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1.
Nat Immunol ; 19(9): 1036, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29915300

RESUMEN

In the version of this article initially published, some identification of the supplementary information was incorrect. The items originally called Supplementary Tables 1, 2, 3, 4 and 5 should be Source Data Figures 1, 2, 4, 5 and 7, respectively; those originally called Supplementary Tables 6, 7 and 8 should be Supplementary Tables 1, 2 and 3, respectively; and those originally called Source Data Figures 1, 2, 4, 5 and 7 should be Supplementary Tables 4, 5, 6, 7 and 8, respectively. The errors have been corrected in the HTML version of the article.

2.
Nat Immunol ; 19(3): 279-290, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29434353

RESUMEN

Deletion of master regulators of the B cell lineage reprograms B cells into T cells. Here we found that the transcription factor Hoxb5, which is expressed in uncommitted hematopoietic progenitor cells but is not present in cells committed to the B cell or T cell lineage, was able to reprogram pro-pre-B cells into functional early T cell lineage progenitors. This reprogramming started in the bone marrow and was completed in the thymus and gave rise to T lymphocytes with transcriptomes, hierarchical differentiation, tissue distribution and immunological functions that closely resembled those of their natural counterparts. Hoxb5 repressed B cell 'master genes', activated regulators of T cells and regulated crucial chromatin modifiers in pro-pre-B cells and ultimately drove the B cell fate-to-T cell fate conversion. Our results provide a de novo paradigm for the generation of functional T cells through reprogramming in vivo.


Asunto(s)
Linfocitos B/citología , Linaje de la Célula/inmunología , Reprogramación Celular/inmunología , Proteínas de Homeodominio/inmunología , Linfocitos T/citología , Animales , Diferenciación Celular , Linaje de la Célula/genética , Reprogramación Celular/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones SCID , Células Precursoras de Linfocitos B/citología
3.
J Med Genet ; 61(2): 125-131, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-37399314

RESUMEN

BACKGROUND: Mitral annular disjunction (MAD) is an under-recognised phenotype associated with severe ventricular arrhythmias. Limited knowledge has been gained on its molecular genesis. METHODS: A total of 150 unrelated deceased Chinese were collected for whole-exome sequencing, with analysis focusing on a panel of 118 genes associated with 'abnormal mitral valve morphology'. Cases were prespecified as 'longitudinally extensive MAD (LE-MAD)' or 'longitudinally less-extensive MAD (LLE-MAD)' according to the gross disjunctional length with a cut-off of 4.0 mm. The pedigree investigation was conducted on a case carrying an ultra-rare (minor allele frequency <0.1%) deleterious variant in DCHS1. RESULTS: Seventy-seven ultra-rare deleterious variants were finally identified. Exclusively, 12 ultra-rare deleterious variants distributed in nine genes occurred in LE-MAD, which were ANK1, COL3A1, DCHS1, FBN2, GNPTAB, LZTR1, PLD1, RYR1 and VPS13B. Ultra-rare deleterious variants in those nine genes were predominantly distributed in LE-MAD compared with LLE-MAD (28% vs 5%, OR 7.30, 95% CI 2.33 to 23.38; p<0.001), and the only gene related to LE-MAD with borderline significance was DCHS1. LE-MAD was consistently observed in a sizeable Chinese family, in which LE-MAD independently co-segregated with an ultra-rare deleterious variant in DCHS1, rs145429962. CONCLUSION: This study initially proposed that isolated LE-MAD might be a particular phenotype of MAD with a complex genetic predisposition. Deleterious variants in DCHS1 might be associated with the morphogenesis of LE-MAD.


Asunto(s)
Enfermedades de las Válvulas Cardíacas , Prolapso de la Válvula Mitral , Humanos , Prolapso de la Válvula Mitral/genética , Válvula Mitral , Mutación/genética , Arritmias Cardíacas , Susceptibilidad a Enfermedades , Factores de Transcripción/genética , Transferasas (Grupos de Otros Fosfatos Sustitutos)/genética
4.
Opt Express ; 32(6): 8778-8790, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571127

RESUMEN

Recent advancements in ptychography have demonstrated the potential of coded ptychography (CP) for high-resolution optical imaging in a lensless configuration. However, CP suffers imaging throughput limitations due to scanning inefficiencies. To address this, we propose what we believe is a novel 'fly-scan' scanning strategy utilizing two eccentric rotating mass (ERM) vibration motors for high-throughput coded ptychographic microscopy. The intrinsic continuity of the 'fly-scan' technique effectively eliminates the scanning overhead typically encountered during data acquisition. Additionally, its randomized scanning trajectory considerably reduces periodic artifacts in image reconstruction. We also developed what we believe to be a novel rolling-shutter distortion correction algorithm to fix the rolling-shutter effects. We built up a low-cost, DIY-made prototype platform and validated our approach with various samples including a resolution target, a quantitative phase target, a thick potato sample and biospecimens. The reported platform may offer a cost-effective and turnkey solution for high-throughput bio-imaging.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39133258

RESUMEN

Sudden cardiac death represents a significant diagnostic challenge for forensic pathologists, particularly in inherited arrhythmia syndromes or cardiomyopathies resulting from genetic defects. Molecular autopsies can reveal the underlying molecular etiology in such cases. In this study, we investigated a family with a history of sudden cardiac death to elucidate the molecular basis responsible for sudden cardiac death. The proband underwent a comprehensive forensic examination. Family members received thorough clinical evaluations, including electrocardiogram, Holter monitoring, echocardiography, and cardiac magnetic imaging. Whole exome sequencing and genetic analysis were performed on the deceased and her parents. In addition, Western blotting and patch-clamp recordings were employed to evaluate the expression and function of the mutant protein in vitro. Forensic examination diagnosed arrhythmogenic right ventricular cardiomyopathy (ARVC) as the cause of sudden death. Genetic analysis identified a novel missense mutation in SCN5A (p.V1323L), which was assessed as likely pathogenic by the ACMG guideline. Another family member carrying the mutation manifested long QT syndrome and mild cardiac fibrosis. The cellular electrophysiological study demonstrated that the mutation resulted in an enhanced late sodium current, suggesting it was a gain-of-function mutation. This study characterizes a novel SCN5A mutation that putatively causes long QT syndrome and may contribute to the development of ARVC. Our work expands the pathogenic spectrum of SCN5A variants and underscores the importance of molecular autopsy in sudden death cases, especially in those with suspected genetic disorders.

6.
Fa Yi Xue Za Zhi ; 38(2): 246-253, 2022 Apr 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-35899514

RESUMEN

OBJECTIVES: By retrospective study of the epidemiological characteristics of sports-related sudden death (SrSD), the risk factors associated with SrSD were analyzed and explored to provide a scientific basis for comprehensive prevention and treatment of SrSD. METHODS: The personal information (sex, age, occupation, etc.), case information (time, place, type of sports, relative time between SrSD occurrence and exercise, etc.), death related information (sign or prodrome, medical history and surgical history, etc.), rescue situation (witnesses, on-site assistance, the availability of paramedics, etc.) of 374 SrSD cases in Guangdong Province from 2017 to 2021 were collected. Statistical analysis was conducted aiming at the key factors. RESULTS: In the 374 cases, there were significantly more males than females (19.78:1); the number of people aged between >39 and 59 was the largest (151, 40.37%); non-manual workers (68.98%) were more than manual workers; the top three sports with the highest number cases were basketball (34.49%), running (19.52%) and badminton (12.03%); from 3 pm to 9 pm (63.10%) was the time period with the highest incidence of events; sudden death mainly occurred during exercise (75.27%) and within 1 h after exercise (20.05%); the on-site rescue rate was very low (6.15%); the rate of autopsies was extremely low (1.07%); sudden cardiac death was the most common cause (67.11%). CONCLUSIONS: SrSD is most common in males aged >39 to 59 years old, mostly in non-manual workers, and usually occurs in basketball and running. Sudden death is more likely to occur during exercise and within 1 h after exercise. Therefore, the above potential risk factors should be focused on and studied in daily comprehensive prevention and treatment to provide scientific basis for accurate prevention and first aid of such sudden death.


Asunto(s)
Deportes , Adulto , Autopsia , China/epidemiología , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
7.
Fa Yi Xue Za Zhi ; 38(5): 618-624, 2022 Oct 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-36727179

RESUMEN

Physical exercise can reduce the overall risk of cardiovascular disease, prolong lifespan and improve the quality of life, but some studies have shown that there is a certain correlation between vigorous physical exercise and sudden cardiac death. A number of retrospective or prospective studies on sports-related sudden cardiac death (SrSCD) have been conducted at home and abroad. This article reviews the related studies on the definition, epidemiological characteristics, common causes of SrSCD and effects of excercise on cardiovascular function, pre-exercise screening and evaluation of SrSCD, in order to understand the latest research progress on SrSCD and provide clues and references for SrSCD research.


Asunto(s)
Muerte Súbita Cardíaca , Calidad de Vida , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Incidencia , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control
8.
Fa Yi Xue Za Zhi ; 38(1): 71-76, 2022 Feb 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-35725707

RESUMEN

OBJECTIVES: To study the phenomenon of pulmonary hypostasis in corpses of various causes of death, and to explore the potential value of this phenomenon in assisting forensic pathological diagnosis of drowning. METHODS: A total of 235 cases with clear cause of death through systematic autopsy were collected from January 2011 to June 2021 in Guangzhou. According to the location of body discovery, the cases were divided into the water body group (97 cases) and the non-water body group (138 cases), and the water body group was further divided into the water drowning group (90 cases) and the water non-drowning group (7 cases). Non-water body group was further divided into the non-water drowning group (1 case) and the non-water non-drowning group (137 cases). Three senior forensic pathologists independently reviewed autopsy photos to determine whether there was hypostasis in the lungs. The detection rate of pulmonary hypostasis was calculated. RESULTS: The detection rate of pulmonary hypostasis in the water drowning group (90 cases) was 0, and the negative rate was 100%. The detection rate of pulmonary hypostasis in the water non-drowning group (7 cases) was 100% and the negative rate was 0. The detection rate of pulmonary hypostasis in the water body group and in the non-water body group (after excluding 2 cases, 136 cases were calculated) was 7.22% and 87.50%, respectively. There were statistically significant differences in the detection rate of pulmonary hypostasis between water body group and non-water body group, and between water drowning group and water non-drowning group (P<0.05). CONCLUSIONS: The disappearance of pulmonary hypostasis can be used as a specific cadaveric sign to assist in the forensic pathological diagnosis of drowning.


Asunto(s)
Ahogamiento , Autopsia , Ahogamiento/diagnóstico , Ahogamiento/patología , Patologia Forense , Humanos , Pulmón/patología , Agua
9.
Opt Lett ; 46(22): 5631-5634, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34780423

RESUMEN

We propose a geometric optimization method combined with the Coulombic energy indicator that can uniformly distribute N polarization states on the Poincaré sphere. Based on this method, we investigate the optimal frames of a rotating polarizer and rotating quarter-wave plate (RPRQ)-based polarization state generator (PSG) at different numbers of modulations. We use the PSG on a dual DoFP polarimeter-based Mueller matrix microscope to measure standard samples and pathological sections for testing the performance of an optimized RPRQ. The experimental results show that this method can effectively restrain noise and improve measurement accuracy.

10.
Fa Yi Xue Za Zhi ; 37(6): 847-858, 2021 Dec 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-35243852

RESUMEN

Since the beginning of this century, three types of coronavirus have widely transmitted and caused severe diseases and deaths, which strongly indicates that severe infectious diseases caused by coronavirus infection are not accidental events. Coronavirus-infected diseases are mainly manifested by respiratory symptoms, with multiple organ dysfunctions. Precisely investigating the pathological process, characteristics and pathogenesis of coronavirus-infected diseases will be beneficial for us to understand clinical manifestations and provide targeted suggestions on prophylaxis and treatment. This paper briefly reviews the pathological findings of three known coronavirus-infected diseases, and attempts to construct the pathological spectrum of coronavirus-infected diseases, aiming to provide reference and thinking for autopsy, histopathological examination and animal infection model study of coronavirus-infected diseases.


Asunto(s)
COVID-19 , Animales , Autopsia , Patologia Forense , SARS-CoV-2
11.
J Cell Physiol ; 235(3): 2080-2090, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31389001

RESUMEN

In vitro generation of hematopoietic stem cells from pluripotent stem cells (PSCs) can be regarded as novel therapeutic approaches for replacing bone marrow transplantation without immune rejection or graft versus host disease. To date, many different approaches have been evaluated in terms of directing PSCs toward different hematopoietic cell types, yet, low efficiency and no function restrict the further hematopoietic differentiation study, our research aims to develop a three dimension (3D) hematopoietic differentiation approach that serves as recapitulation of embryonic development in vitro to a degree of complexity not achievable in a two dimension culture system. We first found that mouse PSCs could be efficiently induced to hematopoietic differentiation with an expression of hematopoietic makers, such as c-kit, CD41, and CD45 within self-assembling peptide hydrogel. Colony-forming cells assay results suggested mouse PSCs (mPSCs) could be differentiated into multipotential progenitor cells and 3D induction system derived hematopoietic colonies owned potential of differentiating into lymphocyte cells. In addition, in vivo animal transplantation experiment showed that mPSCs (CD45.2) could be embedded into nonobese diabetic/severe combined immunodeficiency mice (CD45.1) with about 3% engraftment efficiency after 3 weeks transplantation. This study demonstrated that we developed the 3D induction approach that could efficiently promote the hematopoietic differentiation of mPSCs in vitro and obtained the multipotential progenitors that possessed the short-term engraftment potential.


Asunto(s)
Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Hidrogeles/administración & dosificación , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Técnicas de Cultivo de Célula/métodos , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Ensayo de Unidades Formadoras de Colonias/métodos , Enfermedad Injerto contra Huésped/metabolismo , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Ratones Endogámicos NOD , Ratones SCID , Células Madre Pluripotentes/metabolismo
12.
Int J Legal Med ; 132(5): 1273-1280, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30056620

RESUMEN

Acute aortic dissection (AAD) is a clinically "silent," but emergent and life-threatening cardiovascular disease, and hereditary factors play an important etiologic role in the development of AAD. The purposes of this study are to definitize the diagnostic yield of 59 AAD patients, investigate the molecular pathological spectrum of AAD by NGS, and explore the future preclinical prospects of genetic diagnosis on AAD high-risk groups. We performed next-generation sequencing (NGS) based on screening of the 69 currently aortic dissections/aneurysms-associated genes on 59 sporadic AAD samples from South China. A Kaplan-Meier survival curve was constructed to compare the event-free survival depending on variant number. Overall, 67 variants were detected in 39 patients, among which 4 patients were identified with pathogenic variants and 13 patients were diagnosed with likely pathogenic variants. Seventeen genotype positive patients were identified in aggregate, and the diagnostic yield of our study is 28.8%. All genotype-positive variants were distributed in 11 genes, FBN1 variants were in the largest number among genotype-positive variants, which were detected for 4 times, ACTA2 for 3 times, ABCC6 and TGFBR1 twice, and NOS3, MYLK, XYLT1, TIMP4, TGFBR2, CNTN3, and PON1 once. Individuals with three or more variants showed shorter mean event-free survival than patients with fewer variants. Our observations broaden the genetic pathological spectrum of AAD. Furthermore, our research uncovered two susceptibility genes FBN1 and ACTA2 for Stanford type A AAD patients. Finally, our study concluded that the number of variants an individual harbored was an important consideration in risk stratification for individualized prediction and disease diagnosis.


Asunto(s)
Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/genética , Disección Aórtica/diagnóstico , Disección Aórtica/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Disección Aórtica/mortalidad , Aneurisma de la Aorta Torácica/mortalidad , Arildialquilfosfatasa , China , Supervivencia sin Enfermedad , Femenino , Estudios de Asociación Genética , Pruebas Genéticas , Genotipo , Humanos , Estimación de Kaplan-Meier , Masculino , Mutación/genética
13.
Int J Legal Med ; 130(2): 317-22, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26585738

RESUMEN

Sudden unexplained nocturnal death syndrome (SUNDS) is a perplexing disorder to both forensic pathologists and clinic physicians. Desmoplakin (DSP) gene was the first desmosomal gene linked to arrhythmogenic right ventricular cardiomyopathy (ARVC) which was associated with sudden death. To identify the genetic variants of the DSP gene in SUNDS in the southern Chinese Han population, we genetically screened the DSP gene in 40 sporadic SUNDS victims, 16 Brugada syndrome (BrS) patients, and 2 early repolarization syndrome (ERS) patients using next generation sequencing (NSG) and direct Sanger sequencing. A total of 10 genetic variants of the DSP gene were detected in 11 cases, comprised of two novel missense mutations (p.I125F and p.D521A) and eight previously reported rare variants. Of eight reported variants, two were previously considered pathogenic (p.Q90R and p.R2639Q), three were predicted in silico to be pathogenic (p.R315C, p.E1357D and p.D2579H), and the rest three were predicted to be benign (p.N1234S, p.R1308Q, and p.T2267S). This is the first report of DSP genetic screening in Chinese SUNDS and Brugada syndrome. Our results imply that DSP mutations contribute to the genetic cause of some SUNDS victims and maybe a new susceptible gene for Brugada syndrome.


Asunto(s)
Síndrome de Brugada/genética , Muerte Súbita/etiología , Desmoplaquinas/genética , Etnicidad/genética , Variación Genética , Mutación Missense , Adulto , China , Genética Forense , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
14.
APL Photonics ; 9(9): 090801, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39301193

RESUMEN

We present deep-ultraviolet Fourier ptychography (DUV-FP) for high-resolution chemical imaging of biological specimens in their native state without exogenous stains. This approach uses a customized 265-nm DUV LED array for angle-varied illumination, leveraging the unique DUV absorption properties of biomolecules at this wavelength region. We implemented a robust feature-domain optimization framework to overcome common challenges in Fourier ptychographic reconstruction, including vignetting, pupil aberrations, stray light problems, intensity variations, and other systematic errors. By using a 0.12 numerical aperture low-resolution objective lens, our DUV-FP prototype can resolve the 345-nm linewidth on a resolution target, demonstrating at least a four-fold resolution gain compared to the captured raw images. Testing on various biospecimens demonstrates that DUV-FP significantly enhances absorption-based chemical contrast and reveals detailed structural and molecular information. To further address the limitations of conventional FP in quantitative phase imaging, we developed a spatially coded DUV-FP system. This platform enables true quantitative phase imaging of biospecimens with DUV light, overcoming the non-uniform phase response inherent in traditional microscopy techniques. The demonstrated advancements in high-resolution, label-free chemical imaging may accelerate developments in digital pathology, potentially enabling rapid, on-site analysis of biopsy samples in clinical settings.

15.
Mol Genet Genomic Med ; 12(1): e2290, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37787490

RESUMEN

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is predominantly caused by mutations in sarcomeric genes. However, a subset of cases is attributed to genetic disorders unrelated to sarcomeric genes, such as Noonan syndrome (NS) and other RASopathies. In this study, we present a family with a history of sudden cardiac death (SCD) and focus on two adults with syndromic left ventricular hypertrophy (LVH). METHODS: Clinical evaluations, including echocardiography, were conducted to assess cardiac manifestations. Whole-exome sequencing was performed to identify potential genetic variants underlying syndromic LVH in the study participants. RESULTS: Whole-exome sequencing revealed a missense variant in the RAF1 gene, c.782C>T (p.Pro261Leu). This variant confirmed the diagnosis of NS in the affected individuals. CONCLUSION: The findings of this study underscore the importance of family history investigation and genetic testing in diagnosing syndromic LVH. By identifying the underlying genetic cause, clinicians can better understand the etiology of RAS-HCM and its association with SCD in young adults.


Asunto(s)
Cardiomiopatía Hipertrófica , Síndrome de Noonan , Humanos , Adulto Joven , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/genética , China , Muerte Súbita Cardíaca/etiología , Mutación , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Proteínas Proto-Oncogénicas c-raf/genética
16.
Stem Cell Res ; 76: 103326, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38324932

RESUMEN

Hoxb5 exhibits preferential expression in hematopoietic stem cells (HSCs) and uniquely marks the long-term HSCs (LT-HSCs). Previous studies have demonstrated the remarkable capability of Hoxb5 to alter cell fates when enforced expression in blood progenitors, such as B cell progenitors and multipotent progenitors. Additionally, Hoxb5 deficiency does not hinder the generation of LT-HSCs. However, the specific impact of Hoxb5 deletion on LT-HSCs has remained unexplored. To address this, we developed a conditional Hoxb5 knockout-reporter mouse model, wherein Hoxb5 was knock out by the Vav-cre recombinase, and the endogenous Hoxb5 promoter drove the expression of the blue fluorescent protein (BFP). Our findings revealed that the primary recipients, who transplanted with HSCs indicating Hoxb5 deficiency by the presence of BFP (BFP-positive HSCs), exhibited comparable levels of donor chimerism and lineage chimerism to recipients transplanted with HSCs that spontaneously did not express Hoxb5 and thus lacked BFP expression (BFP-negative HSCs). However, during the secondary transplantation, recipients receiving total bone marrow (BM) from the primary recipients with BFP-positive HSCs showed significantly higher levels of donor chimerism and more robust multi-lineage chimerism compared to those receiving total BM from the primary recipients with BFP-negative HSCs. Our results indicate that deleting Hoxb5 in LT-HSCs transiently influences their lineage differentiation bias without compromising their long-term self-renewal capacity. These findings highlight the primary role of Hoxb5 in regulating lineage commitment decisions in LT-HSCs, while emphasizing that its presence is not indispensable for the maintenance of long-term self-renewal capacity.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Factores de Transcripción , Animales , Ratones , Médula Ósea , Diferenciación Celular/fisiología , Células Madre Hematopoyéticas/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Ratones Noqueados , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
17.
Forensic Sci Int Genet ; 71: 103051, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38670007

RESUMEN

PURPOSE: Thoracic aortic dissection (TAD) is a life-threatening cardiovascular disease that often results in sudden cardiac death (SCD). However, the genetic characteristics of individuals with TAD confirmed at autopsy have been rarely studied. Our objective was to determine the prevalence of pathogenic variants in TAD-associated genes in a cohort of sporadic deaths resulting from spontaneous rupture of TAD and identify relevant genotype-phenotype relationships in Han Chinese population. METHODS: We included sixty-one consecutive sporadic decedents whose primary cause of death was spontaneous rupture of TAD, and performed a whole exome sequencing based strategy comprising 26 known TAD-associated genes. RESULTS: We identified 7 pathogenic or likely pathogenic (P/LP) variants in 7 cases (11.48 %) and 22 variants of uncertain significance (VUS) in 22 cases (36.07 %). The FBN1 gene was found to be the major disease-causing gene. Notably, TAD decedents with P/LP variant exhibited significantly earlier mortality. Moreover, we reported for the first time that TAD decedents with P/LP variant had a shorter diagnosis and treatment time. CONCLUSION: Our study investigated the genetic characteristics of TAD individuals confirmed until autopsy in Han Chinese population. The findings enhanced the understanding of the genetic underpinnings of TAD and have significant implications for clinical management and forensic investigations.


Asunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Secuenciación del Exoma , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adipoquinas , Aneurisma de la Aorta Torácica/genética , Aneurisma de la Aorta Torácica/mortalidad , Disección Aórtica/genética , Disección Aórtica/mortalidad , Rotura de la Aorta/genética , China , Estudios de Cohortes , Disección de la Aorta Torácica , Pueblos del Este de Asia/genética , Fibrilina-1/genética , Rotura Espontánea/genética
18.
Front Immunol ; 15: 1402250, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855107

RESUMEN

Background: This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters. Results: Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05). Conclusion: Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.


Asunto(s)
Angioplastia de Balón , Biomarcadores , Hipertensión Pulmonar , Embolia Pulmonar , Humanos , Masculino , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/terapia , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , Embolia Pulmonar/sangre , Embolia Pulmonar/terapia , Anciano , Proteómica/métodos , Enfermedad Crónica
19.
Fa Yi Xue Za Zhi ; 28(5): 337-41, 346, 2012 Oct.
Artículo en Zh | MEDLINE | ID: mdl-23213782

RESUMEN

OBJECTIVE: To investigate KCNQ1, KCNH2, KCNE1 and KCNE2 gene variants in the cases of sudden manhood death syndrome (SMDS). METHODS: One hundred and sixteen sporadic cases of SMDS and one hundred and twenty-five healthy controlled samples were enrolled. Genomic DNA was extracted from blood samples. Gene variants of KCNQ1, KCNH2, KCNE1 and KCNE2 were screened by direct sequencing. RESULTS: A total of 14 mutations and 14 SNP were detected. Two non-synonymous mutations of them were newfound. There was no non-synonymous mutation found in the control group. CONCLUSION: There are KCNQ1, KCNH2, KCNE1 and KCNE2 gene variants found in Chinese SMDS cases. KCNQ1, KCNH2, KCNE1 and KCNE2 gene mutation may correlate partly with the occurrence of some cases of the SMDS in China.


Asunto(s)
Muerte Súbita/etnología , Canales de Potasio Éter-A-Go-Go/genética , Canal de Potasio KCNQ1/genética , Canales de Potasio con Entrada de Voltaje/genética , Secuencia de Bases , Estudios de Casos y Controles , China , Análisis Mutacional de ADN , Canal de Potasio ERG1 , Humanos , Síndrome de QT Prolongado , Mutación , Polimorfismo de Nucleótido Simple , Canales de Potasio
20.
Front Surg ; 9: 1056664, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36700027

RESUMEN

As a substitute for a scalp needle, the intravenous indwelling needle is easy to operate and easy to use. it is not only conducive to the rescue of critically ill children, improves nursing efficiency, but also avoids pain caused by repeated venipuncture. However, cases of indwelling needle catheter breaking and remaining in scalp vessels are rarely reported. This study collected 12 cases of scalp vein indwelling needle rupture and retention in scalp vessels in our center from January 2012 to January 2022. It was found that there were 7 males and 5 females, with an average age of 19.17 ± 8.96 months. The average length of the severed end was 15.00 ± 1.54 mm. In 8 cases, the catheter was broken during the haircut, and in 2 cases, the wall structure was damaged and broken after repeated folding of the catheter. In 2 cases, the children did not cooperate during extubation, the head twisted violently and the catheter was broken.5 cases tried to extract it by manipulation and hemostatic forceps, of which 4 cases were successful, and 1 case was successfully removed after the completion of three-dimensional computerized tomography (3D-CT) imaging positioning. The remaining 7 cases were removed by operation, and the success rate of the first operation was 100% in 4 cases who chose 3D-CT. The other 3 cases chose ordinary CT plain scan positioning, the success rate of the first operation was 66.6%, and one child was successfully removed after the second operation after the failure of the operation plus 3D-CT scan positioning. All the children were in stable condition after the operation and were discharged smoothly. When the broken catheter is relatively shallow and the scalp is not completely closed, we could choose the preliminary positioning of B-ultrasound or ordinary CT, and then try to remove it by manual squeezing combined with hemostatic forceps. However B-ultrasound and ordinary CT could not meet the requirements of accurate location, 3D-CT has a very important localization value for surgery, which can improve the success rate and help successfully remove the ruptured catheter.

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