Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 116
Filtrar
2.
Artigo em Inglês | MEDLINE | ID: mdl-35438852

RESUMO

OBJECTIVES: Iodide transport defect (ITD) is one of the principal causes of congenital hypothyroidism (CH) and its primary molecular mechanism is a mutation of the sodium/iodide symporter (NIS) gene. This study aims to analyse the clinical characteristics and genetic mutations of ITD. METHODS: The participants were a pair of siblings diagnosed with congenital hypothyroidism. Inductively coupled plasma mass spectrometry was used to determine the concentration of salivary iodine and serum iodine and to calculate their ratio. At the same time, next-generation sequencing (NGS) was applied to detect all exons of congenital hypothyroidism-related genes. All suspicious variants were further validated in the patients and their parents by PCR and Sanger sequencing. RESULTS: Both patients were conclusively diagnosed with thyroid iodine transport defect (ITD). NGS identified two variants of the NIS gene in the siblings: c.1021G>A (p.Gly341Arg) with paternal origin and c.1330-2A>C with maternal origin. Both of these variants have not been reported to date. They are predicted to be pathogenic based on these clinical symptoms and comprehensive software analysis. CONCLUSIONS: This is the first reported family study of congenital hypothyroidism with SLC5A5 mutation in China. Next-generation sequencing technology is an effective means of studying the genetics of congenital hypothyroidism. The therapeutic effect of potassium iodide needs to be further evaluated.

5.
Blood Purif ; 51(3): 270-279, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34753147

RESUMO

BACKGROUND: Heart failure (HF) is one of the main comorbidities in patients receiving maintenance hemodialysis (HD). Sacubitril/valsartan (SAC/VAL) is widely used in HF patients with reduced ejection fraction (HFrEF) or HF mid-range ejection fraction (HFmrEF). However, the pharmacokinetic (PK) and pharmacodynamic properties of SAC/VAL in HD patients with HF remain uncertain. OBJECTIVES: This study aimed to analyze the efficacy and PK properties of SAC/VAL in HD patients with HFrEF or HFmrEF. METHODS: HD patients with HFrEF or HFmrEF were treated with SAC/VAL 50 or 100 mg twice a day (BID) and the concentrations of valsartan and LBQ657 (active metabolite of SAC) were determined by high-performance liquid chromatography-tandem mass spectrometry during HD and on the days between HD sessions (interval days). N-terminal-pro B-type natriuretic peptide and high-sensitivity troponin T were measured, and left ventricular ejection fraction (LVEF) was evaluated by echocardiography. RESULTS: The mean maximum plasma concentrations (Cmax) of LBQ657 and VAL on the interval days were 15.46 ± 6.01 and 2.57 ± 1.23 mg/L, respectively. Compared with previous values in patients with severe renal impairment and healthy volunteers, these levels both remained within the safe concentration ranges during treatment with SAC/VAL 100 mg BID. Moreover, SAC/VAL significantly improved LVEF in HD patients with HFrEF or HFmrEF (p < 0.05). CONCLUSIONS: HD did not remove the SAC metabolite LBQ657 or VAL in patients with HF. However, SAC/VAL 100 mg BID was safe and effective in patients undergoing HD.

6.
Hepatol Int ; 15(6): 1318-1327, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34843068

RESUMO

BACKGROUND AND AIM: Antiviral therapy is effective in decreasing disease progression in HBV cirrhosis. However, the long-term effect of antiviral therapy on health-related quality of life (HRQoL) in patients with compensated HBV cirrhosis is unknown. METHODS: The patients with compensated HBV cirrhosis enrolled in a randomized controlled trial of entecavir-based therapy were recruited in the present study, if they had HRQoL score at 5-year follow-up or who developed liver-related events (LRE) during follow-up were included. HRQoL was measured with 36-Item Short-Form Health Survey (SF-36) and EuroQol-5D (EQ-5D) at baseline and yearly during follow-up. LRE was defined as the development of decompensation, HCC, or death. RESULTS: A total of 161 patients were included in the present study, with a median age of 48.0 (41.0, 53.0) years, 77.6% being male and 37.2% being HBeAg-positive. During 5 years, 45 patients developed LRE. All eight dimensions of SF-36 were significantly improved after 5 years of antiviral therapy (all p < 0.001), with all dimensions improved more than five points except for physical functioning. Proportion of patients reporting no problems in all five dimensions in EQ-5D increased from 57.8 to 72.0%; visual analogue scale (VAS) and utility index (UI) increased significantly (VAS 79.8 ± 16.4 to 84.4 ± 13.2, UI 0.91 ± 0.13 to 0.95 ± 0.10, both p < 0.001). HRQoL improved or kept stable in the majority of patients who had LRE during follow-up, even stratified by Baveno VI criteria for clinically significant portal hypertension. CONCLUSION: After 5 years of ETV treatment, HRQoL significantly improved in patients with compensated HBV cirrhosis. (NCT01943617, NCT02849132).


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Feminino , Guanina/análogos & derivados , Vírus da Hepatite B , Humanos , Cirrose Hepática/tratamento farmacológico , Masculino , Qualidade de Vida , Inquéritos e Questionários
7.
BMC Oral Health ; 21(1): 542, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674671

RESUMO

BACKGROUND: In recent years, the concept of minimally invasive endodontics has been proposed, which could be described as preventing or treating diseases by preserving more dental tissue and creating minimal damage. In the process of root canal preparation, it was recommended to use instruments with a smaller taper to preserve more tooth tissue and improve the preservation rate of the affected teeth. Photon-induced photoacoustic streaming (PIPS) was a new type of laser-activated irrigation technology, which was now widely used in endodontic treatment. The purpose of this article was to evaluate the bactericidal effect of PIPS with NaOCl in root canals with different widths or tapers. METHODS: Twenty-three maxillary first molars with three independent root canals were included in this study. The mesiobuccal (MB), distobuccal (DB), and palatal (P) root canals were prepared at sizes of #10/.02, #25/.02, and #25/.06, respectively. After being incubated with a bacterial suspension for 4 weeks, the specimen were irrigated with 2% NaOCl activated by conventional needle irrigation (CNI) (n = 10) or PIPS (n = 10). Three specimen were not treated (control group). Before and after irrigation, the presence of bacteria was assessed with an adenosine 5'-triphosphate (ATP) assay kit and biofilms were assessed using confocal laser scanning microscopy and scanning electron microscopy. RESULTS: In specimen prepared using PIPS irrigation, the ATP was reduced by more than 98%. When the root canal taper was 0.02, the size #25 root canals had a higher percentage of dead bacteria than the size #10 root canals in all regions (P < 0.05) in the PIPS group. When the root canal width was #25, the 0.02 taper group had a higher percentage of dead bacteria than the 0.06 taper group in the apical region (P < 0.05), except coronal and middle regions (P > 0.05). PIPS irrigation results in a greater percentage of dead bacteria and reduction of ATP in size #10/.02 root canals than CNI in size #25/.06 root canals in three regions (P < 0.05). CONCLUSION: Increasing the width from #10 to #25 improves the bactericidal effect of PIPS in the root canal. Increasing the taper of the root canal from 0.02 to 0.06 at size #25 did not affect the bactericidal effects of PIPS. PIPS resulted in more dead bacteria in specimen with smaller tapers and root canal widths than CNI. PIPS can be used to clean the smear layer in the coronal region and open the dentin tubules. CLINICAL SIGNIFICANCE: Activation of irrigants with PIPS brought about significant bacterial reduction smaller tapers and width root canals compared to CNI, which was beneficial to prevent excessive loss of tooth tissue and conserve the structural integrity of teeth.


Assuntos
Cavidade Pulpar , Irrigantes do Canal Radicular , Antibacterianos , Humanos , Preparo de Canal Radicular , Hipoclorito de Sódio/uso terapêutico
8.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(4): 514-523, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34704422

RESUMO

Hereditary tyrosinemia type Ⅰ (HT-1) is a severe autosomal recessive inherited metabolic disease. Due to the deficiency of fumarylacetoacetase hydrolase (FAH), the toxic metabolites are accumulated in the body, resulting in severe liver dysfunction, renal tubular dysfunctions, neurological crises, and the increased risk of hepatocellular carcinoma. Clinical symptoms typically begin at after the birth; the prognosis of patients is poor if they are not treated timely. Succinylacetone is a specific and sensitive marker for HT-1, and the screening in newborns can make early diagnosis of HT-1 at the asymptomatic stage. The diagnosis of HT-1 can be confirmed based on the characteristic biochemical findings and molecular testing of mutations in both alleles of gene. Combined treatment with nitisinone and a low tyrosine diet may significantly improve outcomes for patients. Liver transplantation is an effective treatment in cases where nitisinone is not available. Some novel HT-1 treatments are in clinical trials, including enzyme replacement therapy, hepatocyte transplantation and gene-targeted therapy.


Assuntos
Transplante de Fígado , Tirosinemias , Humanos , Recém-Nascido , Fígado , Mutação , Triagem Neonatal , Tirosinemias/diagnóstico , Tirosinemias/terapia
9.
Lancet Reg Health West Pac ; 16: 100249, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34590058

RESUMO

BACKGROUND: High uptake of hepatitis B virus (HBV) tests and antiviral therapy are required to improve the clinical outcomes of patients with chronic hepatitis B (CHB) at the population level. In the current study, we used the Basic Medical Care Insurance for Employees (BMCIE) to investigate the changes of clinical care cascade of CHB in Beijing, China. METHODS: Records for medical service of CHB patients from January 1, 2010 to December 31, 2018 were retrieved from the BMCIE database. The annual and cumulative rates of CHB patients in care, receiving HBV tests and on antiviral therapy were calculated. The trends of annual percentage changes (APCs) were estimated using Joinpoint regression model. FINDINGS: Among estimated HBsAg positive employees, the rate of CHB patients in care increased from 4•77% in 2010 to 18•61% in 2018 (APC=17•3, 95%CI: 14•4-20•4). The rate of HBV tests increased from 4•41% in 2010 to 16•39% in 2018. Among the estimated eligible employees for treatment, the rate of antiviral therapy increased from 3•92% in 2010 to 30•88% in 2018. The proportion of hospital visits for HBV≥4 times per year had increased from 47•07% in 2010 to 65•31% in 2018. By 2018, entecavir (65•07%) and tenofovir (12•98%) had become the predominantly prescribed antiviral agents. INTERPRETATION: The rates of CHB patients in care, receiving HBV tests and on antiviral therapy substantially increased in Beijing, China. However, more efforts are still needed to increase the uptake of HBV tests and treatment for achieving the goal of HBV elimination by 2030. FUNDING: Beijing Municipal Science and Technology Commission (No.D161100002716003), National Science and Technology Major Special Project for Infectious Diseases (No.Z191100007619037, No.2018ZX10302204), and Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals (No. XXX 0104).

10.
EPMA J ; 12(2): 103-115, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34194583

RESUMO

The early identification of Suboptimal Health Status (SHS) creates a window opportunity for the predictive, preventive, and personalized medicine (PPPM) in chronic diseases. Previous studies have observed the alterations in several mRNA levels in SHS individuals. As a promising "omics" technology offering comprehension of genome structure and function at RNA level, transcriptome profiling can provide innovative molecular biomarkers for the predictive identification and targeted prevention of SHS. To explore the potential biomarkers, biological functions, and signalling pathways involved in SHS, an RNA sequencing (RNA-Seq)-based transcriptome analysis was firstly conducted on buffy coat samples collected from 30 participants with SHS and 30 age- and sex-matched healthy controls. Transcriptome analysis identified a total of 46 differentially expressed genes (DEGs), in which 22 transcripts were significantly increased and 24 transcripts were decreased in the SHS group. A total of 23 transcripts were selected as candidate predictive biomarkers for SHS. Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that several biological processes were related to SHS, such as ATP-binding cassette (ABC) transporter and neurodegeneration. Protein-protein interaction (PPI) network analysis identified 10 hub genes related to SHS, including GJA1, TWIST2, KRT1, TUBB3, AMHR2, BMP10, MT3, BMPER, NTM, and TMEM98. A transcriptome predictive model can distinguish SHS individuals from the healthy controls with a sensitivity of 83.3% (95% confidence interval (CI): 73.9-92.7%), a specificity of 90.0% (95% CI: 82.4-97.6%), and an area under the receiver operating characteristic curve of 0.938 (95% CI: 0.882-0.994). In the present study, we demonstrated that blood (buffy coat) samples appear to be a very promising and easily accessible biological material for the transcriptomic analyses focused on the objective identification of SHS by using our transcriptome predictive model. The pattern of particularly determined DEGs can be used as predictive transcriptomic biomarkers for the identification of SHS in an individual who may, subjectively, feel healthy, but at the level of subcellular mechanisms, the changes can provide early information about potential health problems in this person. Our findings also indicate the potential therapeutic targets in dealing with chronic diseases related to SHS, such as T2DM and CVD, and an early onset of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, as well as the findings suggest the targets for personalized interventions as promoted in PPPM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-021-00238-1.

11.
Ital J Pediatr ; 47(1): 160, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289880

RESUMO

BACKGROUND: Wiedemann-Rautenstrauch syndrome (WRS) is a rare autosomal recessive neonatal progeroid disorder characterized by prenatal and postnatal growth retardation, short stature, a progeroid appearance, hypotonia, and mental impairment. CASE PRESENTATION: A 6-year-old patient, who initially presented with multiple postnatal abnormalities, facial dysplasia, micrognathia, skull appearance, hallux valgus, and congenital dislocation of the hip, was recruited in this study. The patient was initially diagnosed with progeria. The mother of the patient had abnormal fetal development during her second pregnancy check-up, and the clinical phenotype of the fetus was similar to that of the patient. Whole-exome sequencing (WES) of the patient was performed, and POLR3B compound heterozygous variants-c.2191G > C:p.E731Q and c.3046G > A:p.V1016M-were identified in the patient. Using Sanger sequencing, we found that the phenotypes and genotypes were segregated within the pedigree. These two variants are novel and not found in the gnomAD and 1000 Genomes databases. The two mutation sites are highly conserved between humans and zebrafish. CONCLUSIONS: Our study not only identified a novel WRS-associated gene, POLR3B, but also broadened the mutational and phenotypic spectra of POLR3B. Furthermore, WES may be useful for identifying rare disease-related genetic variants.


Assuntos
Retardo do Crescimento Fetal/genética , Progéria/genética , RNA Polimerase III/genética , Sequenciamento Completo do Exoma , Criança , Genótipo , Humanos , Masculino , Linhagem , Fenótipo
12.
BMC Oral Health ; 21(1): 307, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34130673

RESUMO

BACKGROUND: This study aimed to compare the use of photon-initiated photoacoustic streaming (PIPS) and conventional needle irrigation (CNI) in conjunction with different concentrations of sodium hypochlorite (NaOCl) to remove Enterococcus faecalis (E. faecalis) suspended bacteria and biofilms from root canal systems with different diameters or tapers. METHODS: Artificial root canal samples (n = 480) were randomly divided into three groups (n = 160/group). The canals were prepared to fit file sizes #10/.02, #25/.02, or #25/.06. The size #10/.02 group was incubated for seven days. The size #25/.02 or #25/.06 group was incubated for 2 days. A stable biological model of E. faecalis infection was established. The root canals were washed with distilled water or with 1%, 2%, or 5.25% NaOCl combined with CNI or PIPS. Bacterial suspensions and biofilms were assessed using an ATP assay kit and fluorescence microscopy. Image-Pro Plus was used to analyse the average fluorescence intensity to determine the most suitable root canal irrigation solution. RESULTS: In the CNI and PIPS groups, the ATP value of the 5.25% NaOCl subgroup was the lowest, followed by that of the 2% and 1% NaOCl subgroups. The ATP value of the distilled water subgroup was the highest (P < 0.05). When the root canal taper was 0.02, the ATP value of the #10/.02 + PIPS group was significantly lower than that of the #25/.02 + CNI group (P < 0.05). The average fluorescence intensity of the #10/.02 + PIPS group was lower than that of the #25/.02 + CNI group (P < 0.05). When the apical diameter was #25, the ATP value of the 0.02 taper in the PIPS group was lower than that of the 0.06 taper in the CNI group (P < 0.05), and the average fluorescence intensity of the 0.02 taper + PIPS group was lower than that of the 0.06 taper + CNI group (P < 0.05). PIPS combined with 2% and 5.25% NaOCl effectively improved the long-term antibacterial effect after irrigation and re-culture for 6 h. CONCLUSIONS: Compared with CNI, PIPS has greater ability to remove bacteria in root canals with a small preparation diameter and a small taper. PIPS with 2% and 5.25% NaOCl exhibited superior antibacterial and bacteriostatic effects.


Assuntos
Cavidade Pulpar , Técnicas Fotoacústicas , Enterococcus faecalis , Humanos , Irrigantes do Canal Radicular/uso terapêutico , Preparo de Canal Radicular , Hipoclorito de Sódio/uso terapêutico
13.
Orphanet J Rare Dis ; 16(1): 224, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001203

RESUMO

BACKGROUND: Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutation of ACAT1 that affects both isoleucine catabolism and ketolysis. There is little information available regarding the incidence, newborn screening (NBS), and mutational spectrum of BKTD in China. RESULTS: We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published data from Chinese BKTD patients. A total of 16,088,190 newborns were screened and 14 patients were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. In total, twenty-nine patients were genetically diagnosed with BKTD, 12 of which were newly identified. Most patients exhibited typical blood acylcarnitine and urinary organic acid profiles. Interestingly, almost all patients (15/16, 94%) showed elevated 3-hydroxybutyrylcarnitine (C4OH) levels. Eighteen patients presented with acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of nine patients were triggered by infections, diarrhea, or an inflammatory response to vaccination. Approximately two-thirds of patients had favorable outcomes, one showed a developmental delay and three died. Twenty-seven distinct variants were identified in ACAT1, among which five were found to be novel. CONCLUSION: This study presented the largest series of BKTD cohorts in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by the addition of C4OH to the current panel of 3-hydroxyisovalerylcarnitine and tiglylcarnitine markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in the Chinese population were expanded with five newly identified variants.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Triagem Neonatal , Acetil-CoA C-Aciltransferase/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/genética , China/epidemiologia , Humanos , Recém-Nascido , Estudos Retrospectivos
14.
J Aerosol Med Pulm Drug Deliv ; 34(3): 155-170, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33887156

RESUMO

Rationale: There is an urgent need to understand the risk of viral transmission during nebulizer treatment of patients with coronavirus disease 2019 (COVID-19). Objectives: To assess the risk of transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS, Middle East respiratory syndrome (MERS), and influenza with administration of drugs via nebulizer. Methods: We searched multiple electronic databases, including PubMed®, China National Knowledge Infrastructure, Wanfang, preprint databases, and clinicaltrials.gov through December 1, 2020. Any study design in any language describing the risk of viral transmission with nebulizer treatment was eligible. Data were abstracted by one investigator and verified by a second. Results: We identified 22 articles: 1 systematic review, 7 cohort/case-control studies, 7 case series, and 7 simulation-based studies. Eight individual studies involved patients with SARS, five involved MERS, and one involved SARS-CoV-2. The seven cohort/case-control studies (four high risk of bias [ROB], three unclear ROB) found mixed results (median odds ratio 3.91, range 0.08-20.67) based on very weak data among a small number of health care workers (HCWs) with variable use of personal protective equipment (PPE). Case series had multiple potential contributors to transmission. Simulation studies found evidence for droplet dispersion after saline nebulization and measureable influenza viral particles up to 1.7 m from the source after 10 minutes of nebulization with a patient simulator. Study heterogeneity prevented meta-analysis. Conclusions: Case series raise concern of transmission risk, and simulation studies demonstrate droplet dispersion with virus recovery, but specific evidence that exposure to nebulizer treatment increases transmission of coronaviruses similar to COVID-19 is inconclusive. Tradeoffs balancing HCW safety and patient appropriateness can potentially minimize risk, including choice of delivery method for inhaled medications (e.g., nebulizer vs. metered dose inhaler) and PPE (e.g., N95 vs. surgical mask).


Assuntos
COVID-19/transmissão , Nebulizadores e Vaporizadores , SARS-CoV-2 , Infecções por Coronavirus/transmissão , Pessoal de Saúde , Humanos , Equipamento de Proteção Individual , Risco , Síndrome Respiratória Aguda Grave/transmissão
15.
Appl Environ Microbiol ; 87(12): e0047421, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-33863706

RESUMO

The genetic regulation of Colletotrichum (Glomerella) sexual reproduction does not strictly adhere to the Ascomycota paradigm and remains poorly understood. Morphologically different but sexually compatible strain types, termed plus and minus, have been recognized, but the biological and molecular distinctions between these strain types remain elusive. In this study, we characterized the sexual behaviors of a pair of plus and minus strains of C. fructicola with the aid of live-cell nucleus-localized fluorescent protein labeling, gene expression, and gene mutation analyses. We confirmed a genetically stable plus-to-minus switching phenomenon and demonstrated the presence of both cross-fertilized and self-fertilized perithecia within the mating line (perithecia cluster at the line of colony contact) between plus and minus strains. We demonstrated that pheromone signaling genes (a-factor-like and α-factor-like pheromones and their corresponding GPCR receptors) were differently expressed between vegetative hyphae of the two strains. Moreover, deletion of pmk1 (a FUS/KSS1 mitogen-activate protein kinase) in the minus strain severely limited mating line formation, whereas deletion of a GPCR (FGSG_05239 homolog) and two histone modification factors (hos2, snt2) in the minus strain did not affect mating line development but altered the ratio between cross-fertilization and self-fertilization within the mating line. We propose a model in which mating line formation in C. fructicola involves enhanced protoperithecium differentiation and enhanced perithecium maturation of the minus strain mediated by both cross-fertilization and diffusive effectors. This study provides insights into mechanisms underlying the mysterious phenomenon of plus-minus-mediated sexual enhancement being unique to Colletotrichum fungi. IMPORTANCE Plus-minus regulation of Colletotrichum sexual differentiation was reported in the early 1900s. Both plus and minus strains produce fertile perithecia in a homothallic but inefficient manner. However, when the two strain types encounter each other, efficient differentiation of fertile perithecia is triggered. The plus strain, by itself, can also generate minus ascospore progeny at high frequency. This nontypical mating system facilitates sexual reproduction and is Colletotrichum specific; the underlying molecular mechanisms, however, remain elusive. The current study revisits this longstanding mystery using C. fructicola as an experimental system. The presence of both cross-fertilized and self-fertilized perithecia within the mating line was directly evidenced by live-cell imaging with fluorescent markers. Based on further gene expression and gene mutation analysis, a model explaining mating line development (plus-minus-mediated sexual enhancement) is proposed. Data reported here have the potential to allow us to better understand Colletotrichum mating and filamentous ascomycete sexual regulation.


Assuntos
Colletotrichum/genética , Colletotrichum/fisiologia , Reprodução/genética , Proteínas Fúngicas/genética , Fenótipo
16.
Clin Gastroenterol Hepatol ; 19(12): 2499-2513, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33667678

RESUMO

BACKGROUND & AIMS: The aim of our study was to characterize the performance of hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B (CHB) patients through meta-analysis followed by external validation. METHODS: We performed a systematic review and meta-analysis of current literature, followed by external validation in independent multi-center cohort with 986 patients with CHB undergoing entecavir treatment (median follow-up: 4.7 years). Model performance to predict HCC within 3, 5, 7, and 10 years was assessed using area under receiver operating characteristic curve (AUROC) and calibration index. Subgroup analysis were conducted by treatment status, cirrhotic, race and baseline alanine aminotransferase. RESULTS: We identified 14 models with 123,885 patients (5,452 HCC cases), with REACH-B, CU-HCC, GAG-HCC, PAGE-B and mPAGE-B models being broadly externally validated. Discrimination was generally acceptable for all models, with pooled AUC ranging from 0.70 (95% CI, 0.63-0.76 for REACH-B) to 0.83 (95% CI, 0.78-0.87 for REAL-B) for 3-year, 0.68 (95% CI, 0.64-0.73 for REACH-B) to 0.81 (95% CI, 0.77-0.85 for REAL-B) for 5-year and 0.70 (95% CI, 0.58-0.80 for PAGE-B) to 0.81 (95% CI, 0.78-0.84 for REAL-B and 0.77-0.86 for AASL-HCC) for 10-year prediction. However, calibration performance was poorly reported in most studies. In external validation cohort, REAL-B showed highest discrimination with 0.76 (95% CI, 0.69-0.83) and 0.75 (95% CI, 0.70-0.81) for 3 and 5-year prediction. The REAL-B model was also well calibrated in the external validation cohort (3-year Brier score 0.066). Results were consistent in subgroup analyses. CONCLUSIONS: In a systematic review of available HCC models, the REAL-B model exhibited best discrimination and calibration.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamento farmacológico , Estudos de Coortes , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Fatores de Risco
17.
Hepatol Int ; 15(3): 611-620, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33677771

RESUMO

BACKGROUND AND AIMS: Antiviral treatment with necleos(t)ide analogues contributes to histological improvement and virologic response in chronic hepatitis B (CHB) patients. However, whether adding pegylated interferon alpha2a (Peg-IFN-α-2a) can help additional clinical benefit, particularly on fibrosis regression was still unknown. METHODS: Chronic hepatitis B patients with pre-treatment biopsy-proven Ishak fibrosis score 2, 3 or 4 were randomly assigned to entecavir (ETV) alone or ETV plus Peg-IFN-α-2a (Peg-IFN-α-2a add-on) group (1:2 ratio). Post-treatment liver biopsy was performed at week 78. Fibrosis regression was defined as decrease in Ishak fibrosis score by ≥ 1 stage or predominantly regressive categorized by P-I-R score. Serum HBV DNA levels were assessed at baseline and every 26 weeks, while HBsAg and HBeAg were evaluated at baseline and every 52 weeks. RESULTS: A total of 218 treatment-naive CHB patients were randomly assigned to ETV alone or Peg-IFN-α-2a add-on group. Totals of 155 patients (ETV alone: Peg-IFN-α-2a add-on, 47:108) were included in statistical analysis. Fibrosis regression rates were 68% (32/47) in the ETV alone and 56% (60/108) in Peg-IFN-α-2a add-on group (p = 0.144). Both groups showed a similar trend of virological suppression during the process of 104-week antiviral therapy (p = 0.132). HBeAg or HBsAg loss or seroconversion rates in the ETV alone group were lower than Peg-IFN-α-2a add-on group though without statistical significance. CONCLUSIONS: Peg-IFN-α-2a add-on therapy did not yield additional fibrosis regression and virologic response than ETV alone therapy.


Assuntos
Fibrose , Guanina/análogos & derivados , Hepatite B Crônica , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Antivirais/uso terapêutico , Combinação de Medicamentos , Guanina/uso terapêutico , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Humanos , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento
18.
Front Pediatr ; 9: 638190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748046

RESUMO

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis, recurrent fever, and intellectual disability. CIPA is mainly caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1). This study aims to identify pathogenic mutations underlying CIPA in two unrelated Chinese families. Methods: DNA was extracted from blood samples of patients and their available family members and subjected to whole exome sequencing (WES). Real-time PCR (qPCR), Gap-PCR, and Sanger sequencing were applied to verify the identified variants. Result: We found novel compound gross deletion mutations [exon1-6 del (g.1-1258_10169del); exon5-7 del (g.6995_11999del)] of NTRK1 (MIM 191315) gene in family 1 and the compound heterozygous mutations [c.851-33T>A; exon5-7 del (g.6995_11999del)] in family 2. Interestingly, we discovered the intragenic novel gross deletion [exon5-7 del (g.6995_11999del)] mediated by recombination between Alu elements. Conclusions: The present study highlights two rare gross deletion mutations in the NTRK1 gene associated with CIPA in two unrelated Chinese families. The deletion of exon1-6 (g.1-1258_10169del) is thought to be the largest NTRK1 deletion reported to date. Our findings expand the mutation spectrum of NTRK1 mutations in the Chinese and could be useful for prenatal interventions and more precise pharmacological treatments to patients. WES conducted in our study is a convenient and useful tool for clinical diagnosis of CIPA and other associated disorders.

19.
Transplant Rev (Orlando) ; 35(1): 100592, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33422927

RESUMO

Background-objectives: Liver transplantation (LT) and combined liver and kidney transplantation (CLKT) have been proposed as enzyme replacement therapies for methylmalonic aciduria (MMA). We aimed to synthesize the available evidence on their safety and efficacy. METHODS: Medline, Embase and Cochrane library were searched to identify studies that reported post-LT/CLKT clinical outcomes of MMA from their inception to February 1, 2020. The pooled rate was calculated using random-effects model with Freeman-Tukey double arcsine transformation method. RESULTS: Thirty-two studies involving 109 patients were included. The pooled estimate rates were 99.9% (95% CI 95.3-100.0) for patient survival, 98.5% (95% CI 91.5-100.0) for graft survival after LT/CLKT. The combined incidence of biliary, vascular complications and rejection were 0.2% (95% CI 0.0-6.6), 7.7% (95% CI 0.1-22.1) and 18.4% (95% CI 4.6-36.3), respectively. The pooled estimate rates were 100.0% (95% CI 99.4-100.0) for metabolic eradication, 61.5% (95% CI: 33.4-87.0) for normalization of kidney function. Chronic kidney disease (CKD) remission is more promising after CLKT (70.3% VS 37.6% in LT group). The pooled estimate rates for neurodevelopmental status improvement and protein intake liberalization were 52.0% (95% CI 2.8-98.8) and 36.3% (95% CI 6.3-71.7), respectively. CONCLUSIONS: This first quantitative systematic review confirms favorable survival outcomes and partially improved disease-related complications in transplanted MMA patients, although some results should be interpreted with caution. Future studies with detailed description of long-term outcomes and consensus on neurodevelopmental evaluation method can help provide a more accurate picture.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Transplante de Rim , Transplante de Fígado , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos
20.
Hepatol Int ; 15(1): 82-92, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33460002

RESUMO

BACKGROUND AND AIMS: Many models have been developed to predict liver-related events (LRE) in chronic hepatitis B, few focused on compensated HBV-induced cirrhosis. We aimed to describe the incidence of LRE and to determine independent risk predictors of LRE in compensated HBV-induced cirrhosis patients receiving antiviral therapy using routinely available parameters. METHODS: Prospective cohorts of treatment-naïve adults with compensated HBV-induced cirrhosis were enrolled. Patients were treated with entecavir (ETV) or ETV + thymosin-alpha1 (Thy-α1) or lamivudine (LAM) + adefovir (ADV). Data were collected at baseline and every 6 months. LRE was defined as development of decompensation, HCC or death. RESULTS: Totally 937 patients were included, 608 patients treated with ETV, 252 with ETV + Thy-α1, and 77 with LAM + ADV. After a median follow-up of 4.5 years, 88 patients developed LRE including 48 with HCC. The cumulative incidence of LRE at year 1, 3, and 5 was 2.1%, 7.0%, and 12.7%, respectively, and was similar for three treatment groups. All models using variables at month 6 or 12 had better fit than models using baseline values. The best model for prediction of LRE used PLT, GGT, and AFP at month 6 [AUC: 0.762 (0.678-0.814)], for hepatic decompensation-PLT, LSM and GGT at month 12 (AUC: 0.834 (0.675-0.919)), and for HCC-AFP and GGT at month 6 [AUC 0.763 (0.691-0.828)]. All models had negative predictive values of 94.0-98.8%. CONCLUSION: Models using on-treatment variables are more accurate than models using baseline variables in predicting LRE in patient with compensated HBV-induced cirrhosis receiving antiviral therapy. ClincialTrials.gov number NCT01943617, NCT01720238, NCT03366571, NCT02849132.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Cirrose Hepática , Adulto , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , DNA Viral , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Lamivudina/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Estudos Prospectivos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...