BACKGROUND The use of network pharmacology and blood metabolomics to study the patho-genesis of violent aggression in patients with schizophrenia and the related drug mechanisms of action provides new directions for r...BACKGROUND The use of network pharmacology and blood metabolomics to study the patho-genesis of violent aggression in patients with schizophrenia and the related drug mechanisms of action provides new directions for reducing the risk of violent aggression and optimizing treatment plans.AIM To explore the metabolic regulatory mechanism of olanzapine in treating patients with schizophrenia with a moderate to high risk of violent aggression.METHODS Metabolomic technology was used to screen differentially abundant metabolites in patients with schizophrenia with a moderate to high risk of violent aggression before and after olanzapine treatment,and the related metabolic pathways were identified.Network pharmacology was used to establish protein-protein interaction networks of the core targets of olanzapine.Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were subsequently performed.RESULTS Compared with the healthy group,the patients with schizophrenia group presented significant changes in the levels of 24 metabolites related to the disruption of 9 metabolic pathways,among which the key pathways were the alanine,aspartate and glutamate metabolism and arginine biosynthesis pathways.After treatment with olanzapine,the levels of 10 differentially abundant metabolites were significantly reversed in patients with schizophrenia.Olanzapine effectively regulated six metabolic pathways,among which the key pathways were alanine,aspartate and glutamate metabolism and arginine biosynthesis pathways.Ten core targets of olanzapine were involved in several key pathways.CONCLUSION The metabolic pathways of alanine,aspartate,and glutamate metabolism and arginine biosynthesis are the key pathways involved in olanzapine treatment for aggressive schizophrenia.展开更多
Background:Compared to adult studies,studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism(CHH)are limited and no universal treatment regimen is available.The aim of this study was ...Background:Compared to adult studies,studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism(CHH)are limited and no universal treatment regimen is available.The aim of this study was to evaluate the feasibility of human chorionic gonadotropin(hCG)/human menopausal gonadotropin(hMG)therapy for treating male adolescents with CHH.Methods:Male adolescent CHH patients were treated with hCG/hMG(n=20)or a gonadotropin-releasing hormone(GnRH)pump(n=21).The treatment was divided into a study phase(0-3 months)and a follow-up phase(3-12 months).The testicular volume(TV),penile length(PL),penis diameter(PD),and sex hormone levels were compared between the two groups.The TV and other indicators between the groups were analyzed using a t-test(equal variance)or a rank sum test(unequal variance).Results:Before treatment,there was no statistical difference between the two groups in terms of the biochemistry,hormones,and other demographic indicators.After 3 months of treatment,the TV of the hCG/hMG and GnRH groups increased to 5.1±2.3 mL and 4.1±1.8 mL,respectively;however,the difference was not statistically significant(P>0.05,t=1.394).The PL reached 6.9±1.8 cm and 5.1±1.6 cm(P<0.05,t=3.083),the PD reached 2.4±0.5 cm and 2.0±0.6 cm(P<0.05,t=2.224),respectively,in the two groups.At the end of 6 months of treatment,biomarkers were in normal range in the two groups.Compared with the GnRH group,the testosterone(T)level and growth of PL and PD were significantly greater in the hCG/hMG group(all P<0.05).While the TV of both groups increased,the difference was not statistically significant(P>0.05,t=0.314).After 9 to 12 months of treatment,the T level was higher in the hCG/hMG group.Other parameters did not exhibit a statistical difference.Conclusions:The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH.The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy.Furthermore,results from the extended time-period showed positive outcomes at the 1-year mark;however,the long-term effectiveness,strengths,and weaknesses of the hCG/hMG regimen require further research.Trial Registration:ClinicalTrials.gov,NCT02880280;https://clinicaltrials.gov/ct2/show/NCT02880280.展开更多
To the Editor:Noonan syndrome (NS)is a common genetic multisystem disorder caused by aberrant signal flux through mitogen-activated protein kinase (Ras-MAPK) and has an estimated prevalence of 1 in 1000-2500[1]. It wa...To the Editor:Noonan syndrome (NS)is a common genetic multisystem disorder caused by aberrant signal flux through mitogen-activated protein kinase (Ras-MAPK) and has an estimated prevalence of 1 in 1000-2500[1]. It was characterized by Jacqueline Noonan,who reported nine patients with pulmonary valve stenosis,small stature, hypertelorism,mild intellectual disability,webbed neck, undescended testes,and skeletal malformations[2], The lymphatic disorders are rare,it can happen at any age but most instances happen at birth,which are known to be particularly associated with NS,though it has not been well characterized to date.Gene mutations identified in individuals with the NS,regulate impertinently the Ras/ MAPK signal transduction pathway and they can currently explain 70 %of the NS cases.Therefore,it is very important for genetic counseling and life management.[2] Here,we reported a rare Noonan syndrome 9 patient in Asian with significant,persistent and progressive bilateral lower limb dysplasia.展开更多
基金Supported by Henan Provincial Science and Technology Research Project,No.242102310203.
文摘BACKGROUND The use of network pharmacology and blood metabolomics to study the patho-genesis of violent aggression in patients with schizophrenia and the related drug mechanisms of action provides new directions for reducing the risk of violent aggression and optimizing treatment plans.AIM To explore the metabolic regulatory mechanism of olanzapine in treating patients with schizophrenia with a moderate to high risk of violent aggression.METHODS Metabolomic technology was used to screen differentially abundant metabolites in patients with schizophrenia with a moderate to high risk of violent aggression before and after olanzapine treatment,and the related metabolic pathways were identified.Network pharmacology was used to establish protein-protein interaction networks of the core targets of olanzapine.Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were subsequently performed.RESULTS Compared with the healthy group,the patients with schizophrenia group presented significant changes in the levels of 24 metabolites related to the disruption of 9 metabolic pathways,among which the key pathways were the alanine,aspartate and glutamate metabolism and arginine biosynthesis pathways.After treatment with olanzapine,the levels of 10 differentially abundant metabolites were significantly reversed in patients with schizophrenia.Olanzapine effectively regulated six metabolic pathways,among which the key pathways were alanine,aspartate and glutamate metabolism and arginine biosynthesis pathways.Ten core targets of olanzapine were involved in several key pathways.CONCLUSION The metabolic pathways of alanine,aspartate,and glutamate metabolism and arginine biosynthesis are the key pathways involved in olanzapine treatment for aggressive schizophrenia.
基金supported by a grant from Jin Lei Pediatric Endocrinology Growth Research Fund for Young Physicians(PEGRF)(No.PEGRF201809006).
文摘Background:Compared to adult studies,studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism(CHH)are limited and no universal treatment regimen is available.The aim of this study was to evaluate the feasibility of human chorionic gonadotropin(hCG)/human menopausal gonadotropin(hMG)therapy for treating male adolescents with CHH.Methods:Male adolescent CHH patients were treated with hCG/hMG(n=20)or a gonadotropin-releasing hormone(GnRH)pump(n=21).The treatment was divided into a study phase(0-3 months)and a follow-up phase(3-12 months).The testicular volume(TV),penile length(PL),penis diameter(PD),and sex hormone levels were compared between the two groups.The TV and other indicators between the groups were analyzed using a t-test(equal variance)or a rank sum test(unequal variance).Results:Before treatment,there was no statistical difference between the two groups in terms of the biochemistry,hormones,and other demographic indicators.After 3 months of treatment,the TV of the hCG/hMG and GnRH groups increased to 5.1±2.3 mL and 4.1±1.8 mL,respectively;however,the difference was not statistically significant(P>0.05,t=1.394).The PL reached 6.9±1.8 cm and 5.1±1.6 cm(P<0.05,t=3.083),the PD reached 2.4±0.5 cm and 2.0±0.6 cm(P<0.05,t=2.224),respectively,in the two groups.At the end of 6 months of treatment,biomarkers were in normal range in the two groups.Compared with the GnRH group,the testosterone(T)level and growth of PL and PD were significantly greater in the hCG/hMG group(all P<0.05).While the TV of both groups increased,the difference was not statistically significant(P>0.05,t=0.314).After 9 to 12 months of treatment,the T level was higher in the hCG/hMG group.Other parameters did not exhibit a statistical difference.Conclusions:The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH.The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy.Furthermore,results from the extended time-period showed positive outcomes at the 1-year mark;however,the long-term effectiveness,strengths,and weaknesses of the hCG/hMG regimen require further research.Trial Registration:ClinicalTrials.gov,NCT02880280;https://clinicaltrials.gov/ct2/show/NCT02880280.
文摘To the Editor:Noonan syndrome (NS)is a common genetic multisystem disorder caused by aberrant signal flux through mitogen-activated protein kinase (Ras-MAPK) and has an estimated prevalence of 1 in 1000-2500[1]. It was characterized by Jacqueline Noonan,who reported nine patients with pulmonary valve stenosis,small stature, hypertelorism,mild intellectual disability,webbed neck, undescended testes,and skeletal malformations[2], The lymphatic disorders are rare,it can happen at any age but most instances happen at birth,which are known to be particularly associated with NS,though it has not been well characterized to date.Gene mutations identified in individuals with the NS,regulate impertinently the Ras/ MAPK signal transduction pathway and they can currently explain 70 %of the NS cases.Therefore,it is very important for genetic counseling and life management.[2] Here,we reported a rare Noonan syndrome 9 patient in Asian with significant,persistent and progressive bilateral lower limb dysplasia.
