Tetramethylpyrazine(TMP) is a traditional Chinese herbal medicine with strong antiinflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly c...Tetramethylpyrazine(TMP) is a traditional Chinese herbal medicine with strong antiinflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly cleared from the joint cavity after intra-articular injection and requires multiple injections to maintain efficacy. The aim of this study was to encapsulate TMP into poly(lactic-co-glycolic acid)(PLGA) microspheres to enhance the TMP retention in the joint, reducing injection frequencies and decreasing dosage. TMP microspheres were prepared by emulsion/solvent evaporation method. The intra-articular retention of the drug was assessed by detecting the drug concentration distributed in the joint tissue at different time points. The therapeutic effect of TMP microspheres was evaluated by the swelling of knee joints and histologic analysis in papain-induced OA rat model. The prepared freezedried microspheres with a particle size of about 10 μm can effectively prolong the retention time of the drug in the articular cavity to 30 d, which is 4.7 times that of the TMP solution.Intra-articular injection of TMP microspheres efficiently relieved inflammatory symptoms,improved joint lesions and decreased the depletion of proteoglycan. In conclusion, intraarticular injection of TMP loaded microspheres was a promising therapeutic method in the treatment of OA.展开更多
AIM: To explore the distribution and metabolism of 131 I-gelatin microspheres ( 131 I-GMSs) in rabbits after direct injection into rabbits’ livers.METHODS: Twenty-eight healthy New Zealand rabbits were divided into s...AIM: To explore the distribution and metabolism of 131 I-gelatin microspheres ( 131 I-GMSs) in rabbits after direct injection into rabbits’ livers.METHODS: Twenty-eight healthy New Zealand rabbits were divided into seven groups,with four rabbits per group.Each rabbit’s hepatic lobes were directly injected with 41.336 ± 5.106 MBq 131 I-GMSs.Each day after 131 I-GMSs administration,4 rabbits were randomly selected,and 250 μL of serum was collected for γ count.Hepatic and thyroid functions were tested on days 1,4,8,16,24,32,48 and 64 after 131 I-GMSs administration.Single-photon emission computed tomography (SPECT) was taken for each group on days 0,1,4,8,16,24,32,48,64 after 131 I-GMSs administration.A group of rabbits were sacrificed respectively on days 1,4,16,24,32,48,64 after 131 I-GMSs administration.Their livers were taken out for histological examination.RESULTS: After 131 I-GMSs administration,the nuclide was collected in the hepatic area with microspheres.The radiation could be detected on day 48 after 131 IGMSs administration,and radiography could be seen in thyroid areas in SPECT on days 4,8,16 and 24.One day after 131 I-GMSs administration,the liver function was damaged but recovered 4 d later.Eight days after 131 I-GMSs administration,the levels of free triiodothyronine and free thyroxin were reduced,which restored to normal levels on day 16.Histological examination showed that the microspheres were degraded to different degrees at 24,32 and 48 d after 131 I-GMSs administration.The surrounding parts of injection points were in fibrous sheathing.No microspheres were detected in histological examination on day 64 after 131 I-GMSs administration.CONCLUSION: Direct in vivo injection of 131 I-GMSs is safe in rabbits.It may be a promising method for treatment of malignant tumors.展开更多
目的:评估基于注射用全氟丁烷微球[商品名示卓安(Sonazoid)]超声造影Kupffer期的深度学习模型预测肝细胞癌(hepatocellular carcinoma,HCC)微血管侵犯(microvascular invasion,MVI)的效能,并将其与影像组学模型及临床模型进行比较。方法...目的:评估基于注射用全氟丁烷微球[商品名示卓安(Sonazoid)]超声造影Kupffer期的深度学习模型预测肝细胞癌(hepatocellular carcinoma,HCC)微血管侵犯(microvascular invasion,MVI)的效能,并将其与影像组学模型及临床模型进行比较。方法:回顾并纳入2020年7月—2022年9月于广西医科大学第一附属医院接受Sonazoid超声造影检查的146例原发性HCC患者,以7∶3随机划分为训练集102例和验证集44例。基于肿瘤感兴趣区,使用ResNet101模型通过迁移学习提取深度学习特征,使用PyRadiomics提取影像组学特征。采用Mann-Whitney U检验、最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)算法进行特征降维。LASSO回归用于构建深度学习模型和影像组学模型,同时还基于临床特征构建一个临床模型。采用受试者工作特征曲线的曲线下面积(area under the curve,AUC)、灵敏度、特异度和准确度评估模型的诊断效能。DeLong检验用于比较模型间的诊断效能。结果:在训练集中,深度学习模型、影像组学模型、临床模型的AUC(95%CI)分别为0.931(0.880~0.981)、0.823(0.744~0.903)、0.719(0.614~0.824)。在验证集中,深度学习模型、影像组学模型、临床模型的AUC(95%CI)分别为0.895(0.757~1.000)、0.711(0.514~0.909)、0.606(0.390~0.822)。DeLong检验表明在训练集和验证集中,深度学习模型的诊断效能均优于影像组学模型及临床模型(P<0.05)。单因素及多因素logistic回归分析示甲胎蛋白和巴塞罗那临床肝癌分期可作为HCC患者MVI的独立预测因子(P<0.01)。结论:基于Sonazoid超声造影Kupffer期的深度学习模型在预测HCC患者MVI方面表现出优异的性能,有望成为预测MVI的无创影像学生物标志物。展开更多
High water-cut has become a worldwide challenge for oil production.It requires extensive efforts to process and dispose.This entails expanding water handling facilities and incurring high power consumption costs.Polym...High water-cut has become a worldwide challenge for oil production.It requires extensive efforts to process and dispose.This entails expanding water handling facilities and incurring high power consumption costs.Polymeric microsphere injection is a cost-effective way to deal with excessive water production from subterranean formations.This study reports a laboratory investigation on polymeric microsphere injection in a large volume to identify its in-depth fluid diversion capacity in a porous media with large pore/particle size ratio.The performance of polymeric microsphere injection was evaluated using etched glass micromodels based on the pore network of a natural carbonate rock,which were treated as water-wet or oil-wet micromodels.Waterflooding was conducted to displace oil at reservoir temperature of 95°C,followed by one pore volume of polymeric microsphere injection.Three polymeric microsphere samples with median particle size of 0.05,0.3,and 20μm were used to investigate the impact of particle size of the polymeric microspheres on incremental oil production capacity.Although the polymeric microspheres were much smaller than the pores,additional oil production was observed.The incremental oil production increased with increasing polymeric microsphere concentration and particle size.As a comparison,polymeric microsphere solutions were injected into oil-wet and water-wet micromodels after waterflooding.It was observed that the oil production in oil-wet micromodel was much higher than that in water-wet micromodel.The wettability of micromodels affected the distribution patterns of the remaining oil after waterflooding and further dominated the performance of the microsphere injection.The study supports the applicability of microsphere injection in oil-wet heterogeneous carbonates.展开更多
As a new type of injectable biomaterials,functional microspheres have attracted increasing attention in tissue regeneration because they possess some advantageous properties compared to other biomaterials,including hy...As a new type of injectable biomaterials,functional microspheres have attracted increasing attention in tissue regeneration because they possess some advantageous properties compared to other biomaterials,including hydrogels.A variety of bio-inspired microspheres with unique structures and properties have been developed as cellular carriers and drug delivery vehicles in recent years.In this review,we provide a comprehensive summary of the progress of functional and biodegradable microspheres that have been used for tissue regeneration over the last two decades.First,we briefly introduce the biomaterials and general methods for microsphere fabrication.Next,we focus on the newly developed technologies for preparing functional microspheres,including macroporous microspheres,nanofibrous microspheres,hollow microspheres,core-shell structured microspheres,and surface-modified functional microspheres.After that,we discuss the application of functional microspheres for tissue regeneration,specifically for bone,cartilage,dental,neural,cardiac,and skin tissue regeneration.Last,we present our perspectives and future directions of functional microspheres as injectable carriers for the future advancement of tissue regeneration.展开更多
Injectable bone cement is especially useful in minimally invasive surgeries to repair small and irregular bone defects.Amongst different kinds of injectable bone cements,bioactive calcium phosphate bone cement(CPC)has...Injectable bone cement is especially useful in minimally invasive surgeries to repair small and irregular bone defects.Amongst different kinds of injectable bone cements,bioactive calcium phosphate bone cement(CPC)has been widely studied due to its biological activity.However,its dense structure and poor biodegradability prevent the ingrowth of living tissue,which leads to undesirable bone regeneration and clinical translation.To address this issue,we prepared bone cement based on Magnesium-containing microspheres(MMSs)that can not only be cured into a 3D porous scaffold but also have controllable biodegradability that continuously provides space for desired tissue ingrowth.Interestingly,magnesium ions released from MMSs cement(MMSC)trigger positive immunomodulation via upregulation of the anti-inflammatory genes IL-10 and M2 macrophage polarization with increased expression of CD206,which is beneficial to osteogenesis.Moreover,the physicochemical properties of MMSC,including heat release,rheology and setting time,can be tuned to meet the requirements of injectable bone cement for clinical application.Using a rat model,we have demonstrated that MMSC promoted osteogenesis via mediation of tissue ingrowth and anti-inflammatory immunomodulation.The study provides a paradigm for the design and preparation of injectable bone cements with 3D porous structures,biodegradability and anti-inflammatory immunoregulation to efficiently promote osteogenesis.展开更多
Local lactate accumulation greatly hinders tissue repair and regeneration under ischemic condition.Herein,an injectable microsphere(MS@MCL)for local lactate exhaustion was constructed by grafting manganese dioxide(MnO...Local lactate accumulation greatly hinders tissue repair and regeneration under ischemic condition.Herein,an injectable microsphere(MS@MCL)for local lactate exhaustion was constructed by grafting manganese dioxide(MnO_(2))-lactate oxidase(LOX)composite nanozyme on microfluidic hyaluronic acid methacrylate(HAMA)microspheres via chemical bonds,achieving a long-term oxygen-promoted lactate exhaustion effect and a long half-life in vivo.The uniform and porous microspheres synthesized by microfluidic technology is beneficial to in situ injection therapy and improving encapsulation efficiency.Furthermore,chemical grafting into HAMA microspheres through amide reactions promoted local enzymatic concentration and activity enhancement.It was showed that the MS@MCL eliminated oxidative and inflammatory stress and promoted extracellular matrix metabolism and cell survival when co-cultured with nucleus pulposus cells(NPCs)in vitro.In the rat degenerative intervertebral disc model caused by lactate injection,MS@MCL showed a long-term therapeutic effect in reducing intervertebral height narrowing and preventing extracellular matrix(ECM)degradation as well as inflammatory damage in vivo.Altogether,this study confirms that this nanozyme-functionalized injectable MS@MCL effectively improves the regenerative and reparative effect in ischemic tissues by disposing of enriched lactate in local microenvironment.展开更多
文摘Tetramethylpyrazine(TMP) is a traditional Chinese herbal medicine with strong antiinflammatory and cartilage protection activities, and thus a promising candidate for treating osteoarthritis. However, TMP is rapidly cleared from the joint cavity after intra-articular injection and requires multiple injections to maintain efficacy. The aim of this study was to encapsulate TMP into poly(lactic-co-glycolic acid)(PLGA) microspheres to enhance the TMP retention in the joint, reducing injection frequencies and decreasing dosage. TMP microspheres were prepared by emulsion/solvent evaporation method. The intra-articular retention of the drug was assessed by detecting the drug concentration distributed in the joint tissue at different time points. The therapeutic effect of TMP microspheres was evaluated by the swelling of knee joints and histologic analysis in papain-induced OA rat model. The prepared freezedried microspheres with a particle size of about 10 μm can effectively prolong the retention time of the drug in the articular cavity to 30 d, which is 4.7 times that of the TMP solution.Intra-articular injection of TMP microspheres efficiently relieved inflammatory symptoms,improved joint lesions and decreased the depletion of proteoglycan. In conclusion, intraarticular injection of TMP loaded microspheres was a promising therapeutic method in the treatment of OA.
基金Supported by Grant from the Science & Technology Pillar Program of Sichuan Province,China,No.2009SZ184
文摘AIM: To explore the distribution and metabolism of 131 I-gelatin microspheres ( 131 I-GMSs) in rabbits after direct injection into rabbits’ livers.METHODS: Twenty-eight healthy New Zealand rabbits were divided into seven groups,with four rabbits per group.Each rabbit’s hepatic lobes were directly injected with 41.336 ± 5.106 MBq 131 I-GMSs.Each day after 131 I-GMSs administration,4 rabbits were randomly selected,and 250 μL of serum was collected for γ count.Hepatic and thyroid functions were tested on days 1,4,8,16,24,32,48 and 64 after 131 I-GMSs administration.Single-photon emission computed tomography (SPECT) was taken for each group on days 0,1,4,8,16,24,32,48,64 after 131 I-GMSs administration.A group of rabbits were sacrificed respectively on days 1,4,16,24,32,48,64 after 131 I-GMSs administration.Their livers were taken out for histological examination.RESULTS: After 131 I-GMSs administration,the nuclide was collected in the hepatic area with microspheres.The radiation could be detected on day 48 after 131 IGMSs administration,and radiography could be seen in thyroid areas in SPECT on days 4,8,16 and 24.One day after 131 I-GMSs administration,the liver function was damaged but recovered 4 d later.Eight days after 131 I-GMSs administration,the levels of free triiodothyronine and free thyroxin were reduced,which restored to normal levels on day 16.Histological examination showed that the microspheres were degraded to different degrees at 24,32 and 48 d after 131 I-GMSs administration.The surrounding parts of injection points were in fibrous sheathing.No microspheres were detected in histological examination on day 64 after 131 I-GMSs administration.CONCLUSION: Direct in vivo injection of 131 I-GMSs is safe in rabbits.It may be a promising method for treatment of malignant tumors.
文摘目的:评估基于注射用全氟丁烷微球[商品名示卓安(Sonazoid)]超声造影Kupffer期的深度学习模型预测肝细胞癌(hepatocellular carcinoma,HCC)微血管侵犯(microvascular invasion,MVI)的效能,并将其与影像组学模型及临床模型进行比较。方法:回顾并纳入2020年7月—2022年9月于广西医科大学第一附属医院接受Sonazoid超声造影检查的146例原发性HCC患者,以7∶3随机划分为训练集102例和验证集44例。基于肿瘤感兴趣区,使用ResNet101模型通过迁移学习提取深度学习特征,使用PyRadiomics提取影像组学特征。采用Mann-Whitney U检验、最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)算法进行特征降维。LASSO回归用于构建深度学习模型和影像组学模型,同时还基于临床特征构建一个临床模型。采用受试者工作特征曲线的曲线下面积(area under the curve,AUC)、灵敏度、特异度和准确度评估模型的诊断效能。DeLong检验用于比较模型间的诊断效能。结果:在训练集中,深度学习模型、影像组学模型、临床模型的AUC(95%CI)分别为0.931(0.880~0.981)、0.823(0.744~0.903)、0.719(0.614~0.824)。在验证集中,深度学习模型、影像组学模型、临床模型的AUC(95%CI)分别为0.895(0.757~1.000)、0.711(0.514~0.909)、0.606(0.390~0.822)。DeLong检验表明在训练集和验证集中,深度学习模型的诊断效能均优于影像组学模型及临床模型(P<0.05)。单因素及多因素logistic回归分析示甲胎蛋白和巴塞罗那临床肝癌分期可作为HCC患者MVI的独立预测因子(P<0.01)。结论:基于Sonazoid超声造影Kupffer期的深度学习模型在预测HCC患者MVI方面表现出优异的性能,有望成为预测MVI的无创影像学生物标志物。
文摘High water-cut has become a worldwide challenge for oil production.It requires extensive efforts to process and dispose.This entails expanding water handling facilities and incurring high power consumption costs.Polymeric microsphere injection is a cost-effective way to deal with excessive water production from subterranean formations.This study reports a laboratory investigation on polymeric microsphere injection in a large volume to identify its in-depth fluid diversion capacity in a porous media with large pore/particle size ratio.The performance of polymeric microsphere injection was evaluated using etched glass micromodels based on the pore network of a natural carbonate rock,which were treated as water-wet or oil-wet micromodels.Waterflooding was conducted to displace oil at reservoir temperature of 95°C,followed by one pore volume of polymeric microsphere injection.Three polymeric microsphere samples with median particle size of 0.05,0.3,and 20μm were used to investigate the impact of particle size of the polymeric microspheres on incremental oil production capacity.Although the polymeric microspheres were much smaller than the pores,additional oil production was observed.The incremental oil production increased with increasing polymeric microsphere concentration and particle size.As a comparison,polymeric microsphere solutions were injected into oil-wet and water-wet micromodels after waterflooding.It was observed that the oil production in oil-wet micromodel was much higher than that in water-wet micromodel.The wettability of micromodels affected the distribution patterns of the remaining oil after waterflooding and further dominated the performance of the microsphere injection.The study supports the applicability of microsphere injection in oil-wet heterogeneous carbonates.
文摘As a new type of injectable biomaterials,functional microspheres have attracted increasing attention in tissue regeneration because they possess some advantageous properties compared to other biomaterials,including hydrogels.A variety of bio-inspired microspheres with unique structures and properties have been developed as cellular carriers and drug delivery vehicles in recent years.In this review,we provide a comprehensive summary of the progress of functional and biodegradable microspheres that have been used for tissue regeneration over the last two decades.First,we briefly introduce the biomaterials and general methods for microsphere fabrication.Next,we focus on the newly developed technologies for preparing functional microspheres,including macroporous microspheres,nanofibrous microspheres,hollow microspheres,core-shell structured microspheres,and surface-modified functional microspheres.After that,we discuss the application of functional microspheres for tissue regeneration,specifically for bone,cartilage,dental,neural,cardiac,and skin tissue regeneration.Last,we present our perspectives and future directions of functional microspheres as injectable carriers for the future advancement of tissue regeneration.
基金This work was supported by the National Key R&D Project(2018YFC1105701)National Natural Science Foundation of China(81801850,81901897,31870960)China Postdoctoral Science Foundation Grant(2018M642851).
文摘Injectable bone cement is especially useful in minimally invasive surgeries to repair small and irregular bone defects.Amongst different kinds of injectable bone cements,bioactive calcium phosphate bone cement(CPC)has been widely studied due to its biological activity.However,its dense structure and poor biodegradability prevent the ingrowth of living tissue,which leads to undesirable bone regeneration and clinical translation.To address this issue,we prepared bone cement based on Magnesium-containing microspheres(MMSs)that can not only be cured into a 3D porous scaffold but also have controllable biodegradability that continuously provides space for desired tissue ingrowth.Interestingly,magnesium ions released from MMSs cement(MMSC)trigger positive immunomodulation via upregulation of the anti-inflammatory genes IL-10 and M2 macrophage polarization with increased expression of CD206,which is beneficial to osteogenesis.Moreover,the physicochemical properties of MMSC,including heat release,rheology and setting time,can be tuned to meet the requirements of injectable bone cement for clinical application.Using a rat model,we have demonstrated that MMSC promoted osteogenesis via mediation of tissue ingrowth and anti-inflammatory immunomodulation.The study provides a paradigm for the design and preparation of injectable bone cements with 3D porous structures,biodegradability and anti-inflammatory immunoregulation to efficiently promote osteogenesis.
基金financially supported by the National Natural Science Foundation of China(82102578,81922045,81772314 and 21604052)the National Natural Science Foundation of Chongqing(cstc2018jcyjAX0059 and cstc2018jcyjAX0797)Applied Basic Research Programs of the Science and Technology Department of Sichuan Province(2021YJ0467).
文摘Local lactate accumulation greatly hinders tissue repair and regeneration under ischemic condition.Herein,an injectable microsphere(MS@MCL)for local lactate exhaustion was constructed by grafting manganese dioxide(MnO_(2))-lactate oxidase(LOX)composite nanozyme on microfluidic hyaluronic acid methacrylate(HAMA)microspheres via chemical bonds,achieving a long-term oxygen-promoted lactate exhaustion effect and a long half-life in vivo.The uniform and porous microspheres synthesized by microfluidic technology is beneficial to in situ injection therapy and improving encapsulation efficiency.Furthermore,chemical grafting into HAMA microspheres through amide reactions promoted local enzymatic concentration and activity enhancement.It was showed that the MS@MCL eliminated oxidative and inflammatory stress and promoted extracellular matrix metabolism and cell survival when co-cultured with nucleus pulposus cells(NPCs)in vitro.In the rat degenerative intervertebral disc model caused by lactate injection,MS@MCL showed a long-term therapeutic effect in reducing intervertebral height narrowing and preventing extracellular matrix(ECM)degradation as well as inflammatory damage in vivo.Altogether,this study confirms that this nanozyme-functionalized injectable MS@MCL effectively improves the regenerative and reparative effect in ischemic tissues by disposing of enriched lactate in local microenvironment.
