Comparison between high-frequency irreversible electroporation and irreversible electroporation ablation of small swine liver: follow-up of DCE-MRI and pathological observations / 中华医学杂志(英文版)

BACKGROUND@#High-frequency irreversible electroporation (H-FIRE) is a novel, next-generation nanoknife technology with the advantage of relieving irreversible electroporation (IRE)-induced muscle contractions. However, the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined. This study aimed to compare the efficacy of the two treatments in vivo.@*METHODS@#Ten Bama miniature swine were divided into two group: five in the 1-day group and five in the 7-day group. The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant (Krans), rate constant (Kep) and extravascular extracellular volume fraction (Ve) value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), size of the ablation zone, and histologic analysis. Each animal underwent the IRE and H-FIRE. Temperatures of the electrodes were measured during ablation. DCE-MRI images were obtained 1, 4, and 7 days after ablation in the 7-day group. All animals in the two groups were euthanized 1 day or 7 days after ablation, and subsequently, IRE and H-FIRE treated liver tissues were collected for histological examination. Student's t test or Mann-Whitney U test was applied for comparing any two groups. One-way analysis of variance (ANOVA) test and Welch's ANOVA test followed by Holm-Sidak's multiple comparisons test, one-way ANOVA with repeated measures followed by Bonferroni test, or Kruskal-Wallis H test followed by Dunn's multiple comparison test was used for multiple group comparisons and post hoc analyses. Pearson correlation coefficient test was conducted to analyze the relationship between two variables.@*RESULTS@#Higher Ve was seen in IRE zone than in H-FIRE zone (0.14 ± 0.02 vs. 0.08 ± 0.05, t = 2.408, P = 0.043) on day 4, but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points (all P > 0.05). For IRE zone, the greatest Ktrans was seen on day 7, which was significantly higher than that on day 1 (P = 0.033). The ablation zone size of H-FIRE was significantly larger than IRE 1 day (4.74 ± 0.88 cm2vs. 3.20 ± 0.77 cm2, t = 3.241, P = 0.009) and 4 days (2.22 ± 0.83 cm2vs. 1.30 ± 0.50 cm2, t = 2.343, P = 0.041) after treatment. Apoptotic index (0.05 ± 0.02 vs. 0.73 ± 0.06 vs. 0.68 ± 0.07, F = 241.300, P  0.05). Electrode temperature variations were not significantly different between the two zones (18.00 ± 3.77°C vs. 16.20 ± 7.45°C, t = 0.682, P = 0.504). The Ktrans value (r = 0.940, P = 0.017) and the Kep value (r = 0.895, P = 0.040) of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.@*CONCLUSIONS@#H-FIRE showed a comparable ablation effect to IRE. DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.

Clinical effect of tacrolimus in the treatment of myasthenia gravis in children / 中国当代儿科杂志

OBJECTIVE@#To evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis (MG).@*METHODS@#A total of 28 children with MG were treated with tacrolimus. MG-Activities of Daily Living (MG-ADL) scale was used to assess clinical outcome and safety after 1, 3, 6, 9, and 12 months of treatment.@*RESULTS@#After tacrolimus treatment, the MG-ADL score at 1, 3, 6, 9 and 12 months was lower than that at baseline (P<0.05), and the MG-ADL score showed a gradually decreasing trend. The response rates to tacrolimus treatment at 1, 3, 6, 9, and 12 months were 59%, 81%, 84%, 88%, and 88% respectively. At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone. No recurrence was observed during treatment. Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child, which turned negative without special treatment, and tacrolimus was not stopped due to such adverse reactions/events. One child was withdrawn from tacrolimus due to recurrent vomiting. According to CYP3A5 genotypes, all of the patients were divided into two groups: slow metabolic type (n=19) and non-slow metabolic type (fast metabolic type + intermediate type; n=9). The non-slow metabolism group received a higher dose of tacrolimus, but had a lower trough concentration of tacrolimus than the slow metabolism group (P<0.05). The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group (P<0.05).@*CONCLUSIONS@#Tacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.

Comparative analysis on morning and evening absolute dose output stability of medical linear accelerator / 医学研究生学报

Objective The ionization chamber of ELEKTA medical linear accelerator monitoring is open to environmental factors such as temperature, air pressure, and humidity that may affect the stability of absolute dose output .The article aimed to ana-lyze the morning and evening absolute dose output stability at different energies of ELEKTA SYNERGY medical linear accelerator . Methods The absolute doses at different energies of medical linear accelerators were calibrated according to the IAEA TRS -277 re-port, and WI3 type solid water was used to perform repeated measurements in the morning and in the evening for 52 consecutive days under the same measurement conditions , during which a water tank measurement was conducted at random intervals per week to verify the accuracy of WI3 solid water measurements. Results The maximum deviation of WI3 solids water and tank measurement at all en -ergies was 0.5％ and the maximum deviations of daily energy stability at different energies were : -2.0％ (6MV), 1.9％ (15MV), 1.8％ (6MeV), -2.4％ (8MeV), -2.3％ (10MeV), -2.0％ (12MeV), 2.1％ (15MeV).The differences of 6MV, 15MV, 8MeV, and 10MeV energies in morning and evening paired t tests were statistically significant (P<0.05) without clinical significance, while no statistic significance was found in the differences of 6MeV, 12MeV, and 15MeV energies ( P >0.05). Conclusion Elekta Synergy medical linear accelerator shows excellent stability in absolute dose output.

Optimization of fermentation conditions for pristinamycin production by immobilized Streptomyces pristinaespiralis using response surface methodology

Response surface methodology was used to optimize the fermentation conditions for the production of pristinamycin by immobilization of Streptomyces pristinaespiralis F213 in shaking flask cultivation. Seed medium volume, fermentation medium volume and shaking speed of seed culture were found to have significant effects on pristinamycin production by the Plackett-Burman design. The steepest ascent method was adopted to approach the vicinity of optimum space, followed by central composite design for further optimization. A quadratic model was built to fit the pristinamycin production. The optimum conditions were found to be seed medium volume of 29.5 ml, fermentation medium volume of 28.8 ml, and shaking speed of seed culture at 204 rpm. At the optimum conditions, a production of 213 mg/l was obtained, which was in agreement with the maximum predicted pristinamycin yield of 209 mg/l. This is the first report on pristinamycins production by immobilized S. pristinaespiralis using response surface methodology.

Phenotype and SCN1A gene mutation screening in 39 families with generalized epilepsy with febrile seizures plus / 中华儿科杂志

<p><b>OBJECTIVE</b>To summarize the phenotypes and identify SCN1A mutations in families with generalized epilepsy with febrile seizures plus (GEFS(+)), and analyze the genotype- phenotype correlations in GEFS(+) families.</p><p><b>METHOD</b>Genomic DNA was extracted from peripheral blood lymphocytes of the proband and other available members in the GEFS(+) families. The phenotypes of the affected members were analyzed. The coding regions and flanking intronic regions of the SCN1A gene were screened for mutations using PCR and direct DNA sequencing.</p><p><b>RESULT</b>In 39 GEFS(+) families, there were 196 affected members, ranging from 2 to 22 affected members in each family. Their phenotypes included febrile seizures (FS) in 92(46.9%), febrile seizures plus (FS(+)) in 62(31.6%), FS or FS(+) with partial seizures in 12(6.1%), afebrile generalized tonic-clonic seizures (AGTCS) in 11(5.6%), myoclonic atonic epilepsy in 8(4.1%), Dravet syndrome in 2(1.0%), childhood absence epilepsy in 1 (0.5%), FS(+) with myoclonic seizures in 1(0.5%), AGTCS and myoclonic seizures in 1 (0.5%), partial seizures in 1 (0.5%), unclassified seizures in 5 (2.6%). Four families were found with SCN1A mutations, including three families with missense mutation (N935H, R101Q, G1382R) and one family with truncation mutation (C373fsx378). In three families with missense mutations, the phenotypes include FS, FS(+), FS(+) with partial seizures, and AGTCS. In one family with truncation mutation, the phenotypes included FS, FS(+), and Dravet syndrome. The mother of proband in the family with missense mutation (R101Q) and the father of proband in the family with truncation mutation (C373fsx378) were both somatic mosaicism. Both of their phenotypes were FS(+).</p><p><b>CONCLUSION</b>The most common phenotypes of GEFS(+) were FS and FS(+), followed by the FS/FS(+) with partial seizures and AGTCS. The most severe phenotype was Dravet syndrome. SCN1A mutation rate in GEFS(+) was about 10%. Missense mutation was common in GEFS(+) families, few with truncation mutation. Few members of GEFS(+) families had somatic mosaicism of SCN1A mutations and their phenotypes were relatively mild.</p>

Clinical analysis of four patients with Schwartz-Jampel syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical manifestation, diagnosis and treatment of Schwartz-Jampel syndrome (SJS).</p><p><b>METHOD</b>The clinical data, including demographic, laboratory tests (creatase, creatine kinase, etc.) and electromyography of 4 children with SJS were analyzed.</p><p><b>RESULT</b>All the 4 patients were male. The age of onset was from 0.5 to 1.25 years (average 0.83 years). The onset of 4 patients was insidious, the age to see doctor was from 2.17 to 10 years (average 5.92 years), body height was less than the third percentile rank in the children of same age and gender, they presented with facial expression stiffness, microstomia, difficult in opening mouth, blepharophimosis, limbs stiffness and, so formed a characteristic phenotype. Investigations showed the creatase in serum increased, creatine kinase (CK): 229 - 1039 U/L (normal value < 200 U/L), Creatine Kinase MB (CK-MB): 30 - 45 U/L (normal value < 25 U/L), lactate dehydrogenase (LDH): 455 - 716 U/L (normal value < 240 U/L). General myotonia potential was found in electromyography, osteoarticular deformities in medical imaging, and muscle biopsy in 2 patients showed type I muscle fibers differed in size and were disproportionate. All the patients took oral vitamin B, and received rehabilitation training, 1 patient took carbamazepine for 1 month, blepharophimosis and limbs stiffness was improved.</p><p><b>CONCLUSION</b>SJS is a rare autosomal recessive inherited disease. Clinical manifestations of SJS are characteristic facies, skeletal abnormalities, generous myotonia and short stature. Carbamazepine is effective for treatment.</p>

Follow-up study on the clinical characteristics and treatment effect of the different types of Guillain-Barré syndrome in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics and effects of immunoglobulin treatment in children with the different types of Guillain-Barré syndrome (GBS).</p><p><b>METHOD</b>Data of 108 patients hospitalized for GBS were retrospectively analyzed; 75 cases in this group were given acute high dose of gamma globulin (IVIG) 400 mg/(kg·d) intravenously for 5 d. Clinical and electrophysiological data and information on treatment and recovery of the children were collected during the follow-up and were analyzed.</p><p><b>RESULT</b>According to the clinical and electrophysiologic findings, 32 patients manifested acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 34 had acute motor axonal neuropathy (AMAN), 3 had acute motor and sensory axonal neuropathy (AMSAN), 4 were inexcitable, 2 were unclassified. The clinical progress of the AMAN was faster than the AIDP group. Except for sensory nerve involvement, there was no significant difference in the clinical feature and severity. The mean time of the muscle strength began to recover was (5.59±3.63) days in the AIDP group and (7.21±4.68) days in the AMAN group after IVIG treatment. The time of the AIDP group was shorter than the AMAN group, but the difference was not statistically significant (t=-1.5702, P>0.05). The mean time of the muscle strength increased one grade was (8.88±4.39) days in the AIDP group and (12.67±8.35) days in the AMAN group. The difference was statistically significant (t=-2.3689, P<0.05). No patients in this group died. Follow-up data showed that the complete recovery time was not significantly different (t=0.2041, P>0.05).</p><p><b>CONCLUSION</b>The clinical progress of the AMAN was faster than the AIDP group. Besides sensory nerve involvement, there was no significant difference in the clinical feature and severity. The AIDP group's clinical recovery was faster than AMAN's after the immunoglobulin treatment. The two groups were not significantly different in long-term prognosis.</p>

Clinical characteristics and diagnosis of acute pandysautonomia in childhood / 中华儿科杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristics of acute pandysautonomia in childhood, to gain better understanding of the diagnosis and differential diagnosis.</p><p><b>METHODS</b>The clinical data of 6 children with acute pandysautonomia were analyzed and followed-up. All the 6 patients had routine blood and cerebrospinal fluid (CSF), electrocardiography (ECG), electromyography (EMG), cranial magnetic resonance imaging (MRI) and autonomic nerve function tests (head upright tilt test, dermatography test, and thermal/sympathetic sweat response). Other laboratory examinations such as immunologic markers of CSF, electroencephalography (EEG), spinal cord MRI and somatosensory evoked potential (SEP) were also performed in some patients.</p><p><b>RESULTS</b>Of the 6 patients, 1 was male, and 5 were female. The age of onset was from 2.3 to 14.5 years (average 8.2 years). The initial symptoms were gastrointestinal dysfunction in 3 patients and somatic motor dysfunction as their initial symptoms, one had irritability in 1 case, pain in 1 and dysphagia in 1, respectively. Autonomic nerve signs and symptoms: (1) Skin and mucosa are rough and dry, there was no or little perspiration, alacrimia or little tear in all patients. (2) Vision problem appeared in 1 patient, blepharoptosis in 3 patients, pupillary abnormality existed in all patients. (3) Gastrointestinal symptoms were present in all patients. Vomiting and constipation were present in 4 patients, diarrhea and constipation were alternatively present in 1 patient, abdominal distention and abdominal pain were present in 2 patients. (4) Cardiovascular system manifestations included postural dizziness or syncope in 3 patients, tightness and palpitation in 2 patients. (5) Urinary dysfunction was present in 4 patients. In addition, mild to moderate somatic motor dysfunction was present in 5 patients, sensory dysfunction in 3 patients. Autonomic nerve function tests were abnormal in all patients. Laboratory findings included serum IgM antibody to herpes simplex virus and antistreptolysin "O" (ASO) test were positive respectively in 1 patient. The immunological markers in CSF were abnormal in 3 patients and the protein level in CSF was slightly elevated in 3 patients. Cranial MRI was slightly abnormal in 4 patients. ECG was slightly abnormal in all patients. EMG was abnormal in 5 patients. SEP was abnormal in 3 patients. Five patients received IVIG therapy. Five patients were followed-up. One patient died, one lost to follow up and one had slight improvement. Significant improvement was seen in 2 patients.</p><p><b>CONCLUSION</b>Acute pandysautonomia in children usually had non-specific symptoms and could affect multiple organs. Heterotropia, cardiovascular dysfunction and gastrointestinal dysfunction were commonly seen in these patients. In acute pandysautonomia patients, IVIG seemed to be effective and the prognosis was poor in severe cases.</p>

Clinical manifestation and EEG characteristics of Angelman syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical manifestations and EEG characteristics of Angelman syndrome in children, and to strengthen the recognition of this disease.</p><p><b>METHOD</b>Fourteen children with Angelman syndrome received video EEG monitoring, head MRI/CT and gene test, 11 patients received the metabolic investigations (e.g., lactic acid, ammonia, GC/MS and MS/MS). Eight patients received Gesell test. The patients were followed up for 1-3 years.</p><p><b>RESULT</b>Of the 14 cases, 4 were male and 10 female, their age was from 8 months to 3 years and 7 months. The clinical characteristics included prominent lower jaw and wide mouth, fair skin and yellow hair, light-colored iris, paroxysmal laughter, astasia and language backward. Twelve patients had epileptic seizures; 10 patients displayed non-convulsive status epilepticus (NCSE), 9 patients displayed myoclonic, atypical absence, and non-convulsive seizure simultaneously; myoclonic, generalized tonic-clonic seizure and complex partial seizure in 1 each; 4 patients had fever in early seizures. The EEG showed paroxysmal middle-high amplitude 2-3 Hz spike and spinous slow-wave in 8 patients. Four patients showed paroxysmal frequently middle-high amplitude 2-3 Hz slow waves mixed with sharps. The other 2 patients showed a normal EEG. All the patients were diagnosed with genetics testing. The results included maternal deletion of chromosome 15q11-13 in 12, paternal uniparental disomy in 1 and imprinting defects in 1.</p><p><b>CONCLUSION</b>There are characteristic clinical manifestation and craniofacial features in Angelman syndrome patients. Some patients have specific EEG patterns. Abnormal region of chromosome 15q11-13 is the basis of diagnosis.</p>

Clinical and laboratory features of the Menkes disease / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the clinical and laboratory features of the patients with Menkes disease.</p><p><b>METHOD</b>Three infants were diagnosed as Menkes disease. Their clinical feature, laboratory findings, radiological manifestation and genes were reviewed.</p><p><b>RESULT</b>All the three cases were male infants. Their clinical manifestations began at the 3, 5 and 6 months after birth. They all had light complexion, sparse fuzzy woolly hair. The main clinical manifestation was severe mental retardation. The first and the third case also had focal clonus seizures. The second case had feeding difficulty after birth. Their hair showed pili torti and trichorrhexis nodosa microscopically. Their ceruloplasmin in plasma were 32.3 mg/L, 72.5 mg/L and 60.7 mg/L, which were significantly lower as compared with the normal values. Their neuroimaging findings were cortical atrophy, delayed myelination of the white matter and tortuosity of the intracranial vessels. The gene examination of the first and the second case showed deletion and nonsense mutation on exon 14 respectively.</p><p><b>CONCLUSION</b>Menkes disease is an X-linked recessive disorder characterized by a copper-transporting ATPase defect. The main clinical manifestation is progressive nerve damage. Patients with the disease have special face and hair abnormality, and have morphological changes of brain blood vessels and cerebral atrophy.</p>

The cross-sectional and longitudinal association of the BODE index with quality of life in patients with chronic obstructive pulmonary disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index was shown at predicting the risk of death, exacerbation and disease severity among patients with COPD, but few studies verified relationship between BODE index and health related quality of life (HRQoL) among Chinese COPD patients. The objective of this study was to evaluate the relationship between BODE index and HRQoL in cross-sectional and longitudinal association analyses.</p><p><b>METHODS</b>A multi-center prospective cohort study was initially conducted in 491 stable COPD patients in Beijing, China. Health status (HRQoL) was assessed by St. George's Respiratory Questionnaire (SGRQ); the BODE index was calculated for each patient; dyspnea was assessed using the 5-grade Medical Research Council dyspnea scale. Other measurements included socio-demographic, body mass index (BMI), lung function test and 6-minute-walk test (6MWT). Patients were then followed monthly for 12 months.</p><p><b>RESULTS</b>Only 450 patients completed the 1-year follow up and were enrolled in our present analyses. Mean age was (65.2 +/- 10.6) years, men 309 (68.7%). The BODE index was categorized into 4 subgroups: 0 - 2, 3 - 4, 5 - 6 and 7 - 10. At baseline BODE index was gradually increased with baseline total SGRQ and SGRQ subscales (P trend < 0.001). For individual components of BODE index, with the decrease of airflow limitation, and 6MWD, and with the increase of Medical Research Council (MRC) dyspnea grade, total SGRQ and SGRQ subscales were increased correspondingly, P trend < 0.05, respectively. Similar association patterns were found between baseline BODE index and its individual components and mean SGRQ scores at the end of 1-year follow up. By multiple linear regression analyses, baseline BODE index was not only significantly associated with SGRQ score at baseline but also with SGRQ score at the end of 1-year follow up after adjustment for age, male, current smoking, betas being 0.434 and 0.378, respectively.</p><p><b>CONCLUSIONS</b>BODE index is associated with SGRQ score cross-sectionally and longitudinally among stable COPD patients. BODE index might have potential to be used as a sensitive tool to assess the status of quality of life and to monitor disease progression among stable COPD patients.</p>

Elemental contents in organs and tissues of Chinese adult men / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To provide basis of reference values for relevant parameters of Chinese Reference Man.</p><p><b>METHODS</b>Eighteen kinds of major organ or tissue samples, including muscle, rib, liver, and so on, were obtained from 4 areas (Hebei, Shanxi, Jiangsu, and Sichuan provinces) with different dietary patterns in China in autopsy of 16 healthy adult men, who had just encountered sudden deaths. At the same time, whole blood samples were collected from 10 volunteers living in each of these areas. The concentrations of 56 elements in these samples were detected by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES), and Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) techniques. Based on obtained concentrations and reference values of these organ or tissue weights for Chinese Reference Man, the relative elemental burdens in these organs or tissues as well whole body were also estimated.</p><p><b>RESULTS</b>The concentrations of 56 elements in 18 main organs or tissues were determined all together and their elemental organ or tissue and whole body burdens were estimated. Furthermore, the distributions of important elements for radiation protection in these organs or tissues were emphatically discussed.</p><p><b>CONCLUSION</b>By summing with past related results, the total results obtained from the series of research may provide more reliable and better representative basis of these reference values for Chinese Reference Man than before.</p>

Diagnosis of congenital muscular dystrophy and clinical significance of merosin expression / 中华儿科杂志

<p><b>OBJECTIVE</b>The congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of neuromuscular disorders with progressive muscle wasting and weakness that begin during neonatal or early infantile period. To study the clinical diagnosis, immunohistochemical feature and follow-up information of CMD, data of 8 cases with CMD were analyzed.</p><p><b>METHODS</b>Immunohistochemical features of biopsied muscle specimens were summarized and analyzed by using anti-laminin alpha2 (merosin), anti alpha-dystroglycan (alpha-DG) and anti beta-dystroglycan (beta-DG) antibodies.</p><p><b>RESULTS</b>These patients mostly presented at birth or during the first six months of life with muscle weakness, hypotonia, contractures, and feeding difficulty or respiratory dysfunction. Hematoxylin-eosin staining of skeletal muscle specimens from these patients showed typical characteristics of CMD. Differences in fiber size, with predominantly small and round fibers, and dense connective tissue infiltration were seen. Four of the 8 patients were merosin-stain negative, which might be due to primary merosin deficiency. T2-weighted magnetic resonance imaging of the brain shows abnormalities of the white matter. Four cases were merosin-stain positive, and two of them also had hypoglycosylation of alpha-dystroglycan. Two patients had mental retardation. One of them had optic nerve atrophy and abnormal brain structure.</p><p><b>CONCLUSIONS</b>Two types of CMD were present in our group. Merosin-deficient congenital muscular dystrophy (congenital muscular dystrophy 1A, MDC1A) was more common, accompanied by abnormalities of the white matter. "Alpha-dystroglycanopathy" could be seen in merosin-positive cases.</p>

Cellular Apoptosis of C6 Mouse Glioma Cells Induced by hING4 Mediated by Adenovirus / 中国生物工程杂志

The known members of inhibitor of growth (ING) gene family are considered as candidate tumor suppressor genes. ING4, a novel member of ING family, is recently reported to regulate brain tumour angiogenesis through transcriptional repression of NF-?B-responsive genes, induce G2/M arrest by the increased p21 expression in a p53-dependent manner, suppress the loss of contact inhibition and represses activation of the hypoxia inducible factor, which plays an important role in the progression of tumorigenesis. However, seldom studies about ING4 inducing tumor cells apoptosis were reported.The C6 cells (mouse glioma cells) were infected respectively with the blank adenovirus carrying GFP (Ad) and the recombinated Ad-hING4-His, then RT-PCR assay was used to detect the transcriptions of hING4, as well Western-blotting assay was ued to detect the expressions of hING4. The effects of hING4 expression upon C6 cells were observed, and the growth curve was drawed and tumor control rates were calculated. The C6 cells, which were affected by blank Ad and Ad-hING4-His, were respectively observed by LSCM (laser scan confocal microscope) and transmission electron microscope (TEM), detected by flow cytometry; and the genomic DNA of both groups were extracted and electrophoresised in agarose gel to examinate the DNA fragments. The results showed hING4 can significantly inhibit the growth of C6 cells by promoting the cell’s apoptosis, which probably is the first one to prove this property of ING4.The experimental and theoretical foundation for gene therapy for gliomas with ING4 in the future was established.

The effect of CACNA1H gene G773D mutation on calcium channel function / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the effect of CACNA1H gene mutation G773D on calcium channel function.</p><p><b>METHODS</b>By the overlap extension PCR we introduced G773D mutation into a human Cav3.2acDNA for constructing the mutant. And then using whole cell clamp technique, we studied the alterations of channel behavior in transfected HEK-293 cells.</p><p><b>RESULTS</b>There were no difference in kinetics of activation and inactivation of calcium channel between wild type and mutant. However comparing with the wild-type Cav3.2 channel, G773D mutant could increase the calcium current density significantly.</p><p><b>CONCLUSION</b>CACNA1H gene G773D mutation is able to increase calcium current and neuronal excitability.</p>

T-type calcium channel gene-CACNA1H is a susceptibility gene to childhood absence epilepsy / 中华儿科杂志

<p><b>OBJECTIVE</b>Childhood absence epilepsy (CAE) is one of the most frequently recognized syndromes among the idiopathic generalized epilepsies (IGEs). It is considered to be a hereditary disease. The possible inheritance pattern of CAE is polygenic. The genes responsible for CAE, however, have not yet been identified. The aim of this study was to further investigate based on the authors' recent work whether or not T-type calcium channel gene-CACNA1H is a susceptibility gene to childhood absence epilepsy.</p><p><b>METHODS</b>The authors conducted the mutation screening of the exons 6-12 and the nearby partial introns of the CACNA1H gene using the method of direct sequencing of PCR products in 48 newly found CAE patients.</p><p><b>RESULTS</b>The authors found 13 single nucleotide polymorphisms (SNPs). They also found 4 mutations which only existed in CAE patients. Both G773D and H515Y mutations were heterozygous. The mutation of H515Y has never been reported previously. The patient inherited the mutation from his mother. The authors found two CAE patients with the mutation of G773D previously. This is the third time that the authors found one more CAE family with this G773D mutation, and the patient with the mutation G773D inherited the mutation from his father.</p><p><b>CONCLUSION</b>T-type calcium channel gene-CACNA1H might be a susceptibility gene to childhood absence epilepsy.</p>

Clinical characteristics and diagnosis of neuronal migration disorders / 中华儿科杂志

<p><b>OBJECTIVE</b>Neuronal migration disorders (NMD) are a group of malformations of the brain which ultimately disrupt migrating neuroblasts from the germinal plate to the cerebral cortex, it consists of agyria-pachygyria, polymicrogyria, schizencephaly, hemimegalencephaly and heterotopia. This study aimed to investigate the clinical characteristics and diagnostic methods of NMD.</p><p><b>METHODS</b>The clinical data, cranial imaging and experimental examinations of 37 patients with NMD were analyzed. The patients consisted of 21 males and 16 females whose age of first hospital visit ranged from 2 months to 14 years and 6 months. Among the 37 cases, 18 were followed up.</p><p><b>RESULTS</b>Of the 37 patients, 21 were agyria-pachygyria, the main clinical manifestations were mental retardation (20 cases), epilepsy (14 cases), hemiparesis (6 cases), and 17 patients had microcephaly which was an important physical sign. Eight patients had agyria-pachygyria with other malformations, they presented mental retardation (6 cases), epilepsy (4 cases), and hemiparesis (2 cases). Of the 5 patients with heterotopia, 4 manifested epilepsy. 3 patients had schizencephaly and 2 presented with hemiparesis. EEG was performed in 16 cases. Generalized irregular sharp and slow wave complexes were present in 10 cases, focal spike and slow complex in one case, hypsarrhythmia in one case, and the normal EEG in 4 cases. Eighteen cases were followed-up from seven months to eight years and three months, 14 patients had epilepsy, and still had epileptic attacks with the treatment with anticonvulsives, motor development was improved but speech development delayed in 4 cases.</p><p><b>CONCLUSION</b>The results of this study suggest that NMD is characterized by mental retardation, epilepsy and hemiparesis. Cranial MRI is the best diagnostic method.</p>

Diagnosis and treatment of methylmalonic acidemia in 14 cases / 中华儿科杂志

<p><b>OBJECTIVE</b>Methylmalonic acidemia (MMA) is one of the most common disorders of congenital organic acid metabolism. This study aimed at exploring the clinical characteristics and treatment of the disease to help improve our understanding of it.</p><p><b>METHODS</b>The clinical data of 14 patients with MMA admitted to our hospital between January 2002 and July 2003 were analyzed and the diagnoses were confirmed by gas chromatography/mass spectrometry (GC/MS). The patients consisted of 4 males and 10 females, whose age of onset ranged from birth to 9 years with 7 cases younger than 1 month (50%) and 10 cases younger than 1 year (71%).</p><p><b>RESULTS</b>The main clinical manifestations were lethargy (6 cases), developmental retardation or regradation (7 cases), convulsion (6 cases), recurrent vomiting (4 cases), difficulty with feeding (4 cases), muscular dystonia (5 cases with hypotonia, 3 with hypertonia) and yellowish hair (4 cases), etc. Some cases were also presented with hair loss, hepatomegaly, ataxic or stiff gait, and motor weakness with muscular atrophy. The laboratory findings showed metabolic acidosis in 6 cases, hyperammonemia in 5 cases, ketonuria in 4 cases and remarkable elevation of urinary methylmalonic acid concentration in all cases. Some abnormalities in globus pallidus and cerebral white matter as well as diffuse cerebral atrophy were noted by the brain CT and MRI in 5 respective cases, while 4 cases did not receive neuroradiological examinations. Peripheral neuropathies were found by electromyography in 2 patients and bilateral optic nerve atrophy was detected by eyeground examination in 1 child. Three patients died before the diagnoses were made. Of the 11 survivals, 10 children have received therapy of vitamin B12 (VitB12) and supplementation of L-carnitine with restricted-protein diet. The follow-up for a period ranging from 3 months to 1.5 year (mean 8.5 months) of 7 cases with medical therapy showed a favorable outcome without any symptoms in 1 case and apparent improvement in 4 cases (the diffuse cerebral atrophy in MRI completely recovered in one case), however, 2 patients died from severe metabolic acidosis.</p><p><b>CONCLUSIONS</b>The main clinical features of MMA include lethargy, developmental retardation or regradation, convulsion, recurrent vomiting, difficulty with feeding, muscular dystonia, yellowish hair, metabolic acidosis, hyperammonemia and ketonuria, etc. Urine organic acids analysis with GC/MS is critical to the early diagnosis of MMA. Early diagnosis and appropriate long-term treatment are essential to improve the prognosis of the disease.</p>

Preliminary attempt at the speciation of 25-elements in the Chinese medicinal herbs / 中国中药杂志

<p><b>OBJECTIVE</b>To make an attempt at the multi-element speciation in the Chinese medicinal herbs by determining the concentrations of 25 elements in different extraction solutions.</p><p><b>METHOD</b>Firstly, five Chinese medicinal herbs (Buddleja officinalis, Dictamnus dasycarpus, Myristica fragrans, Albizia judibrissin and Inula japonica) from the same region of China were treated to obtain water-soluble phase, lipid-soluble phase and non-soluble phase by water extraction, organic solvent extraction and acid digestion, respectively. Secondly, Phytolacca acinosa, a Chinese medicinal herb collected from 9 regions of China, was extracted by 0% EtOH, 50% EtOH, 75% EtOH, 95% EtOH, respectively, referring the Chinese Pharmacopoeia. Finally, the concentrations of 25 elements, such as Be, Cr, Cu, Zn, Ge, Sr, Y, Mo, Cd, Tl, Pb and REEs, in the above three phases were determined by ICP-MS.</p><p><b>RESULT</b>Under the optimal conditions, all the 25 elements could be determined with detection limits ranged from 0.003 to 0.71 ng x g(-1). The average recoveries of the elements in P. acinosa were 88% approximately 119%, with the relative standard deviations 1.7% approximately 13.3%. It was observed that the determined 25 elements distributed in all the water-soluble, lipid-soluble and non-soluble phases, indicating that the inorganic species, organicspecies, as well as the protein bound species were coexisted in the herbs. Big differences of the element extraction rates could be found by using different ethanol solutions.</p><p><b>CONCLUSION</b>With the aid of the obtained results, we may increase the extraction of necessary elements while decrease that of the toxic elements from the herbs by choosing a suitable solvent during the drug production.</p>

Case-control study and transmission/disequilibrium tests of the genes encoding GABRA5 and GABRB3 in a Chinese population affected by childhood absence epilepsy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Childhood absence epilepsy (CAE) is one of the most frequently recognized syndromes among the idiopathic generalized epilepsies (IGEs). CAE is considered to be a genetic disease, with a possible polygenic inheritance pattern. The genes responsible for CAE have not been identified yet. The object of this study was to investigate whether or not CAE is associated with the gene encoding the gamma-aminobutyric acid (GABA) type-A receptor subunits alpha5 (GABRA5) and beta3 (GABRB3) in a Chinese population.</p><p><b>METHODS</b>Five microsatellite DNA repeats, 69CA, 85CA, 155CA1, 155CA2, and A55CA1, adjoining chromosome 15q11-q13, were used as genetic markers. Both case-control study and transmission/disequilibrium tests (TDTs), as well as fluorescence-based semi-automated genotyping techniques, were used in 90 CAE patient-mother-father trios and 100 normal controls of Han ethnicity to conduct association analysis.</p><p><b>RESULTS</b>The frequencies of allele 5 of 69CA, alleles 2 and 8 of 85CA, alleles 6 and 7 of 155CA1, allele 2 of 155CA2, and alleles 1 and 11 of A55CA1 were significantly higher in CAE patients than in normal controls. To prevent spurious associations arising from population admixture, we further conducted TDT tests in the 90 CAE trios. The results of TDT analysis further suggested that microsatellite DNA repeats 85CA, 155CA1, and 155CA2 were associated with CAE.</p><p><b>CONCLUSIONS</b>GABA type-A receptor subunit genes GABRA5 and GABRB3 may be either directly involved in the etiology of CAE in the Chinese population or in linkage disequilibrium with disease-predisposing sites.</p>