Objective To evaluate the inhibitory effect of Gnaphalium affine extracts on xanthine oxidase(XO) activity in vitro and to analyze the mechanism of this effect. Methods In this in vitro study, Kinetic measurements wer...Objective To evaluate the inhibitory effect of Gnaphalium affine extracts on xanthine oxidase(XO) activity in vitro and to analyze the mechanism of this effect. Methods In this in vitro study, Kinetic measurements were performed in 4 different inhibitor concentrations and 5 different xanthine concentrations(60, 100, 200, 300, 400 μmol/L). Dixon and Lineweaver-Burk plot analysis were used to determine Ki values and the inhibition mode for the compounds isolated from Gnaphalium affine extract. Results Four potent xanthine oxidase inhibitors were found in 95% ethanolic(v/v) Gnaphalium affine extract. Among them, the f lavone Eupatilin exhibited the strongest inhibitory effect on XO with a inhibition constant(Ki) of 0.37 μmol/L, lower than the Ki of allopurinol(4.56 mol/L), a known synthetic XO inhibitor. Apigenin(Ki of 0.56 μmol/L, a proportion of 0.0053‰ in Gnaphalium affine), luteolin(Ki of 2.63 μmol/L, 0.0032‰ in Gnaphalium affine) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone(Ki of 3.15 μmol/L, 0.0043‰ in Gnaphalium affine) also contributed to the inhibitory effect of Gnaphalium affine extract on XO activity. Conclusions These results suggest that the use of Gnaphalium affine in the treatment of gout could be attributed to its inhibitory effect on XO. This study provides a rational basis for the traditional use of Gnaphalium affine against gout.展开更多
The exact mechanism by which knockout of Toll-like receptor 4(TLR4)attenuates the liver injury remains unclear.The present study aimed to examine the role of TLR4 in the pathogenesis of bile duct ligation(BDL)-induced...The exact mechanism by which knockout of Toll-like receptor 4(TLR4)attenuates the liver injury remains unclear.The present study aimed to examine the role of TLR4 in the pathogenesis of bile duct ligation(BDL)-induced liver cholestatic injury and the underlying mechanism.Wild type(WT)mice and TLR4 knockout(TLR4-KO)mice were used for the establishment of the BDL model.Metabolomics were applied to analyze the changes of small molecular metabolites in the serum and liver of the two groups.The serum biochemical indexes and the HE staining results of liver tissue showed that liver damage was significantly reduced in TLR4-KO mice after BDL when compared with that in WT mice.The metabolite analysis results showed that TLR4 KO could maintain the metabolisms of amino acids-and choline-related metabolites.After BDL,the amino acids-and choline-related metabolites,especially choline and 3-hydroxybutyrate,were significantly increased in WT mice(both in serum and liver),but these metabolites in the liver of TLR4-KO mice after BLD were not significant different from those before BLD.In conclusion,TLR4 KO could attenuate BDL-induced liver cholestatic injury through regulating amino acid and choline metabolic pathways.展开更多
Objective:To compare the clinical effectiveness of gamma knife radiosugery combined with acupuncture therapy and microvascular decompression in the treatment of idiopathic trigeminal neuralgia.Methods:A total of 93 pa...Objective:To compare the clinical effectiveness of gamma knife radiosugery combined with acupuncture therapy and microvascular decompression in the treatment of idiopathic trigeminal neuralgia.Methods:A total of 93 patients with primary trigeminal neuralgia added to Nanchang University Hospital from November 2016 to October 2018 were selected,it was divided randomly into the control group(45 cases)and the study group(48 cases).The control group was treated with microvascular decompression and the study group used gamma knife radiosurgery combined with acupuncture therapy.The study compared the immediate pain relief rate,Visual Analogue Scale(VAS)scores,completion rate,recurrence rate,hospitalization days,total treatment duration,total treatment cost and total effective rate of treatment in 2 groups.Results:Comparison of the same group after treatment:the VAS score with 24 hours of treatment in the control group was(5.33±0.49),with a significant difference from the pre-treatment VAS score(8.62±0.13);The VAS score with 24 hours of treatment in the study group was(5.96±0.58),with a significant difference from the pre-treatment VAS score(8.54±0.25).After treatment,immediate effect,parent effect,acute and chronic complements of the control group was 25,5,2 and 7 cases,and the study group was 6,25,7 and 1,respectively.There were significant differences between the two groups;The comparison of hospitalization days,total treatment duration,total treatment cost was statistically significant(P<0.05);There were no significant difference in immediate pain rate,VAS score,total incidence of complications,recurrence rate,and total effectiveness of treatment between the two groups(P>0.05).Conclusion:Both microvascular decompression and gamma knife radiosurgery combined with acupuncture therapy can safe and effective treatment idiopathic trigeminal neuralgia patients,and for patients with good health,can tolerance all-hemp surgery,there are contraindicaindications to acupuncture therapy,microvascular decompression treatment can be chosen,while patients who are weak,cannot tolerante all-hemp surgery or resist surgery,economic difficulties,and can choose gamma knife radiosurgery combined with acupuncture therapy treatment.展开更多
Background:Globally,the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%.Differences of cause in neonate death exist in different regions as well as in different economic de...Background:Globally,the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%.Differences of cause in neonate death exist in different regions as well as in different economic development countries.The specific aim of this study was to investigate the causes,characteristics,and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.Methods:All the dead neonates admitted to 26 NICUs were included between January 1,2011,and December 31,2011.All the data were collected retrospectively from clinical records by a designed questionnaire.Data collected from each NICU were delivered to the leading institution where the results were analyzed.Results:A total of 744 newborns died during the l-year survey,accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals.Preterm neonate death accounted for 59.3% of all the death.The leading causes of death in preterm and term infants were pulmonary disease and infection,respectively.In early neonate period,pulmonary diseases (56.5%) occupied the largest proportion ofpreterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths.In late neonate period,infection was the leading cause of both preterm and term neonate deaths.About two-thirds of neonate death occurred after medical care withdrawal.Of the cases who might survive if receiving continuing treatment,parents' concern about the long-term outcomes was the main reason of medical care withdrawal.Conclusions:Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age.Our study showed the majority of neonate death occurred in preterm infants.Cause of death varied with the age of death and gestational age.Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.展开更多
Background:Ketogenic diet(KD)therapy is one of the main treatments for drug-resistant epilepsy.However,the KD therapy has been applied in only a small number of infantile spasm cases.In this large multicenter study,we...Background:Ketogenic diet(KD)therapy is one of the main treatments for drug-resistant epilepsy.However,the KD therapy has been applied in only a small number of infantile spasm cases.In this large multicenter study,we investigated the efficacy of KD therapy in the treatment of infantile spasms.Methods:In this retrospective,multicenter cohort study,clinical data from main epilepsy centers were analyzed.Patients were classified into different groups according to age,type of drug and whether glucocorticoid was used before initiation of KD.Results:From October 2014 to March 2020,481 patients(308 males and 173 females)with infantile spasms were treated with the KD therapy.The age of the patients ranged from 2 months to 20 years,with a mean age of 1 year and 10 months.The number of anti-seizure medications(ASMs)used before KD initiation ranged 0-6,with a median of 3.In different time from initiation(1,3,6,and 12 months),the rates of seizure freedom after KD were 6.9,11.6;16.0 and 16.8%,respectively(x^(2)=27.1772,P<0.0001).There was a significant difference in the rate of seizure freedom between 3 months and 1 month(x^(2)=6.5498,P=0.0105)groups,and 6 months and 3 months(x^(2)=3.8478,P=0.0498)groups,but not between 12 months and 6 months(x^(2)=0.1212,P=0.7278)groups.The rates of effectiveness were 44.7;62.8,49.1 and 32.0%(x^(2)=93.2674,P<0.0001),respectively.The retention rates were 94.0,82.5,55.7 and 33.1%(x^(2)=483.7551,P<0.0001),correspondingly.The rate of effectiveness and the retention rate of KD were significantly different among the 1,3,6 and 12 months.KD treatment was the first choice in 25 patients(5.2%),55 patients(11.4%)started KD after the failure of the first ASM,158 patients(32.8%)started KD after the failure of the second ASM,157 patients(32.6%)started KD after the failure of the third drug,and 86 patients(17.9%)started KD after the failure of the fourth and more.The KD effect was not related to the number of ASMs used before KD startup(P>0.05).Two hundred and eighteen patients(45.3%)failed to respond to corticotropin or glucocorticoid before initiation.There was no significant difference in the effectiveness rate at different time points between the group of KD therapy after glucocorticoid failure and the group after non-hormone failure (x^(2)=0.8613,P=0.8348).The rate of adverse events of KD in 1,3,6,and 12 months after KD initiation were 22.3,21.7,16.8 and 6.9%,respectively.The adverse events mainly occurred during the first 3 months of KD,and the main adverse events were gastrointestinal disturbance and constipation.Conclusions:The efficacy of the KD treatment for infantile spasms was not affected by age,medication,and glucocorticoid use before initiation.KD is one of the effective treatments for infantile spasms.展开更多
Background: With the progress ofperinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term ontcome...Background: With the progress ofperinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term ontcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China. Methods: All infants admitted to 26 NICUs with a birth weight (BW) 〈1000 g were included between January 1,2011 and December 31,2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors. Results: A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW 〈750 g and GA 〈28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization. Conclusions: Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.展开更多
Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and val...Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society(ICCS)recommended voiding diary.Methods A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary.The primary outcome measure was the compliance,assessed by comparing the completing index and the quality score of diaries between two groups.The secondary outcome measure was the validity,evaluated by comparing the constituent of subtypes,micturition parameters and response rate to desmopressin.Results Among the 1200 participants enrolled in the study,447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary.The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group.In addition,there was no significant difference between these two groups in the subtype classification,or in the response rate to desmopressin.Conclusions The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.展开更多
文摘Objective To evaluate the inhibitory effect of Gnaphalium affine extracts on xanthine oxidase(XO) activity in vitro and to analyze the mechanism of this effect. Methods In this in vitro study, Kinetic measurements were performed in 4 different inhibitor concentrations and 5 different xanthine concentrations(60, 100, 200, 300, 400 μmol/L). Dixon and Lineweaver-Burk plot analysis were used to determine Ki values and the inhibition mode for the compounds isolated from Gnaphalium affine extract. Results Four potent xanthine oxidase inhibitors were found in 95% ethanolic(v/v) Gnaphalium affine extract. Among them, the f lavone Eupatilin exhibited the strongest inhibitory effect on XO with a inhibition constant(Ki) of 0.37 μmol/L, lower than the Ki of allopurinol(4.56 mol/L), a known synthetic XO inhibitor. Apigenin(Ki of 0.56 μmol/L, a proportion of 0.0053‰ in Gnaphalium affine), luteolin(Ki of 2.63 μmol/L, 0.0032‰ in Gnaphalium affine) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone(Ki of 3.15 μmol/L, 0.0043‰ in Gnaphalium affine) also contributed to the inhibitory effect of Gnaphalium affine extract on XO activity. Conclusions These results suggest that the use of Gnaphalium affine in the treatment of gout could be attributed to its inhibitory effect on XO. This study provides a rational basis for the traditional use of Gnaphalium affine against gout.
基金the National Natural Science Foundation of China(Nos.81960101,81860483).
文摘The exact mechanism by which knockout of Toll-like receptor 4(TLR4)attenuates the liver injury remains unclear.The present study aimed to examine the role of TLR4 in the pathogenesis of bile duct ligation(BDL)-induced liver cholestatic injury and the underlying mechanism.Wild type(WT)mice and TLR4 knockout(TLR4-KO)mice were used for the establishment of the BDL model.Metabolomics were applied to analyze the changes of small molecular metabolites in the serum and liver of the two groups.The serum biochemical indexes and the HE staining results of liver tissue showed that liver damage was significantly reduced in TLR4-KO mice after BDL when compared with that in WT mice.The metabolite analysis results showed that TLR4 KO could maintain the metabolisms of amino acids-and choline-related metabolites.After BDL,the amino acids-and choline-related metabolites,especially choline and 3-hydroxybutyrate,were significantly increased in WT mice(both in serum and liver),but these metabolites in the liver of TLR4-KO mice after BLD were not significant different from those before BLD.In conclusion,TLR4 KO could attenuate BDL-induced liver cholestatic injury through regulating amino acid and choline metabolic pathways.
基金Science and Technology Plan Project of Jiangxi Provincial Health and Health Commission(20200506).
文摘Objective:To compare the clinical effectiveness of gamma knife radiosugery combined with acupuncture therapy and microvascular decompression in the treatment of idiopathic trigeminal neuralgia.Methods:A total of 93 patients with primary trigeminal neuralgia added to Nanchang University Hospital from November 2016 to October 2018 were selected,it was divided randomly into the control group(45 cases)and the study group(48 cases).The control group was treated with microvascular decompression and the study group used gamma knife radiosurgery combined with acupuncture therapy.The study compared the immediate pain relief rate,Visual Analogue Scale(VAS)scores,completion rate,recurrence rate,hospitalization days,total treatment duration,total treatment cost and total effective rate of treatment in 2 groups.Results:Comparison of the same group after treatment:the VAS score with 24 hours of treatment in the control group was(5.33±0.49),with a significant difference from the pre-treatment VAS score(8.62±0.13);The VAS score with 24 hours of treatment in the study group was(5.96±0.58),with a significant difference from the pre-treatment VAS score(8.54±0.25).After treatment,immediate effect,parent effect,acute and chronic complements of the control group was 25,5,2 and 7 cases,and the study group was 6,25,7 and 1,respectively.There were significant differences between the two groups;The comparison of hospitalization days,total treatment duration,total treatment cost was statistically significant(P<0.05);There were no significant difference in immediate pain rate,VAS score,total incidence of complications,recurrence rate,and total effectiveness of treatment between the two groups(P>0.05).Conclusion:Both microvascular decompression and gamma knife radiosurgery combined with acupuncture therapy can safe and effective treatment idiopathic trigeminal neuralgia patients,and for patients with good health,can tolerance all-hemp surgery,there are contraindicaindications to acupuncture therapy,microvascular decompression treatment can be chosen,while patients who are weak,cannot tolerante all-hemp surgery or resist surgery,economic difficulties,and can choose gamma knife radiosurgery combined with acupuncture therapy treatment.
文摘Background:Globally,the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%.Differences of cause in neonate death exist in different regions as well as in different economic development countries.The specific aim of this study was to investigate the causes,characteristics,and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.Methods:All the dead neonates admitted to 26 NICUs were included between January 1,2011,and December 31,2011.All the data were collected retrospectively from clinical records by a designed questionnaire.Data collected from each NICU were delivered to the leading institution where the results were analyzed.Results:A total of 744 newborns died during the l-year survey,accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals.Preterm neonate death accounted for 59.3% of all the death.The leading causes of death in preterm and term infants were pulmonary disease and infection,respectively.In early neonate period,pulmonary diseases (56.5%) occupied the largest proportion ofpreterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths.In late neonate period,infection was the leading cause of both preterm and term neonate deaths.About two-thirds of neonate death occurred after medical care withdrawal.Of the cases who might survive if receiving continuing treatment,parents' concern about the long-term outcomes was the main reason of medical care withdrawal.Conclusions:Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age.Our study showed the majority of neonate death occurred in preterm infants.Cause of death varied with the age of death and gestational age.Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.
基金This study was supported by the Sanming Project of Medicine in Shenzhen(SZSM201812005)Shenzhen Key Medical Discipline Construction Fund(No.SZXK033)Shenzhen Fund for Guangdong Provincial High Level Clinical Key Specialties(No.SZGSPO12).
文摘Background:Ketogenic diet(KD)therapy is one of the main treatments for drug-resistant epilepsy.However,the KD therapy has been applied in only a small number of infantile spasm cases.In this large multicenter study,we investigated the efficacy of KD therapy in the treatment of infantile spasms.Methods:In this retrospective,multicenter cohort study,clinical data from main epilepsy centers were analyzed.Patients were classified into different groups according to age,type of drug and whether glucocorticoid was used before initiation of KD.Results:From October 2014 to March 2020,481 patients(308 males and 173 females)with infantile spasms were treated with the KD therapy.The age of the patients ranged from 2 months to 20 years,with a mean age of 1 year and 10 months.The number of anti-seizure medications(ASMs)used before KD initiation ranged 0-6,with a median of 3.In different time from initiation(1,3,6,and 12 months),the rates of seizure freedom after KD were 6.9,11.6;16.0 and 16.8%,respectively(x^(2)=27.1772,P<0.0001).There was a significant difference in the rate of seizure freedom between 3 months and 1 month(x^(2)=6.5498,P=0.0105)groups,and 6 months and 3 months(x^(2)=3.8478,P=0.0498)groups,but not between 12 months and 6 months(x^(2)=0.1212,P=0.7278)groups.The rates of effectiveness were 44.7;62.8,49.1 and 32.0%(x^(2)=93.2674,P<0.0001),respectively.The retention rates were 94.0,82.5,55.7 and 33.1%(x^(2)=483.7551,P<0.0001),correspondingly.The rate of effectiveness and the retention rate of KD were significantly different among the 1,3,6 and 12 months.KD treatment was the first choice in 25 patients(5.2%),55 patients(11.4%)started KD after the failure of the first ASM,158 patients(32.8%)started KD after the failure of the second ASM,157 patients(32.6%)started KD after the failure of the third drug,and 86 patients(17.9%)started KD after the failure of the fourth and more.The KD effect was not related to the number of ASMs used before KD startup(P>0.05).Two hundred and eighteen patients(45.3%)failed to respond to corticotropin or glucocorticoid before initiation.There was no significant difference in the effectiveness rate at different time points between the group of KD therapy after glucocorticoid failure and the group after non-hormone failure (x^(2)=0.8613,P=0.8348).The rate of adverse events of KD in 1,3,6,and 12 months after KD initiation were 22.3,21.7,16.8 and 6.9%,respectively.The adverse events mainly occurred during the first 3 months of KD,and the main adverse events were gastrointestinal disturbance and constipation.Conclusions:The efficacy of the KD treatment for infantile spasms was not affected by age,medication,and glucocorticoid use before initiation.KD is one of the effective treatments for infantile spasms.
文摘Background: With the progress ofperinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term ontcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China. Methods: All infants admitted to 26 NICUs with a birth weight (BW) 〈1000 g were included between January 1,2011 and December 31,2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors. Results: A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW 〈750 g and GA 〈28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization. Conclusions: Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.
基金funding from the National Natural Foundation of China(81770710)Key Research and Development Plan of Zhejiang Province(2019C03028)+1 种基金the Major projects jointly constructed by the Zhejiang province and National Health Commission(WKJ-ZJ-1908)the Natural Science Foundation of Zhejiang Province(LQ18H050001).
文摘Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society(ICCS)recommended voiding diary.Methods A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary.The primary outcome measure was the compliance,assessed by comparing the completing index and the quality score of diaries between two groups.The secondary outcome measure was the validity,evaluated by comparing the constituent of subtypes,micturition parameters and response rate to desmopressin.Results Among the 1200 participants enrolled in the study,447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary.The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group.In addition,there was no significant difference between these two groups in the subtype classification,or in the response rate to desmopressin.Conclusions The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.