Objective To develop a humidification fluid dropping joint for the breathing machine to solve the problems in humidification fluid retension,pipeline leakage,pipeline fixation and etc.Methods A Infusion extension tube was involved in with 10 cm length left at the injector end.A hole was made at the side wall of the L-shaped joint of the breathing machine,whose internal diameter equaled to the external diameter of the extension tube.The extension tube was put into the joint through the hole,and the depth of imbedded tube was within 4 and 6 cm.Sealing and fixation at the connection between the tube and hole were executed with 502 glue and short tourniquet.Results The humidification fluid dropping joint could be connected with infusion apparatus of the pump or the infusion extension tube of the micro pump,which behaved well in eliminating accumulated humidification fluid,sputum suction,humidification and facilitating mechanical ventilation.Conclusion The joint developed gains advantages in easy manufacture,reducing complications and increasing the dependence on artificial airway,and thus is worthy promoting clinically.

Objective To investigate the effects of insulin-like growth factor 1 (IGF 1) and transforming growth factor beta 1 (TGF-β1) in he pathogenesis of children with allergic purpura kidney damage.Methods 135 henoch-schonlein purpura (HSP) children with kidney damage were divided into HSP and HSPN group according to whether associated with renal damage,blood IGF 1,TGF-β1,urinary inhibition C (Cys C),creatinine (SCr) and content of urea nitrogen (BUN) were compared,and blood IGF-1,TGF-β1 and Cys C content of HSPN patients in different pathological grading were compared,the correlation of blood IGF 1,TGF-β1 and Cys C content of the HSPN group were analyzed,Results Blood IGF 1,TGF-β1 and Cys C content of the control group(117.2±18.8 ng/L,164.2±18.4 ng/L,0.9±0.2 mg/L),the HSP group(131.7±19.6 ng/L,282.1±28.3 ng/L,1.1±0.2 mg/L) and the HSPN group (205.3±24.5 ng/L,489.2±32.7 ng/L,1.3±0.3 mg/L) showed a trend of increasing gradually (F=4.824～45.066,P value＜0.01),the HSP group and the HSPN group were higher than that of the control group (q=3.397～58.931,P value＜0.01),the HSPN group was higher than that of the HSP group (q=16.997,35.193,P value＜0.01),the difference was statistically significant.Blood IGF-1 (level Ⅱ 175.6 ± 20.4 ng/L,level m198.5±23.3 ng/L,level Ⅳ241.7±25.1 ng/L),TGF-β1(level Ⅱ 392.8±38.9 ng/L,level Ⅲ 481.3± 44.03 ng/L,level Ⅳ 537.6±42.9 ng/L),Cys C (level 11 1.1±0.3 mg/L,level Ⅲ 1.3±0.4 mg/L,level Ⅳ1.6±0.4 mg/L) content of children with HSPN increased with the increase of renal pathology classification (F=6.594～ 28.317,P value ＜0.01),blood IGF-1,TGF-β1 and Cys C content of kidney pathology classification of Ⅵ level in children was higher than that of the level of Ⅱ and Ⅲ in children (q=2.415～11.818,P＜0.05 or P＜0.01),while the contern of blood IGF-1,TGF-β1 and Cys C of level Ⅲ in children was higher than that of the level Ⅱ in children (q=2.577～6.244,P＜0.05 orP＜ 0.01),the difference was statistically significant.Blood IGF-1,TGF-β1 content of children with HSPN were positively correlated with Cys C content of children (r=0.648,0.719,P＜0.05),but blood IGF 1 content was significantly positive correlated with TGF-β1 content (r=0.748,P＜0.05).Conclusion IGF 1 and TGF-β31 partieipated in the pathogenesis of HSPN,and both were correlated with the degree of the pathological damage.

Objective To investigate the safety of tanshinone Ⅱ A sodium sulfonate in treatment of acute cerebral hemorrhage.Methods One hundred and seventy-two patients with acute cerebral hemorrhage were divided into tanshinone treatment group with 84 cases (tanshinone Ⅱ A sodium sulfonate + traditional treatment) and traditional treatment group with 88 cases (traditional treatment) according to the method of treatment.The safety (including neural function defect,adverse reactions,rebleeding rate and mortality and so on) were determined before treatment,and 2,4 weeks after treatment.Results The chinese stroke scale (CSS) scores in tanshinone treatment group after treatment of 2,4 weeks were lower than those in traditional treatment group [(13.2 ± 4.3) scores vs.(17.4 ± 5.6) scores,(8.7 ± 3.5) scores vs.(12.8 ± 4.6) scores],there were significant differences (t =5.498,6.556,P ＜ 0.01).The total effective rate in tanshinone treatment group was significantly higher than that in treatment group [83.3 ％ (70/84) vs.65.9 ％ (58/88)],there was significant difference (x2 =6.854,P ＜ 0.01).After treatment with tanshinone Ⅱ A sodium sulfonate in tanshinone treatment group,5 cases of mild skin rash,3 cases of nausea,vomiting,to turn for the better after symptomatic treatment.There was not other adverse reactions in the observation period.The mortality,rebleeding rate in tanshinone treatment group were lower than those in traditional treatment group,but there were no significant differences (P ＞ 0.05).Conclusions Early application of tanshinone Ⅱ A sulfonate treatment in acute cerebral hemorrhage has significantly efficacy,in the process of the clinical application is safe amd reliable.It is worthy of clinical popularization.

Objective To detect chromosomal aberrations of autism spectrum disorder (ASD), we performed karyo?types analyses in 632 ASD trios and then investigated whether copy number variants and neurodevelopment related genes are present in the regions of chromosomal aberrations. Methods Karyotypes analyses were performed in 632 ASD trios (1896 individuals). In addition, we investigated whether there were pathogenic copy number variants located in the rele?vant regions of detected aberrant karyotypes by using the database of the International Standards for Cytogenomic Arrays (ISCA) and the Genomic Variation and Phenotype in Humans using Ensembl Resources (DECIPHER) for ASD patients. Results We detected aberrant results in 22 of 632 patients (3.48%) by karyotypes analyses. Of these 22 aberrant karyo?types, 5 were de novo (0.79%), including the duplication, the translocation, karyotypes of Turner syndrome and the addi?tional material with unknown origin. Seventeen children affected with autism had aberrant karyotypes inherited from one of their parents. By using the ISCA and the DECIPHER database, we found that several copy number variants with high pathogenicity were located in 1q25 and 3p24. Further, these copy number variants consisted of several genes related to neurodevelopment such as TNR, ASTN1, and NMNAT2. Conclusion There are a few de novo chromosomal aberrations in some patients affected with ASD. Copy number variants of several pathogenic neurodevelopmental related genes may exist in the regions of chromosomal aberrations. Karyotypes analyses may be applied to explore the genetic etiology in some patients affected with ASD.

AIM: To observe the effect of osthole on tricalcium phosphate (TCP) particles-induced calvarial osteolysis in vivo.METHODS:Male ICR mice were randomly divided into sham group , TCP group and osthole group .A mouse calvarial model of osteolysis was established by TCP particles .On the second postoperative day , osthole (20 mg/kg) was locally injected into the calvarium under the periosteum 3 times a week.Two weeks after osthole treatment , blood and calvaria were collected to determine the level of bone turnover markers such as alkaline phosphatase ( ALP) , osteocalcin and tartrate-resistant acid phosphatase ( TRACP) .The periosteum was performed to examine the release of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and IL-1βby ELISA.The calvaria was obtained for histological and molecular analyses.RESULTS:Data from HE and TRACP staining revealed that osthole prevented TCP particles-induced obvious increase in osteoclastogenesis and resorption area in the metaphysis of mouse calvaria .Osthole treatment increased ALP ac-tivity and osteocalcin level , and dncreased the activity of TRACP in the mouse serum compared with TCP group .Further-more, TCP particles-induced the releases of TNF-α, IL-6 and IL-1βwere significantly suppressed by osthole treatment .In addition, Western blot demonstrated that endoplasmic reticulum ( ER) stress markers such as glucose-regulated protein 78 (GRP78) and CAAT/enhancer binding protein homologous protein (CHOP) were significantly up-regulated in TCP parti-cles-implanted calvarial mice , indicating that TCP particles triggered an ER stress response in the mouse calvarial osteolysis model , which obviously attenuated by osthole .CONCLUSION:Osthole inhibits TCP particles-induced calvarial osteolysis in mice, which is mediated by inhibition of ER stress signaling pathway .

Objective: To investigate the dynamic expression of placenta growth factor (PlGF) in the lungs and its role in paraquat-induced pulmonary fibrosis and to evaluate the effect of ACEI captopril and AT (1) -receptor blocker losartan on paraquat-induced pulmonary fibrosis. Methods: 84 adult healthy female Sprague-Dawley (SD) rats were randomly divided into four groups of different treatments designated as: Control, PQ alone (PQ) , captopril treatment, losartan treatment. Each group was divided into three subgroups of seven animals each. The animals were killed at either 7, 14 or 28 days after PQ administration. The rats in PQ group, treatment group were treated intragastrically (ig) with PQ (40 mg/kg) and the rats in control group were treated with the same dose of saline at the beginning of the experiment. The treatment group received Captopril (60 mg/kg; ig) or Losartan (10 mg/kg; ig) once a day respectively after PQ administration and the other two groups received saline. At the given timepoint, animals were sacrificed and lungs were harvested. A semiquantitative assay of histological examination, hydroxyproline in lung tissues were used to determine the severity of alveolitis and fibrosis. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of PlGF. Results: Inflammatory cell infiltration and fibrotic scores were more prominent in the model group, hydroxyproline contents in lung tissue were significantly increased after PQ administration compared to the control group. Captopril, losartan apparently attenuated the degree of lung injury and pulmonary fibrosis. On 7th, 14th days, the levels of alveolitis in the intervention groups were significantly alleviated as compared with the model group (P<0.05) . On 28th days, the levels of pulmonary fibrosis in the intervention groups were significantly alleviated as compared with model group (P<0.05) . The hydroxyproline contents in the intervention groups were significantly decreased as compared with model group (P<0.01) . PlGF mRNA on day 7, 14, 28 (1.28±0.29vs0.10±0.01、0.80±0.07vs0.10±0.01、0.65±0.13vs0.10±0.01) in the PQ group were all upregulated as compared with that of the control group. PlGF mRNA on day 7, 14, 28 in the captopril and Losartan intervention groups were significantly decreased (0.94±0.04、0.71±0.09、0.52±0.24 and 0.80±0.12、0.66±0.11、0.51±0.03) . PlGF positive expression index on day 7, 14, 28 (2.27±0.34 vs0.13±0.01、1.78±0.41 vs0.14±0.03、1.25±0.69 vs0.13±0.01) in the PQ group were all upregulated as compared with that of the control group. PlGF positive expression index on day 7, 14, 28 in the captopril and Losartan treatment groups were significantly decreased (1.53±0.78、1.17±0.79、0.97±0.61 and 1.36±0.63、1.24±0.80、0.83±0.47) . PlGF positive expression index on day 7 in the two intervention groups were significantly decreased, as compared with PQ group (P<0.05) . Conclusion PlGF may plays an important role in the development of pulmonary fibrosis following paraquat-induced lung injury in rats. Captopril and losartan had an inhibitory effect on paraquat-induced pulmonary fibrosis, and the effect may be due to inhibition of angiotensin II and, in part, be associated with reduction in PlGF.

OBJECTIVETo analyze the clinical and PMM2 gene mutation features of congenital disturbance of glycosylation caused by PMM2 gene mutation (PMM2-CDG, previously known as CDG 1a).

METHODThe clinical data of two Chinese patients who were clinically diagnosed as PMM2-CDG at neurology department of Beijing Children's Hospital in 2012 were retrospectively collected. The gene mutations were identified by Sanger sequencing.

RESULTBoth patients were female, aged 1 year and 1 month and 8 months respectively. The main clinical features of the two cases were developmental delay after birth, chronic diarrhea and metabolic acidosis, associated with elevated serum transaminases, and decreased antithrombin III activity. Physical examination showed esotropia, inverted nipples, and abnormal subcutaneous fat pads. The cranial MRI showed cerebellar atrophy. Both cases were treated with occupational therapy, physical therapy and speech therapy. The development was gradually improved but also delayed as compared with normal peers during follow-up for more than 3 years. Genetic analysis showed that patient 1 was compound heterozygous for c. 422G>A(p.Arg141His), which was reported for known pathogenic mutation, and c. 669C>A(p.Asp223Glu), was a new mutation. The patient 2 showed compound heterozygous mutation for c. 634A>G (p.Met212Val)and c. 713G>C(p.Arg238Pro), which were both new mutations.

CONCLUSIONPMM2-CDG is a rare metabolic disease, and the diagnosis should be considered in a child with developmental delay, elevated serum transaminases, decreased antithrombin III activity, inverted nipples, abnormal subcutaneous fat pads, esotropia, and cerebellar atrophy on MRI. It can be confirmed by PMM2 gene analysis.

Asian Continental Ancestry Group ; Congenital Disorders of Glycosylation ; genetics ; DNA Mutational Analysis ; Developmental Disabilities ; Female ; Genetic Testing ; Glycosylation ; Heterozygote ; Humans ; Infant ; Magnetic Resonance Imaging ; Mutation ; Phosphotransferases (Phosphomutases) ; genetics ; Retrospective Studies

OBJECTIVETo investigate the clinical and genetic features of a Chinese girl with Schwartz-Jampel syndrome (SJS).

METHODTo analyze the clinical and genetic data of a girl with Schwartz-Jampel syndrome who was sent to neurology outpatient department of Beijing Children's Hospital in Auguest of 2010. Reports on Schwartz-Jampel syndrome published until July of 2015 were searched and the clinical and genetic characteristics of reported cases were summarized.

RESULTAt 8 months after birth, the girl showed myotonia; at 1 year old when she was walking alone she had myotonia of lower limbs, both feet evaginated, walked slowly and was prone to fall. At 2 years of age, she could not climb up stairs, at 3 years she could not jump continuously. At 3 years and 7 months of age when the girl was taken to neurology outpatient department, on examination, she had a dull facial expression, rigid lips and could not fully open her mouth, a micromandible, low-set and prominent ears, systemic muscle rigidity, there were muscular nodes formation on the limbs and gait stiffness. She had high level of creatine kinase and atlanto-axial joint subluxation on cervical CT reconstruction. She also had spontaneous myotonia-like discharges on needle electromyography (NEMG). X-ray of limbs showed metaphyseal dysplasia. The patient was treated with neurologic rehabilitation and carbamazepine. The myotonia at the last follow-up at her 8 years of age was the same as at the onset. On her HSPG2 gene, two novel heterozygous mutations c.10776delT on exon 78 and c.5702-5G>A on intron 45 were found. c.10776delT resulted in the amino acid change on p.Ala3592fsX6 and c.5702-5G>A maybe changed protein splicing. No reports were found among Chinese journals, while 7 reports were found in English literature. The total 34 mutations were known in reviewed reports, which included eleven deletion or insertion, twelve splice site, eight missense, and three nonsense mutations. Four patients had a single mutation. No definite genotype-phenotype correlation was identified.

CONCLUSIONSchwartz-Jampel syndrome is a rare autosomal-recessive hereditary disease appears to be slowly progressive, in which distinctive clinical features were induced by HSPG2 gene mutation. We reported the c.10776delT on exon 78 and c.5702-5G>A on intron 45 which were not reported previously. This is the first report of Schwartz-Jampel syndrome of which genetic mutations was identified in a Chinese child.

Asian Continental Ancestry Group ; Carbamazepine ; therapeutic use ; Child ; Child, Preschool ; Exons ; Female ; Heterozygote ; Humans ; Infant ; Introns ; Mutation ; Osteochondrodysplasias ; diagnosis ; genetics

Objective:To investigate the genetic association of single nucleotide polymorphisms (SNPs) in gamma-aminobutyric acid type A (GABAA) receptor genes cluster on chromosome 15q12 with autism in Chinese Han population.Methods:Totally 502 autism trios of Chinese Han ethnicity (including 502 autism individuals and 1004 healthy biological parents) were selected.All children met the autism diagnosis of Diagnostic and Statistical Manual of Mental Disorders,Fourth edition (DSM-Ⅳ).Genotyping for 15 selected tag SNPs in three GABAA receptor genes (GABRB3,GABRA5,and GABRG3) was performed using Agena Bioscience MassARRAY platform.The family-based association test for 15 tag SNPs was performed to compare the transmitted frequency of al leles of heterozygous genotypes from parents to offspring in autism trios.Results:The C allele of rs7180500 in GABRG3 and the A allele of rs4906902 in GABRB3 exhibited the preferential transmission from parents to affected offspring (Z =3.573,P ＜0.001;Z =3.141,P =0.002),and the association was significant after Bonferroni correction.Conclusion:It suggests that GABRG3 and GABRB3 which located in chromosome 15q12 might be susceptibility genes in Chinese Han population.

Objective: To summarize the clinical features of leukoencephalopathy with vanishing white matter disease (VWM) in children. Methods: A retrospective cohort study was performed on 54 genetically diagnosed VWM patients in Peking University First Hospital from January 2007 to March 2019. Paper registration form and electronic medical record system were used to collect the data,and the children were divided into five groups according to the age of disease onset:<1 year, 1-<2 years, 2-<4 years, 4-<8 years and 8-<18 years respectively. The progression of motor function, episodic aggravation, epileptic seizures, survival time, brain magnetic resonance imaging (MRI) and genotype features were analyzed and compared. Non-parametric test, χ² test or Fisher′s exact test were used for comparison among groups; Kaplan-Meier survival curve was adopted to delineate the survival status of the children. Results: Fifty-four VWM patients were included in the study, including 34 males and 20 females.The age of disease onset was 2 years and 8 months (ranged from 6 months to 9 years and 7 months). Onset age was less than 1 year in 5 cases; onset age was 1-<2 years in 12 cases; onset age was 2-<4 years in 25 cases; onset age was 4-<8 years, in 10 cases; onset age was 8-<18 years in 2 cases; 94% (51/54) of patients had complaint of motor regression at the first visit; 87% (47/54) of patients suffered from episodic aggravation. Episodic seizures occurred in 43% (23/54) patients. In survivors with disease durations of 1-3 years, in 38% (9/24) patients the disease was classified as grades Ⅳ-Ⅴ by gross motor function classification system (GMFCS). For the onset age 1-<2 years group, 1 patient was classified as GMFCS Ⅳ among 3 survivors with disease durations of 1-3 years. As for the 2-<4 years group, 6 patients were classified as GMFCS Ⅳ-Ⅴ among 15 patients with disease durations of 1-3 years, whereas 1 patient was classified as GMFCS Ⅳ-Ⅴ among 4 patients with disease durations of 1-3 years in the 4-<8 years group. Lesions, liquefaction and diffusion restriction in brain MRI were compared among different groups, and it was revealed that the earlier the age of disease onset was, the more likely the subcortical white matter (frontal lobe P<0.01,temporal and parieto-occipital lobe both P=0.002), internal capsule (anterior limb P<0.01, posterior limb P=0.00) and brain stem (midbrain P=0.001, pons P<0.01) were to be involved. In addition, internal capsule (anterior limb P=0.002, posterior limb P=0.005) and brain stem (midbrain P=0.001, pons P=0.003) showed more diffuse restricted diffusion. Moreover, the subcortical white matter (frontal and parieto-occipital lobe both P<0.01, temporal lobe P=0.005) showed earlier rarefaction. The 1-year and 2-year survival rates of the overall patients were 81% and 75% respectively, while the 15-year survival rate was 45%. EIF2B5 gene variation was the most common, which accounts for 43% (23/54), followed by EIF2B3 (22%, 12/54). Conclusions The majority of VWM patients complained of motor regression at the first visit, episodic aggravation and epileptic seizures are common in the course. Earlier age at onset is associated with more rapid clinical progression, shorter survival time as well as more extensive lesions, liquefaction and diffusion restriction in brain MRI. The most common variant gene is EIF2B5, followed by EIF2B3.