Application value of whole exome sequencing in critically ill neonates with inherited diseases / 中国当代儿科杂志

OBJECTIVE@#To study the application value of whole exome sequencing (WES) in critically ill neonates with inherited diseases.@*METHODS@#A total of 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis who were admitted to the neonatal intensive care unit were enrolled as subjects. The clinical data of the neonates were collected, and venous blood samples were collected from the neonates and their parents for WES. The clinical manifestations of the neonates were observed to search for related pathogenic gene mutations.@*RESULTS@#Among the 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis (34 boys and 32 girls), 14 (21%) were found to have gene mutations by WES. One neonate had no gene mutation detected by WES but was highly suspected of pigment incontinence based on clinical manifestations, and multiplex ligation-dependent probe amplification detected a heterozygous deletion mutation in exons 4-10 of the IKBKG gene. Among the 15 neonates with gene mutations, 10 (67%) had pathogenic gene mutation, 1 (7%) was suspected of pathogenic gene mutation, and 4 (27%) had gene mutations with unknown significance. Among the 15 neonates, 13 underwent chromosome examination, and only 1 neonate was found to have chromosome abnormality.@*CONCLUSIONS@#Chromosome examination cannot be used as a diagnostic method for inherited diseases, and WES detection technology is an important tool to find inherited diseases in critically ill neonates with suspected inherited diseases or unclear clinical diagnosis; however WES technology has some limitation and it is thus necessary to combine with other sequencing methods to achieve an early diagnosis.

Treatment of congenital hypertrophic pyloric stenosis with endoscopic pyloromyotomy / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of the treatment of congenital hypertrophic pyloric stenosis (CHPS) with endoscopic pyloromyotomy.</p><p><b>METHOD</b>Nine consecutive infants (7 boys, 2 girls; age range 26 - 70 days; weight range 2.65 - 6.10 kg), with a diagnosis of CHPS according to typical clinical manifestations, transabdominal ultrasound (US), gastroenterography and gastroscope. All the cases had accompanying malnutrition, anaemia, metabolic alkalosis, and some were complicated with congenital heart disease. In gastroscope operating room, all the patients were given pentobarbital and midazolam intravenously. A gastroscope with an outer diameter of 5.9 mm was passed through mouth, stomach, pylorus to the descending segment of duodenum. Under gastroscopy, two incisions were made along the anterior and posterior wall of pylorus from the duodenal bulb to the antrum by using endoscopic electrosurgical needle knife and an arch sphincter sarcosome. Incisions were deepened by 2 to 3 procedures until the longitudinal muscle was exposed, about 2 to 4 mm according to transabdominal US performed before operation. The incision depth was 2 - 3 mm if pylorus wall was 4 - 6 mm in thickness; or 3 - 4 mm when the wall was thicker than 6 mm.</p><p><b>RESULT</b>The endoscope was easily passed through the pylorus to the duodenum post-operation. The transabdominal US and gastroenterography showed that liquid easily flew through pylorus. All patients were able to have regular feeding about 2 to 10 hours after the operation. Vomiting in all patients was significantly decreased in frequency and amount, and in 8 infants vomiting stopped within 1 week, in one case it did not stop until 1 month after the treatment. Some cases showed slight adverse reaction, no perforation or massive haemorrhage in stomach or intestines occurred in any of the patients during and post-operation. Eight infants were doing well at follow-up (range 2 to 9 months). One girl had recurred vomiting at normal feeding after a period of 1 month postoperation without vomiting. This case was cured by second endoscopic pyloromyotomy.</p><p><b>CONCLUSIONS</b>Endoscopic pyloromyotomy is effective, safe, simple, and offers several advantages: no need for open-abdomen surgery, feeding can be initiated rapidly.</p>

Effects of fosinopril on proliferation and secretion of extracellular matrix of rat glomerular mesangial cell / 中华儿科杂志

<p><b>OBJECTIVE</b>To observe the effects of fosinopril (FOS) on proliferation and secretion of extracellular matrix of rat glomerular mesangial cell induced by LPS.</p><p><b>METHODS</b>In vitro culture method for glomerular mesangial cells (GMC) of rat was established and passages 3 - 10 of the cells were used in the experiment after identification. The experiment included the following 5 groups: control group (Ctrl), LPS group (LPS), high, medium and low dose FOS groups (FOS1, FOS2 and FOS3 groups, respectively). GMC proliferation was detected by methyl thiazolyl tetrazolium (MTT) incorporation method at 24 and 48 h; the changes of laminin (LN), fibronectin (FN) and ColIV protein secretion was detected by the enzyme-linked immunosorbent assay (ELISA). The changes of LNbeta(2) mRNA expression was detected by semi-quantitative real-time RT-PCR.</p><p><b>RESULTS</b>(1) LPS could induce the mesangial cell proliferation, FOS inhibited this effect of proliferation induced by LPS. (2) Mesangial cells could secrete some extracellular matrix (ECM) protein in normal culture medium, mesangial cell secreted ECM protein was significantly higher in LPS group than that in Ctrl group (P < 0.01), but significantly lower in all FOS groups than that in LPS group (P < 0.01). (3) Mesangial cell could express LNbeta(2) mRNA in normal culture medium, LNbeta(2) mRNA expression was significantly higher in LPS group than that in Ctrl group at all time points, but was significantly lower in FOS group than that in LPS group.</p><p><b>CONCLUSIONS</b>LPS could induce increased secretion of the ECM, including LN, FN, ColIV; FOS could inhibit the secretion of ECM in GMC in a dose-dependent manner at mRNA and protein levels.</p>

Therapeutic effect of Ginkgo biloba leaf extract on hypercholestrolemia in children with nephrotic syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the therapeutic effects of the extract of Ginkgo biloba leaf on hypercholestrolemia in children with primary nephritic syndrome (NS).</p><p><b>METHODS</b>Thirty-five children with NS were randomized into 2 groups for treatment with prednisone plus Ginkgo biloba leaf extract (18 cases) or with prednisone plus dipyridamole (17 cases) for 8 weeks. After completion of the treatments, the therapeutic effects were evaluated and the changes in the blood biochemical markers assayed.</p><p><b>RESULTS</b>The 8-week treatment with the extract significantly ameliorated the clinical symptoms and blood biochemistry as compared with prednisone plus dipyridamole group (P<0.01). The levels of urinic protein and blood lipid in Ginkgo leaf group were significantly lower than those in prednisome plus dipyridamole group (P<0.05).</p><p><b>CONCLUSION</b>The extract from Ginkgo biloba leaf can lower blood lipid levels and urinic protein in children with NS and improve their clinical syptoms and the renal function, therefore has much clinical value as an adjuvant treatment of steroid therapy in such children.</p>

Effects of Fosinopril on Transforming Growth Factor-Beta 1 Secretion and mRNA Expression of Cultured Rats Glomerular Mesangial Cell / 实用儿科临床杂志

Objective To observe the effects of fosinopril(FOS),a new generation angiotensin-converting enzyme inhibitor(ACEI),on protein and mRNA expression of transforming growth factor-?_1(TGF-?_1) of rat glomerular mesangial cell(GMC) induced by lipopolysaccharide(LPS);to demonstrate the preventive mechanism against glomerular sclerosis by applying FOS.Methods The cultured GMC in classic way were divided into 3 groups:control group;LPS group;LPS+FOS group.TGF-?_1 concentration in GMC supernatant fluid was detected by ELISA;TGF-?_1 mRNA expression was determined by semiquantitative real-time RT-PCR.Results LPS group was obviously higher than control groups in TGF-?_1 secretion and mRNA expression,while LPS+FOS group decreased distinctively in TGF-?_1 secretion and mRNA expression compared with LPS group.Conclusions FOS has obviously inhibited on TGF-?_1 expression of rat GMC both at protein level and mRNA level,which reveals that it may be an important mechanism by FOS on restraining the development of glomerulosclerosis.

Change of transforming growth factor beta in peripheral blood mononuclear cell of children with nephrotic syndrome and its significance / 中华儿科杂志

<p><b>OBJECTIVE</b>Idiopathic nephrotic syndrome (INS) is a common glomerular disease. The pathogenesis of the disease remains unclear. Recent studies indicate that transforming growth factor beta (TGF beta) is the main cytokine involved in glomerular disease. It plays an important role in the development of INS and in occurrence of glomerulosclerosis. The present study aimed to study changes and significance of TGF beta in children with idiopathic nephrotic syndrome (INS).</p><p><b>METHODS</b>Totally 35 cases with INS (13 males, 22 females) were studied. The age of onset was between 2 years and 1 months and 14 years with an average of 8 years and 3 months. The active stage group had 35 cases and the remission stage groups had 25 cases. The cases in active stage group had first onset of the disease with obvious clinical symptoms and abnormal laboratory findings without use of corticosteroids. The cases in remission stage group were asymptomatic without abnormal laboratory findings. Protein in urine was negative over 4 weeks after oral administration of prednisone for 8 weeks. Twenty five cases were steroid responsive and 10 cases were steroid non-responsive among the 35 cases. Thirty healthy young children were enrolled as control. TGF beta was detected by ELISA in peripheral blood mononuclear cell (PBMC) culture medium. The TGF beta mRNA gene expression was measured by in situ PCR in PBMC.</p><p><b>RESULTS</b>(1) Concentration of TGF beta(247 +/- 26) ng/L and TGF beta mRNA expression (0.57 +/- 0.18) in active stage of simple type or nephritis type INS were higher than those of remission stage and control (P < 0.01). Concentration of TGF beta[(125 +/- 16) ng/L] and TGF beta mRNA expression (0.30 +/- 0.12) in remission stage were higher than that of control (P < 0.05). (2) The level of TGF beta protein in nephritis type [(275 +/- 26) ng/L] was significantly higher than that in simple type [(220 +/- 18) ng/L] in active stage INS (t = 6.45, P < 0.01). No significant difference in TGF beta mRNA expression was found between the nephritis type (0.58 +/- 0.15) and simple type (0.55 +/- 0.16) in active stage INS, either (P > 0.05). But these two types were different from the control (P < 0.01). (3) Concentration of TGF beta and TGF beta mRNA expression after therapy was clearly lower than that before therapy in steroid responsive group (P < 0.01). Whereas no significant change was seen in steroid non-responsive group. Both indicators were higher in steroid non-responsive group than in steroid responsive group whether before or after therapy.</p><p><b>CONCLUSION</b>TGF beta may play an important role in the mechanism of INS and its level in PBMC can be used as an immunological indicator for the illness state, therefore, determination of TGF beta level and mRNA may be of some clinical significance.</p>

Clinical and Pathological Analysis on 66 Cases of Neonatal Pulmonary Hemorrhage / 实用儿科临床杂志

Objective To explore the higher dangerous factors,the early clinical performances and its contents of neonatal pulmonary hemorrhage(NPH).Methods The clinical performances,chest radiograms and autoptical pathological materials of 66 cases of newborns who died of NPH at our neonatal department during 1993 to 2003 were reviewed and analyzed.Results The higher dangerous factors of NPH were premature delivery/low birth weight,serious diseases lead to hypoxia and severe infections.The early clinical performances of NPH were the suddenly aggravation of dyspnea and the increasing of moist sounds.The early X-ray performances were lower penetrance of lung fields extensively and well-distributly with path clouds,the intercostals space usually increased.According to the autoptical(patho)-logy,this X-ray perfomance indicated the edema of the pulmonary with small amount of hemorrhage.Conclusion The patients with the higher dangerous factors and the early clinical performances of NPH,must be diagnosed and interfered it as early as possible to reduce the mortality of NPH.

Therapeutic Effect of Oral Indomethacin for Patent Ductus Arteriosus in Full-Term Infants / 实用儿科临床杂志

Objective To explore therapeutic effect and side effect of oral indomethacin for treating patent ductus arteriosus(PDA)in full-term infants.Methods Forty-one full-term infants confirmed PDA by echocardiographically,who were admitted to the neonatal intensive care unit of our hospital from Jan.2004 to Dec.2007,were randomly divided into experimental group(21 cases)and control group(20 cases).Three oral doses of indomethacin [0.2 mg/(kg?time),at an interval of 12 hours] were administered in experimental group,while nothing in control group.Hepatorenal function and blood routine were measured in both groups in 2 days before and after treatment.Urine output and level of serum blood sugar were measured,and abdominal distension,vomiting,bloating,and bleeding were recorded during treatment.Color Doppler echocardiographic examination was performed,heart murmur was stethoscopied,and the rate of ductal closure was recorded at 5 to 7 days after treatment.The infants were followed up at out-patient department at 6 to 12 months after treatment,color Doppler echocardiographic examination was performed,and ductal closure condition was recorded.Results Hepatorenal function and blood routine were normal in experimental group in 2 days before and after treatment.Except that a little gastrointestinal bleeding occurred in one case of experimental group after the second dose of indomethacin,other adverse reactions were not observed during treatment.The ductus was closed in 16 infants in experimental group,the rate of ductal closure was 76.19%,while the ductus was closed naturally in 5 infants in control group,the rate of ductal closure was 25.0% at 5 to 7 days after treatment.There was significant difference in the rate of ductal closure between the experimental and control groups(?2=10.74 P