Community associated methicillin-resistant Staphylococcus aureus is a human pathogen.It can cause a series of infections cause morbidity and mortality,including bacteremia,pneumonia and soft tissue infections.USA300 clone is highly toxic and contagious.Its prevalence in the United States continues to rise,and has begun to spread to the rest of the world.This article briefly reviews the recent research on relevant aspects of molecular epidemiological characteristics,grug resistance mechanisms and treatment of USA300 clone.

Objective To assess the efficacy and safety of two different protocols of ketogenic diet (KD)-eating on demand or eating at regular intervals for refractory epilepsy in children.Methods Sixty children with refractory epilepsy were randomly divided into eating on demand group (n =30) and eating at regular intervals group (n =30) by random number table method.After taking the whole amount of KD,the capillary blood ketone and glucose level and urine ketone were monitored every 6 hours in 72 continuous hours.Seizure frequency and onset time were recorded.Antiepileptic efficacy and diet tolerability of the two groups were evaluated on 4 weeks,12 weeks,24 weeks and 48 weeks after initiating the diet.Adverse effects were monitored.Results After treatment of 4 weeks,the complete seizure remission rates of eating on demand group and eating at regular intervals group were 33.3％ (10/30) and 30.0％ (9/30) respectively,which suggested a comparable efficacy for two groups (P ＞ 0.05).The day when KD started to work was averaged (6.18 ± 2.42) d and (8.63 ± 2.63) d respectively.The group of eating on demand showed a faster onset of action (P ＜0.05).After treatment of 12 weeks,24 weeks and 48 weeks,complete seizure remission rates of eating on demand group were 30.0％ (9/30),34.8％ (8/23) and 36.8％ (7/19) respectively;the eating at regular intervals group were 33.3％ (10/30),30.4％ (7/23) and 44.4％ (8/18) respectively.The two groups had no significant difference (P ＞ 0.05).One year later,the treatment retention rates of the two groups were 63.3 ％ (19/30) and 60.0％ (18/30) respectively.There was no significant difference (P ＞ 0.05).The adverse effects mainly including transient gastrointestinal symptoms and metabolic disturbances were mostly tolerable and curable.Conclusion The two different protocols of KD-eating on demand and eating at regular intervals are both effective and well-tolerated for refractory epilepsy in children.While protocol of eating on demand is more easier to achieve ketotic state and the effect is more quickly,so it can be more easily received by children.Therefore in clinical practice,we can choose flexible eating time according to children's eating habits,which can improve the therapeutic compliance.

BACKGROUND: Growth factors and other biological methods have become very popular in the repair of degenerative interevrtebral disc. Insulin-like growth factor-1 (IGF-1) can promote the proliferation of nucleus pulposus cells, and synthesis of functional extracellular matrix, but the mechanisms remain unclear.OBJECTIVE: To investigate the effect of IGF-Ⅰ on the expressions of aggrecan and collagen type Ⅱ in nucleus pulposus cells, and to explore its signal transduction mechanism.METHODS: The human nucleus pulposus cells were isolated and cultured. Passage 3 nucleus pulposus cells were induced in different concentrations of IGF-1 (0, 20, 50, 100 and 200 μg/L), respectively. The expressions of aggrecan and collagen type Ⅱ were detected by reverse transcription PCR and western blot assay. Western blot assay was adopted to observe the effect of 100 μg/L IGF-1 on the activation of PI3K/Akt signaling pathway in nucleus pulposus cells,and the expression of aggrecan and collagen type Ⅱ was detected after the inhibition of PI3K/Akt pathway by LY294002.RESULTS AND CONCLUSION: With the increase of IGF concentration, the expression levels of aggrecan and collagen type Ⅱ were increased gradually. 100 μg/L IGF-1 could significantly promote the expressions of p-PI3K and p-Akt (P <0.01), while LY294002 reversed this effcet (P < 0.01). 100 μg/L IGF-1 significantly upregulated the expression levels of aggrecan and collagen type Ⅱ in nucleus pulposus cells (P < 0.01); in contrast, LY294002 significantly downregulated the expression levels of aggrecan and collagen type Ⅱ promoted by IGF-1(P < 0.01). These results indicate that IGF-1 can promote the expression levels of aggrecan and collagen type Ⅱ in nucleus pulposus cells via the PI3K/Akt signaling pathway.

Objective To compare the clinical and electroencephalogram(EEG)characteristics and therapeutic response prognosis of different age groups of children with epileptic spasm .Methods From January 2002 to October 2011 the clinical data ,EEG fea-tures of epileptic spasms children under 15 years old with unknown disease cause(cryptogenic) were retrospectively reviewed .74 of them were followed up for 12 to 92 months .All of them were divided into two groups on the basis of onset age :3 -12 months of onset as group infantile-onset spasms(group IOS ,n=60);and 12 months to 7 years old of onset as group late-onset epileptic spasms (group LOS ,n=14) .Clinical process ,seizure semiology and EEG features were compared between two groups .Results Semiologic features of two groups were similar ,but they showed differences in interictal EEG features including the background ,the location of discharges ;The response to drugs between the two groups are also different .Conclusion There are differences between group IOS and group LOS when comparing EEG features and response to drugs .

OBJECTIVETo report the clinical characteristics, biochemical profiles, diagnosis and treatment of one Chinese pedigree with glucocorticoid-remediable aldosteronism (GRA) and to study its molecular mechanism.

METHODSPlasma and urinary aldosterone, cortisol and plasma renin activities were dynamically tested and diagnostic therapy with dexamethasone was undergone in 3 affected subjects. Long-distance PCR as well as DNA sequencing were applied to detect the fusion gene in this pedigree.

RESULTSIn this GRA pedigree, there were 4 affected subjects who had hypertension, hypokalemia and low basic and provoked renin activity. Three patients were given dexamethasone treatment, and had a significant decrease in plasma aldosterone concentrations (PACs) (from 192 +/- 9 ng/L to 87 +/- 7ng/L, P < 0.05) after 5 days. Among them, one patient (II -3) responded quite satisfactorily to the therapy, with serum K(+) rising from baseline value of 2.5 to 2.9, 3.8 and 4.15 mEq/L on the 10th, 28th and 35th days after treatment respectively. Three weeks later, his blood pressure decreased from its original level of 146.3 +/- 1 0.7/94.6 +/- 5.3 mm Hg to 138.3 +/- 3.1/87.3 +/- 6.1 mm Hg (P < 0.05). The other 2 members (III -2 and III -4) showed modest improvement although their PACs decreased significantly. Using long-distance PCR, we found a 3.9 kb band in all 4 affected individuals, which was absent in 5 unaffected members from this pedigree or 8 patients with aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). By DNA sequence analysis, we found that the breakpoint of "unequal crossing-over" is both within intron 2 of the 11beta-hydroxylase gene (CYP11B1) and the aldosterone synthase gene (CYP11B2).

CONCLUSIONSThe excess of mineralocorticoid in patients with GRA can be inhibited by exogenous glucocorticoids. The fusion gene resulting from unequal crossing-over between the 11beta-hydroxylase gene and the aldosterone synthase gene is the pathogenesis of this Chinese GRA pedigree.

Adrenocorticotropic Hormone ; physiology ; Adult ; Aldosterone ; blood ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Hyperaldosteronism ; blood ; drug therapy ; genetics ; Mutation ; Pedigree

OBJECTIVE To generate hemophilia A (HA) patient-specific inducible pluripotent stem cells (iPSCs) and induce endothelial differentiation. METHODS Tubular epithelial cells were isolated and cultured from the urine of HA patients. The iPSCs were generated by forced expression of Yamanaka factors (Oct4, Sox2, c-Myc and Klf4) using retroviruses and characterized by cell morphology, pluripotent marker staining and in vivo differentiation through teratoma formation. Induced endothelial differentiation of the iPSCs was achieved with the OP9 cell co-culture method. RESULTS Patient-specific iPSCs were generated from urine cells of the HA patients, which could be identified by cell morphology, pluripotent stem cell surface marker staining and in vivo differentiation of three germ layers. The teratoma experiment has confirmed that such cells could differentiate into endothelial cells expressing the endothelial-specific markers CD144, CD31 and vWF. CONCLUSION HA patient-specific iPSCs could be generated from urine cells and can differentiate into endothelial cells. This has provided a new HA disease modeling approach and may serve as an applicable autologous cell source for gene correction and cell therapy studies for HA.
Cell Differentiation ; Hemophilia A ; pathology ; therapy ; urine ; Humans ; Induced Pluripotent Stem Cells ; cytology ; transplantation ; Urine ; cytology

OBJECTIVE: To explore the prenatal screening and diagnosis for a pair of monochorionic-diamniotic (MCDA) twins discordant for 45,X/46,XX mosaicism. METHODS: Amniotic fluid samples were taken from both twins for whom non-invasive prenatal testing has signaled a high risk for sex chromosomal abnormality. Uncultured amniotic fluid was analyzed by fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array). Conventional G-banded karyotyping analysis was performed on the cultured amniotic fluid. RESULTS: Metaphase chromosome analysis showed that one of the twins had a mos 45,X[11]/46,XX[26] karyotype, while the other had a normal karyotype. FISH and SNP-array applied on uncultured amniotic fluid revealed about 30% mosaicism in one of the twins. The twins were confirmed to be monozygotic by SNP-array analysis. CONCLUSION To avoid confusion arising from discordant karyotypes in MCDA twins with abnormal non-invasive prenatal testing (NIPT) results, dual amniocentesis should be carried out to obtain amniotic fluid samples for chromosomal as well as molecular analysis. To determine the ratio of 45,X and 46,XX cells in Turner syndrome can provide valuable information for prenatal genetic counseling.
Amniocentesis ; Chromosomes, Human, X ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Mosaicism ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To explore the genetic basis of a child featuring intellectual disability, developmental delay and epilepsy. METHODS: Cytogenetic and molecular analysis including chromosomal karyotyping analysis, single nucleotide polymorphism array (SNP array) and qPCR were performed. RESULTS: The karyotype of the child was determined as 46, XX; SNP array: arr [19]21q22.12q22.13(36 860 195-38 801 482)×1 dn. A heterozygous 1.9 Mb microdeletion was detected at 21q22.12q22.13. qPCR has confirmed deletion of exon 1 of the DYRK1A gene, which has occurred de novo. CONCLUSION A 21q22 deletion was diagnosed with multiple genetic methods. Genotype-phenotype correlation suggested DYRK1A to be a candidate for intellectual disability.
Child ; Developmental Disabilities ; genetics ; Epilepsy ; genetics ; Genetic Association Studies ; Humans ; Intellectual Disability ; genetics ; Karyotyping ; Protein-Serine-Threonine Kinases ; genetics ; Protein-Tyrosine Kinases ; genetics ; Sequence Deletion

OBJECTIVE: To explore the genetic etiology of a pedigree with mental retardation and hypotonia by using chromosome microarray analysis (CMA), low coverage massive parallel copy number variation sequencing (CNV-seq) and quantitative PCR (qPCR). METHODS: Genomic DNA was extracted from peripheral blood samples from two male patients and healthy members from the pedigree. CNV-seq was carried out for one patient. Suspected CNV was verified by qPCR. CNV-seq or single nucleotide polymorphism array (SNP array) were carried out for another patient and his family members. RESULTS: Both patients showed severe hypotonia and global development delay, in particular language delay. CNV-seq and SNP array indicated that both patients had carried a Xq28 duplication, with spanned 0.26 Mb and 0.42 Mb, respectively. Both duplications encompassed the MECP2 gene. CNV-seq analysis of their family members confirmed that the mother and one sister had carried similar duplications, while an elder brother was normal. CONCLUSION CNV-seq and CMA are rapid and effective tools for the diagnosis of MECP2 duplication syndrome in children with mental retardation, hypotonia and recurrent infections.

Objective:To analyze fetal sex chromosome abnormalities in prenatal diagnosis based on amniotic fluid cell culture.Methods:Clinical data of 12 164 pregnant women who underwent amniocentesis in Maternal and Child Health Hospital of Hunan Province from January 2017 to December 2020 were retrospectively analyzed. For those diagnosed with fetal sex chromosome abnormalities, the results of karyotyping and chromosome microarray analysis (CMA) were analyzed and described.Results:(1) Among the 12 164 cases, fetal sex chromosome abnormalities were detected in 387 cases (3.2%), including 351 cases with abnormal sex chromosome karyotype and 36 with sex chromosome microdeletion/microduplication. (2) High-risk patients indicated by non-invasive prenatal test (NIPT) had the highest proportion of sex chromosomes abnormalities (74.2%, 287/387), followed by those with other ultrasound abnormalities (8.5%, 33/387), high risk of Down syndrome screening (7.0%, 27/387), advanced maternal age (4.7%, 18/387), history of adverse pregnant or delivery (3.3%, 13/387), and nuchal translucency thickening or cervical lymphatic hygroma (2.3%, 9/387). (3) Detected chromosome karyotype abnormalities included numerical abnormalities [73.2%(257/351)], mosaicism [18.8(66/351)], and structural abnormalities [8.0%(28/351)], among which, 47,XXY [46.7%(120/257)], 45,X/46,XX[48.5%(32/66)], and X chromosome deletion [39.3%(11/28)] were the most common, respectively. Among 36 sex chromosome microdeletions/microduplications cases, 15(41.7%) were with pathogenic copy number variation (CNV), including 14 cases of X chromosome microdeletion/microduplication; 7(19.4%) with benign CNV, and 14(38.9%) with CNV of unknown clinical significance. The fragment size [ M (min-max)] of the 15 pathogenic CNV was 1.68 Mb(0.37-9.20 Mb). Of the nine cases with microdeletions, seven were found with deletion in the Xp22.31 region. Conclusions:Numerical abnormalities are the most common fetal sex chromosome abnormalities detected from amniotic fluid samples. Others included mosaicism and chromosome structure abnormalities.