[Investigation of influencing factors and reference ranges for thyroid function in hospitalized preterm infants at the age of 7 days]. / 7æ—¥é¾„ä½é™¢æ—©äº§å„¿ç”²çŠ¶è ºåŠŸèƒ½å½±å“å› ç´ åŠå‚è€ƒå€¼èŒƒå›´æŽ¢è®¨.

OBJECTIVES: To investigate the influencing factors and reference ranges for thyroid function in preterm infants at the age of 7 days, with the aim of avoiding unnecessary clinical reexamination and intervention. METHODS: A retrospective analysis was performed for the data of 685 preterm infants from January 2020 to January 2023. According to gestational age and birth weight, they were divided into a high-risk group (gestational age <34 weeks or birth weight<2 000 g; 228 infants) and a low-risk group (gestational age ≥34 weeks and birth weight ≥2 000 g;457 infants). The influencing factors for thyroid function were analyzed, and 95% reference range was calculated. RESULTS: Gestational age, birth weight, birth season, sex, and assisted reproduction were the influencing factors for thyroid function (P<0.05). For the preterm infants in the high-risk group, the reference ranges of free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH) were 2.79-5.40 pmol/L, 8.80-25.64 pmol/L, 0.80-2.15 nmol/L, 50.06-165.09 nmol/L, and 0.80-18.57 µIU/mL, respectively. For those in the low-risk group, the reference ranges of these indicators were 3.08-5.93 pmol/L, 11.17-26.24 pmol/L, 1.02-2.27 nmol/L, 62.90-168.95 nmol/L, and 0.69-13.70 µIU/mL, respectively. FT3, FT4, TT3, and TT4 were positively correlated with gestational age (P<0.05); FT3, FT4, TT3, and TT4 were positively correlated with birth weight (P<0.05); TSH was negatively correlated with birth weight (P<0.05). CONCLUSIONS: Thyroid function in preterm infants at the age of 7 days is affected by the factors such as gestational age and birth weight, and the reference ranges of thyroid function in preterm infants at the age of 7 days should be established based on gestational age and birth weight.

Study on the Chronic Diseases Curative Care Expenditure in Jilin under the Background of Health Care Grading System / 中国卫生经济

Objective:To comprehensively analyze the present situation and characteristics otthe curative care expenditure of chronic diseases in Jilin,and to provide data support and suggestions for health policy formulation.Methods:The System of Health Accounts 2011 (SHA2011) was used to analyze the total and composition of curative care expenditure of non-communicable chronic diseases in Jilin province.Results:In 2014,the curative care expenditure of chronic diseasesin Jilin province reached to 32.02 billion yuan,which accounted for 65.51％ of curative care expenditureof the all diseases in Jilin.From the perspective of disease costs,the curative care expenditure of chronic diseases occurred in cardiovascular disease,malignancy and other chronic diseases reachedto 66.22％.From the perspective of service composition,the curative care expenditure ofchronic diseases except oral disease occurred more in the hospital.From the perspective of medical institutions costs,thecurative care expenditureof chronic diseases occurred in urban medical institutions reached to 65.83％.From the perspective of care financing,the household out-of-pocket (OOP) accounted for 41.77％of curative care financing forchronic diseases in Jilin.Condusion:Thecurative care expenditureof chronic diseases in Jilin had a large scale.The distribution of medical institutions costsof chronic diseases showed as "inverted triangle" in Jilin.The financing structure of thecurative care expenditureof chronic diseases needed to be improved.

Study on the Chronic Diseases Curative Care Expenditure in Jilin under the Background of Health Care Grading System / 中国卫生经济

Objective:To comprehensively analyze the present situation and characteristics otthe curative care expenditure of chronic diseases in Jilin,and to provide data support and suggestions for health policy formulation.Methods:The System of Health Accounts 2011 (SHA2011) was used to analyze the total and composition of curative care expenditure of non-communicable chronic diseases in Jilin province.Results:In 2014,the curative care expenditure of chronic diseasesin Jilin province reached to 32.02 billion yuan,which accounted for 65.51％ of curative care expenditureof the all diseases in Jilin.From the perspective of disease costs,the curative care expenditure of chronic diseases occurred in cardiovascular disease,malignancy and other chronic diseases reachedto 66.22％.From the perspective of service composition,the curative care expenditure ofchronic diseases except oral disease occurred more in the hospital.From the perspective of medical institutions costs,thecurative care expenditureof chronic diseases occurred in urban medical institutions reached to 65.83％.From the perspective of care financing,the household out-of-pocket (OOP) accounted for 41.77％of curative care financing forchronic diseases in Jilin.Condusion:Thecurative care expenditureof chronic diseases in Jilin had a large scale.The distribution of medical institutions costsof chronic diseases showed as "inverted triangle" in Jilin.The financing structure of thecurative care expenditureof chronic diseases needed to be improved.

[Molecular diagnosis of children with unexplained intellectual disability/ developmental delay by array-CGH].

OBJECTIVE: To analyze the potential pathogenic genomic imbalance in children with unexplained intellectual disability (ID) and/or developmental delay (DD) and its association with phenotypes, and to investigate the value of array-based comparative genomic hybridization (array-CGH) in clinical molecular genetic diagnosis. METHODS: The whole genome of 16 children with ID/DD was scanned by the array-CGH for detection of genomic copy number variations (CNVs), and the revealed genomic imbalance was confirmed by multiplex ligation-dependent probe amplification. RESULTS: G-band karyotyping of peripheral blood cells showed no abnormalities in the 16 children. The results of the array-CGH revealed that 6 (38%) of the 16 patients had genomic CNVs, and 3 cases of CNVs were normal polymorphic changes; 1 CNV was a microdeletion of 4p16.3, which was the critical region for Wolf-Hirschhorn syndrome, and 1 CNV was a microdeletion of 7q11.23, which was the critical region for Williams-Beuren syndrome. Moreover, a CNV was identified with two duplications at 2q22.2 and 15q21.3 in a boy, which proved to have a clinical significance due to its association with ID, brain DD, unusual facies, cryptorchidism, irregular dentition, etc. CONCLUSIONS: Array-CGH allows for the etiological diagnosis in some of the children with unexplained ID/DD. As a high-throughput and rapid tool, it has a great clinical significance in the etiological diagnosis of ID/DD.

Whole dystrophin gene analysis by next-generation sequencing: a comprehensive genetic diagnosis of Duchenne and Becker muscular dystrophy.

Duchenne/Becker muscular dystrophies are the most frequent inherited neuromuscular diseases caused by mutations of the dystrophin gene. However, approximately 30% of patients with the disease do not receive a molecular diagnosis because of the complex mutational spectrum and the large size of the gene. The introduction and use of next-generation sequencing have advanced clinical genetic research and might be a suitable method for the detection of various types of mutations in the dystrophin gene. To identify the mutational spectrum using a single platform, whole dystrophin gene sequencing was performed using next-generation sequencing. The entire dystrophin gene, including all exons, introns and promoter regions, was target enriched using a DMD whole gene enrichment kit. The enrichment libraries were sequenced on an Illumina HiSeq 2000 sequencer using paired read 100 bp sequencing. We studied 26 patients: 21 had known large deletion/duplications and 5 did not have detectable large deletion/duplications by multiplex ligation-dependent probe amplification technology (MLPA). We applied whole dystrophin gene analysis by next-generation sequencing to the five patients who did not have detectable large deletion/duplications and to five randomly chosen patients from the 21 who did have large deletion/duplications. The sequencing data covered almost 100% of the exonic region of the dystrophin gene by ≥10 reads with a mean read depth of 147. Five small mutations were identified in the first five patients, of which four variants were unreported in the dmd.nl database. The deleted or duplicated exons and the breakpoints in the five large deletion/duplication patients were precisely identified. Whole dystrophin gene sequencing by next-generation sequencing may be a useful tool for the genetic diagnosis of Duchenne and Becker muscular dystrophies.

The SEPS1 G-105A polymorphism is associated with risk of spontaneous preterm birth in a Chinese population.

Inflammation plays an important role in the etiology and pathophysiology of spontaneous preterm birth (SPTB), and selenoprotein S (SEPS1) is involved in regulating the inflammatory response. Recently the G-105A promoter polymorphism in SEPS1 was shown to increase pro-inflammatory cytokine expression. We examined whether this functional polymorphism was related to the risk of SPTB in a Chinese population. We also examined the impact of premature rupture of membranes (PROM) on susceptibility to SPTB. The SEPS1 G-105A polymorphism was genotyped in 569 preterm singleton neonates and 673 term neonates by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. χ (2) tests and logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs). We observed that, compared with the GG genotype, -105A positive genotypes (GA + AA genotypes) were associated with significantly increased susceptibility to SPTB (adjusted OR, 1.87; 95% CI, 1.36-2.57; P<0.001). The -105A positive genotypes were also significantly associated with increased susceptibility to SPTB, both in the patients with PROM (adjusted OR, 2.65; 95% CI, 1.73-4.03; P<0.001) and in those without PROM (adjusted OR, 1.56; 95% CI, 1.09-2.24; P = 0.015). The -105A positive genotypes were also significantly associated with increased susceptibility to SPTB between extremely preterm neonates and controls (adjusted OR, 4.46; 95% CI, 1.86-10.73; P = 0.002) and between moderately preterm neonates and controls (adjusted OR, 1.76; 95% CI, 1.25-2.47; P = 0.001). Our findings suggest that the SEPS1 G-105A polymorphism contributes to the risk of developing SPTB in a Chinese population.

[Congenital central hypoventilation syndrome, report of three cases].

OBJECTIVE: To evaluate clinical characteristics and PHOX2B gene mutations in congenital central hypoventilation syndrome (CCHS) and to facilitate the early diagnosis and management of CCHS and reduce the misdiagnosis. METHOD: Clinical data of 3 infants with CCHS who had recurrent respiratory failure episodes and dependent on mechanical ventilation support in 3 from March 2008 to April 2012 were analyzed, and blood gas analysis was performed respectively in the awaken and sleeping status. Gene sequencing was used for detection of PHOX2B gene mutation. RESULT: All the three patients had adequate ventilation during awaken time, but they presented with abnormal frequency and shallow breathing associated with alveolar hypoventilation after falling asleep. Blood gas analysis showed hypercapnia and CO2 partial pressure was consistently over 60 mm Hg (1 mm Hg = 0.133 kPa) after falling asleep, which is in accordance with the clinical features of CCHS. The PHOX2B gene sequencing showed that 6 GCN repeats were inserted at exon3 of PHOX2B in case 1, at same position, 5 GCN repeats were inserted in case 2 and 3. CONCLUSION: Normal ventilation in awaken status while shallow slow breathing accompanied with hypercapnia in sleep are the main clinical characteristics of CCHS, which requires mechanical ventilation. Acquired mutation in exon 3 of PHOX2B gene encoding repeated GCN sequence seems to be the molecular etiology of these three patients.

[Clinical and molecular genetic analysis for a patient with glycogen storage disease â a].

OBJECTIVE: To investigate the mutation of glucose-6-phosphatase gene (G6PC gene) in a patient with glycogen storage disease Ⅰa. METHODS: PCR was used to amplify all five exons of G6PC gene. The PCR products were directly sequenced to detect the mutations. RESULTS: A heterozygous 743G>A mutation was found in the patient and his mother, resulting in the substitution of glycine (G) by arginine (R) in codon 222(G222R) in the putative membrane-spanning domain in human G6Pase, but not in his father and his sister. CONCLUSIONS: G222R mutation in G6PC gene was first identified in a patient with glycogen storage disease Ⅰa in mainland China.

[Clinical application of proportional assist ventilation in very low birth weight infants with ventilator dependence].

OBJECTIVE: To study the effect of proportional assist ventilation (PAV) on physiology and respiratory mechanics in very low birth weight (VLBW) infants with ventilator dependence by comparison with conventional assist/control (A/C) ventilation. METHODS: Forty-six infants with ventilator dependence were randomly divided into two groups according to the ventilation model: PAV (n=23) and A/C (n=23). The gain of resistive and elastic unloading was set based on the runway method in the PAV group. Ventilation parameters were set based on the conventional method in the A/C group. Infants were observed for 30 minutes three times per day for three consecutive days. Arterial gas analysis results, transcutaneous saturation of oxygen (SPO2), heart rate, blood pressure (BP), respiratory rate (RR), mean airway pressure (MAP), peak inspiratory pressure (PIP), tide volume (VT), minute volume (MV) and oxygenation index (OI), were compared between the two groups. RESULTS: Compared with the A/C group, PaO2 and OI in the PAV group were significantly higher while PIP and MAP were significantly lower. There were no significant differences in FiO2, SPO2, pH, PaCO2, PEEP, VT, MV and RR between the two groups. Although mean arterial blood pressure and heart rate in the PAV group were not different from the A/C group, beat-to-beat variabilities in systolic and diastolic arterial blood pressure were significantly lower in the PAV group than in the A/C group. CONCLUSIONS: PAV may safely maintain gas exchange at lower airway pressures compared with A/C ventilation in VLBW infants. It can also improve oxygenation and infant-ventilator synchronization.

[Value of methylation-specific mutiplex ligation-dependent probe in the diagnosis of Prader-Willi syndrome].

OBJECTIVE: Prader-Willi syndrome (PWS) with different pathogenesis has different clinical manifestations, prognosis and genetic risks. Pathogenesis of the disease cannot be explained by conventional diagnostic method MS-PCR. This study employed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) for the diagnosis of PWS in order to explore the role of this method in the diagnosis and assessment of pathogenesis of PWS. METHODS: A system antithetical method was employed. Peripheral blood samples were collected from 30 children for MS-PCR. Of the 30 children, 16 were diagnosed with PWS by MS-PCR and the other 14 showed negative MS-PCR. MS-MLPA kit Me028 was used to detect DNA extracted from the 30 samples. RESULTS: The results showed by MS-MLPA and MS-PCR were identical. MS-MLPA demonstrated that 4 cases were maternal uniparental disomy and 12 cases were paternal dfeletion in 15q11-q13 region. CONCLUSIONS: MS-MLPA is a reliable method of genetic testing for PWS which can distinguish pathogenesis of PWS.

[Chromosome analysis in 92 children with congenital mental retardation].

OBJECTIVE: To explore the chromosome karyotypes in children with mental retardation. METHODS: The peripheral blood lymphocytes from 92 children with congenital mental retardation were cultured and analysed by the G-band technique. RESULTS: Of the 92 cases, 43 cases (47%) showed chromosome abnormalities. Autosomal abnormalities were found in 35 cases (38%) and sex chromosome abnormalities were found in 8 cases (9%). A novel abnormal karyotype 45, XX, psu dic (11;9) (p15;p24) was found in a child. CONCLUSIONS: Chromosome abnormalities may be important cytogenetic factors for congenital mental retardation. Cytogenetic chromosome karyotypic analysis appears to be an important method for genetic screening of congenital mental retardation.

A novel RSK2 (RPS6KA3) gene mutation associated with abnormal brain MRI findings in a family with Coffin-Lowry syndrome.

Coffin-Lowry syndrome (CLS) is an X-linked mental retardation syndrome caused by defects in the RSK2 gene. We have identified a CLS family with four patients in two generations. The patients in this family, a mother and her three children (a male and two females), all have severe mental retardation with the typical CLS phenotype. In addition, brain MRI studies on the three siblings revealed abnormalities in deep subcortical white matter, thinning of the corpus callosum, hypoplastic cerebellar vermis, and asymmetry of the lateral ventricles. The degree of severity of the MRI findings correlated with the severity of mental retardation in the patients. Extensive mutation screening was performed on the entire RSK2 gene in this family. Twenty-two exons including the intron/exon junctions were amplified by PCR and subsequently sequenced on both strands. A novel mutation, a two-nucleotide insertion (298 ins TG), was identified. The insertion creates a stop codon at codon 100, resulting in a 99 amino acid truncated RSK2 protein. All patients tested have the same mutation, and no other mutation could be found in the RSK2 gene from the proband. The mutation was confirmed by PCR/RFLP. X-chromosome inactivation assay on the female patients revealed significant skewing toward inactivation of the normal RSK2 allele. Thus, this novel mutation is likely to be responsible for the unusual clinical presentation in this family, which includes full phenotypic expression in females and unique brain MRI abnormalities. The pathological function of the mutation and genotype/phenotype correlation between the mutation and this unusual clinical presentation await further clarification.

Development of a molecular screening test for hereditary hearing loss and genetic susceptibility to aminoglycoside toxicity for Chinese population.

OBJECTIVE: To develop a molecular screening test for genetic defects on hearing loss related genes has significant impacts on early identification of hereditary hearing loss and genetic susceptibility to aminoglycoside ototoxicity. Early identification of pre-lingual hearing loss is very important for patient' s language development, academic achievement, and social skill. Two common mutations, the 235delC in GJB2 gene and the mutation A1555G in mitochondrial DNA, are included in the newly developed screening panel for Chinese population. METHODS: A molecular genetic assay, based on fluorescent labeled multiplex PCR and automatic DNA fragment analyzing techniques, was developed to detect both mutations simultaneously. RESULTS: This assay was able to detect both mutations from patient's samples, and pooled DNA tests, as well as suitable to detect mutation from the DNA extracted from dried blood spot and buccal swab. CONCLUSION: This assay could be a useful tool for newborn screening and carrier screening for the hereditary hearing loss for the Chinese population.