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1.
Artículo en Inglés | MEDLINE | ID: mdl-38719186

RESUMEN

INTRODUCTION: Mycobacterium abscessus complex (MABC) is the most common rapidly growing Mycobacterium species in structural pulmonary diseases and can be life-threatening. This study aimed to assess the clinical characteristics and drug susceptibility statuses of different Mycobacterium abscessus (MAB) subspecies. METHODS: DNA sequencing was used to differentiate clinical MABC subspecies isolates. The Clinical and Laboratory Standards Institute guidelines were used to determine vitro susceptibility of imipenem-relebactam, omadacycline, and other conventional antibiotics. Patient's clinical characteristics were collected and analysed. RESULTS: There were 139 M. abscessus, 39 M. massiliense, and 1 M. bolletii, accounting for 77.7%, 21.8%, and 0.5% of the MABC isolates, respectively. Patients with M. abscessus pulmonary disease (M.ab-PD) had higher proportions of older adults, tuberculosis history, chronic pulmonary disease, and malignancy than those with M. massiliense pulmonary disease (M.ma-PD). Patients with M.ab-PD had higher rates of bilateral middle- and lower-lobe involvement than patients with M.ma-PD. Both subspecies showed high resistance rates to doxycycline and moxifloxacin, and clarithromycin-induced resistance was more common in M.ab than in M.ma. Relebactam with imipenem resulted in a 2-fold reduction in the minimum inhibitory concentration (MIC) value compared to imipenem alone among MAB; furthermore, the MIC was lower in M.ab than in M.ma. Omadacycline and tigecycline had comparable in vitro susceptibility, and the MIC showed no statistically significant difference between M.ab and M.ma. CONCLUSIONS: M.ab is the most prevalent MABC subspecies in the Zhejiang Province. Patients with M.ab-PD have complex underlying diseases and broader lobar lesions. Imipenem-relebactam and omadacycline are promising antibiotics for MABC infection treatment.

2.
Int J Antimicrob Agents ; 62(2): 106875, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37276894

RESUMEN

Central nervous system (CNS) tuberculosis (TB) is a devastating and often life-threatening disease caused by Mycobacterium tuberculosis. Contezolid, a new oxazolidinone, has demonstrated potent antimycobacterial activity in both in-vivo and in-vitro studies, with lower toxicity than linezolid. However, pharmacokinetic data are still not available for contezolid in the CNS of patients with CNS TB. This article reports the steady-state concentrations of contezolid in serum and cerebrospinal fluid (CSF) of a patient receiving contezolid as part of multi-drug treatment for tuberculous meningoencephalitis. At weeks 7 and 11 (7 h post-dose) after initiation of contezolid therapy, the serum concentrations of contezolid were 9.64 mg/L and 9.36 mg/L, respectively. In CSF, the observed concentrations of contezolid were 0.54 mg/L and 1.15 mg/L, respectively. The CSF:serum concentration ratios were 0.056 and 0.123 at weeks 7 and 11, respectively. The observed concentrations in CSF were above the minimum inhibitory concentration of contezolid against M. tuberculosis, and were close to the estimated serum unbound fraction of contezolid (10%), suggesting that unbound contezolid has high CSF permeability.


Asunto(s)
Meningoencefalitis , Mycobacterium tuberculosis , Oxazolidinonas , Tuberculosis Meníngea , Humanos , Tuberculosis Meníngea/tratamiento farmacológico , Piridonas , Meningoencefalitis/tratamiento farmacológico , Líquido Cefalorraquídeo
3.
Gut Microbes ; 15(1): 2221450, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37309179

RESUMEN

With the drive of the endogenous circadian clock and external cues such as feeding behavior, the microbial community generates rhythmic oscillations in composition and function. Microbial oscillations are crucial in orchestrating host metabolic homeostasis during the predictable 24-hour diurnal cycle. A time-restricted feeding (TRF) regimen is a promising dietary strategy to optimize energy utilization, alleviate metabolic syndrome and reinforce microbial cyclical fluctuations. However, the causative relationship between reinforced microbial rhythmicity and TRF-induced metabolic improvement remains elusive. In this study, we corroborated that the TRF regimen notably alleviated obesity and nonalcoholic steatohepatitis (NASH) with reinstated rhythmicity of genera such as Lactobacillus, Mucispirillum, Acetatifactor, and Lachnoclostridium. The reshaped microbial oscillations correlate with cyclical fluctuations in intestinal amino acids. Furthermore, fecal microbiota transplantation (FMT) indicated that only the TRF feeding phase-derived microbiota, but not the TRF fasting phase-derived microbiota, could protect mice from NASH and reinstate microbial rhythmicity, confirming that the microbiota improved NASH in a time-of-day-specific manner. The unique role of the TRF-feeding phase-derived microbiota was accompanied by regulation of the serotonergic synapse pathway and rejuvenation of the microbial production of indole derivatives. Our results revealed the discrepant characteristics between the feeding and fasting phases and the time-of-day-specific configuration of microbiota functionality in the TRF regimen.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Ayuno , Ayuno Intermitente , Clostridiales
4.
Int J Infect Dis ; 132: 99-107, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37068583

RESUMEN

OBJECTIVES: Faropenem has antituberculosis activity in vitro but its utility in treating patients with tuberculosis (TB) is unclear. METHODS: We conducted an open-label, randomized trial in China, involving newly diagnosed, drug-susceptible pulmonary TB. The control group was treated with the standard 6-month regimen. The experimental group replaced ethambutol with faropenem for 2 months. The primary outcome was the treatment success rate after 6 months of treatment. Noninferiority was confirmed if the lower limit of a 95% one-sided confidence interval (CI) of the difference was greater than -10%. RESULTS: A total of 227 patients eligible for the study were enrolled in the trial group and the control group in a ratio of 1:1. Baseline characteristics of participants were similar in both groups. In the modified intention-to-treat population, 88.18% of patients in the faropenem group achieved treatment success, and 85.98% of those in the control group were successfully treated, with a difference of 2.2% (95% CI, -6.73-11.13). In the per-protocol population, treatment success was 96.04% in the faropenem group and 95.83% in the control group, with a difference of 2.1% (95% CI, -5.31-5.72). The faropenem group showed noninferiority to the control group in the 6-month treatment success rates. The faropenem group had significantly fewer adverse events (P <0.01). CONCLUSIONS: Our study proved that oral faropenem regimen can be used for the treatment of TB, with fewer adverse events. (Chinese Clinical Trial Registry, ChiCTR1800015959).


Asunto(s)
Antituberculosos , Tuberculosis Pulmonar , Humanos , Quimioterapia Combinada , Etambutol/uso terapéutico , Resultado del Tratamiento , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/diagnóstico
5.
Front Public Health ; 11: 1125306, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36844847

RESUMEN

Background: Leptospirosis is a widespread zoonotic disease caused by pathogenic Leptospira spp. The treatment of penicillin or tetracycline can cause a Jarisch-Herxheimer reaction (JHR), which can lead to acute respiratory distress syndrome (ARDS) and multi-organ failure in severe cases. The overall course of evolution and imaging features of a JHR exacerbation of leptospirosis have rarely been reported. Case presentation: We present a case of leptospirosis complicated by pulmonary alveolar hemorrhage and a Jarisch-Herxheimer reaction (JHR) that required respiratory and vasopressor support. This case demonstrates a well-defined course of evolution of JHR and the imaging features. Conclusions: Leptospirosis is easily misdiagnosed in some sporadic areas, and JHR complicates its management. Early diagnosis and appropriate treatment can reduce the mortality of severe leptospirosis with JHR.


Asunto(s)
Leptospirosis , Insuficiencia Respiratoria , Humanos , Leptospirosis/complicaciones , Leptospirosis/diagnóstico , Leptospirosis/tratamiento farmacológico , Penicilinas/efectos adversos , Antibacterianos/efectos adversos , Tetraciclina , Insuficiencia Respiratoria/etiología
6.
J Cutan Pathol ; 50(5): 466-470, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36749118

RESUMEN

BACKGROUND: Histopathology protocols for processing dermatopathology specimens vary among laboratories. OBJECTIVE: To determine an optimal histopathology protocol to minimize cost and turnaround time (TAT) for biopsy specimens in a dermatopathology laboratory. METHODS: A prospective, 4-month study compared the mean cost and TAT of producing one versus two initial H&E slides, and zero versus three unstained slides that could be used for frequently used special or immunohistochemical (IHC) stains. RESULTS: For all cases, cost was lower for one versus two initial H&E slides, with an insignificant increase in TAT. Producing three vs zero unstained slides incurred higher cost, with no reduction in TAT. In a subset of cases in which frequently used special or IHC stains were performed, cost and TAT were optimized by producing one initial H&E and three unstained slides. CONCLUSION: A protocol of one initial H&E slide and zero unstained slides optimizes cost and TAT in our dermatopathology laboratory. Pigmented lesions and inflammatory dermatoses may benefit from the addition of unstained slides. Further study is needed to quantify this benefit and evaluate for other cases for which an alternative protocol is advantageous.


Asunto(s)
Laboratorios , Patología Quirúrgica , Humanos , Estudios Prospectivos , Mejoramiento de la Calidad
7.
Clin Dermatol ; 41(1): 178-186, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36252728

RESUMEN

Since the recent establishment of a single graduate medical education organization, there has been a declining match rate of osteopathic students to competitive specialties, particularly dermatology residency, despite the increasing number of osteopathic medical students in the United States. The aim of this study was to investigate attitudes and potential sources of bias affecting osteopaths in the dermatology residency application process. This was an online survey-based study to analyze dermatology faculty and resident considerations. Data were analyzed using descriptive and inferential statistics. Sixteen percent (3 of 18) of allopathic residents and 73.68% (14 of 19) of osteopathic residents experienced bias based on their allopathic or osteopathic status (P < .002). Compared with allopathic graduates, the main barrier for osteopathic graduates was research (P = .00105). Being an osteopathic candidate was associated with a lower likelihood of consideration for mentorship by both allopathic and osteopathic faculty (P = .044). Faculty members who mentor osteopathic candidates are 1.83 times more comfortable with knowledge of osteopathic schools and their respective curricula (P = .029) and 1.77 times more comfortable with reviewing letters of recommendation written by osteopathic faculty (P = .037). Limitations include self-selection bias, small sample size, and overrepresentation of faculty and residents who participate in research studies. Additional research opportunities for osteopathic students, more diverse mentorship programs, and education for faculty on osteopathic concepts may promote equity during the residency application process and professional diversity within the field of dermatology.


Asunto(s)
Internado y Residencia , Medicina Osteopática , Médicos Osteopáticos , Humanos , Estados Unidos , Medicina Osteopática/educación , Educación de Postgrado en Medicina , Actitud
8.
Infect Drug Resist ; 15: 5449-5454, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36128436

RESUMEN

Linezolid-induced black hairy tongue is a self-limiting benign disease that is rare. Here, we report three patients who developed black hairy tongue after linezolid treatment. The severe dysbiosis of oral bacterial communities was observed in all these patients. Proteobacteria was the most prevalent phylum (over 90%) at the black tongue stage. Furthermore, the dramatic oral bacterial alteration took a long time to reverse after the BHT resolved.

9.
Clin Dermatol ; 40(6): 782-787, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35948236

RESUMEN

Lack of standardized dermatoscopy training limits confidence and accuracy. We assessed the effect of a dermatoscopy lecture series on the diagnostic accuracy of dermatology residents' biopsies. Additionally, we evaluated resident comfort with and knowledge of dermatoscopy before and after the curriculum. Twelve dermatology residents were enrolled in a 5-month dedicated dermatoscopy curriculum. To assess knowledge of and comfort with dermatoscopy, residents were given a 50-question assessment and 21-question survey before and after the curriculum. Change in diagnostic accuracy was assessed by comparing the suspected clinical diagnosis to the final histopathologic diagnosis of lesions biopsied by residents before and after the course. Upon completion of the curriculum, residents felt significantly more comfortable performing dermatoscopy (P = .002) and using dermatoscopy to identify melanocytic nevi (P = .037) and melanomas (invasive and in situ) (P = .012). Postgraduate year 2 residents also showed significantly improved diagnostic accuracy after the training course (odds ratio, 1.33; 95% confidence interval, 1.06-1.67; P = .013). Our study was limited by a small sample size of 12 residents from a single academic institution. A formal dermatoscopy course can effectively improve dermatology residents' knowledge, confidence, and diagnostic accuracy when using dermatoscopy.


Asunto(s)
Dermatología , Internado y Residencia , Melanoma , Nevo Pigmentado , Neoplasias Cutáneas , Humanos , Nevo Pigmentado/diagnóstico por imagen , Nevo Pigmentado/patología , Melanoma/diagnóstico por imagen , Melanoma/patología , Curriculum , Competencia Clínica , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Estudios de Casos y Controles
10.
Infect Drug Resist ; 15: 2633-2638, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35634580

RESUMEN

Tuberculous aortitis (TA) is a rare disease with a high mortality rate. Aortic pseudoaneurysm is the most common vascular pattern of TA, and isolated arterial wall thickening and arterial stenosis can also be seen in TA. We report two cases of disseminated tuberculosis involving the aorta with clinical improvement after treatment. One patient who had an aortic ulcer and intermural hematoma received anti-tuberculosis along with steroids therapy. The other patient, who developed a tubercular abdominal aortic pseudoaneurysm during anti-tuberculosis therapy, successfully received endovascular stent implantation. Clinicians should be aware that TA should be considered in patients with aortitis and active tuberculosis.

11.
Int J Infect Dis ; 122: 46-62, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35577247

RESUMEN

OBJECTIVES: To track the prevalence trends of latent tuberculosis infection (LTBI) at the global, regional, and national levels. METHODS: Data on the prevalence of LTBI were extracted from the Global Burden of Disease database. The average annual percent change (AAPC) was estimated by joinpoint regression and was used to evaluate the epidemic of the disease. RESULTS: Globally, the prevalence rate of LTBI decreased from 30.66% in 1990 to 23.67% in 2019, with an AAPC of -0.9%. The prevalence rate of LTBI varied from 5.02% (Jordan) to 48.35% (Uganda) in 1990 and from 2.51% (Jordan) to 43.75% (Vietnam) in 2019 at the country level. The prevalence decreased in all the six World Health Organization (WHO) regions and in most countries, with the AAPC ranging from -0.5% in the Western Pacific Region to -2.1% in the European Region and from -4.3% (Bhutan) to -0.1% (Malaysia, Myanmar, South Africa, Tokelau, and Vietnam), respectively. Disparities were also observed among different sex and age groups. CONCLUSION: The prevalence of LTBI decreased slightly worldwide in the last three decades, but the decrease is slow and not sufficient to meet the targets of WHO tuberculosis elimination. Much more effort and progress should be made in order to decrease the prevalence of LTBI.


Asunto(s)
Tuberculosis Latente , Tuberculosis , Humanos , Tuberculosis Latente/epidemiología , Prevalencia , Sudáfrica , Tuberculosis/epidemiología , Organización Mundial de la Salud
12.
Front Med (Lausanne) ; 9: 798465, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35308541

RESUMEN

Objective: To estimate the epidemic trends of tuberculosis (TB) in 30 high burden countries (HBCs) over the past 30 years, which is crucial for tracking the status of disease control, especially at the country level. Methods: Annual data on incidence and mortality of TB in these 30 HBCs were extracted from the Global Burden of Disease database. The average annual percent change (AAPC) was used to evaluate the trends of incidence and mortality. The trajectory analysis was used to identify different trends among the subgroup countries. The predicted incidence and mortality rates in 2025, 2030, and 2035 were also calculated. Results: The incidence and mortality decreased in most of the HBCs. The AAPCs of incidence ranged between -4.0 (Indonesia) and -0.2% (DR Congo) (all p < 0.05). The incidence trends in Lesotho (AAPC: 0%, 95% CI: -0.4, 0.3, p = 0.8) and South Africa (AAPC: -0.2%, 95% CI: -0.5, 0, p = 0.1) were stable, and increased in Kenya with AAPC of 0.1% (95% CI: 0.1, 0.2, p < 0.05). The AAPCs for mortality ranged between -5.8 (Ethiopia) and -0.6% (Central African Republic) (all p < 0.05). The mortality trends in DPR Korea (AAPC: 0.1%, 95% CI: -0.3, 0.4, p = 0.6) and Russian Federation (AAPC: -0.5%, 95% CI: -1.9, 0.9, p = 0.5) were stable, and increased in Lesotho and Zimbabwe with AAPC of 1.3% (95% CI: 1.1, 1.4, p < 0.05) and 1.6% (95% CI: 1.0, 2.2, p < 0.05), respectively. Trajectory analysis showed that the Central African Republic, Lesotho, Cambodia, Namibia, and South Africa had higher incidences, and the Central African Republic had higher mortality. Brazil and China had relatively lower rates of incidence and mortality. Predictions showed that reduction rates of incidence and mortality could hardly be reached compared with those set for the global targets for the majority HBCs. Conclusions: The disease burden of TB has been reduced among the majority HBCs over the last three decades. According to the current control levels, achieving the ambitious global targets at the country level for these 30 HBCs is challenging.

13.
Zookeys ; 1108: 89-118, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36760703

RESUMEN

The javanicus-group of Glyphiulus is re-assessed and its Chinese component species are presently divided between the following two newly-circumscribed species groups, i.e. the formosus- and the sinensis-group. The two can be differentiated, based on the diagnostic characters of the first pair of legs in the male. In addition, metatergal crests being complete and the carinotaxy formula on the collum being I-III+P+M are only characteristic of the formosus-group. A molecular phylogeny of the genus, based on DNA sequencing of four gene fragments of four genes, allows for Glyphiulus to be recovered as a monophyletic group, the phylogenetic relationship being ((Clade A, Clade B), Clade C). Molecular evidence is fully congruent with the morphological one. In addition, based on barcoding data, interspecific p-distances between Glyphiulus species amount to 11.2-24.9%, vs. 0-8.2% for intraspecific p-distances. Five new species of Glyphiulus, all cavernicolous, are described from China: G.sinuatoprocessus Zhao & Liu, sp. nov., G.conuliformis Zhao & Liu, sp. nov. (both from Guangdong Province), G.xiniudong Zhao & Liu, sp. nov., G.scutatus Zhao & Liu, sp. nov. and G.portaliformis Zhao & Liu, sp. nov. (all three from Guangxi Zhuang Autonomous Region). The known Chinese species of the formosus-group appear to mainly be confined to the South China region.

14.
Insects ; 12(11)2021 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-34821802

RESUMEN

Cave-dwelling ground beetles in China represent the most impressive specific diversity and morphological adaptations of the cavernicolous ground beetles in the world, but they have not been systematically examined in quantitative terms. The present study focuses on the application of geometric morphological methods to address the morphological adaptations of the tribe Trechini, the most representative group in China. We have employed a geometric morphometry analysis of the head, pronotum, and elytra of 53 genera of Trechini, including 132 hypogean and 8 epigean species. Our results showed that the overall morphological variation of cave carabids has gradually specialized from an anophthalmic to semi-aphaenopsian to aphaenopsian type. There were extremely significant differences (p < 0.01) among four different adaptive types including aphaenopsian, semi-aphaenopsian, anophthalmic, and surface-dwelling Trechini when their adaptability to a cave environment was used as the basis for grouping. Furthermore, there were differences in the phenotypic tree of the head, pronotum, and elytra, and an integrated morphology. To the best of our knowledge, this is the first report on the analysis of the head, pronotum, and elytra of four different adaptive types of ground beetles in order to clarify the morphological adaptations of cavernicolous carabids to the cave environment.

15.
BMC Med ; 19(1): 191, 2021 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-34365975

RESUMEN

BACKGROUND: Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge. METHODS: A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated. RESULTS: A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0-2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older (p = 0.01), with higher rate in current smokers (p = 0.04), higher rate in hypertensives (p = 0.05), lower SaO2 (p = 0.004), and higher prevalence of secondary bacterial infections during acute phase (p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01-1.15, p = 0.02). Pulmonary functions of total lung capacity (p = 0.008) and residual volume (p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores. CONCLUSION: During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age.


Asunto(s)
COVID-19 , Diabetes Mellitus Tipo 2 , Adulto , COVID-19/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2 , Tomografía Computarizada por Rayos X
16.
Int J Nanomedicine ; 16: 4813-4830, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34290504

RESUMEN

Human coronaviruses present a substantial global disease burden, causing damage to populations' health, economy, and social well-being. Glycans are one of the main structural components of all microbes and organismic structures, including viruses-playing multiple essential roles in virus infection and immunity. Studying and understanding virus glycans at the nanoscale provide new insights into the diagnosis and treatment of viruses. Glycan nanostructures are considered potential targets for molecular diagnosis, antiviral therapeutics, and the development of vaccines. This review article describes glycan nanostructures (eg, glycoproteins and glycolipids) that exist in cells, subcellular structures, and microbes. We detail the structure, characterization, synthesis, and functions of virus glycans. Furthermore, we describe the glycan nanostructures of different human coronaviruses, such as human coronavirus 229E (HCoV-229E), human coronavirus OC43 (HCoV-OC43), severe acute respiratory syndrome-associated coronavirus (SARS-CoV), human coronavirus NL63 (HCoV-NL63), human coronavirus HKU1 (HCoV-HKU1), the Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and how glycan nanotechnology can be useful to prevent and combat human coronaviruses infections, along with possibilities that are not yet explored.


Asunto(s)
Betacoronavirus/química , Nanoestructuras/análisis , Nanoestructuras/química , Polisacáridos/análisis , Polisacáridos/química , Humanos
17.
Front Cell Infect Microbiol ; 11: 783568, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35096640

RESUMEN

BACKGROUND: Fever of unknown origin (FUO) is still a challenge for clinicians. Next-generation sequencing technologies, such as whole exome sequencing (WES), can be used to identify genetic defects in patients and assist in diagnosis. In this study, we investigated the application of WES in individuals with FUO. METHODS: We performed whole-exome sequencing on 15 FUO patients. Clinical information was extracted from the hospital information system. RESULTS: In 7/15 samples, we found positive results, including potentially causative mutations across eight different genes: CFTR, CD209, IRF2BP2, ADGRV 1, TYK2, MEFV, THBD and GATA2. CONCLUSIONS: Our results show that whole-exome sequencing can promote the genetic diagnosis and treatment of patients with FUO.


Asunto(s)
Fiebre de Origen Desconocido , Exoma , Fiebre de Origen Desconocido/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Mutación , Secuenciación del Exoma/métodos
18.
Infect Drug Resist ; 13: 4347-4353, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33293838

RESUMEN

Individuals with genetic defects show an increased susceptibility to poorly pathogenic mycobacteria including nontuberculous mycobacteria and Bacillus Calmette-Guerin (BCG). In previous studies, defects in multiple genes were identified to be associated with mycobacterium infection including tyrosine kinase 2 (TYK2). The mutations lead to insufficient production of interferon (IFN)-γ or an insufficient response to IFN-α/ß, interleukin (IL)-6, IL-10, IL-12 and IL-23. Herein, we describe a case of Mycobacterium intracellulare infection in a male with abdominal pain and diarrhea. Whole exome sequencing of the genomes revealed a compound heterozygous mutation (c.3083A>G/c.2590C>T, p.N1028S/p.R864C) in the TYK2 gene. The patient recovered after two years of anti-mycobacterial treatment and no relapse was observed so far. We also reviewed 24 cases of mycobacterial infection associated with TYK2 deficiency which provides evidence of how personalised genomics can improve outcomes.

19.
Infect Drug Resist ; 13: 4223-4234, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33262617

RESUMEN

PURPOSE: To identify candidate hub genes and miRNAs associated with active tuberculosis (ATB) and reveal the potential molecular mechanisms of disease progression. PATIENTS AND METHODS: The expression of mRNA and miRNA was evaluated in peripheral blood mononuclear cells (PBMC) from 4 ATB patients and 4 healthy donors (HD) using high throughput sequencing (HTS) and bioinformatics analysis. Moreover, differentially expressed miRNAs were validated with 35 ATB patients and 35 HDs using reverse transcription quantitative real-time PCR (RT-qPCR). RESULTS: A total of 2658 significantly differentially expressed genes (DEG) including 1415 up-regulated genes and 1243 down-regulated genes were identified in the ATB group compared with HDs, and the DEGs enriched in immune-related pathways, especially in TNF signaling pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase (MAPK) signaling pathways and tuberculosis. Additionally, 10 hub genes were acquired according to protein-protein interaction (PPI) analysis of DEGs. Moreover, 26 differentially expressed miRNAs were found in ATB group compared with HDs. Furthermore, RT-qPCR results showed that hsa-miR-23a-5p (P=0.0106), hsa-miR-183-5p (P=0.0027), hsa-miR-193a-5p (P=0.0021) and hsa-miR-941(P=0.0001) were significantly increased in the ATB patients compared with HD group, and the hsa-miR-16-1-3p was significantly decreased (P=0.0032). CONCLUSION: Our research provided a characteristic profile of mRNAs and miRNAs expressed in ATB subjects, and 10 hub genes related with ATB were found, which will contribute to explore the role of miRNAs and hub genes in the pathogenesis of ATB, and improve the ability of differential diagnosis and treatment for the disease.

20.
Infect Drug Resist ; 13: 1663-1672, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32606817

RESUMEN

PURPOSE: Tuberculosis remains a major public health problem globally, especially in undeveloped countries. This study aimed to evaluate and review the long-term epidemic trends of tuberculosis in China. METHODS: Data were extracted from the Global Health Data Exchange. Metrics (prevalence, incidence and mortality) and Joinpoint regression were used to identify the epidemic trends. RESULTS: From 1990 to 2017, decreasing trends in prevalence (average annual percent change, AAPC: -0.5%, 95% CI: -0.6% to -0.5%), incidence (-3.2%, 95% CI: -3.5% to -2.9%), and mortality (-5.7%, 95% CI: -6.2% to -5.3%) of tuberculosis were observed. The incidence and mortality of multidrug-resistant tuberculosis (MDR-TB) decreased with AAPC of -2.3% (-3.1% to -1.4%) and -4.9% (-5.4% to -4.5%), respectively, while the prevalence increased with an AAPC of 1.2% (0.3% to 2.0%). The burden of extensively drug-resistant tuberculosis (XDR-TB) increased with an AAPC of 12.5% (11.9% to 13.2%) in prevalence, 7.6% (6.5% to 8.7%) in incidence, and 4.5% (3.6% to 5.4%) in mortality. The disease burden of tuberculosis increased with age and peaked among those aged over 70. CONCLUSION: The epidemic of tuberculosis decreased in China, while the disease burden was still challenging to control. MDR-TB and XDR-TB should be emphasized along with the epidemic. It will certainly be a difficult task to achieve the post-2015 global targets by 2025 and 2035.

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