RESUMO
OBJECTIVE: To explore the cause of inconsistency between the results of trisomy 7 by expanded non-invasive prenatal testing (NIPT-PLUS) and trisomy 18 by prenatal diagnosis. METHODS: A pregnant woman who received genetic counseling at Jiaozuo Maternal and Child Health Care Hospital on July 5, 2020 was selected as the study subject. NIPT-PLUS, systematic ultrasound and interventional prenatal testing were carried out. The middle segment and root of umbilical cord, center and edge of the maternal and fatal surface of the placenta were sampled for the validation by copy number variation sequencing (CNV-seq). RESULTS: The result of NIPT-PLUS indicated that the fetus has trisomy 7. Systematic ultrasound has shown multiple malformations including atrioventricular septal defect, horseshoe kidney, and rocker-bottom feet. However, QF-PCR, chromosomal karyotyping analysis, and CNV-seq of amniotic fluid samples all showed that the fetus was trisomy 18. Validation using multiple placental samples confirmed that the middle segment of the umbilical cord contains trisomy 18, the center of the placenta contained trisomy 7, and other placental sites were mosaicism for trisomy 7 and trisomy 18. Notably, the ratio of trisomy 18 became lower further away from the umbilical cord. CONCLUSION: The false positive results of trisomy 7 and false negative trisomy 18 by NIPT-PLUS was probably due to the existence of placental mosaicism. Strict prenatal diagnosis is required needed aneuploidy is detected by NIPT-PLUS to exclude the influence of placental mosaicisms.
Assuntos
Transtornos Cromossômicos , Trissomia , Criança , Gravidez , Feminino , Humanos , Trissomia/diagnóstico , Trissomia/genética , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/genética , Placenta , Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal/métodos , Transtornos Cromossômicos/genética , AneuploidiaRESUMO
MAIN CONCLUSION: Sixteen Lhc genes representing 13 phylogenetic groups were identified from the full-length transcriptome of tigernut, exhibiting development regulation and diurnal fluctuation expression patterns in leaves. Nuclear encoded light-harvesting chlorophyll a/b-binding (Lhc) proteins play indispensable roles in oxygenic photosynthesis. In this study, we present the first transcriptome-based characterization of Lhc family genes in tigernut (Cyperus esculentus L.), a Cyperaceae C4 plant producing oil in underground tubers. A number of 16 Lhc genes representing 13 phylogenetic groups identified from the full-length tigernut transcriptome are equal to that found in both Carex littledalei (another Cyperaceae plant) and papaya, slightly more than 15 members present in both rice and jatropha, but relatively less than 18, 20, and 21 members present in sorghum, cassava, and Arabidopsis, respectively. Nevertheless, nearly one-vs-one orthologous relationship was observed in most groups, though some of them are no longer located in syntenic blocks and species-specific expansion was frequently found in Lhcb1. Comparative genomics analysis revealed that the loss of two groups (i.e., Lhca2 and Lhca5) in C. littledalei is species-specific, sometime after the split with tigernut, and the expansion of Lhcb1 was mainly contributed by tandem duplication as observed in most species. Interestingly, a transposed duplication, which appears to be shared by monocots, was also identified in Lhcb1. Further transcriptome profiling revealed a predominant expression pattern of most CeLhc family genes in photosynthetic tissues and enhanced transcription during leaf maturation, reflecting their key roles in light absorption. Moreover, qRT-PCR analysis revealed an apparent diurnal fluctuation expression pattern of 11 dominant CeLhc genes. These findings not only highlight species-specific evolution of Lhc genes in the Cyperaceae family as well as the monocot lineage, but also provide valuable information for further functional analysis and genetic improvement in tigernut.
Assuntos
Arabidopsis , Cyperaceae , Cyperus , Filogenia , Clorofila A , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de PlantasRESUMO
KEY MESSAGE: CeOLE genes exhibit a tuber-predominant expression pattern and their mRNA/protein abundances are positively correlated with oil accumulation during tuber development. Overexpression could significantly increase the oil content of tobacco leaves. Oleosins (OLEs) are abundant structural proteins of lipid droplets (LDs) that function in LD formation and stabilization in seeds of oil crops. However, little information is available on their roles in vegetative tissues. In this study, we present the first genome-wide characterization of the oleosin family in tigernut (Cyperus esculentus L., Cyperaceae), a rare example accumulating high amounts of oil in underground tubers. Six members identified represent three previously defined clades (i.e. U, SL and SH) or six out of seven orthogroups (i.e. U, SL1, SL2, and SH1-3) proposed in this study. Comparative genomics analysis reveals that lineage-specific expansion of Clades SL and SH was contributed by whole-genome duplication and dispersed duplication, respectively. Moreover, presence of SL2 and SH3 in Juncus effuses implies their appearance sometime before Cyperaceae-Juncaceae divergence, whereas SH2 appears to be Cyperaceae specific. Expression analysis showed that CeOLE genes exhibit a tuber-predominant expression pattern and transcript levels are considerably more abundant than homologs in the close relative Cyperus rotundus. Moreover, CeOLE mRNA and protein abundances were shown to positively correlate with oil accumulation during tuber development. Additionally, two dominant isoforms (i.e. CeOLE2 and -5) were shown to locate in LDs as well as the endoplasmic reticulum of tobacco (Nicotiana benthamiana) leaves, and are more likely to function in homo and heteromultimers. Furthermore, overexpression of CeOLE2 and -5 in tobacco leaves could significantly increase the oil content, supporting their roles in oil accumulation. These findings provide insights into lineage-specific family evolution and putative roles of CeOLE genes in oil accumulation of vegetative tissues, which facilitate further genetic improvement for tigernut.
Assuntos
Cyperaceae , Cyperus , Cyperus/genética , Cyperus/metabolismo , Cyperaceae/genética , Cyperaceae/metabolismo , Óleos de Plantas/metabolismo , Sementes/genética , Tubérculos/genética , Tubérculos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Dipeptidyl peptidase-4 (DPP4) has been proven to exert its functions by both enzymatic and nonenzymatic pathways. The nonenzymatic function of DPP4 in diabetes-associated cognitive impairment remains unexplored. We determined DPP4 protein concentrations or its enzymatic activity in type 2 diabetic patients and db/db mice and tested the impact of the non-enzymatic function of DPP4 on mitochondrial dysfunction and cognitive impairment both in vivo and in vitro. The results show that increased DPP4 activity was an independent risk factor for incident mild cognitive impairment (MCI) in type 2 diabetic patients. In addition, DPP4 was highly expressed in the hippocampus of db/db mice and contributed to mitochondria dysfunction and cognitive impairment. Mechanistically, DPP4 might bind to PAR2 in the hippocampus and trigger GSK-3ß activation, which downregulates peroxisome proliferator-activated receptor gamma coactivator 1 alpha expression and leads to mitochondria dysfunction, thereby promoting cognitive impairment in diabetes. Our findings indicate that the nonenzymatic function of DPP4 might promote mitochondrial dysfunction and cognitive impairment in diabetes.
Assuntos
Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Dipeptidil Peptidase 4 , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Diabetes Mellitus Tipo 2/complicações , Dipeptidil Peptidase 4/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Camundongos , MitocôndriasRESUMO
A coumarin-based probe, FP2, was designed for the differential detection of fluoride anions and thiols, i.e., the corresponding nucleophilic substitution products from fluorine-containing G agents and sulfur-containing V agents, thus having the potential to discriminate between these two nerve agents. FP2 with two functional reaction groups, α, ß-unsaturated ketone and silyl groups, can react selectively with fluoride anions and thiols at the µM level respectively. Intriguingly, in the THF solution, FP2 reacts with the fluoride anion but not with the thiol, whereas in the EtOH/HEPES solution, FP2 reacts with the thiol but not with the fluoride anion. As a result, FP2 can produce different fluorophores in the two detection solutions, thus displaying significant fluorescence changes. In addition, the FP2 detection system can show a significant color change from colorless to yellow within seconds when detecting fluoride anions in THF detection solutions, and from yellow to light blue when detecting thiols in EtOH/HEPES solutions, which will facilitate visual detection by emergency responders at the scene of an incident involving a nerve agent.
Assuntos
Corantes Fluorescentes/química , Fluoretos/química , Agentes Neurotóxicos/química , Compostos de Sulfidrila/química , Enxofre/química , Concentração de Íons de HidrogênioRESUMO
OBJECTIVE: To detect genomic copy number variations (CNVs) among 145 children with unexplained mental retardation/developmental delay (MR/DD) by using low-depth whole-genome copy number variation sequencing (CNV-seq). METHODS: Peripheral blood samples were collected from the patients and subjected to DNA extraction and CNV-seq. The results were analyzed by a combination of bioinformatic tools. RESULTS: Forty-nine patients were found to carry a total of 67 CNVs with an average size of 5.27 Mb. Among these, 22 patients were assessed to carry MR/DD-related CNVs involving 21 syndromes. This gave a diagnostic rate of 15.17%(22/145) for CNVs associated with unexplained MR/DD. The corresponding regions of the 22 MR/DD-related CNVs in the human genome covered 174 MR/DD-related pathogenic genes, which have mapped to 18 sections on 10 chromosomes. CONCLUSION: Genomic CNVs-related microdeletions/duplications account for a significant proportion of unexplained MR/DD, for which CNV-seq can provide an accurate diagnosis.
Assuntos
Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento , Deficiência Intelectual , Sequenciamento Completo do Genoma , Criança , Deleção Cromossômica , Duplicação Cromossômica , Deficiências do Desenvolvimento/genética , Genômica , Humanos , Deficiência Intelectual/genéticaRESUMO
OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the analysis of 824 samples from miscarriage or stillbirth. METHODS: Copy number variations (CNVs) in the abortic chorionic villi or stillbirth tissues were detected by CMA. RESULTS: All specimens were successfully analyzed, among which 381 (46.2%) were diagnosed with chromosomal abnormalities, which included 312 (81.9%) numerical abnormalities, 66 (17.3%) structural abnormalities and 3 (0.8%) uniparental disomies. Among numerical chromosomal abnormalities, aneuploidies was most common (92.0%), with trisomy 16 and 45,X accounting for 41 (13.1%) and 63 (20.2%) of the cases, respectively. Among the 66 structural chromosomal aberrations, there were 26 (39.4%) CNVs duplications, 20 (30.3%) CNVs deletions, and 20 (30.3%) CNVs duplication and deletions. 33 CNVs were predicted as have a high chance to lead to a disease. CONCLUSION: CMA is a reliable, robust, and high-resolution method for the analysis of miscarriage or stillbirth samples. Numerical aberrations, in particular chromosomal aneuploides, are the main cause for spontaneous abortions and stillbirths.
Assuntos
Aborto Espontâneo/genética , Aberrações Cromossômicas , Transtornos Cromossômicos , Análise em Microsséries , Natimorto/genética , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Variações do Número de Cópias de DNA , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Previous studies have found that bone mesenchymal stem cells (BMSCs) were capable of self-replication, multi-differentiation, and regeneration. The aim of this study was to carry out a systematic review and meta-analysis of the efficacy of BMSC therapy for ovariectomized rats. METHODS: The PubMed, Embase, Web of Science, China National Knowledge Infrastructure, VIP, and Chinese Sinomed databases were searched systematically from their initiation date to October 5, 2018. Two researchers independently screened the literatures, which used the bone mineral density (BMD), total bone volume by total tissue volume (BV/TV) (%), and trabecular thickness/spacing (Tb/Sp) as the outcome measures. RESULTS: Five eligible studies were selected. In the BMSC treatment groups, the BMD values and normalized BV/TV values remarkably increased. In addition, in the BMSCs plus other treatment groups, the BMD and Tb/Sp values significantly increased. CONCLUSION: This study showed that BMSCs could accelerate callus maturity, ossification and restore mechanical properties of bones in osteoporotic fractures.
Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Osteoporose Pós-Menopausa/patologia , Osteoporose Pós-Menopausa/terapia , Ovariectomia/tendências , Animais , Feminino , Humanos , Osteoporose Pós-Menopausa/etiologia , Ovariectomia/efeitos adversos , Ratos , Ratos Sprague-DawleyRESUMO
Calcium-dependent protein kinases are involved in various biological processes, including hormone response, growth and development, abiotic stress response, disease resistance, and nitrogen metabolism. We identified a novel mutant of a calcium-dependent protein-kinase-encoding gene, esl4, by performing map cloning. The esl4 mutant was nitrogen deficient, and expression and enzyme activities of genes related to nitrogen metabolism were down-regulated. ESL4 was mainly expressed in the vascular bundles of roots, stems, leaves, and sheaths. The ESL4 protein was localized in the cell membranes. Enzyme activity and physiological index analyzes and analysis of the expression of nitrogen metabolism and senescence-related genes indicated that ESL4 was involved in nitrogen metabolism. ESL4 overexpression in transgenic homozygous T2 plants increased nitrogen-use efficiency, improving yields when little nitrogen was available. The seed-set rates, yields per plant, numbers of grains per plant, grain nitrogen content ratios, and total nitrogen content per plant were significantly or very significantly higher for two ESL4 overexpression lines than for the control plants. These results suggest that ESL4 may function upstream of nitrogen-metabolism genes. The results will allow ESL4 to be used to breed novel cultivars for growing in low-nitrogen conditions.
Assuntos
Genes de Plantas , Mutação/genética , Nitrogênio/deficiência , Nitrogênio/metabolismo , Oryza/genética , Proteínas de Plantas/genética , Proteínas Quinases/genética , Membrana Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Fenótipo , Floema/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Proteínas Recombinantes/metabolismo , Frações Subcelulares/metabolismoRESUMO
Two new coumarins, (E)-2-(4-hydroxy-3-methoxybenzylidene)-5-methoxy-2H-[1,4]dioxino[2,3-h]chromene-3,9-dione (indicumin E, 1) and 7-hydroxy-6,8-dimethoxy-3-(4'-hydroxy-3'-methoxyphenyl)-coumarin (2), together with two known coumarins isofraxidin (3) and fraxetin (4), were isolated from the Solanum indicum seeds. Their structures were established on the basis of 1D and 2D spectroscopic data. Compound 1 was the rarest coumarinolignoid known to date.
Assuntos
Cumarínicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Solanum/química , Cumarínicos/química , Medicamentos de Ervas Chinesas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Sementes/químicaRESUMO
Two new flavonols, 6-p-hydroxybenzyl kaempferol (1) and 6-p-hydroxybenzyl quercetin (2), together with six known compounds were isolated from the roots of Cudrania cochinchinensis and their structures elucidated on the basis of spectroscopic methods. Their antioxidant capacities were evaluated by 1,1-diphenyl-2-picryl-hydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging assays. The results suggested that compounds 2, 4, and 7 showed significant radical-scavenging activities.
Assuntos
Antioxidantes/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Flavonóis/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Quempferóis/isolamento & purificação , Moraceae/química , Quercetina/análogos & derivados , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Bifenilo/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Flavonóis/química , Flavonóis/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Quempferóis/química , Quempferóis/farmacologia , Estrutura Molecular , Picratos/farmacologia , Raízes de Plantas/química , Quercetina/química , Quercetina/isolamento & purificação , Quercetina/farmacologiaRESUMO
INTRODUCTION: Skeletal unloading during a spaceflight could result in bone loss and osteopenia, ultimately leading to poor bone strength. The purpose of the present study was to investigate the influence of bone loss on the dynamic behavior of cancellous bone. METHODS: Microgravity-induced bone loss and osteopenia were simulated in a macaque head-down bed rest (HDBR) model, in which 20 macaques were laid on a bed tilted by -6 degrees from the horizontal. These macaques were randomly divided into control (Con) and head down bed rest (HDBR) groups. After 28 d, 5 macaques chosen at random from each group were tested for bone density and mechanical properties, and the obtained data was used to develop a density-based constitutive equation; the remaining animals were tested only for bone density in order to attain statistical power. A split Hopkinson bar was used to monitor the dynamic response of cancellous bone. Cancellous bone deformation under high strain rate conditions was recorded by high-speed videos. RESULTS: Compared with the Con group, the Young's modulus of cancellous bone from HDBR macaque lumbar vertebrae were decreased by 6.03%. Based on the static and dynamic experimental results, parameters in the Maxwell nonlinear viscoelasticity material model were estimated. DISCUSSION: This model of cancellous bone under high strain rate was useful to establish the medical tolerance and evolution criteria of impact-related trauma by finite element method calculations.
Assuntos
Repouso em Cama/efeitos adversos , Doenças Ósseas Metabólicas/fisiopatologia , Reabsorção Óssea/fisiopatologia , Decúbito Inclinado com Rebaixamento da Cabeça/efeitos adversos , Vértebras Lombares/fisiopatologia , Animais , Densidade Óssea , Doenças Ósseas Metabólicas/etiologia , Reabsorção Óssea/etiologia , Módulo de Elasticidade , Macaca , Voo Espacial , Ausência de Peso/efeitos adversosRESUMO
INTRODUCTION: The objective of this study was to observe the differences in the biodynamic responses of male and female crewmembers during a simulated Soyuz spacecraft (short-duration flights) impact landing. METHODS: There were 16 volunteers (8 men and 8 women) recruited to sit in a pseudo-supine position and be exposed to several impact acceleration pulses. The acceleration peaks ranged from 7.7 to 11.8 g with a duration of around 50 ms. Acceleration responses from the drop platform and seat, and at the volunteers' head, shoulder, chest, and ilium were measured. RESULTS: Results indicated that there were significant gender-based differences in the peak acceleration measured from volunteers' shoulders and iliums. The peak decelerations measured at the head and ilium were relatively higher than those measured at other levels on the seat. DISCUSSION: It was recommended that more attention be focused on the sex differences of biodynamic responses of crews in the study of new protective designs for space capsule and personal life support equipment.
Assuntos
Aceleração , Fatores Sexuais , Voo Espacial , Adulto , Fenômenos Biomecânicos , China , Feminino , Humanos , Ílio , Masculino , Segurança , Ombro , Decúbito DorsalRESUMO
OBJECTIVE: Immune tolerance and evasion play a critical role in virus-driven malignancies. However, the phenotype and clinical significance of programmed cell death 1 (PD-1) and its ligands, PD-L1 and PD-L2, in aggressive acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) remain poorly understood, particularly in the Epstein-Barr virus (EBV)-positive subset. METHODS: We used in situ hybridization with EBV-encoded RNA (EBER) to assess the EBV status. We performed immunohistochemistry and flow cytometry analysis to evaluate components of the PD-1/PD-L1/L2 pathway in a multi-institutional cohort of 58 patients with AR-NHL and compared EBV-positive and EBV-negative cases. RESULTS: The prevalence of EBV+ in AR-NHL was 56.9% and was associated with a marked increase in the expression of PD-1/PD-L1/PD-L2 in malignant cells. Patients with AR-NHLs who tested positive for both EBER and PD-1 exhibited lower survival rates compared to those negative for these markers (47.4% vs. 93.8%, p = 0.004). Similarly, patients positive for both EBER and PD-L1 also demonstrated poorer survival (56.5% vs. 93.8%, p = 0.043). Importantly, PD-1 tissue-expression demonstrated independent prognostic significance for overall survival in multivariate analysis and was correlated to elevated levels of LDH (r = 0.313, p = 0.031), increased PD-1+ Tregs (p = 0.006), and robust expression of EBER (r = 0.541, p < 0.001) and PD-L1 (r = 0.354, p = 0.014) expression. CONCLUSIONS: These data emphasize the importance of PD-1-mediated immune evasion in the complex landscape of immune oncology in AR-NHL co-infected with EBV, and contribute to the diagnostic classification and possible definition of immunotherapeutic strategies for this unique subgroup.
Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por Vírus Epstein-Barr , Linfoma não Hodgkin , Humanos , Receptor de Morte Celular Programada 1/genética , Antígeno B7-H1/genética , Infecções por Vírus Epstein-Barr/complicações , Prognóstico , Herpesvirus Humano 4/genéticaRESUMO
PURPOSE: To determine the prevalence of anxiety and depression in patients with nasopharyngeal carcinoma (NPC) and to identify central symptoms and bridge symptoms among psychiatric disorders. METHODS: This cross-sectional study recruited patients with NPC in Guangzhou, China from May 2022, to October 2022. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used for screening anxiety and depression, respectively. Network analysis was conducted to evaluate the centrality and connectivity of the symptoms of anxiety, depression, quality of life (QoL) and insomnia. RESULTS: A total of 2806 respondents with complete GAD-7 and PHQ-9 scores out of 3828 were enrolled. The incidence of anxiety in the whole population was 26.5% (depression, 28.5%; either anxiety or depression, 34.8%). Anxiety was highest at caner diagnosis (34.2%), while depression reached a peak at late-stage radiotherapy (48.5%). Both moderate and severe anxiety and depression were exacerbated during radiotherapy. Coexisting anxiety and depression occurred in 58.3% of those with either anxiety or depression. The generated network showed that anxiety and depression symptoms were closely connected; insomnia was strongly connected with QoL. "Sad mood", "Lack of energy", and "Trouble relaxing" were the most important items in the network. Insomnia was the most significant bridge item that connected symptom groups. CONCLUSION: Patients with NPC are facing alarming disturbances of psychiatric disorders; tailored strategies should be implemented for high-risk patients. Besides, central symptoms (sad mood, lack of energy, and trouble relaxing) and bridge symptoms (insomnia) may be potential interventional targets in future clinical practice.
Assuntos
Ansiedade , Depressão , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Qualidade de Vida , Humanos , Estudos Transversais , Masculino , Feminino , Carcinoma Nasofaríngeo/psicologia , Carcinoma Nasofaríngeo/epidemiologia , Pessoa de Meia-Idade , Depressão/epidemiologia , Depressão/etiologia , Ansiedade/epidemiologia , Ansiedade/etiologia , Neoplasias Nasofaríngeas/psicologia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/epidemiologia , Incidência , China/epidemiologia , Adulto , Idoso , Prevalência , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/etiologiaRESUMO
Three new germacrane-type sesquiterpenoids, volvalerenal F (1), volvalerenal G (2) and volvalerenic acid D (3), along with five known compounds 4-8, were isolated from the CHCl3 soluble partition of the ethanol extract of Valeriana officinalis var. latiofolia. The structures of the new compounds were determined on the basis of spectroscopic evidence, including their 1D- and 2D-NMR spectra, as well as mass spectrometry. The eight germacrane-type sesquiterpenoids showed nerve growth factor (NGF) potentiating activity, which mediates the neurite outgrowth in PC 12D cells. This study intends to reveal the chemical basis of the use of V. officinalis var. latiofolia as a dietary supplement.
Assuntos
Fator de Crescimento Neural/farmacologia , Neuritos/efeitos dos fármacos , Sesquiterpenos de Germacrano/química , Valeriana/química , Animais , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Células PC12 , Ratos , Sesquiterpenos de Germacrano/farmacologiaRESUMO
BACKGROUND: The risk of hepatitis B virus (HBV) reactivation after biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) therapy in patients with rheumatoid arthritis (RA) combined with HBsAg-/HBcAb+ is still inconsistent. METHODS: We conducted a systematic review of existing databases from 1977 to August 22, 2021. Studies of RA patients combined with HBsAg-/HBcAb +, treated with b/tsDMARDs and the reported number of HBV reactivation were included. RESULTS: We included 26 studies of 2252 HBsAg-/HBcAb+ RA patients treated with b/tsDMARDs. The pooled HBV reactivation rate was 2.0% (95% confidence interval [CI]: 0.01-0.04; I2 = 66%, p < .01). In the subgroup analysis, the HBV reactivation rate of rituximab (RTX), abatacept, and inhibitors of Janus kinase (JAK), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were 9.0% (95% CI: 0.04-0.15; I2 = 61%, p = .03), 6.0% (95% CI: 0.01-0.13; I2 = 40%, p = .19), 1.0% (95% CI: 0.00-0.03; I2 = 41%, p = .19), 0.0% (95% CI: 0.00-0.02; I2 = 0%, p = .43), 0.0% (95% CI: 0.00-0.01; I2 = 0%, p = .87), respectively. While HBsAb- patients have a significant risk of reactivation (odds ratio [OR] = 4.56, 95% CI = 2.45-8.48; I2 = 7%, p = .37), low HBsAb+ group also display a significant risk of reactivation (OR = 5.45, 95% CI: 1.35-21.94; I2 = 0%, p = .46). CONCLUSIONS: This meta-analysis demonstrates the highest potential risk of HBV reactivation in HBsAg-/HBcAb+ RA patients receiving RTX treatment, especially HBsAb- patients. Our study furthers the understanding of the prophylactic use of anti-HBV drugs in such patients. However, it is relative safety to use the inhibitors of IL-6, TNF-α, and JAK in these patients.
Assuntos
Artrite Reumatoide , Produtos Biológicos , Hepatite B , Inibidores de Janus Quinases , Humanos , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Hepatite B/induzido quimicamente , Hepatite B/tratamento farmacológico , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/fisiologia , Interleucina-6 , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Fator de Necrose Tumoral alfaRESUMO
Background: The brain and kidney have similar microvascular structure, which makes them susceptible to certain common pathophysiological processes. In this study, we examined several indicators of kidney injury/function associated with cognitive function in older diabetic patients in the hope of finding effective markers for detecting cognitive impairment (CI). Methods: A total of 2209 older participants (aged ≥60 years) from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed for the association between diabetes and CI using a multiple linear regression analysis model. Using the same approach, we also analyzed the relationship between indicators of kidney injury/function and cognitive function (Animal Fluency Test, Digit Symbol Substitution Test) in the diabetic population. Results: Diabetes was associated with CI. In age-adjusted model, older diabetics performed significantly poorer on tests of cognitive function compared to normoglycaemic individuals (1.145 points lower on the Animal Fluency Test (P = 0.005) and 7.868 points reduced on the Digit Symbol Substitution Test (P < 0.001)). In diabetics, we found elevated serum creatinine (SCr) (especially at SCr≥300uM) was associated with lower scores on cognitive function tests after strict adjustment for potential influences on cognitive function. While, albumin/creatinine ratio (ACR) was only associated with Digit Symbol Substitution score (DSS) not Animal Fluency score (AFS), and estimated glomerular filtration rate (eGFR) was only associated with CI (AFS and DSS) at the end-stage renal disease. Conclusion: SCr, as a sensitive indicator of kidney injury, was significantly associated with CI and can potentially be used as an effective marker for screening CI in older diabetics.
Assuntos
Disfunção Cognitiva , Diabetes Mellitus , Humanos , Idoso , Creatinina , Inquéritos Nutricionais , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Diabetes Mellitus/epidemiologia , RimRESUMO
BACKGROUND: Talaromyces marneffei (T. marneffei) is a heat-dimorphic fungus that commonly causes fatal opportunistic infections in immunocompromised patients, such as those with human immunodeficiency virus (HIV) infection. CASE PRESENTATION: In this case report we describe a case of intracranial infection of T. marneffei in a 42-year-old AIDS patient. Contrast enhanced MRI showed the left occipital lobe mass with ring enhancement, MRS showed elevated AAs and Lip waves in the mass. Surgical resection of the occipital lobe confirmed the lesion to be T. marneffei infection and possibly with tuberculosis after a pathological examination. Patients with intracranial ring enhancing space-occupying lesions on MRI should be considered for intracranial T. marneffei infection. Intracranial T. marneffei infection is relatively rarely reported and recently studied. CONCLUSION: The MRI, in this case, suggests that ring enhancement mass and elevated AAs and Lip waves are helpful in the diagnosis of T. marneffei infection.
Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Micoses , Talaromyces , Humanos , Adulto , Síndrome da Imunodeficiência Adquirida/complicações , Micoses/complicações , Micoses/diagnóstico por imagem , Infecções por HIV/complicações , Infecções por HIV/microbiologiaRESUMO
To study the liver histopathological features that are distinctive between chronic hepatitis B virus (HBV) infection patients who have normal serum alanine aminotransferase (ALT)/asparatate aminotransferase (AST) and those with mildly elevated serum ALT/AST. One-hundred-and-thrity-four chronic HBV infection patients with normal serum ALT/AST and 165 chronic HBV infection patients with mildly elevated serum ALT/AST were included in the study. Liver biopsies were performed and used to assess the histological changes by hematoxylin-eosin and reticular fiber staining; mild to severe scoring for inflammation was made as grade G0-G4 and for fibrosis stage as S0-S4. HBV DNA levels were detected by fluorescent quantitative PCR. HBV serological markers were examined by chemiluminescence. The mildly elevated serum ALT/AST group had more male patients than the normal serum ALT/AST group. In the normal serum ALT/AST group, 50.0% (67/134) of the patients had moderate histological changes and only 3.0% (4/134) had severe changes (G3-4 and/or S3-4). In the mildly elevated ALT/AST group, 65.7% (174/265) of patients had moderate histological changes and 16.2% (43/265) had severe changes (G3-4 and/or S3-4). Hepatic inflammation and fibrosis were significantly more severe in the mildly elevated serum ALT/AST group than in the normal ALT/AST group (x2 = 26.386, P less than 0.01; x2 = 15.299, P less than 0.01). In the normal ALT/AST group, the severity of inflammation and fibrosis were positively correlated with age (rs = 0.620, P less than 0.01; rs = 0.347, P less than 0.01). In the mildly elevated ALT/AST group, the severity of inflammation and fibrosis were negatively correlated with age (rs = -0.807, P less than 0.01; rs = -0.557, P less than 0.01). In both groups, the severity of inflammation and fibrosis were negatively correlated with HBV DNA levels (rs = -0.215, P less than 0.01, rs = -0.527, P less than 0.01, rs = -0.951, P less than 0.01; rs = -0.715, P less than 0.01) and were not positively correlated with HBeAg. The majority of the chronic HBV infection patients with normal serum ALT/AST and those with mildly elevated serum ALT/AST had moderate liver pathological changes. All patients with low HBV DNA levels were closely followed-up, regardless of HBeAg-positive status.