Rapamycin in the treatment of renal diseases associated with tuberous sclerosis complex / 中华儿科杂志

Objective@#To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease.@*Methods@#A prospective self-control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People′s Liberation Army General Hospital from January 2011 to January 2019 were collected. The long-term rapamycin treatment for all patients initiated at 1 mg/(m2·d), which was gradually adjusted to reach a blood concentration of 5-10 μg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test.@*Results@#Ninety-two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow-up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0,7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750,P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and ≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102,P=0.393,0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and ≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0,18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm)(Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214,P=0.345,0.225,0.301,0.058,0.109,0.225, respectively).Twenty-nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed.@*Conclusions@#Rapamycin could decrease the diameter of TSC-related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.

The preliminary study on the measurement of(1,3)β-D glucan in plasma for the diagnosis of pulmonary fungal infections in pulmonary tuberculosis patients / 实用医学杂志

Objective To explore the measurement of(1,3)-β-D glucan in plasma for the diagnosis of pulmonary fungal infections in pulmonary tuberculosis patients. Methods 40 pulmonary tuberculosis patients with pulmonary fungal infections in Guangzhou chest hospital from January 2015 to December 2015 were enrolled as a test group,among which 35 were confirmed and 5 were suspected pulmonary fungal infections. 52 pulmonary tuber-culosis patients without fungal infections were selected as a control group.(1,3)-β-D glucan content(G test)in this 92 patients plasma were detected. The results of G tests were compared with those from etiological diagnosis to assess the performance of G test. Results 13 strains of candida albicans,13 strains of aspergillus,2 strains of candida tropicalis,2 strains of candida glabrata and 6 strains of other yeast were obtained from patients of test group,but no fungal identified from those of control group. The median of G test in test group and in control group was 126.1 and 29.56 pg/mL,respectively,the level in test group was significantly higher than that in control group (P<0.001). 35 cases were identified as positive and 5 were negative in test group by G test ,while 41 cases were identified as negative and 11 were positive in control group. The sensitivity,specificity,positive predictive value, negative predictive value ,concordance and Youden index of G test were 87.5%,78.85%,76.09%,89.13%, 82.6%and 0.663,respectively. Conclusions Candida albicans and aspergillus are more common pathogens than the other fungi isolated from pulmonary tuberculosis patients with pulmonary fungal infection. G test ,used in pul-monary tuberculosis with pulmonary fungal infections diagnosis,is reliable and fast,and has a higher sensitivity, specificity and accuracy.

Efficacy and safety of rapamycin in treatment of children with epilepsy complicated with tuberous sclerosis / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect and safety of rapamycin in treatment of children with tuberous sclerosis complex (TSC) complicated with epilepsy.</p><p><b>METHOD</b>This was an open-label, prospective, self-controlled study. From Sep. 2011 to Sep. 2013, 52 patients with the diagnosis of tuberous sclerosis complicated with epilepsy receiving rapamycin treatment for at least 24 weeks were enrolled.</p><p><b>RESULT</b>Of the 52 children, 34 were male and 18 female. The median age at onset of epilepsy was 4.8 months (4 days-49 months), the median age for treatment with rapamycin was 27 months (4.5-172.5 months). Ten children had a family history of TSC. In 24 children TSC gene detection was carried out, among whom TSC1 mutation was detected in 4 cases and TSC2 mutation in 20. Before rapamycin therapy, 59.62%, (31/52) patients took more than 3 antiepileptic drugs, of whom 10 cases even took more than 5 kinds of antiepileptic drugs. Fifty-two patients received rapamycin treatment for 24 weeks, seizure free rate was 25.00% (13 cases), the total effective rate was 73.08% (38 cases); 31 cases received treatment for 48 weeks, seizure free 6 cases, total effective 23 cases; 17 cases accepted treatment for 72 weeks, seizure free 5 cases, total effective 13 cases; 12 cases received treatment for 96 weeks, seizure free 3 cases, total effective 9 cases. With the decrease of seizure attacks, use of antiepileptic drug types were reduced simultaneously, they had a negative correlation. Before rapamycin therapy, the average frequency of seizures was 70.27 times/d, the number of antiepileptic drug kinds was 1.30. After 24, 48, 72, 96 weeks' treatment, the average seizure frequency was reduced to 1.94-2.80 times /d and the antiepileptic drugs were reduced to 0.83-0.97 kinds. On every visit during the follow-up, blood and urine routine tests, liver and kidney function test showed no abnormality in the 52 cases. The drug dosage was 1 mg/(m(2)×d), average 0.7 mg/d (0.35-1.20 mg/d). Blood concentrations of rapamycin remained below 10 µg/L (average 6.5 µg/L). The main side effect was oral ulcer which happened in 23.08% (12/52). The oral ulcer would disappeared 2-3 days later. 17.31% (9/52 cases) had upper respiratory infection.</p><p><b>CONCLUSION</b>Rapamycin was effective in children with tuberous sclerosis and epilepsy with few adverse reactions. The daily dose of rapamycin for children patients is 1 mg/m(2), which has a certain effect on seizures and a good safety profile.</p>

Sleep frequent tongue bite / 中华实用儿科临床杂志

The 10-month baby boy,with normal development,mainly due to sleep in frequent tongue bite nearly 4 months.Bitten his tongue after faring asleep,biting bleeding,bite pain awake.Many of his tongue ulcers,serious impact on children's lives,family companionship in suffering.History found in the supplementary week before the onset of the left frontal children hurt skin bruising.Electroencephalogram showed:Sleep of epileptiform discharges in the left frontal and central anterior temporal areas,but bite the tongue during sleep electroencephalogram synchronization no relevant abnormal discharge.The final diagnosis of traumatic epilepsy,frontal lobe epilepsy syndrome automatically lead to tongue bite tongue with traumatic ulcers.Oral Clonazepam 0.25 mg before sleep,the symptoms disappeared that night,nighttime sleep peacefully.His tongue ulceration has healed after a month.Readers are advised to take advantage of these key parts of the diagnostic process and diagnostic thinking or diagnostic procedures,combined with their own clinical practice,serious thinking,learning,summarized,and benefit from it.

A family with two children diagnosed with aspartylglucosaminuria-case report and literature review / 中华儿科杂志

<p><b>OBJECTIVE</b>The authors sought to investigate the clinical features and characteristics of genetic mutation in patients with aspartylglucosaminuria.</p><p><b>METHOD</b>Clinical data of two pediatric siblings in a family were analyzed retrospectively and relative literature was reviewed in order to study the clinical features, imaging and enzymatic characteristics and genetic mutations.</p><p><b>RESULT</b>Case 1, the proband, male, he was hospitalized at 20 months of age because of fever and hepatosplenomegaly for nine days. This child was of moderate nutritional status and normal development. Blood tests showed hemoglobin 78.0 g/L, RBC3.18 × 10¹²/L, WBC 4.06 × 10⁹/L, neutrophils 0.236, lymphocytes 0.631, platelets 34 × 10⁹/L, C-reactive protein 17 mg/L. Blood biochemistry showed alanine aminotransferase 67.1 U/L, aspartate aminotransferase 74.1 U/L, serum albumin 32.8 g/L, direct bilirubin 10.5 µmol/L, lactate dehydrogenase 301.7 U/L. Bone marrow cytology showed reactive morphological changes in bone marrow cells. Atypical lymphocytes could be seen in both peripheral blood and bone marrow smears. Cranial MRI showed poor myelination. Aspartylglucosaminidase activity in peripheral leucocytes of the proband 5.7 nmol/(g × min) vs. normal control>26.6 nmol/(g × min). On his AGA gene and that of his parents, a heterozygous mutation site located in exon 3, c.392C>T (p.S131L), was identified as a novel mutation inherited from his father. The mutation from his mother has not been detected. The proband was not responsive to the anti-infectious medication, nutritional intervention and symptomatic treatment.He died one month after diagnosis.His elder brother, Case 2, showed fever, recurrent respiratory tract infection and progressive psychomotor regression with hepatosplenomegaly from the age of four years. Cranial MRI revealed extensive symmetrical leukodystrophy in bilateral cerebra, cerebellum and brainstem.He died at the age of six years.Related literature was summarized, and no Chinese AGU cases had been reported; 221 foreign cases were collected. The clinical and imaging characteristics were summarized. Delay in language development was one of the clinical symptoms that the majority of parents of AGU children first noted.</p><p><b>CONCLUSION</b>Patients with aspartylglucosaminuria lack of specific symptoms.For children with unexplained delayed speech and progressive mental retardation, the possibility of AGU should be considered, and efforts be made for enzymatic and genetic diagnosis. c.392C> T (p.S131L) was identified as a novel mutation of AGA gene.</p>

Synapse function of neuron-like cells induced from mesenchymal stem cells by Salvia miltiorrhiza / 第三军医大学学报

Objective To explore whether the neurons induced from mesenchymal stem cells(MSCs) have synapse function or not.Methods Passage 4-5 MSCs in good shape was induced by Salvia miltiorrhiza with optimized protocol for several times,and then the observation under inverted phase contrast microscope,immunofluorocytochemistry and the measurement of neurophysiological function were carried out.Ca2+ influx and synapse function were detected with laser-scanning confocal microscopy(LSCM),taking 50 mmol/L KCl as stimuli to evoke action potential.Results The cells that had been induced for 5 h at 4th time from MSCs,looked like neurons and displayed that the processes stretched out to form complex net.Immunofluorocytochemistry presented that the rate of TUJ-1 expression was(96.7?2.8)% and that of synaptophysin was(96.2?2.1)%.When the neuron-like cells were stimulated by high concentration of KCl,intracellular Ca2+ influx enhanced quickly.When the neuron-like cells were stimulated by high KCl solution for the first time,SynaptoRed-C2 anchored onto the membrane,and after the second excitation,the fluorescence intensity decreased quickly.Conclusion The neuron-like cells derived from MSCs that are induced by salvia miltiorrhiza with optimized protocol have synapse function.