ObjectiveTo investigate the effects of metformin on the immune functions of immature dendritic cells （imDCs） and the underlying mechanisms. MethodsMouse bone marrow-derived imDCs were treated with different concentrations of metformin. The working concentration and treatment time of metformin in this study were determined based on the results of cell apoptosis and cell viability assays. The effects of metformin on the phagocytic capacity of imDCs was evaluated using an antigen endocytosis assay. The expression of cluster of differentiation 205 （CD205）， the polymerization of filamentous actin （F-actin）， and the underlying regulatory mechanisms were investigated through flow cytometry， laser confocal fluorescence microscopy， and Western blot. ResultsThe working concentrations of metformin were 1， 2， 4 mmol/L for 24 h determined by the apoptosis and cell viability assays.Metformin significantly suppressed the phagocytic capacity of imDCs， down-regulated the expression of the mannose receptor CD205 on the cell surface， which was closely associated with phagocytic function； metformin inhibited the RhoA-ROCK1-LIMK1-Cofilin signaling pathway， which inhibited the polymerization of F-actin and disturbed its dynamic remodeling of imDCs. ConclusionMetformin can inhibit the expression of CD205 and disrupt the remodeling of F-actin， thereby suppressing the antigen-capturing capacity of imDCs.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective:To summarize the clinical characteristics of children with mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) caused by c.489G>A (p.Pro163=) compound heterozygous variants in the ECHS1 gene, and to explore genotype-phenotype correlations.Methods:A case series study was performed to analyze clinical, biochemical, metabolic, imaging, genetic, treatment and follow-up outcomes of 24 children with ECHS1 gene c.489G>A(p.Pro163=) variant, who were diagnosed in the Department of Neurology, Beijing Children′s Hospital from July 2010 to June 2024. Disease severity was assessed using the Newcastle Paediatric Mitochondrial Disease Scale, and Fisher exact test was applied to compare the improvement rate between valine-restricted and non-restricted groups.Results:These 24 children were all diagnosed after 2022, with a disease duration of 3.35 (1.25, 6.52) years at diagnosis. A total of 8 children initially had negative genetic results, and were finally confirmed by abnormal splicing of ECHS1 gene via skin fibroblast RNA sequencing, with the longest diagnostic time of 14 years. All 24 children presented with Leigh syndrome, including 11 boys and 13 girls, with an onset age of 1.46 (0.96, 2.79) years; 16 children (67%) were mild cases. Common initial symptoms included developmental delay (9 cases) and paroxysmal dystonia (9 cases), followed by developmental regression (3 cases), nystagmus (2 cases), and epilepsy (1 case). Main manifestations were dystonia (18 cases), developmental regression (14 cases), nystagmus (12 cases), developmental delay (11 cases), ataxia (10 cases), vision loss (9 cases), seizures (2 cases), and hearing impairment (1 case). Among 22 children who underwent blood and urine metabolic screening, 21 children (95%) had elevated urinary 2, 3-dihydroxy-2-methylbutyric acid and 19 children (86%) had elevated urinary S-(2-hydroxypropyl) cysteamine. All 24 children had symmetric abnormal signals in bilateral globus pallidus on cranial magnetic resonance imaging, 10 children had isolated globus pallidus involvement, and other common involved sites included caudate nucleus and brainstem (9 cases each), putamen (7 cases), and cerebral white matter (5 cases). At last follow-up, all 24 children survived, with a follow-up duration of 5.40 (2.75, 8.02) years and a maximum age of 17.8 years; 17 children (71%) had varying degrees of clinical improvement. There was no statistical difference in the improvement rate between children with or without valine-restricted diet (12/14 vs. 5/8, P=0.309). A total of 18 pathogenic variants in the ECHS1 gene were identified among 24 children, 13 of which were distributed in exons 7 and 8; those carrying c.308T>C, c.523G>A, c.796A>G, and c.832G>A variants were mostly severe cases. Conclusions:Children carrying ECHS1 gene c.489G>A(p.Pro163=) compound heterozygous variants face significant diagnostic delay. Clinical awareness of this synonymous variant needs further improvement for timely diagnosis. All these cases present as Leigh syndrome, mostly mild, with no clear genotype-phenotype correlation identified.

Objective:To summarize the long-term efficacy of nicotinamide in treating pediatric early-onset progressive encephalopathy with brain edema and (or) leukoencephalopathy-2 (PEBEL2) caused by NAXD gene variation .Methods:This was a case report conducted from February 2019 to January 2025. The long-term efficacy of nicotinamide was observed by following up a child with PEBEL2 who received the treatment in the Department of Neurology, Beijing Children′s Hospital Affiliated to Capital Medical University. The clinical data included changes in skin lesions, neurological symptoms. The modified Rankin scale (mRS) was used to evaluate the recovery of neurological function.Results:A boy was diagnosed with PEBEL2 caused by NAXD gene variation via genetic testing at Beijing Children′s Hospital Affiliated to Capital Medical University in February 2019, when he was 4 years and 6 months of age. Immediately after diagnosis, nicotinamide treatment was initiated at an initial dose of 100 mg/d, which was increased by 100 mg per week and gradually increased to 500 mg/d; meanwhile, other therapeutic drugs were gradually discontinued. After 1 year and 8 months of treatment, the child′s skin lesions had completely resolved; at the 2-year follow-up, dystonia in both upper limbs and swallowing dysfunction was alleviated significantly; by 2.5-year follow-up, his cognitive function also showed improvement. When the child was treated with 500 mg/d for 3 years, a rash appeared around the mouth. After the dose was reduced to 250 mg/d, the rash resolved, and the dose of 250 mg/d was maintained until the last follow-up. At the last follow-up in January 2025, the child was 10 years and 5 months of age. His mRS score decreased from 5 (before treatment) to 4. During the 6-year of continuous nicotinamide treatment, the child′s condition remained stable without progression. Drug-related skin rashes occurred, but no severe drug-related adverse reactions were observed.Conclusions:PEBEL2 is a treatable mitochondrial disease. Nicotinamide treatment can effectively improve skin lesions and neurological symptoms in PEBEL2 patients, and the long-term administration demonstrates a favorable safety profile.

Objective:To construct an integrated early rehabilitation program for healthcare and rehabilitation system based on the information-motivation-behavioral skills (IMB) model and evaluate its application effect in patients treated with total hip arthroplasty (THA).Methods:Construction of the rehabilitation program: An integrated research team was established, composed of head burse of orthopedics, orthopedic nursing specialists, orthopedic surgeons, anesthesiologists, and rehabilitation therapists. Considering the key points of perioperative early rehabilitation of THA patients, an integrated early rehabilitation program was constructed based on the IMB model through literature review and expert panel method. Clinical application of the rehabilitation program: A retrospective cohort study was conducted to analyze the clinical data of 100 THA patients admitted to Qingdao Municipal Hospital from March to December 2023, including 47 males and 53 females, aged 60-85 years [(69.8±5.5)years]. Patients were divided into two groups according to their admission time: 50 patients admitted from March to July 2023, receiving routine care (routine care group) and 50 admitted from August to December 2023, receiving intervention through an early rehabilitation program of an integrated healthcare and rehabilitation system based on routine care (integrated care group). The first postoperative ambulation time and length of hospital stay were compared between the two groups. The Harris hip function score was used to assess hip function in both groups at 3 days, 1, 3, and 6 months postoperatively; the Barthel index was used to assess the daily living self-care capacity in both groups preoperatively, at 1, 3, and 6 months postoperatively. The incidence of complications within 6 months after surgery was compared between the two groups.Results:An early integrated rehabilitation program based on the IMB model comprised 25 specific measures of three domains: information support, motivational intervention, and behavioral skills. All the patients were followed up for 6 months. The first postoperative ambulation time and length of hospital stay in the integrated care group were (1.3±0.5)days and (7.4±2.3)days, shorter than (1.5±0.5)days and (8.5±2.3)days in the routine care group ( P<0.05). There were no statistically significant differences in the Harris hip function scores at 3 days postoperatively or preoperative Barthel index between the two groups ( P>0.05). At 1, 3, and 6 months postoperatively, the Harris hip function scores in the integrated care group were (80.3±6.0)points, (88.6±5.2)points, and (92.5±4.1)points, respectively, higher than (75.1±6.3)points, (84.2±5.7)points, and (88.0±5.2)points in the routine care group ( P<0.01); the Barthel index in the integrated care group were (79.2±8.7)points, (87.7±5.7)points, and (92.3±4.9)points, respectively, higher than (72.1±9.0)points, (83.5±6.6)points, and (88.6±5.0)points in the routine care group ( P<0.01). At 6 months postoperatively, the incidence of complications in the integrated care group was 4% (2/50), lower than 16% (8/50) in the routine care group ( P<0.05). Conclusion:Compared with the routine care, an integrated early rehabilitation program for medical care and health based on the information-motivation-behavioral skills model for THA patients can shorten the first postoperative ambulation time and length of hospital stay, restore hip joint function, improve daily living self-care capacity and reduce the incidence of complications.

Objective:To evaluate the clinical efficacy of Jianpi Bushen Prescription in treating acute gouty arthritis with spleen-kidney deficiency syndrome using propensity score matching method.Methods:A retrospective analysis method was used to select 156 patients with acute gouty arthritis with spleen kidney deficiency type admitted from March 2022 to March 2024. They were divided into an observation group of 89 cases and a control group of 67 cases according to the treatment method. Propensity score matching (PSM) was further adopted to balance the confounding factors before treatment in a 1:1 ratio. Finally, 42 patients in each group were successfully matched. The control group received conventional Western medicine, the observation group received additional treatment with Jianpi Bushen Prescription on the basis of the control group. The treatment for both groups lasted for 1 month. TCM syndrome scores were performed before and after treatment, and the levels of serum uric acid (UA), ESR, and pH were measured using an automatic dry biochemical analyzer. The VAS scale was used to assess the degree of pain, the Oswestry Disability Index (ODI) was used to evaluate the degree of joint function improvement, and the Quality of Life Scale-36 (SF-36) was used to evaluate the quality of life of patients. Adverse reactions during treatment were observed and recorded to evaluate clinical efficacy.Results:The total effective rate of the observation group 92.86% (39/42) was higher than that of the control group 73.81% (31/42), with statistical significance ( χ2=5.49, P<0.05). After treatment, the joint pain, soreness and weakness of the waist and knees, poor flexion and extension, and pale and greasy tongue coating, were lower than those in the control group ( t values were 3.38, 4.26, 3.96, 3.97, 4.41, respectively, P<0.01). After treatment, the serum uric acid (UA) [(351.84±36.46) μmol/L vs. (380.19±39.42) μmol/L, t=3.42] and erythrocyte sedimentation rate (ESR) [(17.91±3.71) mm/h vs. (21.43±3.90) mm/h, t=4.24] of the observation group were lower than those in the control group, and the pH value (7.24±0.49 vs. 6.98±0.57, t=2.24) was higher than that of the control group ( P<0.05). After treatment, the VAS and ODI of the observation group were lower than those of the control group ( t values were 5.80, 6.25, respectively, P<0.01), and the SF-36 score was higher than that of the control group ( t=3.23, P<0.05). During the treatment, the incidence of adverse reactions was 14.29% (6/42) in the observation group and 9.52% (4/42) in the control group. There was no statistical significance in the incidence of adverse reactions between the two groups ( χ2=0.45, P>0.05). Conclusions:Jianpi Bushen Prescription has good efficacy on the treatment of acute gouty arthritis with spleen-kidney deficiency syndrome. It can reduce the levels of uric acid, improve the life quality of patients, and enhance efficacy, with good treatment safety.

Objective To investigate the expression of regional cerebral oxygen saturation(rSO2)in preterm infants with brain injury(BIPI)and its relationship with amplitude-integrated electroencephalogram(aEEG)parameters and neurodevelopment.Methods Retrospectively,116 cases of BIPI(Bilateral Intra-ventricular Perforation)born in the hospital between February 2022 and February 2023 were selected as the study subjects.According to the Expert Consensus on the Diagnosis and Prevention of Premature Infant Brain Injury,these cases were categorized into mild,moderate,and severe groups,with 59,35,and 22 cases,respectively.The study compared the general characteristics of premature infants with different brain injury levels.Regression analysis was conducted to identify the factors affecting brain injury in premature infants,and correlation analyses were performed on aEEG scores,rSO2,and GMS scores.ROC curve analysis was used to evaluate the value of combining brain oxygen saturation monitoring with aEEG in predicting abnormal whole-body motor quality assessment.Results On the 3rd and 7th days after birth,severe brain-injured premature infants had significantly lower rSO2 and aEEG scores compared to those with mild and moderate brain injuries(P<0.05).At 7 days,these infants also had lower scores for graph continuity,sleep-wake cycles,lower boundary amplitude,bandwidth,total score,rSO2,gestational age,and birth weight,and a higher proportion of abnormal developmental outcomes(PR+CS)(P<0.05).Multivariate logistic regression analysis revealed that the 3-day aEEG total score(OR=0.448,95％CI:0.094～0.890),7-day aEEG total score(OR=0.384,95％CI:0.058～0.726),3-day rSO2(OR=0.574,95％CI:0.398～0.750),and 7-day rSO2(OR=0.431,95％CI:0.115～0.777)were all protective factors for brain injury in premature infants,P<0.05.Correlation analysis showed that brain oxygen saturation was negatively correlated with aEEG scores and overall motor quality.The prediction value for abnormal overall motor quality using 7-day rSO2,aEEG,and the combination of 7-day rSO2 and 7-day aEEG scores was as follows:the positive predictive value for rSO2 was 86.46％,the negative predictive value was 96.85％,the sensitivity was 92.31％,the specificity was 92.21％,and the cut-off value was 0.845;The positive predictive value(PPV)of aEEG was 78.26％,the negative predictive value(NPV)was 96.86％,the sensitivity was 89.74％,and the specificity was 92.21％,with a cut-off value of 0.820.The positive predictive value(PPV)of 7-day rSO2 combined with 7-day aEEG score was 89.04％,the NPV was 96.88％,the sensitivity was 94.90％,and the specificity was 93.51％,with a cut-off value of 0.884,P<0.05.ROC curve analysis showed that the AUC of 7-day rSO2+7-day aEEG score was 0.895,De-long test P<0.005,indicating high predictive value for overall exercise quality.Conclusion Combined with rSO2 and EEG,the prediction of overall motor quality is better,which may have clinical value for excluding high-risk children.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective To investigate the expression of regional cerebral oxygen saturation(rSO2)in preterm infants with brain injury(BIPI)and its relationship with amplitude-integrated electroencephalogram(aEEG)parameters and neurodevelopment.Methods Retrospectively,116 cases of BIPI(Bilateral Intra-ventricular Perforation)born in the hospital between February 2022 and February 2023 were selected as the study subjects.According to the Expert Consensus on the Diagnosis and Prevention of Premature Infant Brain Injury,these cases were categorized into mild,moderate,and severe groups,with 59,35,and 22 cases,respectively.The study compared the general characteristics of premature infants with different brain injury levels.Regression analysis was conducted to identify the factors affecting brain injury in premature infants,and correlation analyses were performed on aEEG scores,rSO2,and GMS scores.ROC curve analysis was used to evaluate the value of combining brain oxygen saturation monitoring with aEEG in predicting abnormal whole-body motor quality assessment.Results On the 3rd and 7th days after birth,severe brain-injured premature infants had significantly lower rSO2 and aEEG scores compared to those with mild and moderate brain injuries(P<0.05).At 7 days,these infants also had lower scores for graph continuity,sleep-wake cycles,lower boundary amplitude,bandwidth,total score,rSO2,gestational age,and birth weight,and a higher proportion of abnormal developmental outcomes(PR+CS)(P<0.05).Multivariate logistic regression analysis revealed that the 3-day aEEG total score(OR=0.448,95％CI:0.094～0.890),7-day aEEG total score(OR=0.384,95％CI:0.058～0.726),3-day rSO2(OR=0.574,95％CI:0.398～0.750),and 7-day rSO2(OR=0.431,95％CI:0.115～0.777)were all protective factors for brain injury in premature infants,P<0.05.Correlation analysis showed that brain oxygen saturation was negatively correlated with aEEG scores and overall motor quality.The prediction value for abnormal overall motor quality using 7-day rSO2,aEEG,and the combination of 7-day rSO2 and 7-day aEEG scores was as follows:the positive predictive value for rSO2 was 86.46％,the negative predictive value was 96.85％,the sensitivity was 92.31％,the specificity was 92.21％,and the cut-off value was 0.845;The positive predictive value(PPV)of aEEG was 78.26％,the negative predictive value(NPV)was 96.86％,the sensitivity was 89.74％,and the specificity was 92.21％,with a cut-off value of 0.820.The positive predictive value(PPV)of 7-day rSO2 combined with 7-day aEEG score was 89.04％,the NPV was 96.88％,the sensitivity was 94.90％,and the specificity was 93.51％,with a cut-off value of 0.884,P<0.05.ROC curve analysis showed that the AUC of 7-day rSO2+7-day aEEG score was 0.895,De-long test P<0.005,indicating high predictive value for overall exercise quality.Conclusion Combined with rSO2 and EEG,the prediction of overall motor quality is better,which may have clinical value for excluding high-risk children.

Objective:To construct an integrated early rehabilitation program for healthcare and rehabilitation system based on the information-motivation-behavioral skills (IMB) model and evaluate its application effect in patients treated with total hip arthroplasty (THA).Methods:Construction of the rehabilitation program: An integrated research team was established, composed of head burse of orthopedics, orthopedic nursing specialists, orthopedic surgeons, anesthesiologists, and rehabilitation therapists. Considering the key points of perioperative early rehabilitation of THA patients, an integrated early rehabilitation program was constructed based on the IMB model through literature review and expert panel method. Clinical application of the rehabilitation program: A retrospective cohort study was conducted to analyze the clinical data of 100 THA patients admitted to Qingdao Municipal Hospital from March to December 2023, including 47 males and 53 females, aged 60-85 years [(69.8±5.5)years]. Patients were divided into two groups according to their admission time: 50 patients admitted from March to July 2023, receiving routine care (routine care group) and 50 admitted from August to December 2023, receiving intervention through an early rehabilitation program of an integrated healthcare and rehabilitation system based on routine care (integrated care group). The first postoperative ambulation time and length of hospital stay were compared between the two groups. The Harris hip function score was used to assess hip function in both groups at 3 days, 1, 3, and 6 months postoperatively; the Barthel index was used to assess the daily living self-care capacity in both groups preoperatively, at 1, 3, and 6 months postoperatively. The incidence of complications within 6 months after surgery was compared between the two groups.Results:An early integrated rehabilitation program based on the IMB model comprised 25 specific measures of three domains: information support, motivational intervention, and behavioral skills. All the patients were followed up for 6 months. The first postoperative ambulation time and length of hospital stay in the integrated care group were (1.3±0.5)days and (7.4±2.3)days, shorter than (1.5±0.5)days and (8.5±2.3)days in the routine care group ( P<0.05). There were no statistically significant differences in the Harris hip function scores at 3 days postoperatively or preoperative Barthel index between the two groups ( P>0.05). At 1, 3, and 6 months postoperatively, the Harris hip function scores in the integrated care group were (80.3±6.0)points, (88.6±5.2)points, and (92.5±4.1)points, respectively, higher than (75.1±6.3)points, (84.2±5.7)points, and (88.0±5.2)points in the routine care group ( P<0.01); the Barthel index in the integrated care group were (79.2±8.7)points, (87.7±5.7)points, and (92.3±4.9)points, respectively, higher than (72.1±9.0)points, (83.5±6.6)points, and (88.6±5.0)points in the routine care group ( P<0.01). At 6 months postoperatively, the incidence of complications in the integrated care group was 4% (2/50), lower than 16% (8/50) in the routine care group ( P<0.05). Conclusion:Compared with the routine care, an integrated early rehabilitation program for medical care and health based on the information-motivation-behavioral skills model for THA patients can shorten the first postoperative ambulation time and length of hospital stay, restore hip joint function, improve daily living self-care capacity and reduce the incidence of complications.