Intestinal failure-associated liver disease(IFALD)is a common complication of long-term parenteral nutrition that is associated with significant morbidity and mortality.It is mainly characterized by cholestasis in chi...Intestinal failure-associated liver disease(IFALD)is a common complication of long-term parenteral nutrition that is associated with significant morbidity and mortality.It is mainly characterized by cholestasis in children and steatohepatitis in adults.Unfortunately,there is no effective approach to prevent or reverse the disease.Regulated cell death(RCD)represents a fundamental biological paradigm that determines the outcome of a variety of liver diseases.Nowadays cell death is reclassified into several types,based on the mechanisms and morphological phenotypes.Emerging evidence has linked different modes of RCD,such as apoptosis,necroptosis,ferroptosis,and pyroptosis to the pathogenesis of liver diseases.Recent studies have shown that different modes of RCD are present in animal models and patients with IFALD.Understanding the pathogenic roles of cell death may help uncover the underlying mechanisms and develop novel therapeutic strategies in IFALD.In this review,we discuss the current knowledge on how RCD may link to the pathogenesis of IFALD.We highlight examples of cell death-targeted interventions aiming to attenuate the disease,and provide perspectives for future basic and translational research in the field.展开更多
AIM： To compare the incidence of persistent submacular fluid（SMF） and visual outcome after pars plana vitrectomy（PPV） for rhegmatogenous retinal detachment（RRD） in different preoperative macular status accordin...AIM： To compare the incidence of persistent submacular fluid（SMF） and visual outcome after pars plana vitrectomy（PPV） for rhegmatogenous retinal detachment（RRD） in different preoperative macular status according to optical coherence tomography（OCT）.METHODS： A non-randomized, retrospective review was performed for patients who underwent successful PPV for RRD. OCT exams were taken preoperatively and 1 mo after surgery, until SMF disappeared. According to the preoperative macular status on OCT, patients were divided into two groups： macula-off RRD（Group A） and maculaon RRD（Group B）. In Group A, there were two subgroups： macula partly detached（Group A1） and macula totally detached（Group A2）. The main outcome measures were the presence of SMF on OCT 1 mo after surgery, and the preoperative and postoperative best corrected visual acuities（BCVA）, among the different groups and depending on the presence or absence of persistent SMF.RESULTS： A total of 139 eyes of 139 patients were included in the study. Persistent SMF at 1 mo after surgery was 15.8%（22/139）, all occurring in Group A（22/101）; Group B had no SMF at 1 mo after surgery（0/38, P=0.002）. The incidence of persistent SMF at 1 mo after surgery in Group A1 was 50%（14/28）, and in Group A2 was 11.0%（8/73, P〈0.001）. Significant differences were shown between the presence and absence of persistent SMF on foveolaoff RRD, the preoperative BCVA, the 1 mo postoperative BCVA, and the degree of the BCVA improvement from 1 mo postoperatively to the final follow-up（P〈0.05）. However, there were no significant differences in the final BCVA（P〉0.05）.CONCLUSION： Persistent SMF after PPV for retinal detachment is associated with preoperative macular status. Macula-uninvolving RRD shows no persistent SMF after PPV. Macular partly detached RRD has a higher incidence of SMF than macula totally detached RRD after PPV. The persistence of SMF may be responsible for the delayed visual recovery, whereas there were no significant differences in the final visual acuity.展开更多
Intestinal failure-associated liver disease(IFALD)is a common hepatobiliary complication resulting from long-term parenteral nutrition(PN)in patients with intestinal failure.The spectrum of IFALD ranges from cholestas...Intestinal failure-associated liver disease(IFALD)is a common hepatobiliary complication resulting from long-term parenteral nutrition(PN)in patients with intestinal failure.The spectrum of IFALD ranges from cholestasis,steatosis,portal fibrosis,to cirrhosis.Development of IFALD is a multifactorial process,in which gut dysbiosis plays a critical role in its initiation and progression in conjunction with increased intestinal permeability,activation of hepatic immune responses,and administration of lipid emulsion.Gut microbiota manipulation including pre/probiotics,fecal microbiota transplantation,and antibiotics has been studied in IFALD with varying success.In this review,we summarize current knowledge on the taxonomic and functional changes of gut microbiota in preclinical and clinical studies of IFALD.We also review the function of microbial metabolites and associated signalings in the context of IFALD.By providing microbiota-targeted interventions aiming to optimize PN-induced liver injury,our review provides perspectives for future basic and translational investigations in the field.展开更多
The canine parvovirus disease is an acute infectious disease caused by canine parvovirus(CPV). It is clinically characterized by severe vomiting,hemorrhagic enteritis,significant reduction in white blood cells and myo...The canine parvovirus disease is an acute infectious disease caused by canine parvovirus(CPV). It is clinically characterized by severe vomiting,hemorrhagic enteritis,significant reduction in white blood cells and myocarditis. The disease with high incidence,highly infectious and high mortality has become one of the serious infectious diseases threatening dog raising industry in China. In this research,260 cases of canine parvovirus case from an Aite Pet Clinic in Taizhou City during January 2010 and March 2011 were analyzed. This study discloses the epidemiology of CPV in Taizhou region of Jiangsu Province,i. e.,the incidence of CPV and canine motility are closely correlated with age,breed,immune inoculation and season. This study provides useful guide for the clinical treatment of CPV in the future.展开更多
Considering the bidirectional crosstalk along the gut-liver axis,gut-derived microorganisms and metabolites can be released into the liver,potentially leading to liver injury.In this editorial,we comment on several st...Considering the bidirectional crosstalk along the gut-liver axis,gut-derived microorganisms and metabolites can be released into the liver,potentially leading to liver injury.In this editorial,we comment on several studies published in the recent issue of the World Journal of Gastroenterology.We focus specifically on the roles of gut microbiota in selected gastrointestinal(GI)diseases that are prevalent,such as inflammatory bowel disease,metabolic dysfunction-associated steatotic liver disease,and hepatitis B virus-related portal hypertension.Over the past few decades,findings from both preclinical and clinical studies have indicated an association between compositional and metabolic changes in the gut microbiota and the pathogenesis of the aforementioned GI disorders.However,studies elucidating the mechanisms underlying the host-microbiota interactions remain limited.The purpose of this editorial is to summarize current findings and provide insights regarding the context-specific roles of gut microbiota.Ultimately,the discovery of microbiome-based biomarkers may facilitate disease diagnosis and the development of personalized medicine.展开更多
Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of actio...Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii.Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components,namely quercetin,β-sitosterol,stigmasterol,7-Omethylluteolin-6-C-beta-glucoside_qt,atropine,and glycitein,were identified to have potency in improving exercise fatigue via multiple pathways,such as the PI3K-Akt,neuroactive ligand-receptor interaction,IL-17,TNF,and MAPK signaling pathways.The immunofluorescence results indicated that quercetin,a significant active component in Fructus lycii,increased the mean staining area of 2-NBDG,TMRM,and MitoTracker,and decreased the area of CellRox compared to the control.Furthermore,the protein expression levels of p-38 MAPK,p-MAPK,p-JNK,p-PI3K,and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways.Among these,quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress.The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.展开更多
Oral squamous cell carcinoma(OSCC)associated pain commonly predicts adverse events among patients.This clinical feature indicates the engagement of nociceptors on sensory neurons during the development of malignancy.H...Oral squamous cell carcinoma(OSCC)associated pain commonly predicts adverse events among patients.This clinical feature indicates the engagement of nociceptors on sensory neurons during the development of malignancy.However,it is yet to be determined if targeting oncometabolite-associated nociception processes can hinder OSCC progression.In this study,we reported that nociceptive endings infiltrating both clinical samples and mouse tumor xenografts were associated with poorer clinical outcomes and drove tumor progression in vivo,as evidenced by clinical tissue microarray analysis and murine lingual denervation.We observed that the OSCC microenvironment was characteristic of excessive adenosine due to CD73 upregulation which negatively predicted clinical outcomes in the TCGA-HNSC patient cohort.Notably,such adenosine concentrative OSCC niche was associated with the stimulation of adenosine A2Areceptor(A2AR)on trigeminal ganglia.Antagonism of trigeminal A2AR with a selective A2AR inhibitor SCH58261 resulted in impeded OSCC growth in vivo.We showed that trigeminal A2AR overstimulation in OSCC xenograft did not entail any changes in the transcription level of CGRP in trigeminal ganglia but significantly triggered the release of CGRP,an effect counteracted by SCH58261.We further demonstrated the pro-tumor effect of CGRP by feeding mice with the clinically approved CGRP receptor antagonist rimegepant which inhibited the activation of ERK and YAP.Finally,we diminished the impact of CGRP on OSCC with istradefylline,a clinically available drug that targets neuronal A2AR.Therefore,we established trigeminal A2AR-mediated CGRP release as a promising druggable circuit in OSCC treatment.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(82100950,81974066)Foundation of Shanghai Municipal Health Commission(shslczdzk05702).
文摘Intestinal failure-associated liver disease(IFALD)is a common complication of long-term parenteral nutrition that is associated with significant morbidity and mortality.It is mainly characterized by cholestasis in children and steatohepatitis in adults.Unfortunately,there is no effective approach to prevent or reverse the disease.Regulated cell death(RCD)represents a fundamental biological paradigm that determines the outcome of a variety of liver diseases.Nowadays cell death is reclassified into several types,based on the mechanisms and morphological phenotypes.Emerging evidence has linked different modes of RCD,such as apoptosis,necroptosis,ferroptosis,and pyroptosis to the pathogenesis of liver diseases.Recent studies have shown that different modes of RCD are present in animal models and patients with IFALD.Understanding the pathogenic roles of cell death may help uncover the underlying mechanisms and develop novel therapeutic strategies in IFALD.In this review,we discuss the current knowledge on how RCD may link to the pathogenesis of IFALD.We highlight examples of cell death-targeted interventions aiming to attenuate the disease,and provide perspectives for future basic and translational research in the field.
基金Supported by the Platform Key Project of Medical Scientific Research Foundation of Zhejiang Province (No.2016ZDA016)
文摘AIM： To compare the incidence of persistent submacular fluid（SMF） and visual outcome after pars plana vitrectomy（PPV） for rhegmatogenous retinal detachment（RRD） in different preoperative macular status according to optical coherence tomography（OCT）.METHODS： A non-randomized, retrospective review was performed for patients who underwent successful PPV for RRD. OCT exams were taken preoperatively and 1 mo after surgery, until SMF disappeared. According to the preoperative macular status on OCT, patients were divided into two groups： macula-off RRD（Group A） and maculaon RRD（Group B）. In Group A, there were two subgroups： macula partly detached（Group A1） and macula totally detached（Group A2）. The main outcome measures were the presence of SMF on OCT 1 mo after surgery, and the preoperative and postoperative best corrected visual acuities（BCVA）, among the different groups and depending on the presence or absence of persistent SMF.RESULTS： A total of 139 eyes of 139 patients were included in the study. Persistent SMF at 1 mo after surgery was 15.8%（22/139）, all occurring in Group A（22/101）; Group B had no SMF at 1 mo after surgery（0/38, P=0.002）. The incidence of persistent SMF at 1 mo after surgery in Group A1 was 50%（14/28）, and in Group A2 was 11.0%（8/73, P〈0.001）. Significant differences were shown between the presence and absence of persistent SMF on foveolaoff RRD, the preoperative BCVA, the 1 mo postoperative BCVA, and the degree of the BCVA improvement from 1 mo postoperatively to the final follow-up（P〈0.05）. However, there were no significant differences in the final BCVA（P〉0.05）.CONCLUSION： Persistent SMF after PPV for retinal detachment is associated with preoperative macular status. Macula-uninvolving RRD shows no persistent SMF after PPV. Macular partly detached RRD has a higher incidence of SMF than macula totally detached RRD after PPV. The persistence of SMF may be responsible for the delayed visual recovery, whereas there were no significant differences in the final visual acuity.
基金This study was supported by grants from the National Natural Science Foundation of China(82100950)Shanghai Natural Sci-ence Foundation(23ZR1452600).
文摘Intestinal failure-associated liver disease(IFALD)is a common hepatobiliary complication resulting from long-term parenteral nutrition(PN)in patients with intestinal failure.The spectrum of IFALD ranges from cholestasis,steatosis,portal fibrosis,to cirrhosis.Development of IFALD is a multifactorial process,in which gut dysbiosis plays a critical role in its initiation and progression in conjunction with increased intestinal permeability,activation of hepatic immune responses,and administration of lipid emulsion.Gut microbiota manipulation including pre/probiotics,fecal microbiota transplantation,and antibiotics has been studied in IFALD with varying success.In this review,we summarize current knowledge on the taxonomic and functional changes of gut microbiota in preclinical and clinical studies of IFALD.We also review the function of microbial metabolites and associated signalings in the context of IFALD.By providing microbiota-targeted interventions aiming to optimize PN-induced liver injury,our review provides perspectives for future basic and translational investigations in the field.
基金Supported by the Special Fund for Special Fund for Veterinary Public Health Security and Management Innovation Team of Chinese Academy of Agricultural Science and Technology Innovation Project(ASTIP-IAS11)the National High Technology Research and Development Program of China(2012AA101302)the Special Fund for Agro-scientific Research in the Public Interest(201303042)
文摘The canine parvovirus disease is an acute infectious disease caused by canine parvovirus(CPV). It is clinically characterized by severe vomiting,hemorrhagic enteritis,significant reduction in white blood cells and myocarditis. The disease with high incidence,highly infectious and high mortality has become one of the serious infectious diseases threatening dog raising industry in China. In this research,260 cases of canine parvovirus case from an Aite Pet Clinic in Taizhou City during January 2010 and March 2011 were analyzed. This study discloses the epidemiology of CPV in Taizhou region of Jiangsu Province,i. e.,the incidence of CPV and canine motility are closely correlated with age,breed,immune inoculation and season. This study provides useful guide for the clinical treatment of CPV in the future.
文摘Considering the bidirectional crosstalk along the gut-liver axis,gut-derived microorganisms and metabolites can be released into the liver,potentially leading to liver injury.In this editorial,we comment on several studies published in the recent issue of the World Journal of Gastroenterology.We focus specifically on the roles of gut microbiota in selected gastrointestinal(GI)diseases that are prevalent,such as inflammatory bowel disease,metabolic dysfunction-associated steatotic liver disease,and hepatitis B virus-related portal hypertension.Over the past few decades,findings from both preclinical and clinical studies have indicated an association between compositional and metabolic changes in the gut microbiota and the pathogenesis of the aforementioned GI disorders.However,studies elucidating the mechanisms underlying the host-microbiota interactions remain limited.The purpose of this editorial is to summarize current findings and provide insights regarding the context-specific roles of gut microbiota.Ultimately,the discovery of microbiome-based biomarkers may facilitate disease diagnosis and the development of personalized medicine.
基金funded by China’s National Key R&D Programmers for“Hi-Tech Winter Olympics”Special Project[2020YFF0305001]。
文摘Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii.Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components,namely quercetin,β-sitosterol,stigmasterol,7-Omethylluteolin-6-C-beta-glucoside_qt,atropine,and glycitein,were identified to have potency in improving exercise fatigue via multiple pathways,such as the PI3K-Akt,neuroactive ligand-receptor interaction,IL-17,TNF,and MAPK signaling pathways.The immunofluorescence results indicated that quercetin,a significant active component in Fructus lycii,increased the mean staining area of 2-NBDG,TMRM,and MitoTracker,and decreased the area of CellRox compared to the control.Furthermore,the protein expression levels of p-38 MAPK,p-MAPK,p-JNK,p-PI3K,and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways.Among these,quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress.The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.
基金National Natural Science Foundation of China(82170971,82373187and 82002888)Fundamental Research Funds for the Central Universities(YJ201987)+2 种基金Sichuan Science and Technology Program(2021ZYD0090 and 2022YFS0207)Scientific Research Foundation,West China Hospital of Stomatology Sichuan University(QDJF2019-3 and RD-03-202110)CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-004)。
文摘Oral squamous cell carcinoma(OSCC)associated pain commonly predicts adverse events among patients.This clinical feature indicates the engagement of nociceptors on sensory neurons during the development of malignancy.However,it is yet to be determined if targeting oncometabolite-associated nociception processes can hinder OSCC progression.In this study,we reported that nociceptive endings infiltrating both clinical samples and mouse tumor xenografts were associated with poorer clinical outcomes and drove tumor progression in vivo,as evidenced by clinical tissue microarray analysis and murine lingual denervation.We observed that the OSCC microenvironment was characteristic of excessive adenosine due to CD73 upregulation which negatively predicted clinical outcomes in the TCGA-HNSC patient cohort.Notably,such adenosine concentrative OSCC niche was associated with the stimulation of adenosine A2Areceptor(A2AR)on trigeminal ganglia.Antagonism of trigeminal A2AR with a selective A2AR inhibitor SCH58261 resulted in impeded OSCC growth in vivo.We showed that trigeminal A2AR overstimulation in OSCC xenograft did not entail any changes in the transcription level of CGRP in trigeminal ganglia but significantly triggered the release of CGRP,an effect counteracted by SCH58261.We further demonstrated the pro-tumor effect of CGRP by feeding mice with the clinically approved CGRP receptor antagonist rimegepant which inhibited the activation of ERK and YAP.Finally,we diminished the impact of CGRP on OSCC with istradefylline,a clinically available drug that targets neuronal A2AR.Therefore,we established trigeminal A2AR-mediated CGRP release as a promising druggable circuit in OSCC treatment.
