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OBJECTIVE: To evaluate the validity of intraoperative evoked potential (EP) including motor evoked potential (MEP) and somatosensory evoked potentials (SEP) as a biomarker for predicting neural function changes after thoracic spinal decompression (TSD) surgery. METHOD: A consecutive series of 336 TSD surgeries were reviewed between 2010 and 2021 from four spine center. All patients with TSD were divided into 3 groups according to different intraoperative EP results: group 1, EP alerts; group 2, no obvious EP deterioration; group 3, EP improvement compared with baselines. The lower limb Japanese Orthopedic Association (JOA) scores (as well as early and long-term JOA recovery rate) were utilized to quantitatively assess pre- and postoperative neural function change. RESULTS: Among the 3 subgroups according to the different EP changes, the early JOA recovery rate (RR%) in the EP improvement group was significantly better than the other two groups (51.3 ± 58.6* vs. 27.5 ± 31.2 and 33.3 ± 43.1; p < 0.01) after 3-month follow-up. The mean MEP and SEP amplitude were from 116 ± 57 µV to 347 ± 71 µV (p < 0.01) and from 1.86 ± 0.24 µV to 2.65 ± 0.29 µV (p < 0.01) between spinal cord pre-decompression and post-decompression. Moreover, multivariate logistic regression analysis revealed that risk factors of EP improvement were duration of symptom (p < 0.001, OR 10.9) and Preop. neurologic deficit degree (p = 0.013, OR 7.46). CONCLUSION: The intraoperative EP can predict postoperative neural function changes as a biomarker during TSD. Patient with EP improvement probably has better prognosis for early neural function recovery. The duration of symptom and preoperative neurologic deficit degree may be related to intraoperative EP improvement.
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Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Humanos , Potenciais Somatossensoriais Evocados/fisiologia , Potencial Evocado Motor/fisiologia , Coluna Vertebral , Biomarcadores , Descompressão , Estudos RetrospectivosRESUMO
BACKGROUND: The term "metabolically healthy obese (MHO)" denotes a hale and salutary status, yet this connotation has not been validated in children, and may, in fact, be a misnomer. As pertains to obesity, the gut microbiota has garnered attention as conceivably a nosogenic or, on the other hand, protective participator. OBJECTIVE: This study explored the characteristics of the fecal microbiota of obese Chinese children and adolescents of disparate metabolic statuses, and the associations between their gut microbiota and circulating proinflammatory factors, such as IL-6, TNF-α, lipopolysaccharide-binding protein (LBP), and a cytokine up-regulator and mediator, leptin. RESULTS: Based on weight and metabolic status, the 86 Chinese children (ages 5-15 years) were divided into three groups: metabolically healthy obese (MHO, n = 42), metabolic unhealthy obese (MUO, n = 23), and healthy normal weight controls (Con, n = 21). In the MUO subjects, the phylum Tenericutes, as well as the alpha and beta diversity, were significantly reduced compared with the controls. Furthermore, Phylum Synergistetes and genus Bacteroides were more prevalent in the MHO population compared with controls. For the MHO group, Spearman's correlation analysis revealed that serum IL-6 positively correlated with genus Paraprevotella, LBP was positively correlated with genus Roseburia and Faecalibacterium, and negatively correlated with genus Lactobacillus, and leptin correlated positively with genus Phascolarctobacterium and negatively with genus Dialister (all p < 0.05). CONCLUSION: Although there are distinct differences in the characteristic gut microbiota of the MUO population versus MHO, dysbiosis of gut microsystem is already extant in the MHO cohort. The abundance of some metabolism-related bacteria associates with the degree of circulating inflammatory compounds, suggesting that dysbiosis of gut microbiota, present in the MHO children, conceivably serves as a compensatory or remedial response to a surfeit of nutrients.
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Microbioma Gastrointestinal , Síndrome Metabólica/metabolismo , Obesidade Infantil/metabolismo , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: The make-up of gut microbiota at different puberty stages has not been reported. This cross-sectional study analyzed the bio-diversity of gut microbiota at different puberty stages. RESULT: The subjects (aged 5-15 years) were divided into non-pubertal (n = 42, male%: 66.7%) or pubertal groups (n = 47, male%:44.68); in both groups, Firmicutes, Bacteroidetes and Proteobacteria were the dominant phylum. There was no difference of alpha- and beta-diversity among disparate puberty stages. Non-pubertal subjects had members of the order Clostridiales, family Clostridiaceae, genus Coprobacillus which were significantly more prevalent than puberty subjects. Also, the pubertal subjects had members of class Betaproteobacteria, order Burkholderiales which were significantly more prevalent than the non-pubertal subjects. Their relative abundance was independent of BMI-Z. In the pubertal subjects, the abundance of genus Adlercreutzia, Ruminococcus, Dorea, Clostridium and Parabacteroides was associated with the level of testosterone. CONCLUSIONS: This is the first report of the diversity of gut microbiota at different puberty stages. The various species of gut microbiota changed gradually associated with puberty stages. Differences in gut microflora at different pubertal status may be related to androgen levels.
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Microbioma Gastrointestinal , Puberdade/fisiologia , Adolescente , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , RNA Ribossômico 16S/genética , Testosterona/sangueRESUMO
BACKGROUND: Accumulating evidence infer that gut microbiome-host relations are key mediators or modulators driving the observed sexual dimorphism in some disease onset and progression. To date, the sex-differences of gut microbiota at different pubertal status have not been reported. OBJECTIVE: To determine the characteristics of gut microbiota of both genders at different pubertal status. METHODS: Gut microbiota was analyzed in 89 Chinese participants aged 5-15 years. Participants were divided into pre-puberty and puberty groups for both male and female. The composition of gut microbiota was investigated by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed. The prediction of metagenomic functional content from 16S rRNA gene surveys was conducted. RESULTS: There were 49 males (9.76 ± 2.15 years) and 40 females (9.74 ± 1.63 years); 21 males and 26 females were at puberty. At genus level, Alistipes, Megamonas, Oscillospira and Parabacteroides were more prevalent in girls than in boys (p < 0.05). There were no significantly differences of alpha-diversity between genders, which was independent of pubertal status. The beta-diversity was significantly different in pubertal subjects between genders. Using statistical analyses, we assigned genera Dorea, Megamonas, Bilophila, Parabacteroides and Phascolarctobacterium as microbial markers for pubertal subjects. The predicted metabolic profiles differ in both pubertal and pre-pubertal groups between genders. CONCLUSION: This cross-sectional study revealed that sex differences in the gut microbiota composition and predicted metabolic profiles exist before puberty, which become more significant at puberty. The identification of novel puberty bacterial markers may disclose a potential effects of gender-related microbiota profiles on puberty onset.
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Bactérias/classificação , Microbioma Gastrointestinal , Metagenômica , Puberdade , Caracteres Sexuais , Adolescente , Criança , Pré-Escolar , China , Estudos Transversais , Fezes/microbiologia , Feminino , Humanos , Masculino , RNA Ribossômico 16S/genéticaRESUMO
OBJECTIVE: The following study investigated the serum adiponectin, chemerin and vaspin levels and their relationship with body mass index (BMI), glucose and lipid metabolism in girls with Turner Syndrome (TS). METHODS: A total of 64 girls with TS (mean age, 12.22⯱â¯3.98â¯years; mean BMI, 18.90⯱â¯3.45â¯kg/m2) were ascertained by chromosome analysis. Height, weight, waist circumference, hip circumference and blood pressure were measured, as well as the levels of fasting plasma glucose (FPG), fasting plasma insulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG). The BMI, BMI standard deviation score (SDS), waist to hip ratio, waist to height ratio and insulin resistance index (HOMA-IR) were calculated. The TS group and the control group were subdivided into non-puberty or puberty subgroup. RESULTS: The TS group had higher waist to hip ratio and waist to height ratio compared to the control group. There was no significant difference in FPG, fasting plasma insulin, HOMA-IR, blood lipid and blood pressure between the two groups. Significantly higher serum levels of adioponectin (12.51⯱â¯4.58⯵g/ml) and chemerin (173.71⯱â¯37.88â¯ng/ml) and significantly lower levels of vaspin (0.67⯱â¯0.47â¯ng/ml) were found in the TS group compared to the control group (9.30⯱â¯3.17⯵g/ml, 159.43⯱â¯23.19â¯ng/ml and 1.06⯱â¯0.49â¯ng/ml, respectively) (all Pâ¯<â¯0.05). In the TS group, adiponectin levels were negatively correlated with age, BMI and TG (râ¯=â¯-0.251, -0.247, -0.294, Pâ¯<â¯0.05 for all). In the control group, adiponectin levels were negatively correlated with BMI and BMI SDS (râ¯=â¯-0.416 and -0.315, Pâ¯<â¯0.05 for both), while vaspin levels were positively correlated with age, fasting plasma insulin and HOMA-IR (râ¯=â¯0.257, 0.273 and 0.282, Pâ¯<â¯0.05 for all). In addition, significantly higher levels of adiponectin were found in the non-puberty subgroup (13.88⯱â¯4.49)⯵g/ml compared to puberty subgroup (9.72⯱â¯3.39)⯵g/ml (Pâ¯<â¯0.05), while no significant differences in chemerin and vaspin were found between the two TS subgroups. CONCLUSIONS: Elevated adiponectin and chemerin levels and significantly reduced vaspin were found in girls with TS. Puberty or estrogen replacement therapy may reduce adiponectin in girls with TS.
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Adipocinas/sangue , Síndrome de Turner/sangue , Síndrome de Turner/metabolismo , Adolescente , Glicemia/fisiologia , Índice de Massa Corporal , Peso Corporal/fisiologia , Quimiocinas/sangue , Criança , Pré-Escolar , Feminino , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Lipídeos/sangue , Obesidade/sangue , Serpinas/sangue , Triglicerídeos/sangue , Síndrome de Turner/fisiopatologia , Circunferência da Cintura/fisiologia , Relação Cintura-Quadril/métodosRESUMO
OBJECTIVE: To explore the changes in T helper lymphocytes and their subsets in children with tic disorders (TD) and their clinical significance. METHODS: Flow cytometry was used to measure the percentages of T helper lymphocytes and their subsets in the peripheral blood of children with TD and healthy children (controls). RESULTS: The percentage of T helper lymphocytes was significantly lower in the TD group than in the control group (P<0.001). The abnormal rate of T helper lymphocytes in the TD group was significantly higher than that in the control group (68.7% vs 18.8%; P<0.001). The percentage of T helper lymphocytes was negatively correlated with Yale Global Tic Severity Scale score (r=-0.3945, P<0.001). As for the subsets of T helper lymphocytes, the TD group had a significantly higher percentage of Th1 cells and a significantly lower percentage of Th2 cells compared with the control group (P<0.001). CONCLUSIONS: The abnormality of T helper lymphocytes and the imbalance of their subsets may be associated with the pathogenesis of TD in children. The percentage of T helper lymphocytes can be used as an indicator for assessing the severity of TD.
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Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Transtornos de Tique/imunologia , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Masculino , Células Th1/imunologia , Células Th2/imunologia , Transtornos de Tique/genéticaRESUMO
PURPOSE: The objective is to compare the intraoperative monitoring (IOM) outcomes between degenerative cervical and thoracic spine decompression surgery. METHOD: A total of 97 patients with cervical compression myelopathy (CCM) and 75 patients with thoracic compression myelopathy (TCM) were prospectively collected between December 2012 and June 2015 in our spine center. Somatosensory-evoked potentials (SSEP) and motor-evoked potentials (MEP) were used for IOM. The postoperative neurologic status of each patient was assessed immediately after surgery. And the IOM and neurological outcomes were mainly analyzed in this study. RESULTS: Under the same alarm criteria, the IOM changes present significant difference between the cervical and thoracic surgery. During the patients with monitoring alerts, the MEPs usually manifest as sudden loss in TCM whereas the gradual loss in CCM. And there were three permanent neurologic injuries in the thoracic cases, but none in cervical cases. CONCLUSION: The IOM loss between CCM and TCM patients present obvious difference and the sudden MEPs loss associated with spinal decompression need to be taken seriously especially in TCM.
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Vértebras Cervicais/cirurgia , Monitorização Neurofisiológica Intraoperatória/métodos , Compressão da Medula Espinal/cirurgia , Vértebras Torácicas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais/diagnóstico por imagem , Descompressão Cirúrgica/efeitos adversos , Descompressão Cirúrgica/métodos , Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Compressão da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/etiologia , Vértebras Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: The relationship between soy isoflavones (SI)-induced gut dysbiosis and puberty onset has not been explored, and the protective effect of probiotic is still controversial. This study investigates the action of daidzein (the main components of SI) and probiotic on the age of puberty onset in female mice. METHODS AND RESULTS: Changes in the gut microbiota and production of short chain fatty acids (SCFAs) metabolism are highlighted to analyze a possible causative relationship to puberty onset in female c57/bl mice. The results demonstrate that daidzein promotes earlier onset of puberty, and can significantly alter the composition of the fecal bacterial community. Furthermore, daidzein alters the gut microbiota such that levels of butyrate, isovalerate, and hexanoate are reduced. Moreover, a probiotic treatment normalizes the timing of puberty onset, likely due to alteration in the gut microbiota to enhance SCFAs production. CONCLUSION: These findings provide evidence that 95% daidzein has the potential to advance the timing of puberty onset in female mice, and the gut microbiome can be a therapeutic target to regulate the timing of puberty onset.
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Isoflavonas , Probióticos , Camundongos , Feminino , Animais , Maturidade Sexual , Ácidos Graxos Voláteis/metabolismo , DisbioseRESUMO
OBJECTIVE: To investigate the characteristics of gut microbiota in children with disparate degrees of adiposity, and analyze the association between gut microbiota, glucose metabolism indicators, and inflammatory factors. METHODS: Clinical data were examined in 89 Chinese children. Children with a body fat percentage ≥ 30% were diagnosed as obese, and ≥ 35% in males and ≥ 40% in females were further defined as severe obesity. The composition of gut microbiota was determined by 16S rDNA-based metagenomics. RESULTS: The study population (9.75 ± 1.92-year-old) was characterized as normal weight (n = 29), mild obesity (n = 27) and severe obesity (n = 33) groups. Linear discriminant analysis Effect Size (LEfSe) analysis found that compared to the severe obesity group, subjects with mild obesity had more prevalent members of the phylum Fusobacteria, the genus Alistipes, and fewer members of genus Granulicatella and Clostridium (p < 0.05). For subjects with mild obesity, Spearman's correlation analysis revealed that fasting plasma glucose positively correlated with species A. indistinctus, A. putredinis, and negatively correlated with species Ruminococcus gnavus; LBP negatively correlated with species Clostridium hathewayi, and Blautia producta. For subjects with severe obesity, oral glucose tolerance test 2 h plasma glucose (OGTT2HPG) negatively correlated with the phylum Synergistetes, genus Pyramidobacter, species Veillonella parvula, P. piscolens, and positively correlated with species B. producta, INS and HOMA-IR negatively correlated with the genus Haemophilus, species H. parainfluenzae, lipopolysaccharide-binding protein (LBP) negatively correlated with the phylum Actinobacteria, genus Bifidobacterium, Lactobacillus, and species B. longum (all p < 0.05). Phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2) analysis discerned that the glucose metabolism pathway, gluconeogenesis I was curtailed in the severe obesity group. CONCLUSION: The gut microbiota could favourably compensate for glucose metabolism in children with obesity. Genus Haemophilus and Bifidobacterium longum may influence glucose tolerance and insulin resistance in children with severe obesity.
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Microbioma Gastrointestinal , Obesidade Mórbida , Masculino , Feminino , Humanos , Criança , Glicemia , Adiposidade , Filogenia , Obesidade/metabolismo , BactériasRESUMO
OBJECTIVE: Heterozygous loss-of-function variants in the NPR2 gene cause short stature with nonspecific skeletal abnormalities and account for about 2 ~ 6% of idiopathic short stature. This study aimed to analyze and identify pathogenic variants in the NPR2 gene and explore the therapeutic response to recombinant growth hormone (rhGH). METHODS: NPR2 was sequenced in three Chinese Han patients with short stature via exome sequencing. In vitro functional experiments, homology modeling and molecular docking analysis of variants were performed to examine putative protein changes and the pathogenicity of the variants. RESULT: Three patients received rhGH therapy for two years, and two NPR2 heterozygous variants were identified in three unrelated cases: c.1579 C > T,p.Leu527Phe in patient 1 and c.2842dupC,p.His948Profs*5 in patient 2. Subsequently, a small gene model was constructed, and transcriptional analysis of the synonymous variant (c.2643G > A) was performed in patient 3, which revealed the deletion of exon 17 and the premature formation of a stop codon (p.His840Gln*). Functional studies showed that both NPR2 variants, His948Profs*5 and His840Gln*, failed to produce cGMP in the homozygous state. Furthermore, the Leu527Phe variant of NPR2 was almost unresponsive to the stimulatory effect of ATP on CNP-dependent guanylyl cyclase activity. This loss of response to ATP has not been previously reported. The average age of patients at the start of treatment was 6.5 ± 1.8 years old, and their height increased by 1.59 ± 0.1 standard deviation score after 2 years of treatment. CONCLUSION: In this report, two novel variants in NPR2 gene were described. Our findings broaden the genotypic spectrum of NPR2 variants in individuals with short stature and provid insights into the efficacy of rhGH in these patients.
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Nanismo , Hormônio do Crescimento , Receptores do Fator Natriurético Atrial , Criança , Pré-Escolar , Humanos , Trifosfato de Adenosina , Estatura , Nanismo/tratamento farmacológico , Nanismo/genética , Hormônio do Crescimento/genética , Hormônio do Crescimento/uso terapêutico , Simulação de Acoplamento Molecular , Mutação , Receptores do Fator Natriurético Atrial/genéticaRESUMO
Objectives: To investigate the associations of obesity with growth and puberty in children. Methods: From November 2017 to December 2019, height, weight, and Tanner stages of 26,879 children aged 3-18 years in Fuzhou, China were assessed. Results: The obese group was significantly taller than the non-obese group after age 4 years for both genders, yet there was no significant difference in height between obese and non-obese group after 15.5 years old for boys and 12.5 years old for girls. The inflection points of significant growth deceleration in obese and non-obese groups were 14.4 and 14.6 years old for boys, and 11.8 and 12.8 years old for girls, respectively. The proportions of testicular development in boys with obesity and non-obesity were 7.96% and 5.08% at 8.5-8.9 years old, respectively, while the proportions of breast development in girls were 17.19% and 3.22% at age 7.5-7.9 years old, respectively. Conclusion: Children with obesity were taller in early childhood, earlier onset of puberty and earlier cessation of growth than children with non-obesity of the same age. However, there was sex dimorphism on the effect of obesity on the incidence of precocious puberty.
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Obesidade , Puberdade Precoce , Humanos , Criança , Pré-Escolar , Feminino , Masculino , Adolescente , Estudos Transversais , Obesidade/epidemiologia , Puberdade , Puberdade Precoce/epidemiologia , China/epidemiologiaRESUMO
OBJECTIVE: Familial male-limited precocious puberty (FMPP) is due to constitutive activation of a mutant luteinizing hormone/choriogonadotropin receptor (LH/CGR) leading to elevated testosterone synthesis in testicular Leydig cells. In the present study, we have analyzed the LHCGR gene for members of a Chinese FMPP family. METHODS: Physical examinations have included assessment of penile length, testicular volume and pubic hair. Bone age assessment, levels of testosterone and gonadotropin-releasing hormone (GnRH) stimulations tests were measured. DNA was extracted from blood samples of the proband and his parents using an QIAGEN Blood DNA Mini Kit. The 11 exons of LHCGR gene were amplified using an AmpliTaq PCR system, and the PCR products were sequenced using an ABI3130xl Genetic Analyzer. RESULTS: The affected boy was 3 year and 1 month old and showed typical clinical manifestation of peripheral precocious puberty. His height was 116.8cm (+5.1s) and Tanner stages were PH 2. Testicular volume was 8 mL bilaterally, penile was 8.5 cm × 2.5 cm. Basal testosterone was 2310 ng/L and bone age was 9 years. GnRH stimulation test revealed a prepubertal response to gonadotropin. The peak of LH was 2.66 IU/L, and the peak of FSH was 1.03 IU/L. Upon sequencing exon 11 of the LHCGR, a heterozygous point mutation of nucleotide 1703 from C to T was detected, which resulted in an amino acid transition from Ala (GCC) to Val (GTC) at position 568. Thus the mutation of LHCGR gene was confirmed to be constitutively active. After treating with aromatase inhibitors for half a year, the patient showed an increase in bone age and height by half a year and 4 cm, respectively. The same point mutation was detected in the patient's father, but did not have any influence on his puberty development. CONCLUSION: A novel point mutation of the LHCGR gene has been identified in a family affected with FMPP. The c.1703C>T mutant LHCGR was confirmed to be constitutively active, which has led to maturation and proliferation of Leydig cells. The variable phenotype within the family suggested variable expressivity of the disease.
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Mutação , Puberdade Precoce/genética , Receptores do LH/genética , Adulto , Substituição de Aminoácidos , Sequência de Bases , Pré-Escolar , Códon , Éxons , Humanos , Masculino , Modelos Moleculares , Conformação Proteica , Puberdade Precoce/diagnóstico , Receptores do LH/químicaRESUMO
Background: In adults, gut dysbiosis may contribute to the pathogenesis of gout. However, the characteristics of gut microbiota in children with hyperuricemia (HUA) in the absence of clinical gout have not been explored. Objective: This present study analyzed the gut microbiota in children with HUA as compared to controls (Con) and explored bacterial associations that may account for differences. Methods: A total of 80 children were enrolled in this study; they were divided into HUA and Con according to the level of serum uric acid (UA). The composition of gut microbiota was investigated by 16S rRNA high-throughput sequencing. Results: Principal coordinate analysis revealed that gut microbiota of the HUA group was clustered together and separated partly from the Con group. There was no difference in alpha-diversity between the two groups. However, Spearman's correlation analysis revealed that serum UA level positively correlated with genera Actinomyces, Morganella, and Streptococcus, and negatively associated with the producers of short-chain fatty acids (SCFAs), such as Alistipes, Faecalibacterium, and Oscillospira, and the sulfidogenic bacteria Bilophila. The members of the genera Alistipes and Bilophila in the Con group were significantly more prevalent than the HUA subjects. Compared to the Con cohort, metabolic pathway predictions found that the superpathways of purine nucleotide de novo biosynthesis were decreased in HUA subjects, whereas the superpathway of purine deoxyribonucleoside de gradation was increased. Conclusion: The composition of the gut microbiota in children with HUA differs from Con. Although causality cannot be established, modification in the microbiota that produces SCFA and sulfide may promote HUA.
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Microbioma Gastrointestinal , Gota , Hiperuricemia , Adulto , Bactérias/genética , Criança , Humanos , RNA Ribossômico 16S/genética , Ácido ÚricoRESUMO
Background: The long-term follow-up in children with familial male-limited precocious puberty (FMPP) who were treated with letrozole, triptorelin, and spironolactone is limited, especially considering the efficiency and safety. Objective: We describe the clinical characteristics and long-term treatment with letrozole on adult height of a boy diagnosed with FMPP, confirmed by analysis of the LHCGR gene. Methods: Physical examinations, bone age (BA), testosterone, and gonadotropin levels were measured as well as gene sequencing of the proband and parents. Results: The boy was referred to the hospital at 3.1 years of age due to peripheral precocious puberty. His height was 116.8cm (+5.1SD) and BA was 9 years. Genetic analysis revealed a patrilineal c.1703C>T.(p.Ala568Val) mutation of the LHCGR gene. After treating with letrozole for 1.6 years, the height according to BA went from -3.52SD to -2.82SD. Triptorelin was added at age 4.7 years based on both the evidence of central puberty and his growth velocity according to BA. During the 6.9 years of treatment, he had a height gain of 51.9cm, and BA increased 5.2 years. At age 10, his present height is 168.7cm (0.05SD) and BA is 14.7 years. No adverse effects of treatment were encountered. Conclusion: A patrilineal mutation of the LHCGR gene has been identified in a boy with FMPP. His height is 168.7cm (-0.05SD) which is approaching his adult height after long-term treatment with letrozole, triptorelin, and spironolactone.
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Puberdade Precoce , Adulto , Criança , Pré-Escolar , Humanos , Letrozol/uso terapêutico , Masculino , Puberdade Precoce/tratamento farmacológico , Puberdade Precoce/genética , Espironolactona/uso terapêutico , Pamoato de Triptorrelina/uso terapêuticoRESUMO
Morroniside is known to improve osteoporosis by promoting osteoblastogenesis. The activation of PI3K/Akt/mTOR signaling is a significant mechanism in morroniside-promoted osteoblastogenesis. It is well known that protective autophagy is an important factor in osteoblastogenesis. However, the activation of mTOR signaling can inhibit autophagy. This study aimed to investigate the relationship between mTOR signaling and autophagy in morroniside-regulated osteoblastogenesis. In this study, we investigated the effect of morroniside on the autophagic activity (LC3 conversion rate, LC3-puncta formation, and autophagosome number) of differentiated osteoblast precursors (MC3T3-E1 cells). Then, we identified the roles of mTOR knockdown in morroniside-regulated alterations of autophagy and osteogenic parameters in MC3T3-E1 cells. Next, mTOR knockdown and overexpression were used to observe the roles of mTOR in morroniside-regulated alterations of autophagic molecules (Atg7, Atg13, and Beclin1). Subsequently, the additional value of the above autophagic molecules on morroniside-regulated osteogenic parameters in MC3T3-E1 cells was analyzed based on lentiviral transduction. Finally, combined with morroniside and TAT-Beclin1, the roles of Beclin1 upregulation in the in vivo effects of morroniside was investigated. Our experimental data showed that morroniside promoted both the mTOR activity and autophagy in MC3T3-E1 cells. Morroniside-upregulated autophagic activity and Atg13 or Beclin1 protein level in MC3T3-E1 cells were enhanced by mTOR knockdown. Furthermore, Morroniside-upregulated Atg13 and Beclin1 expression was reversed by mTOR overexpression. Importantly, autophagy upregulation with overexpression of the autophagic gene, Atg13 or BECN1 (gene form of Beclin1), significantly promoted osteoblastogenesis regulated by morroniside. The promotional effect of morroniside on bone microarchitecture, bone mass, and bone parameters (including trabecular bone area and OCN expression in trabecular bone) in ovariectomized (OVX) mice was enhanced by TAT-Beclin1 administration. In conclusion, the autophagy-enhancing drugs related to Beclin1 or Atg13 may be an effective adjuvant therapy in the treatment of osteoporosis with morroniside.
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Proteínas Reguladoras de Apoptose , Proteína Beclina-1 , Osteoporose , Fosfatidilinositol 3-Quinases , Animais , Camundongos , Autofagia , Proteína Beclina-1/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas Reguladoras de Apoptose/metabolismoRESUMO
OBJECTIVE: To study the causes and prognosis of peripheral precocious puberty. METHODS: The levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were detected by a simplified gonadotrophin-releasing hormone (GnRH) stimulation test. The etiologies of 125 children with peripheral precocious puberty were explored by ultrasound scans and bone age assessment. A total of 102 cases were followed up for 3 months to 7.5 years. RESULTS: The etiological distribution of these children was as follows: exogenous hormones intake (n=80), ovarian cyst (n=11), McCune-Albright syndrome (n=11), congenital adrenal hyperplasia (CAH) (n=5), ovarian teratoma (n=1), masculine adrenal tumor (n=1), feminine adrenal tumor (n=1), and handle pituitary tumor (n=1). The causes in 14 cases were unknown. Follow-up showed that the sexual characteristics of 72 cases due to exogenous hormones intake subsided after 1-6 months. Of 11 cases with ovarian cysts, the sexual characteristics subsided spontaneously in 8 cases after 1 to 4 months, but one case was transformed to central precocious puberty after 2 years and three months. One child with ovarian cysts underwent an operation and than the sexual characteristics subsided. The sexual characteristics of the patient who had an ovarian teratoma subsided after operation. The clinical symptoms of children with McCune-Albright syndrome or CAH were alliaviated partly after treatment, and 7 cases were transformed to central precocious puberty. The clinical symptoms of 2 cases of adrenal tumors subsided after operation. One child with handle pituitary tumor died one year after operation. CONCLUSIONS: Varied causes may contribute to peripheral precocious puberty and therefore must be carefully identified through history taking, physical examination, and auxiliary examinations. The prognosis may differ for patients with different etiologies of peripheral precocious puberty.
Assuntos
Puberdade Precoce/etiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prognóstico , Puberdade Precoce/diagnóstico , Puberdade Precoce/terapiaRESUMO
Objective: The intestinal flora of gut microbiota in obese Chinese children and adolescents with and without insulin resistance (IR) was analyzed, as well as associations between the gut microbiota and two serum cytokines related to glucose metabolism, adropin and angiopoietin-like 4 (ANGPTL4). Methods: Clinical data, fecal bacterial composition, glucose-related hormones, and serum adipokines (adropin and ANGPTL4) were analyzed in 65 Chinese children with exogenous obesity. The composition of the gut microbiota was determined by 16S rRNA-based metagenomics and IR was calculated using the homeostasis model assessment (HOMA). Results: The 65 obese subjects were divided into two groups: insulin sensitive (IS) (n=40, 57.5% males) or IR (n=25, 60% males). Principal coordinates analysis revealed that the gut microbiota samples from the IS group clustered together and separated partly from the IR group (p=0.008). By Mann-Whitney U-test, at a phylum level, a reduction of Firmicutes and an increase of Bacteroidetes in the IR subjects was observed. LEfSe analysis revealed that IS subject, when compared to their IR counterparts, harbored members of the order Coriobacteriales, Turicibacterales, Pasteurellales and family Turicibacteraceae, that were significantly more abundant. In contrast, the IR subjects had members of family Peptococcaceae that were significantly more prevalent than the IS subjects (all p<0.05). Spearman's correlation analysis revealed that serum ANGPTL4 was positively associated with genus Bacteroides, Butyricimonas, and Alistipes, and adropin was positively associated with genus Anaerostipes and Alistipes, and negatively associated with genus Blautia (all p<0.05). Conclusion: In obese children, the gut microbiome in IR subjects was significantly discordant from the IS subjects, and the abundance of some metabolism-related bacteria correlated with the serum concentrations of adropin and ANGPTL4. These observations infer that the gut microbiota may be involved in the regulation of glucose metabolism in obesity.
Assuntos
Proteína 4 Semelhante a Angiopoietina/biossíntese , Microbioma Gastrointestinal , Resistência à Insulina , Obesidade Infantil/metabolismo , Adolescente , Bactérias/genética , Bactérias/metabolismo , Criança , China/epidemiologia , Estudos Transversais , Citocinas/sangue , Citocinas/metabolismo , Dieta , Fezes , Feminino , Genômica , Glucose/metabolismo , Humanos , Masculino , Metagenoma , Análise de Componente Principal , RNA Ribossômico 16S/metabolismoRESUMO
OBJECTIVE: Vitamin D-dependent rickets type IA (VDDR-IA) is a rare autosomal recessive disorder characterized by the early onset of severe rickets. The objectives of this study were twofold: (1) to analyze the clinical characteristics and therapy of two patients with VDDR-IA from two separate Chinese families, and (2) investigate the CYP27B1 gene mutations in two large pedigrees. METHODS: Medical history, clinical manifestations, physical examination, radiological findings and laboratory data were analyzed from two patients with VDDR-IA. Serum 1, 25-dihydroxyvitamin D [1, 25-(OH)2D3] of the two patients and their respective families were measured by ELISA and blood samples from both families was obtained for CYP27B1 gene sequence. RESULTS: Two patients had typical manifestations and radiological evidence of rickets. Laboratory data showed hypocalcaemia and hypophosphataemia, along with high levels of serum alkaline phosphatase, parathyroid hormone and 25-hydroxyvitamin D3. However, serum 1,25-(OH)2D3 level were low in the patients but normal in their family members. Genetic sequence identified two patients were homozygous for a duplication mutation in exon 8 of CYP27B1 gene (c.1319_1325dupCCCACCC, p.Phe443Profs * 24). After treating with calcitriol and calcium, there was biochemical improvement with normalization of serum calcium and phosphorus, and radiographic evidence of compensatory skeletal mineralization. One patient developed nephrocalcinosis during follow-up. CONCLUSIONS: This study identified a recurrent seven-nucleotide insertion of CYP27B1 in two large pedigrees, and compared the clinical characteristics and individual therapy of two affected patients. Additionally, our experience further supports the notion that nephrocalcinosis can occur even on standard doses of calcitriol and oral calcium, and normal level of serum calcium, phosphorus, PTH and 25-(OH)D3.
Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase , Raquitismo Hipofosfatêmico Familiar , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , China , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Raquitismo Hipofosfatêmico Familiar/genética , Seguimentos , Humanos , Vitamina DRESUMO
Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive diseases characterized by enzymatic defects in steroid synthesis. Lipoid congenital adrenal hyperplasia (LCAH) is the most severe form of CAH, insofar as the initial step of steroid synthesis is impaired. Variants in the steroid acute regulatory (STAR) gene are responsible for LCAH. To describe the clinical and genetic characteristics of three Chinese patients with LCAH. We analyzed the history, clinical manifestations, physical examination, laboratory data, and computed tomography findings of three girls with LCAH. The STAR gene of the probands and their parents were sequenced using genomic DNA. The wild-type and mutant STAR cDNAs were inserted into the pcDNA3.1(+) plasmid vector and transiently transfected into COS7 cells. The enzymatic activities of the wild-type and mutant STAR were evaluated by the enzyme-dependent conversion efficiency of cholesterol to pregnenolone. We identified the molecular genetic abnormalities in three patients with LCAH. All three patients had a female phenotype: karyotype of patients 1 and 2 was 46, XY and patient 3 was 46, XX. DNA sequencing revealed compound heterozygous variants in STAR for three probands. Two variants, c.659Aâ¯>â¯G/p.His220Arg and exon 2-3 deletion, were novel. In vitro functional studies uncovered that the His220Arg variant retained 19.2 % of enzymatic activity compared to that of the wild type.
Assuntos
Hiperplasia Suprarrenal Congênita/genética , Povo Asiático/genética , Transtorno 46,XY do Desenvolvimento Sexual/genética , Fosfoproteínas/genética , Hiperplasia Suprarrenal Congênita/metabolismo , Colesterol/metabolismo , Transtorno 46,XY do Desenvolvimento Sexual/metabolismo , Feminino , Variação Genética , Humanos , Lactente , Recém-Nascido , Cariótipo , Fenótipo , Fosfoproteínas/metabolismoRESUMO
Background The relationship between cytokines and lipid metabolism has garnered attention given their potential metabolic interaction. However, the relationship between adropin and lipopolysaccharide-binding protein (LBP) and obesity-related inflammation has not been reported, as well as their relationship with serum lipid profiles. Objective This study analyzed the association of serum adropin, leptin, LBP levels and lipid profiles in obese children ranging from 5 to 14 years old. Methods Plasma lipid measurements included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) by standard methods, and serum adropin, leptin and LBP levels was measured by enzyme-linked immunosorbent assay (ELISA). Results One hundred and twenty-four children (9.25 ± 1.59 years) with obesity and 42 controls (8.81 ± 1.94 years) were assessed. Compared with the control group, the serum adropin concentrations in the obesity group were significantly lower, whereas the serum leptin and LBP levels were significantly higher. Pearson's correlation analysis showed that serum adropin levels negatively correlated with TG, waist to hip ratio (WHR) and body mass index (BMI), and positively correlated with HDL-c. Serum LBP levels positively correlated with LDL-c and WHR. After adjusting for LBP, the correlation coefficients of adropin with TG, HDL-c and leptin were more robust. Also, after adjusting for serum LBP, the correlation coefficient of leptin with TG was attenuated, yet remained statistically significant, and the correlation coefficient of leptin with HDL-c was enhanced. Conclusions Children with obesity have decreased serum adropin levels and elevated leptin and LBP levels. Each of the three serum cytokines were associated with lipid metabolism, and this association warrants further study.