Background The dead space fraction(VD/VT)has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome(ARDS).However,its measurement relies on expired carbon dioxide,limiting its wid...Background The dead space fraction(VD/VT)has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome(ARDS).However,its measurement relies on expired carbon dioxide,limiting its widespread application in clinical practice.Several estimates employing routine variables have been found to be reliable substitutes for direct measurement of VD/VT.In this study,we evaluated the prognostic value of these dead space estimates obtained in the first 7 days following the initiation of ventilation.Methods This retrospective observational study was conducted using data from the Chinese database in intensive care(CDIC).Eligible participants were adult ARDS patients receiving invasive mechanical ventilation while in the intensive care unit between 1st January 2014 and 31st March 2021.We collected data during the first 7 days of ventilation to calculate various dead space estimates,including ventilatory ratio(VR),corrected minute ventilation(V_(Ecorr)),VD/VT(Harris–Benedict),VD/VT(Siddiki estimate),and VD/VT(Penn State estimate)longitudinally.A time-dependent Cox model was used to handle these time-varying estimates.Results A total of 392 patients(median age 66[interquartile range:55–77]years,median SOFA score 9[interquartile range:7–12])were finally included in our analysis,among whom 132(33.7%)patients died within 28 days of admission.VR(hazard ratio[HR]=1.04 per 0.1 increase,95%confidence interval[CI]:1.01 to 1.06;P=0.013),V_(Ecorr)(HR=1.08 per 1 increase,95%CI:1.04 to 1.12;P<0.001),VD/VT(Harris–Benedict)(HR=1.25 per 0.1 increase,95%CI:1.06 to 1.47;P=0.006),and VD/VT(Penn State estimate)(HR=1.22 per 0.1 increase,95%CI:1.04 to 1.44;P=0.017)remained significant after adjustment,while VD/VT(Siddiki estimate)(HR=1.10 per 0.1 increase,95%CI:1.00 to 1.20;P=0.058)did not.Given a large number of negative values,VD/VT(Siddiki estimate)and VD/VT(Penn State estimate)were not recommended as reliable substitutes.Long-term exposure to VR>1.3,V_(Ecorr)>7.53,and VD/VT(Harris–Benedict)>0.59 was independently associated with an increased risk of mortality in ARDS patients.These findings were validated in the fluid and catheter treatment trial(FACTT)database.Conclusions In cases where VD/VT cannot be measured directly,early time-varying estimates of VD/VT such as VR,,V_(Ecorr),and VD/VT(Harris–Benedict)can be considered for predicting mortality in ARDS patients,offering a rapid bedside application.展开更多
Non-alcoholic fatty liver disease(NAFLD)represents the most common chronic liver disease in Western countries,being considered as the hepatic manifestation of metabolic syndrome.NAFLD has a common pathogenic backgroun...Non-alcoholic fatty liver disease(NAFLD)represents the most common chronic liver disease in Western countries,being considered as the hepatic manifestation of metabolic syndrome.NAFLD has a common pathogenic background to that of metabolic syndrome,and shares many risk factors such as obesity,hypertension,insulin resistance and dyslipidemia.Although there is no currently available evidence-based established treatment for NAFLD,all the recommendations from the medical associations indicate that the most effective treatment is to reduce weight through lifestyle modifications.Diet,indeed,plays a key role in the management of NAFLD patients,as both the quantity and quality of the diet have been reported to have a beneficial role in the onset and severity of the liver disease.Among all the diets that have been proposed,a Mediterranean diet was the most effective dietary option for inducing weight loss together with beneficial effects on all the risk factors associated with metabolic syndrome and NAFLD.Over the last few years,research has demonstrated a beneficial effect of a Mediterranean diet in NAFLD.In this review,we will examine all the available data on the association between diet,nutrients and the Mediterranean diet in association with onset and severity of NAFLD.展开更多
AIM:To review pediatric cases of orofacial granulomatosis(OFG),report disease characteristics,and explore the association between OFG and Crohn’s disease.METHODS:We conducted a systematic review according to the PRIS...AIM:To review pediatric cases of orofacial granulomatosis(OFG),report disease characteristics,and explore the association between OFG and Crohn’s disease.METHODS:We conducted a systematic review according to the PRISMA guidelines.We searched Medline,LILACS,Virtual Health Library,and Web of Knowledge in September 2013 for cases of OFG in the pediatric age range(<18 years),with no language limitations.All relevant articles were accessed in full text.The manual search included references of retrieved articles.We extracted data on patients’characteristics,disease characteristics,association with other diseases,and treatment.We analyzed the data and reported the results in tables and text.RESULTS:We retrieved 173 reports of OFG in children.Mean age at onset was 11.1±3.8 years(range:2.0-18years).Prevalence in males was significant higher than in females(P<0.001),with a male:female ratio of 2:1.Gastrointestinal signs or symptoms were present in 26.0%of children at the time of OFG diagnosis.Overall,70/173(40.4%)children received a concomitant diagnosis of Crohn’s disease.In about half(51.4%)of the cases the onset of OFG anticipated the diagnosis of Crohn’s disease,with a mean time between the two diagnoses of 13.1±11.6 mo(range:3-36 mo).Overall,21/173(12.1%)of the children with OFG had perianal disease,while 11/173(6.4%)had a family history of Crohn’s disease.Both perianal disease and a family history of Crohn’s disease were significantly associated with a higher risk of Crohn’s disease diagnosis in children with OFG[relative risk(RR)=3.10,95%confidence interval(CI):2.46-3.90;RR=2.74,95%CI:2.24-3.36,P<0.0001 for both).Treatment of OFG included steroids(70.8%of children)and other immunosuppressive drugs(42.7%),such as azathioprine,thalidomide and infliximab.CONCLUSION:High prevalence of Crohn’s disease in children with OFG suggests that OFG may be a subtype of Crohn’s disease.展开更多
The dual-specificity tyrosine-regulated kinase (DYRK) family is evolutionarily conserved from invertebrate to mammals. DYRKs regulate cell proliferation, apoptosis, survival, and differentiation by modifying the prote...The dual-specificity tyrosine-regulated kinase (DYRK) family is evolutionarily conserved from invertebrate to mammals. DYRKs regulate cell proliferation, apoptosis, survival, and differentiation by modifying the protein activation state, cellular localization, and turnover. In contrast to several studies in cellular models, the available evidence regarding the in vivo roles of DYRKs in mammalian development is limited. This review summarizes the in vivo studies on Dyrks which provide insight into their roles in mammalian tissue development and congenital diseases. In vivo evidence obtained using knockout and genetically modified animals helps to understand and develop novel clinical therapies and drug for human congenital diseases, such as Down syndrome and neuronal disorders (associated with DYRK1A) and skeletal ciliopathies (associated with DYRK2).展开更多
Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is one of the critical pattern recognition receptors which participates in the regulation of multiple inflammatory responses. Mutations in NLRP12 ca...Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is one of the critical pattern recognition receptors which participates in the regulation of multiple inflammatory responses. Mutations in NLRP12 cause exceptionally rare NLRP12-associated autoinflammatory disease (NLRP12-AID). So far, very few patients with NLRP12-AID have been identified worldwide;therefore, data on the clinical phenotype and genetic profile are limited. In this study, we reported 10 patients who presented mainly with periodic fever syndrome or arthritis. Next-generation sequencing (NGS) identified 6 heterozygous mutations of NLRP12, including 2 novel null mutations. Of the patients, some with same mutations showed different clinical features. Compared to healthy controls, the increased levels of cytokines were revealed in the patients' plasmas, as well as in the supernatants of patients’ cells stimulated with lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α). The missense mutations did not change the protein expression;but decreased level of NLRP12 protein was shown in the null mutations. And in vitro expression assay demonstrated a truncating protein induced by the frameshift mutation. Further functional studies revealed the deleterious effect of mutations on nuclear factor-kappa B (NF-κB) signaling. Both the null and missense mutations impaired their inhibition of NF-κB activation induced by p65. Collectively, this study reported a relatively large NLRP12-AID case series. Our findings expand the clinical spectrum, and reinforce the diversity of genetic mutations and clinical phenotypes. The NLRP12-associated disorder should be considered when autoinflammatory diseases are encountered in the clinical practice, especially for patients presenting with periodic fever but no other genetic cause identified.展开更多
基金supported by the Key Technologies Research and Development Program(Grant numbers:2022YFC2504400 and 2021YFC2500804)the Jiangsu Provincial Key Research and Development Program(Grant number:BE2022854).
文摘Background The dead space fraction(VD/VT)has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome(ARDS).However,its measurement relies on expired carbon dioxide,limiting its widespread application in clinical practice.Several estimates employing routine variables have been found to be reliable substitutes for direct measurement of VD/VT.In this study,we evaluated the prognostic value of these dead space estimates obtained in the first 7 days following the initiation of ventilation.Methods This retrospective observational study was conducted using data from the Chinese database in intensive care(CDIC).Eligible participants were adult ARDS patients receiving invasive mechanical ventilation while in the intensive care unit between 1st January 2014 and 31st March 2021.We collected data during the first 7 days of ventilation to calculate various dead space estimates,including ventilatory ratio(VR),corrected minute ventilation(V_(Ecorr)),VD/VT(Harris–Benedict),VD/VT(Siddiki estimate),and VD/VT(Penn State estimate)longitudinally.A time-dependent Cox model was used to handle these time-varying estimates.Results A total of 392 patients(median age 66[interquartile range:55–77]years,median SOFA score 9[interquartile range:7–12])were finally included in our analysis,among whom 132(33.7%)patients died within 28 days of admission.VR(hazard ratio[HR]=1.04 per 0.1 increase,95%confidence interval[CI]:1.01 to 1.06;P=0.013),V_(Ecorr)(HR=1.08 per 1 increase,95%CI:1.04 to 1.12;P<0.001),VD/VT(Harris–Benedict)(HR=1.25 per 0.1 increase,95%CI:1.06 to 1.47;P=0.006),and VD/VT(Penn State estimate)(HR=1.22 per 0.1 increase,95%CI:1.04 to 1.44;P=0.017)remained significant after adjustment,while VD/VT(Siddiki estimate)(HR=1.10 per 0.1 increase,95%CI:1.00 to 1.20;P=0.058)did not.Given a large number of negative values,VD/VT(Siddiki estimate)and VD/VT(Penn State estimate)were not recommended as reliable substitutes.Long-term exposure to VR>1.3,V_(Ecorr)>7.53,and VD/VT(Harris–Benedict)>0.59 was independently associated with an increased risk of mortality in ARDS patients.These findings were validated in the fluid and catheter treatment trial(FACTT)database.Conclusions In cases where VD/VT cannot be measured directly,early time-varying estimates of VD/VT such as VR,,V_(Ecorr),and VD/VT(Harris–Benedict)can be considered for predicting mortality in ARDS patients,offering a rapid bedside application.
文摘Non-alcoholic fatty liver disease(NAFLD)represents the most common chronic liver disease in Western countries,being considered as the hepatic manifestation of metabolic syndrome.NAFLD has a common pathogenic background to that of metabolic syndrome,and shares many risk factors such as obesity,hypertension,insulin resistance and dyslipidemia.Although there is no currently available evidence-based established treatment for NAFLD,all the recommendations from the medical associations indicate that the most effective treatment is to reduce weight through lifestyle modifications.Diet,indeed,plays a key role in the management of NAFLD patients,as both the quantity and quality of the diet have been reported to have a beneficial role in the onset and severity of the liver disease.Among all the diets that have been proposed,a Mediterranean diet was the most effective dietary option for inducing weight loss together with beneficial effects on all the risk factors associated with metabolic syndrome and NAFLD.Over the last few years,research has demonstrated a beneficial effect of a Mediterranean diet in NAFLD.In this review,we will examine all the available data on the association between diet,nutrients and the Mediterranean diet in association with onset and severity of NAFLD.
文摘AIM:To review pediatric cases of orofacial granulomatosis(OFG),report disease characteristics,and explore the association between OFG and Crohn’s disease.METHODS:We conducted a systematic review according to the PRISMA guidelines.We searched Medline,LILACS,Virtual Health Library,and Web of Knowledge in September 2013 for cases of OFG in the pediatric age range(<18 years),with no language limitations.All relevant articles were accessed in full text.The manual search included references of retrieved articles.We extracted data on patients’characteristics,disease characteristics,association with other diseases,and treatment.We analyzed the data and reported the results in tables and text.RESULTS:We retrieved 173 reports of OFG in children.Mean age at onset was 11.1±3.8 years(range:2.0-18years).Prevalence in males was significant higher than in females(P<0.001),with a male:female ratio of 2:1.Gastrointestinal signs or symptoms were present in 26.0%of children at the time of OFG diagnosis.Overall,70/173(40.4%)children received a concomitant diagnosis of Crohn’s disease.In about half(51.4%)of the cases the onset of OFG anticipated the diagnosis of Crohn’s disease,with a mean time between the two diagnoses of 13.1±11.6 mo(range:3-36 mo).Overall,21/173(12.1%)of the children with OFG had perianal disease,while 11/173(6.4%)had a family history of Crohn’s disease.Both perianal disease and a family history of Crohn’s disease were significantly associated with a higher risk of Crohn’s disease diagnosis in children with OFG[relative risk(RR)=3.10,95%confidence interval(CI):2.46-3.90;RR=2.74,95%CI:2.24-3.36,P<0.0001 for both).Treatment of OFG included steroids(70.8%of children)and other immunosuppressive drugs(42.7%),such as azathioprine,thalidomide and infliximab.CONCLUSION:High prevalence of Crohn’s disease in children with OFG suggests that OFG may be a subtype of Crohn’s disease.
基金supported by JSPS KAKENHI(No.21K06192 to S.Y.and 17H03584,18K19484,and 20H03519 to K.Y.)the Jikei University Research Fund(to K.Y.)+1 种基金the Takeda Science Foundation(to S.Y.)the Uehara Memorial Foundation(to S.Y.and K.Y.).
文摘The dual-specificity tyrosine-regulated kinase (DYRK) family is evolutionarily conserved from invertebrate to mammals. DYRKs regulate cell proliferation, apoptosis, survival, and differentiation by modifying the protein activation state, cellular localization, and turnover. In contrast to several studies in cellular models, the available evidence regarding the in vivo roles of DYRKs in mammalian development is limited. This review summarizes the in vivo studies on Dyrks which provide insight into their roles in mammalian tissue development and congenital diseases. In vivo evidence obtained using knockout and genetically modified animals helps to understand and develop novel clinical therapies and drug for human congenital diseases, such as Down syndrome and neuronal disorders (associated with DYRK1A) and skeletal ciliopathies (associated with DYRK2).
基金supported in part by the National Key Research and Development Program of China(No.2021YFC2702005)National Natural Science Foundation of China(No.81971547)+1 种基金the Research Fund for Outstanding Youth Scholar of Chongqing Talents(No.CQYC201905003)the High-level Medical Reserved Personnel Training Project of Chongqing(No.2019181).
文摘Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is one of the critical pattern recognition receptors which participates in the regulation of multiple inflammatory responses. Mutations in NLRP12 cause exceptionally rare NLRP12-associated autoinflammatory disease (NLRP12-AID). So far, very few patients with NLRP12-AID have been identified worldwide;therefore, data on the clinical phenotype and genetic profile are limited. In this study, we reported 10 patients who presented mainly with periodic fever syndrome or arthritis. Next-generation sequencing (NGS) identified 6 heterozygous mutations of NLRP12, including 2 novel null mutations. Of the patients, some with same mutations showed different clinical features. Compared to healthy controls, the increased levels of cytokines were revealed in the patients' plasmas, as well as in the supernatants of patients’ cells stimulated with lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α). The missense mutations did not change the protein expression;but decreased level of NLRP12 protein was shown in the null mutations. And in vitro expression assay demonstrated a truncating protein induced by the frameshift mutation. Further functional studies revealed the deleterious effect of mutations on nuclear factor-kappa B (NF-κB) signaling. Both the null and missense mutations impaired their inhibition of NF-κB activation induced by p65. Collectively, this study reported a relatively large NLRP12-AID case series. Our findings expand the clinical spectrum, and reinforce the diversity of genetic mutations and clinical phenotypes. The NLRP12-associated disorder should be considered when autoinflammatory diseases are encountered in the clinical practice, especially for patients presenting with periodic fever but no other genetic cause identified.
