The binding of drugs with human serum albumin(HSA) is a crucial factor influencing the distribution and bioactivity of drugs in the body.To understand the action mechanisms between gallic acid(GA,3,4,5-trihydroxybe...The binding of drugs with human serum albumin(HSA) is a crucial factor influencing the distribution and bioactivity of drugs in the body.To understand the action mechanisms between gallic acid(GA,3,4,5-trihydroxybenzoic acid) and HSA,the binding of GA with HSA was investigated by a combined experimental and computational approach.The fluorescence properties of HSA and the binding parameters of GA collectively indicate that the binding is characterized by static quenching mechanism at one high affinity binding site.According to the estimated molecular distance between the donor(HSA) and the acceptor(GA),the binding is related to the fluorescence resonance energy transfer.As indicated by the thermodynamic parameters,hydrophobic interaction plays a major role in the GA-HSA complex.Further,the experimental results reveal that GA is bound in the large hydrophobic cavity of subdomain IIA in the site I of HSA,which is well approved by molecular docking.展开更多
目的探究营养一体化管理模式下夜间加餐对肝硬化患者血清白蛋白和血清前白蛋白的影响。方法选取本院2022年5月-2022年11月收住超15 d的肝硬化患者62例,随机分加餐组31例,营养风筛阳性后纳入营养一体化管理并给予夜间加餐;对照组31例,仅...目的探究营养一体化管理模式下夜间加餐对肝硬化患者血清白蛋白和血清前白蛋白的影响。方法选取本院2022年5月-2022年11月收住超15 d的肝硬化患者62例,随机分加餐组31例,营养风筛阳性后纳入营养一体化管理并给予夜间加餐;对照组31例,仅在营养风筛阳性后纳入营养一体化管理。入院第二日检测空腹血清白蛋白、血清前白蛋白并与15日后复查结果对比。结果2组患者的血清白蛋白、前白蛋白均较治疗前改善(加餐组31.76±5.21 VS 38.46±3.52、85.18±36.72 VS 157.82±24.62;对照组31.74±5.57 VS 35.69±3.77、85.79±37.68 VS 135.53±25.82;P<0.05),加餐组改善程度优于对照组(38.46±3.52 VS 35.69±3.77;157.82±24.62 VS 135.53±25.82;P<0.05)。结论营养一体化管理模式下给予肝硬化住院患者夜间加餐,可更显著改善患者的营养状况。展开更多
AIM:To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B(CHB) patients.METHODS:Seventy-eight CHB pat...AIM:To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B(CHB) patients.METHODS:Seventy-eight CHB patients were consecutively enrolled in this study.Liver biopsy was performed and blood serum was obtained at admission.Histological diagnosis was made according to the METAVIR system.Significant fibrosis was defined as stage score ≥ 2,severe fibrosis as stage score ≥ 3.The diagnostic accuracy of 6 noninvasive liver fibrosis models,including serum aspartate aminotransferase(AST) to platelet ratio index(APRI),FIB-4,Forn's index,Fibrometer,Hepascore,and Shanghai Liver Fibrosis Group's index(SLFG),was investigated.RESULTS:The APRI,FIB-4 and Forn's index under receiver operating characteristic curve(AUROC) for sig-nificant fibrosis were 0.71,0.75 and 0.79,respectively,with a diagnosis accuracy of 67%,77% and 80%,respectively,and 0.80,0.87 and 0.86,respectively,under the AUROC for severe fibrosis.The Hepascore,SLFG,and Fibrometer were 0.80,0.83 and 0.85,respectively under the AUROC for significant fibrosis(P < 0.01).The diagnosis accuracy of Hepascore and SLFG was 86% and 88%,respectively.The Hepascore,SLFG,and Fibrometer were 0.95,0.93,and 0.94,respectively,under the AUROC for severe fibrosis(P < 0.01).CONCLUSION:The models containing direct serum markers have a better diagnostic value than those not containing direct serum markers.展开更多
Flavonoids are structurally diverse and the most ubiquitous groups of polyphenols distributed in the various plants,which possess intensive biological activities.In this study,the interaction mechanisms between four f...Flavonoids are structurally diverse and the most ubiquitous groups of polyphenols distributed in the various plants,which possess intensive biological activities.In this study,the interaction mechanisms between four flavonoids containing one glucose unit with similar molecular weight isolated from the Tibetan medicinal herb Pyrethrum tatsienense,namely.apigenin-7-O-β-D-glucoside(1),luteolin-7-O-β-D-glucoside(2).quercetin-7-O-β-D-glucoside(3).quercetin-3-O-β-D-glycoside(4).and human serum albumin(HSA),were investigated by fluorescence.UV-vis absorbance,circular dichroism,and molecular modeling.The effects of biological metal ions Mg2+,Zn2+,and Cu2+ on the binding affinity between flavonoids and HSA were further examined.Structure-activity relationships of four flavonoids binding to HSA were discussed in depth and some meaningful conclusions have been drawn by the experiment data and theoretical simulation.In addition,an interesting phenomenon was observed that the microenvironment of the binding site I in HSA has hardly changed in the presence of 4 differentiating from the other three flavonoids on the basis of conformation investigations.展开更多
Objective: To identify potential serum markers of hepatic carcinoma in rats through Surface-Enhanced Laser Desorption Ionization-Time of Flight-Mass Spectrometry(SELDI-TOF-MS) Technology. Methods: A rat model of h...Objective: To identify potential serum markers of hepatic carcinoma in rats through Surface-Enhanced Laser Desorption Ionization-Time of Flight-Mass Spectrometry(SELDI-TOF-MS) Technology. Methods: A rat model of hepatic carcinoma was established. The serum samples of hepatic carcinoma and normal rats were analyzed via SELDI-TOF-MS Technology. The changes of the serum protein fingerprint patterns were observed between the experimental group of hepatic carcinoma and the controls. The analysis was conducted by statistical software-Biomarker Wizard. Results: Fifty-six protein peaks in the serums were found. Within m/z 0-20 000, the protein peaks of rrdz 1158, 8 835 and 15 302 of hepatic carcinoma serums were obviously higher in the rat models compared with those in the controls(P 〈 0.01). Conclusion: Three peaks were considered as potential biomarkers according to the serum protein fingerprint patterns of the hepatic carcinoma group and the control group.展开更多
Objective:To evaluate preoperative serum calcium concentration and investigate the association between calcium level and positive peritoneal cytology in endometrial carcinoma(EC).Methods:A total of 510 patients who we...Objective:To evaluate preoperative serum calcium concentration and investigate the association between calcium level and positive peritoneal cytology in endometrial carcinoma(EC).Methods:A total of 510 patients who were diagnosed with EC and had surgery were initially enrolled in this study at Peking University People's Hospital between January 2012 and December 2016.Clinical characteristics and preoperative serum calcium,albumin,carbohydrate antigen(CA)125,CA19-9,carcinoembryonic antigen(CEA)were extracted from patient records and evaluated according to postoperative peritoneal cytology.Predictive factors were assessed with Cox univariate and multivariate analyses.Factors selected from multivariate analysis results were used to build a predictive model.Results:A total of 510 patients are identified in our database and 444 patients who fulfilled inclusion and exclusion criteria are included in this study.Univariate analysis revealed that ionized calcium concentration was closely related to positive peritoneal cytology,tumor grade and lymph-vascular space invasion(LVSI).Moreover,peritoneal cytology was significantly associated with hypertension,tubal ligation,serum CA125,CA19-9,CEA and ionized calcium level.Multivariate analysis revealed that albumin-adjusted calcium level,CA125 and tubal ligation were independent predictive factors of positive peritoneal cytology(P<0.05).A combination of ionized calcium level with the other two indexes yielded significantly great area under the curve(AUC=0.824).Conclusions:This study enhanced the value of preoperative ionized calcium level.We also identified several potential biomarkers to predict positive peritoneal cytology in EC patients before surgery.展开更多
Solid lipid nanoparticles loaded with bovine serum albumin(BSA) were prepared by a double emulsion method. As the mass fraction of the model drug BSA increased from 0 to 15%, the particle size gradually increased. T...Solid lipid nanoparticles loaded with bovine serum albumin(BSA) were prepared by a double emulsion method. As the mass fraction of the model drug BSA increased from 0 to 15%, the particle size gradually increased. The physical stability of the nanoparticles was investigated by zeta potential measurement and they were shown to be quite stable. Fluorescence spectroscopy confirmed that the loaded position of BSA was on the interface between the inner aqueous phase and the solid lipid phase. Both Fourier-transform infrared spectroscopy and circular dichroism spectra indicate that BSA in the nanoparticles was not destroyed, but the secondary structure was disrupted slightly.展开更多
AIM: To investigate the prognostic value of the model for end-stage liver disease (MELD) and three new MELD-based models combination with serum sodium in decompensated cirrhosis patients-the MELD with the incorporatio...AIM: To investigate the prognostic value of the model for end-stage liver disease (MELD) and three new MELD-based models combination with serum sodium in decompensated cirrhosis patients-the MELD with the incorporation of serum sodium (MELD-Na), the integrated MELD (iMELD), and the MELD to sodium (MESO) index. METHODS: A total of 166 patients with decompensated cirrhosis were enrolled into the study. MELD, MELD- Na, iMELD and MESO scores were calculated for each patient following the original formula on the first day of admission. All patients were followed up at least 1 year. The predictive prognosis related with the four models was determined by the area under the receiver operating characteristic curve (AUC) of the four parameters. Kaplan-Meier survival curves were made using the cut-offs identif ied by means of receiver operating characteristic (ROC). RESULTS: Out of 166 patients, 38 patients with signifi cantly higher MELD-Na (28.84 ± 2.43 vs 14.72 ± 0.60), iMELD (49.04 ± 1.72 vs 35.52 ± 0.67), MESO scores (1.59 ± 0.82 vs 0.99 ± 0.42) compared to the survivors died within 3 mo (P < 0.001). Of 166 patients, 75 with markedly higher MELD-Na (23.01 ± 1.51 vs 13.78 ± 0.69), iMELD (44.06 ± 1.19 vs 34.12 ± 0.69), MESO scores (1.37 ± 0.70 vs 0.93 ± 0.40) than the survivors died within 1 year (P < 0.001). At 3 mo of enrollment, the iMELD had the highest AUC (0.841), and was followed by the MELD-Na (0.766), MESO (0.723), all larger than MELD (0.773); At 1year, the iMELD still had the highest AUC (0.783), the difference between the iMELD and MELD was statistically significant (P < 0.05). Survival curves showed that the three new models were all clearly discriminated the patients who survived or died in short-term as well as intermediate-term (P < 0.001). CONCLUSION: Three new models, changed with serum sodium (MELD-Na, iMELD, MESO) can exactly predict the prognosis of patients with decompensated cirrhosis for short and intermediate period, and may enhance the prognostic accuracy of MELD. The iMELD is better prognostic model for outcome prediction in patients with decompensated cirrhosis.展开更多
Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination....Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination.Focal demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal loss.The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity.MicroRNAs(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord tissue.The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue.Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease.Interestingly,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and miR-873.Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course.Additionally,studies should be performed with male mice of a similar age,and with aged male and female mice.展开更多
AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum ...AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum lactate.METHODS This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and compared.RESULTS Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P < 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P < 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P < 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresponding mortality rates within three months were 75% and 90%, respectively.CONCLUSION The short-term prognosis of HBV-related ACLF was improved by using a modified MELD including serum lactate from the present 6-year clinical study.展开更多
基金Supported by the Project of Department of Science and Technology of Jilin Province,China(No.20070424)
文摘The binding of drugs with human serum albumin(HSA) is a crucial factor influencing the distribution and bioactivity of drugs in the body.To understand the action mechanisms between gallic acid(GA,3,4,5-trihydroxybenzoic acid) and HSA,the binding of GA with HSA was investigated by a combined experimental and computational approach.The fluorescence properties of HSA and the binding parameters of GA collectively indicate that the binding is characterized by static quenching mechanism at one high affinity binding site.According to the estimated molecular distance between the donor(HSA) and the acceptor(GA),the binding is related to the fluorescence resonance energy transfer.As indicated by the thermodynamic parameters,hydrophobic interaction plays a major role in the GA-HSA complex.Further,the experimental results reveal that GA is bound in the large hydrophobic cavity of subdomain IIA in the site I of HSA,which is well approved by molecular docking.
文摘目的探究营养一体化管理模式下夜间加餐对肝硬化患者血清白蛋白和血清前白蛋白的影响。方法选取本院2022年5月-2022年11月收住超15 d的肝硬化患者62例,随机分加餐组31例,营养风筛阳性后纳入营养一体化管理并给予夜间加餐;对照组31例,仅在营养风筛阳性后纳入营养一体化管理。入院第二日检测空腹血清白蛋白、血清前白蛋白并与15日后复查结果对比。结果2组患者的血清白蛋白、前白蛋白均较治疗前改善(加餐组31.76±5.21 VS 38.46±3.52、85.18±36.72 VS 157.82±24.62;对照组31.74±5.57 VS 35.69±3.77、85.79±37.68 VS 135.53±25.82;P<0.05),加餐组改善程度优于对照组(38.46±3.52 VS 35.69±3.77;157.82±24.62 VS 135.53±25.82;P<0.05)。结论营养一体化管理模式下给予肝硬化住院患者夜间加餐,可更显著改善患者的营养状况。
基金Supported by Grant for Master Degree Students of Fudan University
文摘AIM:To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B(CHB) patients.METHODS:Seventy-eight CHB patients were consecutively enrolled in this study.Liver biopsy was performed and blood serum was obtained at admission.Histological diagnosis was made according to the METAVIR system.Significant fibrosis was defined as stage score ≥ 2,severe fibrosis as stage score ≥ 3.The diagnostic accuracy of 6 noninvasive liver fibrosis models,including serum aspartate aminotransferase(AST) to platelet ratio index(APRI),FIB-4,Forn's index,Fibrometer,Hepascore,and Shanghai Liver Fibrosis Group's index(SLFG),was investigated.RESULTS:The APRI,FIB-4 and Forn's index under receiver operating characteristic curve(AUROC) for sig-nificant fibrosis were 0.71,0.75 and 0.79,respectively,with a diagnosis accuracy of 67%,77% and 80%,respectively,and 0.80,0.87 and 0.86,respectively,under the AUROC for severe fibrosis.The Hepascore,SLFG,and Fibrometer were 0.80,0.83 and 0.85,respectively under the AUROC for significant fibrosis(P < 0.01).The diagnosis accuracy of Hepascore and SLFG was 86% and 88%,respectively.The Hepascore,SLFG,and Fibrometer were 0.95,0.93,and 0.94,respectively,under the AUROC for severe fibrosis(P < 0.01).CONCLUSION:The models containing direct serum markers have a better diagnostic value than those not containing direct serum markers.
基金financially supported by the National Natural Science Foundation of China(30960530)
文摘Flavonoids are structurally diverse and the most ubiquitous groups of polyphenols distributed in the various plants,which possess intensive biological activities.In this study,the interaction mechanisms between four flavonoids containing one glucose unit with similar molecular weight isolated from the Tibetan medicinal herb Pyrethrum tatsienense,namely.apigenin-7-O-β-D-glucoside(1),luteolin-7-O-β-D-glucoside(2).quercetin-7-O-β-D-glucoside(3).quercetin-3-O-β-D-glycoside(4).and human serum albumin(HSA),were investigated by fluorescence.UV-vis absorbance,circular dichroism,and molecular modeling.The effects of biological metal ions Mg2+,Zn2+,and Cu2+ on the binding affinity between flavonoids and HSA were further examined.Structure-activity relationships of four flavonoids binding to HSA were discussed in depth and some meaningful conclusions have been drawn by the experiment data and theoretical simulation.In addition,an interesting phenomenon was observed that the microenvironment of the binding site I in HSA has hardly changed in the presence of 4 differentiating from the other three flavonoids on the basis of conformation investigations.
基金the Science Foundation of the Ministryof Health of China(No.wkj2004-2-12).
文摘Objective: To identify potential serum markers of hepatic carcinoma in rats through Surface-Enhanced Laser Desorption Ionization-Time of Flight-Mass Spectrometry(SELDI-TOF-MS) Technology. Methods: A rat model of hepatic carcinoma was established. The serum samples of hepatic carcinoma and normal rats were analyzed via SELDI-TOF-MS Technology. The changes of the serum protein fingerprint patterns were observed between the experimental group of hepatic carcinoma and the controls. The analysis was conducted by statistical software-Biomarker Wizard. Results: Fifty-six protein peaks in the serums were found. Within m/z 0-20 000, the protein peaks of rrdz 1158, 8 835 and 15 302 of hepatic carcinoma serums were obviously higher in the rat models compared with those in the controls(P 〈 0.01). Conclusion: Three peaks were considered as potential biomarkers according to the serum protein fingerprint patterns of the hepatic carcinoma group and the control group.
基金supported by National Natural Science Foundation of China (No. 81874108, No. 81802607)
文摘Objective:To evaluate preoperative serum calcium concentration and investigate the association between calcium level and positive peritoneal cytology in endometrial carcinoma(EC).Methods:A total of 510 patients who were diagnosed with EC and had surgery were initially enrolled in this study at Peking University People's Hospital between January 2012 and December 2016.Clinical characteristics and preoperative serum calcium,albumin,carbohydrate antigen(CA)125,CA19-9,carcinoembryonic antigen(CEA)were extracted from patient records and evaluated according to postoperative peritoneal cytology.Predictive factors were assessed with Cox univariate and multivariate analyses.Factors selected from multivariate analysis results were used to build a predictive model.Results:A total of 510 patients are identified in our database and 444 patients who fulfilled inclusion and exclusion criteria are included in this study.Univariate analysis revealed that ionized calcium concentration was closely related to positive peritoneal cytology,tumor grade and lymph-vascular space invasion(LVSI).Moreover,peritoneal cytology was significantly associated with hypertension,tubal ligation,serum CA125,CA19-9,CEA and ionized calcium level.Multivariate analysis revealed that albumin-adjusted calcium level,CA125 and tubal ligation were independent predictive factors of positive peritoneal cytology(P<0.05).A combination of ionized calcium level with the other two indexes yielded significantly great area under the curve(AUC=0.824).Conclusions:This study enhanced the value of preoperative ionized calcium level.We also identified several potential biomarkers to predict positive peritoneal cytology in EC patients before surgery.
基金Supported by the National Natural Scientific Foundation of China(No.50472069)the Key Scientific Project from the Chinese Education Ministry(No.106100)
文摘Solid lipid nanoparticles loaded with bovine serum albumin(BSA) were prepared by a double emulsion method. As the mass fraction of the model drug BSA increased from 0 to 15%, the particle size gradually increased. The physical stability of the nanoparticles was investigated by zeta potential measurement and they were shown to be quite stable. Fluorescence spectroscopy confirmed that the loaded position of BSA was on the interface between the inner aqueous phase and the solid lipid phase. Both Fourier-transform infrared spectroscopy and circular dichroism spectra indicate that BSA in the nanoparticles was not destroyed, but the secondary structure was disrupted slightly.
基金Supported by the Postdoctoral Science Foundation of China, No.1999-10the Science and Technology Foundation of Shaanxi Province, China, No. 2003K10G63
文摘AIM: To investigate the prognostic value of the model for end-stage liver disease (MELD) and three new MELD-based models combination with serum sodium in decompensated cirrhosis patients-the MELD with the incorporation of serum sodium (MELD-Na), the integrated MELD (iMELD), and the MELD to sodium (MESO) index. METHODS: A total of 166 patients with decompensated cirrhosis were enrolled into the study. MELD, MELD- Na, iMELD and MESO scores were calculated for each patient following the original formula on the first day of admission. All patients were followed up at least 1 year. The predictive prognosis related with the four models was determined by the area under the receiver operating characteristic curve (AUC) of the four parameters. Kaplan-Meier survival curves were made using the cut-offs identif ied by means of receiver operating characteristic (ROC). RESULTS: Out of 166 patients, 38 patients with signifi cantly higher MELD-Na (28.84 ± 2.43 vs 14.72 ± 0.60), iMELD (49.04 ± 1.72 vs 35.52 ± 0.67), MESO scores (1.59 ± 0.82 vs 0.99 ± 0.42) compared to the survivors died within 3 mo (P < 0.001). Of 166 patients, 75 with markedly higher MELD-Na (23.01 ± 1.51 vs 13.78 ± 0.69), iMELD (44.06 ± 1.19 vs 34.12 ± 0.69), MESO scores (1.37 ± 0.70 vs 0.93 ± 0.40) than the survivors died within 1 year (P < 0.001). At 3 mo of enrollment, the iMELD had the highest AUC (0.841), and was followed by the MELD-Na (0.766), MESO (0.723), all larger than MELD (0.773); At 1year, the iMELD still had the highest AUC (0.783), the difference between the iMELD and MELD was statistically significant (P < 0.05). Survival curves showed that the three new models were all clearly discriminated the patients who survived or died in short-term as well as intermediate-term (P < 0.001). CONCLUSION: Three new models, changed with serum sodium (MELD-Na, iMELD, MESO) can exactly predict the prognosis of patients with decompensated cirrhosis for short and intermediate period, and may enhance the prognostic accuracy of MELD. The iMELD is better prognostic model for outcome prediction in patients with decompensated cirrhosis.
文摘Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination.Focal demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal loss.The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity.MicroRNAs(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord tissue.The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue.Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease.Interestingly,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and miR-873.Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course.Additionally,studies should be performed with male mice of a similar age,and with aged male and female mice.
文摘AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum lactate.METHODS This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and compared.RESULTS Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P < 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P < 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P < 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresponding mortality rates within three months were 75% and 90%, respectively.CONCLUSION The short-term prognosis of HBV-related ACLF was improved by using a modified MELD including serum lactate from the present 6-year clinical study.