RESUMEN
Mutations in the Paraoxonase 1 (Pon1) gene underlie aging, cardiovascular disease, and impairments of the nervous and gastrointestinal systems and are linked to the intestinal microbiome. The potential role of Pon1 in modulating the intestinal microbiota and serum metabolites is poorly understood. The present study demonstrated that mice with genomic excision of Pon1 by a multiplexed guide RNA CRISPR/Cas9 approach exhibited disrupted gut microbiota, such as significantly depressed alpha-diversity and distinctly separated beta diversity, accompanied by varied profiles of circulating metabolites. Furthermore, genomic knock in of Pon1 exerted a distinct effect on the intestinal microbiome and serum metabolome, including dramatically enriched Aerococcus, linoleic acid and depleted Bacillus, indolelactic acid. Specifically, a strong correlation was established between bacterial alterations and metabolites in Pon1 knockout mice. In addition, we identified metabolites related to gut bacteria in response to Pon1 knock in. Thus, the deletion of Pon1 affects the gut microbiome and functionally modifies serum metabolism, which can lead to dysbiosis, metabolic dysfunction, and infection risk. Together, these findings put forth a role for Pon1 in microbial alterations that contribute to metabolism variations. The function of Pon1 in diseases might at least partially depend on the microbiome.
Asunto(s)
Microbioma Gastrointestinal , Microbiota , Animales , Ratones , Microbioma Gastrointestinal/genética , ARN Guía de Sistemas CRISPR-Cas , Modelos Animales de Enfermedad , Arildialquilfosfatasa/genética , Ratones NoqueadosRESUMEN
The epithelium of the pulmonary airway is composed of several distinct cell types that differentiate from common progenitor cells to provide defense against environmental insults. Epigenetic mechanisms regulating lineage differentiation of airway epithelial progenitors remain poorly understood. Protein arginine methyltransferase 5 (Prmt5) is a predominant type II arginine methyltransferase that methylates >85% of symmetric arginine residues. Here, we provide evidence for the function of Prmt5 in promoting ciliated cell fate specification of airway epithelial progenitors. We show that lung epithelial-specific deletion of Prmt5 resulted in a complete loss of ciliated cells, an increased number of basal cells, and ecotopic-expressed Tp63-Krt5+ putative cells in the proximal airway. We further identified that transcription factor Tp63 is a direct target of Prmt5, and Prmt5 inhibited Tp63 transcription expression through H4R3 symmetric dimethylation (H4R3sme2). Moreover, inhibition of Tp63 expression in Prmt5-deficient tracheal progenitors could partially restore the ciliated cell deficient phenotype. Together, our data support a model where Prmt5-mediated H4R3sme2 represses Tp63 expression to promote ciliated cell fate specification of airway progenitors.
Asunto(s)
Regulación de la Expresión Génica , Factores de Transcripción , Animales , Humanos , Ratones , Diferenciación Celular , Línea Celular Tumoral , Pulmón/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Factores de Transcripción/metabolismo , Ratones Endogámicos C57BLRESUMEN
Zearalenone (ZEN) is an extremely hazardous chemical widely existing in cereals, and its high-sensitivity detection possesses significant significance to human health. Here, the cathodic aggregation-induced electrochemiluminescence (AIECL) performance of tetraphenylethylene nanoaggregates (TPE NAs) was modulated by solvent regulation, based on which an electrochemiluminescence (ECL) aptasensor was constructed for sensitive detection of ZEN. The aggregation state and AIECL of TPE NAs were directly and simply controlled by adjusting the type of organic solvent and the fraction of water, which solved the current shortcomings of low strength and weak stability of the cathode ECL signal for TPE. Impressively, in a tetrahydrofuran-water mixed solution (volume ratio, 6:4), the relative ECL efficiency of TPE NAs reached 16.03%, which was 9.2 times that in pure water conditions, and the maximum ECL spectral wavelength was obviously red-shifted to 617 nm. In addition, "H"-shape DNA structure-mediated dual-catalyzed hairpin self-assembly (H-D-CHA) with higher efficiency by the synergistic effect between the two CHA reactions was utilized to construct a sensitive ECL aptasensor for ZEN analysis with a low detection limit of 0.362 fg/mL. In conclusion, solvent regulation was a simple and efficient method for improving the performance of AIECL materials, and the proposed ECL aptasensor had great potential for ZEN monitoring in food safety.
Asunto(s)
Técnicas Electroquímicas , Electrodos , Mediciones Luminiscentes , Solventes , Zearalenona , Zearalenona/análisis , Zearalenona/química , Solventes/química , Estilbenos/química , Límite de Detección , Técnicas Biosensibles , Aptámeros de Nucleótidos/químicaRESUMEN
BACKGROUND: The prevalence of chronic kidney disease (CKD) is on the rise, posing a significant public health challenge. Although gut microbiome dysbiosis has been implicated in the impairment of kidney functions, the existence of pathological subtypes-linked differences remains largely unknown. We aimed to characterize the intestinal microbiota in patients with membranous nephropathy (MN), IgA nephropathy (IgAN), minimal change disease (MCD), and ischemic renal injury (IRI) in order to investigate the intricate relationship between intestinal microbiota and CKD across different subtypes. METHODS: We conducted a cross-sectional study involving 94 patients with various pathological patterns of CKD and 54 healthy controls (HCs). The clinical parameters were collected, and stool samples were obtained from each participant. Gut microbial features were analyzed using 16S rRNA sequencing and taxon annotation to compare the HC, CKD, MN, IgAN, MCD, and IRI groups. RESULTS: The CKD subjects exhibited significantly reduced alpha diversity, modified community structures, and disrupted microbial composition and potential functions compared to the control group. The opportunistic pathogen Klebsiella exhibited a significant enrichment in patients with CKD, whereas Akkermansia showed higher abundance in HCs. The study further revealed the presence of heterogeneity in intestinal microbial signatures across diverse CKD pathological types, including MN, IgAN, MCD, and IRI. The depression of the family Lachnospiraceae and the genus Bilophila was prominently observed exclusively in patients with MN, while suppressed Streptococcus was detected only in individuals with MCD, and a remarkable expansion of the genus Escherichia was uniquely found in cases of IRI. The study also encompassed the development of classifiers employing gut microbial diagnostic markers to accurately discriminate between distinct subtypes of CKD. CONCLUSIONS: The dysregulation of gut microbiome was strongly correlated with CKD, exhibiting further specificity towards distinct pathological patterns. Our study emphasizes the significance of considering disease subtypes when assessing the impact of intestinal microbiota on the development, diagnosis, and treatment of CKD.
Asunto(s)
Microbioma Gastrointestinal , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/microbiología , Insuficiencia Renal Crónica/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios de Casos y Controles , Adulto , ARN Ribosómico 16S/genética , Estudios Transversales , Disbiosis/microbiología , Disbiosis/complicaciones , Heces/microbiologíaRESUMEN
BACKGROUND: Appendiceal pseudomyxoma peritonei (PMP), a rare tumor from mucinous appendiceal origins, is treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). However, tubing blockages during HIPEC treatment pose a common challenge, impeding the smooth progression of therapy. Few studies to date have explored the incidence and risk factors of tube occlusion during HIPEC in patients with appendiceal PMP, as well as its adverse impact on postoperative complications. METHODS: From October 2017 to June 2023, a total of 80 patients with appendiceal PMP undergoing combined CRS and HIPEC were included in this study. Tubing blockage events were strictly defined, with patients experiencing blockages during HIPEC treatment allocated to the study group, while those with unobstructed perfusion were assigned to the control group. A comparative analysis was conducted between the two groups regarding post-HIPEC health assessments and occurrence of complications. Risk factors for luminal occlusion during closed HIPEC procedures were identified through univariate and multivariate analysis of data from 303 HIPEC treatments. RESULTS: Tubing blockages occurred in 41 patients (51.3%). The study group experienced prolonged gastrointestinal decompression time (4.1 ± 3.0 vs. 2.5 ± 1.7 days, P = 0.003) and prolonged time to bowel movement (6.1 ± 2.3 vs. 5.1 ± 1.8 days, P = 0.022) compared to the control group. There was no significant difference in the incidence of complications between the two groups. The 1-year survival rate postoperatively was 97%, and the 3-year survival rate was 81%, with no association found between tubing blockage and poorer survival. Additionally, In 303 instances of HIPEC treatment among these 80 patients, tube occlusion occurred in 89 cases (89/303, 29.4%). Multivariable logistic regression analysis revealed age, diabetes, hypertension, and pathology as independent risk factors for tube occlusion. CONCLUSION: Tubing blockages are a common occurrence during HIPEC treatment, leading to prolonged postoperative gastrointestinal functional recovery time. When patients are elderly and have concomitant hypertension and diabetes, along with a histological type of low-grade mucinous tumor, the risk of tube occlusion increases. However, this study did not find a significant correlation between tubing blockage and the incidence of postoperative complications or overall patient survival.
Asunto(s)
Neoplasias del Apéndice , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales , Complicaciones Posoperatorias , Seudomixoma Peritoneal , Humanos , Seudomixoma Peritoneal/terapia , Seudomixoma Peritoneal/patología , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/patología , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/terapia , Neoplasias del Apéndice/mortalidad , Pronóstico , Quimioterapia Intraperitoneal Hipertérmica/métodos , Quimioterapia Intraperitoneal Hipertérmica/efectos adversos , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Estudios de Seguimiento , Complicaciones Posoperatorias/etiología , Adulto , Estudios Retrospectivos , Terapia Combinada , Tasa de Supervivencia , Anciano , Factores de Riesgo , Hipertermia Inducida/efectos adversos , Hipertermia Inducida/métodosRESUMEN
BACKGROUND: Silica-induced pulmonary fibrosis (silicosis) is a diffuse interstitial fibrotic disease characterized by the massive deposition of extracellular matrix in lung tissue. Fibroblast to myofibroblast differentiation is crucial for the disease progression. Inhibiting myofibroblast differentiation may be an effective way for pulmonary fibrosis treatment. METHODS: The experiments were conducted in TGF-ß treated human lung fibroblasts to induce myofibroblast differentiation in vitro and silica treated mice to induce pulmonary fibrosis in vivo. RESULTS: By quantitative mass spectrometry, we revealed that proteins involved in mitochondrial folate metabolism were specifically upregulated during myofibroblast differentiation following TGF-ß stimulation. The expression level of proteins in mitochondrial folate pathway, MTHFD2 and SLC25A32, negatively regulated myofibroblast differentiation. Moreover, plasma folate concentration was significantly reduced in patients and mice with silicosis. Folate supplementation elevated the expression of MTHFD2 and SLC25A32, alleviated oxidative stress and effectively suppressed myofibroblast differentiation and silica-induced pulmonary fibrosis in mice. CONCLUSION: Our study suggests that mitochondrial folate pathway regulates myofibroblast differentiation and could serve as a potential target for ameliorating silica-induced pulmonary fibrosis.
Asunto(s)
Fibrosis Pulmonar , Silicosis , Humanos , Ratones , Animales , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Miofibroblastos , Dióxido de Silicio/toxicidad , Pulmón/patología , Fibroblastos/metabolismo , Silicosis/metabolismo , Silicosis/patología , Factor de Crecimiento Transformador beta/metabolismo , Diferenciación Celular , Ratones Endogámicos C57BLRESUMEN
AIMS: This study aimed to investigate the clinical, histological, immunohistochemical and chromosomal features of primary cutaneous adenoid cystic carcinoma (PCACC). METHODS AND RESULTS: We retrospectively analysed 13 cases identified on their clinicopathological features and performed fluorescence in-situ hybridisation (FISH) on six available cases. Head and neck (46.2%) were most commonly involved. The median age was 53 years, with a male predilection. Histologically, tumours were classified as grades 1 (eight), 2 (four) and 3 with high-grade transformation (HGT) (one). The HGT component was demonstrated as poorly differentiated carcinoma with multifocal necrosis and myoepithelial differentiation. Patients with one of the following factors: longest diameter of the lesion (≥ 1 cm), involvement of subcutaneous fat tissue and widely infiltrative border had a relatively higher rate of local recurrence, distant metastasis and death. Five of six cases were confirmed to have MYB translocation, while nuclear staining for MYB proto-oncogene, transcription factor (MYB) protein was found in four cases. During the follow-up (median = 64 months), two patients experienced local recurrences. One patient, who was classified as grade III PCACC with HGT, developed multiple metastases and died of disease. Another patient was alive with multiple metastases. CONCLUSIONS: This is the largest single-institution study, to our knowledge, of PCACC in an Asian population. We describe the first case of scalp PCACC with HGT, which is the only death case in our series. PCACC tends to recur locally and has metastatic potential. PCACC with HGT has a poor prognosis.
Asunto(s)
Carcinoma Adenoide Quístico/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Carcinoma Adenoide Quístico/genética , Carcinoma Adenoide Quístico/metabolismo , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismoRESUMEN
Accurate workload prediction plays a key role in intelligent scheduling decisions on cloud platforms. There are massive amounts of short-workload sequences in the cloud platform, and the small amount of data and the presence of outliers make accurate workload sequence prediction a challenge. For the above issues, this paper proposes an ensemble learning method based on sample weight transfer and long short-term memory (LSTM), termed as Tr-Predictor. Specifically, a selection method of similar sequences combining time warp edit distance (TWED) and transfer entropy (TE) is proposed to select a source domain dataset with higher similarity for the target workload sequence. Then, we upgrade the basic learner of the ensemble model two-stage TrAdaBoost.R2 to LSTM in the deep model and enhance the ability of the ensemble model to extract sequence features. To optimize the weight adjustment strategy, we adopt a two-stage weight adjustment strategy and select the best weight for the learner according to the sample error and model error. Finally, the above process determines the parameters of the target model and uses the target model to predict the short-task sequences. In the experimental validation, we arbitrarily select nine sets of short-workload data from the Google dataset and three sets of short-workload data from the Alibaba cluster to verify the prediction effectiveness of the proposed algorithm. The experimental results show that compared with the commonly used cloud workload prediction methods Tr-Predictor has higher prediction accuracy on the small-sample workload. The prediction indicators of the ablation experiments show the performance gain of each part in the proposed method.
RESUMEN
BACKGROUND: Hypertension (HTN) is one of the major cardiovascular risk factors, which contributes to increasing target organ damages and cardiovascular morbidity and mortality worldwide. Isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) are two important subtypes of HTN. Previous researches have demonstrated the alteration of fecal bacteria in HTN, but not down to these two sub-types. In order to identify whether the composition of bacterial taxa and functional modules shift in ISH and IDH, we performed a metagenomic sequencing analysis of fecal samples from 15 controls, 14 ISH, and 11 IDH. RESULTS: Compared with control and ISH, IDH patients showed decreased gene number, bacterial richness, and evenness, although the bacterial alterations did not reach statistical significance in the Shannon index. Also, at the genus level, the ß-diversity for intestinal flora in IDH was distinguishable from those with ISH. Furthermore, the taxonomic composition of ISH or IDH was different from that of healthy control at genus and species levels. Patients with IDH or ISH were confirmed to be enriched with Rothia mucilaginosa, along with reduced Clostridium sp. ASBs410. Lastly, the altered KEGG modules were significantly decreased in IDH compared with the control group, such as sodium transport system; while for ISH, functions relevant to biotin biosynthesis were decreased. CONCLUSIONS: Overall, our results showed the disordered fecal bacteria profiles in subjects with ISH and especially IDH, emphasizing the significance of early intervention for IDH.
Asunto(s)
Biodiversidad , Heces/microbiología , Hipertensión/microbiología , Microbiota/fisiología , Genes Bacterianos/genética , HumanosRESUMEN
Quaternary climate oscillations and geographical heterogeneity play important roles in determining species and genetic diversity distribution patterns, but how these factors affect the migration and differentiation of East Asian plants species at the population level remains poorly understood. The Aquilegia ecalcarata complex, a group that originated in the Late Tertiary and is widely distributed throughout East Asia, displays high genetic variation that is suitable for studying elaborate phylogeographic patterns and demographic history related to the impact of Quaternary climate and geography. We used plastid genome data from 322 individuals in 60 populations of the A. ecalcarata complex to thoroughly explore the impact of Quaternary climate oscillations and geography on the phylogeographic patterns and demographic history of the A. ecalcarata complex through a series of phylogenetic, divergence time estimation, and demographic history analyses. The dry, cold climate and frequent climate oscillations that occurred during the early Pleistocene and the Mid-Pleistocene transition led to the differentiation of the A. ecalcarata complex, which was isolated in various areas. Geographically, the A. ecalcarata complex can be divided into Eastern and Western Clades and five subclades, which conform to the divergence of the East Asian flora. Our results clearly show the impact of Quaternary climate and geography on evolutionary history at the population level. These findings promote the understanding of the relationship between plant genetic differentiation and climate and geographical factors of East Asia at the population level.
Asunto(s)
Aquilegia , Genoma de Plastidios , Clima , Variación Genética , Haplotipos , Humanos , Filogenia , FilogeografíaRESUMEN
The main aim of this research work was to develop and evaluate a drug delivery system with compression coating technology to control drug release at a constant rate. The compression coated tablets (CCTs) consist of the hydrophilic matrix core and the hydrophobic waxy coating. The presence of hydrophobic waxy coating could provide sufficient time for hydration of the core to prevent initial burst release. The mechanism research revealed that erosion was the main way of drug release and the releasing area was constant during the entire release process because the core tablet was located in the cup-shaped coating after one side cover was dropped at the lag time. This made the release behavior exhibit zero-order kinetics (R2>0.99). The coating rupture strength and the core swelling force at the lag time influenced erosion rate thus affecting release rate. Different solubility of drugs (propranolol hydrochloride, melatonin, and nifedipine) was selected as model drugs and the properties of the prepared CCTs in terms of formulations and in vitro release were evaluated. The release rate was independent of solubility, medium pH, and osmotic pressure. This zero-order controlled system could be applied to both controlled drug delivery and chrono pharmaceutical drug delivery.
Asunto(s)
Celulosa , Tecnología , Preparaciones de Acción Retardada , Solubilidad , ComprimidosRESUMEN
Alternations of gut microbiota (GM) in atrial fibrillation (AF) with elevated diversity, perturbed composition and function have been described previously. The current work aimed to assess the association of GM composition with AF recurrence (RAF) after ablation based on metagenomic sequencing and metabolomic analyses and to construct a GM-based predictive model for RAF. Compared with non-AF controls (50 individuals), GM composition and metabolomic profile were significantly altered between patients with recurrent AF (17 individuals) and non-RAF group (23 individuals). Notably, discriminative taxa between the non-RAF and RAF groups, including the families Nitrosomonadaceae and Lentisphaeraceae, the genera Marinitoga and Rufibacter and the species Faecalibacterium spCAG:82, Bacillus gobiensis and Desulfobacterales bacterium PC51MH44, were selected to construct a taxonomic scoring system based on LASSO analysis. After incorporating the clinical factors of RAF, taxonomic score retained a significant association with RAF incidence (HR = 2.647, P = .041). An elevated AUC (0.954) and positive NRI (1.5601) for predicting RAF compared with traditional clinical scoring (AUC = 0.6918) were obtained. The GM-based taxonomic scoring system theoretically improves the model performance, and the nomogram and decision curve analysis validated the clinical value of the predicting model. These data provide novel possibility that incorporating the GM factor into future recurrent risk stratification.
Asunto(s)
Fibrilación Atrial/microbiología , Fibrilación Atrial/patología , Microbioma Gastrointestinal , Perfilación de la Expresión Génica , Metaboloma , Anciano , Área Bajo la Curva , Bacillus , Faecalibacterium , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Metabolómica , Persona de Mediana Edad , Nitrosomonadaceae , Recurrencia , Medición de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: The gut bacteria-derived metabolite trimethylamine-N-oxide (TMAO) has been discussed in various cardiometabolic diseases. However, evidence characterizing the microbial population responsible for TMAO accumulation in patients with atrial fibrillation (AF), an increasingly prevalent arrhythmia, is yet lacking. In order to understand the key gut microorganisms that produce TMAO in AF, trimethylamine (TMA)-synthesis enzymes and metabolic pathways, as well as the potential TMA-producers in gut microbiome were assessed based on metagenomic data-mining in a northern Chinese cohort consisting of 50 non-AF controls and 50 patients with different types of AF. RESULTS: Compared to the control subjects, AF patients showed a marked increase in the microbial genes underlying TMA formation in the gut, which included 12 potential TMA-synthesis functional orthologs and 1 module. The specific bacterial genes, including choline-TMA lyase, carnitine monooxygenase, glycine betaine reductase, and TMAO reductase, were elevated in the gut of AF patients. Furthermore, 16 genera were assigned and significantly correlated with TMA-enzymatic genes, where 9 genera were remarkably enriched in the gut communities of AF patients. Neither of these TMA-synthesis pathways nor the microbial players showed a significant discrepancy between different types of AF in the current cohort. These gut microbes might participate in the formation of TMA by activating the key TMA-synthesis enzymes and contributing to the functional pathways in AF patients. CONCLUSIONS: The present study provides an in-depth insight into the potential bacteria and metabolic pathways involved in TMA production in the gut of AF patients. These findings emphasize a key role of the gut bacteria in driving TMAO formation during AF pathogenesis, thereby indicating its therapeutic potential as an intervention strategy of AF by targeting TMA-synthesis pathways and dysbiotic gut microbiota.
Asunto(s)
Fibrilación Atrial , Microbioma Gastrointestinal , Minería de Datos , Humanos , Metilaminas , ÓxidosRESUMEN
Branching morphogenesis is essential for the successful development of a functional lung to accomplish its gas exchange function. Although many studies have highlighted requirements for the bone morphogenetic protein (BMP) signaling pathway during branching morphogenesis, little is known about how BMP signaling is regulated. Here, we report that the protein arginine methyltransferase 5 (Prmt5) and symmetric dimethylation at histone H4 arginine 3 (H4R3sme2) directly associate with chromatin of Bmp4 to suppress its transcription. Inactivation of Prmt5 in the lung epithelium results in halted branching morphogenesis, altered epithelial cell differentiation and neonatal lethality. These defects are accompanied by increased apoptosis and reduced proliferation of lung epithelium, as a consequence of elevated canonical BMP-Smad1/5/9 signaling. Inhibition of BMP signaling by Noggin rescues the lung branching defects of Prmt5 mutant in vitro Taken together, our results identify a novel mechanism through which Prmt5-mediated histone arginine methylation represses canonical BMP signaling to regulate lung branching morphogenesis.
Asunto(s)
Arginina/metabolismo , Proteína Morfogenética Ósea 4/metabolismo , Histonas/química , Histonas/metabolismo , Pulmón/crecimiento & desarrollo , Morfogénesis , Proteína-Arginina N-Metiltransferasas/metabolismo , Secuencias de Aminoácidos , Animales , Arginina/genética , Cromatina/genética , Cromatina/metabolismo , Femenino , Histonas/genética , Pulmón/metabolismo , Metilación , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Organogénesis , Proteína-Arginina N-Metiltransferasas/genética , Transducción de Señal , Proteínas Smad/genética , Proteínas Smad/metabolismoRESUMEN
AIMS: Longitudinal melanonychia in paediatric patients often represents a difficult diagnostic challenge, and studies emphasising its clinical and histopathological features are limited due to its low incidence in childhood. METHODS AND RESULTS: We retrospectively analysed 35 paediatric cases identified by excision specimens on their clinicopathological features, and performed fluorescence in-situ hybridisation on 13 available cases. Fingernails (77.1%) were more likely to be affected. Total melanonychia and Hutchinson's sign were observed in 10 (28.6%) and 14 (40.0%) cases, respectively. Nail dystrophy at diagnosis was present in five cases. After complete excision of the lesions, four patients relapsed during follow-up (mean = 38 months). Seventeen cases were diagnosed as lentigines and 18 as naevi, among which 11 cases were categorised as lentigines/naevi with atypical melanocytic hyperplasia. Mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and peri-ungual skin involvement were found in 25.7% (9 of 35), 40.0% (14 of 35), 40.0% (14 of 35) and 40.0% (14 of 35) of cases, respectively. Thirteen cases tested by fluorescence in-situ hybridisation showed no copy number aberration at the probed loci. There was a statistically significant difference in the following features between patients aged less and more than 10 years (P < 0.05): cytomorphology, mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and melanocyte count. CONCLUSIONS: Some concerning clinicopathological characteristics, which are signs indicative of melanoma in adults, are not uncommon in paediatric longitudinal melanonychia, especially in patients aged ≤ 10 years. Owing to the extremely low incidence of melanoma in paediatric longitudinal melanonychia, in most circumstances a more conservative clinical management strategy should be adopted.
Asunto(s)
Lentigo/patología , Enfermedades de la Uña/patología , Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Melanocitos/patologíaRESUMEN
We report a case of nevus cell aggregates (NCAs) in an external iliac lymph node from a patient with a compound congenital nevus in the corresponding drainage skin. Melanocytes in parenchyma were in band, nest-like or nodular fashion, and partly continuous with those in capsule and trabeculae. The largest nodule in parenchyma measured 6.5 mm. Melanocytes mostly exhibited benign appearance identical to cutaneous nevus. A few regions abundant in cells displayed atypical features, including increased nucleo-cytoplasmic ratio, small nucleoli, and occasional mitotic figures. Immunohistochemistry showed that melanocytes stained positive for p16, but negative for HMB-45 and nestin. Ki-67 labeling was less than 1% and reticulin mainly surrounded individual melanocytes. Besides, Vysis melanoma fluorescence in situ hybridization (FISH) plus another 2 probes targeting 9p21(CDKN2A) and 8q24(MYC) showed normal results. The patient is alive without malignant tumor after 52-month follow up. Our case provides a new evidence for the existence of intraparenchymal NCAs in deep lymph node and indicates that melanocytes with some atypical features can occur in nodal nevi. Nevus cells in parenchyma connected to those in capsule and trabeculae are a significant clue to distinguish nodal nevi from metastatic melanomas. Additionally, immunohistochemistry and FISH assay are useful in differential diagnosis.
Asunto(s)
Ilion/patología , Ganglios Linfáticos/patología , Melanocitos/patología , Nevo Pigmentado/patología , Adolescente , Adulto , Anciano , Agregación Celular , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ/métodos , Metástasis Linfática/diagnóstico , Metástasis Linfática/patología , Masculino , Melanocitos/metabolismo , Melanoma/diagnóstico , Melanoma/secundario , Persona de Mediana Edad , Nevo/patología , Nevo Pigmentado/congénito , Nevo Pigmentado/ultraestructura , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/secundario , Melanoma Cutáneo MalignoRESUMEN
INTRODUCTION AND HYPOTHESIS: To describe the knowledge and perceptions of obstetric fistula (OF) among affected and unaffected women. METHODS: Twenty-five semi-structured interviews were conducted with women who had received OF repair. Three focus groups were conducted: one group of women with urinary incontinence but no OF, one group of women with OF, and one group of women without genitourinary complaints. Interviews and focus groups were conducted using the grounded theory approach. This study took place in two urban hospitals in Rwanda from April to November 2015. Transcripts were coded using MAXDA11 and analyzed using the axial technique and the constant comparative method. RESULTS: Nearly all participants correctly described OF and its symptoms, and 93% of interviewed women attributed OF to complications in vaginal delivery or cesarean section. Several participants described renouncing stigmatizing beliefs after learning about OF from the radio, health workers, or word of mouth. Still, it was found that women with OF were more knowledgeable about OF etiology than women without genitourinary conditions. CONCLUSIONS: Compared to prior studies, women's knowledge about OF appears to be more medically based, with media and health workers playing a role in reducing stigmatizing beliefs. These findings support continued investment in OF awareness campaigns, which seem to be increasing knowledge about OF and reducing stigma.
Asunto(s)
Cesárea , Fístula , Parto Obstétrico , Femenino , Humanos , Percepción , Embarazo , Investigación Cualitativa , Estigma SocialRESUMEN
OBJECTIVE: The purpose of this study is to compare the difference of clinical efficacy between conventional intraperitoneal chemotherapy and HIPEC, so as to explore the clinical application value and advantages of HIPEC. DESIGN: A retrospective analysis was conducted on 80 patients with malignant ascites admitted to our hospital from June 2017 to June 2019. The general clinical data and qualitative data of the treatment results of 80 patients with malignant ascites were processed by SPSS19.0 using χ2 test, and quantitative data were processed by t test. P < 0.05, statistical data can be considered statistically significant. RESULTS: 1. There was no significant change in vital signs and temperature in the observation group during the treatment, and the difference was not statistically significant. 2. The short-term total effective rate of patients in the observation group was 91.11%, and the short-term total effective rate of the patients in the control group was 40%. 3. There was no significant difference in the incidence of adverse reactions between the two groups of patients. CONCLUSION: Intraperitoneal hyperthermic chemotherapy combined with intravenous chemotherapy can significantly control malignant ascites and has small adverse reactions, which is worthy of clinical promotion and application.
Asunto(s)
Hipertermia Inducida , Quimioterapia Intraperitoneal Hipertérmica , Ascitis/etiología , Ascitis/terapia , Terapia Combinada , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the relationship between single nucleotides polymorphism of catalase(CAT) gene and susceptibility to noise-induced hearing loss(NIHL) in occupational noise exposed population. METHODS: A case-control study of 1â¶1 was conducted to select 286 workers with binaural high frequency average hearing threshold ≥40 dB(HL), from 2006 to 2015 in a cohort study of occupational noise exposure workers in Henan Province. According to the type of work, the age difference was not more than 5 years and the length of exposure to noise was not more than 2 years. The polymorphism of 8 single nucleotides in CAT gene was detected by medium SNPscanTM, and the relationship between 8 single nucleotides polymorphism of CAT gene and NIHL susceptibility was analyzed by multivariate conditional logistic regression. RESULTS: Under the dominant model of rs208679 locus of CAT gene [(GA GG)/AA], the risk of NIHL in individuals carrying GA or GG genotype was 1. 431 times higher than that in individuals carrying AA genotype(95%CI 1. 020-2. 009), and P=0. 038. CONCLUSION: G, a mutant at rs208679 site of CAT gene, may be one of the risk factors for NIHL susceptibility.
Asunto(s)
Pérdida Auditiva Provocada por Ruido , Estudios de Casos y Controles , Catalasa/genética , Estudios de Cohortes , Predisposición Genética a la Enfermedad , Pérdida Auditiva Provocada por Ruido/epidemiología , Pérdida Auditiva Provocada por Ruido/genética , Humanos , NucleótidosRESUMEN
Objective: Lymph node metastasis (LNM) is one of the important prognostic factors of early gastric cancer (EGC). Moreover, LNM is also important when choosing therapeutic intervention for EGC patients. The purpose of this study is to explore the risk factors of LNM in EGC and to discuss the corresponding treatment. Design: We retrospectively reviewed the medical records of 253 patients with EGC who underwent surgical therapy in our department between 2012 and 2015. Univariate analysis and Multivariate Cox regression were used to evaluate the independent risk factors of LNM. Results: LNM was present in 38 cases among 253 patients (15%). Univariate analysis showed an obvious correlation between LNM and tumour location, tumour size, depth of invasion, morphological classification, gross type of the lesion and venous invasion. Multivariate analysis indicated that poorly differentiated carcinoma, submucosal cancer, tumour size ≥2 cm and venous invasion were the independent risk factors for LNM. Conclusion: Tumour size, depth of invasion, morphological classification and blood vessel invasion were predictive risk factors for LNM in EGC. We propose that EGC patients with those risk factors should be accepted gastrectomy with LN dissection.