Introduction: 5-Fluorouracil (5-FU) is the basis of most combination chemotherapies for gastrointestinal tumors. It is generally well tolerated, but side-effects might require dose-adjustment. As adverse events are no...Introduction: 5-Fluorouracil (5-FU) is the basis of most combination chemotherapies for gastrointestinal tumors. It is generally well tolerated, but side-effects might require dose-adjustment. As adverse events are not specific to the 5-FU component of the chemotherapy-combination, i.e. neutropenia, diarrhea or cardiotoxicity, the knowledge of 5-FU serum levels might help to attribute these side effects to the 5-FU compound. The optimal concentration-range (AUC, area under the curve) has been described to be within 20-25 mgh/l. The aim of this study was to analyse the intra- and interindividual variability of 5-FU AUC-levels in patients with 5-FU infusion therapy. Methods: 230 blood samples were obtained from 31 different gastrointestinal cancer patients (esophagus (8), stomach (10), ileum (1), colorectum (12)) treated with 5-FU-infusional regimes, based on a 24- or 48-hour AIO treatment-schedule. 5-FU plasma concentrations were measured using an immunolinked Elisa assay (Saladax 5-FU PCMTM). Intra- and interindividual differences were analysed before (0 h;n = 115), at 2 - 3 hours after the start of infusional 5-FU treatment (n = 19) (early sampling) and towards the end of the infusion (n = 96) (late sampling). Results: Early blood sampling resulted in low 5-FU plasma concentrations (541 ± 127 g/ml) due to saline prefilling (2 - 3 ml) of the Baxter pump. Blood sampling at the later time-point resulted in reproducible values (971 ± 81 ng/ml). 5-FU concentrations were dose-dependent with low intra- and interindividual variability. However, care has to be taken, as the results can be influenced by inaccurate blood sampling: too early or late sampling (when the folfusor-pump is empty), delayed centrifugation of the tube or hemolysis. Conclusions: With critical analysis of the measurements and correct performance of blood sampling, the measurement of 5-FU plasma concentrations with the immunoassay may in the future allow to optimize 5-FU dosing and to identify the cause of toxicity. Changes of 5-FU clearance in long-term therapy still have to be studied.展开更多
BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predi...BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain.AIM To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS levels.METHODS This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service.The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography.The patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were explored.RESULTS Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female patients.Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects.In male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total scores.CONCLUSION Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.展开更多
The present study investigated the effect of body weight on body composition, digestive and absorptive capacity, transaminase activities in hepatopancreas and muscle, and plasma ammonia concentration of Jian carp(Cypr...The present study investigated the effect of body weight on body composition, digestive and absorptive capacity, transaminase activities in hepatopancreas and muscle, and plasma ammonia concentration of Jian carp(Cyprinus carpio var.Jian). A total of 750 Jian carps(18.0 ± 0.2 g) were randomly distributed into five groups with three replicates and fed the same diet for 56 days. Tissue and plasma samples were collected on days 14, 28,42, and 56. The results were used to develop a mathematical model for specific growth rate, body moisture and fat content, aspartate transaminase activity and alanine aminotransferase activity in hepatopancreas and muscle, plasma ammonia concentration, and trypsin, chymotrypsin, lipase, and amylase activities in hepatopancreas and intestine, activities of creatine kinase, Na^+/K^+-ATPase, alkaline phosphatase, and γ-glutamyl transpeptidase in intestine in Jian carp. There were linear relationships between natural logarithms of above indexes and body weight. The body moisture and fat content, digestive and absorptive enzymes activities, and transaminase activities showed negative allometry against body weight of Jian carp which were partial reasons to explain fish growth rate decreasing.展开更多
Background:Since the diagnostic value of aldosterone to renin ratio(ARR)calculated by plasma renin concentration(PRC)or plasma renin activity(PRA)is still inconclusive,we conducted a meta-analysis by systematically re...Background:Since the diagnostic value of aldosterone to renin ratio(ARR)calculated by plasma renin concentration(PRC)or plasma renin activity(PRA)is still inconclusive,we conducted a meta-analysis by systematically reviewing relevant literature to explore the difference in the diagnostic efficacy of ARR calculated by PRC or PRA,so as to provide guidance for clinical diagnosis.Methods:We searched PubMed,Embase,and Cochrane Library from the establishment of the database to March 2021.We included studies that report the true positive,false positive,true negative,and false negative values for the diagnosis of primary aldosteronism,and we excluded duplicate publications,research without full text,incomplete information,or inability to conduct data extraction,animal experiments,reviews,and systematic reviews.STATA 15.1 was used to analyze the data.Results:The pooled results showed that ARR(plasma aldosterone concentration[PAC]/PRC)had a sensitivity of 0.82(95%confidence interval[CI]:0.78-0.86),a specificity of 0.94(95%CI:0.92-0.95),a positive-likelihood ratio(LR)of 12.77(95%CI:7.04-23.73),a negative LR of 0.11(95%CI:0.07-0.17),and symmetric area under the curve(SAUC)of 0.982,respectively.Furthermore,the diagnostic odds ratio(DOR)of ARR(PAC/PRC)was 180.21.Additionally,the pooled results showed that ARR(PAC/PRA)had a sensitivity of 0.91(95%CI:0.86-0.95),a specificity of 0.91(95%CI:0.90-0.93),a positive LR of 7.30(95%CI:2.99-17.99),a negative LR of 0.10(95%CI:0.04-0.26),and SAUC of 0.976,respectively.The DOR of ARR(PAC/PRA)was 155.52.Additionally,we conducted a subgroup analysis for the different thresholds(<35 or≥35)of PAC/PRC.The results showed that the DOR of the cut-off≥35 groups was higher than the cut-off<35 groups(DOR=340.15,95%CI:38.32-3019.66;DOR=116.40,95%CI=23.28-581.92).Conclusions:The research results suggest that the determination of ARR(PAC/PRC)and ARR(PAC/PRA)was all effective screening tools for PA.The diagnostic accuracy and diagnostic value of ARR(PAC/PRC)are higher than ARR(PAC/PRA).In addition,within a certain range,the higher the threshold,the better the diagnostic value.展开更多
Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration(PPC)and is often clinically complicated by malignant diseases or severe infections.At present,however,research on the mol...Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration(PPC)and is often clinically complicated by malignant diseases or severe infections.At present,however,research on the molecular mechanism underlying high PPC(HPPC)is scant.Here,an animal model of primary hyperproteinemia was constructed in an invertebrate(Bombyx mori)to investigate the effects of HPPC on circulating blood cells.Results showed that HPPC affected blood cell homeostasis,leading to increased reactive oxygen species levels,and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway.HPPC induced the proliferation of blood cells,mainly granulocytes,by activating the Janus kinase/signal transducer and activator of transcription(JAK/STAT)signaling pathway.Supplementation with the endocrine hormone active substance 20 E significantly reduced the impact of HPPC on blood cell homeostasis.Thus,we identified a novel signaling pathway by which HPPC affects blood cell homeostasis,which differs from hyperglycemia,hyperlipidemia,and hypercholesterolemia.In addition,we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.展开更多
OBJECTIVE:To examine whether specific stimulation of Shenshu(BL23)affects sympathetic nervous activity(SNA)-associated plasma renin concentration(PRC).METHODS:Eight healthy volunteers participated in three pattern con...OBJECTIVE:To examine whether specific stimulation of Shenshu(BL23)affects sympathetic nervous activity(SNA)-associated plasma renin concentration(PRC).METHODS:Eight healthy volunteers participated in three pattern conditions in random order:control(Cont),stimulation of Shenshu(BL23),and stimulation of sham point(Sham).All participants were initially in the supine position for>60 min,and then remained in the standing position during the experimental procedure to increase SNA.An electrocardiogram was used to calculate low frequency/high frequency(LF/HF)ratio;blood was collected to analyze PRC.RESULTS:The LF/HF ratio was significantly increased in the standing position when compared with the supine position(P<0.01).There was no difference in LF/HF ratio during or after stimulation of Shenshu(BL23)in the standing position when compared with before the stimulation in the supine position;however,the LF/HF ratio was significantly increased in Cont and Sham conditions(P<0.01).There was no difference in PRC after stimulation of Shenshu(BL23)in the standing position when compared with before the stimulation in the supine position;however,there was a significant increase in PRC in the Cont and Sham conditions(Cont P<0.05,Sham P<0.01).CONCLUSION:Our results demonstrated that specific acupuncture stimulation of Shenshu(BL23)in the standing position decreased SNA-associated PRC,which was not observed during acupuncture stimulation of the sham point.展开更多
文摘Introduction: 5-Fluorouracil (5-FU) is the basis of most combination chemotherapies for gastrointestinal tumors. It is generally well tolerated, but side-effects might require dose-adjustment. As adverse events are not specific to the 5-FU component of the chemotherapy-combination, i.e. neutropenia, diarrhea or cardiotoxicity, the knowledge of 5-FU serum levels might help to attribute these side effects to the 5-FU compound. The optimal concentration-range (AUC, area under the curve) has been described to be within 20-25 mgh/l. The aim of this study was to analyse the intra- and interindividual variability of 5-FU AUC-levels in patients with 5-FU infusion therapy. Methods: 230 blood samples were obtained from 31 different gastrointestinal cancer patients (esophagus (8), stomach (10), ileum (1), colorectum (12)) treated with 5-FU-infusional regimes, based on a 24- or 48-hour AIO treatment-schedule. 5-FU plasma concentrations were measured using an immunolinked Elisa assay (Saladax 5-FU PCMTM). Intra- and interindividual differences were analysed before (0 h;n = 115), at 2 - 3 hours after the start of infusional 5-FU treatment (n = 19) (early sampling) and towards the end of the infusion (n = 96) (late sampling). Results: Early blood sampling resulted in low 5-FU plasma concentrations (541 ± 127 g/ml) due to saline prefilling (2 - 3 ml) of the Baxter pump. Blood sampling at the later time-point resulted in reproducible values (971 ± 81 ng/ml). 5-FU concentrations were dose-dependent with low intra- and interindividual variability. However, care has to be taken, as the results can be influenced by inaccurate blood sampling: too early or late sampling (when the folfusor-pump is empty), delayed centrifugation of the tube or hemolysis. Conclusions: With critical analysis of the measurements and correct performance of blood sampling, the measurement of 5-FU plasma concentrations with the immunoassay may in the future allow to optimize 5-FU dosing and to identify the cause of toxicity. Changes of 5-FU clearance in long-term therapy still have to be studied.
基金Supported by Shanghai Civil Administration Bureau,No.8-2-50.
文摘BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain.AIM To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS levels.METHODS This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service.The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography.The patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were explored.RESULTS Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female patients.Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects.In male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total scores.CONCLUSION Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.
基金financially supported by the National Department Public Benefit Research Foundation(Agriculture)of China(2010003020)
文摘The present study investigated the effect of body weight on body composition, digestive and absorptive capacity, transaminase activities in hepatopancreas and muscle, and plasma ammonia concentration of Jian carp(Cyprinus carpio var.Jian). A total of 750 Jian carps(18.0 ± 0.2 g) were randomly distributed into five groups with three replicates and fed the same diet for 56 days. Tissue and plasma samples were collected on days 14, 28,42, and 56. The results were used to develop a mathematical model for specific growth rate, body moisture and fat content, aspartate transaminase activity and alanine aminotransferase activity in hepatopancreas and muscle, plasma ammonia concentration, and trypsin, chymotrypsin, lipase, and amylase activities in hepatopancreas and intestine, activities of creatine kinase, Na^+/K^+-ATPase, alkaline phosphatase, and γ-glutamyl transpeptidase in intestine in Jian carp. There were linear relationships between natural logarithms of above indexes and body weight. The body moisture and fat content, digestive and absorptive enzymes activities, and transaminase activities showed negative allometry against body weight of Jian carp which were partial reasons to explain fish growth rate decreasing.
基金supported by a grant from the Science and Technology Project of Guangdong Province(No.2016A020215136)。
文摘Background:Since the diagnostic value of aldosterone to renin ratio(ARR)calculated by plasma renin concentration(PRC)or plasma renin activity(PRA)is still inconclusive,we conducted a meta-analysis by systematically reviewing relevant literature to explore the difference in the diagnostic efficacy of ARR calculated by PRC or PRA,so as to provide guidance for clinical diagnosis.Methods:We searched PubMed,Embase,and Cochrane Library from the establishment of the database to March 2021.We included studies that report the true positive,false positive,true negative,and false negative values for the diagnosis of primary aldosteronism,and we excluded duplicate publications,research without full text,incomplete information,or inability to conduct data extraction,animal experiments,reviews,and systematic reviews.STATA 15.1 was used to analyze the data.Results:The pooled results showed that ARR(plasma aldosterone concentration[PAC]/PRC)had a sensitivity of 0.82(95%confidence interval[CI]:0.78-0.86),a specificity of 0.94(95%CI:0.92-0.95),a positive-likelihood ratio(LR)of 12.77(95%CI:7.04-23.73),a negative LR of 0.11(95%CI:0.07-0.17),and symmetric area under the curve(SAUC)of 0.982,respectively.Furthermore,the diagnostic odds ratio(DOR)of ARR(PAC/PRC)was 180.21.Additionally,the pooled results showed that ARR(PAC/PRA)had a sensitivity of 0.91(95%CI:0.86-0.95),a specificity of 0.91(95%CI:0.90-0.93),a positive LR of 7.30(95%CI:2.99-17.99),a negative LR of 0.10(95%CI:0.04-0.26),and SAUC of 0.976,respectively.The DOR of ARR(PAC/PRA)was 155.52.Additionally,we conducted a subgroup analysis for the different thresholds(<35 or≥35)of PAC/PRC.The results showed that the DOR of the cut-off≥35 groups was higher than the cut-off<35 groups(DOR=340.15,95%CI:38.32-3019.66;DOR=116.40,95%CI=23.28-581.92).Conclusions:The research results suggest that the determination of ARR(PAC/PRC)and ARR(PAC/PRA)was all effective screening tools for PA.The diagnostic accuracy and diagnostic value of ARR(PAC/PRC)are higher than ARR(PAC/PRA).In addition,within a certain range,the higher the threshold,the better the diagnostic value.
基金supported by the National Natural Science Foundation of China(31972625)China Postdoctoral Science Foundation(2020M681718)+2 种基金Priority Academic Program Development(PAPD)of Jiangsu Higher Education InstitutionsPostgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX21_2963)China Agriculture Research System(CARS)of Ministry of Finance and Ministry of Agriculture and Rural Areas。
文摘Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration(PPC)and is often clinically complicated by malignant diseases or severe infections.At present,however,research on the molecular mechanism underlying high PPC(HPPC)is scant.Here,an animal model of primary hyperproteinemia was constructed in an invertebrate(Bombyx mori)to investigate the effects of HPPC on circulating blood cells.Results showed that HPPC affected blood cell homeostasis,leading to increased reactive oxygen species levels,and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway.HPPC induced the proliferation of blood cells,mainly granulocytes,by activating the Janus kinase/signal transducer and activator of transcription(JAK/STAT)signaling pathway.Supplementation with the endocrine hormone active substance 20 E significantly reduced the impact of HPPC on blood cell homeostasis.Thus,we identified a novel signaling pathway by which HPPC affects blood cell homeostasis,which differs from hyperglycemia,hyperlipidemia,and hypercholesterolemia.In addition,we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.
文摘OBJECTIVE:To examine whether specific stimulation of Shenshu(BL23)affects sympathetic nervous activity(SNA)-associated plasma renin concentration(PRC).METHODS:Eight healthy volunteers participated in three pattern conditions in random order:control(Cont),stimulation of Shenshu(BL23),and stimulation of sham point(Sham).All participants were initially in the supine position for>60 min,and then remained in the standing position during the experimental procedure to increase SNA.An electrocardiogram was used to calculate low frequency/high frequency(LF/HF)ratio;blood was collected to analyze PRC.RESULTS:The LF/HF ratio was significantly increased in the standing position when compared with the supine position(P<0.01).There was no difference in LF/HF ratio during or after stimulation of Shenshu(BL23)in the standing position when compared with before the stimulation in the supine position;however,the LF/HF ratio was significantly increased in Cont and Sham conditions(P<0.01).There was no difference in PRC after stimulation of Shenshu(BL23)in the standing position when compared with before the stimulation in the supine position;however,there was a significant increase in PRC in the Cont and Sham conditions(Cont P<0.05,Sham P<0.01).CONCLUSION:Our results demonstrated that specific acupuncture stimulation of Shenshu(BL23)in the standing position decreased SNA-associated PRC,which was not observed during acupuncture stimulation of the sham point.
