Research Advance of Gene Mutation and Targeted Drug Therapy in Childhood Acute Myeloid Leukemia --Review / 中国实验血液学杂志

The clinical therapeutic regimen for acute myeloid leukemia (AML) is not significantly different between adults and children, which is mostly based on IA (idarubicin and cytosine arabinoside) induction chemotherapy. With the rapid development of sequencing technique, people's understandings towards the molecular and biological abnormalities of AML are increasing, diverse AML gene mutation-based targeted drugs have been rapidly developed and applied. In this review, several commonly gene mutations in AML (such as FLT3, NPM1 and C/EBPA) was described, and the therapeutic effects and differences of targeted drugs that used in clinical treatment or had been reported (like tyrosine kinase inhibitor, IDH1 mutation inhibitor and epigenetic modification inhibitor) in child and adult AML patients were summrized.

Clinical efficacy of creatine phosphate sodium combined with ribavirin in treating infantile viral myocarditis and its effect on myocardial enzyme levels in children / 吉林大学学报(医学版)

Objective:To investigate the clinical efficacy of creatine phosphate sodium combined with ribavirin in the treatment of infantile viral myocarditis,and to elucidate its mechanism of the effects on myocardial enzyme levels in the children.Methods:A total of 96 children with viral myocarditis were selected;according to the random number grouping method,they were divided into observation group and control group (n=48).The myocardial enzymes and cardiac troponin Ⅰ (cTnI) of the patients in two groups were detected,and anti-infection,supplementation of electrolytes,and nutritional support for myocardial treatment were performed;then intravenous infusion therapy of ribavirin was used.On this basis,the patients in observation group were given intravenous infusion of creatine phosphate sodium for 14 d.After treatment,the total effective rate of treatment of the patients in two groups,the levels of myocardial enzymes and cTnI and electrocardiogram were compared before and after treatment.Results:The total effective rate of the patients in observation group was 87.50％ (42/48),and it was 70.83％ (34/48) in control group;there was significant difference (x2 =4.04,P=0.04).After treatment,the levels of lactate dehydrogenase (LDH),hydroxybutyrate dehydrogenase (HBDH),aspartate transaminase (AST),creatine phosphokinase (CPK),creatine kinase isoenzyme-MB (CK-MB) and CTnI of the patients in two groups after treatment were lower than before treatment (P＜0.05).The indicators mentioned above of patients in observation group were lower than those in control group (P ＜0.05).The total improvement rate of electrocardiogram in the observation group (89.58％) was significantly higher than that in control group (72.92 ％),and the difference was statistically significant (x2 =4.38,P =0.04).Conclusion:The total effective rate of creatine phosphate sodium combined with ribavirin in the treatment of infantile viral myocarditis is higher,and they can significantly reduce the levels of myocardial enzymes and improve the cardiac function;it is worth to apply in the clinical treatment.

Forty cases of cerebral palsy treated with human neural stem cell transplantation / 中华行为医学与脑科学杂志

Objective To assess the clinical efficacy of human neural stem cell (hNSC) transplantation in the treatment of severe cerebral palsy (CP) in children.Methods hNSCs were obtained from the forebrain of 10 to 12-week-fetus.Forty children with CP were voluntarily received hNSC transplantation that were injected into cerebral ventricle.The development of motor and fine motor functions were evaluated by GMFM and PDMS-FM 1 month before hNSC transplantation.as well as 3 and 6 months after hNSC transplantation.Results Twenty six (65％) cases displayed improvement from day 5 to month 6 after hNSC transplantation.GMFM assessment showed that the percentage was (4.52±2.50) ％ 1 month before hNSC transplantation,(7.74±2.94) ％ 3 months after hNSC transplantation and (13.01±6.71)％ 6 months after hNSC transplantation,indicating a significant improvement by the treatment of hNSC transplantation(P＜0.05).The percentage in PDMS-FM evaluation was (15.01± 12.00)％,(20.34± 11.91) ％ and (30.02± 12.50) ％ one month before hNSC transplantation,3 and 6 months after hNSC transplantation,respectively,also suggesting a significant improvement induced by hNSC transplantation treatment (P＜0.05).Moreover,the developmental improvement was the most prominent among 1-3 months post hNSC transplantation.Then the development slowed down.Significantly,patients received no hNSC transplantation experienced serious adverse events or complications.Conclusions hNSC transplantation is an effective and safer therapy for severe CP.Future observations are needed to evaluate long-term clinical efficacy of the therapy.

Clinical effect of stem cell transplantation via hepatic artery in the treatment of type II hyperammonemia: a report on 6 cases / 中国当代儿科杂志

This study aimed to investigate the clinical effect of transplantation of CD133⁺ peripheral blood stem cells or umbilical cord mesenchymal stem cells via the hepatic artery in children with type II hyperammonemia and its possible action mechanism. Umbilical cord mesenchymal stem cells were obtained by collecting cord blood (100-150 mL) from healthy fetuses and separating stem cell suspension (5 mL) from the cord blood by hydroxyethyl starch sedimentation. CD133⁺ peripheral blood stem cells were obtained by mobilizing peripheral blood from the fathers of sick children using recombinant human granulocyte colony-stimulating factor for 5 days, collecting mononuclear cells (120 mL), and separating out CD133⁺ cells by sorting. With catheterization and percutaneous puncture, the obtained stem cells were slowly injected into the liver of sick children via the hepatic artery. The changes in clinical symptoms and laboratory indices such as blood ammonia, liver function, and arginine and citrulline concentrations were observed. After stem cell transplantation via the hepatic artery, the 6 children showed significantly decreased blood ammonia levels, and their blood ammonia levels slowly increased 1 to 2 weeks later, but remained below 100 μmol/L, and changes in glutamic-pyruvic transaminase levels were similar to blood ammonia. Plasma citrulline and arginine concentrations increased significantly after transplantation and the increase in citrulline level exceeded the increase in arginine level. An 8 months follow-up visit for one typical patient showed that the weight and height increased after transplantation and sleep was improved without night crying. The child could actively gaze at interesting objects instead of responding indifferently and started to say simple words. With regard to fine motor skills, the child could pinch things with the thumb and middle finger instead of displaying a lack of hand-eye coordination and progress was also made in gross motor skills. Gesell test showed that the child made progress for an average of 3.82 months in all areas. It was concluded that after stem cell transplantation, children with type II hyperammonemia have decreased blood ammonia levels, stable and improved liver function and steadily increased plasma citrulline and arginine concentrations. They display a progressive trend in such aspects as movement, language and environmental adaptability. It is hypothesized that stem cell transplantation via the hepatic artery partially or totally activates, or provides supplementary ornithine carbamoyl transferase, so that plasma citrulline and arginine concentrations increase and urea cycle disorder can be corrected to some extent.

Transplantation of human neural precursor cells in the treatment of children with pervasive developmental disorder / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To assess the efficiency and safety of human neural progenitor cells (hNPCs) transplantation in the treatment of pervasive developmental disorder (PDD) in children.</p><p><b>METHODS</b>Twenty-two children with PDD were treated, including 13 children with Rett syndrome and 9 children with autism. They accepted hNPCs transplantation voluntarily. hNPCs derived from aborted fetal tissue were injected into the lateral ventricle of the patients under supersonic guidance. All patients were assessed according to the Autism Behavior Checklist before operation, at one and six months post operation, and one year later.</p><p><b>RESULTS</b>No delayed complications resulting from this therapy were observed. The clinical symptoms of 17 patients, including 8 patients with autism and 9 patients with Rett syndrome, improved in varying degrees. The assessment results of the Autism Behavior Checklist for children with autism showed that compared with pre-operative function, social communication scores were significantly reduced at six months after transplantation, and total scores and social communication and language scores were also significantly reduced 1 year after transplantation (P<0.05).</p><p><b>CONCLUSIONS</b>These results suggest that hNPCs transplantation is effective and safe for treatment of PPD in children. It deserves a further study.</p>

Acute encephalopathy due to late-onset maple syrup urine disease in a school boy / 中国当代儿科杂志

Maple syrup urine disease is a common amino acids metabolic disease. In most patients, onset occurs in the neonatal period and infancy. In this study, the case of a school boy with acute encephalopathy due to late-onset maple syrup urine disease is summarized. The boy (8.5 years) was admitted because of acute encephalopathy after suffering from infection for two days at the age of eight and a half years. Metabolic acidosis, hyperuricemia and decreased protein level in cerebrospinal fluid were found by general laboratory tests. Magnetic resonance imaging of the brain revealed signal intensity abnormalities in the bilateral cerebellum dentate nucleus, brainstem, thalamus, putamen, caudate nucleus and cortex of the cerebral hemispheres. On T1WI and T2WI scanning, hyperintensive signal was found. Blood leucine and valine were significantly elevated. Urinary 2-hydroxy isovaleric acid, 3-hydroxybutyric acid, 2-keto isovaleric acid, and 2-keto acid also increased. Both the blood amino acid and urine organic acid profiles led to the diagnosis of maple syrup urine disease. In the acute period, the patient was treated with a large dose of vitamin B1, glucose, L-carnitine and a protein-restrict diet. The patient's condition improved significantly after five days of treatment, and he recovered completely two days later. Afterwards, treatment with vitamin B1, L-carnitine and a protein-restrict diet (1 g/kg/day) was continued. One and a half months later, blood amino acids and urine organic acids returned to normal. Magnetic resonance imaging of the brain also indicated a great improvement. It was concluded that inborn metabolic disease should be considered in the patients with an onset similar to acute encephalopathy. Early diagnosis and proper treatment can prevent brain damage and improve prognosis.

Clinical application of bone marrow mesenchymal stem cell transplantation in children with severe mental retardation / 中华神经医学杂志

Objective To observe the clinical efficacy of transplantation with autologous bone marrow mesenchymal stem cells (MSCs) in the treatment of children with severe mental retardation (MR). Methods Fifty children with severe MR (2-6 years old), admitted to our hospital from May 2008 to December 2009, were chosen; self-control observation on the mental and motor developments of these children in the same length of time periods was performed 6 months before and 6 months after the autologous bone marrow MSCs transplantation. Meanwhile, the improvements of each patient were followed up and analyzed 1, 3 and 6 months after the transplantation. Results Two patients failed in the culture of bone marrow MSCs; 6 patients failed in follow-up; the other 42 were observed completely.Significant improvement was noted in 25 patients after the transplantation with an effective rate reaching 59.5%; gradual mental and motor improvements appeared in these 25 patients 1 month after the transplantation, and lasted till the 6th month of transplantation. The average scores of mental improvement were (4.67±4.20) in 6 months before transplantation, and (17.12±13.05) in 6 months after transplantation (t=6.816, P=0.000). The average times having gross motor improvement 6 months before and 6 months after transplantation were (1.019±0.78) and (1.15±0.91), respectively (t=1.610, P＞0.05); the average times having fine motor improvement were (0.89±0.79) and (3.40±3.16) months in 6 months before and 6months after transplantation (t=5.030, P＜0.05); the average times having language improvement were (0.99±0.95) and (3.23±3.30) months in 6 months before and 6 months after transplantation (t=4.000, P＜0.05); the average times having personal-social behavior progress were (1.03±0.81) and (2.95±3.68)months in 6 months before and 6 months after transplantation (t=3.509, P＜0.05); the average times having adaptive behavior progress were (0.88±1.22) and (1.19±1.48) months in 6 months before and 6 months after transplantation (t=1.322, P＞0.05). Conclusion Autologous bone marrow MSCs transplantation can improve the intellectual development in a short time, mainly in the fine motor, language and personal-social behavior, in children with severe MR. Bone marrow MSCs transplantation for severe MR is safe and effective in a short-term.

The effect of diabetes on expression of the glucose transporter-1 in blood brain barrier endothelial cell of diabetic rats at different time points / 中华神经科杂志

Objective To investigate the effect of diabetes on the expression of the glucose transporter (GLUT-1) in blood brain barrier (BBB) endothelial cell at different time points. Methods Forty male SD rats were randomly divided into normal control and diabetic group. Diabetic model of SD rats was established by intravenous streptozotocin(50 mg/kg) injection. Ten rats in each group were sacrificed on the 2nd month and 10th month respectively. The rat' s prefrontal cortex was removed to observe the expression of GLUT-1 in BBB EC with immunohistochemical(IHC) staining. Results By IHC method, the number of GLUT-1 positive microvessels was significantly decreased in diabetic group in the 2nd month (4. 3 ± 0. 9) compared with that of control group (6.4 ± 1.7, t = 7. 586, P < 0. 01 ) ; the number of GLUT-1 positive microvessels was significantly increased in the diabetic group in the 10th month (8.4 ± 1.4) compared with that of control group (5. 8 ± 1.7, t = 15.922,P < 0. 01 ). Conclusions Short-term diabetes GLUT-1 expression in BBB EC is downregulated in early stage, while it is upregulated in advanced stage.

Difference of Endothelial Cell in Ultrastructure,Markers and Permeability between Blood-Brain Barrier and Blood-Nerve Barrier / 中国康复理论与实践

@#Objective To investigate the difference of endothelial cell (EC) in ultrastructure,markers and permeability between blood-brain barrier (BBB) and blood-nerve barrier (BNB).MethodsThe rat brain cortex and sciatic nerve were removed.Ultrastructure of endothelial cell was observed with electron microscopy.Employing immunohistochemical (IHC)staining,the relative distribution was determined for the OX-26,endothelial barrier antigen (EBA)and extravasated fibrinogen around microvessels.ResultsMicrovessels both in BBB and in BNB did share the same tight junctions.However,BNB had a significantly larger number of vesicles than that of BBB.Microvessels in BNB did not express the OX-26 and EBA,but staining weakly positive for fibrinogen,while microvessels in BBB showed strong positive for OX-26 and EBA,perivascular staining of fibrinogen had not been seen.ConclusionTight junctions were present in both BBB and BNB endothelial cell,but there was a significant difference between them in the number of the pinocytotic vesicles,markers expression and permeability.

Characteristics of the Patients with Post-stroke Depression:208 Cases Report / 中国康复理论与实践

@#Objective To investigate the characteristics of the patients with post-stroke depression (PSD).Methods208 cases of patients with stroke were analyzed retrospectively. Results and ConclusionThe PSD occurred more frequently within the first month but less on the first week (P<0.001). The incidence of PSD was higher in female than in male (P<0.001).Frontal, temporal, parietal cortices lesion significantly increased the incidence of the PSD compared with in other area(P<0.01). The more severely the neural function was damaged, the higher the incidence of the PSD was. The muscle strength of patients with PSD recovered poorer than those without PSD. There was significant difference in the incidence of the PSD between the middle age group and aged group (P<0.01).