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In this study, super-resolution structured illumination microscope (SIM) was used to analyze molecular mechanism of endocytic acidification inhibitors in the SARS-CoV-2 pandemic, such as Chloroquine (CQ), Hydroxychloroquine (HCQ) and Bafilomycin A1 (BafA1). We fluorescently labeled the SARS-CoV-2 RBD and its receptor ACE2 protein with small molecule dyes. Utilizing SIM imaging, the real-time impact of inhibitors (BafA1, CQ, HCQ, Dynasore) on the RBD-ACE2 endocytotic process was dynamically tracked in living cells. Initially, the protein activity of RBD and ACE2 was ensured after being labeled. And then our findings revealed that these inhibitors could inhibit the internalization and degradation of RBD-ACE2 to varying degrees. Among them, 100â nM BafA1 exhibited the most satisfactory endocytotic inhibition (~63.9 %) and protein degradation inhibition (~97.7 %). And it could inhibit the fusion between endocytic vesicles in the living cells. Additionally, Dynasore, a widely recognized dynein inhibitor, also demonstrated cell acidification inhibition effects. Together, these inhibitors collectively hinder SARS-CoV-2 infection by inhibiting both the viral internalization and RNA release. The comprehensive evaluation of pharmacological mechanisms through super-resolution fluorescence imaging has laid a crucial theoretical foundation for the development of potential drugs to treat COVID-19.
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Liver cancer (LC) poses a significant global health challenge due to its high incidence and poor prognosis. Current systemic treatment options, such as surgery, chemotherapy, radiofrequency ablation, and immunotherapy, have shown limited effectiveness for advanced LC patients. Moreover, owing to the heterogeneous nature of LC, it is crucial to uncover more in-depth pathogenic mechanisms and develop effective treatments to address the limitations of the existing therapeutic modalities. Increasing evidence has revealed the crucial role of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in the pathogenesis of LC. The specific mechanisms driving the JAK-STAT pathway activation in LC, participate in a variety of malignant biological processes, including cell differentiation, evasion, anti-apoptosis, immune escape, and treatment resistance. Both preclinical and clinical investigations on the JAK-STAT pathway inhibitors have exhibited potential in LC treatment, thereby opening up avenues for the development of more targeted therapeutic strategies for LC. In this study, we provide an overview of the JAK-STAT pathway, delving into the composition, activation, and dynamic interplay within the pathway. Additionally, we focus on the molecular mechanisms driving the aberrant activation of the JAK-STAT pathway in LC. Furthermore, we summarize the latest advancements in targeting the JAK-STAT pathway for LC treatment. The insights presented in this review aim to underscore the necessity of research into the JAK-STAT signaling pathway as a promising avenue for LC therapy.
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BACKGROUND: Remote ischemic perconditioning (RIPerC) has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury (IRI). This study investigated the role of exosomes in RIPerC of liver grafts in rats. METHODS: Twenty-five rats (including 10 donors) were randomly divided into five groups (n = 5 each group): five rats were used as sham-operated controls (Sham), ten rats were for orthotopic liver transplantation (OLT, 5 donors and 5 recipients) and ten rats were for OLT + RIPerC (5 donors and 5 recipients). Liver architecture and function were evaluated. RESULTS: Compared to the OLT group, the OLT + RIPerC group exhibited significantly improved liver graft histopathology and liver function (P < 0.05). Furthermore, the number of exosomes and the level of P-Akt were increased in the OLT + RIPerC group. CONCLUSIONS: RIPerC effectively improves graft architecture and function, and this protective effect may be related to the increased number of exosomes. The upregulation of P-Akt may be involved in underlying mechanisms.
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Exosomas , Trasplante de Hígado , Daño por Reperfusión , Ratas , Animales , Trasplante de Hígado/efectos adversos , Proteínas Proto-Oncogénicas c-akt , Exosomas/patología , Daño por Reperfusión/etiología , Daño por Reperfusión/prevención & control , Daño por Reperfusión/patología , Isquemia , Hígado/cirugía , Hígado/patología , ReperfusiónRESUMEN
OBJECTIVE: Diabetic ketoacidosis (DKA) is the leading cause of mortality in children with type 1 diabetes. Diagnosis of DKA is difficult in resource-limited areas owing to the unavailability of blood gas test, the gold standard for DKA diagnosis. The Simplified Pediatric Diabetes Severity Warning System (SPDSWS) has been developed to identify high-risk DKA patients with limited resources in China. Here we optimized and validated this system. METHODS: This study included 835 children admitted between January 2011 and June 2020 with the principal diagnosis of type 1 diabetes. Data were collected based on demographic and clinical characteristics. DKA and its severity were defined according to the criteria of ISPAD. SPDSWS was optimized based on logistic regression analyses and then was validated in a validation cohort. RESULTS: The 20-point optimized SPDSWS included strong positive urine ketone, young age, dehydration, fatigue, anorexia, vomiting, abdominal pain, abnormal pulse, and high blood glucose. The optimized SPDSWS predicted DKA with an AUC value of 0.882 in the derivation cohort. When the cut-point score ≥7 was used, the sensitivity and specificity were 75.5% and 86.0%, respectively, in the derivation cohort and were 90.0% and 85.8%, respectively, in the validation cohort. The optimized SPDSWS also predicted the moderate/severe DKA with an AUC value of 0.911 in the derivation cohort and 0.937 in the validation cohort. A score > 11 was associated with an extremely high incidence of DKA. CONCLUSIONS: The optimized SPDSWS could assist health care practitioners in underdeveloped remote areas to identify the children at high risk of DKA as early as on admission.
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Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Niño , Estudios de Cohortes , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Cetoacidosis Diabética/diagnóstico , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/etiología , Hospitalización , Humanos , Incidencia , Estudios RetrospectivosRESUMEN
OBJECTIVE: The incidence of non-alcoholic fatty liver disease (NAFLD) in children increased rapidly. However, the pathogenesis of NAFLD, especially how non-alcoholic fatty liver progress to non-alcoholic steatohepatitis, is still unclear. This study aims to explore the exosomal miRNAs profiles and the underline pathogenesis of child NAFLD. METHODS: Twenty NAFLD and 20 health control were enrolled in this study. Circulating exosomes were isolated, and RNA sequencing was performed in test set (3 NAFLD/3 Controls). The differentially expressed miRNAs (DEM) were further validated in validation set (17 NAFLD/17 Controls). Spearman correlation -analysis was used to investigate the association between DEM and clinical parameters. RESULTS: Eighty-two miRNAs were differentially expressed (absolute fold change >2 and p < 0.05) in the 2 groups, they were involved in fat acid metabolism, starch and sucrose metabolism, bile acid metabolism and inflammation. miRNA122-5p, miRNA34a-5p, -miRNA155-5p and miRNA146b-3p were up-regulated in NAFLD group (p < 0.05) and positively correlated with body mass index (r, 0.41-0.59), alanine aminotransferase (r, 0.36-0.52), aspartate transaminase (r, 0.31-0.48) and uric acid (UA, r, 0.51-0.69; p < 0.05). CONCLUSIONS: Circulating exosomal miRNAs may be involved in the pathogenesis of NAFLD and correlated with transaminase and UA.
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MicroARNs , Enfermedad del Hígado Graso no Alcohólico , Alanina Transaminasa , Aspartato Aminotransferasas , Niño , Humanos , Hígado/metabolismo , MicroARNs/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Ácido ÚricoRESUMEN
BACKGROUND: Development of an entry-level physiotherapy curriculum in China currently follows the World Confederation for Physical Therapy (WCPT) guidelines, however there is no standard, validated, assessment tool for physiotherapy practice in use in China. This article reports the process of translation of the "Assessment of Physiotherapy Practice" (APP), a validated assessment instrument adopted by all universities in Australia and New Zealand, into Chinese (APP-Chinese) and its implementation by Chinese physiotherapy clinical educators (CEs) and students during clinical placements. METHODS: The process of forward and backward translation of the APP was undertaken by a team of academics from universities in Shanghai, Hong Kong, United States and Australia. An APP-Chinese version was produced and used for assessment of the clinical performance of 4th year students at a university in Shanghai. Feedback on the implementation of the APP-Chinese was solicited from students and CEs using the same two questionnaires employed to assess implementation of the original APP. RESULTS: All CEs agreed that the rules used to score the APP-Chinese were helpful in assessing student performance. Over 90% of the CEs considered the APP-Chinese was pragmatic for use in the clinical environment in China. All students agreed with the rating of their performance on the APP-Chinese marked by their educators, and that the performance indicators were useful in guiding their expected performance behaviour. CONCLUSION: The APP-Chinese is the first standardised assessment tool for evaluation of clinical performance of physiotherapy students in China and was shown to be well accepted by both students and CEs in the clinical education unit and university involved in this study.
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Curriculum/normas , Evaluación Educacional/normas , Especialidad de Fisioterapia/educación , Especialidad de Fisioterapia/normas , Competencia Profesional/normas , Estudiantes del Área de la Salud/estadística & datos numéricos , Australia , China , Humanos , Modalidades de Fisioterapia/educación , Modalidades de Fisioterapia/normas , UniversidadesRESUMEN
OBJECTIVE: To analyze the results of screening for hereditary tyrosinemia (HT) in newborns and its clinical features and genotype. METHODS: The HT screening was conducted among 2 188 784 newborns from November 2013 to November 2018. The tyrosine (TYR)/ succinylacetone (SA) levels were detected by tandem mass spectrometry (MS-MS). The clinical characteristics, genetic results and following up data of identified patients were analyzed. RESULTS: The normal ranges (0.5%-95.5%) of TYR and SA were 34.5-280.0 µmol/L and 0.16-2.58 µmol/L, respectively. Three HT cases were confirmed with a detection rate of 1â¶729 595. There was 1 case of tyrosinemia type â (HTâ ) (homozygous variations of c.455G>A in FAH gene), 1 case of tyrosinemia type â ¡(HTâ ¡) (heterozygous variations of c.890G>T and c.408+1G>A in TAT gene), and 1 case of tyrosinemia type â ¢ (HT â ¢) (homozygous variations of c.257T>C in HPD gene). The variations of c.890G>T, c.4081G>A of TAT and c.257T>C of HPD were novel. The positive predictive value of the screening was 3.4%. Case 1 (HTâ ) with TYR and SA values of 666.9 µmol/L and 3.87 µmol/L respectively, presented cholestasis, mild elevated of liver enzyme and lactic acid, who were although fed with TYR and phenylalanine free milk, but died at 2 months of age. Case 2 (HTâ ¡) with higher TYR (625.6 µmol/L) and normal SA at screening, received medical milk treatment; during the 7 months of follow-up the baby showed normal score of Bayley assessment and normal TYR without eye and skin symptoms. Case 3 (HT â ¢) with TYR of 1035.3 µmol/L and normal SA at screening; during the 29 months of follow-up the value of TYR fluctuated from 532.1 µmol/L to 1060.3 µmol/L due to irregular medical milk treatment, while the score of Bayley assessment was normal. CONCLUSIONS: HT is rare in the southern Chinese population, and the gene spectrum is scattered. Early treatment with nitisinone is recommended in children with HTâ , otherwise the prognosis is poor; the prognosis of children with HTâ ¡ is good when early treated with special diet; the prognosis of children with HTâ ¢ needs to be determined with more data.
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Tamizaje Neonatal , Tirosinemias , Niño , Ciclohexanonas/uso terapéutico , Genotipo , Humanos , Lactante , Recién Nacido , Nitrobenzoatos/uso terapéutico , Espectrometría de Masas en Tándem , Tirosinemias/diagnóstico , Tirosinemias/tratamiento farmacológico , Tirosinemias/genéticaRESUMEN
OBJECTIVE: To investigate the epidemiological characteristics, phenotype, genotype, and prognosis of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in the Chinese population. METHODS: A retrospective analysis was performed for the clinical data of the neonates who underwent screening with high-performance liquid chromatography-tandem mass spectrometry from January 2009 to June 2018 and were diagnosed with MCADD by gene detection. RESULTS: A total of 2 674 835 neonates underwent neonatal screening, among whom 12 were diagnosed with MCADD. Gene detection was performed for 10 neonates with MCADD and found 13 mutation types at 16 mutation sites of the ACADM gene, among which there were 7 reported mutations (p.T150Rfs*4, p.M1V, p.R206C, p.R294T, p.G310R, p.M328V, and p.G362E), 5 novel mutations (p.N194D, p.A324P, p.N366S, c.118+3A>G, and c.387+1del G), and 1 exon 11 deletion; p.T150Rfs*4 was the most common mutation (4/16). The detection rate of mutation sites in the ACADM gene was 80%. No phenotype-genotype correlation was observed. Dietary guidance and symptomatic treatment were given after confirmed diagnosis. No acute metabolic imbalance was observed within 4-82 months of follow-up. All neonates had good prognosis except one who had brain dysplasia. CONCLUSIONS: MCADD is relatively rare in southern China, and p.T150Rfs*4 is a common mutation in the Chinese population. Cases with positive screening results should be evaluated by octanoylcarnitine C8 value and gene detection.
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Acil-CoA Deshidrogenasa/deficiencia , Errores Innatos del Metabolismo Lipídico , Carnitina , China , Estudios de Seguimiento , Humanos , Recién Nacido , Mutación , Tamizaje Neonatal , Estudios RetrospectivosRESUMEN
As a typical tool of risk analysis in practical engineering, failure mode and effects analysis (FMEA) theory is a well known method for risk prediction and prevention. However, how to quantify the uncertainty of the subjective assessments from FMEA experts and aggregate the corresponding uncertainty to the classical FMEA approach still needs further study. In this paper, we argue that the subjective assessments of FMEA experts can be adopted to model the weight of each FMEA expert, which can be regarded as a data-driven method for ambiguity information modeling in FMEA method. Based on this new perspective, a modified FMEA approach is proposed, where the subjective uncertainty of FMEA experts is handled in the framework of Dempster-Shafer evidence theory (DST). In the improved FMEA approach, the ambiguity measure (AM) which is an entropy-like uncertainty measure in DST framework is applied to quantify the uncertainty degree of each FMEA expert. Then, the classical risk priority number (RPN) model is improved by aggregating an AM-based weight factor into the RPN function. A case study based on the new RPN model in aircraft turbine rotor blades verifies the applicable and useful of the proposed FMEA approach.
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OBJECTIVE: To delineate the clinical, biochemical and genetic mutational characteristics of a child with mitochondrial complex III deficiency. METHODS: Clinical information and results of auxiliary examination of the patient were analyzed. Next-generation sequencing of the mitochondrial genome and related nuclear genes was carried out. Suspected mutation was confirmed in both parents with Sanger sequencing. Heterozygous deletion was mapped with chromosomal microarray analysis and confirmed with real-time PCR. RESULTS: The patient presented with vomiting, polypnea, fever, metabolic acidosis, hyperlactatemia, hypoglycemia, dysfunction of coagulation and immune system, in addition with increased lactate dehydrogenase and creatine kinase isoenzyme. Elevation of blood alanine and acylcarnitines as well as urinary ketotic dicarboxylic acid were also noted. The patient also presented development delay, mental retardation and hypotonia. Sequence analysis revealed two mutations in the nuclear gene UQCRB, which included a previously reported frameshift mutation c.306_309delAAAA(p.Arg105Lysfs*22) and a novel large deletion encompassing the entire UQCRB gene. CONCLUSION: The clinical, biochemical and gene mutation characteristics of a child with mitochondrial complex III deficiency caused by mutations of the UQCRB gene have been delineated.
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Proteínas Portadoras/genética , Complejo III de Transporte de Electrones/deficiencia , Enfermedades Mitocondriales/genética , Mutación , Adulto , Secuencia de Bases , Complejo III de Transporte de Electrones/genética , Femenino , Humanos , Lactante , Masculino , Datos de Secuencia MolecularRESUMEN
OBJECTIVE: To analyze the result and follow-up data of screening for newborn amino acid metabolic disorders in Zhejiang province. METHODS: A total of 1 861 262 newborns were screened for amino acid metabolic disorders during January 2009 and December 2016 in Zhejiang province. The screening results and the follow-up data were analyzed retrospectively. RESULTS: One hundred and sixty four cases were diagnosed as amino acid metabolic disorders with a prevalence of 1:11 349, including 83 with hyperphenylalaninaemia (1:22 400), 29 with neonatal intrahepatic cholestasis caused by citrin deficiency (1:64 138), 16 with methionine S-adenosyltransferase deficiency (1:116 250), 9 with maple syrup urine disease (1:206 667), 8 with argininemia (1:232 500), 7 with citrullinemia type â (1:265 700), 6 with hyperprolinemia type â (1:310 000), and 2 with carbamylphosphate synthetase â deficiency(1:930 000). In addition, ornithine transcarbamylase deficiency, cystathionine ß-synthase deficiency, argininosucoinate aciduria and tyrosinemia type â were detected in one patient for each, respectively. Two patients had developmental delay, 7 patients were dead, and 2 cases of maple syrup urine disease were lost to follow-up. CONCLUSIONS: Hyperphenylalaninaemia is the most common amino acid metabolic disease in newborns in Zhejiang province. Patients with amino acid metabolic disorders identified in newborn screening program can have chance for normal growth development by intervention.
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Errores Innatos del Metabolismo de los Aminoácidos , Tamizaje Neonatal , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Errores Innatos del Metabolismo de los Aminoácidos/terapia , China/epidemiología , Estudios de Seguimiento , Humanos , Recién Nacido , Prevalencia , Estudios RetrospectivosRESUMEN
OBJECTIVE: To analyze the results and follow up data of screening for newborn organic aciduria in Zhejiang province. METHODS: The results and follow-up data of 1 861 262 newborns from Zhejiang province undergoing screening for organic aciduria during January 2009 and December 2016 were retrospectively analyzed. The acylcarnitine spectrum in urine samples was detected by tandem mass spectrum (MS/MS) and the positive patients were confirmed by urine gas chromatography mass spectrometry and/or gene analysis. RESULTS: Ninety two cases of organic aciduria were confirmed with a prevalence of 1:20 200. Among 40 cases of methylmalonic academia (MMA), 13 (32.5%) were of MMA simple type and 27 (67.5%) were combined type. Genetic analysis showed 6 cases of MUT type and 1 case of CblB type out of 7 patients with MMA simple type, 10 cases of CblC and 1 case of CblF out of 11 patients with combined type, respectively. Six patients had propionic academia with a prevalence of 1:310 200, 7 had isovaleric academia (1:265 900), 6 had glutaric academia type 1 (1:310 200), 27 had 3-methylcrotonyl-CoA carboxylase deficiency (MCC, 1:68 900), 1 had 3-hydroxy-3-methylglutaric aciduria (1:1 861 300), 2 had ß-ketothiolase deficiency (1:960 600), and 3 had biotinidase deficiency/holocarboxylase synthetase deficiency (1:620 400). Thirty-one patients had a disease onset at neonatal period, and 15 at post-neonatal period. Thirty-three patients had brain involvements or cranial imaging disorders. Three patients with MMA had kidney diseases or heomlytic uremic syndrome, and 3 had myocardial impairments. Twenty patients died during the follow-up. CONCLUSIONS: MMA is the most common newborn organic aciduria in Zhejiang province. Except MCC, most organic aciduria may lead to metabolism decompensation, complications or even death.
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Alcaptonuria , Tamizaje Neonatal , Alcaptonuria/diagnóstico , Alcaptonuria/epidemiología , Alcaptonuria/terapia , China/epidemiología , Estudios de Seguimiento , Humanos , Recién Nacido , Prevalencia , Estudios Retrospectivos , Espectrometría de Masas en TándemRESUMEN
OBJECTIVE: To screen fatty acid oxidation disorders (FAOD) in newborns in Zhejiang province. METHODS: A total of 1 861 262 newborns were screened for FAOD in Neonatal Screening Center of Zhejiang Province during January 2009 and December 2016. The blood samples from newborns were screened by tandem mass spectrometry, and diagnosis of FAOD was confirmed by urine organic acid measurement combined with genetic analysis. The prognosis and follow-up of patients with FAOD were also evaluated. RESULTS: Of 1 861 262 newborns screened, 121 cases of FAOD were diagnosed. Among 121 cases of FAOD, primary carnitine deficiency (PCD) was the most common type (n=78, 64.5%), which was followed by short-chain acyl-CoA dehydrogenase deficiency (SCADD, n=27, 22.3%), medium-chain acyl-CoA dehydrogenase deficiency (n=5, 4.1%), multiple acyl-CoA dehydrogenase deficiency (MADD, n=4, 3.3%), very long-chain acyl-CoA dehydrogenase deficiency (n=3, 2.5%), carnitine palmitoyltransferase â deficiency(n=2, 1.7%)and carnitine palmitoyltransferase â ¡ deficiency (CPTâ ¡D, n=2, 1.7%). During 2-82 month follow-up, 15 patients were lost, 4 were dead (1 PCD, 1 MADD, and 2 CPTâ ¡D), and the remaining 102 subjects had normal intelligence and physical development without any clinical symptoms. CONCLUSIONS: PCD and SCADD are the most common FAODs in newborns in Zhejiang province. Most of FAOD patients are asymptomatic, and have normal growth and development after early intervention and management.
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Errores Innatos del Metabolismo Lipídico , Tamizaje Neonatal , Acil-CoA Deshidrogenasa/deficiencia , Cardiomiopatías/diagnóstico , Cardiomiopatías/epidemiología , Carnitina/deficiencia , China/epidemiología , Estudios de Seguimiento , Humanos , Hiperamonemia/diagnóstico , Hiperamonemia/epidemiología , Recién Nacido , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/epidemiología , Errores Innatos del Metabolismo Lipídico/terapia , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/epidemiología , PrevalenciaRESUMEN
In this study, a compressed oxygen gas supply was connected to a sealed aerated stirred tank reactor (COS-SSTR) bio-system, leading to a high-oxygen pressure bioreactor used to improve the bio-transformative performance in the production of 1,3-dihydroxyacetone (DHA) from glycerol using Gluconobacter oxydans NL71. A concentration of 301.2 ± 8.2 g L(-1) DHA was obtained from glycerol after 32 h of fed-batch fermentation in the COS-SSTR system. The volumetric productivity for this process was 9.41 ± 0.23 g L(-1) h(-1), which is presently the highest obtained level of glycerol bioconversion into DHA. These results show that the application of this bioreactor would enable microbial production of DHA from glycerol at the industrial scale.
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Dihidroxiacetona/química , Gluconobacter oxydans/química , Glicerol/química , Oxígeno/química , FermentaciónRESUMEN
OBJECTIVE: To explore the effects of obesity on the peak level of luteinizing hormone (LH) in the gonadotropin-releasing hormone (GnRH) agonist test and obesity-related hormones in girls with central precocious puberty (CPP). METHODS: Three hundred and thirty-three girls with CPP who underwent the GnRH agonist test between 2012 and 2014 were classified into three groups: normal weight (n=123), overweight (n=108), and obesity (n=102), according to body mass index (BMI). The sexual development indices were compared between the three groups. Twenty girls were randomly selected from each group for evaluation of the serum levels of leptin, sex hormone binding globulin (SHBG), neurokinin B, and kisspeptin. The correlation of BMI with the levels of various hormones was assessed using Pearson correlation analysis. RESULTS: There was no significant difference in mean age at diagnosis between the three groups; however, the bone age was significantly higher in the overweight and obesity groups than in the normal weight group (P<0.05). The peak level of LH in the GnRH agonist test and SHBG level in the normal weight group were significantly higher than those in the overweight and the obesity groups, while the serum levels of leptin and neurokinin B were significantly lower in the normal weight group than in the overweight and the obesity groups (P<0.05). BMI was negatively correlated with the peak level of LH in the GnRH agonist test and SHBG level (P<0.05), and positively correlated with the levels of leptin and neurokinin B (P<0.05). CONCLUSIONS: The effects of BMI on the result of the GnRH agonist test and levels of obesity-related hormones should be taken into account in girls with precocious puberty.
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Hormona Liberadora de Gonadotropina/agonistas , Leptina/sangre , Hormona Luteinizante/sangre , Obesidad/sangre , Pubertad Precoz/sangre , Índice de Masa Corporal , Niño , Femenino , Humanos , Neuroquinina B/sangre , Globulina de Unión a Hormona Sexual/análisisRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of a phenylalanine-free amino acid-based enteral formula (AA-PKU2) in the treatment of children with phenylketonuria (PKU) aged 1-8 years. METHODS: A prospective, open, self-controlled, multi-center trial was performed, enrolling 121 PKU children (1-8 years in age) consecutively between July, 2009 and May, 2011. Enteral nutrition therapy was administered for 32 weeks. The data on blood phenylalanine (PHE) levels, metal development, weight, height, head circumference, serum nutritional biomarkers (total protein, pre-albumin, albumin, total cholesterol, total triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), and measurements from routine blood and urine examinations and from renal and hepatic function tests were collected before the therapy and at 8 weeks and 32 weeks after the therapy and were comparatively analyzed. RESULTS: The mean blood PHE level at 8 and 32 weeks of AA-PKU2 treatment was 353±253 and 361±280 µmol/L respectively, significantly lower than that before the treatment (487±327 µmol/L; P<0.01). The difference in intelligence quotient scores before and after AA-PKU2 treatment was not significant (P>0.05) when assessed by the Gesell tests in children aged 1-4 years but significant (P<0.01) when assessed by WPPSI or WISR-R tests in children over 4 years. The average height, weight and head circumference at 8 and 32 weeks after treatment were significantly increased as compared to these measurements before treatment (P<0.01) with absolute levels similar to those in the control children. In contrast, the mean values of total protein, pre-albumin, albumin, total cholesterol, total triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol at both time points were not different either from those prior to the treatment or from those in the control children. Mild diarrhea was the adverse events associated with AA-PKU2 treatment, which occurred in 3 (2.5%) cases. All these 3 patients fully recovered without treatment. CONCLUSIONS: The phenylalanine-free amino acid-based formula, AA-PKU2, is effective and safe in controlling blood PHE levels and improving mental development with adequate nutritional support in PKU.
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Nutrición Enteral , Fenilcetonurias/dietoterapia , Niño , Preescolar , Femenino , Humanos , Lactante , Inteligencia , Masculino , Fenilalanina/sangre , Fenilcetonurias/psicología , Estudios ProspectivosRESUMEN
Background: Hyperuricemia is a common metabolic disorder linked to various health conditions. Its prevalence varies among populations and genders, and high-altitude environments may contribute to its development. Understanding the connection between blood cell parameters and hyperuricemia in high-altitude areas can shed light on the underlying mechanisms. This study aimed to investigate the relationship between blood cell parameters and hyperuricemia in high-altitude areas, with a particular focus on gender differences. Methods: We consecutively enrolled all eligible Tibetan participants aged 18-60 who were undergoing routine medical examinations at the People's Hospital of Chaya County between January and December 2022. During this period, demographic and laboratory data were collected to investigate the risk factors associated with hyperuricemia. Results: Among the participants, 46.09% were diagnosed with hyperuricemia. In the male cohort, significant correlations were found between serum uric acid (SUA) levels and red blood cell (RBC) count, creatinine (Cr). Urea, alanine transaminase (ALT), and albumin (ALB). Notably, RBC exhibited the strongest association. Conversely, in the female cohort, elevated SUA levels were associated with factors such as white blood cell (WBC) count. Urea, ALT, and ALB, with WBC demonstrating the most significant association. Further analysis within the female group revealed a compelling relationship between SUA levels and specific white blood cell subtypes, particularly neutrophils (Neu). Conclusion: This study revealed gender-specific associations between SUA levels and blood cell parameters in high-altitude areas. In males, RBC count may play a role in hyperuricemia, while in females, WBC count appears to be a significant factor. These findings contribute to our understanding of metabolic dynamics in high-altitude regions but require further research for comprehensive mechanistic insights.
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Hiperuricemia , Humanos , Masculino , Femenino , Hiperuricemia/epidemiología , Altitud , Ácido Úrico , Células Sanguíneas , UreaRESUMEN
Objective: Evaluating changes over time in the odds of obesity according to sex. Methods: PubMed, Embase, Cochrane Library, and China National Knowledge Database were searched for relevant studies. Full-text studies evaluating the influence of sex on obesity were analyzed. We used R 3.4.3 to assess the impact of results in the selected studies, calculated pooled prevalence and odds ratio (OR) with their respective 95% confidence intervals (CIs). P<0.10 and I2>50% indicated high heterogeneity, and the random-effects model was used, otherwise, the fixed-effects model was used. Results: The included studies reported the prevalence of obesity in children covering 1987-2017 intervals. The pooled prevalence of obesity in boy and girl groups were 0.13 (95% CI: 0.08, 0.20) and 0.10 (95% CI: 0.07, 0.13). In the analysis of the boy group, the pooled OR in earlier time (1987-2013) vs. recent time (2011-2017) was 0.98 (95% CI: 0.76, 1.26). The estimated OR for girls in earlier vs. recent time was 1.01 (95% CI: 0.80, 1.28). In the analysis of studies with follow-up period ≥ 10 years, the pooled OR for obesity in earlier vs. recent time period was 0.99 (95% CI: 0.76, 1.30). For those with follow-up period < 10 years, the pooled OR in earlier vs. recent time period was 0.94 (95% CI: 0.57, 1.54). Conclusions: Comprehensive measurements are required to control obesity among children albeit with nonsignificant gender difference and time trend for obesity rates in children.
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Zein is the main vegetable protein from maize. In recent years, Zein has been widely used in pharmaceutical, agriculture, food, environmental protection, and other fields because it has excellent biocompatibility and biosafety. However, there is still a lack of systematic review and research on Zein-based nano-delivery systems. This paper systematically reviews preparation and modification methods of Zein-based nano-delivery systems, based on the basic properties of Zein. It discusses the preparation of Zein nanoparticles and the influencing factors in detail, as well as analyzing the advantages and disadvantages of different preparation methods and summarizing modification methods of Zein nanoparticles. This study provides a new idea for the research of Zein-based nano-delivery system and promotes its application.
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Current DES pretreatment is often performed under relatively severe conditions with high temperature, long time, and high DES usage. This work studied a short-time diol DES (deep eutectic solvent) pretreatment under mild conditions to fractionate the bamboo, facilitate enzymatic hydrolysis, and obtain high-quality lignin. At an optimized condition of 130 °C for only 10â min, lignin and xylan removal reached 61.34 % and 84.15 %, with residual glucan showing a ~90 % enzymatic hydrolysis yield. Equally important, the dissolved lignin could be readily recovered with 97.51 % yield, exhibiting 96.65 % ß-O-4 preservation. The fractionation and lignin protection mechanisms were unveiled by XRD, FTIR, cellulose-DP, 2D HSQC NMR, 31Pâ NMR and GPC analysis. This study highlighted that short-time fractionation of bamboo can be achieved by a diol-based DES which is an ideal strategy to upgrade the lignocellulose biomass for high enzymatic hydrolysis yields and high-quality lignin stream.