Clinical characteristics, gene mutations and enzyme replacement therapy of 13 children with Pompe disease / 中华实用儿科临床杂志

Objective:To summarize the clinical features, gene mutations and experience of standardized enzyme replacement therapy (ERT) of Pompe disease (PD) in children.Methods:A retrospective analysis was performed on the clinical data of 13 children with PD, who were hospitalized in Qingdao Women and Children′s Hospital from December 2016 to August 2021.According to the age at onset, the children were divided into the infantile-onset Pompe disease (IOPD) group and late-onset Pompe disease (LOPD) group.At the same time, they were divided into the ERT group and non-ERT group according to whether recombinant human acid alpha-glucosidase (rhGAA) was infused.Furthermore, the ERT group was divided into the standard ERT group and non-standard ERT group.The standard ERT group received a dose of 20 mg/kg every 2 weeks for 52 weeks.The survival rate was compared between groups by using the Kaplan-Meier method.Results:Among the 13 children with PD, there were 7 males and 6 females.Ten cases belonged to the IOPD group and 3 cases belonged to the LOPD group.The most common cause of initial consultation in the IOPD group was cardiac involvement, which accounted for 60.0% (6/10 cases), while the LOPD group mainly presented with myasthenia, cardiac involvement and respiratory tract infection at the first diagnosis.The serum level of creatine kinase (CK) in all cases increased to varying degrees.Acid alpha-glucosidase (GAA) was completely deficient in 1 case and decreased in 12 cases.All the children in the IOPD group showed myocardial hypertrophy, electrocardiograph (ECG) suggested a short PR interval, increased QRS voltage and extensive T-wave inversion.Three new mutations were found by GAA gene analysis, and they were c. 1861T>G (p.Trp621Gly), c.2278A>T (p.K760X), and c. 949G>A (p.A317T). Five cases in the IOPD group were given ERT.Two of them were given standard ERT for 52 weeks, and the other 3 cases were treated with non-standard ERT.At the end of follow-up, 2 cases treated with standardized ERT survived and the remaining 8 cases died of heart failure or respiratory failure.In the LOPD group, only 1 case was given ERT one time.Finally, 2 cases survived and one died of respiratory failure.The total fatality rate was 69.2%(9/13 cases). The survival rate of the ERT group (50.0%) and standard ERT group (100.0%) was significantly higher than that of the non-ERT group (14.3%) ( Log Rank P=0.037, 0.044). Conclusions:The clinical manifestations of PD are diverse.GAA activity examination and GAA gene analysis are important for clinical diagnosis of PD.Standardized ERT can significantly delay the progression of PD and even reverse myocardial hypertrophy in children with IOPD.

Clinical characteristics, gene mutations and enzyme replacement therapy of 13 children with Pompe disease / 中华实用儿科临床杂志

Objective:To summarize the clinical features, gene mutations and experience of standardized enzyme replacement therapy (ERT) of Pompe disease (PD) in children.Methods:A retrospective analysis was performed on the clinical data of 13 children with PD, who were hospitalized in Qingdao Women and Children′s Hospital from December 2016 to August 2021.According to the age at onset, the children were divided into the infantile-onset Pompe disease (IOPD) group and late-onset Pompe disease (LOPD) group.At the same time, they were divided into the ERT group and non-ERT group according to whether recombinant human acid alpha-glucosidase (rhGAA) was infused.Furthermore, the ERT group was divided into the standard ERT group and non-standard ERT group.The standard ERT group received a dose of 20 mg/kg every 2 weeks for 52 weeks.The survival rate was compared between groups by using the Kaplan-Meier method.Results:Among the 13 children with PD, there were 7 males and 6 females.Ten cases belonged to the IOPD group and 3 cases belonged to the LOPD group.The most common cause of initial consultation in the IOPD group was cardiac involvement, which accounted for 60.0% (6/10 cases), while the LOPD group mainly presented with myasthenia, cardiac involvement and respiratory tract infection at the first diagnosis.The serum level of creatine kinase (CK) in all cases increased to varying degrees.Acid alpha-glucosidase (GAA) was completely deficient in 1 case and decreased in 12 cases.All the children in the IOPD group showed myocardial hypertrophy, electrocardiograph (ECG) suggested a short PR interval, increased QRS voltage and extensive T-wave inversion.Three new mutations were found by GAA gene analysis, and they were c. 1861T>G (p.Trp621Gly), c.2278A>T (p.K760X), and c. 949G>A (p.A317T). Five cases in the IOPD group were given ERT.Two of them were given standard ERT for 52 weeks, and the other 3 cases were treated with non-standard ERT.At the end of follow-up, 2 cases treated with standardized ERT survived and the remaining 8 cases died of heart failure or respiratory failure.In the LOPD group, only 1 case was given ERT one time.Finally, 2 cases survived and one died of respiratory failure.The total fatality rate was 69.2%(9/13 cases). The survival rate of the ERT group (50.0%) and standard ERT group (100.0%) was significantly higher than that of the non-ERT group (14.3%) ( Log Rank P=0.037, 0.044). Conclusions:The clinical manifestations of PD are diverse.GAA activity examination and GAA gene analysis are important for clinical diagnosis of PD.Standardized ERT can significantly delay the progression of PD and even reverse myocardial hypertrophy in children with IOPD.

Clinical analysis of 103 children with Angelman syndrome / 中华实用儿科临床杂志

Objective@#To investigate the correlation between clinical phenotype, electroencephalogram (EEG) characteristics and genotype in children with Angelman syndrome(AS).@*Methods@#A total of 103 children with AS at Department of Neurology, Children′s Hospital of Fudan University from June 2017 to June 2018, were included in this study.The information of clinical characteristics, EEG manifestations, genotypes as well as the epileptic outcome were collected retrospectively.The correlations between clinical phenotype, genotype, and epileptic outcome were evaluated.@*Results@#(1) Of the 103 cases, 48 were male (46.6%) and 55 were female (53.4%). (2) Genotypes on AS critical region were maternal chromosome 15q11.2-q13 [86.4%(89/103 cases)], paternal uniparental disomy [3.9%(4/103 cases)], imprinting defects [1.9%(2/103 cases)], and mutations in the maternal copy of UBE3A [7.8%(8/103 cases)]. (3) Apparent happy demeanor or smile and general developmental delay were observed in all AS children.Dyskinesia accounted for 98.1% (101/103 cases), followed by oral movement or suck disorders [97.1%(100/103 cases)] and abnormal posture [67.0%(69/103 cases)]. The proportion of acquired small head circumfe-rence or microcephaly, flat occiput or occipital groove and wide-spaced teeth were 61.2%(63/103 cases), 85.4%(88/103 cases) and 44.7%(46/103 cases), respectively.(4) Behavioral problems like fascination with water, sleep problems and feeding difficulties were found in 86.4%(89/103 cases), 89.3%(92/103 cases) and 85.5%(88/103 cases) of the children, respectively.Sleep disorders [94.4%(84/89 cases) vs.57.1%(8/14 cases)] and feeding difficulties [93.3%(83/89 cases) vs.35.7%(5/14 cases)] were more frequently seen in children with maternal absence group, compared those with no absence, and the differences were statistically significant (all P<0.05). (5) Epilepsy was present in 77.7% (80/103 cases) of children with onset age varying from 8 to 72 months and 80.8% (59/73 cases) were developing seizures prior to 3 years old.Children with maternal absence showed more multiple seizure types than those with no absence[41.7%(32/68 cases) vs.0(0 case)], and the difference was statistically significant(P<0.05). Children with well-controlled epilepsy had more atonic seizure, compared with those with poorly controlled seizure [48.3%(14/29 cases) vs.18.5%(4/27 cases)], and the difference was statistically significant(P<0.05).@*Conclusions@#Sleep disorders, feeding difficulties in infancy and multiple seizure types are more commonly seen in AS children with maternal absence.Atonic seizure is easier to be controlled over other types of seizures.

Clinical analysis of 103 children with Angelman syndrome / 中华实用儿科临床杂志

Objective To investigate the correlation between clinical phenotype,electroencephalogram(EEG) characteristics and genotype in children with Angelman syndrome(AS). Methods A total of 103 children with AS at Department of Neurology,Children′s Hospital of Fudan University from June 2017 to June 2018,were included in this study. The information of clinical characteristics,EEG manifestations,genotypes as well as the epileptic outcome were collected retrospectively. The correlations between clinical phenotype,genotype,and epileptic outcome were evaluated. Results (1)Of the 103 cases,48 were male(46. 6﹪)and 55 were female(53. 4﹪).(2)Genotypes on AS criti﹣cal region were maternal chromosome 15q11. 2－q13[86. 4﹪(89/103 cases)],paternal uniparental disomy[3. 9﹪(4/103 cases)],imprinting defects[1. 9﹪(2/103 cases)],and mutations in the maternal copy of UBE3A[7. 8﹪(8/103 cases)].(3)Apparent happy demeanor or smile and general developmental delay were observed in all AS children. Dyskinesia accounted for 98. 1﹪(101/103 cases),followed by oral movement or suck disorders[97. 1﹪(100/103 cases)]and abnormal posture[67. 0﹪(69/103 cases)]. The proportion of acquired small head circumfe﹣rence or microcephaly,flat occiput or occipital groove and wide－spaced teeth were 61. 2﹪(63/103 cases),85. 4﹪(88/103 cases)and 44. 7﹪(46/103 cases),respectively.(4)Behavioral problems like fascination with water,sleep problems and feeding difficulties were found in 86. 4﹪(89/103 cases),89. 3﹪(92/103 cases)and 85. 5﹪(88/103 cases)of the children,respectively. Sleep disorders[94. 4﹪(84/89 cases)νs. 57. 1﹪(8/14 cases)]and feeding difficulties[93. 3﹪(83/89 cases)νs. 35. 7﹪(5/14 cases)]were more frequently seen in children with maternal ab﹣sence group,compared those with no absence,and the differences were statistically significant(all P＜0. 05).(5)Epi﹣lepsy was present in 77. 7﹪(80/103 cases)of children with onset age varying from 8 to 72 months and 80. 8﹪(59/73 cases)were developing seizures prior to 3 years old. Children with maternal absence showed more multiple seizure types than those with no absence[41. 7﹪(32/68 cases)νs. 0(0 case)],and the difference was statistically significant (P＜0. 05). Children with well－controlled epilepsy had more atonic seizure,compared with those with poorly con﹣ trolled seizure[48. 3﹪(14/29 cases)νs. 18. 5﹪(4/27 cases)],and the difference was statistically significant( P＜0. 05). Conclusions Sleep disorders,feeding difficulties in infancy and multiple seizure types are more commonly seen in AS children with maternal absence. Atonic seizure is easier to be controlled over other types of seizures.

Effect of dexmedetomidine hydrochloride on H2O2-induced oxidative stress and inflammatory response in Kupffer cells / 中南大学学报(医学版)

OBJECTIVE@#To evaluate whether dexmedetomidine hydrochloride, an α(2)-adrenergic receptor agonist, can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells.
@*METHODS@#H(2)O(2)-induced oxidative damage model of Kupffer cell was established. Kupffer cells were pre-conditioned by dexmedetomidine hydrochloride or Yohimbine for 24 h. MTT colorimetry was used to demonstrate the survival rate of Kupffer cells. The levels of lactate dehydrogenase (LDH), malonaldehyde (MDA) and TNF-α in the culture medium were assessed by corresponding kits.
@*RESULTS@#Dexmedetomidine hydrochloride protected Kupffer cells from H(2)O(2)-induced oxidative damage, showing an increase in the cell survival rate while a decrease in LDH, MDA and TNF-α release in the culture supernatant. Yohimbine, an α(2)-adrenergic receptor antagonist, completely neutralized the protective effect of Dexmedetomidine hydrochloride on Kupffer cells. Yohimbine itself had no effect on H(2)O(2)-induced oxidative damage and inflammatory response.
@*CONCLUSION@#Dexmedetomidine hydrochloride can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells through activation of α(2)-adrenergic receptors.

Clinical studies on patient-controlled intravenous analgesia for postoperative pain relief in breast cancer patients with radical mastectomy / 中国医师杂志

Objective To investigate the analgesic effect and adverse reactions of patient-controlled intravenous analgesia (PCIA) in breast cancer patients with radical mastectomy.Methods A total of 210 breast cancer patients who underwent radical mastectomy was randomly divided into two groups,experimental (group A) and control (group B) groups (n =105 cases per group).Patients in group A was used PCIA for 48 hours analgesia,while group B weas applied routine intramuscular injections of pethidine.Visual analogue score (VAS) at 4,8,12,24,and 48 hours after operation were recorded.Pulse,respiration,and blood pressure were monitored and side effects e.g.existed skin itching,nausea,vomiting,and respiratory repression were observed.Results The VAS of group A patients on 4,8,12,24,and 48 hours were2.02 ± 1.47,1.73 ± 1.38,1.68 ± 0.91,1.44 ± 0.65,and 1.21 ± 0.61,respectively;and the VAS of group B patients were 6.95 ± 1.96,6.42 ± 1.57,5.63 ± 1.66,4.99 ± 1.62,and 3.72 ± 1.46,respectively.The VAS was significantly lower in group A patients than in group B (P ＜ 0.05).The incidence of skin itching,nausea,vomiting,and respiratory repression was also distinctly decreased in group A than in group B (P ＜0.05).The overall satisfaction of patients in group A (96.2％) was remarkably higher than in group B (67.6％) (P ＜0.01).Conclusions Patient-controlled intravenous analgesia pump can more effectively alleviate the degree of pain,reduce the incidence of skin itching,nausea,vomiting and respiratory repression,improve the satisfactory degree for analgesia in breast cancer patients with radical mastectomy compared to traditional intramuscular way.

Effect of dexmedetomidine hydrochloride on H2O2-induced oxidative stress in alveolar macrophages / 中南大学学报(医学版)

OBJECTIVE@#To evaluate whether dexmedetomidine hydrochloride, an α2-adrenergic receptor agonist, can prevent oxidative damage to alveolar macrophages induced by H2O2.@*METHODS@#We used methyl thiazolyl tetrazolium (MTT) colorimetry to test the effect of different concentrations and action time of H2O2 on the survival rate of alveolar macrophages, and then we chose the appropriate H2O2 concentration and action time to build NR8383 cell oxidative damage model. After pre-conditioning of 0.01, 0.10, and 1.00 μmol/L dexmedetomidine hydrochloride for 24 hours, MTT colorimetry was used to demonstrate the survival rate of NR8383 cells damaged by H2O2, and the release of lactate dehydrogenase (LDH) and TNF-α by H2O2-damaged NR8383 cells was detected by corresponding kit.@*RESULTS@#At 50-300 μmol/L, H2O2 caused concentration-dependent oxidative damage in the alveolar macrophages, decreased the cell survival rate, and increased LDH and TNF-α release. At 0.01-1.00 μmol/L dexmedetomidine hydrochloride concentration-dependently protected NR8383 cells from oxidative damage induced by H2O2, significantly increased the cell survival rate, decreased LDH and TNF-α release, and this effect of dexmedetomidine hydrochloride was dose-dependent. Yohimbine, an α2 - adrenergic receptor antagonist, completely neutralized the protective effect of dexmedetomidine hydrochloride on NR8383 cells without affecting the oxidative damage of NR8383 cells.@*CONCLUSION@#Dexmedetomidine hydrochloride can prevent alveolar macrophages from oxidative damage induced by H2O2, which may play a protective role through α2 - adrenergic receptors.

Role of Clara cells in lung ischemia-reperfusion injury in rabbits / 中华麻醉学杂志

Objective To investigate the role of Clara cells in lung ischemia-reperfusion (I/R) injury in rabbits.Methods Twenty-four healthy 10-12 month old rabbits of either sex weighing 1.5-2.0 kg were randomly divided into 3 groups ( n = 8 each) ; group A sham operation (group S) ; group B lung I/R and group C Clara cell elimination+ lung I/R. The animals were anesthetized with iv pentobarbital 30 mg/kg , tracheostomized and mechanically ventilated. In group B and C lung I/R was induced by clamping the left hilum of lung for 60 min followed by 120 min repeffusion. In group C Clara ceils were eliminated by ventilating the lungs with 89.28 mg/m2 naphthalin vapor for 12 h before lung I/R. The animals were killed by iv KCI at the end of 120 min reperfusion after lung isehemia. The left lung was immediately removed for microscopic examination, determination of W/D lung weight ratio and serum TNF-α level and MDA content. The percentage of neutrophi] in bronchoalveolar lavage fluid (BALF) was detected as index of lung injury. The expression of Clara cell secreting protein (CCSP) in the lung was detected by immuno-histoebemistry to indicate the number and distribution of Clara cells in the lung.Results Microscopic examination showed that there were severe leukocyte infiltration in alveolar spaces, alveolar edema and destroyed alveolar structure in group B and C. The serum TNF-u leve],W/D ratio and MDA content in the left lung and neutrophil percentage and WBC counts in BALF were significantly higher in group C than in group B. Conclusion Clara cells can protect the lungs against I/R injury through inhibiting inflammatory responses.

The Protective Effect of Ulinastatin on Myocardial Reperfusion Injury during Cardiopulmonary Bypass in Patients Underwent Valve Replacement / 中国医师杂志

Objective To investigate the protective effects of ulinastatin on myocardial reperfusion injury during cardiopulmonary bypass(CPB) in patients underwent valve replacement. Methods 26 ASA Ⅱ-Ⅲ patients scheduled for valve replacement were randomly divided into control group (group C) and ulinastatin group ( group W), each group containing 13 patients. In group W, the patients received ulinastatin 12000U?kg -1 , half dose of which was given before CPB, and the other half was added into the primary solution. Plasma levels of CK,CK-MB and cTnI were measured before operation(T 1), 20 min after starting CPB(T 2), 30 min after declamping aorta (T 3), and 4h(T 4) and 24h(T 5) after operation. Results The plasma level of CK, CK-MB and cTnI increased significantly at T 3, T 4 and T 5 in the both groups compared with T 1(P

Changes of plasma cytokines and myocardial enzymes in different doses of fentanyl in patients undergoing valve replacement / 中华麻醉学杂志

Objective To investigate the changes of plasma cytokines and myocardial enzymes in different doses of fentanyl in patients undergoing valve replacement under cardiopulmonary bypass (CPB) and evaluate its anti-inflammatory and myocardial protective effects.Methods Thirty ASAⅡ-Ⅲ patients undergoing elective valve replacement under CPB were studied. We excluded patients having infection, abnormal immunological function of receiving steroid or immune- modulatory drugs. The patients were premedicated with intramuscular phenobarbital 0.1 g and scopolamine 0.3 mg. Anesthesia was induced with midazolam modulate 0.1 mg ?kg-1 , fentanyl 10 ?g?kg-1 and vecuronium 0.1 mg?kg-1 and maintained with continuous infusion of fentanyl and intermittent i.v. boluses of midazolam and vecuronium. The total dose of fentanyl amounted to 30, 60 and 100 ?g?kg-1 (group 1, 2 and 3, n = 10) and was infused before CPB was started. MAP, CVP, HR, ECG, SpO2, PETCO2 and naso-pharyngeal and rectal temperature were continuously monitored during operation. Blood samples were taken before anesthesia (T1 ,baseline) , before CPB (T2 ) , 30 min and 2 h after release of aortic cross-clamping (T3 , T4 ) and 24 h after operation (T5 ) for determination of plasma levels of TNF-?, IL-6, IL-10 and creatine kinase (CK) and CK-MB activity.Results The three groups were comparable with respect to age, body weight, aortic cross-clamping time, CPB time and duration of operation. The plasma levels of TNF-?, IL-6, IL-10, CK and CK-MB activities were significantly increased after CPB compared to baseline (T1) (P

Effects of ulinastatin on cytoldnes and respiratory index during open heart surgery with CPB / 中华麻醉学杂志

Objective To investigate the effects of ulinastatin on pro- and anti-inflammatory cytokines and respiratory index during open heart surgery under CPB. Methods Twenty ASA Ⅱ- Ⅲ patients of either sex (9 males, 11 females) scheduled for elective valve replacement under CPB were randomly divided into two groups of 10 each : control group (C) and ulinastatin group (W) . Patients with hepato-renal dysfunction or taking glucocorticoid were excluded. The patients were premedicated with intramuscular phenobarbital 0.1 g and scopolamine 0.3 mg. Anesthesia was induced with midazolam 0.1 mg?kg-1 , fentanyl 10?g?kg-1 and vecuronium 0.1mg?kg-1 . After tracheal intubation anesthesia was maintained with midazolam and fentanyl. The patients were mechanically ventilated. VT was set at 8-12 ml?kg-1 , RR 10-12 bpm and I: E 1:2. PETCO2 was maintained at 35-45 mg. In ulinastatin group, the patients received ulinastatin 12 000 U?kg-1 of which half was given i.v. before CPB and half was added to the priming fluid, while group C received normal saline instead of ulinastatin. Blood samples were taken from radial artery for determination of plasma TNF-?, IL-6, and IL-10 concentrations and blood gas analysis before operation (T1 ) , 30 min after initiation of CPB (T2), 1 h (T3 ) , 4 h (T4 ) and 24 h (T5 ) after CPB. Respiratouy index (PA-aDO2/ PaO2) was calculated at T1-5 .Results There were no significant differences in sex, age, weight, height, duration of CPB, and aortic cross-clamping time between the two groups. In group C the plasma levels of TNF-?, IL-6 and IL-10 were significantly higher than the baseline values (T1 ) during and after CPB (P

Protective effect of ulinastatin on erythrocyte in patients undergoing open heart surgery with cardiopulmonary bypass / 中华麻醉学杂志

Objective To investigate the protective effect of ulinastatin on erythrocyte in patients undergoing open heart surgery with cardiopulmonary bypass (CPB) .Methods Twenty NYHA class Ⅱ-Ⅲ patients (10 male, 10 female) aged 16-66 yr undergoing elective valve replacement under CPB were randomly divided into two groups: ulinastatin group (U, n = 10) and control group (C, n = 10) . Patients with hepato-renal disease, hyperlipoproteinemia, respiratory dysfunction, blood diseases or pulmonary hypertension were excluded. The patients were premedicated with intramuscular morphine 0.08 mg ? kg-1 and scopolamine 0.006 mg?kg-1 . Anesthesia was induced with midazolam 0.1 mg?kg-1 , fentanyl 10 ?g?kg-1 and vecuronium 0.1 mg?kg-1 and maintained with intravenous midazolam and fentanyl. In group U the patients received ulinastatin 12000 U?kg-1 , of which half was given i.v. before CPB and the other half was added to the priming solution. In control group the patients received normal saline instead of ulinastatin. Blood samples were taken from radial artery before operation (T1), 15 min after initiation of CPB (T2), 15 min (T3) and 30 min (T4) after aortic declamping and 24 h after operation (T5) , for determination of plasma and erythrocyte MDA (P-MDA, E-MDA) levels and erythrocyte SOD (E-SOD) , Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase activities.Results The levels of P-MDA and E-MDA were significantly increased at T2_5 in group C but only at T3 and T4 in group U compared to the baseline at T1 . The levels of P-MDA and E-MDA at T2-5 were significantly higher in group C than in group U. The E-SOD, Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase activities significantly increased at T2 compared to baseline at T1 , then gradually decreased in both groups. They were significantly higher at T3-5 in group U than in group C. Conclusion Ulinastatin can alleviate erythrocyte lipid peroxidation and protect erythrocyte during CPB.