Effects of icariin-astragaloside IV-puerarin mixture on cognitive function and ferroptosis amino acid metabolism pathway in APP/PS1 HAMP-/-mice / 中国病理生理杂志

AIM:To observe the effect of icariin-astragaloside Ⅳ-puerarin mixture(Yin-Huang-Ge mixture,YHG)on cognitive function and ferroptosis amino acid metabolism pathway in hepcidin(HAMP)knockout APPswe/PS1dE9(APP/PS1 HAMP-/-)mice.METHODS:The mice were divided into 7 groups:negative control(C57BL/6 mice)group,APP/PS1 group,APP/PS1 HAMP-/-group,APP/PS1+YHG group,APP/PS1 HAMP-/-+YHG group,APP/PS1+de-ferasirox(DFX)group,and APP/PS1 HAMP-/-+DFX group,with 6 mice in each group.The YHG and DFX were adminis-tered intragastrically,while the mice in C57 group,APP/PS1 group and APP/PS1 HAMP-/-group were given intragastric administration of distilled water,once a day for 2 months.The iron content in mouse brain tissues was detected by tissue iron kit.The morphological changes of the mitochondria in hippocampal neurons were observed by transmission electron microscopy.Morris water maze was used to detect the learning and memory ability of the mice.The content of neuronal nu-clear antigen(NeuN)in mouse brain tissues was detected by immunofluorescence staining.The expression of glutathione(GSH)in mouse brain tissues was detected by biochemical kit.The expression levels of glutamate-cysteine ligase catalytic subunit(GCLC)and glutamatase 2(GLS2)in mouse brain tissues were detected by Western blot.RESULTS:Compared with C57BL/6 mice,the brain iron content of APP/PS1 mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seri-ously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.01).Compared with APP/PS1 mice,the brain iron content of APP/PS1 HAMP-/-mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seriously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.05).After treatment with YHG and DFX,the brain iron content was significantly decreased(P＜0.01),the mitochondrial damage was alleviated,the learning and memory ability was significantly increased(P＜0.05),the brain neuron damage was alleviated(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly increased(P＜0.05).CONCLUSION:The YHG can improve the cognitive function of APP/PS1 HAMP-/-mice,and its mechanism may be related to the regulation of ferroptosis amino acid metabolism and the enhancement of antioxidant capacity.

Prevalence, risk factors and characteristics of delirium in intensive care unit patients: a prospective observational study / 中华危重病急救医学

OBJECTIVE@#To investigate the prevalence, risk factors, duration and outcome of delirium in intensive care unit (ICU) patients.@*METHODS@#A prospective observational study was conducted for critically ill patients admitted to the department of critical care medicine, the Affiliated Hospital of Guizhou Medical University from September to November 2021. Delirium assessments were performed twice daily using the Richmond agitation-sedation scale (RASS) and confusion assessment method of ICU (CAM-ICU) for patients who met the inclusions and exclusion criteria. Patient's age, gender, body mass index (BMI), underlying disease, acute physiologic assessment and chronic health evaluation (APACHE) at ICU admission, sequential organ failure assessment (SOFA) at ICU admission, oxygenation index (PaO2/FiO2), diagnosis, type of delirium, duration of delirium, outcome, etc. were recorded. Patients were divided into delirium and non-delirium groups according to whether delirium occurred during the study period. The clinical characteristics of the patients in the two groups were compared, and risk factors for the development of delirium were screened using univariate analysis and multivariate Logistic regression analysis.@*RESULTS@#A total of 347 ICU patients were included, and delirium occurred in 57.6% (200/347) patients. The most common type was hypoactive delirium (73.0% of the total). Univariate analysis showed statistically significant differences in age, APACHE score and SOFA score at ICU admission, history of smoking, hypertension, history of cerebral infarction, immunosuppression, neurological disease, sepsis, shock, glucose (Glu), PaO2/FiO2 at ICU admission, length of ICU stay, and duration of mechanical ventilation between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.045, 95% confidence interval (95%CI) was 1.027-1.063, P < 0.001], APACHE score at ICU admission (OR = 1.049, 95%CI was 1.008-1.091, P = 0.018), neurological disease (OR = 5.275, 95%CI was 1.825-15.248, P = 0.002), sepsis (OR = 1.941, 95%CI was 1.117-3.374, P = 0.019), and duration of mechanical ventilation (OR = 1.005, 95%CI was 1.001-1.009, P = 0.012) were all independent risk factors for the development of delirium in ICU patients. The median duration of delirium in ICU patients was 2 (1, 3) days. Delirium was still present in 52% patients when they discharged from the ICU.@*CONCLUSIONS@#The prevalence of delirium in ICU patients is over 50%, with hypoactive delirium being the most common. Age, APACHE score at ICU admission, neurological disease, sepsis and duration of mechanical ventilation were all independent risk factors for the development of delirium in ICU patients. More than half of patients with delirium were still delirious when they discharged from the ICU.

Recommendations for prescription review of commonly used anti-seizure medications in treatment of children with epilepsy / 中华实用儿科临床杂志

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Safety and efficacy of oral Lacosamide as an add-on therapy in Chinese children with partial-onset seizures / 中华实用儿科临床杂志

Objective:To evaluate the long-term safety, tolerability and efficacy of Lacosamide add-on therapy in Chinese children with partial-onset seizures.Methods:SP848 was a global multicenter single-arm study involving 60 Chinese children with partial-onset seizures with the age of 4-17 years who were managed by Lacosamide add-on therapy at seven hospitals across China from April 2018 to May 2019.After treatment with at least two kinds of anti-seizure medications simultaneously or sequentially, partial seizures were still poorly controlled and Lacosamide oral solution (syrup) or tablets were added.The minimum initial oral dose was 2 mg/(kg·d), and the maximum allowable dose was 12 mg/(kg·d)or 600 mg/d during the study period.The dose was adjusted according to the tolerance and seizure control level of partial-onset seizures children.Seizure frequency and the median percentage change in partial-onset seizures per 28 days from baseline to the final visit were recorded, including 50% responder rate and 75% responder rate.Results:A total of 60 Chinese children with the mean age of 9.18 (4.00-15.40) years were included in this interim analysis, involving 39 males and 21 females.The mean course of epilepsy was 5.04 (0.50-15.20) years.A total of 43 patients (71.7%) still have been treated.One patient (1.7%) has completed the 6-12 months of follow-up, and 14 patients (23.3%) have completed the follow-up for less than 6 months.The median change in the frequency of partial seizures every 28 days from baseline to the last visit was -2.91, with its median percentage as -25.46%, and the proportions of ≥50%, while ≥75% responder rate were 40.0% and 28.3%, respectively.A total of 52 patients (86.7%) had 265 treatment emergent adverse events (TEAE), 11 patients (18.3%) had 19 serious TEAE, 37 patients (61.7%) had 127 drug-related TEAE, and 11 patients (18.3%) had 16 TEAE leading to the discontinuation of the trial.The most common TEAE were upper respiratory tract infections (20 cases, 33.3%), followed by drowsiness (16 cases, 26.7%), dizziness (15 cases, 25.0%) and vomiting (13 cases, 21.7%). There were no abnormal changes in the electrocardiographic findings during the treatment.Conclusions:For Chinese patients with partial seizures who are older than the age of 4 years and poorly controlled by other drugs, Lacosamide is effective and well tolerated as an add-on therapy drug.The safety characteristics are consistent with those reported in children and adults.No new safety concerns are identified.

Advance on vitamin D in the pathogenesis of autism spectrum disorders / 中华实用儿科临床杂志

Autism spectrum disorder(ASD)is a kind of neurodevelopmental disorder.Despite the high prevalence of ASD, no definite pathogenesis of ASD has yet been elucidated to date.Accumulating evidence indicated that the pathogenesis of ASD may be related to genetic, environmental and immune factors.Studies has been shown that vitamin D(Vit D)deficiency is negatively correlated with the prevalence of ASD, and that supplementation with Vit D may reduce the risk of ASD.Because of the extensive physiological functions of Vit D, it can act as a steroid hormone in multiple aspects such as genetic, environment and immune profiles.Meanwhile, the genetic, environmental and immune changes could also affect the metabolism and function of Vit D, and vice versa.Therefore, Vit D deficiency probably lead to the development of ASD.This review focuses on the relationship between Vit D and environmental, genetic and immune factors of ASD.

Clinical application of metagenomics sequencing in children with acute bacterial meningitis / 中华实用儿科临床杂志

Objective:To explore the application value of metagenomics sequencing in the etiological diagnosis of bacterial meningitis(BM) in children and improve the diagnosis and treatment effect of BM in children.Methods:All BM cases were collected from Jiangxi Provincial Children′s Hospital from February 1, 2018 to January 31, 2020.Meanwhile, such biological samples as blood and cerebrospinal fluid were collected for traditional etiological testing and metagenomics sequencing.The results of traditional etiological testing were regarded as the gold standard, and the specificity and sensitivity of metagenomics sequencing in the diagnosis of BM in children were confirmed.Results:A total of 45 cases were collected in this study, including 31 males and 14 females, with the age between (74.74 ± 58.67) months.Twenty-six cases were identified by metagenomics sequencing, with the positive rate being 57.78%.Among them, there were 8 cases of Streptococcus pneumoniae, 2 cases of Escherichia coli, 2 cases of Neisseria meningitidis, 2 cases of Staphylococcus, 2 cases of Salmonella, 2 cases of Mycobacterium multiplex, 1 case of Streptococcus intermedius, 1 case of Streptococcus pyogenes, 1 case of Streptococcus paris, 1 case of Streptococcus salivarius, 1 case of Haemophilus influenzae, 1 case of Pseudomonas aeruginosa, 1 case of Acinetobacter baumannii, and 1 case of Aspergillus.The traditional etiological positive rate was 17.78%, and the metagenomic next-generation sequencing (mNGS) positive rate was 57.78% ( P=0.014, kappa=0.273). As per the comparison results, the sensitivity, specificity, positive predictive value, negative predictive value, Youden index and misdiagnosis rate were 100.00%, 51.35%, 30.76%, 100.00%, 51.36%, 48.64% and 0, respectively. Conclusions:Metagenomics examination had high sensitivity, which can improve the etiological diagnosis rate of acute BM in children, especially in case of high clinical suspicion of infection.Therefore, metagenomics examination should be selected as early as possible when the etiology cannot be determined by traditional approaches.

Research progress of copy number variations associated with infantile spasms / 中华实用儿科临床杂志

Infantile spasms (ISs) is an age-dependent epileptic encephalopathy, which is highly associated with cognitive impairment, autism spectrum disorder and developmental delay.At present, inheritance patterns, including chromosomal abnormalities, copy number variations (CNVs), and monogenic diseases have been found to correlated with the etiology of ISs.Among them, CNVs or structural chromosome rearrangements are of great significance in the pathogenesis of ISs.This article aims to review the research progress of CNVs and ISs, thus providing references for further clarifying the molecular mechanism and genetic basis of ISs.

Clinical observation of rotavirus associated mild encephalopathy/encephalitis with reversible splenial lesion / 中华实用儿科临床杂志

Objective To explore the clinical characteristics of rotavirus associated mild encephalopathy/encephalitis with reversible splenial lesion(RAMERS).Methods RAMERS cases were collected from December 2017 to January 2018 at the Department of Neurology,Jiangxi Children's Hospital.The clinical and electroencephalogram characteristics of 14 patients with RAMERS were retrospectively investigated.Data was analyzed by using SPSS 19.0 software.Results Fourteen cases of RAMERS were tested,9 males,and 5 females,with the average age of (27.00 ±6.45) months,and all cases suffered from the generalized tonic-clonic seizures,57.14％ (8/14 cases) had cluster seizure (at lest 2 times/day),convulsions occurred (3.14 ± 1.29) days after gastroenteritis,and 64.29％ (9/14 cases) had pathologic fever (38 ℃ or higher).The background of electroencephalogram(EEG) was characterized by nonspecific rhythmic slow waves in 10 cases (71.43 ％,10/14 cases),normal in 3 cases (21.43 ％,3/14 cases),and interictal EEG performed in 1 case(7.14％,1/14 cases) which was characterized by focal discharges of spikes in the forehead,central,and all of the EEG manifestations go back to normal after 2 weeks.Twelve patients' brain MRI showed solitary splenium of corpus callosum lesion,and two showed splenium of corpus callosum and bilateral symmetry white matter lesion.Conclusions RAMERS is a special type of reversible splenial lesion syndrome,which occurs predominantly in infants and young children.It is characterized by gastroenteritis,benign infantile convulsion,cluster seizure and nonspecific rhythmic slow waves in the background of EEG.Prognosis is usually excellent.Head MRI reexamination is not recommended as a routine procedure to avoid overtreatment.

The efficacy of prednisone in the treatment of infantile spasm and HPA axis mechanism analysis / 国际儿科学杂志

Objective By studying the changes of the seizures of infantile spasm(IS)、EEG and HPA axis function before and after the treatment of prednisone,to explore the efficacy of prednisone in treating infan-tile spasm,the role of HPA axis in the pathogenesis of IS,and elucidate the HPA axis mechanism of prednisone in controling seizure.Methods A total of 30 patients with IS (IS group) and 30 cases of healthy infants and young children (control group) were recruited.Number of seizures、EEG、HPA axis function was detected be-fore and after the treatment of prednisone in patients with infantile spasm.Serum cortisol,ACTH were deter-mined by the chemiluminescence analysis,serum CRH was measured by enzyme-linked immunosorbent assay. Results serum CRH levels of IS group was significantly higher than normal control group(P<0.05).Serum cortisol,ACTH in IS group were no evidently different compared with control group (P>0.05).The average number of daily ictal clusters and the average daily total seizure number positively correlated with CRH respec-tively.After the application of the prednisolone,seizure of 19 cases of the IS were controlled,11 cases were not controlled,18 cases of hyperarrhythmia were completely remited and 12 cases of hyperarrhythmia were not com-pletely remited.The average number of daily ictal clusters and The average daily total seizure number after treat-ment were significantly lower than before treatment(P<0.05);DQ after treatment was higher than DQ before treatment(P<0.05);The pathogenesis was the main influencing factor of the prednisone treatment effect,the length of the disease,the worse the treatment(P<0.05).CRH、cortisol、ACTH after treatment were significantly lower than before treatment(P<0.05).Conclusion Prednisone can effectively control the onset of infantile spasms,and early treatment is better.IS patient has HPA axis dysfunction,and prednisone can regulate HPA axis dysfunction to control spasm.

Influencing factors of infantile spasms relapse after remission / 中华实用儿科临床杂志

Objective To analyze the potential risk factors of infantile spasms (IS) relapse through following up the respondents with IS after different treatment protocols.Methods Sixty-nine cases were collected in the Department of Pediatric Neurology,Jiangxi Children's Hospital from May 2011 to September 2013,who had complete cessation of spasms for at least 28 days or more after the different treatment protocols.The follow-up was performed on these patients until spasms seizure relapse or at least 1 year for those without recurrence.According to the literature review,8 possible risk factors of IS recurrence (gender,age of onset,course of diseases,etiology,high irregular types of electroencephalogram,development quotient,onset time,treatment protocols) were selected,and then Logistic multiple regression was used to analyze the relationship of various potential risk factors with the relapse of spasms.Results (1) The recurrence rate at 6 months and 12 months were 40.6％ (28/69 cases)and 43.5 ％ (30/69 cases),respectively.(2) Among the various potential factors,the age at onset and the time to response were closely related to the IS recurrence.Namely,the non-classic onset(early-onset and late-onset) of IS were more likely to relapse than the classic onset[66.7％ (14/21 cases) vs 33.3％ (16/48 cases),x2 =6.605,P =0.010];the responders beyond 1 week were more likely to relapse than those within 1 week[63.6％ (14/22 cases) vs 34.0％ (16/47 cases),x2 =5.341,P =0.021].There were significant differences between the 2 groups (all P ＜ 0.05).(3) Logistic multiple regression analysis demonstrated that age at onset (Wald =3.603) was most closely related to the relapse of spasms.Conclusions (1) The relapse rate of IS in children was high,and the majority of them relapsed within 6 months.So a long-term,rational and effective clinical management solution should be explored.(2) The age at onset and the time to response are very important risk factors of the IS recurrence,and the former was more significant.So,early diagnosis and early treatment are more likely to improve the efficacy of IS,and reduce the risks of recurrence and improve the prognosis.

Advances on medical management of Lennox-Gastaut syndrome / 国际儿科学杂志

Lennox-Gastaut syndrome ( LGS) is an globally recognized refractory epilepsy,also known as an age-dependent epileptic encephalopathy. It is characterized by multiple seizure types, mental retardation, and slow spike-wave complexes discharges or fast rhythmic bursts during sleep on electroencephalographic re-cordings. Many antiepileptic drugs were reported for the treatment of LGS,but it was difficult to compare their efficacy because of the small sample size and design limitations. Valproate,topiramate and lamotrigine are rec-ommended to be the first-line drugs by most guidelines or expert consensus,and the combination of valproate and lamotrigine or the combination of lamotrigine and topiramate should be preferred as early as possible for initial treatment of LGS in children. Recent progresses of medical treatment of LGS are reviewed and some optical re-gimes are proposed in this paper.

Efficacy and safety of different doses of prednisone combined with topiramate for the children with infantile spasms / 中华实用儿科临床杂志

Objective To evaluate the clinical efficacy and safety of different doses of prednisone combined with topiramate(TPM) in the treatment of infantile spasms(IS),in order to provide a new choice of the therapy of IS.Methods Fifty-six cases were collected in the Department of Neurology of Jiangxi Children's Hospital from May.2011 to Dec.2012.They were randomly divided into 2 groups:control group and trial group.The patients in control group took prednisone tablet of 1 mg/kg,2 times a day for 2 weeks;and the patients in trial group took prednisone tablet of 10 mg/ d,4 times a day for 2 weeks.In addition,TPM was used in both groups by initial dose 1 mg/(kg · d) or 2 times a day,and then was gradually increased to 3-5 mg/(kg · d) within 2 weeks.For those children in whom the spasms seizure completely ceased after 2 weeks,prednisone was then reduced by degrees to be discontinued for a 7-weeks course(extending to 4 weeks with the initial doses if spasms continued after 2 weeks).All patients underwent the assessment of spasms seizure and a 3-12 h video-electroencephalogram monitoring including wake and sleep states,which were performed before treatment,after 2 weeks and the end of the courses (7 or 9 weeks after treatment),respectively.Meanwhile,the side effects of the drugs during the treatment were recorded.The developmental quotient (DQ) tests of children with complete cessation of spasms more than 6 months were performed before treatment and after 6 months.All patients had been followed up for 2-18 months.Results 1.After 2 weeks of the therapy,the rate of cessation of spasms were 75.00％ (21/28 cases) and 28.57％ (8/28 cases) in the trial group and the control group,respectively,there was significant difference (x2 =12.087,P =0.001).And in the same term,the rate of complete resolution of hypsrrhythmia were 60.71％ (17/28 cases) and 21.43 ％ (6/28 cases),respectively,there was significant difference (x2 =8.928,P =0.003).At the end of treatment,the rate of cessation of spasms were 67.86％ (19/28 cases) and 35.71％ (10/28 cases) in the trial group and control group,respectively,there was significant difference (x2 =5.793,P =0.016).And in the mean time,the rate of complete resolution of hypsrrhythmia were 57.14％ (16/28 cases) and 14.29％ (4/28 cases),respectively,there was significant difference (x2 =11.200,P =0.001).2.Weight gain and increased appetite were the most frequent side effects.The incidence of side effects were 82.14％ (23/28 cases) and 67.86％ (19/28 cases) in the trial group and control group,respectively,there was no significant difference between the 2 groups (x2 =1.524,P =0.217).No death occurred in this clinical trail and no one discontinued the treatment protocol as result of the adverse events.3.The recurrence rate in the trial group and the control group were 31.82％ and 72.73％,respectively.And there was significant difference between the 2 groups (x2 =4.950,P =0.026).In the trial group,there were 9 cases with cessation of spasms more than 6 months,whose average business development values had no significant difference before and after treatment (t =2.271,P =0.053).Conclusion The efficacy of large-dose prednisone combined with TPM for IS was significantly better than that of conventional dose prednisone combined with TPM.

Adrenocortical hormone in the treatment of pediatric epilepsy / 国际儿科学杂志

Adrenocortical hormone (ACH) has been used in the treatment of the epilepsies,especially for epileptic encephalopathy,for over 70 years.ACH is clearly established as fast line treatment of infantile spasm and the Landau-Kleffner syndrome.This is typically as monotherapy in infantile spasm,but often in conjunction with anti-epileptic drugs in Landau-Kleffner syndrome,though the mechanism of ACH for epilepsies is not clear.However,in view of these potential adverse side effects,the use of ACH in the treatment of the epilepsies in children must be determined on a risk-benefit basis.

Diagnosis and emergency treatment of convulsion in children / 中国小儿急救医学

Convulsion is a common pediatric emergency and the most frequent clinical feature among the diseases of nervous system in children.Convulsion emergencies are potèntially life-threatening events.Brief convulsions rarely produce lasting effects on the brain.Prolonged convulsions,especially status epilepticus,can lead to permanent neurologic damage.Airway management and timely termination of the convulsion are the initial priorities.Early recognition and accurate diagnosis are crucial for effective emergency treatment of convulsion.

Effect of Dredging Acupoints Combined with Vojta Training on Spastic Type Cerebral Palsy / 中国康复理论与实践

@#Objective To observe the effect of dredging acupoints combined with Vojta training on spastic type cerebral palsy (CP).Methods220 children with spastic type CP were randomly divided into the treatment group and control group with 110 cases in each group. The children in the treatment group were treated with traditional Chinese medicine acupuncture and Vojta training, and those in the control group were treated with drug through intravenous dropping. The gross motor function of all children in two groups was assessed with Gross Motor Function Measure (GMFM) before and after treatment.ResultsThe GMFM scores of children in the treatment group were significantly higher than that of the cases in the control group ( P<0.001).ConclusionThe dredging acupoints combined with Vojta training can improve motor function of children with spastic type CP obviously.

PURIFICATION AND PHYSICOCHEMICAL CHARACTERIZATION OF ALLERGEN I from Dermatophagoides farinae / 中国寄生虫学与寄生虫病杂志

Dermatophagoid.es farinae allergen Ⅰ (Der f Ⅰ ) has been extracted and purified from spent culture medium of Dermatophagoid.es farinae by affinity chromatography coupled with anti-Der f Ⅰ McAb for the first time in China. Furthermore,its physicochemical properties were analysed. By SDS-PAGE,.Der f Ⅰ was estimated to have a molecular weight of 24 kDa and appeared as only one protein band. By isoelectric focusing ,it was revealed to have pIs of 4. 8 - 7. 5 with six protein bands,suggesting that Der f Ⅰ is heterogeneous with complicated composition.