Objective To explore the clinical curative effect of pidotimod on patients with respiratory tract infection and effect on immune function. Methods 120 children with recurrent respiratory tract infection in the Third Hospital of Qinhuangdao,the Third Staff Hospital of Baogang Group,the Third Hospital of Wulanchabu were selected,and were divided into two groups according to random number table.60 cases in control group were treated with routine treatment of anti-infection,relieving cough,eliminating phlegm,antipyretic;60 cases in experimental group were treated with pidotimod on the basis of routine treatment,oral with boiled water,0.4g per times,2 times a day,with a course of 60 days.Clinical curative effect after treatment and serum immunoglobulin (IgG,IgA,IgM)levels,T lymphocyte subsets (CD3+,CD4+,CD8+)levels and NK cells relative activities before and after treatment were compared between two groups.Results After treatment,the total effective rate of experimental group (95.00%)was significantly higher than that of control group (81.67%),and the difference was statistically significant (P<0.05);the immune indexes before treatment had no significant difference,and levels of serum immunoglobulin and T lymphocyte subsets were improved,and levels of serum immunoglobulin (IgG,IgA,IgM)and T lymphocyte subsets (CD3+,CD4+,CD8+)of experimental group were more higher than those of control group,and the difference was statistically significant (P<0.05 );relative activity of NK cells in both groups improved after treatment,but relative activity of NK cells in experimental group was significantly higher than that in control group,and the difference was statistically significant (P<0.05 );adverse reactions according minor rashes and anemia were observed in two groups,and there was no significant differece in the incidence of adverse reactions,and ADR was tolerable after symptomatic treatment.Conclusion Pidotimod could significantly improve the clinical curative effect of patients with respiratory tract infections and effectively improve the immune function of patients with recurrent respiratory tract infections with high security,which has a clinical significance.

Objective To investigate the clinical and biochemical metabolic features of 12 patients with systemic primary carnitine deficiency(CDSP) and to identify the SLC22A5 gene mutation types of the disease. Method The clinical and biochemical data were collected by retrospective analysis. DNA direct sequencing and multiplex ligation dependent probe amplification(MLPA)were applied for SLC22A5 gene analysis. Result Among 12 patients with CDSP, 3 cases had evident infection factors, 6 cases with convulsions, 5 cases manifested liver hypertrophy, 8 cases with hyperammonemia, and 9 cases showed myocardial damage. All CDSP patients were detected biallelic pathogenic mutation in SLC22A5 gene by direct sequencing. The gene types include IVS2+1G>T, c.3G>T(p.Met1Ile), c.760C>T(p.Arg254X), c.1400C>G(p.Ser467Cys), c.844dupc(p.Arg282fs), c.338G>A(p.Cys113Tyr), c.51C>G(p.Phe17Leu), c.659A>T(p.Glu220Val), and c.1365dupC(p.Thr456fs). c.659A>T(p.Glu220Val) and c.1365dupC(p.Thr456fs)are novel mutations. One female patient was maternal CDSP, her child had abnormal newborn screening. The allele frequency of c.760C>T(p.Arg254X) and c.1400C>G(p.Ser467Cys) were 37.5%(9/24)and 29.2%(7/24)respectively. The MLPA test results of all patients were negative. Conclusion The clinical manifestations are complex and various in patients with CDSP. Point and small InDel(insertions/deletions)mutation constitute the major alteration in SLC22A5 gene. c.1400C>G(p.Ser467Cys) might be another prevalence mutation type in Chinese CDSP patient.

Objective To investigate the cliuical phenotype and the genotype of forty-one patients with steroid 5α-reductase type 2 deficiency.Methods The clinical data were collected including physical examination,medical history,laboratory test,as well as ultrasonic examination.Genomic DNA was extracted from peripheral blood leukocytes.Sanger sequencing and targeted gene captured next-generation sequencing were applied to detect the SRDSA2 gene mutation.Results All the patients are Han nationality and their ages ranged from 4 months to 11 years old.The karyotypes of 41 patients were 46,XY and all SRY genes were detected as positive.There were 26 (63％) patients manifested isolated micropenis,and the rest of fifteen patients were hypospadias associated with microphallus accounting for 37％.There were 39 patients who carried biallelic mutation.Two cases just identified one allele mutation.Sixteen gene mutation types were confirmed.Among them c.725A ＞ G (p.Tyr242Cys),c.694C ＞ G (p.His232Asp),and c.548-9T＞G are the novel gene types.The allele frequency of c.680G＞A (p.Arg227Gln) is 60％ (48/80).Conclusion The primary manifestations of patients with steroid 5α-reductase type 2 deficiency were micropenis or hypospadias accompanied with micropenis.c.680G＞A (p.Arg227Gln) is the predominantly mutation type of Chinese patient with steroid 5α-reductase type 2 deficiency.

OBJECTIVETo analyze PCCA and PCCB gene mutations in 10 Chinese patients with propionic acidemia(PA).

METHODSGenomic DNA was extracted from peripheral blood leukocytes. The 39 exons and flanking sequences of the PCCA and PCCB genes were amplified with polymerase chain reaction and subjected to direct DNA sequencing.

RESULTSDNA sequencing has revealed that 7 patients have carried a PCCA gene mutation, 2 patients carried PCCB gene mutation and 1 patient carried mutations in both PCCA and PCCB genes. Ten PA mutations were confirmed, including 8 affecting the PCCA gene and 2 affecting the PCCB gene. Three PCCA mutations c.245G>A, IVS15+5del5, c.1288C>T and 2 PCCB mutations c.838insC, c.1087T>C were found for the first time.

CONCLUSIONAmong Chinese patients with propionic acidemia patients, their genetic mutations are mainly found on the PCCA gene.

Child, Preschool ; Female ; Humans ; Infant ; Male ; Methylmalonyl-CoA Decarboxylase ; genetics ; Mutation ; Propionic Acidemia ; genetics

OBJECTIVETo identify the types of OTC gene mutations in three male patients with late onset ornithine transcarbamylase deficiency (OTCD, MIM #311250).

METHODSGenomic DNA was extracted from peripheral blood leukocytes. The 10 exons and their flanking sequences of the OTC gene were amplified with polymerase chain reaction and subjected to direct DNA sequencing.

RESULTSBased on DNA sequence analysis, all of the three patients have carried OTC gene mutations. Patients 1 and 2 were both hemizygous for mutation c.586G> A(p.D196N). A novel mutation c.800G> C(p.S267T) were confirmed in patient 3.

CONCLUSIONp.S267T mutation has affected the conserved amino acid motif of the OTC protein, and is therefore a pathogenic mutation.

Age of Onset ; Amino Acid Sequence ; Base Sequence ; Child ; Humans ; Infant ; Male ; Molecular Sequence Data ; Mutation ; Ornithine Carbamoyltransferase ; genetics ; Ornithine Carbamoyltransferase Deficiency Disease ; epidemiology ; genetics ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid

Objective: To observe the effects of minimally invasive tangential excision in treating deep partial-thickness burn wounds on trunk and limbs in pediatric patients in the early stage post burn. Methods: Clinical data of 40 children with deep partial-thickness burn wounds on trunk and limbs, admitted to our burn ward from January 2016 to June 2017, conforming to the study criteria, were retrospectively analyzed. They were divided into conventional treatment group (CT, n=19) and minimally invasive tangential excision group (MITE, n=21) according to the different treatments. The patients in group CT were treated with eschar-reserving therapy firstly. When tangential excision was performed, the roller knife was used, and no necrotic tissue left on the wound bed was considered the proper depth of excision. Razor-thickness skin grafting was performed to cover the wound when adipose tissue exposed markedly after tangential excision. Dressing change was performed within 48 h after the operation and repeated every 2 days. Unhealed wounds were covered by razor-thickness skin grafting. The patients in group MITE were treated with tangential excision in the early stage post burn. The tangential excision was operated with electric dermatome, and the thickness was set at 0.1 mm to excise the surface of eschar until the sporadic punctate hemorrhage on wound surface was observed and some necrotic tissue was left on the wound bed. Porcine acellular dermal matrix was applied after tangential excision. The first dressing change was often performed about 1 week after the operation. Razor-thickness skin grafting was performed to cover the unhealed wounds. The length of wound healing, high fever, antibiotic usage, and hospital stay, times of later operation, and hospitalization expenses of patients in the 2 groups were recorded. The excisional eschar and wound bed tissue of patients in group MITE were harvested for pathological observation. Data were processed with t test and Fisher′s exact probability test. Results: (1) There were no statistically significant differences in length of high fever and length of hospital stay and hospitalization expenses between patients in the 2 groups (t=-1.67, -1.93, 0.31, P>0.05). The lengths of wound healing [(24.8±2.5) d] and antibiotic usage [(4.4±0.7) d] of patients in group MITE were significantly shorter than those in group CT [(33.3±2.5) and (7.0±0.7) d, t=-2.44, -2.44, P<0.05], and times of later operation of patients in group MITE [(0.29±0.14) times] were significantly less than those in group CT [(0.79±0.21) times, t=-2.03, P<0.05]. (2) The thickness of the excisional eschar of patients in group MITE was about 150 μm. The eschar has epidermis and upper dermis. Some necrotic tissue was left on the wound bed. Conclusions The treatment for pediatric deep partial-thickness burn wounds on trunk and limbs with minimally invasive tangential excision using electric dermatome in the early stage post burn can accelerate wound healing, shorten length of antibiotic usage, and reduce times of later operations.

OBJECTIVETo analyze the clinical features and mutation of MUT gene in a Chinese patient with isolated methylmalonic acidemia.

METHODSThe clinical characteristics and laboratory tests data were collected. Genomic DNA was extracted from peripheral blood leukocytes. The 13 exons and their flanking sequences of the MUT gene were amplified with polymerase chain reaction and subjected to direct DNA sequencing.

RESULTSThe patient has featured failure to thrive, lethargy, seizure, hypotonia, severe ketoacidosis and hyperammonemia. Tandem mass results showed reduction of multiple acylcarnitine. Urine organic acid testing showed pronounced increase in methylmalonate excretion. Homocysteine was normal. The patient showed no response to vitamin B12 treatment. The above results suggested that the patient had isolated methylmalonic acidemia. DNA sequencing analysis confirmed that the patient has carried two MUT gene mutations, c.755dupA and a novel mutation c.944dupT.

CONCLUSIONInherited metabolic disease screening plays an important role in the diagnosis of clinical diseases. However, to confirm the results will need gene mutation analysis.

Amino Acid Metabolism, Inborn Errors ; enzymology ; genetics ; Base Sequence ; Female ; Humans ; Infant, Newborn ; Methylmalonyl-CoA Mutase ; genetics ; Molecular Sequence Data ; Mutation

OBJECTIVETo investigate the clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency (BKTD).

METHODSClinical features and laboratory test data were collected. The probands were monozygotic twin brothers. Genomic DNA was isolated from peripheral blood leukocytes obtained from the probands and their family members. Molecular genetic testing of the ACAT1 gene was carried out.

RESULTSThe probands have presented with fever, vomiting and severe ketoacidosis. By arterial blood gas testing, pH was determined to be 7.164, bicarbonate was 4.0 mmol/L, and urine ketone was ++++. Urinary organic acid gas chromatography-mass spectrometry analysis showed excessive excretion of 3-hydroxybutyric acid, 2-methyl-3-hydroxybutyric acid and tiglylglycine. Increased 3-hydroxybutyrylcarnitine (C4-OH), tiglylcarnitine(C5:1) and 3-hydroxyisovalerylcarnitine (C5-OH) levels. The clinical phenotype of proband's parents were both normal, but an elder sister turned out to be an affected patient. Genetic analysis has identified two heterozygous mutations [c.622C>T(p.R208X) and c.653C>T (p.S218F)] in the proband, which were respectively detected in the mother and father. The c.653C>T (p.S218F) mutation was not found among the 100 healthy controls and has not been included in the Human Gene Mutation Database(HGMD).

CONCLUSIONThe primary clinical manifestations of BKTD is ketoacidosis. Urine organic acid and blood acylcarnitine analyses play an important role in the diagnosis of the disease. The compound heterozygous of ACAT1 gene mutations probably underlie the BKTD in our patient.

Acetyl-CoA C-Acetyltransferase ; genetics ; Acetyl-CoA C-Acyltransferase ; deficiency ; genetics ; Amino Acid Metabolism, Inborn Errors ; genetics ; Computational Biology ; Female ; Humans ; Infant ; Male ; Mutation ; Phenotype

OBJECTIVETo explore pathogenic mutation in a family affected with 2-hydroxyglutaric aciduria.

METHODSExons of 3 candidate genes, including L2HGDH, D2HGDH and SLC25A1, were amplified with polymerase chain reaction and subjected to direct sequencing.

RESULTSDNA sequencing has found that the proband and his affected younger brother have both carried a heterozygous mutation c.845G>A (p.R282Q) in the exon 7 of the L2HGDH gene. The same mutation was not detected in the his sister who was healthy. Pedigree analysis has confirmed that the above mutation was inherited from the mother. No mutation was detected in exons and flanking sequences of the D2HGDH and SLC25A1 genes.

CONCLUSIONMutation of the L2HGDH gene probably underlies the 2-hydroxyglutaric aciduria in this family.

Alcohol Oxidoreductases ; genetics ; Base Sequence ; Brain ; diagnostic imaging ; Brain Diseases, Metabolic, Inborn ; diagnostic imaging ; enzymology ; genetics ; Child ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Radiography ; Young Adult

OBJECTIVETo detect potential mutations of Y9ASS1, ASL and SLC25A13 genes in four patients manifesting citrullinemia.

METHODSGenomic DNA was extracted from peripheral blood leukocytes. Exons and their flanking sequences of the three genes were amplified with polymerase chain reaction and subjected to direct DNA sequencing.

RESULTSBased on DNA sequence analysis, one case was diagnosed with argininosuccinate synthetase deficiency, and the mutation type (ASS1 gene) was c.236C>T (p.S79F) + c.431C>G (p.P144R). Two cases were diagnosed with argininosuccinic aciduria (ASL gene), and their gene mutations were c.434A>G (p.D145G) + c.1366C>T (p.R456W) and c.331C>T (p.R111W) + IVS8+2insT, respectively. A thirteen months boy who carried a heterozygous 851del4 mutation (SLC25A13 gene) was diagnosed with citrullinemia adult-onset type II.

CONCLUSIONThrough analysis of relevant pathogenic genes, four patients have been diagnosed.

Adult ; Amino Acid Sequence ; Argininosuccinate Lyase ; genetics ; metabolism ; Argininosuccinate Synthase ; genetics ; metabolism ; Base Sequence ; Citrullinemia ; enzymology ; genetics ; Female ; Humans ; Infant ; Male ; Mitochondrial Membrane Transport Proteins ; genetics ; metabolism ; Molecular Sequence Data ; Pedigree ; Point Mutation