AIM: To assess the necessity of esophagogastroduodenoscopy (EGD) to predict the outcome of caustic ingestion in children. METHODS: The study included 206 children who underwent EGD because of ingestion of caustic subs...AIM: To assess the necessity of esophagogastroduodenoscopy (EGD) to predict the outcome of caustic ingestion in children. METHODS: The study included 206 children who underwent EGD because of ingestion of caustic substances between January 2005 and August 2010. Retrospective analysis of data of the patients was performed. RESULTS: The male/female ratio was 1.6 and mean age was 38.1 ± 28.8 mo. The caustic substances were acidic in 72 (34.9%) cases, alkaline in 56 (27.2%), liquid household bleach in 62 (30.1%), and unknown in 16 (7.8%). Fifty-seven (27.7%) patients were symptom-free. Significant clinical findings were observed in 149 (72.3%) patients. Upper gastrointestinal endoscopy findings of esophageal injury were grade 0 in 86 (41.7%) patients, grade 1 in 49 (23.8%), grade 2a in 42 (20.4%), grade 2b in 28 (13.6%), and grade 3a in 1 (0.5%) patient. 35 patients with grade 2a, 2b, and 3a injuries underwent esophageal dilation at second week of ingestion. Esophageal stricture, which necessitated a regular dilation program developed in 13 of the aforementioned 35 patients. There is no statistically significant difference in the rate of development of esophageal stricture between the patients who ingested acidic (15.3%) and alkaline (8.9%) substances (P = 0.32). Severe gastric injury was detected in 38 (18.5%) patients. The rate of development of gastric injury was significantly higher in the acidic group (14%) than in the alkaline group (2.9%) (P = 0.001). Out of 149 patients with clinical findings, 49 (32.9%) patients had no esophageal injury and 117 (78.5%) patients had no gastric lesion. Esophageal and severe gastric injuries were detected in 20 (35.1%) and 8 (14%) of patients with no clinical findings respectively. Pyloric stenosis developed in 6 patients. Pyloric obstruction improved with balloon dilation in 2 patients. Mean hospitalization time were 1.2 ± 0.5 d for grade 0 and 2.3 ± 5 d for grade 1 and 6.3 ± 6.2 d for grade 2a and 15.8 ± 18.6 d for grade 2b. It was significantly longer for patients with grade 2a and 2b injuries (P = 0.000). CONCLUSION: Endoscopy is an effective technique for determining the presence of esophageal and gastric damage and to avoid unnecessary treatment in patients with no or mild injury.展开更多
A field experiment established in 1997 was conducted to study the effect of long-term N fertilizer application on N mineralization in a paddy soil determined using a laboratory anaerobic incubation followed with a fie...A field experiment established in 1997 was conducted to study the effect of long-term N fertilizer application on N mineralization in a paddy soil determined using a laboratory anaerobic incubation followed with a field incubation and to measure the relationship between in situ N mineralization and crop N uptake. To estimate N mineralization in the laboratory, soil samples were collected from plots with N application at different rates for six years and were incubated. Soils treated with fertilizer N mineralized more N than unfertilized soils and mineralization increased with N application rates. Also, the fraction of total N mineralized increased with increasing N fertilizer application. These findings meant that a substantial portion of previously applied N could be recovered slowly over time in subsequent crops. The field incubation of the plot receiving no fertilizer N showed that the NH4^+-N concentration varied greatly during the rice-growing season and seasonal changes of N mineralization were due more to accumulation of NH4^+-N than NO3^-N. Hice N uptake increased up to a maximum of 82 kg N ha^-1 during the season. The close agreement found between in situ N mineralization and rice N uptake suggested that the measurement of in situ N mineralization could provide useful recommendations for adequate fertilizer N application.展开更多
The cytotoxicity and non-specific cellular uptake of the most popular composition of upconversion nanoparticle (UCNP), NaYF4:Yb^3+:Er^3+, is reported using normal human skin cells, including dermal fibroblasts a...The cytotoxicity and non-specific cellular uptake of the most popular composition of upconversion nanoparticle (UCNP), NaYF4:Yb^3+:Er^3+, is reported using normal human skin cells, including dermal fibroblasts and immortalized human epidermal linear keratinocytes (HaCaT). A new hydrophilization reaction of as-synthesized UCNPs based on tetramethylammonium hydroxide (TMAH) enabled evaluation of the intrinsic cytotoxicity of bare UCNPs. The cytotoxicity effects of the UCNP surface-coating and polystyrene host were investigated over the concentration range 62.5-125 μg/mL with 24-h incubation, using a MTT test and optical microscopy. The fibroblast viability was not compromised by UCNPs, whereas the viability of keratinocytes varied from 52% ± 4% to 100% ± 10% than the control group, depending on the surface modification. Bare UCNPs reduced the keratinocyte viability to 76% ± 3%, while exhibiting profound non-specific cellular uptake. Hydrophilic poly(D,L-lactide)- and poly(maleic anhydride-alt-l-octadecene)-coated UCNPs were found to be least cytotoxic among the polymer-coated UCNPs, and were readily internalized by human skin cells. Polystyrene microbeads impregnated with UCNPs remained nontoxic. Surprisingly, no correlation was found between UCNP cytotoxicity and the internalization level in cells, although the latter ranged broadly from 0.03% to 59%, benchmarked against 100% uptake level of TMAH-UCNPs.展开更多
Porous silicon nanoparficles (pSiNPs) are a promising nanocarrier system for drug delivery owing to their biocompatibility, biodegradability, and non-inflammatory nature. Here, we investigate the fabrication and cha...Porous silicon nanoparficles (pSiNPs) are a promising nanocarrier system for drug delivery owing to their biocompatibility, biodegradability, and non-inflammatory nature. Here, we investigate the fabrication and characterization of thermally hydrocarbonized pSiNPs (THCpSiNPs) and chitosan-coated THCpSiNPs for therapeutic oligonucleotide delivery. Chitosan coating after oligonucleotide loading significantly improves sustained oligonucleotide release and suppresses burst release effects. Moreover, cellular uptake, endocytosis, and cytotoxicity of oligonucleotide-loaded THCpSiNPs have been evaluated in vitro. Standard cell viability assays demonstrate that cells incubated with the NPs at a concentration of 0.1 mg/mL are 95% viable. In addition, chitosan coating significantly enhances the uptake of oligonucleotide-loaded THCpSiNPs across the cell membrane. Moreover, histopathological analysis of liver, kidney, spleen, and skin tissue collected from mice receiving NPs further demonstrates the biocompatible and non-inflammatory properties of the NPs as a gene delivery vehicle for intravenous and subcutaneous administration in vivo. Taken together, these results suggest that THCpSiNPs provide a versatile platform that could be used as efficient vehicles for the intracellular delivery of oligonucleotides for gene therapy.展开更多
Drug resistance of anthracycline in the invasive cancer is associated with the lowered cellular drug uptake and diminished co-localization of drug with nuclei. In the present study, we aimed to construct the folate-co...Drug resistance of anthracycline in the invasive cancer is associated with the lowered cellular drug uptake and diminished co-localization of drug with nuclei. In the present study, we aimed to construct the folate-conjugated epirubicin liposomes by incorporating a synthesized folate-lipid derivative; and to assess the effects on cellular drug uptake, co-localization of drug with nuclei and efficacy in treatment of invasive breast cancer cells. The studies were performed on invasive human breast cancer cells. The folate-PEG2ooo-DSPE conjugate was synthesized, and the constructed folate-conjugated epirubicin liposomes were approximately 1 O0 nm in size. The in vitro studies demonstrated that the folate-conjugated epirubicin liposomes had the strongest cellular drug uptake and co-localization with nuclei of the invasive breast cancer cells. Besides, the liposomes displayed the most significant efficacy in killing the invasive cancer cells, in preventing their invasive potential, and in penetrating ability into breast cancer spheroid as well. In conclusion, the constructed folate-conjugated epirubicin liposomes were able to enhance the efficacy in treatment of invasive breast cancer by improving the cellular drug uptake and increasing the co-localization with nuclei, hence offering a new strategy for potentially eradicating the invasive breast cancer cells.展开更多
Clearance of apoptotic neutrophils by macrophages is important for both the successful resolution of acute inflammation and homeostasis.However,the dynamic process of phagocytosis of apoptotic neutrophils by macrophag...Clearance of apoptotic neutrophils by macrophages is important for both the successful resolution of acute inflammation and homeostasis.However,the dynamic process of phagocytosis of apoptotic neutrophils by macrophages and the fate of macrophages after the ingestion of apoptotic neutrophils has not been well documented.In the present study,we staged the recognition and tethering,internalization,digestion and exocytosis steps of phagocytosis of apoptotic neutrophils.Furthermore,we found that after the ingestion of apoptotic cells,a subset of macrophages underwent cell death by autophagy,apoptosis or oncosis as revealed by transmission electron microscopy and confocal microscopy combined with specific dyes.The percentage of autophagic,apoptotic and oncotic macrophages were 8.00%±2.00%,12.33%±2.08%,and 3.66%±1.50%,respectively.These results indicated that after ingestion of apoptotic neutrophils,a subset of macrophages undergoes autophagy and apoptosis.We propose that autophagy of macrophages after the ingestion of apoptotic cells may be a new mechanism present in the resolution of inflammation.展开更多
With the increasingly promising role of nanomaterials in tissue engineering and regenerative medicine, the interaction between stem cells and nanoparticles has become a critical focus. The entry of nanoparticles into ...With the increasingly promising role of nanomaterials in tissue engineering and regenerative medicine, the interaction between stem cells and nanoparticles has become a critical focus. The entry of nanoparticles into cells has become a primary issue for effectively regulating the subsequent safety and performance of nanomaterials in vivo. Although the influence of nanomaterials on endocytosis has been extensively studied, reports on the influence of stem cells are rare.Moreover, the effect of nanomaterials on stem cells is also dependent upon the action mode. Unfortunately, the interaction between stem cells and assembled nanoparticles is often neglected. In this paper, we explore for the first time the uptake of γ-Fe2O3 nanoparticles by adipose-derived stem cells with different passage numbers. The results demonstrate that cellular viability decreases and cell senescence level increases with the extension of the passage number. We found the surface appearance of cellular membranes to become increasingly rough and uneven with increasing passage numbers. The iron content in the dissociative nanoparticles was also significantly reduced with increases in the passage number. However, we observed multiple-passaged stem cells cultured on assembled nanoparticles to have similarly low iron content levels. The mechanism may lie in the magnetic effect of γ-Fe2O3 nanoparticles resulting from the field-directed assembly. The results of this work will facilitate the understanding and translation of nanomaterials in the clinical application of stem cells.展开更多
Incorporating functional ligands and biodegradable bonds into biocompatible low-molecular-weight(LMW)polymers,such as 1.8 kDa poly(ethylenimine)(PEI1.8 k),is a common strategy to improve the properties of LMW polymers...Incorporating functional ligands and biodegradable bonds into biocompatible low-molecular-weight(LMW)polymers,such as 1.8 kDa poly(ethylenimine)(PEI1.8 k),is a common strategy to improve the properties of LMW polymers including biosafety and delivery efficacy.This study demonstrates the hypothesis that introducing different functional ligands and linked reductive disulfides in PEI 1.8k will achieve superior siRNA transfection efficiency.By incorporating PEI-X(X represents cholesterol(Ch),heptafluorobutyric anhydride(HFBA,F)and 4-carboxyphenylboronic acid(PBA))functional ligands into PEI 1.8k and subsequently crosslinking with each other via disulfide bond links,reductive-responsive PEI-X-SS-X-PEI copolymers were constructed to enhance the cellular transfection via the synergistic effect of the high affinity of Ch,F and PBA to cell membranes and the disulfide reduction triggered intracellular disassembly of micelles and subsequent siRNA release.Extraordinarily,ternary Ch-SS-F-SS-PBA micelles exhibited the strongest siRNA transfection efficiencies in in vitro cell experiments and in vivo animal experiments due to the coordination of enhanced serum stability,promoted cell uptake and endosomal escape,and cell targeting ability.This strategy of constructed multifunctional polymer here we called"building-block crosslinking"showed a simple and smart way to synthesize new materials.Also this strategy of constructing ligands-directed reduction-sensitive micelles improves the transfection efficiency of LMW PEI and provides a valuable insight to develop novel gene delivery systems.展开更多
文摘AIM: To assess the necessity of esophagogastroduodenoscopy (EGD) to predict the outcome of caustic ingestion in children. METHODS: The study included 206 children who underwent EGD because of ingestion of caustic substances between January 2005 and August 2010. Retrospective analysis of data of the patients was performed. RESULTS: The male/female ratio was 1.6 and mean age was 38.1 ± 28.8 mo. The caustic substances were acidic in 72 (34.9%) cases, alkaline in 56 (27.2%), liquid household bleach in 62 (30.1%), and unknown in 16 (7.8%). Fifty-seven (27.7%) patients were symptom-free. Significant clinical findings were observed in 149 (72.3%) patients. Upper gastrointestinal endoscopy findings of esophageal injury were grade 0 in 86 (41.7%) patients, grade 1 in 49 (23.8%), grade 2a in 42 (20.4%), grade 2b in 28 (13.6%), and grade 3a in 1 (0.5%) patient. 35 patients with grade 2a, 2b, and 3a injuries underwent esophageal dilation at second week of ingestion. Esophageal stricture, which necessitated a regular dilation program developed in 13 of the aforementioned 35 patients. There is no statistically significant difference in the rate of development of esophageal stricture between the patients who ingested acidic (15.3%) and alkaline (8.9%) substances (P = 0.32). Severe gastric injury was detected in 38 (18.5%) patients. The rate of development of gastric injury was significantly higher in the acidic group (14%) than in the alkaline group (2.9%) (P = 0.001). Out of 149 patients with clinical findings, 49 (32.9%) patients had no esophageal injury and 117 (78.5%) patients had no gastric lesion. Esophageal and severe gastric injuries were detected in 20 (35.1%) and 8 (14%) of patients with no clinical findings respectively. Pyloric stenosis developed in 6 patients. Pyloric obstruction improved with balloon dilation in 2 patients. Mean hospitalization time were 1.2 ± 0.5 d for grade 0 and 2.3 ± 5 d for grade 1 and 6.3 ± 6.2 d for grade 2a and 15.8 ± 18.6 d for grade 2b. It was significantly longer for patients with grade 2a and 2b injuries (P = 0.000). CONCLUSION: Endoscopy is an effective technique for determining the presence of esophageal and gastric damage and to avoid unnecessary treatment in patients with no or mild injury.
基金Project supported by the Knowledge Innovation Program of the Chinese Academy of Sciences (No. KZCX2-413-4)the National Basic Research Program of China (No. 2005CB121107).
文摘A field experiment established in 1997 was conducted to study the effect of long-term N fertilizer application on N mineralization in a paddy soil determined using a laboratory anaerobic incubation followed with a field incubation and to measure the relationship between in situ N mineralization and crop N uptake. To estimate N mineralization in the laboratory, soil samples were collected from plots with N application at different rates for six years and were incubated. Soils treated with fertilizer N mineralized more N than unfertilized soils and mineralization increased with N application rates. Also, the fraction of total N mineralized increased with increasing N fertilizer application. These findings meant that a substantial portion of previously applied N could be recovered slowly over time in subsequent crops. The field incubation of the plot receiving no fertilizer N showed that the NH4^+-N concentration varied greatly during the rice-growing season and seasonal changes of N mineralization were due more to accumulation of NH4^+-N than NO3^-N. Hice N uptake increased up to a maximum of 82 kg N ha^-1 during the season. The close agreement found between in situ N mineralization and rice N uptake suggested that the measurement of in situ N mineralization could provide useful recommendations for adequate fertilizer N application.
文摘The cytotoxicity and non-specific cellular uptake of the most popular composition of upconversion nanoparticle (UCNP), NaYF4:Yb^3+:Er^3+, is reported using normal human skin cells, including dermal fibroblasts and immortalized human epidermal linear keratinocytes (HaCaT). A new hydrophilization reaction of as-synthesized UCNPs based on tetramethylammonium hydroxide (TMAH) enabled evaluation of the intrinsic cytotoxicity of bare UCNPs. The cytotoxicity effects of the UCNP surface-coating and polystyrene host were investigated over the concentration range 62.5-125 μg/mL with 24-h incubation, using a MTT test and optical microscopy. The fibroblast viability was not compromised by UCNPs, whereas the viability of keratinocytes varied from 52% ± 4% to 100% ± 10% than the control group, depending on the surface modification. Bare UCNPs reduced the keratinocyte viability to 76% ± 3%, while exhibiting profound non-specific cellular uptake. Hydrophilic poly(D,L-lactide)- and poly(maleic anhydride-alt-l-octadecene)-coated UCNPs were found to be least cytotoxic among the polymer-coated UCNPs, and were readily internalized by human skin cells. Polystyrene microbeads impregnated with UCNPs remained nontoxic. Surprisingly, no correlation was found between UCNP cytotoxicity and the internalization level in cells, although the latter ranged broadly from 0.03% to 59%, benchmarked against 100% uptake level of TMAH-UCNPs.
文摘Porous silicon nanoparficles (pSiNPs) are a promising nanocarrier system for drug delivery owing to their biocompatibility, biodegradability, and non-inflammatory nature. Here, we investigate the fabrication and characterization of thermally hydrocarbonized pSiNPs (THCpSiNPs) and chitosan-coated THCpSiNPs for therapeutic oligonucleotide delivery. Chitosan coating after oligonucleotide loading significantly improves sustained oligonucleotide release and suppresses burst release effects. Moreover, cellular uptake, endocytosis, and cytotoxicity of oligonucleotide-loaded THCpSiNPs have been evaluated in vitro. Standard cell viability assays demonstrate that cells incubated with the NPs at a concentration of 0.1 mg/mL are 95% viable. In addition, chitosan coating significantly enhances the uptake of oligonucleotide-loaded THCpSiNPs across the cell membrane. Moreover, histopathological analysis of liver, kidney, spleen, and skin tissue collected from mice receiving NPs further demonstrates the biocompatible and non-inflammatory properties of the NPs as a gene delivery vehicle for intravenous and subcutaneous administration in vivo. Taken together, these results suggest that THCpSiNPs provide a versatile platform that could be used as efficient vehicles for the intracellular delivery of oligonucleotides for gene therapy.
基金The National Natural Science Foundation of China(Grant No.81373343 and 81673367)
文摘Drug resistance of anthracycline in the invasive cancer is associated with the lowered cellular drug uptake and diminished co-localization of drug with nuclei. In the present study, we aimed to construct the folate-conjugated epirubicin liposomes by incorporating a synthesized folate-lipid derivative; and to assess the effects on cellular drug uptake, co-localization of drug with nuclei and efficacy in treatment of invasive breast cancer cells. The studies were performed on invasive human breast cancer cells. The folate-PEG2ooo-DSPE conjugate was synthesized, and the constructed folate-conjugated epirubicin liposomes were approximately 1 O0 nm in size. The in vitro studies demonstrated that the folate-conjugated epirubicin liposomes had the strongest cellular drug uptake and co-localization with nuclei of the invasive breast cancer cells. Besides, the liposomes displayed the most significant efficacy in killing the invasive cancer cells, in preventing their invasive potential, and in penetrating ability into breast cancer spheroid as well. In conclusion, the constructed folate-conjugated epirubicin liposomes were able to enhance the efficacy in treatment of invasive breast cancer by improving the cellular drug uptake and increasing the co-localization with nuclei, hence offering a new strategy for potentially eradicating the invasive breast cancer cells.
文摘Clearance of apoptotic neutrophils by macrophages is important for both the successful resolution of acute inflammation and homeostasis.However,the dynamic process of phagocytosis of apoptotic neutrophils by macrophages and the fate of macrophages after the ingestion of apoptotic neutrophils has not been well documented.In the present study,we staged the recognition and tethering,internalization,digestion and exocytosis steps of phagocytosis of apoptotic neutrophils.Furthermore,we found that after the ingestion of apoptotic cells,a subset of macrophages underwent cell death by autophagy,apoptosis or oncosis as revealed by transmission electron microscopy and confocal microscopy combined with specific dyes.The percentage of autophagic,apoptotic and oncotic macrophages were 8.00%±2.00%,12.33%±2.08%,and 3.66%±1.50%,respectively.These results indicated that after ingestion of apoptotic neutrophils,a subset of macrophages undergoes autophagy and apoptosis.We propose that autophagy of macrophages after the ingestion of apoptotic cells may be a new mechanism present in the resolution of inflammation.
基金supported by the National Basic Research Program of China(2013CB733801)the National Key Research and Development Program of China(2017YFA0104301)thankful to the supports from the Fundamental Research Funds for the Central Universities
文摘With the increasingly promising role of nanomaterials in tissue engineering and regenerative medicine, the interaction between stem cells and nanoparticles has become a critical focus. The entry of nanoparticles into cells has become a primary issue for effectively regulating the subsequent safety and performance of nanomaterials in vivo. Although the influence of nanomaterials on endocytosis has been extensively studied, reports on the influence of stem cells are rare.Moreover, the effect of nanomaterials on stem cells is also dependent upon the action mode. Unfortunately, the interaction between stem cells and assembled nanoparticles is often neglected. In this paper, we explore for the first time the uptake of γ-Fe2O3 nanoparticles by adipose-derived stem cells with different passage numbers. The results demonstrate that cellular viability decreases and cell senescence level increases with the extension of the passage number. We found the surface appearance of cellular membranes to become increasingly rough and uneven with increasing passage numbers. The iron content in the dissociative nanoparticles was also significantly reduced with increases in the passage number. However, we observed multiple-passaged stem cells cultured on assembled nanoparticles to have similarly low iron content levels. The mechanism may lie in the magnetic effect of γ-Fe2O3 nanoparticles resulting from the field-directed assembly. The results of this work will facilitate the understanding and translation of nanomaterials in the clinical application of stem cells.
基金supported by the National Natural Science Foundation of China(81903556)the Natural Science Fund for Colleges and Universities in Jiangsu Province(19KJB350004)supported by the National Health and Medical Research Council(NHMRC)Early Career Fellowship(1112258)of Australia。
文摘Incorporating functional ligands and biodegradable bonds into biocompatible low-molecular-weight(LMW)polymers,such as 1.8 kDa poly(ethylenimine)(PEI1.8 k),is a common strategy to improve the properties of LMW polymers including biosafety and delivery efficacy.This study demonstrates the hypothesis that introducing different functional ligands and linked reductive disulfides in PEI 1.8k will achieve superior siRNA transfection efficiency.By incorporating PEI-X(X represents cholesterol(Ch),heptafluorobutyric anhydride(HFBA,F)and 4-carboxyphenylboronic acid(PBA))functional ligands into PEI 1.8k and subsequently crosslinking with each other via disulfide bond links,reductive-responsive PEI-X-SS-X-PEI copolymers were constructed to enhance the cellular transfection via the synergistic effect of the high affinity of Ch,F and PBA to cell membranes and the disulfide reduction triggered intracellular disassembly of micelles and subsequent siRNA release.Extraordinarily,ternary Ch-SS-F-SS-PBA micelles exhibited the strongest siRNA transfection efficiencies in in vitro cell experiments and in vivo animal experiments due to the coordination of enhanced serum stability,promoted cell uptake and endosomal escape,and cell targeting ability.This strategy of constructed multifunctional polymer here we called"building-block crosslinking"showed a simple and smart way to synthesize new materials.Also this strategy of constructing ligands-directed reduction-sensitive micelles improves the transfection efficiency of LMW PEI and provides a valuable insight to develop novel gene delivery systems.