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1.
Virulence ; 15(1): 2387180, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39192572

RESUMEN

Streptococcus pneumoniae is a common pathogen associated with community-acquired bacterial meningitis, characterized by high morbidity and mortality rates. While vaccination reduces the incidence of meningitis, many survivors experience severe brain damage and corresponding sequelae. The pathogenesis of pneumococcal meningitis has not been fully elucidated. Currently, meningitis requires bacterial disruption of the blood - brain barrier, a process that involves the interaction of bacterial surface components with host cells and various inflammatory responses. This review delineates the global prevalence, pathogenesis, and treatment strategies of pneumococcal meningitis. The objective is to enhance the thorough comprehension of the clinical manifestations and biological mechanisms of the disease, thereby enabling more efficient prevention, diagnosis, and therapeutic interventions.


Asunto(s)
Meningitis Neumocócica , Streptococcus pneumoniae , Humanos , Meningitis Neumocócica/microbiología , Meningitis Neumocócica/tratamiento farmacológico , Meningitis Neumocócica/terapia , Streptococcus pneumoniae/patogenicidad , Barrera Hematoencefálica/microbiología , Vacunas Neumococicas/inmunología , Animales , Infecciones Comunitarias Adquiridas/microbiología , Antibacterianos/uso terapéutico
2.
Med Microbiol Immunol ; 213(1): 12, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954065

RESUMEN

Streptococcus pneumoniae infection is a major public health concern with high morbidity and mortality rates. This study aimed to evaluate the serotype distribution, antimicrobial resistance changes, clonal composition, and virulence factors of S. pneumoniae isolates causing pneumococcal disease in northeast China from 2000 to 2021. A total of 1,454 S. pneumoniae isolates were included, with 568 invasive strains and 886 non-invasive strains. The patients from whom the S. pneumoniae were isolated ranged in age from 26 days to 95 years, with those ≤ 5 years old comprising the largest group (67.19%). 19 F, 19 A, 23 F, 14, and 6B were the most common serotypes, of which 19 A and 19 F were the main serotypes of invasive and non-invasive S. pneumoniae, respectively. CC271 was the most common multilocus sequence type. Serotype 14 had the lowest expression of cbpA, rrgA, and psrP genes, but expression levels of 19 A and 19 F genes were similar. All isolates were sensitive to ertapenem, moxifloxacin, linezolid, and vancomycin but highly resistant to macrolides, tetracyclines, and cotrimoxazole. Simultaneous resistance to erythromycin, clindamycin, tetracyclines, and trimethoprim/sulfamethoxazole was common pattern among multidrug-resistant isolates. Non-invasive S. pneumoniae had higher resistance to ß-lactam antibiotics than invasive strains. 19 A and 19 F were the main strains of penicillin-resistant S. pneumoniae. The resistance rate of ß-lactam antibiotics decreased from 2017 to 2021 compared to previous periods. Including PCV13 in the national immunization program can reduce the morbidity and mortality rates of pneumococcal disease effectively.


Asunto(s)
Antibacterianos , Tipificación de Secuencias Multilocus , Infecciones Neumocócicas , Serogrupo , Streptococcus pneumoniae , Factores de Virulencia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/patogenicidad , Streptococcus pneumoniae/aislamiento & purificación , Humanos , China/epidemiología , Factores de Virulencia/genética , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/epidemiología , Preescolar , Lactante , Persona de Mediana Edad , Adolescente , Antibacterianos/farmacología , Adulto , Niño , Anciano , Adulto Joven , Anciano de 80 o más Años , Recién Nacido , Pruebas de Sensibilidad Microbiana , Femenino , Masculino , Farmacorresistencia Bacteriana , Farmacorresistencia Bacteriana Múltiple/genética
3.
J Transl Med ; 22(1): 451, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741136

RESUMEN

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a high-prevalence autosomal dominant neuromuscular disease characterized by significant clinical and genetic heterogeneity. Genetic diagnosis of FSHD remains a challenge because it cannot be detected by standard sequencing methods and requires a complex diagnosis workflow. METHODS: We developed a comprehensive genetic FSHD detection method based on Oxford Nanopore Technologies (ONT) whole-genome sequencing. Using a case-control design, we applied this procedure to 29 samples and compared the results with those from optical genome mapping (OGM), bisulfite sequencing (BSS), and whole-exome sequencing (WES). RESULTS: Using our ONT-based method, we identified 59 haplotypes (35 4qA and 24 4qB) among the 29 samples (including a mosaic sample), as well as the number of D4Z4 repeat units (RUs). The pathogenetic D4Z4 RU contraction identified by our ONT-based method showed 100% concordance with OGM results. The methylation levels of the most distal D4Z4 RU and the double homeobox 4 gene (DUX4) detected by ONT sequencing are highly consistent with the BSS results and showed excellent diagnostic efficiency. Additionally, our ONT-based method provided an independent methylation profile analysis of two permissive 4qA alleles, reflecting a more accurate scenario than traditional BSS. The ONT-based method detected 17 variations in three FSHD2-related genes from nine samples, showing 100% concordance with WES. CONCLUSIONS: Our ONT-based FSHD detection method is a comprehensive method for identifying pathogenetic D4Z4 RU contractions, methylation level alterations, allele-specific methylation of two 4qA haplotypes, and variations in FSHD2-related genes, which will all greatly improve genetic testing for FSHD.


Asunto(s)
Metilación de ADN , Distrofia Muscular Facioescapulohumeral , Secuenciación Completa del Genoma , Distrofia Muscular Facioescapulohumeral/genética , Distrofia Muscular Facioescapulohumeral/diagnóstico , Humanos , Metilación de ADN/genética , Haplotipos/genética , Masculino , Estudios de Casos y Controles , Proteínas de Homeodominio/genética , Femenino , Secuenciación de Nanoporos/métodos , Adulto
4.
Neurol Sci ; 45(9): 4269-4278, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38642322

RESUMEN

BACKGROUND: Early identification individuals at high risk of mild cognitive impairment (MCI) is essential for prevention and intervention strategies of dementia, such as Alzheimer's disease. MCI prediction considering the interdependence of predictors in longitudinal data needs to be further explored. We aimed to employ machine learning (ML) to develop and verify a prediction model of MCI. METHODS: In a longitudinal population-based cohort of China Health and Retirement Longitudinal Study (CHARLS), 8390 non-MCI participants were enrolled. The diagnosis of MCI was based on the aging-associated cognitive decline (AACD), and 13 factors (gender, education, marital status, residence, diabetes, hypertension, depression, hearing impairment, social isolation, physical activity, drinking status, body mass index and expenditure) were finally selected as predictors. We implemented a long short-term memory (LSTM) to predict the MCI risks in middle-aged and older adults within 7 years. The Receiver Operating Characteristic curve (ROC) and calibration curve were used to evaluate the performance of the model. RESULTS: Through 7 years of follow-up, 1925 participants developed MCI. The model for all incident MCI achieved an AUC of 0.774, and its deployment to the participants followed 2, 4, and 7 years achieved results of 0.739, 0.747, and 0.750, respectively. The model was well-calibrated with predicted probabilities plotted against the observed proportions of cognitive impairment. Education level, gender, marital status, and depression contributed most to the prediction of MCI. CONCLUSIONS: This model could be widely applied to medical institutions, even in the community, to identify middle-aged and older adults at high risk of MCI.


Asunto(s)
Disfunción Cognitiva , Humanos , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/diagnóstico , Estudios Longitudinales , Masculino , Femenino , Persona de Mediana Edad , Anciano , China/epidemiología , Aprendizaje Automático , Factores de Riesgo
5.
Int Immunopharmacol ; 131: 111829, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38489974

RESUMEN

BACKGROUND: Following the COVID-19 pandemic, studies have identified several prevalent characteristics, especially related to lymphocyte subsets. However, limited research is available on the focus of this study, namely, the specific memory cell subsets among individuals who received COVID-19 vaccine boosters and subsequently experienced a SARS-CoV-2 breakthrough infection. METHODS: Flow cytometry (FCM) was employed to investigate the early and longitudinal pattern changes of cellular immunity in patients with SARS-CoV-2 breakthrough infections following COVID-19 vaccine boosters. XGBoost (a machine learning algorithm) was employed to analyze cellular immunity prior to SARS-CoV-2 breakthrough, aiming to establish a prognostic model for SARS-CoV-2 breakthrough infections. RESULTS: Following SARS-CoV-2 breakthrough infection, naïve T cells and TEMRA subsets increased while the percentage of TCM and TEM cells decreased. Naïve and non-switched memory B cells increased while switched and double-negative memory B cells decreased. The XGBoost model achieved an area under the curve (AUC) of 0.78, with an accuracy rate of 81.8 %, a sensitivity of 75 %, and specificity of 85.7 %. TNF-α, CD27-CD19+cells, and TEMRA subsets were identified as high predictors. An increase in TNF-α, cTfh, double-negative memory B cells, IL-6, IL-10, and IFN-γ prior to SARS-CoV-2 infection was associated with enduring clinical symptoms; conversely, an increase in CD3+ T cells, CD4+ T cells, and IL-2 was associated with clinical with non-enduring clinical symptoms. CONCLUSION: SARS-CoV-2 breakthrough infection leads to disturbances in cellular immunity. Assessing cellular immunity prior to breakthrough infection serves as a valuable prognostic tool for SARS-CoV-2 infection, which facilitates clinical decision-making.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , SARS-CoV-2 , Infección Irruptiva , Pandemias , Pronóstico , Estudios Prospectivos , Factor de Necrosis Tumoral alfa , Inmunidad Celular , Anticuerpos Antivirales
6.
Diagnostics (Basel) ; 14(2)2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38248042

RESUMEN

Optical genome mapping (OGM) has been known as an all-in-one technology for chromosomal aberration detection. However, there are also aberrations beyond the detection range of OGM. This study aimed to report the aberrations missed by OGM and analyze the contributing factors. OGM was performed by taking both GRCh37 and GRCh38 as reference genomes. The OGM results were analyzed in blinded fashion and compared to standard assays. Quality control (QC) metrics, sample types, reference genome, effective coverage and classes and locations of aberrations were then analyzed. In total, 154 clinically reported variations from 123 samples were investigated. OGM failed to detect 10 (6.5%, 10/154) aberrations with GRCh37 assembly, including five copy number variations (CNVs), two submicroscopic balanced translocations, two pericentric inversion and one isochromosome (mosaicism). All the samples passed pre-analytical and analytical QC. With GRCh38 assembly, the false-negative rate of OGM fell to 4.5% (7/154). The breakpoints of the CNVs, balanced translocations and inversions undetected by OGM were located in segmental duplication (SD) regions or regions with no DLE-1 label. In conclusion, besides variations with centromeric breakpoints, structural variations (SVs) with breakpoints located in large repetitive sequences may also be missed by OGM. GRCh38 is recommended as the reference genome when OGM is performed. Our results highlight the necessity of fully understanding the detection range and limitation of OGM in clinical practice.

7.
HIV Med ; 25(1): 60-71, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37574804

RESUMEN

OBJECTIVES: Despite the improved survival of patients with AIDS and Kaposi's sarcoma (KS), competing events are a non-negligible issue affecting the survival of such patients. In this study, we explored the prognostic factors of KS-specific and non-KS-specific mortality in patients with AIDS-related KS (AIDS-KS), accounting for competing risk. METHODS: We identified 17 103 patients with AIDS-KS aged 18-65 years between 1980 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) 18 registry database. Prognostic factors for KS-specific and non-KS-specific mortality were determined by the Fine and Grey proportional subdistribution hazard model. We built competing risk nomograms and assessed their predictive performance based on the identified prognostic factors. RESULTS: In total, 12 943 (75.68%) patients died, 1965 (15.50%) of whom died from competing events. The KS-specific mortality rate was 14 835 per 100 000 person-years, and the non-KS specific mortality rate was 2719 per 100 000 person-years. Specifically, age >44 years was associated with an 11% decrease in the subdistribution hazard of KS-specific mortality compared with age <43 years but a 50% increase in the subdistribution hazard of non-KS-specific mortality. Being male was associated with a 26% increase in the subdistribution hazard of KS-specific mortality compared with being female but a 32% decrease in the subdistribution hazard of non-KS-specific mortality. Notably, being in the antiretroviral therapy (ART) era consistently showed a decrease in the subdistribution hazard of both KS-specific and non-KS-specific mortality than being in the pre-ART era. CONCLUSIONS: Competing events commonly occurred among patients with AIDS-KS, which deserves further attention to improve the prognosis of these patients.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Sarcoma de Kaposi , Humanos , Masculino , Femenino , Sarcoma de Kaposi/epidemiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Infecciones por VIH/complicaciones , Pronóstico
9.
Clin Chim Acta ; 553: 117744, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38158003

RESUMEN

BACKGROUND: It remains controversial whether prenatal screening or diagnostic testing should be offered to fetuses with nasal bone (NB) absence or hypoplasia, and there are no studies comparing the yield of chromosomal microarray analysis (CMA) to non-invasive prenatal screening (NIPS). The aim of this study was to evaluate the residual risk of clinically significant copy number variations (CNVs) in fetuses with NB absence or hypoplasia after excluding theoretically NIPS-detectable abnormalities, and to assess their clinical outcomes. METHODS: This prospective study encompassed 400 fetuses with NB absence or hypoplasia undergoing CMA testing between 2015 and 2022. Clinically significant CMA findings were categorized into three subgroups, including three-NIPS-detectable (trisomies 21, 18 and 13), five-NIPS-detectable (trisomies 21, 18 and 13 and sex chromosome aneuploidies) and genome-wide NIPS-detectable (variants over 7 Mb). We calculated the theoretical residual risk and compared it with the results of a control cohort of low-risk pregnancies. We further evaluated their clinical outcomes. RESULTS: The overall diagnostic yield in our cohort was 7.8% (31/400). The detection rate of clinically significant CMA findings in fetuses with non-isolated NB absence or hypoplasia was significantly higher than that in fetuses with isolated NB absence or hypoplasia (20.0% vs. 6.6%, P =.005). The theoretical residual risks in all NIPS models were significantly higher when compared with the control cohort. The normal infant rate in fetuses with normal CMA results was 97.9% (323/330), and a significant higher incidence was observed in fetuses with isolated NB absence or hypoplasia compared with non-isolated NB absence or hypoplasia (98.4% vs. 91.7%, P =.028). CONCLUSIONS: The residual risk of clinically significant CNVs in fetuses with NB absence or hypoplasia following the exclusion of theoretically NIPS-detectable findings was higher than that in low-risk pregnancies. This risk should be considered in genetic counseling to make a more comprehensive and precise choice regarding prenatal genetic testing.


Asunto(s)
Variaciones en el Número de Copia de ADN , Diagnóstico Prenatal , Embarazo , Femenino , Humanos , Diagnóstico Prenatal/métodos , Trisomía , Estudios Prospectivos , Hueso Nasal/anomalías , Feto/anomalías , Análisis por Micromatrices , Aberraciones Cromosómicas
10.
Food Chem X ; 20: 100890, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-38144759

RESUMEN

Citrus aurantium L. fruit is a commonly used Chinese medicine whose therapeutic effects tends to be affected by growing conditions. In order to gain insights into the effects of growing location on the cuticular wax composition of C. aurantium L. fruit, we analyzed the differences in the wax composition of its fruits collected from different regions. The findings showed that the cuticular waxes in the fruit peels were mainly composed of fatty acids, which differed quantitatively in the chemical profiles of C. aurantium L. samples from different geographical conditions. Particularly, the concentrations of linoleic acid and stearic acid in the total component content of the fruit peel were above 1%, with a greater level in the geo-authentic samples. Thus, GC-MS-based wax analysis was first used for the chemical characterization and quantification of cuticular waxes, which could be considered as a rapid way for evaluating the quality of medicinal fruits.

11.
Ann Med ; 55(2): 2276824, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37917952

RESUMEN

Background: Copy number variants of uncertain significance (VUS) has brought much distress for patients and great counselling challenges for clinicians. Of these, a special type of VUS (HT-VUS), harbouring one or both breakpoints within the established haploinsufficient or triplosensitive genes, were considered to be more likely to cause clinical effects compared with other types of VUS.Methods: We retrospectively evaluated the properties and clinical significance of those HT-VUS samples in clinical testing for chromosome microarray analysis (CMA).Results: A total of 7150 samples were selected for HT-VUS screening, and 75 (1.05%) subjects with 75 HT-VUS were found. The majority of these HT-VUS were heterozygous duplications and chromosome X had the most HT-VUS. The prevalence of HT-VUS was 0.90% (28/3116) for prenatal low-risk samples, 1.18% (26/2196) for prenatal high-risk samples, 1.37% (10/728) for postnatal samples and 0.99% (11/1110) for early pregnancy loss samples. However, the incidence of HT-VUS was not statistically different between different groups.Conclusions: HT-VUS (deletions or duplications) involving introns and HT-VUS (duplications) including terminal coding exons (either the first or last exons) might be clinically neutral. Our study will be helpful for both interpretation and genetic counselling in the future.


This study assessed the clinical impact and features of a special type of copy number variants of uncertain significance (HT-VUS) in samples from CMA retrospectively.Out of 7150 samples screened, 75 (1.05%) subjects had HT-VUS. Most HT-VUS were heterozygous duplications and chromosome X had the highest frequency of HT-VUS.HT-VUS (deletions or duplications) involving introns and HT-VUS (duplications) including terminal coding exons might be clinically neutral. This study would be helpful for future interpretation and genetic counselling.


Asunto(s)
Variaciones en el Número de Copia de ADN , Pruebas Genéticas , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Análisis por Micromatrices
12.
Front Cell Infect Microbiol ; 13: 1273813, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37860067

RESUMEN

Extracellular vesicles (EVs) are nano-sized particles released from cells into the extracellular environment, and are separated from eukaryotic cells, bacteria, and other organisms with cellular structures. EVs alter cell communication by delivering their contents and performing various functions depending on their cargo and release into certain environments or other cells. The cell walls of Gram-positive bacteria have a thick peptidoglycan layer and were previously thought to be unable to produce EVs. However, recent studies have demonstrated that Gram-positive bacterial EVs are crucial for health and disease. In this review, we have summarized the formation, composition, and characteristics of the contents, resistance to external stress, participation in immune regulation, and other functions of Gram-positive bacterial EVs, as well as their application in clinical diagnosis and treatment, to provide a new perspective to further our understanding of Gram-positive bacterial EVs.


Asunto(s)
Vesículas Extracelulares , Bacterias Grampositivas , Bacterias , Membranas
13.
Open Forum Infect Dis ; 10(8): ofad435, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37636520

RESUMEN

Background: Kaposi sarcoma, caused by the pathogen Kaposi sarcoma-associated herpesvirus (KSHV), is the most common neoplasm for patients with AIDS. Susceptibility to KSHV has been associated with several different genetic risk variants. The purpose of this study was to test whether variants of killer cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA-I) ligands influence the risk of KSHV infection. Methods: A case-control study was performed in Xinjiang, a KSHV-endemic region of China. We recruited 299 individuals with HIV, including 123 KSHV-seropositive persons and 176 KSHV-seronegative controls. We used logistic regression and the MiDAS package to evaluate the association between KIR/HLA-I polymorphisms and KSHV infection. Results: HLA-A*31:01, HLA-C*03:04, and HLA-C*12:03 were found to be associated with KSHV infection, with A*31:01 showing a protective effect under 3 different models (dominant: 0.30 [95% confidence interval {CI}, .08-.82], P = .031; additive: 0.30 [95% CI, .09-.80], P = .030; overdominant: 0.31 [95% CI, .09-.88], P = .042). The effect of A*31:01 might cause the variants of amino acid at HLA-A position 56, with individuals carrying an arginine having a lower KSHV infection risk. The increased homozygous KIR2DL3 was associated with a relatively high KSHV viral load (16.30% vs 41.94%, P = .010). Conclusions: This study provides further insight into the link between HLA-I alleles and KIR genes and KSHV infection, highlighting KSHV-susceptible variants of HLA-I and KSHV replication caused by specific KIR genotype, and revealing a potential role of KIR-mediated natural killer cell activation in anti-KSHV infection.

14.
Acta Obstet Gynecol Scand ; 102(8): 1053-1062, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37366235

RESUMEN

INTRODUCTION: Chromosomal aberrations are the most important etiological factors for birth defects. Optical genome mapping is a novel cytogenetic tool for detecting a broad range of chromosomal aberrations in a single assay, but relevant clinical feasibility studies of optical genome mapping in prenatal diagnosis are limited. MATERIAL AND METHODS: We retrospectively performed optical genome mapping analysis of amniotic fluid samples from 34 fetuses with various clinical indications and chromosomal aberrations detected through standard-of-care technologies, including karyotyping, fluorescence in situ hybridization, and/or chromosomal microarray analysis. RESULTS: In total, we analyzed 46 chromosomal aberrations from 34 amniotic fluid samples, including 5 aneuploidies, 10 large copy number variations, 27 microdeletions/microduplications, 2 translocations, 1 isochromosome, and 1 region of homozygosity. Overall, 45 chromosomal aberrations could be confirmed by our customized analysis strategy. Optical genome mapping reached 97.8% concordant clinical diagnosis with standard-of-care methods for all chromosomal aberrations in a blinded fashion. Compared with the widely used chromosomal microarray analysis, optical genome mapping additionally determined the relative orientation and position of repetitive segments for seven cases with duplications or triplications. The additional information provided by optical genome mapping will be conducive to characterizing complex chromosomal rearrangements and allowing us to propose mechanisms to explain rearrangements and predict the genetic recurrence risk. CONCLUSIONS: Our study highlights that optical genome mapping can provide comprehensive and accurate information on chromosomal aberrations in a single test, suggesting that optical genome mapping has the potential to become a promising cytogenetic tool for prenatal diagnosis.


Asunto(s)
Trastornos de los Cromosomas , Embarazo , Femenino , Humanos , Trastornos de los Cromosomas/diagnóstico , Trastornos de los Cromosomas/genética , Hibridación Fluorescente in Situ , Variaciones en el Número de Copia de ADN , Estudios Retrospectivos , Aberraciones Cromosómicas , Diagnóstico Prenatal/métodos , Mapeo Cromosómico
15.
Viral Immunol ; 36(4): 290-297, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37040285

RESUMEN

Toll-like receptors (TLRs) play a crucial role in the innate immune response to pathogens, and TLR3 could recognize and control the herpesvirus. We studied the effect of TLR3 polymorphisms on the risk of Kaposi's sarcoma-associated herpesvirus (KSHV) infection. A cross-sectional study was performed among human immunodeficiency virus (HIV)-infected individuals in Xinjiang, a KSHV-endemic region of China. The frequencies of nine single-nucleotide polymorphisms (SNPs) in TLR3 in 370 KSHV-infected patients and 558 controls, and their impact on plasma IFN-γ levels, were compared. The effect of TLR3 SNPs on the KSHV viral load in KSHV-infected subjects was also assessed. The minor allelic variant at rs13126816 was more common among KSHV-seronegative than KSHV-infected individuals. Two TLR3 SNPs (rs13126816 and rs3775291) showed a protective effect against KSHV infection (rs13126816: odds ratio [OR]dominant = 0.66, 95% confidence interval [CI]: 0.50-0.87; ORoverdominant = 0.65, 95% CI: 0.49-0.87; rs3775291: ORdominant = 0.76, 95% CI: 0.58-0.99; ORoverdominant = 0.75, 95% CI: 0.57-0.98). These associations were stronger in the Uyghur compared with the Han population. The haplotype, CGAC, significantly correlated with the risk of KSHV infection (OR = 0.72, p = 0.029). KSHV-infected individuals with homozygous rs13126816 AA genotypes had a lower KSHV viral load (aOR = 0.14; p = 0.038). However, no association was observed between TLR3 SNPs and plasma levels of IFN-γ. Genetic variants in TLR3 reduce the risk of KSHV infection and affect KSHV reactivation among HIV-infected individuals, especially in the Uyghur population.


Asunto(s)
Infecciones por VIH , VIH-1 , Infecciones por Herpesviridae , Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Estudios Transversales , Infecciones por Herpesviridae/genética , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 8/genética , Infecciones por VIH/complicaciones , Infecciones por VIH/genética , Sarcoma de Kaposi/complicaciones , Receptor Toll-Like 3/genética
16.
Opt Express ; 30(26): 46227-46235, 2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36558581

RESUMEN

Ultrasound-modulated optical tomography (UOT), which combines the advantages of both light and ultrasound, is a promising imaging modality for deep-tissue high-resolution imaging. Among existing implementations, camera-based UOT gains huge advances in modulation depth through parallel detection. However, limited by the long exposure time and the slow framerate of modern cameras, the measurement of UOT signals always requires holographic methods with additional reference beams. This requirement increases system complexity and is susceptible to environmental disturbances. To overcome this challenge, we develop coaxial interferometry for camera-based UOT in this work. Such a coaxial scheme is enabled by employing paired illumination with slightly different optical frequencies. To measure the UOT signal, the conventional phase-stepping method in holography can be directly transplanted into coaxial interferometry. Specifically, we performed both numerical investigations and experimental validations for camera-based UOT under the proposed coaxial scheme. One-dimensional imaging for an absorptive target buried inside a scattering medium was demonstrated. With coaxial interferometry, this work presents an effective way to reduce system complexity and cope with environmental disturbances for camera-based UOT.


Asunto(s)
Iluminación , Tomografía Óptica , Fantasmas de Imagen , Ultrasonografía/métodos , Tomografía Óptica/métodos , Interferometría/métodos
17.
Medicine (Baltimore) ; 101(46): e31327, 2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36401439

RESUMEN

Traditional Chinese tongue diagnosis plays an irreplaceable role in disease diagnosis. This study aimed to describe the tongue characteristics of patients with granulomatous lobular mastitis (GLM). Forty GLM patients and 40 non-GLM controls were evaluated using the Traditional Chinese Medicine subjective clinical interpretation and a TDA-1 Tongue Diagnostic and Analysis system. The associations between the image features of the tongue body and coating and the profiling of immune-inflammatory parameters were analyzed. GLM patients were prone to a reddish tongue bodies with thick, white, and greasy coatings. Thick and greasy tongue coating features are risk factors for GLM. GLM patients had higher levels of white blood cells (WBC), platelets, C-reactive protein, interleukin-2, and transforming growth factor-ß (TGF-ß) than non-GLM controls (P < .05). Also, tongue coating contrast and entropy values were significantly correlated with WBC or TGF-ß levels in GLM patients (r < -0.310 and P < .05). We demonstrated that the hot evil and phlegm-dampness constitutions are the main characteristics of GLM. This might provide a reference for GLM diagnosis.


Asunto(s)
Mastitis Granulomatosa , Lengua , Humanos , Femenino , Mastitis Granulomatosa/diagnóstico , Medicina Tradicional China , Factor de Crecimiento Transformador beta
18.
Stem Cell Res Ther ; 13(1): 331, 2022 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-35870968

RESUMEN

BACKGROUND: Due to the large area and deep width of the artificial neovagina after vaginoplasty, it takes a considerable amount of time to achieve complete epithelization of the neovagina. Currently, the clinical therapies for vaginal epithelization after vaginoplasty are still dissatisfactory. Recent studies showed that small extracellular vesicles (sEVs) derived from stem cells could accelerate wound epithelization. The sustained release of sEVs from optimized hydrogels may be a promising strategy to accelerate vaginal epithelization after vaginoplasty. METHODS: The efficacy of phototriggered imine crosslink hydrogels (piGEL) containing sEVs derived from human urine-derived stem cells (hUSC-sEVs, piGEL-sEVs) on vaginal mucosa defects in rabbits was assessed by wound closure rates, histological analysis and immunofluorescence staining analysis. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine and scratch wound assays were performed to assess the effects of hUSC-sEVs on the proliferation and migration ability of vaginal epithelial cells (VK2/E6E7). Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to test the expression of epithelial differentiation markers in VK2 cells. Moreover, a microRNA (miRNA) microarray was used to find hUSC-sEVs-specific miRNAs that potentially affected the proliferation, migration and differentiation ability of VK2 cells. RESULTS: The in vitro release profile revealed that the piGEL could ensure sustained release of hUSC-sEVs. The in vivo results showed that piGEL-sEVs effectively promoted epithelization and angiogenesis of vaginal mucosa defects in rabbits. According to miRNA microarray and qRT-PCR results, miR-126-3p might be the crucial molecule among the various miRNAs contained in hUSC-sEVs. The data showed that hUSC-sEVs promoted the migration and differentiation of VK2 cells by delivering miR-126-3p to suppress the expression of Spred1 and PIK3R2, thereby activating the ERK1/2 and ATK signaling pathways. CONCLUSION: The results indicated that piGEL-sEVs could be a novel promising approach for enhancing the epithelization of the neovagina after vaginoplasty and provided useful data for understanding the underlying mechanism of the effect of hUSC-sEVs on epithelization.


Asunto(s)
Vesículas Extracelulares , MicroARNs , Animales , Preparaciones de Acción Retardada/metabolismo , Vesículas Extracelulares/metabolismo , Femenino , Humanos , Hidrogeles/farmacología , Iminas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Conejos , Células Madre/metabolismo
19.
J Clin Endocrinol Metab ; 107(9): 2522-2529, 2022 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-35763044

RESUMEN

CONTEXT: Findings from observational studies indicate an association of thyroid hormone levels with the risk of nonalcoholic fatty liver disease (NAFLD); however, conflicting results remain and reverse causality may be a possibility. OBJECTIVE: This study aimed to evaluate the associations between NAFLD and both plasma thyroxine (T4) and thyroid stimulating hormone (TSH) at the phenotypic and genetic levels. METHODS: We included 14 797 participants, aged 20 to 74 years who had undergone abdominal ultrasonography during the Third National Health and Nutrition Examination Survey (NHANES III). Multivariable logistic regression analyses were used to examine the observational associations of TSH and T4 with NAFLD. Mediation analyses were performed to study whether the relationship between NAFLD and TSH levels was mediated via potential confounders. A bidirectional, two-sample Mendelian randomization (MR) analysis was used to determine the potential causal relationship. RESULTS: Multivariable logistic regression model suggested a "dose-response" relationship between TSH (Q4 vs Q1: OR = 1.29; 95% CI, 1.10-1.52; Ptrend = 0.001) and NAFLD. BMI and ALT partially mediated the association between TSH and NAFLD, while the proportion of the mediation effects of BMI and ALT were 39.1% and 22.3%, respectively. In MR analyses, the inverse-variance weighted method was selected as primary method and suggested a putative causal effect of NAFLD on serum TSH levels (OR = 1.022; 95% CI, 1.002-1.043). The result was further validated in the sensitivity analyses. CONCLUSION: Circulating TSH levels were associated with the risk of NAFLD. MR analysis suggested a putative causal effect of NAFLD on TSH levels.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Análisis de la Aleatorización Mendeliana , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/genética , Encuestas Nutricionales , Glándula Tiroides , Tirotropina , Tiroxina
20.
Front Genet ; 13: 792558, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35656325

RESUMEN

Background and Aim: Aberrant sleep parameters are associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, existing information is inconsistent among studies and involves reverse causation. Therefore, we aimed to investigate the observational associations and causations between sleep traits and NAFLD. Methods: We performed multivariable regression to assess observational associations of seven sleep traits (sleep duration, easiness of getting up in the morning, chronotype, nap during day, snoring, insomnia, and narcolepsy), and NAFLD in the UK Biobank (1,029 NAFLD). The Cox proportional hazards model was applied to derive hazard ratios and 95% confidence intervals (CIs). Furthermore, a bidirectional two-sample Mendelian randomization (MR) approach was used to explore the causal relationships between sleep traits and NAFLD. Results: In the multivariable regression model adjusted for potential confounders, getting up in the morning not at all easy (HR, 1.51; 95% CI, 1.27-1.78) and usually insomnia (HR, 1.46; 95% CI, 1.21-1.75) were associated with the risk of NAFLD. Furthermore, the easiness of getting up in the morning and insomnia showed a dose-response association with NAFLD (Ptrend <0.05). MR analysis found consistent causal effects of NAFLD on easiness of getting up in the morning (OR, 0.995; 95% CI, 0.990-0.999; p = 0.033) and insomnia (OR, 1.006; 95% CI, 1.001-1.011; p = 0.024). These results were robust to weak instrument bias, pleiotropy, and heterogeneity. Conclusions: Findings showed consistent evidence of observational analyses and MR analyses that trouble getting up in the morning and insomnia were associated with an increased risk of NAFLD. Bidirectional MR demonstrated causal effects of NAFLD on sleep traits.

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