It is urgent to find a technology accurately to better diagnose and treat to brain tumor.Eu-doped Gd2 O3 nanorods(Eu-Gd2 O3 NRs)with paramagnetic and fluorescent properties were conjugated with doxorubicin(Dox)and chl...It is urgent to find a technology accurately to better diagnose and treat to brain tumor.Eu-doped Gd2 O3 nanorods(Eu-Gd2 O3 NRs)with paramagnetic and fluorescent properties were conjugated with doxorubicin(Dox)and chlorotoxin(CTX)via PEGylation,hydrazone bond and sulfur bond(named as CTXNRs-Dox),and these NRs could release more Dox in lower pH environment.The results of cell experiments indicated that CTX-NRs-Dox had obvious targeting and toxic effects on U251 cells,as well as good fluorescence imaging behavior.The orthotopic glioma-transplanted mice models were constructed via the intracranial injection of glioma cells(U87 MG).The result of experiments after the tail-vein injection of the prepared NRs suggested that CTX-NRs-Dox could target to brain tumors via the long-time blood circulation,leading to their obvious contrast enhancement of MR imaging of the intracranial tumor and their significant inhibitory effect on the growth and metastasis of brain tumors.A mechanism of synergistic effect of CTX-NRs-Dox on targeting and inhabiting the brain tumor was proposed.Our research suggested that CTX-NRs-Dox had potential application prospect in the detection and treatment of glioma.展开更多
Background:Platinum can cause chemotherapy-related cognitive impairment.Low-intensity focused ultrasound(LIFUS)is a promising noninvasive physical stimulation method with a unique advantage in neurological rehabilitat...Background:Platinum can cause chemotherapy-related cognitive impairment.Low-intensity focused ultrasound(LIFUS)is a promising noninvasive physical stimulation method with a unique advantage in neurological rehabilitation.We aimed to investigate whether LIFUS can alleviate cisplatin-induced cognitive impairment in rats and explore the related neuropatho-logical mechanisms.Methods:After confirming the target position for LIFUS treatment in 18 rats,64 rats were randomly divided into four groups:control,model,sham,and LIFUS groups.Before and after LIFUS treatment,detailed biological behavioral assessments and magnetic resonance imaging were performed.Finally,the rats were euthanized,and relevant histopathological and molecular biological experiments were conducted and analyzed.Results:In the Morris water maze,the model group showed fewer platform crossings(1.250.93 vs.5.691.58),a longer escape latency(41.6536.55 s vs.6.382.11 s),and a lower novel object recognition index(29.7711.83 vs.83.695.67)than the control group.LIFUS treatment improved these metrics,with more platform crossings(3.130.34),a higher recognition index(65.588.71),and a shorter escape latency(6.452.27 s).Longitudinal analysis of the LIFUS group further confirmed these improvements.Neuroimaging revealed significant differences in diffusion tensor imaging metrics of specific brain regions pre-and post-LIFUS.Moreover,neuropathology showed higher dendritic spine density,less myelin loss,fewer apoptotic cells,more synapses,and less mitochondrial autophagy after LIFUS treatment.The neuroimaging indicators were correlated with behavioral improvements,highlighting the potential of LIFUS for alleviating cognitive impairment(as demonstrated through imaging and analysis).Our investigation of the molecular biological mechanisms revealed distinct protein expression patterns in the hippocampus and its subregions.In the model group,glial fibrillary acidic protein(GFAP)and ionized calcium-binding adaptor molecule 1(IBA1)expression levels were elevated across the hippocampus,whereas neuronal nuclei(NeuN)expression was reduced.Subregional analysis revealed higher GFAP and IBA1 and lower NeuN,especially in the dentate gyrus subregion.Moreover,positive cell areas were larger in the cornu ammonis(CA)1,CA2,CA3,and dentate gyrus regions.In the CA2 and CA3,significant differences among the groups were observed in GFAP-positive cell counts and areas,and there were variations in NeuN expression.Conclusions:Our results suggest that LIFUS can reverse cisplatin-induced cognitive impairments.The neuroimaging findings were consistent with the behavioral and histological results and suggest a neuropathological basis that supports further research into the clinical applications of LIFUS.Furthermore,LIFUS appeared to enhance the plasticity of neuronal synapses in the rat hippocampus and reduce hippocampal inflammation.These findings highlight the clinical potential of LIFUS as an effective,noninvasive therapeutic strategy and monitoring tool for chemotherapy-induced cognitive deficits.展开更多
Ambroxol hydrochloride(2-amino-3,5-dibromo-N-methylbenzylamine hydrochloride)has been used as a mucolytic agent in the treatment of respiratory diseases since the late 1970s.Its effects on mucus membranes such as mucu...Ambroxol hydrochloride(2-amino-3,5-dibromo-N-methylbenzylamine hydrochloride)has been used as a mucolytic agent in the treatment of respiratory diseases since the late 1970s.Its effects on mucus membranes such as mucus disruption,increased mucus production,and low toxicity profile were addressed in its original German patent in 1966.These first described properties have kept Ambroxol available worldwide and over the counter in the pharmaceutical market to this day.展开更多
Positron emission tomography(PET)has been successfully applied to an increasing number of cardiovascular conditions.This review will highlight the status of cardiovascular PET,including the present state of the art an...Positron emission tomography(PET)has been successfully applied to an increasing number of cardiovascular conditions.This review will highlight the status of cardiovascular PET,including the present state of the art and the expanding pool of clinical evidence guiding its use.Additionally,we highlight upcoming developments in the fi eld,including the development of new tracers and applications of PET to novel indications within cardiovascular medicine.展开更多
Purpose: To determine the relationship between the dental root indentation and maxillary sinusitis. Methods: We assessed the records of the patients who underwent paranasal sinus computed tomography imaging for suspec...Purpose: To determine the relationship between the dental root indentation and maxillary sinusitis. Methods: We assessed the records of the patients who underwent paranasal sinus computed tomography imaging for suspected sinusitis. Results: We identified a total of 52 patients with a pre-diagnosis of maxillary sinusitis. Dental indentation was detected in 58 of 104 (55.7%) sinuses. Forty six of 58 sinuses (79.3%) with dental indentation had mucosal thickening higher than 2 mm. The difference between the groups was statistically significant (p = 0.007). Conclusion: Dental indentation should be kept in mind as a reason for chronic maxillary sinus inflammation, if an underlying cause cannot be identified.展开更多
Background: Although perceptual and representational neglect are frequently associated, the demonstration of a double dissociation between both neglect forms suggests that both rely on different central mechanisms. In...Background: Although perceptual and representational neglect are frequently associated, the demonstration of a double dissociation between both neglect forms suggests that both rely on different central mechanisms. In addition, perceptual neglect can be selectively observed within personal space or extrapersonal space. However, it is not known whether the latter dissociation also exists in representational neglect. Methods: The authors investigated this question in two brain-damaged patients with anatomically different lesions sites, using neuropsychological tests specifically designed to assess perceptual and representational neglect in both personal and extrapersonal space. Results: Patients presented a double dissociation with respect to personal and extrapersonal space in representational neglect. Conclusions: These data suggest that the cerebral networks that process mental space representation use similar principles of space compartmentalization as those used by cerebral networks processing perceived space.展开更多
Background Metformin is the most widely used anti-diabetic drug in the world.An increasing body of evidence shows metformin also blocks cell cycle progression and selectively induces apoptosis via caspase activation i...Background Metformin is the most widely used anti-diabetic drug in the world.An increasing body of evidence shows metformin also blocks cell cycle progression and selectively induces apoptosis via caspase activation in some breast tumor cells.Diffusion-weighted imaging （DWl） and bioluminescence imaging （BLI） have great potential in the evaluation of the early response to cancer therapies.We used DWl and BLI in evaluating the response of breast cancer to metformin.Methods The luciferase-engineered human breast cancer cell line MDA-MB-231 was inoculated into the mammary fat pad of nude mice.Twelve female nude mice bearing tumors were divided into two groups.The mice in the treatment group received metformin （2 mg/ml in drinking water daily） after tumor inoculation,and the mice in the control group were offered drinking water without any drug added.We performed 7T magnetic resonance imaging and optical imaging every week.Imaging included T1-and T2-weighted imaging,DWl,and BLI.After imaging.The tumors were collected and subjected to histological analysis.Results The mean photons/second of tumors in the treatment group was （3.00±0.43）×106 at day one,（1.01±0.14）×107 at 2 weeks,（5.79±1.42）×107 at 4 weeks,and （2.33±0.70）×107 at 8 weeks.The mean photons/second of tumors in the control group was （3.29±0.59）×106 at day one,（3.59±0.63）×107 at 2 weeks,（3.87±0.56）×108 at 4 weeks,and （4.12±1.72）x108 at 8 weeks.Compared to the control group,the treatment group showed an obvious decrease in the mean bioluminescence （photons/s） of the tumors and fewer metastases.Histological examination confirmed the presence of fewer metastases.DWI showed the apparent diffusion coefficient （ADC） value of the tumors; the mean ADC value was （0.9287±0.04346）x10-3 mm2/s in the treated tumors and （0.7553±0.01804）x103 mm2/s in the untreated tumors.The ADC value of tumors in the treatment group was significantly higher than the control tumors （P=0.0013）.Conclusions The growth and metastasis of MDA-MB-231 breast cancer may be inhibited by metformin.DWI and BLI have great potentials in the evaluation of the early response to metformin treatment.BLI has a high degree of sensitivity and is able to detect micrometastasis,thus can be used for identifying tumor metastasis in vivo.展开更多
基金supported by the National Natural Science Foundation of China (Nos.51273122,51872190)Sichuan Science and Technology Project (No.2018JY0535)supported by the Fundamental of Research Funds for the Central University (Nos.SCU2017A001,2018SCUH0024)
文摘It is urgent to find a technology accurately to better diagnose and treat to brain tumor.Eu-doped Gd2 O3 nanorods(Eu-Gd2 O3 NRs)with paramagnetic and fluorescent properties were conjugated with doxorubicin(Dox)and chlorotoxin(CTX)via PEGylation,hydrazone bond and sulfur bond(named as CTXNRs-Dox),and these NRs could release more Dox in lower pH environment.The results of cell experiments indicated that CTX-NRs-Dox had obvious targeting and toxic effects on U251 cells,as well as good fluorescence imaging behavior.The orthotopic glioma-transplanted mice models were constructed via the intracranial injection of glioma cells(U87 MG).The result of experiments after the tail-vein injection of the prepared NRs suggested that CTX-NRs-Dox could target to brain tumors via the long-time blood circulation,leading to their obvious contrast enhancement of MR imaging of the intracranial tumor and their significant inhibitory effect on the growth and metastasis of brain tumors.A mechanism of synergistic effect of CTX-NRs-Dox on targeting and inhabiting the brain tumor was proposed.Our research suggested that CTX-NRs-Dox had potential application prospect in the detection and treatment of glioma.
基金supported by the National Natural Science Foundation of China(82171908 and 82102015)the General Project of the Nanjing Medical Science and Technology Development Program(YKK21075)the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515140030).
文摘Background:Platinum can cause chemotherapy-related cognitive impairment.Low-intensity focused ultrasound(LIFUS)is a promising noninvasive physical stimulation method with a unique advantage in neurological rehabilitation.We aimed to investigate whether LIFUS can alleviate cisplatin-induced cognitive impairment in rats and explore the related neuropatho-logical mechanisms.Methods:After confirming the target position for LIFUS treatment in 18 rats,64 rats were randomly divided into four groups:control,model,sham,and LIFUS groups.Before and after LIFUS treatment,detailed biological behavioral assessments and magnetic resonance imaging were performed.Finally,the rats were euthanized,and relevant histopathological and molecular biological experiments were conducted and analyzed.Results:In the Morris water maze,the model group showed fewer platform crossings(1.250.93 vs.5.691.58),a longer escape latency(41.6536.55 s vs.6.382.11 s),and a lower novel object recognition index(29.7711.83 vs.83.695.67)than the control group.LIFUS treatment improved these metrics,with more platform crossings(3.130.34),a higher recognition index(65.588.71),and a shorter escape latency(6.452.27 s).Longitudinal analysis of the LIFUS group further confirmed these improvements.Neuroimaging revealed significant differences in diffusion tensor imaging metrics of specific brain regions pre-and post-LIFUS.Moreover,neuropathology showed higher dendritic spine density,less myelin loss,fewer apoptotic cells,more synapses,and less mitochondrial autophagy after LIFUS treatment.The neuroimaging indicators were correlated with behavioral improvements,highlighting the potential of LIFUS for alleviating cognitive impairment(as demonstrated through imaging and analysis).Our investigation of the molecular biological mechanisms revealed distinct protein expression patterns in the hippocampus and its subregions.In the model group,glial fibrillary acidic protein(GFAP)and ionized calcium-binding adaptor molecule 1(IBA1)expression levels were elevated across the hippocampus,whereas neuronal nuclei(NeuN)expression was reduced.Subregional analysis revealed higher GFAP and IBA1 and lower NeuN,especially in the dentate gyrus subregion.Moreover,positive cell areas were larger in the cornu ammonis(CA)1,CA2,CA3,and dentate gyrus regions.In the CA2 and CA3,significant differences among the groups were observed in GFAP-positive cell counts and areas,and there were variations in NeuN expression.Conclusions:Our results suggest that LIFUS can reverse cisplatin-induced cognitive impairments.The neuroimaging findings were consistent with the behavioral and histological results and suggest a neuropathological basis that supports further research into the clinical applications of LIFUS.Furthermore,LIFUS appeared to enhance the plasticity of neuronal synapses in the rat hippocampus and reduce hippocampal inflammation.These findings highlight the clinical potential of LIFUS as an effective,noninvasive therapeutic strategy and monitoring tool for chemotherapy-induced cognitive deficits.
基金partly funded by the Clinician-Scientist grant(No.472-0-0)by the medical faculty of the University of Tübingen(to SCV).
文摘Ambroxol hydrochloride(2-amino-3,5-dibromo-N-methylbenzylamine hydrochloride)has been used as a mucolytic agent in the treatment of respiratory diseases since the late 1970s.Its effects on mucus membranes such as mucus disruption,increased mucus production,and low toxicity profile were addressed in its original German patent in 1966.These first described properties have kept Ambroxol available worldwide and over the counter in the pharmaceutical market to this day.
文摘Positron emission tomography(PET)has been successfully applied to an increasing number of cardiovascular conditions.This review will highlight the status of cardiovascular PET,including the present state of the art and the expanding pool of clinical evidence guiding its use.Additionally,we highlight upcoming developments in the fi eld,including the development of new tracers and applications of PET to novel indications within cardiovascular medicine.
文摘Purpose: To determine the relationship between the dental root indentation and maxillary sinusitis. Methods: We assessed the records of the patients who underwent paranasal sinus computed tomography imaging for suspected sinusitis. Results: We identified a total of 52 patients with a pre-diagnosis of maxillary sinusitis. Dental indentation was detected in 58 of 104 (55.7%) sinuses. Forty six of 58 sinuses (79.3%) with dental indentation had mucosal thickening higher than 2 mm. The difference between the groups was statistically significant (p = 0.007). Conclusion: Dental indentation should be kept in mind as a reason for chronic maxillary sinus inflammation, if an underlying cause cannot be identified.
文摘Background: Although perceptual and representational neglect are frequently associated, the demonstration of a double dissociation between both neglect forms suggests that both rely on different central mechanisms. In addition, perceptual neglect can be selectively observed within personal space or extrapersonal space. However, it is not known whether the latter dissociation also exists in representational neglect. Methods: The authors investigated this question in two brain-damaged patients with anatomically different lesions sites, using neuropsychological tests specifically designed to assess perceptual and representational neglect in both personal and extrapersonal space. Results: Patients presented a double dissociation with respect to personal and extrapersonal space in representational neglect. Conclusions: These data suggest that the cerebral networks that process mental space representation use similar principles of space compartmentalization as those used by cerebral networks processing perceived space.
基金This work was supported by a grant from the Major State Basic Research Development of China （973 Program, No. 2011 CB935800） and National Natural Science Foundation of China （No. 81130027 and No. 81071204）.
文摘Background Metformin is the most widely used anti-diabetic drug in the world.An increasing body of evidence shows metformin also blocks cell cycle progression and selectively induces apoptosis via caspase activation in some breast tumor cells.Diffusion-weighted imaging （DWl） and bioluminescence imaging （BLI） have great potential in the evaluation of the early response to cancer therapies.We used DWl and BLI in evaluating the response of breast cancer to metformin.Methods The luciferase-engineered human breast cancer cell line MDA-MB-231 was inoculated into the mammary fat pad of nude mice.Twelve female nude mice bearing tumors were divided into two groups.The mice in the treatment group received metformin （2 mg/ml in drinking water daily） after tumor inoculation,and the mice in the control group were offered drinking water without any drug added.We performed 7T magnetic resonance imaging and optical imaging every week.Imaging included T1-and T2-weighted imaging,DWl,and BLI.After imaging.The tumors were collected and subjected to histological analysis.Results The mean photons/second of tumors in the treatment group was （3.00±0.43）×106 at day one,（1.01±0.14）×107 at 2 weeks,（5.79±1.42）×107 at 4 weeks,and （2.33±0.70）×107 at 8 weeks.The mean photons/second of tumors in the control group was （3.29±0.59）×106 at day one,（3.59±0.63）×107 at 2 weeks,（3.87±0.56）×108 at 4 weeks,and （4.12±1.72）x108 at 8 weeks.Compared to the control group,the treatment group showed an obvious decrease in the mean bioluminescence （photons/s） of the tumors and fewer metastases.Histological examination confirmed the presence of fewer metastases.DWI showed the apparent diffusion coefficient （ADC） value of the tumors; the mean ADC value was （0.9287±0.04346）x10-3 mm2/s in the treated tumors and （0.7553±0.01804）x103 mm2/s in the untreated tumors.The ADC value of tumors in the treatment group was significantly higher than the control tumors （P=0.0013）.Conclusions The growth and metastasis of MDA-MB-231 breast cancer may be inhibited by metformin.DWI and BLI have great potentials in the evaluation of the early response to metformin treatment.BLI has a high degree of sensitivity and is able to detect micrometastasis,thus can be used for identifying tumor metastasis in vivo.
