Objective:To summarize the clinical and prognostic features of children with opsoclonus-myoclonus-ataxia syndrome (OMAS).Methods:A total of 46 patients who met the diagnostic criteria of OMAS in the Department of Neurology, Beijing Children′s Hospital from June 2015 to June 2023 were retrospectively analyzed. Centralized online consultations or telephone visits were conducted between June and August 2023. The data of the children during hospitalization and follow-up were collected, including clinical manifestations, assistant examination, treatment and prognosis. According to the presence or absence of tumor, the patients were divided into two groups. The chi-square test or Mann-Whitney U test was used to compare the differences between the two groups. Univariate Logistic regression was used to analyze the factors related to OMAS recurrence and prognosis. Results:There were 46 patients, with 25 males and the onset age of 1.5 (1.2, 2.4) years. Twenty-six (57%) patients were diagnosed with neuroblastoma during the course of the disease, and no patients were categorized into the high-risk group. A total of 36 patients (78%) were followed up for≥6 months, and all of them were treated with first-line therapy with glucocorticoids, gammaglobulin and (or) adrenocorticotrophic hormone. Among the 36 patients, 9 patients (25%) were treated with second-line therapy for ≥3 months, including rituximab or cyclophosphamide, and 17 patients (47%) received chemotherapy related to neuroblastoma. At the follow-up time of 4.2 (2.2, 5.5) years, 10 patients (28%) had relapsed of OMAS. The Mitchell and Pike OMS rating scale score at the final follow-up was 0.5 (0, 2.0). Seven patients (19%) were mildly cognitively behind their peers and 6 patients (17%) were severely behind. Only 1 patient had tumor recurrence during follow-up. The history of vaccination or infection before onset was more common in the non-tumor group than in the tumor group (55%(11/20) vs. 23%(6/26), χ2=4.95, P=0.026). Myoclonus occurred more frequently in the non-tumor group (40%(8/20) vs. 4%(1/26), χ2=7.23, P=0.007) as the onset symptom. Univariate Logistic regression analysis showed that the tumor group had less recurrence ( OR=0.19 (0.04-0.93), P=0.041). The use of second-line therapy or chemotherapy within 6 months of the disease course had a better prognosis ( OR=11.64 (1.27-106.72), P=0.030). Conclusions:OMAS in children mostly starts in early childhood, and about half are combined with neuroblastoma. Neuroblastoma in combination with OMAS usually has a low risk classification and good prognosis. When comparing patients with OMAS with and without tumors, the latter have a more common infection or vaccination triggers, and myoclonus, as the onset symptom, is more common. Early addition of second-line therapy is associated with better prognosis in OMAS.

Transforming growth factor (TGF)-β is a group of cytokines with anti-inflammatory effects in the TGF family, which participates in the development of stress and depression-related mechanisms, and plays roles in the regulation of inflammatory response in depression and the recovery of various cytokine imbalances. The core symptoms of depression is associated with TGF-β level, and the psychological symptoms of depression are related to TGF-β gene polymorphism. Various antidepressants may up-regulate TGF-β level through the complex interaction between neurotransmitters and inflammatory factors, inhibiting inflammatory response and regulating cytokine imbalance to improve depressive symptoms. Studies have shown that recombinant TGF-β1 protein has beneficial effects in mouse depression models, indicating TGF-β1 might be a potential therapeutic target for depression and nasal sprays having the advantage of being fast acting delivery method. This article reviews the research progress on dynamic changes of TGF-β level before and after depression treatment and the application of TGF-β level as an indicator for the improvement of depressive symptoms. We provide ideas for the development of new antidepressants and for the evaluation of the treatment efficacy in depression.
Animals ; Mice ; Transforming Growth Factor beta/metabolism* ; Transforming Growth Factor beta1 ; Depression ; Cytokines ; Antidepressive Agents/therapeutic use* ; Transforming Growth Factors

Objective:To investigate the clinical characteristics, laboratory characteristics and genetic diagnosis of aromatic L-amino acid decarboxylase deficiency (AADCD), and to improve the understanding of this disease.Methods:Four children diagnosed with AADCD from the Department of Neurology, Beijing Children′s Hospital Affiliated to Capital Medical University from August 2016 to June 2020 were collected, and their clinical manifestations, laboratory and imaging data, and genetic test results were retrospectively analyzed.Results:All the 4 cases were diagnosed in early infancy, with the first symptom of feeding difficulties. They developed paroxysmal dyspraxia accompanied by eye movement crisis, movement regression, hypotonia, growth retardation, sleep disorders and autonomic nervous symptoms such as ptosis, excessive sweating and nasal congestion at the age of 2-4 months, respectively. The 4 children were siblings from 2 families with healthy parents. The dihydroxyphenylalanine decarboxylase ( DDC) gene mutations in cases 1 and 2 were derived from the maternal missense mutation c.1040G>A(P.RG347gln), and from the paternal deletion of exons 11 and 12, respectively. The DDC gene mutation in case 3 was derived from the maternal mutation c.419G>A(p.G140E) and the paternal mutation c.1375C>T(p.H459Y), respectively. Case 4 did not undergo genetic testing. Blood amino acid and acylcarnitine profiles and urine organic acid analyses were performed in 3 cases, and no specific abnormalities were found. In case 3, the results of 3-O-methyldopa (3-OMD) screening by blood dry filter paper increased significantly. Cerebrospinal fluid neurotransmitter detection results showed that the concentrations of 3-methoxy-4-hydroxyphenyldiol, vanillic acid and 5-hydroxyindoleacetic acid were significantly decreased, while the levels of 5-hydroxytryptophan and 3-OMD were increased in case 3. Blood aromatic L-amino acid decarboxylase (AADC) activity decreased significantly in case 3. Cranial magnetic resonance imaging (MRI) and electroencephalogram (EEG) examinations were performed in cases 1, 3, and 4, among which the cranial MRI in case 1 was normal, while the cranial MRI in cases 3 and 4 suggested that myelination was slightly backward. The EEG was normal in all the 3 cases. Cases 1 and 2 died of pneumonia and respiratory failure at the age of 1 year and 10 months. Case 3 was given clonazepam, benxel hydrochloride tablets and vitamin B6 tablets orally after diagnosis at the age of 4 months, and then treated with selegiline hydrochloride tablets and pramexol hydrochloride tablets. At the follow-up of 1 year and 6 months, the frequency of eye movement crisis and movement disorder was reduced, sleep was improved and autonomic nervous symptoms were alleviated, but there was no improvement in developmental delay. Case 4 was diagnosed with cerebral palsy and epilepsy, but failed various antiepileptic drugs and rehabilitation training, and died at the age of 10 due to heart failure and kidney failure. Conclusions:The clinical manifestations of AADCD are complicated and the misdiagnosis rate is high. Infants with early-onset hypotonia, developmental retardation, eye movement crisis, and movement disorders should be screened with dry filter paper as soon as possible for 3-OMD level, and suspicious cases should be diagnosed by cerebrospinal fluid neurotransmitter detection, plasma AADC activity determination, and gene examination. Early diagnosis of AADCD in children and gene mutation carriers can guide treatment and provide genetic counseling to reduce the incidence of the offspring.

Fetal echocardiography is the first-line imaging tool for diagnosing coarctation of aorta (CoA). Currently, there are some typical ultrasonic features, but no single one can be used for accurate prenatal diagnosis or differential diagnosis of fetal CoA and ultrasonic scoring system remains under investigation in diagnosing or risk classification of CoA. This paper reviews the progress in prenatal ultrasound diagnosis of fetal CoA.

Objective:To investigate the prognostic value and related factors of heart-type fatty acid binding protein (H-FABP) in patients with heart failure.Methods:A total of 877 consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed as heart failure from July 2015 to July 2017 were enrolled in this study. Baseline serum H-FABP concentration was measured by fluorescence lateral flow immunoassay. According to serum H-FABP levels, patients were divided into three groups: low H-FABP group (H-FABP≤4.04 ng/ml, n=292), middle H-FABP group (H-FABP 4.04-7.02 ng/ml, n=292) and high H-FABP group (H-FABP≥7.02 ng/ml, n=293). The general clinical characteristics were collected and compared among the three groups. According to whether heart failure was caused by coronary artery disease or not, patients with heart failure were divided into ischemic heart failure and non-ischemic heart failure. Multivariate linear regression analysis was performed to explore the independent risk factors of H-FABP. The primary endpoint events were the composite of all-cause death or heart transplantation. Multivariate Cox regression analyses, receiver operating characteristic (ROC) curves, risk prediction tests with multivariate Cox regression model and Kaplan-Meier analyses were conducted to investigate the relationship between H-FABP and the prognosis of heart failure. Results:Multivariate linear regression analysis showed that age, coronary artery disease, alanine aminotransferase, uric acid and N-terminal pro-B type natriuretic peptide (NT-proBNP) were positively associated with H-FABP (β=0.012, 0.238, 0.001, 0.345 and 0.063 respectively,all P<0.05), while female, hemoglobin, albumin, sodium, and estimated glomerular filtration rate (eGFR) were negatively associated with H-FABP (β=-0.184, -0.006, -0.016, -0.034 and -0.006 respectively, all P<0.05). One hundred and nineteen patients (13.6%) lost to follow-up, and 246 patients (32.5%) suffered from all-cause death or heart transplantation during the median follow-up duration of 931 (412-1 185) days. Multivariate Cox regression analysis showed that baseline H-FABP (log 2H-FABP) level was the independent predictor of all-cause death or heart transplantation in patients with heart failure ( HR=1.39, P<0.001). ROC curves showed that baseline H-FABP was a predictor of all-cause death or heart transplantation in patients with heart failure within 3 months, 1 year and 2 years (areas under the curves were 0.69, 0.69 and 0.71 respectively), and the best cut-off values were 5.85 ng/ml, 6.54 ng/ml and 6.54 ng/ml respectively. Risk prediction test with multivariate Cox regression model showed that baseline H-FABP could provide additional prognostic value in predicting all-cause death or heart transplantation for patients with heart failure on top of basic model and baseline NT-proBNP ( P<0.001). Taking 6.54 ng/ml and trisected levels of H-FABP as cut-off values respectively, Kaplan-Meier analyses showed that the survival rates were significantly different among the two or three groups ( P<0.001). Subgroup analyses showed that baseline H-FABP (log 2H-FABP) level was an independent predictor of all-cause death or heart transplantation in patients with ischemic heart failure ( HR=1.74, P<0.001), as well as in patients with non-ischemic heart failure ( HR=1.28, P=0.027). Conclusions:Age, sex, coronary artery disease, hemoglobin, albumin, alanine aminotransferase, sodium, eGFR, uric acid and NT-proBNP are associated with H-FABP level. Baseline H-FABP level is an independent predictor of all-cause death or heart transplantation in patients with heart failure. On top of basic model and baseline NT-proBNP, baseline H-FABP could provide additional prognostic value in predicting adverse events for patients with heart failure.

Objective:To evaluate the efficacy of sugammadex for the reversal of residual neuromuscular blockade after laparoscopic radical gastrectomy in elderly patients.Methods:Sixty patients of both sexes, aged 65-85 yr, with body mass index of 20-26 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, undergoing elective laparoscopic radical gastrectomy under general anesthesia, were divided into 2 groups ( n=30 each) by a random number table method: sugammadex group (S group) and neostigmine group (N group). Rocuronium 0.3-0.6 mg·kg -1·h -1 was intravenously infused during operation, and the muscle relaxation was monitored by a Veryark-TOF monitor, maintaining TOF ratio=0 and counting 1 or 2 after tonic stimulation.Rocuronium was discontinued when the peritoneum was closed.The patients were admitted to the PACU after operation.When the muscle relaxation monitoring T 2 appeared, sugammadex 2 mg/kg was intravenously injected in S group, and neostigmine 0.03 mg/kg plus atropine 0.015 mg/kg was intravenously injected in N group.The tracheal tube was removed after the patient′s consciousness and spontaneous breathing recovered.Before anesthesia (T 1) and 5 and 30 min after tracheal extubation (T 2, 3), arterial blood samples were collected for blood gas analysis, PaO 2 and PaCO 2 were recorded, and ultrasound was used to measure the diaphragm end-inspiratory thickness, end-expiratory thickness and mobility of diaphragm muscle at the above time points.The diaphragm thickening fraction was calculated.The time of T 2 appeared, time of extubation, time of postanesthesia care unit (PACU) stay, postoperative hospital stay, and residual neuromuscular blockade (TOF ratio <0.9) and hypoxemia occurred within 30 min after extubation were recorded.The pulmonary complications within 7 days after operation were recorded. Results:Compared with group N, PaO 2 was significantly increased and PaCO 2 was decreased at T 2, 3, the mobility of diaphragm muscle and diaphragm thickening fraction were increased at T 2, the tracheal extubation time, time of PACU stay and postoperative hospital stay were shortened, the residual neuromuscular blockade and hypoxemia occurred after extubation and incidence of pulmonary complications after operation were decreased ( P<0.05), and no significant change was found in the time of T 2 appeared in group S ( P>0.05). Conclusion:Sugammadex can quickly and effectively reverse the residual neuromuscular blockade after laparoscopic radical gastrectomy, which is helpful for early postoperative recovery in elderly patients.

Objective:To evaluate the effect of operation duration on the pharmacokinetics of desflurane in the patients undergoing tumor resection.Methods:One hundred and fifty patients of both sexes, aged 18-75 yr, with body mass index of 19-25 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, in whom abnormal preoperative lung function was not found, undergoing elective surgery with general anesthesia from November 2019 to March 2020, were enrolled in this study.Anesthesia was induced with intravenous injection of sufentanil 0.3 μg/kg, cisatracurium besylate 0.2 mg/kg and propofol 2 mg/kg.The patients were tracheally intubated after mechanical ventilation.Anesthesia was maintained with inhalation of desflurane, the vaporizer dial was adjusted to 6% with fresh gas flow rate of 2 L/min, and sufentanil and cisatracurium besylate were intermittently injected intravenously according to the changes in hemodynamics and degree of muscle relaxation during operation.The duration required for the end-tidal concentration of desflurane reaching 0.5 minimum alveolar concentration (MAC), time when the ratio of the end-tidal concentration of desflurane to the pre-set concentration of the vaporizer reached 1/2, time when the ratio of the end-tidal concentration of desflurane to the inhaled concentration reached 1/2, time for the end-tidal concentration of desflurane to decrease to 0.5 MAC and time for the end-tidal concentration to decrease from 0.5 MAC to 0.2 MAC immediately after closing the volatile tank were recorded.The patients were divided into 3 groups according to the operation time: operation time <2 h group (group S), operation time 2-4 h group (group M), and operation time >4 h group (group L). Results:There were no significant differences among the 3 groups in the duration required for the end-tidal concentration of desflurane reaching 0.5 MAC, time when the ratio of the end-tidal concentration of desflurane to the pre-set concentration of the vaporizer reached 1/2, time when the ratio of the end-tidal concentration of desflurane to the inhaled concentration reached 1/2, time for the end-tidal concentration of desflurane to decrease to 0.5 MAC and time for the end-tidal concentration to decrease from 0.5 MAC to 0.2 MAC immediately after closing the vaporizer ( P>0.05). Conclusion:Operation duration does not affect the pharmacokinetics of desflurane in the patients undergoing tumor resection.

Objective:To evaluate the effect of remimazolam pretreatment on brain injury following thalamic hemorrhage in mice.Methods:Sixty clean-grade healthy adult CD1 male mice, weighing 25-30 g, aged 7-8 weeks, were divided into 3 groups ( n=20 each) by using a random number table method: sham operation group (Sham group), brain injury group (BI group) and remimazolam pretreatment group (Rem group). Remimazolam 25 mg/kg was intravenously injected via the tail vein in group Rem.and the equal volume of normal saline was given instead in Sham group and BI group.Ten min later, type Ⅳ collagenase 0.01 U/10 nl was microinjected into unilateral ventroposterolateral nucleus and ventromedial nucleus to develop a mouse model of brain jury induced by thalamic hemorrhage.The rats were sacrificed at 6 h after developing the model, brain tissues were taken for measurement of the wet/dry weight (W/D) ratio, and hippocampal tissues were taken and stained with haematoxylin and eosin for determination of the count of the viable neurons in the hippocampal dentategyrus area, count of apoptotic neurons in the hippocampal CA1 region (by TUNEL), expression of CCAAT/enhancer-binding protein homologous protein (CHOP), activating transcription factor 4 (ATF4) and X-box binding protein-1 (XBP1) mRNA (by real-time polymerase chain reaction) and expression of CHOP, Bcl-2, Bax and caspase-3 (by Western blot) and for microscopic examination of ultrastructure of hippocampal tissues (with a transmission electron microscope). Results:Compared with group Sham, the W/D ratio of brain tissues and count of apoptotic neurons in the hippocampal CA1 area were significantly increased, the count of viable neurons in the hippocampal dentate gyrus was decreased, the expression of CHOP, ATF4 and XBP1 mRNA in hippocampal tissues was up-regulated, the expression of CHOP, caspase-3 and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in BI and Rem groups ( P<0.05). Compared with group BI, the W/D ratio of brain tissues and count of apoptotic neurons in the hippocampal CA1 area were significantly decreased, the number of viable neurons in the hippocampal dentate gyrus was increased, the expression of CHOP, ATF4 and XBP1 mRNA in hippocampal tissues was down-regulated, the expression of CHOP, caspase-3 and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group Rem ( P<0.05). Conclusion:Remimazolam pretreatment can reduce the brain injury following thalamic hemorrhage in mice, and the mechanism may be related to inhibition of cell apoptosis induced by endoplasmic reticulum stress in hippocampus.

Objective:To analyze the clinical and imaging features of influenza associated encephalopathy(IAE) in children, thus contributing to enhance the efficacy of early identification, timely treatment and prognosis.Methods:Clinical data, laboratory examination, imaging data, treatment and outcomes of 40 children with IAE diagnosed and treated in the Beijing Children′s Hospital, Capital Medical University from December 2016 to January 2020 were retrospectively analyzed.Clinical features were summarized and they were further classified according to clinical imaging features.The prognosis was compared and analyzed.Results:A total of 20 boys and 20 girls were recruited, with the age of attending hospital at (4.0±2.3) years (median, 3.2 years). There were 28 children with influenza A and 12 with influenza B. All children initially had fever, and the interval between fever and symptoms of neurological onset was 24 hours (0-120 hours). The most-common symptom of neurological onset was seizures(32 cases), among which 17 patients showed continuous seizures.All children presented encephalopathy at varying degrees, including 33 cases in coma and 7 in drowsiness or cognitive decline.Thirty cases developed central respiratory failure and received mechanical ventilation.Examination results showed 30 cases had elevated aspartate transaminase (AST), 18 cases had elevated alanine transaminase (ALT), 14 cases had elevated creatinine, 31 cases had elevated lactate dehydrogenase, 16 cases had elevated blood glucose and 1 case had significantly lowered blood glucose.Blood ammonia testing was performed in 38 children and 9 cases had elevated level.The whole exon sequencing in 6 cases showed de novo heterozygous mutation of the SCN1A gene in 1 case, and heterozygous mutation of the ATP1A2 gene inherited from the mother in another case.Lumbar puncture was performed in 35 cases, and all of them had a normal range of cerebrospinal fluid leukocyte counts, while 12 cases had elevated cerebrospinal fluid proteins.Abnormal image findings were examined in 33 cases and the acute necrotizing encephalopathy was the most common one (14 cases). All children received Peramivir or Oseltamivir after admission.A total of 28 cases were treated with glucocorticoids, and 29 cases were treated with immunoglobulin.Seventeen cases died, 9 cases had disability at varying degrees, and 14 cases recovered to the baseline.Patients were divided into good prognosis group and poor prognosis group.(1) Patients in good prognosis group presented significantly shorter interval between fever and first neurological symptoms[(22.7±12.2) h vs.(38.6± 30.9) h], higher Glasgow score on admission[(7.6±2.5) points vs.(4.5 ± 1.6) points], lower ALT [15.6 (9.0-1 631.5) U/L vs.140.2 (12.3-3 232.4) U/L] and lower AST [47.6 (25.4-1 721.3) U/L vs.251.8 (21.7-4 991.6) U/L] than those in poor prognosis group (all P<0.05). (2) Glucocorticoids were applied to 17 and 11 cases in good prognosis group and poor prognosis group, while immunoglobulins were applied to 17 and 12 cases, respectively ( P>0.05). (3) Patients were further classified into cytokine storm group, excitotoxicity group and unclassifiable group according to clinical imaging findings.The Glasgow score [ (4.6±1.7) points vs.(7.6±2.2) point vs.(7.3±2.8) points] and median modified Rankin Scale score (6.0 points vs.1.5 points vs.0) were significantly different among 3 groups (all P<0.01). Conclusions:Influenza associated encephalopathy is common in infants and young children.Fever, convulsions and rapidly progressing disturbance of consciousness are the most common clinical manifestations.Acute necrotizing encephalopathy is the most common subtype of clinical imaging syndrome.Acute onset and rapid progression predict the poor prognosis of influenza associated encephalopathy.

Objective:To systematically review the effects of limited fluid intake on the prognosis of patients with heart failure.Methods:RCTs about the effects of limited fluid intake on the prognosis of patients with heart failure published up to March 31, 2021 were retrieved from PubMed, The Cochrane Library, CINAHL, Embase, Web of Science, CNKI, Wanfang, VIP, and SinoMed. Two independent researchers were employed to extract data and evaluate the quality of included literature. Rev Man 5.3 was used for Meta-analysis, sequential analysis to evaluate the reliability and authenticity of the research results, and the Egger's test for publication bias.Results:A total of 7 articles were included, with a sample size of 867 cases. Meta-analysis showed that the body weight [ MD=-3.04, 95% CI (-4.70, -1.38) , P<0.001], B-type natriuretic peptide [ MD=-249.32, 95% CI (-305.00, -193.63) , P<0.001], blood creatinine [ MD=-22.03, 95% CI (-24.98, -19.09) , P<0.001], readmission rate [ OR=0.30, 95% CI (0.20, 0.45) , P<0.001] of the limited fluid intake group in the chronic phase of heart failure were lower than those in the control group; the body weight [ MD=1.41, 95% CI (-3.73, 6.55) , P=0.59], B-type natriuretic peptide [ MD=64.52, 95% CI (-50.01, 179.06) , P=0.27], serum creatinine [ MD=3.83, 95% CI (-9.69, 17.36) , P=0.58], readmission rate [ OR=1.21, 95% CI (0.65, 2.27) , P=0.55] of the acute fluid intake group were not statistically different from those in the control group. Conclusions:Limiting fluid intake in the chronic phase of heart failure can effectively improve the patients' heart and kidney function and the prognosis of the disease. In the acute phase of heart failure, it may be necessary to combine multiple treatments to keep the patients at the best volume state.