Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progr...Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progressive skin ischemia,large areas of painful malodorous ulcers,and mummified legs.Because of the worsening symptoms and signs refractory to conventional therapies,treatment with human amnion-derived mesenchymal stem cells(hAMSCs)was approved.Preclinical release inspections of hAMSCs,efficacy,and safety assessment,including cytokine secretory ability,immunocompetence,tumorigenicity,and genetics analysis in vitro,were introduced.We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats,abnormal immune response tests in C57BL/6 mice,and tumorigenicity tests in neonatal Balbc-nu nude mice.After the preclinical research,the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers.When followed up to 15 months,the blood-based markers of bone and mineral metabolism improved,with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells.Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis,and 20 months later,the re-epithelialization restored the integrity of the damaged site.No infusion or local treatment-related adverse events occurred.Thus,this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,anti-inflammatory and immune modulation,multidifferentiation,re-epithelialization,and restoration of integrity.展开更多
Background:Crohn’s disease(CD)has a tendency for recurrence and requires adequate monitoring and personalized treatment.Since endoscopy is considerably invasive,serum biomarkers are required as alternatives for CD mo...Background:Crohn’s disease(CD)has a tendency for recurrence and requires adequate monitoring and personalized treatment.Since endoscopy is considerably invasive,serum biomarkers are required as alternatives for CD monitoring.Toward this,exosomal microRNAs(miRNAs)may serve as promising candidates.In this study,we aimed to assess the role of serum exosomal microRNA-144-3p(miR-144-3p)as a biomarker for CD monitoring.Methods:We prospectively recruited 154 patients without a history of surgery(Cohort 1)and 75 patients who were to undergo intestinal resection(Cohort 2).Serum samples were collected from Cohort 1 before colonoscopy and from Cohort 2 before surgery and during post-operative colonoscopic examination.The serum levels of exosomal miR-144-3p were measured using quantitative reverse-transcription polymerase chain reaction(PCR).Correlations between relative exosomal miR-144-3p levels,disease activity,and disease behavior were analysed.The area under the receiver-operating characteristic curve(AUC)was used to assess the predictive value of exosomal miR-144-3p regarding mucosal activity and postoperative recurrence.Results:A 3.33-fold increase in serum exosomal miR-144-3p levels was recorded in patients with CD compared with those in healthy controls(P<0.001).The exosomalmiR-144-3p levels were positively correlated with the simple endoscopic score of CD(q=0.547,P<0.001)as well as the Rutgeerts score(q=0.478,P<0.001).Elevated exosomalmiR-144-3p levels were correlated with the penetrating disease with high specificity(100%[95%confidence interval,95.1%–100%]).The accuracy of exosomalmiR-144-3p for identifying post-operative recurrence was higher than that of C-reactive protein(CRP)(AUC,0.775 vs 0.639;P<0.001).Conclusions:Serum exosomal miR-144-3p is a reliable biomarker of mucosal inflammation and penetrating CD.It may identify endoscopic CD recurrence after intestinal resection with higher accuracy than CRP testing.展开更多
Background:The natural disease course for patients with ulcerative colitis(UC)is heterogeneous and few data are available on the indolent course of UC and its related factors.We aimed to develop and validate a nomogra...Background:The natural disease course for patients with ulcerative colitis(UC)is heterogeneous and few data are available on the indolent course of UC and its related factors.We aimed to develop and validate a nomogramto predict indolent course in patients with UC.Methods:Data of patients diagnosed with UC in the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between April 2007 and February 2021 were retrospectively analysed.Indolent course was defined as a disease course without need for strict interventions(steroids,immunomodulators,biological agents,hospitalization,or surgery therapy)during the follow-up period.The whole cohort was randomly divided into training set and validation set.The nomogram was constructed in the training set based on the results of univariate and multivariate Cox regression analyses.The performance of the nomogram was assessed by the concordance index(C-index),area under the receiver-operating characteristic curve(AUC),and calibration plots.In addition,we internally validated the nomogramvia the bootstrap method and the validation set.Results:Of 969 treatment-naive patients with UC,771(79.6%)had an indolent course after diagnosis.Of these,313 patients were included in the development and validation of the nomogram.The nomogram incorporating age,disease activity,C-reactive protein,and platelet count showed good calibration and discrimination.The C-index was 0.759(0.741 in bootstrap validation)and the AUC at 2,4,and 6 years was 0.767,0.782,and 0.775,respectively.The nomogramperformed well when applied to the validation set.Conclusion:A majority of patients with UC had an indolent course after diagnosis.The nomogram developed in this study might be useful in therapeutic decision-making and follow-up management for patients with UC.展开更多
基金funded by the National Natural Science Foundation of China(81270408,81570666,81730041,and 81671447)the International Society of Nephrology(ISN)Clinical Research Program(18-01-0247)+7 种基金Construction Program of Jiangsu Provincial Clinical Research Center Support System(BL2014084)Jiangsu Province Key Medical Personnel Project(ZDRCA2016002)CKD Anemia Research Foundation from China International Medical Foundation(Z-2017-24-2037)Outstanding Young and Middle-Aged Talents Support Program of The First Affiliated Hospital of Nanjing Medical University(Jiangsu Province Hospital)the National Key Research and Development Program of China(2017YFC1001303)the Program of Jiangsu Province Clinical Medical Center(YXZXB2016001,BL2012009)the State Key Laboratory of Reproductive Medicine Program(SKLRM-GC201803)the Program of Jiangsu Commission of Health(H201605).
文摘Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progressive skin ischemia,large areas of painful malodorous ulcers,and mummified legs.Because of the worsening symptoms and signs refractory to conventional therapies,treatment with human amnion-derived mesenchymal stem cells(hAMSCs)was approved.Preclinical release inspections of hAMSCs,efficacy,and safety assessment,including cytokine secretory ability,immunocompetence,tumorigenicity,and genetics analysis in vitro,were introduced.We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats,abnormal immune response tests in C57BL/6 mice,and tumorigenicity tests in neonatal Balbc-nu nude mice.After the preclinical research,the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers.When followed up to 15 months,the blood-based markers of bone and mineral metabolism improved,with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells.Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis,and 20 months later,the re-epithelialization restored the integrity of the damaged site.No infusion or local treatment-related adverse events occurred.Thus,this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,anti-inflammatory and immune modulation,multidifferentiation,re-epithelialization,and restoration of integrity.
基金supported by the National Natural Science Foundation of China[grant numbers 81630018,82070538,,81870374]Guangdong Science and Technology Department[grant number 2017A030306021]Guangzhou Science and Technology Department[grant number 202002030041].
文摘Background:Crohn’s disease(CD)has a tendency for recurrence and requires adequate monitoring and personalized treatment.Since endoscopy is considerably invasive,serum biomarkers are required as alternatives for CD monitoring.Toward this,exosomal microRNAs(miRNAs)may serve as promising candidates.In this study,we aimed to assess the role of serum exosomal microRNA-144-3p(miR-144-3p)as a biomarker for CD monitoring.Methods:We prospectively recruited 154 patients without a history of surgery(Cohort 1)and 75 patients who were to undergo intestinal resection(Cohort 2).Serum samples were collected from Cohort 1 before colonoscopy and from Cohort 2 before surgery and during post-operative colonoscopic examination.The serum levels of exosomal miR-144-3p were measured using quantitative reverse-transcription polymerase chain reaction(PCR).Correlations between relative exosomal miR-144-3p levels,disease activity,and disease behavior were analysed.The area under the receiver-operating characteristic curve(AUC)was used to assess the predictive value of exosomal miR-144-3p regarding mucosal activity and postoperative recurrence.Results:A 3.33-fold increase in serum exosomal miR-144-3p levels was recorded in patients with CD compared with those in healthy controls(P<0.001).The exosomalmiR-144-3p levels were positively correlated with the simple endoscopic score of CD(q=0.547,P<0.001)as well as the Rutgeerts score(q=0.478,P<0.001).Elevated exosomalmiR-144-3p levels were correlated with the penetrating disease with high specificity(100%[95%confidence interval,95.1%–100%]).The accuracy of exosomalmiR-144-3p for identifying post-operative recurrence was higher than that of C-reactive protein(CRP)(AUC,0.775 vs 0.639;P<0.001).Conclusions:Serum exosomal miR-144-3p is a reliable biomarker of mucosal inflammation and penetrating CD.It may identify endoscopic CD recurrence after intestinal resection with higher accuracy than CRP testing.
基金supported by the National Natural Science Foundation of China[grant number 8210031148]the Guangdong Basic and Applied Basic Research Foundation[grant number 2020A1515111087]the China Postdoctoral Science Foundation[grant number 2021M703750].
文摘Background:The natural disease course for patients with ulcerative colitis(UC)is heterogeneous and few data are available on the indolent course of UC and its related factors.We aimed to develop and validate a nomogramto predict indolent course in patients with UC.Methods:Data of patients diagnosed with UC in the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between April 2007 and February 2021 were retrospectively analysed.Indolent course was defined as a disease course without need for strict interventions(steroids,immunomodulators,biological agents,hospitalization,or surgery therapy)during the follow-up period.The whole cohort was randomly divided into training set and validation set.The nomogram was constructed in the training set based on the results of univariate and multivariate Cox regression analyses.The performance of the nomogram was assessed by the concordance index(C-index),area under the receiver-operating characteristic curve(AUC),and calibration plots.In addition,we internally validated the nomogramvia the bootstrap method and the validation set.Results:Of 969 treatment-naive patients with UC,771(79.6%)had an indolent course after diagnosis.Of these,313 patients were included in the development and validation of the nomogram.The nomogram incorporating age,disease activity,C-reactive protein,and platelet count showed good calibration and discrimination.The C-index was 0.759(0.741 in bootstrap validation)and the AUC at 2,4,and 6 years was 0.767,0.782,and 0.775,respectively.The nomogramperformed well when applied to the validation set.Conclusion:A majority of patients with UC had an indolent course after diagnosis.The nomogram developed in this study might be useful in therapeutic decision-making and follow-up management for patients with UC.