests indicated that the n-HA/SAL/CS cement could promote cell proliferation and was biocompatible. CONCLUSIONS: Compressive strength of n-HA/SAL/CS can satisfy the needs of cancellous bone, and in vitro bioactivity and cytotoxicity tests results indicated that the n-HA/SAL/CS composite could act as an optimal bone repair material.

Evaluation of the osteoconductive potential of poly(propylene carbonate)/nano-hydroxyapatite composites mimicking the osteogenic niche for bone augmentation.

Nano-hydroxyapatite (n-HA) reinforced poly(propylene carbonate) (PPC) composites were prepared for bone repair and reconstruction. The effects of reinforcement on the morphology, mechanical properties and biological performance of n-HA/PPC composites were investigated. The surface morphology and mechanical properties of the composites were characterized by scanning electron microscopy (SEM) and universal material testing machine. The analytical data showed that good incorporation and dispersion of n-HA crystals could be obtained in the PPC matrix at a 30:70 weight ratio. With the increase of n-HA content, the tensile strength increased and the fracture elongation rate decreased. In vitro cell culture revealed that the composite was favorable template for cell attachment and growth. In vivo implantation in femoral condyle defects of rabbits confirmed that the n-HA/PPC composite had good biocompatibility and gradual biodegradability, exhibiting good performance in guided bone regeneration. The results demonstrates that the incorporation of n-HA crystals into PPC matrix provides a practical way to produce biodegradable and cost-competitive composites mimicking the osteogenic niche for bone augmentation.

Synthesis and characterization of nano-hydroxyapatite/polyamide 66 biocomposites reinforced with multi-walled carbon nanotubes.

In this work, we investigate the enhanced mechanical properties of nano-hydroxyapatite/polyamide 66 (nHA/PA66) composites reinforced with multi-walled carbon nanotubes (MWCNTs) by means of the blending method. The MWCNTs-nHA/PA66 composites were characterized by various techniques, and the obtained results indicated that the MWCNTs were evenly distributed in the composite and that good interfacial bonding was formed between MWCNTs and PA66. The addition of MWCNTs improved the crystallinity of PA66, while it had little or no effect either on the composition or on the crystal structure of the composites. Moreover, the addition of MWCNTs in nHA/PA66 significantly improved the mechanical strength, and the tensile and compressive strengths attained maximum values of 90.3 and 126.8 MPa, respectively, with the addition of 0.1 wt% MWCNTs, whereas the bending strength attained a maximum value of 105.5 MPa with the addition of 0.05 wt% MWCNTs. Finally, L929 cells co-cultured with the MWCNTs-nHA/PA66 composite exhibited comparatively uninhibited cell growth, indicating that the addition of MWCNTs had negligible effect on the cytocompatibility of the original nHA/PA66 composite.

Preparation, characterization and properties of nano-hydroxyapatite/polypropylene carbonate biocomposite.

The combination of nano-hydroxyapatite (n-HA) and polypropylene carbonate (PPC) was used to make a composite materials by a coprecipitation method. The physical and chemical properties of the composite were tested. Scanning electron microscope (SEM) observation indicated that the biomimetic n-HA crystals were uniformly distributed in the polymer matrix. As the n-HA content increased in the composite, the fracture mechanism of the composites changes from gliding fracture to gliding and brittle fracture. Furthermore, the chemical interaction between inorganic n-HA and polypropylene carbonate was also investigated and discussed in detail. The hydrogen bonds might be formed between -OH/CO3(2-) of n-HA crystal and the ester group (-COO-) of PPC. The tensile strength of n-HA/PPC (40/60) was similar to that of the cancellous bone, and reached ca 58 MPa. The osteoblasts were cultured for up to 7 days, and then the adhesion and proliferation of osteoblasts were measured by Methyl thiazolyl tetrazolium (MTT) colorimetry assay and SEM. The cells proliferated, grew normally in fusiform shape and well attached. The in vitro test confirmed that the n-HA/PPC composites were biocompatible and showed undetectable negative effect on osteoblasts. In vivo implantation of the composite in New Zealand white rabbits was performed. It can stimulate the growth of a new bone, and at the same time the material begins to degrade. These results suggested that the composite may be suitable for the reparation or replacement of bone defects and possessed the potential for clinical applications.

[Synthesis and characterization of CO-3(2-) doping nano-hydroxyapatite].

CO3(2-) doping is an effective method to increase the biological activity of nano-hydroxyapatite (n-HA). In the present study, calcium nitrate and trisodium phosphate were chosen as raw materials, with a certain amount of Na2CO3 as a source of CO-3(2-) ions, to synthesize nano-carbonate hydroxyapatite (n-CHA) slurry by solution precipitation method. The structure and micro-morphology of n-CHA were characterized by transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FTIR) and Raman spectroscopy (RS). The results revealed that the synthetic n-HA crystals are acicular in nanometer scale and have a crystal size of 20-30 nm in diameter and 60-80 nm in length, which are similar to natural bone apatite. And the crystallinity of n-CHA crystals decreases to the increment of CO3(2-). Samples with more CO3(2) have composition and structure more similar to the bone apatite. The value of lattice parameters a decreases, value of c increases, and c/a value increases with the increase in the amount of CO3(2-), in accordance with crystal cell parameters change rule of type B replacement. In the AB mixed type (substitution OH- and PO4(3-)) CHA, IR characteristic peak of CO3(2-) out-of-plane bending vibration appears at 872 cm(-1), meanwhile, the asymmetry flexible vibration band is split into band at 1 454 cm(-1) and band at 1 420 cm(-1), while weak CO3(2)-peak appears at 1 540 cm(-1). CO3(2-) Raman peak of symmetric stretching vibration appears at 1 122 cm(-1). CO3(2-) B-type (substitution PO4(3-)) peak appeared at 1 071 cm(-1). Through the calculation of integral area ratio of PO4(3-)/ CO3(2-), OH-/CO3(2-), and PO4(3-)/OH-, low quantity CO3(2-) is B-type and high quantity CO3(2-) is A-type (substitution OH-). The results show that the synthesized apatite crystals are AB hybrid substitued nano-carbonate hydroxyapatite, however B-type replacement is the main substitute mode. Due to similarity inthe shape, size, crystal structure and growth mode, the synthesized apatite crystals can be called a kind of bone-like apatite.

Development of nanohydroxyapatite/polycarbonate composite for bone repair.

In this study, nano-hydroxyapatite (n-HA) combined polycarbonate was synthesized by a novel method. The physical and chemical property of the composite was tested. The results indicated the n-HA a crystal has the similar grain size, phase composition and crystal structure as. TEM photos results show the n-HA crystals were uniformly distributed in the polymer matrix. Then, the chemical bond between inorganic n-HA and polycarbonate was investigated and discussed. Proliferation of MSCs/composite cultured for up to 11 days the adhesion were tested by MTT and SEM. The in vitro test confirmed that the n-HA/PC composite was biocompatible and no negative effect on MSCs has found. The composite is proved to be osteoconductive, and can stimulate the growth of new bone. These results indicated that the composite meet the basic requirement of bone substitute material, and be potentially applied for clinic.

Artificial neural network to predict skeletal metastasis in patients with prostate cancer.

The application of an artificial neural network (ANN) in prediction of outcomes using clinical data is being increasingly used. The aim of this study was to assess whether an ANN model is a useful tool for predicting skeletal metastasis in patients with prostate cancer. Consecutive patients with prostate cancer who underwent the technetium-99m methylene diphosphate (Tc-99m MDP) whole body bone scintigraphies were retrospectively analyzed between 2001 and 2005. The predictors were the patient's age and radioimmunometric serum PSA concentration. The outcome variable was dichotomous, either skeletal metastasis or non-skeletal metastasis, based on the results of Tc-99m MDP whole body bone scintigraphy. To assess the performance for classification model in clinical study, the discrimination and calibration of an ANN model was calculated. The enrolled subjects consisted of 111 consecutive male patients aged 72.41 +/- 7.69 years with prostate cancer. Sixty-seven patients (60.4%) had skeletal metastasis based on the scintigraphic diagnosis. The final best architecture of neural network model was four-layered perceptrons. The area under the receiver-operating characteristics curve (0.88 +/- 0.07) revealed excellent discriminatory power (p < 0.001) with the best simultaneous sensitivity (87.5%) and specificity (83.3%). The Hosmer-Lemeshow statistic was 6.74 (p = 0.08 > 0.05), which represented a good-fit calibration. These results suggest that an ANN, which is based on limited clinical parameters, appears to be a promising method in forecasting of the skeletal metastasis in patients with prostate cancer.