Dl-tetrahydropalmatine (THP) 5 ~ 15 mg ? kg-1 iv markedly reduced the incidences of cardiac arrhythmias and myocardial lipidperoxide content after reperfusion of the is-chemic myocardium in rats. In isolated rat ventricular muscles, THP 1,3 and 10 ?mol?L-1 shifted the concentration-effect curves for phenylephrine to the right unparally, together with decreasing their maximal responses,exhibiting a non-competed antagonistic action. It was also found that THP 10 ?mol?L-1was able to reduce the amplitude of delayed afterdepolar-izations and to stop triggered activity and/or ab-normal automatic activity induced by reoxygena-tion of hypoxic myocardium in isolated ventricular muscles of guinea pig. These results suggest that the protective effects of THP might be attributed, at least in part, to the depression of delayed afterdepolarizations and the prevention of oxygen free radical injury without the involvement of the cardiac ?1-adrenoceptors.

Objective To observe the effect of Toll interleukin-1 recptor homology/BB-loop mimetic hydrocinnamoyl-L-valyl pyrrolidine (AS-1) on the healing quality of deep partial-thickness scald wound in mice.Methods Forty-two adult C57BL/6 mice were divided into sham injury group (SI),scald group (S),early AS-1 treatment group (EAT),early dimethyl sulfoxide (DMSO) control group (EDC),late AS-1 treatment group (LAT),late DMSO control group (LDC) according to the random number table,with 7 mice in each group.Mice in group SI were sham injured without other treatment.Deep partial-thickness scald model with 10％ total body surface area was reproduced on the back of the other mice,and the wound was treated by daily wound cleaning with saline and dressing changing with vaseline gauze after injury.Mice in group EAT and those in group LAT were intraperitoneally injected with 20 mg/mL AS-1 50 mg/kg each day respectively from post scald hour (PSH) 8 and post scald day (PSD) 15 on.Mice in group EDC and those in group LDC were intraperitoneally injected with 20 mg/mL DMSO 50 mg/kg each day respectively from PSH 8 and PSD 15 on.On PSD 21,the gross condition of wound healing of mice with scald was observed,and the wound healing rate was calculated.Tissue samples of healed wound were collected and stained with HE and Masson respectively to observe the histomorphological change and fibrosis of collagen,and the percentage of fibrosis of collagen was calculated.The mRNA expressions of interleukin-1 β (IL-1β),tumor necrosis factor α (TNF-α),transforming growth factor β1 (TGF-β1),matrix metalloproteinase-1 (MMP-1),tissue inhibitors of metalloproteinase 1 (TIMP-1),connective tissue growth factor (CTGF),type Ⅰ collagen and type Ⅲ collagen in healed wound tissue were detected by real time fluorescent quantirive reverse transcription polymerase chain reaction.The protein expressions of type Ⅰ collagen and type Ⅲ collagen in healed wound tissue were detected by Western blotting.Skin tissue of mice in group SI at the same area as that observed and collected in mice with scald was performed with the same observation and detection as mentioned above at the same time.Data were processed with one-way analysis of variance and Tukey test.Results On PSD 21,no abnormal appearance was found in skin tissue of mice in group SI.Wounds of mice in group EAT were healed completely without scar formation,while those in the other four groups were not completely healed with scars formed in different degree.The wound healing rate of mice in group EAT was (97 ±4)％,close to that of group SI (100％,q =1.753,P ＞0.05),and both of them were obviously higher than those of groups S,EDC,LAT,and LDC [respectively (83 ± 8)％,(87 ± 6)％,(85 +9)％,and (85 ±7)％,withq values from 4.819 to 6.803,P ＜0.05 orP ＜0.01].On PSD 21,no abnormal appearance was found in morphology of skin tissue of mice in group SI.The morphology of healed wound tissue of mice in group EAT was close to that in group SI,with little epidermis hyalinosis and few newly formed collagen fibers arranged orderly.Epidermis hyalinosis in band-or flake-shape and obvious proliferation of collagen fibers arranged disorderly were observed in healed wound tissue of mice in the other four groups.Much infiltration of inflammatory cells was found in group S.The percentage of fibrosis of collagen in healed wound tissue of mice in group EAT was (30 ± 3) ％,close to that of group SI [(30 ± 4) ％,q =0.159,P ＞0.05],and both of them were obviously lower than those of groups S,EDC,LAT,and LDC [respectively (86+9)％,(74+5)％,(82±4)％,and (82±7)％,with q values from 12.080 to 15.530,P values below 0.01].On PSD 21,compared with those of group SI,the mRNA expressions of IL-1β,TNF-α,TGF-β1,MMP-1,and CTGF in healed wound tissue of mice in group S,the mRNA expressions of TGF-β1 in healed wound tissue of mice in groups EDC and LDC,and the mRNA expression of MMP-1 in healed wound tissue of mice in group LAT were significantly increased (with q values from 4.039 to 5.232,P values below 0.05),while the mRNA expression of TIMP-1 in healed wound tissue of mice in group S was significantly decreased (q =4.921,P ＜ 0.05).Compared with those of group S,the mRNA expressions of IL-1 β,TNF-α,TGF-β1,MMP-1,and CTGF in healed wound tissue of mice in group EAT and the mRNA expressions of IL-1 β and CTGF in healed wound tissue of mice in group LAT were significantly decreased (with q values from 4.418 to 6.402,P ＜ 0.05 or P ＜ 0.01),while the mRNA expressions of TIMP-1 in healed wound tissue of mice in groups EAT and LAT were significantly increased (with q values respectively 3.929 and 8.299,P ＜0.05 orP ＜0.01).Compared with those of group SI,the mRNA and protein expressions of type Ⅲ collagen in healed wound tissue of mice in the other groups and the mRNA and protein expressions of type Ⅰ collagen in healed wound tissue of mice in groups S,EDC,LAT,and LDC were significantly increased (with q values from 7.054 to 11.650,P values below 0.01).Compared with those of group EAT,the mRNA and protein expressions of type Ⅰ collagen in healed wound tissue of mice in groups S,EDC,LAT,and LDC were significantly increased (with q values from 5.156 to 7.451,P ＜0.05 orP ＜0.01).Conclusions AS-1 can effectively promote wound healing and reduce fibrosis degree in the early stage of inflammation response after deep partial-thickness scald in mice,which may be related to its effect in decreasing the expression of inflammation related factors IL-1β and TNF-α and fibrosis related factors TGF-β1,MMP-1,CTGF,and type Ⅰ collagen.

Objective:To summarize the clinical features of developmental epileptic encephalopathy children with DNM1 gene variants. Methods:The genotypes and clinical features of 15 children with DNM1 variants related epilepsy in the Department of Pediatrics, Peking University First Hospital from June 2017 to October 2021 were retrospectively analyzed. Results:A total of 8 male and 7 female epilepsy patients with DNM1 gene variants with the age of seizure onset ranging from 15 days to 22 months were recruited, median age was 8 months.All cases belonged to de novo heterozygous variants of the DNM1 gene, including 13 cases of missense variants, 1 case of frame shift variant and 1 case of nonsense variant, 8 cases of ectopic sites have not been reported.Multiple seizure types were observed, including epileptic spasms in 15 patients, focal seizure in 9 patients, atypical absence seizure in 2 patients and tonic seizure in 2 patients.There were various types of seizures in 7 children.Nine cases occurred as infantile spasm for the first time.All 15 patients showed varied degrees of development delay, among them, 11 cases had developmental retardation before epilepsy.Three patients had slow rhythm of electroencephalogram background activity, the electroencephalography showed hypsarrhythmia in 13 patients; clinical seizures were detected in 8 cases, among them, epileptic spasms were captured in 7 patients, tonic seizure was captured in 1 patient.Widened frontotemporal subarachnoid space, cerebral atrophy, and corpus callosum dysplasia were examined in 6, 2 and 3 patients by cranial magnetic resonance imaging, respectively.All 15 cases were diagnosed as developmental epileptic encephalopathy, of which 13 cases were consistent with infantile spasms.The age of the last follow-up ranged from 1 year old to 7 years old.After multi-antiepileptic drug treatment, 2 patients were remission, 1 patient(small size of identical twins) died of severe pneumonia at the age of 2 years, and 12 patients still had intermittent seizures, of which 1 patient was transformed from infantile spasms to Lennox-Gastaut syndrome. Conclusions:The onset age of developmental epileptic encephalopathy caused by the DNM1 gene variant usually begins in the infantile period, the peak onset age was 8 months.The main types of seizures include epileptic spasms and focal seizures, developmental retardation can occur before seizures.The clinical manifestations are mostly infantile spasms syndrome, and some children can be transformed into Lennox-Gastaut syndrome.

Objective:To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE).Methods:Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children′s Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children′s characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed.Results:Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications.Conclusions:The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.

Objective:To summarize the clinical features of epilepsy and (or) developmental delay associated with KCNB1 gene variants in children.Methods:A case series study was conducted on 24 children with KCNB1 gene variants associated with epilepsy and (or) developmental delay who were treated at the Children′s Medical Center of Peking University First Hospital and the Department of Neurology of Shenzhen Children′s Hospital from July 2015 to June 2024. The manifestations of seizures, electroencephalogram (EEG) and genetic test results of those children were analyzed.Results:All the KCNB1 gene variants were de novo, involving 20 different variation, including 15 missense variations, 3 frameshift variations and 2 nonsense variations. There were 7 novel variations. Among the 24 developmental and epileptic encephalopathy children, there were 14 boys and 10 girls. The last follow-up age ranged from 9 months to 13 years and 9 months. Seizures were present in 21 children (88%), with onset ranging from 1 month to 7 years, and 76% (16/21) began before 2 years of age. The seizure types included focal seizures in 15 children (71%), epileptic spasms, myoclonic seizures, and generalized tonic-clonic seizures in 6 children respectively, atypical absence seizures in 4 children, and myoclonic atonic seizures in 1 child. Seventeen children (81%) had a cluster of seizures and 5 had a history of focal status epilepticus with impaired consciousness. All 24 children had varying degrees of developmental delay, with 3 presenting solely developmental delay. EEG abnormalities were present in all the 21 children with seizures, including focal or multifocal discharges in 20 children, generalized discharges in 10 children, hypsarrhythmia in 2 children, and electrical status epilepticus during sleep in 3 children. Magnetic resonance imaging abnormalities were found in 5 of the 24 children. Among the 21 children with seizures, 57% (12/21) achieved seizure control.Conclusions:KCNB1 gene variants are predominantly de novo missense variation. Most affected children present with epilepsy, though some may exhibit only developmental delay. Epilepsy often begins before 2 years of age, with focal seizures being the most common type. About 80% of patients experience clustered seizures. Although most patients achieve seizure control, they still exhibit varying degrees of developmental delay, consistent with developmental epileptic encephalopathy.