Objective:To summarize the clinical characteristics of children carrying the m.8344A>G variant of MT-TK gene.Methods:A case series study was conducted to retrospectively collect data of 22 children with mitochondrial disease caused by MT-TK gene m.8344A>G variation who were treated at the Department of Neurology of Beijing Children′s Hospital of Capital Medical University from January 2012 to January 2024. Their clinical data, laboratory tests, muscle pathology, genetic testing, and the follow-up results were analyzed. Pearson correlation analysis was used for correlation analysis.Results:Among the 22 children, there were 13 boys and 9 girls. The age of onset was 5.00 (2.75, 9.00) years. Fifteen children had myoclonic epilepsy with ragged-red fibers (MERRF), 3 had Leigh syndrome (LS), and 4 had LS-MERRF overlap syndrome (LS-MERRF). Myoclonus presented and worsened progressively in all 15 MERRF children, with 10 as the initial symptom and 5 developing progressively during the disease course. Myoclonus was predominantly focal, worsening with fine motor tasks or stress. Electroencephalogram monitoring in the 15 MERRF children revealed myoclonic seizures in 10 children, with 6 classified as myoclonic epilepsy, and 4 as subcortical myoclonus. Two children had generalized myoclonic seizures, and 1 each had absence seizures and generalized seizures. Twelve children had cerebellar ataxia, 10 children exhibited exercise intolerance, and 8 children had muscle weakness. Magnetic resonance imaging (MRI) revealed periventricular white matter involvement in 1 child and bilateral hippocampal involvement in 1 child, likely due to frequent seizures. All 3 children with LS exhibited developmental regressions, accompanied with 2 symptoms include cerebellar ataxia, muscle weakness, and dysphagia. The clinical manifestations of 4 LS-MERRF overlap children presented with combined features of MERRF and LS. Cranial MRI in the 7 LS and LS-MERRF children showed brainstem involvement (all affecting the midbrain) in 6 children and basal ganglia involvement in 4 children. Among the 22 children, 12 had m.8344A>G variant levels >90%, 3 had >80%-90%, 4 had >70%-80%, and 3 had >60%-70%. Higher variant level correlated with the LS phenotype and earlier onset age ( r=0.47, -0.50; P=0.018 and 0.029, respectively). Sanger sequencing in 19 mothers revealed m.8344A>G variations in 18, with 4 showing exercise intolerance. Follow-up of 13 children on antimyoclonic treatment showed>75% reduction in seizures with levetiracetam monotherapy in 2 children, with combination therapy required in others. Most achieved >50% seizures reduction within 2 years, but the effectiveness declined with disease progression. Conclusions:The m.8344A>G variant is rare, with MERRF being the most common phenotype, while LS and LS-MERRF are less common. Children with higher ratio of the m.8344A>G variant are more likely to present LS phenotype. Myoclonus, primarily focal, is a key feature, with levetiracetam as the first-line treatment and benzodiazepines recommended for refractory cases.

AIM: To compare the results calculated by population pharmacokinetic analysis tools Phoenix NLME, Monolix, R nlmixr package and CPhaMAS cloud platform with the gold standard sofeware NONMEM. METHODS: Fifty sparse sampling data sets based on a one-compartment model and fifty dense sampling data sets based on a two-compartment model were simulated, and the above five analysis tools were used to calculate the population typical value, individual variability and individual pharmacokinetic parameters. RESULTS: The population typical value and individual variability calculated by CPhaMAS and Phoenix NLME had the highest matching degree with NONMEM, followed by nlmixr. Monolix had the lowest matching degree, but Monolix and nlmixr might be more robust. The correspondence between clearance and distribution volume was better than the absorption rate constant. Except the absorption rate constant calculated by Monolix and intercompartmental clearance calculated by nlmixr, the correlation coefficients of individual pharmacokinetic parameters calculated by all analytical tools were greater than 0.99. CONCLUSION: The results calculated by the above four population pharmacokinetic analysis tools are highly correlated with that of NONMEM.

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

Objective :To analyze correlation among fasting (FBL) and postprandial blood lipids (PBL) ,blood lipid fluctuation (absolute value of PBL‐FBL) and severity of coronary artery disease .Methods :Cross‐sectional study was performed among 264 patients undergoing coronary angiography (CAG) in our hospital .According to percutaneous coronary intervention (PCI) or not based on CAG results ,patients were divided into plaque group (n＝128) and PCI group (n＝136).Gensini score was used to assess severity of coronary artery disease .Blood lipid levels and its fluctu‐ation were compared between two groups .Correlation among blood lipid levels ,blood lipid fluctuation and severity of coronary artery disease were analyzed .Results :Compared with plaque group ,there were significant rise in per‐centages of men and smokers ,waist circumference ,levels of postprandial‐fasting (P‐F ) serum LDL‐C (ΔLDL‐C ) and P‐F plasma apolipoprotein B (ΔApoB ) , and significant reduction in plasma level of P‐F apolipoprotein A1 (ΔApoA1) in PCI group , P＜0. 05 or ＜ 0. 01. Pearson correlation analysis indicated that serum fasting and post‐prandial HDL‐C levels ,plasma fasting and postprandial levels of ApoA1 and ΔApoA1 were significant inversely cor‐related with Gensini score ( r＝ －0. 130～ －0.218 , P＜0. 05 or ＜0. 01) ,and levels of plasma fasting lipoprotein a (Lp (a)) ,serum fasting and postprandial levels of free fatty acid (FFA) ,serum P‐F FFA (Δ FFA) were significant positively correlated with Gensini score ( r＝0. 139－0. 176 , P＜0.05 or ＜0.01).Multifactor linear regression anal‐ysis indicated that postprandial serum HDL‐C was protective factor for Gensini score (B＝ －22.274 , P＝0.002 ) , while postprandial serum FFA ,Δ FFA ,waist circumference and hyperlipidemia history were its influencing factors (B＝0. 388～24. 135 , P＜0. 05 or ＜0.01).Conclusion :Measurements of fasting and postprandial blood lipid levels and their fluctuation contribute to more comprehensively and objectively assessing blood lipid levels and severity of coronary disease in patients with coronary artery disease .

Objective To test the the reliability and validity of the Chinese version of the adult haemophilia activities list (HAL).Methods A Chinese version of the HAL was prepared by translation,back-translation and revision.Adult hemophilia patients were used to test it and a short-form arthritis impact measurement scale (AIMS-SF) simultaneously.A total of 98 valid questionnaires were collected.The internal consistency,reliability,split-half reliability,content validity,construct validity and convergent validity were tested.Results The Cronbach's α coefficients for the total questionnaire and its dimensions were all 0.7 or more.The half-reliability test produced a Spearman.correlation coefficient of 0.97.The Pearson correlation coefficients relating each dimension score with the total score and each dimension's entry score with the dimension score were all greater than 0.6.The correlation coefficient between the dimensions of the two questionnaires was smaller than the correlation coefficients relating each dimension with the total scale.There was relatively good correlation between the HAL sum score and the AIMS2-SF sum score (r=0.640,P≤0.01),as well as between the HAL sum score and the AIMS2-SF physical score (r=0.576,P≤0.01).Conclusion The Chinese version of the adult HAL has good reliability and validity.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Constipation ; physiopathology ; therapy ; Defecation ; Humans ; Male

Contracture and spasticity of ankle joints were major sources of disability in neurological impairment including stroke and cerebral palsy, etc. The manual stretching used in physical therapy might be laborious and time-consuming to the therapists and the outcome was dependent on the experience and the subjectiveend feelingof the therapists. A device was developed that could safely stretch the an-kle joint to its extreme positions with quantitative control of the resistance torque and stretching velocity. Furthermore, it could satisfy a strong need for quantitative and objective measures of the impairment and rehabilitation outcome. This was just the meaning intelligent stretching referred to. This article described the origin of the concept of intelligent stretching and its definition, operational principle, and su-periority and weakness, as well as its application in ankle joint spasticity and contracture in patients with stroke and cerebral palsy.

Objective To observe the clinical efficacy of electroacupuncture in treating functional constipation. Method Sixty patients with functional constipation were randomized into a treatment group and a control group, 30 in each group. The treatment group was intervened by electroacupuncture, while the control group was by sham-electroacupuncture. The Clinic Constipation Score (CCS), therapeutic efficacy index, plasma NOS, and plasma 5-HT were observed before and after intervention.Result The CCS was changed significantly after intervention in both groups (P<0.05). After intervention, there was a significant difference in comparing the CCS between the two groups (P<0.05). The total effective rate was 93.3% in the treatment group versus 66.7% in the control group, and the difference was statistically significant (P<0.05). The NOS and 5-HT contents were changed significantly after intervention in both groups (P<0.05). After intervention, there were significant differences in comparing the NOS and 5-HT contents between the two groups (P<0.05).Conclusion Electroacupuncture is an effective approach in treating functional constipation, and it can improve NOS and 5-HT contents in gastrointestinal tract.

Objective To compare the efficacy of different rehabilitation models on acalculia after acquired brain injury. Methods 113 cases were randomly assigned to 3 groups: control group(n=37), computer-assisted training group(n=38) and face-to-face training group(n=38). The control group just received cognitive dysfunction evaluation. The training groups received cognitive rehabilitation training 5 days a week and 30 minutes a day which sustained for 6 weeks. And 33 patients were selected to prolong for 12 weeks. They were evaluated with Revised EC301Calculation and Number Processing Battery in Chinese version (EC301-CR) at the beginning, the 6th week point and the 12th week point respectively. Results 6-week after treatment, The performance of both the computer-assisted training group and face-to-face training group significantly improved(P<0.001); It showed that computer-assisted group>face-to-face group>control group(P<0.001) both 6 weeks and 12 weeks latter. Significant negative correlation was found between age and performance of EC301-CR(P<0.05).Conclusion The effect of computer-assisted training on acalculia is superior to face-to-face training; The first 6 weeks of training is the best period for rehabilitation; The younger the patient is, the better results are.

Objective To study the effects caused by novel antipsychotics quetiapine and aripiprazole on concentrations of platelet 5-HT in patients with schizophrenia,and to explore the relationships among the change of platelet 5-HT concentrations, psychiatric symptoms and the sensitivity of therapy. Methods Sixty-eight patients with schizophrenia meeting International Classification of Diseases-10 (ICD-10) were enrolled in the study. They were divided into quetiapine group(n=34) and aripiprazole group(n=34) according to the sequence of admis-sion. The platelet 5-HT concentrations were measured with high performance liquid chromatography method(HPLC-ECD). The positive and negative syndrome scale (PANSS) was used to evaluate the psychopathology. Treatment emergent symptom scale (TESS) was used to evaluate the side effects. PANSS,TESS were used at pre-treatment,the end of 4th and 8th week of treatment. Results The platelet 5-HT concentrations in two groups were higher af-ter 8 weeks treatment,but had no statistically significant difference (P>0.05). In quetiapine group, the platelet 5-HT concentration was (458.89±233.36) ng/10~9 at the pre-treatment, and (554.31±313.22) ng/10~9 at the end of treatment (t=1.709, P=0.099). In aripiprazole group, the platelet 5-HT concentration was (409.83±149.32)ng/10~9 at the pretreatment, and (421.27±245.96)ng/10~9 at the end of treatment (t=0.321, P=0.819). There was no difference between two groups(P>0.05). Stepwise regression analysis showed the changing rate of platelet 5-HT concentrations was positively correlated with the dosage of quetiapine (r=0.385, P=0.039).It was positively correlated with the decreasing rate of PANSS in aripiprazole group(r=0.391, P=0.040). Con-dusion The changes of psychiatric symptoms and the dosages of antipsychotics maybe have intimate relationships with platelet 5-HT concentrations in the course of medication.