The development of microenvironment-responsive nanoprobes has shown great promise for use in magnetic resonance imaging(MRI),with the advantage of significantly improved specificity and good biocompatibility.However,t...The development of microenvironment-responsive nanoprobes has shown great promise for use in magnetic resonance imaging(MRI),with the advantage of significantly improved specificity and good biocompatibility.However,the clinical application of responsive probes is hampered by a lack of biological sensitivity for early molecular diagnostics and visualizing microenvionment of metabolism reprogramming in tumor progression.Here,we report on a dual-ratiometric magnetic resonance tunable(DMRT)nanoprobe designed by crosslinking different ratios of transferrin chelating gadolinium and superparamagnetic nanoparticles,complexed to a pH responsive biocompatible polymer.This dually activatable nanoprobe enables pH-dependent tumor microenvironment visualization,providing exceptional quantitative pathophysiological information in vitro and in vivo.When used in combination with dual-contrast enhancement triple subtraction imaging technique(DETSI),this smart nanoprobe guarantees the diagnosis of early-stage diseases.We envisage that this novel integrated nanoplatform will provide a new paradigm for the clinical translation of robust DMRT nanoprobes for early disease detection and staging,as well as microenvironment visualization and disease progression monitoring.展开更多
BACKGROUND:The plasma concentration of paraquat is closely related to the prognosis of patients with paraquat toxication,and the most common cause of death from paraquat poisoning is multiple organ failure(MOF).This s...BACKGROUND:The plasma concentration of paraquat is closely related to the prognosis of patients with paraquat toxication,and the most common cause of death from paraquat poisoning is multiple organ failure(MOF).This study aimed to evaluate therapeutic effect of smecta on the plasma concentrations of paraquat and multi-organ injury induced by paraquat intoxication in rats.METHODS:A total of 76 healthy adult SD rats were randomly divided into group A(control group,/7=6),group B(poisoned group,n=30) and group C(smecta-treated group,n=30).Rats in groups B and C were treated intragastrically with PQ at 50 mg/kg,and rats in group A was treated intragastrically with saline(1 ml_).Rats in group C were given intragastrically smecta at 400 mg/kg 10 minutes after administration of PQ,while rats in other two groups were treated intragastrically with 1ml_ saline at the same time.Live rats in groups B and C were sacrificed at 2,6,24,48,72 hours after administration of PQ for the determination of paraquat plasma concentrations and for HE staining of the lung,stomach and jejunum.The rats were executed at the end of trial by the same way in group A.RESULTS:The plasma concentration of paraquat(ng/mL) ranged from 440.314±49.776 to4320.6150±413.947.Distinctive pathological changes were seen in the lung,stomach and jejunum in group B.Lung injuries deteriorated gradually,edema,leukocyte infiltration,pneumorrhagia,incrassated septa and lung consolidation were observed.Abruption of mucosa,hyperemic gastric mucosa and leukocyte infiltration were obvious in the stomach.The hemorrhage of jejunum mucosa,the abruption of villus,the gland damage with the addition of inflammatory cell infiltration were found.Compared to group B,the plasma concentration of paraquat reduced(P<0.01) and the pathological changes mentioned above were obviously alleviated in group C(P<0.05,P<0.01).CONCLUSION:Smecta reduced the plasma concentration of paraquat and alleviated pathologic injury of rats with PQ poisoning.展开更多
There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts.Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been cruci...There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts.Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface;however,studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models.Here,we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status.Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment.Furthermore,the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment,and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed.In addition to inducing aberrant morphology of small intestinal villi,the depletion of gut commensal bacteria led to increased proportions of CD3+T,CD4+T,and CD16+NK cells in peripheral blood mononuclear cells(PBMCs),but decreased numbers of Treg and CD20+B cells.The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes,including IL-13,VCAM1,and LGR4.展开更多
On March 3,2020,the National Health Commission and the National Administration of Traditional Chinese Medicine of China jointly promulgated the Notice on Printing and Distributing the Diagnosis and Treatment Protocol ...On March 3,2020,the National Health Commission and the National Administration of Traditional Chinese Medicine of China jointly promulgated the Notice on Printing and Distributing the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia(Trial Version 7).The content has been revised and supplemented on the basis of the Version 6,including etiological characteristics and pathological changes in lung,heart,kidney,spleen,liver,gallbladder,esophagus,stomach and intestinal mucosal epithelium.In particular,the diagnosis and treatment methods of traditional Chinese medicine are supplemented.It provides an evidence-based diagnosis and treatment protocol for the treatment and recovery of suspected and confirmed cases of novel coronavirus pneumonia with traditional Chinese medicine and Western medicine.展开更多
Since December 2019,the novel coronavirus(severe acute respiratory syndrome coronavirus 2(SARS-CoV-2))has spread to many countries around the world,developing into a global pandemic with increasing numbers of deaths r...Since December 2019,the novel coronavirus(severe acute respiratory syndrome coronavirus 2(SARS-CoV-2))has spread to many countries around the world,developing into a global pandemic with increasing numbers of deaths reported worldwide.To data,although some vaccines have been developed,there are no ideal drugs to treat novel coronavirus pneumonia(coronavirus disease 2019(COVID-19)).By examining the structure of the coronavirus and briefly describing its possible pathogenesis based on recent autopsy reports conducted by various teams worldwide,this review analyzes the possible structural and functional changes of the human body upon infection with SARS-CoV-2.We observed that the most prominent pathological changes in COVID-19 patients are diffuse alveolar damage(DAD)of the lungs and microthrombus formation,resulting in an imbalance of the ventilation/perfusion ratio and respiratory failure.Although direct evidence of viral infection can also be found in other organs and tissues,the viral load is relatively small.The conclusion that the injuries of the extrapulmonary organs are directly caused by the virus needs further investigation.展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.81971664 and 82272057)the Shanghai Pujiang Program(No.2019PJD044).
文摘The development of microenvironment-responsive nanoprobes has shown great promise for use in magnetic resonance imaging(MRI),with the advantage of significantly improved specificity and good biocompatibility.However,the clinical application of responsive probes is hampered by a lack of biological sensitivity for early molecular diagnostics and visualizing microenvionment of metabolism reprogramming in tumor progression.Here,we report on a dual-ratiometric magnetic resonance tunable(DMRT)nanoprobe designed by crosslinking different ratios of transferrin chelating gadolinium and superparamagnetic nanoparticles,complexed to a pH responsive biocompatible polymer.This dually activatable nanoprobe enables pH-dependent tumor microenvironment visualization,providing exceptional quantitative pathophysiological information in vitro and in vivo.When used in combination with dual-contrast enhancement triple subtraction imaging technique(DETSI),this smart nanoprobe guarantees the diagnosis of early-stage diseases.We envisage that this novel integrated nanoplatform will provide a new paradigm for the clinical translation of robust DMRT nanoprobes for early disease detection and staging,as well as microenvironment visualization and disease progression monitoring.
文摘BACKGROUND:The plasma concentration of paraquat is closely related to the prognosis of patients with paraquat toxication,and the most common cause of death from paraquat poisoning is multiple organ failure(MOF).This study aimed to evaluate therapeutic effect of smecta on the plasma concentrations of paraquat and multi-organ injury induced by paraquat intoxication in rats.METHODS:A total of 76 healthy adult SD rats were randomly divided into group A(control group,/7=6),group B(poisoned group,n=30) and group C(smecta-treated group,n=30).Rats in groups B and C were treated intragastrically with PQ at 50 mg/kg,and rats in group A was treated intragastrically with saline(1 ml_).Rats in group C were given intragastrically smecta at 400 mg/kg 10 minutes after administration of PQ,while rats in other two groups were treated intragastrically with 1ml_ saline at the same time.Live rats in groups B and C were sacrificed at 2,6,24,48,72 hours after administration of PQ for the determination of paraquat plasma concentrations and for HE staining of the lung,stomach and jejunum.The rats were executed at the end of trial by the same way in group A.RESULTS:The plasma concentration of paraquat(ng/mL) ranged from 440.314±49.776 to4320.6150±413.947.Distinctive pathological changes were seen in the lung,stomach and jejunum in group B.Lung injuries deteriorated gradually,edema,leukocyte infiltration,pneumorrhagia,incrassated septa and lung consolidation were observed.Abruption of mucosa,hyperemic gastric mucosa and leukocyte infiltration were obvious in the stomach.The hemorrhage of jejunum mucosa,the abruption of villus,the gland damage with the addition of inflammatory cell infiltration were found.Compared to group B,the plasma concentration of paraquat reduced(P<0.01) and the pathological changes mentioned above were obviously alleviated in group C(P<0.05,P<0.01).CONCLUSION:Smecta reduced the plasma concentration of paraquat and alleviated pathologic injury of rats with PQ poisoning.
基金supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2016-I2M-1-014)
文摘There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts.Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface;however,studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models.Here,we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status.Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment.Furthermore,the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment,and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed.In addition to inducing aberrant morphology of small intestinal villi,the depletion of gut commensal bacteria led to increased proportions of CD3+T,CD4+T,and CD16+NK cells in peripheral blood mononuclear cells(PBMCs),but decreased numbers of Treg and CD20+B cells.The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes,including IL-13,VCAM1,and LGR4.
基金The 3rd Session of National TCM Master/National Famous TCM Doctor Inheritance Studio Construction Project of National Administration of Traditional Chinese Medicine[Guo Zhong Yi Yao Ban Ren Jiao Han(2018)119].
文摘On March 3,2020,the National Health Commission and the National Administration of Traditional Chinese Medicine of China jointly promulgated the Notice on Printing and Distributing the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia(Trial Version 7).The content has been revised and supplemented on the basis of the Version 6,including etiological characteristics and pathological changes in lung,heart,kidney,spleen,liver,gallbladder,esophagus,stomach and intestinal mucosal epithelium.In particular,the diagnosis and treatment methods of traditional Chinese medicine are supplemented.It provides an evidence-based diagnosis and treatment protocol for the treatment and recovery of suspected and confirmed cases of novel coronavirus pneumonia with traditional Chinese medicine and Western medicine.
基金supported by the National Key R&D Program of China(No.2018YFC1105100)the Zhejiang Provincial Natural Science Foundation of China(No.LY19H090021)。
文摘Since December 2019,the novel coronavirus(severe acute respiratory syndrome coronavirus 2(SARS-CoV-2))has spread to many countries around the world,developing into a global pandemic with increasing numbers of deaths reported worldwide.To data,although some vaccines have been developed,there are no ideal drugs to treat novel coronavirus pneumonia(coronavirus disease 2019(COVID-19)).By examining the structure of the coronavirus and briefly describing its possible pathogenesis based on recent autopsy reports conducted by various teams worldwide,this review analyzes the possible structural and functional changes of the human body upon infection with SARS-CoV-2.We observed that the most prominent pathological changes in COVID-19 patients are diffuse alveolar damage(DAD)of the lungs and microthrombus formation,resulting in an imbalance of the ventilation/perfusion ratio and respiratory failure.Although direct evidence of viral infection can also be found in other organs and tissues,the viral load is relatively small.The conclusion that the injuries of the extrapulmonary organs are directly caused by the virus needs further investigation.
