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1.
Dokl Biochem Biophys ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700816

RESUMO

Study of CD4+ T cell response and T cell receptor (TCR) specificity is crucial for understanding etiology of immune-mediated diseases and developing targeted therapies. However, solubility, accessibility, and stability of synthetic antigenic peptides used in T cell assays may be a critical point in such studies. Here we present a T cell activation reporter system using recombinant proteins containing antigenic epitopes fused with bacterial thioredoxin (trx-peptides) and obtained by bacterial expression. We report that co-incubation of CD4+ HA1.7 TCR+ reporter Jurkat 76 TRP cells with CD80+ HLA-DRB1*01:01+ HeLa cells or CD4+ Ob.1A12 TCR+ Jurkat 76 TRP with CD80+ HLA-DRB1*15:01+ HeLa cells resulted in activation of reporter Jurkat 76 TPR after addition of recombinant trx-peptide fusion proteins, containing TCR-specific epitopes. Trx-peptides were comparable with corresponding synthetic peptides in their capacity to activate Jurkat 76 TPR. These data demonstrate that thioredoxin as a carrier protein (trx) for antigenic peptides exhibits minimal interference with recognition of MHC-specific peptides by TCRs and consequent T cell activation. Our findings highlight potential feasibility of trx-peptides as a reagent for assessing the immunogenicity of antigenic fragments.

2.
Sud Med Ekspert ; 67(2): 20-27, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38587154

RESUMO

OBJECTIVE: To study emergence mechanism, physical nature, pattern of intravital and postmortem changes of biological and non-biological objects originated in the period from 1550 to 1918 yr. using traditional X-ray and X-ray computed tomography. MATERIAL AND METHODS: The relics of Saint Macarius the Roman of Novgorod, the remains of the First Reverend of the Resurrection Novodevichy Convent in Saint Petersburg Mother Superior Theophania, damages on the chair leg on which Tsesarevich Alexey sat during the shooting of Russian Emperor Nicholas II, his family and entourage in 1918 in Yekaterinburg were stidued. RESULTS AND CONCLUSION: The application of highly informative methods of traditional X-ray and X-ray computed tomography of biological and non-biological objects showed their high informativity and allowed to correctly interpret the emergence mechanism, physical nature, pattern of intravital and postmortem changes of skeleton bones and historical artefact (chair legs) originated long ago. The necessity of special professional training and advanced training of experts in forensic radiology to prevent possible diagnostic and expert errors has been substantiated.


Assuntos
Artefatos , Mudanças Depois da Morte , Humanos , Raios X , Tomografia Computadorizada por Raios X/métodos
3.
Sud Med Ekspert ; 67(2): 39-42, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38587157

RESUMO

A rare clinical observation of death from prolonged uneven external irradiation due to the deliberate use of an ionizing radiation source for illegal purposes has been presented. The main difficulties of postmortem diagnosis of this type of radiation-induced injury, considering the features of histological examinations and special methods of retrospective dosimetric evaluations, have been identified.


Assuntos
Radiação Ionizante , Estudos Retrospectivos
4.
Bull Exp Biol Med ; 176(4): 515-518, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38492109

RESUMO

We studied the effect of structural properties of deproteinized spongy bone (DSB) on functional activity of adipose tissue mesenchymal stromal cells of (MSC) for the potential use of these materials as components of a combined tissue-engineered construct. The porosity of the structure of DSB samples and the pore size promote MSC adhesion, migration, and proliferation on their surface and in the depth, revealing the architectonics of this bone matrix. The depth of cell penetration into the samples (from 273 to 702 µm) and an increase in the total number of cells (from 302 on day 1 to 1744 on day 7) demonstrated MSC adhesion, migration, and proliferation. The viability of cultured MSC was preserved for up to 7 days. The obtained results prove the possibility of using allogeneic DSB from femoral heads as a bone matrix in tissue-engineered constructs in combination with MSC. Such constructs can be used to efficiently restore the structural and functional integrity of the bone tissue in abnormal processes of various etiopathogenesis associated with the formation of bone defects or bone tissue deficiency.


Assuntos
Osso Esponjoso , Células-Tronco Mesenquimais , Engenharia Tecidual/métodos , Matriz Óssea , Tecido Adiposo , Células Cultivadas , Diferenciação Celular
5.
Phys Rev Lett ; 132(9): 099901, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489658

RESUMO

This corrects the article DOI: 10.1103/PhysRevLett.123.107703.

6.
Zhonghua Wei Chang Wai Ke Za Zhi ; 27(1): 35-40, 2024 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-38262898

RESUMO

The clinical application of robotic gastrointestinal surgery has made significant progress during the past 20 years. Increasing research have demonstrated that the robotic gastrointestinal surgery is safe and feasible, with the advantages in lymph node dissection, precise manipulation in narrow space, intraoperative suturing, and achieves satisfactory clinical outcomes. However, it also face challenges such as high costs, lack of high quality studies, and limited intelligent level. With the advancement of more high-quality evidence-based medical research and the development of new intelligent surgical robots, the robotic gastrointestinal surgery will be further standardized. We believe that the robotic surgery will become the mainstream of surgical treatment for gastrointestinal surgery.


Assuntos
Pesquisa Biomédica , Procedimentos Cirúrgicos do Sistema Digestório , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Excisão de Linfonodo
7.
Zhonghua Wei Chang Wai Ke Za Zhi ; 27(1): 47-53, 2024 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-38262900

RESUMO

Objective: In this study, we aimed to compare the short-term safety of two digestive tract reconstruction techniques, laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis, following radical resection of Siewert Type II adenocarcinoma of the esophagogastric junction. Methods: In this retrospective cohort study, we analyzed relevant clinical data of 139 patients who had undergone radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. These included 89 patients treated at the First Affiliated Hospital of Air Force Medical University from November 2021 to July 2023, 36 patients treated at the First Affiliated Hospital of Xi'an Jiaotong University from December 2020 to June 2021, and 14 patients treated at the Yuncheng Central Hospital in Shanxi Province from September 2021 to November 2022. The group consisted of 107 men (77.0%) and 32 women (23.0%) of mean age 62.5±9.3 years. Forty-eight patients underwent laparoscopic total abdominal overlap anastomosis (overlap group), and 91 laparoscopic-assisted end-to-side anastomosis (end-to-side group). Clinical data, surgical information, pathological findings, postoperative recovery, and related complications were compared between the two groups. Results: There were no significant differences in general clinical data between the overlap and end-to-side anastomosis groups (all P>0.05), indicating comparability. There was no significant difference in operation time (267.2±60.1 minutes vs. 262.8±70.6 minutes, t=0.370, P=0.712). However, the intraoperative blood loss in the overlap group (100 [50, 100] mL) was significantly lower compared to the end-to-side group (100[50, 175] mL, Z=2.776, P=0.005). Compared to the end-to-side group, longer distances between the tumor and distal resection margin proximal(1.7±1.0 cm vs. 1.3±0.9 cm, t=2.487, P=0.014) and the tumor and distal resection margin (9.5±2.9 cm vs. 7.9±3.5 cm, t=2.667, P=0.009) were achieved in the overlap group. Compared with the end-to-side group, the overlap group achieved significantly earlier postoperative ambulation (1.0 [1.0, 2.0] days vs. 2.0 [1.0, 3.0] days, Z=3.117, P=0.002), earlier time to first drink (4.7±2.6 days vs. 6.2±3.0 days, t=2.851, P=0.005), and earlier time to first meal (6.0±2.7 days vs. 7.1±3.0 days, t=2.170, P=0.032). However, the hospitalization costs were higher in the overlap group (113, 105.5±37, 766.3) yuan vs. (97, 250.2±27, 746.9) yuan; this difference is significant (t=2.818, P=0.006). There were no significant differences between the two groups in postoperative hospital stay, total number of lymph nodes cleared, or time to first postoperative flatus (all P>0.05). The incidence of surgery-related complications was 22.9%(11/48) in the overlap group and 19.8% (18/91) in the end-to-side group; this difference is not significant (χ²=0.187, P=0.831). Further comparison of complications using the Clavien-Dindo classification also showed no significant differences (Z=0.406, P=0.685). Conclusions: Both laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis are feasible for radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. Laparoscopic total abdominal overlap anastomosis achieves longer proximal and distal resection margins and better postoperative recovery; however, end-to-side anastomosis is more cost-effective.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Margens de Excisão , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Anastomose Cirúrgica , Junção Esofagogástrica
8.
Mol Psychiatry ; 29(2): 369-386, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38102482

RESUMO

Understanding the role of small, soluble aggregates of beta-amyloid (Aß) and tau in Alzheimer's disease (AD) is of great importance for the rational design of preventative therapies. Here we report a set of methods for the detection, quantification, and characterisation of soluble aggregates in conditioned media of cerebral organoids derived from human iPSCs with trisomy 21, thus containing an extra copy of the amyloid precursor protein (APP) gene. We detected soluble beta-amyloid (Aß) and tau aggregates secreted by cerebral organoids from both control and the isogenic trisomy 21 (T21) genotype. We developed a novel method to normalise measurements to the number of live neurons within organoid-conditioned media based on glucose consumption. Thus normalised, T21 organoids produced 2.5-fold more Aß aggregates with a higher proportion of larger (300-2000 nm2) and more fibrillary-shaped aggregates than controls, along with 1.3-fold more soluble phosphorylated tau (pTau) aggregates, increased inflammasome ASC-specks, and a higher level of oxidative stress inducing thioredoxin-interacting protein (TXNIP). Importantly, all this was detectable prior to the appearance of histological amyloid plaques or intraneuronal tau-pathology in organoid slices, demonstrating the feasibility to model the initial pathogenic mechanisms for AD in-vitro using cells from live genetically pre-disposed donors before the onset of clinical disease. Then, using different iPSC clones generated from the same donor at different times in two independent experiments, we tested the reproducibility of findings in organoids. While there were differences in rates of disease progression between the experiments, the disease mechanisms were conserved. Overall, our results show that it is possible to non-invasively follow the development of pathology in organoid models of AD over time, by monitoring changes in the aggregates and proteins in the conditioned media, and open possibilities to study the time-course of the key pathogenic processes taking place.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Síndrome de Down , Células-Tronco Pluripotentes Induzidas , Organoides , Proteínas tau , Humanos , Organoides/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Proteínas tau/metabolismo , Síndrome de Down/metabolismo , Síndrome de Down/genética , Síndrome de Down/patologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Neurônios/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Trissomia/genética , Estresse Oxidativo , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Meios de Cultivo Condicionados , Microscopia de Fluorescência/métodos
9.
Zhonghua Yan Ke Za Zhi ; 59(12): 1003-1011, 2023 Dec 11.
Artigo em Chinês | MEDLINE | ID: mdl-38061901

RESUMO

Objective: To analyze the relationships between preoperative ocular parameters and postoperative anomalous vaults, and research their predictive diagnostic value. Methods: In this retrospective case series study, 664 eyes from 332 patients underwent posterior chamber phakic intraocular lens (pIOL) implantation at Shanghai Bright Eye Hospital and Wuxi Huaxia Eye Hospital from November 2020 to November 2021. Preoperative ocular parameters, including spherical equivalent, intraocular pressure, horizontal/vertical ciliary sulcus diameters (HCS/VCS), white-to-white diameters (WTW), corneal steep/flat curvature, central corneal thickness, anterior chamber depth (ACD), lens thickness (LT), and axial length were collected. The pIOL vaults were measured 3 months after surgery. Patients were categorized into low vault group, optimal vault group, and high vault group based on whether the vault fell within the ideal range (250 to 750 µm). Using the optimal vault group as a benchmark, receiver operating characteristic (ROC) curves were drawn for each ocular parameter of the low and high vault groups to analyze diagnostic efficiency and cut-off values for abnormal vaults after pIOL operation. Each ocular parameter was used as an independent variable to establish a multivariate logistic regression model for two different vault anomalies. ROC curves were drawn and analyzed again based on the regression results. Results: Statistically significant differences were observed in WTW, HCS-WTW, ACD, and LT among the three groups. Comparisons between each pair of groups indicated that WTW in the high vault group significantly differed from the other two groups (P<0.05), HCS-WTW in the low vault group significantly differed from the other groups (P<0.05), and ACD and LT explained statistical differences among the three groups (P<0.05), while other parameters showed no differences. ROC curves illustrated that independent ocular parameters such as LT, HCS-WTW, and ACD had clinical predictive diagnostic significance for low vault abnormalities. The area under the curve (AUC), sensitivity, and specificity for these parameters were 0.829(0.952, 0.561), 0.745(0.857, 0.644), and 0.730(0.619, 0.853), respectively. The diagnostic cut-off values were 3.745, 0.020, and 2.975 mm, respectively. The clinical predictive significance of independent ocular parameters in diagnosing the high vault group was poor (AUC<0.7). The predictive Logistic model equation for low vault was Logistic(V1)=-10.067+5.328·HCS-3.620·WTW+6.263·LT, and the predictive model for high vault was Logistic(V2)=6.232+1.323·WTW-3.358·LT. The new parameters in the predictive equation significantly improved the diagnostic efficiency of low and high vault abnormalities, reaching 0.884(0.810, 0.824) and 0.736(0.810, 0.554), respectively. Conclusions: Preoperative predictive diagnostic parameters for postoperative low vault group included LT, HCS-WTW, and ACD, while the high vault group had no independent predictive diagnostic parameters. Logistic regression improved the predictive diagnostic efficiency of abnormal vaults.


Assuntos
Miopia , Lentes Intraoculares Fácicas , Humanos , Estudos Retrospectivos , Miopia/cirurgia , Miopia/diagnóstico , China , Câmara Anterior
10.
Artigo em Inglês | MEDLINE | ID: mdl-38082588

RESUMO

Neuromuscular electrical stimulation (NMES) has been demonstrated to effectively modulate cortical activities by evoking muscle contraction in upper limb and generating joint movements, which showed an excellent performance in motor rehabilitation. However, due to hand loss and cortical function reorganization induced by hand amputation, how neural activities in sensorimotor cortex response to NMES-evoked muscle contraction in the end of an amputation stump is not clear. In this paper, Ischemic nerve block (INB) technique was used to build an acute hand loss model, and 64-channel EEG signals were recorded from 11 healthy subjects to perform a 2×2 factorial design protocol, with the INB state and the current intensity as factors. The changes of NMES-evoked sensorimotor cortical activities were quantified by computing Beta-band event-related desynchronization (Beta ERD) patterns and the time-varying functional connectivity using adaptive directed transfer function (ADTF) before and during INB. The acute hand "loss" resulted in ipsilateral dominance of Beta ERD induced by NMES with two current intensities in the topographic maps, that is, ipsilateral Beta ERD was significantly higher than that the contralateral one (p<0.05). However, before INB, Beta ERD in the contralateral sensorimotor cortex induced by NMES above motor threshold was significantly higher than that in the ipsilateral area (p< 0.01). Meanwhile, whatever before or during INB, clustering coefficients of the ADTF network in sensorimotor cortex showed temporal dynamics during two NMES tasks. During INB, NMES above motor threshold-evoked lower clustering coefficients of the time-varying network in sensorimotor cortex than that before INB (p<0.05). The present results suggest that the loss of the hand proprioception will degrade cortical activities in the contralateral area, and increase cortical activities in the ipsilateral area compensatively responding to NMES. This finding may be particularly important to improve the reconstruction of the proprioception function of hand prosthesis.


Assuntos
Córtex Motor , Córtex Sensório-Motor , Humanos , Córtex Motor/fisiologia , Córtex Sensório-Motor/fisiologia , Mãos , Movimento/fisiologia , Cotos de Amputação
12.
Zhonghua Yu Fang Yi Xue Za Zhi ; 57(11): 1901-1907, 2023 Nov 06.
Artigo em Chinês | MEDLINE | ID: mdl-38008584

RESUMO

High density lipoprotein (HDL) is an important biochemical index of clinical cardiovascular disease. Many new studies have demonstrated abnormalities of plasma HDL subfractions in patients with this disease,and their clinical significance is greater than the overall abnormalities of HDL. Therefore,the HDL subfraction as an important factor in cardiovascular disease has attracted extensive research and attention. This article summarizes current research on HDL subfractions,their measurements and their relationships with atherosclerosis and coronary artery disease.


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Humanos , Relevância Clínica , HDL-Colesterol , Lipoproteínas HDL
13.
Zhonghua Wei Chang Wai Ke Za Zhi ; 26(10): 922-928, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37849261

RESUMO

Radiation-induced intestinal injury is a radiation injury of the colon and rectum after radiotherapy for pelvic malignant tumors. This condition affects multiple organs in the pelvis, making treatment challenging. In clinical practice, the most effective protocol is often determined through discussion by a multi-disciplinary team (MDT). However, due to the severity and complexity of radiation enteritis, many patients still experience poor diagnosis and treatment outcomes. Holistic integrative management (HIM) is a rapidly developing concept that has greatly enhanced clinical medicine in recent years. It improves the level of diagnosis, treatment, prevention, and rehabilitation from multiple dimensions of prevention, screening, diagnosis, treatment, and rehabilitation. In the context of radiation-induced intestinal injury, HIM also calls for the implementation of an individualized management system that focuses on the patient as a whole within the healthcare team. From the perspective of HIM, this article introduces some of the latest progress of radiation-induced intestinal injury in recent years.


Assuntos
Enterite , Neoplasias Pélvicas , Lesões por Radiação , Humanos , Reto , Resultado do Tratamento , Neoplasias Pélvicas/radioterapia , Lesões por Radiação/terapia , Equipe de Assistência ao Paciente
14.
Anal Chem ; 95(41): 15254-15263, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37782556

RESUMO

The formation of soluble α-synuclein (α-syn) and amyloid-ß (Aß) aggregates is associated with the development of Parkinson's disease (PD). Current methods mainly focus on the measurement of the aggregate concentration and are unable to determine their heterogeneous size and shape, which potentially also change during the development of PD due to increased protein aggregation. In this work, we introduce aptamer-assisted single-molecule pull-down (APSiMPull) combined with super-resolution fluorescence imaging of α-syn and Aß aggregates in human serum from early PD patients and age-matched controls. Our diffraction-limited imaging results indicate that the proportion of α-syn aggregates (α-syn/(α-syn+Aß)) can be used to distinguish PD and control groups with an area under the curve (AUC) of 0.85. Further, super resolution fluorescence imaging reveals that PD serums have a higher portion of larger and rounder α-syn aggregates than controls. Little difference was observed for Aß aggregates. Combining these two metrics, we constructed a new biomarker and achieved an AUC of 0.90. The combination of the aggregate number and morphology provides a new approach to early PD diagnosis.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Agregados Proteicos , alfa-Sinucleína/metabolismo , Peptídeos beta-Amiloides/metabolismo
15.
Vavilovskii Zhurnal Genet Selektsii ; 27(5): 530-538, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37867609

RESUMO

The etiology of essential hypertension is intricate, since it employs simultaneously various body systems related to the regulation of blood pressure in one way or another: the sympathetic nervous system, renin-angiotensin-aldosterone and hypothalamic-pituitary-adrenal systems, renal and endothelial mechanisms. The pathogenesis of hypertension is influenced by a variety of both genetic and environmental factors, which determines the heterogeneity of the disease in human population. Hence, there is a need to perform research on experimental models - inbred animal strains, one of them being ISIAH rat strain, which is designed to simulate inherited stress-induced arterial hypertension as close as possible to primary (or essential) hypertension in humans. To determine specific markers of diseases, various omics technologies are applied, including metabolomics, which makes it possible to evaluate the content of low-molecular compounds - amino acids, lipids, carbohydrates, nucleic acids fragments - in biological samples available for clinical analysis (blood and urine). We analyzed the metabolic profile of the blood serum of male ISIAH rats with a genetic stress-dependent form of arterial hypertension in comparison with the normotensive WAG rats. Using the method of nuclear magnetic resonance spectroscopy (NMR spectroscopy), 56 metabolites in blood serum samples were identified, 18 of which were shown to have significant interstrain differences in serum concentrations. Statistical analysis of the data obtained showed that the hypertensive status of ISIAH rats is characterized by increased concentrations of leucine, isoleucine, valine, myo-inositol, isobutyrate, glutamate, glutamine, ornithine and creatine phosphate, and reduced concentrations of 2-hydroxyisobutyrate, betaine, tyrosine and tryptophan. Such a ratio of the metabolite concentrations is associated with changes in the regulation of glucose metabolism (metabolic markers - leucine, isoleucine, valine, myo-inositol), of nitric oxide synthesis (ornithine) and catecholamine pathway (tyrosine), and with inflammatory processes (metabolic markers - betaine, tryptophan), all of these changes being typical for hypertensive status. Thus, metabolic profiling of the stress-dependent form of arterial hypertension seems to be an important result for a personalized approach to the prevention and treatment of hypertensive disease.

16.
J Nutr Health Aging ; 27(9): 767-774, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37754217

RESUMO

BACKGROUND: Osteoporosis is a highly prevalent disease with distinct sex pattern. We aimed to estimate the sex specific incidence, prevalence, and disability-adjusted life (DALYs) years of osteoporosis between 1990 and 2019, with additional predictions from 2020 to 2034. METHODS: We collected osteoporosis disease burden data from the Global Burden of Disease study covering the years 1990 through 2019 in 204 countries and territories. The data included information on the number of incident cases of osteoporosis, DALYs, age-standardized incidence rates (ASIR), age-standardized prevalence rates (ASPR) and age-standardized DALYs rates. Additionally, we performed an age-period-cohort analysis to forecast the burden of osteoporosis. RESULTS: The global number of incidence cases of osteoporosis, in 2019, reached 41.5 million cases. From 1990 to 2019, the low-middle socio-demographic index (SDI) region had the highest estimated annual percentage change in the world. Compared to males, female's ASIR and ASPR were all about 1.5 times higher than males for the same years in the same SDI regions. The projected global total number of incidence cases for osteoporosis between 2030 and 2034 is estimated to reach 263.2 million (154.4 million for females and 108.8 for males). Additionally, the burden in terms of DALYs is predicted to be 128.7 million (with 78.4 million for females and 50.3 million for males). CONCLUSION: The global burden of osteoporosis is still increasing, mainly observed in high SDI countries. Females bear a burden 1.5 times higher than males in terms of incidence and DALYs. Steps should be taken to reduce the osteoporosis burden, especially in high SDI countries.


Assuntos
Pessoas com Deficiência , Masculino , Humanos , Feminino , Anos de Vida Ajustados por Qualidade de Vida , Estudos de Coortes , Efeitos Psicossociais da Doença , Incidência
17.
Microbiol Spectr ; : e0118123, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37750685

RESUMO

Rhinovirus (RV) is the leading pathogen causing childhood wheezing, with rhinovirus C (RV-C) species reported to cause asthma exacerbation. Allele A of single-nucleotide polymorphism (SNP) CDHR3_rs6967330 upregulates epithelial expression of RV-C receptors which results in more severe asthma exacerbations in children. Nevertheless, there are limited data on interactions between CDHR3 variants and their impact on severity of RV-related pediatric respiratory tract infections (RTIs). Medical records of RV-related RTIs in children aged below 18 years who were hospitalized in two public hospitals in 2015-2016 were independently reviewed by two paediatricians. Archived nasopharyngeal aspirates were retrieved for RV detection and sequencing as well as CDHR3 genotyping. HaploView v.5.0 and generalized multifactor dimensionality reduction (GMDR) analysis were employed for haplotypic assignment and gene-environment interaction analyses. Among 1019 studied cases, our results confirmed the relationship between RV-C species and more severe RTIs. Besides the top risk variant rs6967330-A, we identified rs140154310-T to be associated with RV-C susceptibility under the additive model [odds ratio (OR) 2.53, 95% CI 1.15-5.56; P = 0.021]. Rs140154310 was associated with wheezing illness (OR 2.38, 95% CI 1.12-5.04; P = 0.024), with such association being stronger in subjects who wheezed due to RV-C infections (OR 2.71, 95% CI 1.32-5.58; P = 0.007). Haplotype GAG constructed from rs4730125, rs6967330, and rs73195665 was associated with increased risk of RV-C infection (OR 1.71, 95% CI 1.11-2.65; P = 0.016) and oxygen supplementation (OR 1.93, 95% CI 1.13-3.30; P = 0.016). GMDR analyses revealed epistatic interaction between rs140154310 and rs6967330 of CDHR3 for RV-C infection (P = 0.001), RV-C-associated lower RTI (P = 0.004), and RV-C-associated wheeze (P = 0.007). There was synergistic gene-environmental interaction between rs3887998 and RV-C for more severe clinical outcomes (P < 0.001). To conclude, rs140154310-T is another risk variant for RV-C susceptibility and more severe RTIs. Synergistic epistatic interaction is found between CDHR3 SNPs and RV-C for RTI severity, which is likely mediated by susceptibility to RV-C. Haplotypic analysis and GMDR should be included in identifying prediction models of CDHR3 for childhood asthma and RTIs. IMPORTANCE This case-control study investigated the interaction between CDHR3 genotypes and rhinovirus (RV) species on disease severity in Hong Kong children hospitalized for respiratory tract infection (RTI). There were synergistic effects between RV-C and CDHR3 SNPs for RTI severity, which was mainly driven by RV-C. Specifically, rs6967330 and rs140154310 alone and their epistatic interaction were associated with RV-C-related and severe RTIs in our subjects. Therefore, genotyping of CDHR3 SNPs may help physicians formulate prediction models for severity of RV-associated RTIs.

18.
Zhonghua Yu Fang Yi Xue Za Zhi ; 57(9): 1434-1439, 2023 Sep 06.
Artigo em Chinês | MEDLINE | ID: mdl-37743305

RESUMO

Objective: To analyze the genetic characteristics of the first human infection with the G4 genotype of Eurasian avian H1N1 swine influenza virus (EA H1N1 SIV) in Shaanxi Province. Methods: The patient's throat swab samples were collected, and MDCK cells were inoculated for virus isolation to obtain the virus strain. The whole genome deep sequencing method was used to obtain the eight gene segments of the isolated strain. The nucleotide homology analysis was conducted through the Blast program in the GenBank database, and a phylogenetic tree was constructed to analyze the genetic characteristics of the virus. Results: The throat swab specimens of the case were confirmed as EA H1N1 SIV in the laboratory, and the isolated strain was named A/Shaanxi-Weicheng/1351/2022(H1N1v). Homology analysis found that the PB2, NP, HA, NA, and M genes of this isolate had the highest nucleotide homology with A/swing/Beijing/0301/2018 (H1N1), about 98.29%, 98.73%, 97.41%, 97.52%, and 99.08%, respectively. The phylogenetic tree showed that the isolate belonged to G4 genotype EA H1N1 SIV, with PB2, PB1, PA, NP and M genes from pdm/09 H1N1, HA and NA genes from EA H1N1, and NS gene from Triple-reassortant H1N1. The cleavage site of the HA protein was IPSIQSR↓G, which was the molecular characteristic of the low pathogenic influenza virus. No amino acid mutations associated with neuraminidase inhibitors were found in the NA protein. PB2 protein 701N mutation, PA protein P224S mutation, NP protein Q357K mutation, M protein P41A mutation, and NS protein 92D all indicated its enhanced adaptability to mammals. Conclusion: The patient is the first human infection with G4 genotype EA H1N1 SIV in Shaanxi province. The virus is low pathogenic, but its adaptability to mammals is enhanced. Therefore, it is necessary to strengthen the monitoring of such SIVs.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Suínos , Humanos , Animais , Vírus da Influenza A Subtipo H1N1/genética , Filogenia , Genótipo , China , Aves , Mamíferos
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