RESUMEN
Shrews being insectivores, serve as natural reservoirs for a wide array of zoonotic viruses, including the recently discovered Langya henipavirus (LayV) in China in 2018. It is crucial to understand the shrew-associated virome, viral diversity, and new viruses. In the current study, we conducted high-throughput sequencing on lung samples obtained from 398 shrews captured along the eastern coast of China, and characterized the high-depth virome of 6 common shrew species (Anourosorex squamipes, Crocidura lasiura, Crocidura shantungensis, Crocidura tanakae, Sorex caecutiens, and Suncus murinus). Our analysis revealed numerous shrew-associated viruses comprising 54 known viruses and 72 new viruses that significantly enhance our understanding of mammalian viruses. Notably, 34 identified viruses possess spillover-risk potential and six were human pathogenic viruses: LayV, influenza A virus (H5N6), rotavirus A, rabies virus, avian paramyxovirus 1, and rat hepatitis E virus. Moreover, ten previously unreported viruses in China were discovered, six among them have spillover-risk potential. Additionally, all 54 known viruses and 12 new viruses had the ability to cross species boundaries. Our data underscore the diversity of shrew-associated viruses and provide a foundation for further studies into tracing and predicting emerging infectious diseases originated from shrews.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Pulmón , Musarañas , Viroma , Animales , Musarañas/virología , China , Pulmón/virología , Viroma/genética , Filogenia , Virus ARN/genética , Virus ARN/clasificación , Virus ARN/aislamiento & purificación , ARN Viral/genética , Virus de la Influenza A/genética , Virus de la Influenza A/clasificación , Virus de la Influenza A/aislamiento & purificación , Virus de la Rabia/genética , Virus de la Rabia/clasificación , Virus de la Rabia/aislamiento & purificación , Reservorios de Enfermedades/virologíaRESUMEN
OBJECTIVES: To determine whether glucocorticoids can improve clinical outcomes of severe fever with thrombocytopenia syndrome (SFTS) patients, and how to identify patients who may benefit from the treatment. METHODS: A retrospective study was performed to include patients with confirmed SFTS from designated hospitals. The effect of glucocorticoids in reducing case fatality rate (CFR) and improving clinical recovery was evaluated by multivariate logistic regression models. RESULTS: A total of 2478 eligible patients were analyzed, of whom 331 received glucocorticoids. An integrated parameter (L-index) based on Log10(lactate dehydrogenase*blood urea nitrogen/lymphocyte count) was constructed to discriminate disease severity. In patients with L-index >3.823 indicating severe SFTS, significantly reduced CFR was observed in patients receiving low-moderate glucocorticoid doses with ≤60 mg daily methylprednisolone or equivalent (odds ratio [OR] 0.46, 95% confidence interval [CI], 0.23-0.88), but not in patients receiving high doses. In patients with L-index ≤3.823 indicating mild SFTS, glucocorticoid treatment was significantly associated with increased CFR (OR 3.34, 95% CI, 1.35-9.51), and mainly attributable to high-dose glucocorticoids (OR 2.83, 95% CI, 1.72-4.96). Disaggregated data analysis revealed a significant effect only in patients ≤65 years old, male, and early admission within 7 days after onset, but not in their counterparts. CONCLUSION: Glucocorticoids are not recommended for mild patients defined by L-index <3.823; however, patients with severe SFTS may benefit from low-moderate doses of glucocorticoids.
Asunto(s)
Phlebovirus , Síndrome de Trombocitopenia Febril Grave , Humanos , Masculino , Anciano , Estudios Retrospectivos , Glucocorticoides/uso terapéutico , Enfermedad Crítica , Resultado del TratamientoRESUMEN
Background context: Cervical kyphosis is a common but potentially debilitating and challenging condition. There is controversy on the optimal surgical strategy for the treatment of kyphotic cervical spondylotic myelopathy (KCSM) using either anterior approach or posterior approach. Introduction: The purpose of this study was to investigate the surgical efficacy of anterior decompression with fusion (ADF) vs. posterior decompression with fixation (PDF) for the treatment of KCSM, and to further analyze the changes of cervical spinal alignment parameters and axial symptoms (AS) severity after kyphotic correction. Materials and methods: We retrospectively reviewed 117 patients with KCSM who had undergone ADF (58 patients) and PDF (59 patients) between January 2016 and December 2020. Cervical spinal alignment parameters, including curvature index (CI) and C2-7 Cobb angle, were measured on the PreOP and PostOP lateral radiographs. Recovery rate was calculated based on the Japanese Orthopedic Association (JOA) score. AS severity was quantified by Neck Disability Index (NDI). A P-value less than 0.05 was considered to be significant. Results: The patient mean age, gender, presenting symptoms and follow-up time were similar between the two groups (P > 0.05). However, there were statistically significant differences (P < 0.001) between the two groups regarding the operation levels, operating time and intraoperative blood loss. Analysis of PostOP follow-up data showed significant differences (P < 0.001) in CI, correction of CI, C2-7 Cobb angle, and NDI between the two groups, whereas no significant differences in JOA score (P = 0.16) and recovery rate (P = 0.14). There were significant differences (P < 0.001) in CI, C2-7 Cobb angle, JOA score, and NDI between PreOP and PostOP follow-up in each group. Correction of CI showed positive correlation with recovery of NDI in Group ADF (r = 0.51, P < 0.001), and in Group PDF (r = 0.45, P < 0.001). Conclusion: Satisfied neurological improvement was obtained by ADF and PDF for patients with KCSM. Cervical kyphotic correction caused significant improvement of AS, and was more favorable with ADF than with PDF. Surgeons should pay full consideration of the merits and shortcomings of each approach when deciding on a surgical plan.
RESUMEN
BACKGROUND: Secondary bradyarrhythmias in hypertrophic cardiomyopathy (HCM) have been extensively reported. The prevalence and characteristics of primary bradyarrhythmias in HCM have yet to be investigated. METHODS: We retrospectively enrolled 101 consecutive patients with HCM who were referred to the arrhythmia center from May 2010 to October 2020. The clinical features of patients with bradyarrhythmias were analyzed. RESULTS: Twenty-nine (28.7%) patients had primary bradyarrhythmias, and six (5.9%) patients had secondary third-degree atrioventricular block (AVB). Of the 29 patients, 17 (58.6%) had sinus node dysfunction (SND), 14 (48.3%) had AVB, and two (6.9%) had both SND and AVB. The median age was 62 years old, and 69% were male. Six (20.7%) patients had left ventricular obstructive outflow tract obstruction, 15 (51.7%) had a history of syncope, and one (3.4%) had a family history of HCM. Most patients (86.2%) had New York Heart Association functional class I or II, and the median left ventricular ejection fraction was 63%. A total of 22 patients received pacemaker implantation, including 17 (77.3%) dual-chamber pacing, four (18.2%) single-chamber ventricular pacing, and one (4.5%) cardiac resynchronization therapy. CONCLUSIONS: Primary bradyarrhythmias need to be evaluated in HCM patients with arrhythmia-related symptoms. Patients with HCM might need pacemaker implantation for primary bradyarrhythmias.
RESUMEN
The planting effect and the planting potential of 12 cover crops (Leguminous: alfalfa, smooth vetch, hairy vetch, red clover, white clover, common vetch; non-leguminous: sudangrass, green radish, Nitro radish, rape, kale, endive) in the Sanjiang Plain of Northeast China were comprehensively evaluated by soil penetration resistance, pre-winter biomass, root characteristics, and plant nitrogen accumulation. The results showed that all the 12 cover crops grew normally during the experimental sowing period. Compared with the control, all the cover crops successfully reduced soil compactness. The planting of green radish, nitro radish, and sudangrass decreased soil penetration resistance by 47.1%, 43.4% and 33.4%, respectively. The pre-winter total fresh biomass of cover crop populations was between 3.38 and 13.98 kg·m-2, and the total dry matter mass was between 0.78 and 2.43 kg·m-2. The biomass of non-leguminous cover crops was significantly higher than that of the leguminous cover crops. The group roots of radish, rape and endive had large volumes. In particular, the nitro radish roots had a vo-lume of 4018.5 cm3·m-2, and the root system of sudangrass extended over the widest horizontal range. The ash content of leguminous cover crops was significantly lower than that of non-leguminous species, which could provide more organic matter with high decomposability. The total nitrogen accumulation of cover crops varied from 18.72 to 53.09 g·m-2. Kale and endive accumulated the highest amount of nitrogen and large biomass, which could facilitate nitrogen fixation and accumulation. According to the type of main crops in Sanjiang Plain and canopy structure, planting leguminous (clover, vetch, and alfalfa) and non-leguminous (radish, kale and sudangrass) cover crops to plant inter-row or in a line mixed cropping pattern could regulate soil structure and promote nutrient cycing, with positive effects on the fertility of black soil in the Sanjiang Plain.
Asunto(s)
Fabaceae , Sorghum , Trifolium , Vicia , Agricultura/métodos , Suelo/química , Productos Agrícolas , Nitrógeno , Biomasa , VerdurasRESUMEN
Karimabad virus (KARV) is an arthropod-borne viral agent originally found in the Mediterranean region that can cause human infection via sandfly as the main vector. The KARV virion has been only detected from sandfly in western Asian countries and specific antibody has been detected from Rhombomys opimus and human in countries in Africa, Western and Central Asia. In this study, by next-generation sequencing (NGS) on a high variety of wild small animals in Xinjiang Autonomous Region in China, we obtained a complete sequence of KARV from Rhombomys opimus. An expanded epidemiological investigation was subsequently performed on 1713 small wild mammals that were widely collected from seven bioclimatic distinct sites in China by applying KARV specific RT-PCR and sequencing. Positive results were only obtained from 8 (2.29%) of the Rhombomys opimus captured in Xinjiang Autonomous Region, while not in 57 rodent species that were captured in other six provinces. Sequence analysis revealed the currently identified KARV was clustered with Gabek Forest virus, and they shared 79.1-93.9% identity with Iranian KARV that differed for L, M and S segments. Phylogenetic analysis based on eight partial L gene sequences demonstrated the separation of two lineages of the current KARV sequences. The first report of KARV in Rhombomys opimus in China expanded the currently known geographic scope, reservoirs types and the genetic heterogeneity of KARV. Our results show a new host, Rhombomys opimus, for KARV and highlight potential zoonotic transmission of KARV in humans.
RESUMEN
We identified relapsing fever (RF) Borrelia in 1.45% (145/10426) of the ticks and 1.40% (40/2850) of the wild mammals in a field investigation in China. Three RF Borrelia species, including human-pathogenic Borrelia miyamotoi, Borrelia persica and unclassified Babesia sp. were determined. Main species determined from ticks was B. miyamotoi (44.14%), followed by the unclassified Borrelia sp. (42.76%), and Borrelia theileri (13.10%). In wild mammals, main species found was B. persica (57.50%), followed by the unclassified Borrelia sp. (40.00%), and B. miyamotoi (2.50%). We determined B. theileri and B. persica in China for the first time. The coexistence of RF Borrelia species in one tick species in a given region was observed, with the most frequent coexistence seen for B. miyamotoi and the unclassified Borrelia sp. in Dermacentor silvarum, Haemaphysalis japonica, Haemaphysalis longicornis, and Ixodes persulcatuss respectively. The wide distribution and high variety of RF Borrelia in China pose a potential threat to public health.
Asunto(s)
Borrelia , Ixodes , Ixodidae , Fiebre Recurrente , Animales , Humanos , Fiebre Recurrente/diagnóstico , Fiebre Recurrente/epidemiología , Fiebre Recurrente/veterinaria , Borrelia/genética , China/epidemiología , MamíferosRESUMEN
Ticks are important vectors of various zoonotic pathogens that can infect animals and humans, and most documented tick-borne pathogens have a strong bias towards microorganisms with strong disease phenotypes. The recent development of next-generation sequencing (NGS) has enabled the study of microbial communities, referred to as microbiome. Herein, we undertake a systematic review of published literature to build a comprehensive global dataset of microbiome determined by NGS in field-collected ticks. The dataset comprised 4418 records from 76 literature involving geo-referenced occurrences for 46 species of ticks and 219 microorganism families, revealing a total of 83 emerging viruses identified from 24 tick species belonging to 6 tick genera since 1980. The viral, bacterial and eukaryotic composition was compared regarding the tick species, their live stage and types of the specimens, or the geographic location. The data can assist the further investigation of ecological, biogeographical and epidemiological features of the tick-borne disease.
Asunto(s)
Microbiota , Garrapatas , Animales , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Metagenoma , Microbiota/genética , Revisiones Sistemáticas como Asunto , Garrapatas/microbiologíaRESUMEN
Objectives: This study aimed to assess the depression and anxiety status and their association with sleep disturbance among one single center Chinese inpatients with arrhythmia and help cardiologists better identify patients who need psychological care. Methods: A cross-sectional survey was conducted among 495 inpatients with arrhythmia treated in Fuwai Hospital from October to December 2019. The psychological status and sleep quality were assessed using the Zung Self-Rating Anxiety Scale (SAS), the Zung Self-Rating Depression Scale (SDS) and the Pittsburgh Sleep Quality Index (PSQI). Multivariate logistic regression was used to identify the potential risk factors for anxiety and depression. Results: The mean age of the participants was 52.8 ± 14.4 years, and 58.0% were male. Approximately 18.3% were in an anxious state, and 33.5% were in a depressive state. In multivariate logistic regression, age from 50 to 59 (p = 0.03), unemployment (p = 0.026) and sleep disturbance (p < 0.001) were the risk factors for anxiety status. Cardiac implanted electronic devices (CIEDs) (p = 0.004) and sleep disturbance (p < 0.001) were the risk factors for depression status. A total of 150 patients (30.3%) were categorized as having poor sleep quality (PSQI > 7). The adjusted odds ratio (OR) of having poor sleep quality was 4.30-fold higher in patients with both anxiety and depression (OR: 4.30; 95% confidence interval [CI]: 2.52-7.35); 2.67-fold higher in patients with depression (OR: 2.67; 95% CI: 1.78-4.00); and 3.94-fold higher in patients with anxiety (OR: 3.94; 95% CI: 2.41-6.44). Conclusions: Psychological intervention is critical for Chinese inpatients with arrhythmia, especially for patients aged 50-59, unemployed, or those using CIEDs. Poor sleep quality could be an important risk factor linked to psychological disturbances.
RESUMEN
BACKGROUND: Percutaneous left atrial appendage (LAA) occlusion is effective for stroke prevention in patients with atrial fibrillation. LAA can have a complex anatomy, such as multiple lobes or a large orifice, which may render it unsuitable for occlusion using regular devices. We aimed to investigate the feasibility, safety, and short-term efficacy of the small-umbrella LAmbre device for morphologically complicated LAA. METHODS: We retrospectively enrolled 129 consecutive patients who underwent LAA occlusion using the LAmbre device; the small-umbrella LAmbre device was used in 30 of these patients. We analyzed patients' characteristics, procedural details, and outcomes. RESULTS: Twenty-two patients (73.3%) had multilobed (≥ 2) LAA. The umbrella of the occluder was anchored in the branch in 9 patients and in the common trunks of branches in 13 patients. The landing zone and orifice diameters were 19.0 ± 4.39 mm and 27.4 ± 3.95 mm, respectively. The sizes of the umbrella and occluder cover were 22.0 ± 3.42 mm and 34.3 ± 2.75 mm, respectively. At 3-month follow-up transesophageal echocardiography in 24 patients, no peri-device residual flow was reported. Device thrombosis was detected in one patient at 3 months and disappeared after 3 months of anticoagulation. Ischemic stroke occurred in one patient; no other adverse events were reported. CONCLUSIONS: Occlusion of morphologically complicated LAA using the small-umbrella LAmbre device was feasible, safe, and effective in patients with atrial fibrillation in this study. This occluder provides an alternative for patients who cannot be treated with regular-sized LAA occlusion devices.
Asunto(s)
Apéndice Atrial , Fibrilación Atrial , Dispositivo Oclusor Septal , Accidente Cerebrovascular , Apéndice Atrial/diagnóstico por imagen , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Cateterismo Cardíaco/efectos adversos , Ecocardiografía Transesofágica/efectos adversos , Humanos , Estudios Retrospectivos , Dispositivo Oclusor Septal/efectos adversos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/prevención & control , Resultado del TratamientoRESUMEN
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever acquired by tick bites. Whether mast cells (MCs), the body's first line of defense against pathogens, might influence immunity or pathogenesis during SFTS virus (SFTSV) infection remained unknown. Here, we found that SFTSV can cause MC infection and degranulation, resulting in the release of the vasoactive mediators, chymase, and tryptase, which can directly act on endothelial cells, break the tight junctions of endothelial cells and threaten the integrity of the microvascular barrier, leading to microvascular hyperpermeability in human microvascular endothelial cells. Local activation of MCs (degranulation) and MC-specific proteases-facilitated endothelial damage were observed in mouse models. When MC-specific proteases were injected subcutaneously into the back skin of mice, signs of capillary leakage were observed in a dose-dependent manner. MC-specific proteases, chymase, and tryptase were tested in the serum collected at the acute phase of SFTS patients, with the higher level significantly correlated with fatal outcomes. By performing receiver operator characteristic curve (ROC) analysis, chymase was determined as a biomarker with the area under the curve value of 0.830 (95% CI = 0.745 to 0.915) for predicting fatal outcomes in SFTS. Our findings highlight the importance of MCs in SFTSV-induced disease progression and outcome. An emerging role for MCs in the clinical prognosis and blocking MC activation as a potential drug target during SFTSV infection was proposed. IMPORTANCE We revealed a pathogenic role for MCs in response to SFTSV infection. The study also identifies potential biomarkers that could differentiate patients at risk of a fatal outcome for SFTS, as well as novel therapeutic targets for the clinical management of SFTS. These findings might shed light on an emerging role for MCs as a potential drug target during infection of other viral hemorrhagic fever diseases with similar host pathology as SFTS.
Asunto(s)
Infecciones por Bunyaviridae , Síndrome de Trombocitopenia Febril Grave , Animales , Biomarcadores , Infecciones por Bunyaviridae/patología , Quimasas , Células Endoteliales/patología , Mastocitos/patología , Ratones , Péptido Hidrolasas/uso terapéutico , Permeabilidad , Phlebovirus , Triptasas/uso terapéuticoRESUMEN
Background: A variety of supraventricular arrhythmias (SVAs) may occur in patients with hypertrophic cardiomyopathy (HCM). The characteristics and long-term ablation outcomes of different types of SVAs in HCM have not been comprehensively investigated. Methods: We retrospectively enrolled 101 consecutive patients with HCM who were referred to the electrophysiology and arrhythmia service from May 2010 to October 2020. The clinical features and ablation outcomes were analyzed. Results: Seventy-eight patients had SVAs, which comprised 50 (64.1%) cases of atrial fibrillation (AF), 16 (20.5%) of atrial flutter (AFL), 15 (19.2%) of atrioventricular reentrant tachycardia (AVRT), 11 (14.1%) of atrial arrhythmia (AT), and 3 (3.8%) of atrioventricular nodal reentrant tachycardia (AVNRT). Thirty-four patients underwent catheter ablation and were followed up for a median (interquartile range) of 58.5 (82.9) months. There was no recurrence in patients with non-AF SVAs. In patients with AF, the 1- and 7-year AF-free survival rates were 87.5 and 49.5%, respectively. A receiver operator characteristic analysis showed that a greater left ventricular end-diastolic dimension (LVEDD) was associated with a higher recurrence of AF, with an optimum cutoff value of 47 mm (c-statistic = 0.91, p = 0.011, sensitivity = 1.00, specificity = 0.82). In Kaplan-Meier analysis, patients with a LVEDD ≥ 47 mm had worse AF-free survival than those with a LVEDD <47 mm (log-rank p = 0.014). Conclusions: In this unique population of HCM, AF was the most common SVA, followed in order by AFL, AVRT, AT, and AVNRT. The long-term catheter ablation outcome for non-AF SVAs in HCM is satisfactory. A greater LVEDD predicts AF recurrence after catheter ablation in patients with HCM.
RESUMEN
Esophageal cancer is an exceedingly aggressive and malignant cancer that imposes a substantial burden on patients and their families. It is usually treated with surgery, chemotherapy, radiotherapy, and molecular-targeted therapy. Immunotherapy is a novel treatment modality for esophageal cancer wherein genetically engineered adoptive cell therapy is utilized, which modifies immune cells to attack cancer cells. Using chimeric antigen receptor (CAR) or T cell receptor (TCR) modified T cells yielded demonstrably encouraging efficacy in patients. CAR-T cell therapy has shown robust clinical results for malignant hematological diseases, particularly in B cell-derived malignancies. Natural killer (NK) cells could serve as another reliable and safe CAR engineering platform, and CAR-NK cell therapy could be a more generalized approach for cancer immunotherapy because NK cells are histocompatibility-independent. TCR-T cells can detect a broad range of targeted antigens within subcellular compartments and hold great potential for use in cancer therapy. Numerous studies have been conducted to evaluate the efficacy and feasibility of CAR and TCR based adoptive cell therapies (ACT). A comprehensive understanding of genetically-modified T cell technologies can facilitate the clinical translation of these adoptive cell-based immunotherapies. Here, we systematically review the state-of-the-art knowledge on genetically-modified T-cell therapy and provide a summary of preclinical and clinical trials of CAR and TCR-transgenic ACT.
RESUMEN
Chimeric antigen receptor T (CAR-T) cell therapy has exhibited a substantial clinical response in hematological malignancies, including B-cell leukemia, lymphoma, and multiple myeloma. Therefore, the feasibility of using CAR-T cells to treat solid tumors is actively evaluated. Currently, multiple basic research projects and clinical trials are being conducted to treat lung cancer with CAR-T cell therapy. Although numerous advances in CAR-T cell therapy have been made in hematological tumors, the technology still entails considerable challenges in treating lung cancer, such as on-target, of-tumor toxicity, paucity of tumor-specific antigen targets, T cell exhaustion in the tumor microenvironment, and low infiltration level of immune cells into solid tumor niches, which are even more complicated than their application in hematological tumors. Thus, progress in the scientific understanding of tumor immunology and improvements in the manufacture of cell products are advancing the clinical translation of these important cellular immunotherapies. This review focused on the latest research progress of CAR-T cell therapy in lung cancer treatment and for the first time, demonstrated the underlying challenges and future engineering strategies for the clinical application of CAR-T cell therapy against lung cancer.
Asunto(s)
Inmunoterapia Adoptiva/métodos , Neoplasias Pulmonares/terapia , Animales , Antígenos de Neoplasias/inmunología , Biomarcadores de Tumor , Técnicas de Cultivo de Célula , Ensayos Clínicos como Asunto , Terapia Combinada/métodos , Manejo de la Enfermedad , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Ingeniería Genética , Humanos , Inmunomodulación , Inmunoterapia Adoptiva/efectos adversos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/mortalidad , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Resultado del TratamientoRESUMEN
Parkinson's disease (PD) is a disease that involves brain damage and is associated with neuroinflammation, mitochondrial damage, and cell aging. However, the pathogenic mechanism of PD is still unknown. Sequencing data and proteomic data can describe the fluctuation of molecular abundance in diseases at the mRNA level and protein level, respectively. In order to explore new targets in the pathogenesis of PD, the study analyzed molecular changes from the database by combining transcriptomic and proteomic analysis. Differentially expressed genes and differentially abundant proteins were summarized and analyzed. Enrichment and cluster analysis emphasized the importance of neurotransmitter release, mitochondrial damage, and vesicle transport. The molecular network revealed a subnetwork of 9 molecules related to SCNA and TH and revealed hub gene with differential expression at both mRNA and protein levels. It found that ACHE and CADPS could be used as new targets in PD, emphasizing that impaired nerve signal transmission and vesicle transport affect the pathogenesis of PD. Our research emphasized that the joint analysis and verification of transcriptomics and proteomics were devoted to understanding the comprehensive views and mechanism of pathogenesis in PD.
Asunto(s)
Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Proteínas/genética , Proteínas/metabolismo , Sustancia Negra/metabolismo , Acetilcolinesterasa/genética , Acetilcolinesterasa/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Análisis por Conglomerados , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Humanos , Enfermedad de Parkinson/patología , ARN Mensajero/genética , Sustancia Negra/patología , Transcriptoma , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMEN
This study aimed to assess the incidence, clinical implications, and treatment strategies of device-related thrombus (DRT) following catheter ablation and percutaneous left atrial appendage occlusion combined in one intervention. A meta-analysis of observational studies was conducted to evaluate the incidence rates, treatment strategies, and clinical implications of DRT. A total of 21 studies describing DRT events and 1 case were included in the current study. The 21 included studies comprised 3 multi-center registries and 18 single-center registries, and we also included 1 case report analyzing the characteristics of DRT. The pooled incidence of DRT in one-stop intervention was 18/1,708 (1.2%; range = 0%-7.3%; 95% CI = 0.7%-1.8%; I 2 = 0). Of these DRT events, 56.25% were diagnosed in the first 3 months after the procedure. All cases were diagnosed via trans-esophagus echocardiogram. All of the patients diagnosed with DRT were prescribed anticoagulation treatment, and 63% (12/19) of the events were reported with an outcome of complete thrombus resolution. The duration of anticoagulation treatment varied greatly, from 30 days to 6 months. Unknown clinical events were reported relating to DRT. Device-related thrombus is an uncommon complication of one-stop intervention. It occurs mainly in the early period following the procedure. Anticoagulation appears to be an appropriate treatment method for dissolving occurrences of DRT.
Asunto(s)
Fibrilación Atrial/complicaciones , Trombosis/etiología , Femenino , Humanos , Incidencia , Masculino , Factores de Riesgo , Trombosis/patología , Resultado del TratamientoRESUMEN
Owing to its potential biological relevance, DNA G-quadruplex has been considered as a prospective anti-cancer target. Some known G-quadruplex-interactive N-containing compounds with low cytotoxicity have become prospective anticancer drugs. Here we reported a new type of N-containing alkaloids 3,8a-disubstituted indolizinones, and investigated their substituent effects at 3- and 8a-positions in targeting to DNA c-myc G-quadruplex. And then we used 3-naphtyl-8a-(pyridin-2-yl) substrate I8 as an example, and investigated its ability in targeting to DNA parallel G-quadruplexes in vitro.
Asunto(s)
Antineoplásicos/química , ADN de Neoplasias/análisis , Indolizinas/química , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , ADN de Neoplasias/genética , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , G-Cuádruplex , Humanos , Indolizinas/síntesis química , Indolizinas/farmacología , Estructura Molecular , Proteínas Proto-Oncogénicas c-myc/análisis , Proteínas Proto-Oncogénicas c-myc/genética , Espectrometría de Fluorescencia , Relación Estructura-ActividadRESUMEN
Aim: This study aimed to explore the genetic and epigenetic similarities between chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma (LUAD). Materials & methods: We mainly used Weighted correlation network analysis, protein-protein interaction network and pivot analysis to identify hub modules, bridge regulators, bridge genes and hub-driving genes in both diseases and carried out verifying using external datasets. Results: We identified eight bridge regulators, 19 key molecules in the COPD model and ten key molecules in the LUAD model. Moreover, we validated that CDC5L could be a reliable biomarker in COPD and may regulate cell proliferation and metastasis in LUAD via promoter methylation. Conclusion: Our results might form a theoretical foundation for future study at an epigenetic level.
Asunto(s)
Adenocarcinoma del Pulmón/genética , Biomarcadores , Proteínas de Ciclo Celular/genética , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Enfermedad Pulmonar Obstructiva Crónica/genética , Proteínas de Unión al ARN/genética , Biomarcadores de Tumor , Proliferación Celular , Metilación de ADN , Epigénesis Genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , HumanosRESUMEN
BACKGROUND: There are many surgical procedures that can be used to relieve compression caused by thoracic ossification of the ligamentum flavum (TOLF). The present study aims to retrospectively observe the differences in subsection laminectomy with pedicle screw fixation (SLPF) and lamina osteotomy and replantation with miniplate fixation (LORF) in the treatment of continuous TOLF. PATIENTS AND METHODS: From March 2014 to October 2017, 61 patients with continuous TOLF underwent SLPF (group A) or LORF (group B). The surgical duration, intraoperative blood loss, change in thoracic kyphosis, and perioperative complications were analyzed. Neurological function was evaluated in accordance with the Japanese Orthopedic Association (JOA) score and the American Spinal Injury Association (ASIA) neurological grading. RESULTS: The surgical duration, intraoperative blood loss, and postoperative bed-rest duration in group A were significantly lower than those observed in group B (P < 0.05). Both groups demonstrated a significant improvement in JOA score and ASIA grade (P < 0.05). The neurological recovery rate was 69.8% ± 13.5% in group A and 68.5% ± 12.7% in group B (P > 0.05). There was also a significant improvement in ASIA grade at the final follow-up (P < 0.05). During follow-up, the Cobb angle was significantly increased in group B (P < 0.05), whereas no significant difference was observed in group A (P > 0.05). The occurrence rate of perioperative complications was 15.6% (5/32 patients) in group A and 37.9% (11/29 patients) in group B (P < 0.05). CONCLUSION: Both SLPF and LORF significantly promote recovery of neurological function. SLPF has a shorter surgical duration, less intraoperative blood loss, and a lower complication rate. SLPF is more conducive to the correction of sagittal sequence and maintenance of thoracic stability.
RESUMEN
BACKGROUND The aim of this study was to explore the expression levels of family with sequence similarity 83, member A (FAM83A) in lung adenocarcinoma (LUAD) and investigate its clinical prognostic value. MATERIAL AND METHODS Bioinformatics mining methods were used to predict the differential expression levels of FAM83A mRNA in LUAD and normal lung tissues based on the TCGA and Oncomine databases. Immunohistochemical staining was performed to demonstrate the FAM83A protein expression levels in 83 cases of LUAD combined with paired normal lung tissues. The correlation between clinicopathologic factors and FAM83A differential expression levels in LUAD was explored by the chi-square test. Kaplan-Meier univariate and Cox multivariate survival analyses were performed to investigate the clinical prognostic value of FAM83A expression in LUAD patients. RESULTS Results from TCGA and Oncomine databases revealed that FAM83A mRNA expression level was significantly higher in LUAD than that in normal lung tissues (both P<0.05). Immunohistochemical findings demonstrated that the high positive rate of FAM83A in LUAD was 73.49% (61/83), while that of matched normal lung tissues was only 22.89% (19/83). Moreover, LUAD patients with FAM83A mRNA or high protein levels had dramatically lower OS times than those with FAM83A mRNA or low protein levels (All P<0.05). Lastly, Cox multivariate survival analysis showed that FAM83A differential expression level (low vs. high) was the only independent factor predicting the prognosis of LUAD patients (P=0.001). CONCLUSIONS FAM83A was overexpressed in LUAD, and FAM83A overexpression could be used as an independent factor of poor prognosis in LUAD patients.