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.

Objective:To evaluate the effect of propofol on excitability of pyramidal neurons in orbitofrontal cortex of mice and the underlying ion channel mechanism.Methods:Brain slices of 400 μm thickness from healthy male C57 mice (aged 8-12 weeks)were prepared.This experiment was performed in two parts.Part Ⅰ The brain slices were divided into 2 groups ( n=7 each) based on the random number table method: control group (C group) and propofol group (P group). Cells were perfused with vehicle in group C and with 10 μmol/L propofol in group P. Part Ⅱ The brain slices were divided into 5 groups ( n=8 each) using the random number table method: propofol group (P group), hyperpolarization-activated non-selective cation channel antagonist ZD7288 plus propofol group (Z + P group), inward rectifier potassium channel antagonist topiramate plus propofol group(T + P group), transient activation of voltage-gated potassium channel antagonist 4-aminopyridine (4AP) plus propofol group (A + P group), and delayed activation of voltage-gated potassium channel antagonist tetraethylammonium (TEA) plus propofol group (TEA + P group). Cells were perfused with 10 μmol/L propofol for 2 min in P group, with 5 μmol/L ZD7288 and 10 μmol/L melatonin for 2 min in Z+ P group, with 5 μmol/L topiramate and 10 μmol/L propofol for 2 min in T + P group, with 10 μ mol/L 4-aminopyridine and 10 μmol/L propofol for 2 min in A+ P group, and with 10 μmol/L TEA and 10 μmol/L propofol for 2 min in TEA+ P group.The whole-cell currents, membrane potential and discharge frequency of pyramidal neurons in the orbitofrontal cortex were recorded by whole-cell patch-clamp. Results:Part Ⅰ Compared with C group, whole-cell currents were significantly increased, and the membrane potential and discharge frequency were decreased in P group ( P<0.01). Part Ⅱ Compared with P group, no significant change was found in the whole-cell currents, membrane potentials and discharge frequency in Z+ P group, T+ P group and A+ P group ( P>0.05), and the whole-cell currents were significantly decreased, and the membrane potentials and discharge frequency were increased in TEA+ P group ( P<0.05). Conclusion:Propofol can inhibit the excitability of pyramidal neurons in the orbitofrontal cortex, and the mechanism is related to activating delayed activation of voltage-gated potassium channels in mice.

Objective: The clinical characteristics of dural arteriovenous fistula with pulsatile tinnitus were analyzed to deepen the understanding of the disease. Methods: The clinical data of five patients complained of pulsatile tinnitus and diagnosed dural arteriovenous fistula in Henan People's Hospital from May 2013 to June 2018 were retrospectively analyzed, including 3 males and 2 females, aged 27-65 years. Results: The main clinical symptoms of the five patients were continuous pulsatile tinnitus, accompanied/not accompanied by headache, memory decline, etc., with a course of three months to 20 years. They were diagnosed as dural arteriovenous fistula by digital subtraction angiography, and three cases of tinnitus disappeared and two cases of tinnitus were relieved after embolization. Conclusions The dural arteriovenous fistula is a rare and complicated disease. When the patient complain of the pulsatile tinnitus, the related etiology should be considered and managed properly.

Objective: To describe the clinical manifestations of central nerve system inflammatory demyelinating disease associated with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IDD) in children, and to explore the clinical characteristics of the children. Methods: The clinical and laboratory characteristics of the patients diagnosed in Beijing Children′s Hospital, Capital Medical University, from October 2016 to August 2018 were described, and the clinical data of the patients with unipolar and recurrent diseases were compared. Results: A total of 50 patients were included, among whom the ratio of male to female was 24:26, and the average age of onset was (6.7±3.1) years old (0.4-12.6 years old). There was no significant difference in the age of onset between boys and girls(t=0.712, P=0.480). The main symptoms included fever (31/50 cases), encephalopathy (26/50 cases) and optic neuritis (22/50 cases), etc.In the last follow-up, 26 patients (52.0%) had a monophasic course and 24 patients (48.0%) had a recurrent course.There were age differences in encephalopathy and ataxia in the first episode of [(5.7±2.8) years old vs.(8.1±3.0) years old, (5.0±2.5) years old vs. (7.7±3.0) years old](t=2.746, P=0.009; t=2.837, P=0.007). The average number of recurrence was (2.1±1.4) times (1-7 times), in which 17 cases (70.8%) of recurrence presented within 12 months and 20 cases (83.3%) of recurrence presented within 24 months after onset.Convulsion incidences of recurrent cases were 10 cases and 13 cases respectively in the first episode and recurrent courses, which were significantly higher than those of monophasic cases (4 cases, 4 cases)(χ²=7.912, P=0.005; χ²=8.365, P=0.004). All patients were sensitive to first-line immunotherapy.Seven patients with recu-rrence were treated with mycophenolatemofetil, and 17 patients with repeated first-line therapy.In the last follow-up, all patients were in remission and 2 patients had mild neurological dysfunction. Conclusions MOG-IDD can occur in childhood.Encephalopathy and optic neuritis are the most common symptoms.Encephalopathy and ataxia are more common in young children.Convulsions may indicate the course of recurrence.

Objective: To characterize fever-induced paroxysmal weakness and encephalopathy (FIPWE) caused by ATP1A3 gene pathogenic variant. Methods: Phenotypic and genotypic characteristics of 4 FIPWE patients (3 boys and 1 girl), who were ascertained from October 2016 to March 2018 in Beijing Children's Hospital due to ATP1A3 heterozygous variants, were retrospectively analyzed. The whole exsome sequencing was used for genetic testing. Results: The onset ages of 4 patients were 2 years and 9 months, 2 years and 4 months, 8 months, 2 years and 5 months respectively. The episode ranged from 1 to 3 times, and at 3 months to 2 years and 10 months intervals. All 4 patients had symptoms of limb weakness and encephalopathy, accompanied with mild to severe ataxia or athetosis. The tendon reflex was absent in all patients, and the Babinski's sign was positive. Three patients had dysphagia and 3 patients had slurred speech. Three patients had abnormal eye movements, including strabismus and opsoclonus. None of the 4 patients exhibited visual impairment, auditory impairment or talipes cavus. The duration of acute phase ranged from 1 week to 3 months. In 3 relapsing patients, symptoms became progressively worse, with relapses occurring frequently and recovery being more difficult, and various sequelae were found after the last relapse. All patients carried heterozygous variant in ATP1A3 gene. The missense variants result in the substitution of an arginine residue at position 756. Three variants were identified, including C. 2267G > T (p. R756L) (1 case), C. 2266C > T (p. R756C) (2 cases), and C. 2267G > A (p. R756H) (1 case). Three were de novo and one inherited from his father, but the grandparents did not carry the variant. All variants were reported as pathogenic. Conclusions FIPWE is one of new clinical phenotypes of ATP1A3 spectrum disease and most cases are sporadic. The missense variants result in the substitution of an arginine residue at position 756. This report provided insights into the phenotype-genotype association in patients with FIPWE caused by pathogenic variants of ATP1A3.

Objective To characterize fever‐induced paroxysmal weakness and encephalopathy (FIPWE) caused by ATP1A3 gene pathogenic variant. Methods Phenotypic and genotypic characteristics of 4 FIPWE patients(3 boys and 1 girl), who were ascertained from October 2016 to March 2018 in Beijing Children′s Hospital due to ATP1A3 heterozygous variants, were retrospectively analyzed. The whole exsome sequencing was used for genetic testing. Results The onset ages of 4 patients were 2 years and 9 months, 2 years and 4 months, 8 months, 2 years and 5 months respectively. The episode ranged from 1 to 3 times, and at 3 months to 2 years and 10 months intervals. All 4 patients had symptoms of limb weakness and encephalopathy, accompanied with mild to severe ataxia or athetosis. The tendon reflex was absent in all patients, and the Babinski′s sign was positive. Three patients had dysphagia and 3 patients had slurred speech. Three patients had abnormal eye movements, including strabismus and opsoclonus. None of the 4 patients exhibited visual impairment, auditory impairment or talipes cavus. The duration of acute phase ranged from 1 week to 3 months. In 3 relapsing patients, symptoms became progressively worse, with relapses occurring frequently and recovery being more difficult, and various sequelae were found after the last relapse. All patients carried heterozygous variant in ATP1A3 gene. The missense variants result in the substitution of an arginine residue at position 756. Three variants were identified, including C. 2267G>T (p. R756L) (1 case), C. 2266C>T (p. R756C) (2 cases), and C. 2267G>A (p. R756H) (1 case). Three were de novo and one inherited from his father, but the grandparents did not carry the variant. All variants were reported as pathogenic. Conclusions FIPWE is one of new clinical phenotypes of ATP1A3 spectrum disease and most cases are sporadic. The missense variants result in the substitution of an arginine residue at position 756. This report provided insights into the phenotype‐genotype association in patients with FIPWE caused by pathogenic variants of ATP1A3.

Two simple and sensitive high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) methods were developed and validated for the determination of fenticonazole in human plasma after percutaneous and intravaginal administration. Mifepristone was used as an internal standard (IS), and simple protein precipitation by acetonitrile containing 2%acetic acid was utilized for extracting the analytes from the plasma samples. Chromatographic separation was performed on a Kinetex XB-C18 column. The quantitation was performed by a mass spectrometer equipped with an electrospray ionization source in multiple reactions monitoring (MRM) positive ion mode using precursor-to-product ion transitions of m/z 455.2–199.1 for fenticonazole and m/z 430.2–372.3 for mifepristone. The validated linear ranges of fenticonazole were 5–1000 pg/mL and 0.1–20 ng/mL in plasma for the methods A and B, respectively. For the two methods, the accuracy data ranged from 85% to 115%, the intra- and inter-batch precision data were less than 15%, the recovery data were more than 90%, and no matrix interference was observed. The methods A and B were successfully validated and applied to the pharmacokinetic studies of fenticonazole gel in Chinese healthy volunteers after percutaneous and intravaginal administration, respectively.

Objective To compare anesthetic effect and safety of general anesthesia and combined spinal and epidural anesthesia used in autonomic nervous hyperresponsive surgery for patients with paraplegia.Methods 26 paraplegic patients were randomly divided into two groups-control group and treatment group from February 2011 to November,2015,each with 13 cases.The control group used general anesthesia,while the treatment group used combined spinal and epidural anesthesia,to observe onset time,duration,intraoperative hemodynamic changes and complications,Complications,length of stay and cost,Days and costs of hospitalization,satisfaction of patients and their families,of anesthesia in two groups.Results The dosage of narcotics and the onset time of the treatment group were better than that of the control group.The difference between the two groups was significant,and had statistical significance (P＜0.05) Two groups of patients after surgery,diastolic blood pressure,systolic blood pressure and heart rate were lower in the treatment group than in the control group,and had statistically significant difference (P＜0.05);The postoperative complications of the treatment group were significantly better than those of the control group,and had statistically significant difference (P＜0.05);There were statistically significant differences in postoperative pain degree between the two groups (P＜0.05);Two groups of patients in hospital days,hospital costs,satisfaction rate had statistically significant difference,Have statistical significance (P＜0.05).Conclusion In autonomic nervous hyperresponsive surgery for patients with paraplegia,anesthetic effect and safety of combined spinal and epidural anesthesia is significantly better than that of general anesthesia,featured by the rapid onset of action,long duration,fewer complications,strong safety and patients' great satisfaction.It is worth generalizing and applying clinically.

Objective To evaluate the clinical and pathological characteristics and risk factors of the prognosis of Cardia cancer.Methods Clinical data of 52 cases of cardiac cancer patients who were treated by surgery and follow-up data were collected from June 2009 to August 2011.Factors influencing the prognosis of the patients were analyzed by univariate and multivariate analysis.Results The survival rates in 1,2,3years were 73％,54％,46％.Single factor analysis showed that there was a significant correlation between T stage,N stage,TNM stage,classification Siewert,MSLN and venous invasion.Stepwise Cox proportional hazard model showed that T stage,N stage and MSLN were independent risk factors.Peritoneal and liver were the main way of recurrence and metastasis.Peritoneal metastasis was related to T stage and lymph node invasion,while the liver metastasis was related to MSLN.The survival curves of patients with Kaplan-Meier showed that the survival period of patients with liver metastasis and peritoneal metastasis was significantly shortened.Conclusion Standardization of lymph node cleaning is a key factor affecting prognosis,D2 surgery should be an operation standard in cardia cancer.

Objective To investigate the protective effect of rosiglitazone on acute necrotizing pancreatitis (ANP) associated lung injury in rats.Methods Seventy-five male Wistar rats were randomly divided into sham operation group (SO group),acute necrotizing pancreatitis group (ANP group) and rosiglitazone pretreatment group (ROSI group).ANP model was induced by retrograde infusion of 5％ sodium taurocholate into the biliopancreatic duct.Thirty minutes after ANP induction,ANP groups were injected with 10％ DMSO (0.2 ml/100 g) through femoral vein,and ROSI group were injected with ROSI dissolved with 10％ DMSO (6 mg/kg) through femoral vein,while SO group was injected with normal saline,and 30 minutes later was injected with same amount of 10％ DMSO.Rats were sacrificed at 3 h,6 h and 12 h after the operation.Serum amylase and lung wet/dry weight ratio (W/D) were measured,lung tissues were harvested for pathologic examinations.STAT1 protein and phosphorylation-STAT1 protein (p-STAT1) expression were detected by Western blot.Results The serum levels of amylase,lung W/D,pathologic score of lung tissues in ANP group were increased with time,and reached the peak at 12 h,which were (5017 ± 203)U/L,3.12 ±1.30,(3.33 ±0.18) score,and these were significantly higher than those in SO group (P ＜ 0.05 or 0.01),the expression of STAT1 protein was not statistically significant,but the expression of p-STAT1 reached the peak at 3 h (5.23 ± 0.03),then it gradually decreased,but it was still significantly higher than that in SO group (0.16 ± 0.04,p ＜ 0.01).The serum levels of amylase,lung W/D,pathologic score of lung tissues in ROSI group at 12 h were (1912 ± 164) U/L,1.83 ± 1.26,(2.78 ± 0.16),which were significantly lower than those in ANP group (P ＜ 0.05).The expression of STAT1 protein was not statistically significant,and the expressions of p-STAT1 at 3 h,6 h,12 h was 0.41 ±0.04,0.22±0.05,0.15 ±0.03,which were significantly lower than those in ANP group (P ＜ 0.05).Conclusions Rosiglitazone has the protective effect on ANP associated lung injury by inhibition of phosphorylation-STAT1 protein expression in the early phase.