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1.
Gastrointest Endosc ; 97(6): 1083-1091.e1, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36720289

RESUMEN

BACKGROUND AND AIMS: The red material occupying the larger portion of the acquired sample in EUS fine-needle biopsy (FNB) is seldom investigated. We aimed to evaluate the composition of the red material. METHODS: Patients with a solid pancreatic mass who received EUS FNB from September 2020 to June 2021 were enrolled. The white or yellowish content with apparent bulk (white material) and the rest of pasta-like red content (red material) were separated immediately after puncture. Needle passes proceeded until 2 specimens with >4 mm of white material were obtained. An extra needle pass was conducted for DNA collection. The DNA amount, Kirsten rat sarcoma virus (K-ras) mutation type, and mutation allele frequency were compared between the white and red material. RESULTS: Forty patients were enrolled with 68 paired white and red materials. The diagnostic accuracy was slightly higher in the white material (92.5% vs 82.5%, P = .219). On the histology slides, the area of the tumor gland was comparable in both materials, but the total tissue area was larger in the red material (9.74 mm2 and 10.74 mm2 larger according to generalized linear model and generalized estimating equation, respectively; both, P < .001). The amount of DNA was significantly higher in the red material (2.99 [interquartile range, 1.59-7.29] µg vs .70 [interquartile range, .27-1.24] µg; P < .001). Common pancreatic adenocarcinoma K-ras mutation was identified at a rate of 85% for the white material and 95% for the red material. Regardless of whether red or white material was used, there was a high concordance of K-ras mutation types (34 of 40 [85%]) and a high correlation of mutation allele frequency (ρ = .66, P < .001). CONCLUSIONS: In EUS FNB, the red material contains a higher amount of tumor DNA and can be an alternative source for tumor DNA analysis.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patología , Adenocarcinoma/genética , Adenocarcinoma/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Neoplasias Pancreáticas
2.
J Formos Med Assoc ; 122(5): 400-410, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36463082

RESUMEN

BACKGROUND: This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer. METHODS: A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not. RESULTS: The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%-40% in all age groups and Correa's steps IV-V increased >35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P < 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P < 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status. CONCLUSION: The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055).


Asunto(s)
Dispepsia , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Úlcera Gástrica , Humanos , Persona de Mediana Edad , Factores de Riesgo , Gastritis/epidemiología , Endoscopía Gastrointestinal , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Mucosa Gástrica
3.
J Virol ; 95(6)2021 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-33408178

RESUMEN

Coxsackievirus A5 (CV-A5) has recently emerged as a main hand, foot, and mouth disease (HFMD) pathogen. Following a large-scale vaccination campaign against enterovirus 71 (EV-71) in China, the number of HFMD-associated cases with EV-71 was reduced, especially severe and fatal cases. However, the total number of HFMD cases remains high, as HFMD is also caused by other enterovirus serotypes. A multivalent HFMD vaccine containing 4 or 6 antigens of enterovirus serotypes is urgently needed. A formaldehyde-inactivated CV-A5 vaccine derived from Vero cells was used to inoculate newborn Kunming mice on days 3 and 10. The mice were challenged on day 14 with a mouse-adapted CV-A5 strain at a dose that was lethal for 14-day-old suckling mice. Within 14 days postchallenge, groups of mice immunized with three formulations, empty particles (EPs), full particles (FPs), and a mixture of the EP and FP vaccine candidates, all survived, while 100% of the mock-immunized mice died. Neutralizing antibodies (NtAbs) were detected in the sera of immunized mice, and the NtAb levels were correlated with the survival rate of the challenged mice. The virus loads in organs were reduced, and pathological changes and viral protein expression were weak or not observed in the immunized mice compared with those in alum-inoculated control mice. Another interesting finding was the identification of CV-A5 dense particles (DPs), facilitating morphogenesis study. These results demonstrated that the Vero cell-adapted CV-A5 strain is a promising vaccine candidate and could be used as a multivalent HFMD vaccine component in the future.IMPORTANCE The vaccine candidate strain CV-A5 was produced with a high infectivity titer and a high viral particle yield. Three particle forms, empty particles (EPs), full particles (FPs), and dense particles (DPs), were obtained and characterized after purification. The immunogenicities of EP, FP, and the EP and FP mixture were evaluated in mice. Mouse-adapted CV-A5 was generated as a challenge strain to infect 14-day-old mice. An active immunization challenge mouse model was established to evaluate the efficacy of the inactivated vaccine candidate. This animal model mimics vaccination, similar to immune responses of the vaccinated. The animal model also tests protective efficacy in response to the vaccine against the disease. This work is important for the preparation of multivalent vaccines against HFMD caused by different emerging strains.


Asunto(s)
Enterovirus Humano A/inmunología , Enfermedad de Boca, Mano y Pie/prevención & control , Vacunación/métodos , Vacunas Virales/administración & dosificación , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Chlorocebus aethiops , Modelos Animales de Enfermedad , Enfermedad de Boca, Mano y Pie/virología , Ratones , Serogrupo , Vacunas Combinadas/administración & dosificación , Vacunas Combinadas/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Células Vero , Carga Viral , Vacunas Virales/inmunología , Virión/inmunología
4.
Nutr Metab Cardiovasc Dis ; 32(4): 948-956, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35067446

RESUMEN

BACKGROUND AND AIMS: The association between the estimated glomerular filtration rate (eGFR) and atherosclerotic cardiovascular disease (ASCVD) risk is unknown. We aimed to evaluate whether eGFR can be used as a predictor in ASCVD risk assessment. METHODS AND RESULTS: Using baseline data from 28,187 participants from Shanghai Suburban Adult Cohort and Biobank study, we adopted Pooled Cohort Equations (PCEs) and Prediction for ASCVD Risk in China (China-PAR) to estimate 10-year ASCVD risk. Multivariate logistic regression was used to analyze the relationship between 10-year ASCVD risk and eGFR. The receiver operating characteristic (ROC) curve was used to evaluate predictive value of eGFR for 10-year high ASCVD risk. Compared with normal eGFR, both men and women with reduced eGFR had a higher prevalence of ASCVD risk factors. With the decrease of eGFR level, the median of 10-year ASCVD risk gradually increased. For men, the adjusted odds ratios (95% confidence interval (CI)) of 10-year high ASCVD risk by PCEs associated with eGFR (60-74 and <60 mL/min/1.73 m2) were 1.52 (95%CI:1.17-1.99) and 2.51 (95%CI:1.27-4.97). The corresponding result was significant only for eGFR < 60 mL/min/1.73 m2, OR of 1.57 (1.14-2.18) for women. Using China-PAR, the adjusted OR of 10-year high risk associated with eGFR < 60 mL/min/1.73 m2 was 1.82 (1.40-2.38) in men. ROC indicated that eGFR has a good predictive value for 10-year high ASCVD risk. CONCLUSION: eGFR may be an important risk factor in predicting and stratifying ASCVD risk. Consideration should be given to integrating eGFR into existing risk assessment tools to improve predictive performance.


Asunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Adulto , Aterosclerosis/diagnóstico , Aterosclerosis/epidemiología , Aterosclerosis/etiología , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , China/epidemiología , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Medición de Riesgo , Factores de Riesgo
5.
J Nanobiotechnology ; 20(1): 207, 2022 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-35501794

RESUMEN

As a typical class of crystalline porous materials, metal-organic framework possesses unique features including versatile functionality, structural and compositional tunability. After being reduced to two-dimension, ultrathin metal-organic framework layers possess more external excellent properties favoring various technological applications. In this review article, the unique structural properties of the ultrathin metal-organic framework nanosheets benefiting from the planar topography were highlighted, involving light transmittance, and electrical conductivity. Moreover, the design strategy and versatile fabrication methodology were summarized covering discussions on their applicability and accessibility, especially for porphyritic metal-organic framework nanosheet. The current achievements in the bioapplications of two-dimensional metal-organic frameworks were presented comprising biocatalysis, biosensor, and theranostic, with an emphasis on reactive oxygen species-based nanomedicine for oncology treatment. Furthermore, current challenges confronting the utilization of two-dimensional metal-organic frameworks and future opportunities in emerging research frontiers were presented.


Asunto(s)
Estructuras Metalorgánicas , Biocatálisis , Conductividad Eléctrica , Nanomedicina , Porosidad
6.
Lipids Health Dis ; 21(1): 72, 2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-35974376

RESUMEN

BACKGROUND: The correlation between nontraditional lipids and ischemic stroke (IS) is inconsistent and controversial. This study aimed to examine the association of four nontraditional lipids with IS risk in Chinese adults. METHODS: This prospective community-based cohort study was performed in Songjiang District, Shanghai, China. The study began in 2016 and included 34,294 participants without stroke before the investigation. The association between nontraditional lipids (nonhigh-density lipoprotein cholesterol [non-HDL-C], total cholesterol/high-density lipoprotein cholesterol [TC/HDL-C], triglyceride [TG]/HDL-C, and low-density lipoprotein cholesterol [LDL-C]/HDL-C) and IS was studied with multivariate Cox regression models. The dose-response associations between these four serum lipids and IS were explored using restricted cubic spline (RCS) analysis. RESULTS: There were a total of 458 IS cases with 166,380 person-years of follow-up. Compared with the lowest tertiles, the highest tertiles of the nontraditional blood lipids showed greater IS risk after controlling for potential confounders. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were as follows: TC/HDL-C, 1.63 (1.28-2.07); TG/HDL-C, 1.65 (1.28-2.13); LDL-C/HDL-C, 1.51 (1.18-1.92); and non-HDL-C, 1.43 (1.13-1.81). The fully adjusted RCS curves presented a nonlinear relationship, and the risk increased when the TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C levels were > 3.47, > 0.92, and > 1.98, respectively. CONCLUSIONS: This community-based cohort study presents a positive association between the four nontraditional lipids and IS incidence. Maintaining relatively low lipid ratios can be beneficial for preventing stroke. Nontraditional lipids can be considered targets for managing blood lipids.


Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adulto , China/epidemiología , Colesterol , HDL-Colesterol , LDL-Colesterol , Estudios de Cohortes , Humanos , Lípidos , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Triglicéridos
7.
Nutr Metab Cardiovasc Dis ; 31(7): 2058-2067, 2021 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-34090771

RESUMEN

BACKGROUND AND AIMS: The accuracy of various 10-year atherosclerotic cardiovascular disease (ASCVD) risk models has been debatable. We compared two risk algorithms and explored clustering patterns across different risk stratifications among community residents in Shanghai. METHODS AND RESULTS: A total of 28,201 residents (aged 40-74 years old) who were free of ASCVD were selected from the Shanghai Survey in China. The 10-year ASCVD risk was estimated by applying the 2013 Pooled Cohort Equations (PCEs) and Prediction for ASCVD Risk in China (China-PAR). The agreement was assessed between PCEs and China-PAR using Cohen's kappa statistics. The mean absolute 10-year ASCVD risk calculated by PCEs and China-PAR was about 10.0% and 6.0%, respectively. PCEs estimated that 44.9% of participants [with a 95% confidence interval (CI):44.0%-45.8%] were at high risk, while China-PAR estimated only 16.7% (95%CI:15.8%-18.0%) were at high risk. In both models, the percentage of high ASCVD risk was higher for participants who were older, men, less educated, current smokers, drinkers and manual workers. Among high-risk individuals, almost all participants (PCEs:90.5%; China-PAR:98.6%) had at least one risk factor; hypertension being the most prevalent. The concordance between PCEs and China-PAR was moderate (kappa:0.428, 95%CI: 0.420-0.434) with a better agreement for women (kappa:0.503,95%CI: 0.493-0.513) than for men (kappa:0.211,95%CI: 0.201-0.221). CONCLUSION: The proportion of participants with a 10-year ASCVD high risk predicted by China-PAR was lower than the results of the PCEs. The risk stratifications of the two algorithms were inconsistent in terms of demographic and life-behaviour characteristics.


Asunto(s)
Algoritmos , Aterosclerosis/epidemiología , Técnicas de Apoyo para la Decisión , Adulto , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Aterosclerosis/diagnóstico , China/epidemiología , Estudios Transversales , Escolaridad , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hipertensión/epidemiología , Perfil Laboral , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Medición de Riesgo , Factores Sexuales , Fumar/efectos adversos , Fumar/epidemiología , Factores de Tiempo
10.
Ann Nutr Metab ; 75(3): 168-178, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31739307

RESUMEN

BACKGROUND/AIMS: Metabolic syndrome (MetS) and its metabolic components, the common risk factors, may be involved in the development and progression of decreased estimated glomerular filtration rate (eGFR). The aim of this study was to examine the association of MetS and its metabolic components with eGFR status and severity among Chinese adults. METHODS: The population-based, cross-sectional study recruited a total of 33,300 Chinese adults (aged ≥18 years) from 4 study community sites in Songjiang District, Shanghai, between June 2016 and December 2017. Decreased eGFR was defined as a value of eGFR below 60 mL/min/1.73 m2. Weighted multiple logistic regression models were used to examine the association of MetS and its components with eGFR status and severity. RESULTS: After adjusting for potential confounders, subjects with MetS had an increased risk of decreased eGFR with an adjusted OR of 1.76 (95% CI 1.53-2.01), and subjects with increasing numbers of MetS components had a gradually increased risk for decreased eGFR (p trend <0.001). The multivariable-adjusted ORs (95% CI) of decreased eGFR were 1.66 (1.44-1.93) for abdominal obesity, 1.37 (1.18-1.60) for elevated triglycerides, 1.13 (0.96-1.33) for reduced high-density lipoprotein cholesterol, 0.84 (0.72-0.98) for elevated fasting glucose, and 1.92 (1.57-2.35) for elevated blood pressure (BP). Furthermore, these associations remained in most of the subgroups analyses. Significant associations between elevated BP and the risks of mildly, moderately, and severely decreased eGFR were also found. CONCLUSIONS: MetS was independently associated with an increased risk of decreased eGFR, and individual components of MetS each play a different role in decreased eGFR. Elevated BP may be an important risk factor for the progression of renal dysfunction or even chronic kidney disease.


Asunto(s)
Tasa de Filtración Glomerular , Síndrome Metabólico/complicaciones , Adulto , Anciano , Pueblo Asiatico , Glucemia , China , HDL-Colesterol/sangre , Estudios Transversales , Registros Electrónicos de Salud , Femenino , Humanos , Hipertensión/complicaciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/complicaciones , Factores de Riesgo , Triglicéridos/sangre
11.
Asian Pac J Allergy Immunol ; 36(3): 145-151, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29223148

RESUMEN

BACKGROUND: Aeroallergen sensitization may predict higher fractional exhaled nitric oxide (FeNO) levels. OBJECTIVE: We evaluate cut-off values of FeNO in asthmatic children with and without positive specific immunoglobulin E (IgE) to at least one of 5 aeroallergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, dog, and cockroach). METHODS: 564 patients with asthma and allergic rhinitis (AR) aged 5 to 18 years were enrolled into two groups. Sensitized group included 378 children with positive IgE to at least one of 5 inhaled allergens. Non-sensitized group included 186 children. Pulmonary function tests, FeNO, eosinophil counts, and IgE levels were examined. Patients were divided into preschool age (5~6 years old), elementary school children (7~11 years old) and adolescents (12~18 years old). RESULTS: In preschool children, FeNO≥15.5 ppb differentiates between non-sensitized and sensitized groups. (sensitivity 54.3%; specificity 87.5%; positive predictive value (PPV) 86.2%; negative predictive value (NPV) 57.1%; area under receiver operating characteristic curve (AUC) 0.72) Among elementary school children, the cut-off value of FeNO≥19.5 ppb showed sensitivity 66.4%; specificity 85.8%; PPV 90.5%; NPV 55.7%; AUC 0.81. In adolescents, FeNO≥27.5 ppb showed sensitivity 60.2%; specificity 85.4%; PPV 91.2%; NPV 46.1%; AUC 0.76. CONCLUSION: In asthmatic children, aeroallergen sensitization appears to contribute to higher FeNO levels than those not sensitized. Cut-off values of FeNO which well discriminate asthmatic children with and without aeroallergen sensitization should be chose according to different ages.


Asunto(s)
Asma/diagnóstico , Asma/inmunología , Hipersensibilidad/diagnóstico , Hipersensibilidad/inmunología , Óxido Nítrico/análisis , Adolescente , Alérgenos/inmunología , Animales , Antígenos Dermatofagoides/inmunología , Gatos , Niño , Preescolar , Perros , Espiración , Femenino , Humanos , Inmunoglobulina E/inmunología , Proteínas de Insectos/inmunología , Masculino , Pruebas de Función Respiratoria/métodos , Estudios Retrospectivos
12.
Front Cell Infect Microbiol ; 14: 1405689, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39239635

RESUMEN

Introduction: Coxsackievirus A6 (CV-A6) has emerged as the predominant epidemic strain responsible for hand, foot and mouth disease (HFMD). CV-A6 infection can result in severe clinical manifestations, including encephalitis, meningitis, and potentially life-threatening central nervous system disorders. Our previous research findings demonstrated that neonatal mice infected with CV-A6 exhibited limb weakness, paralysis, and ultimately succumbed to death. However, the underlying mechanism of CV-A6-induced nervous system injury remains elusive. Numerous reports have highlighted the pivotal role of miRNAs in various viral infections. Methods: Separately established infection and control groups of mice were used to create miRNA profiles of the brain tissues before and after CV-A6 transfection, followed by experimental verification, prediction, and analysis of the results. Results: At 2 days post-infection (dpi), 4 dpi, and 2dpi vs 4dpi, we identified 175, 198 and 78 significantly differentially expressed miRNAs respectively using qRT-PCR for validation purposes. Subsequently, we predicted target genes of these differentially expressed miRNAs and determined their potential targets through GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Finally, we verified the miRNA-mRNA pairing via double luciferase experiments while confirming functional enrichment of target genes through Western Blotting analyses. Discussion: The results from this study suggest that transcriptional regulation, neuronal necrosis, pro-inflammatory cytokine release, and antiviral immunity are all implicated in the pathogenesis of central nervous system injury in mice infected with CV-A6. Brain injury resulting from CV-A6 infection may involve multiple pathways, including glial cell activation, neuronal necrosis, synaptic destruction, degenerative diseases of the nervous system. It can even encompass destruction of the blood-brain barrier, leading to central nervous system injury. The dysregulated miRNAs and signaling pathways discovered in this study provide valuable insights for further investigations into the pathogenesis of CV-A6.


Asunto(s)
Modelos Animales de Enfermedad , MicroARNs , Animales , MicroARNs/genética , MicroARNs/metabolismo , Ratones , Encéfalo/virología , Encéfalo/patología , Encéfalo/metabolismo , Infecciones por Coxsackievirus/virología , Infecciones por Coxsackievirus/genética , Lesiones Encefálicas/virología , Lesiones Encefálicas/genética , Perfilación de la Expresión Génica , Enterovirus Humano A/genética , Enterovirus Humano A/patogenicidad , Enterovirus/genética , Enterovirus/patogenicidad , Enfermedad de Boca, Mano y Pie/virología
13.
ACS Appl Mater Interfaces ; 16(40): 54799-54806, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39315994

RESUMEN

Chemo-biocatalytic cascades have emerged as a promising approach in the realm of advanced synthesis. However, reconciling the incompatible reaction conditions among distinct catalytic species presents a significant challenge. Herein, we introduce an innovative solution using an emulsion system stabilized by Janus silica nanoparticles, which serve as a bridge for both chemo-catalysts and biocatalysts at the interface. The chemo-catalyst is securely anchored within a hydrophobic polymer matrix, ensuring its residence in an organic environment. Meanwhile, the negatively charged E. coli cells containing enzymes are attracted to the aqueous phase at the interface, facilitating their optimal positioning. We demonstrate the efficacy of this system through a two-step cascade reaction. Initially, the oxidation of styrene to acetophenone using palladium as a chemocatalyst achieves a 6-fold increase in yield compared to the control system. Subsequently, the reduction of achiral acetophenone to its chiral alcohol derivative presents a 17-fold yield enhancement relative to that of the control reaction. Importantly, our system exhibits versatility, accommodating a wide range of substrates for both individual and sequential reactions. This work not only validates the concept but also paves the way for the integration of chemo- and biocatalysts in the synthesis of a broader array of high-value chemical compounds.

14.
Pathology ; 56(3): 367-373, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38290893

RESUMEN

BLS-type diffuse large B-cell lymphoma (DLBCL) denotes an uncommon, aggressive variant of DLBCL presenting initially in bone marrow, liver and spleen without lymphadenopathy or mass lesion. Patients with BLS-type DLBCL present frequently with haemophagocytic syndrome which often leads to early patient demise. Programmed death ligand 1 (PD-L1) plays a negative regulatory role on effector T cells and is an important target of immunotherapy. Assessment of PD-L1 expression in BLS-type DLBCL may carry therapeutic implications and provide mechanistic insights. Standard immunohistochemical analysis for PD-L1 was performed in seven cohorts for this study: (1) DLBCL-not otherwise specified (NOS) (n=201); (2) Epstein-Barr virus (EBV)-positive DLBCL (n=26); (3) thymic (primary mediastinal) DLBCL (n=12); (4) intravascular LBCL (n=3); (5) high-grade B-cell lymphoma, NOS (n=12); (6) BLS-type DLBCL (n=37); and (7) systemic DLBCL involving bone marrow (n=28). We found that PD-L1 was positive in 12.9% of DLBCL-NOS cases, 46.2% of EBV-positive DLBCL, 91.7% of thymic LBCL, none of intravascular LBCL, 8.3% of high-grade B-cell lymphoma-NOS, and 56.8% of BLS-type DLBCL. By comparison, only 14.3% of bone marrow cases involved by systemic DLBCL were positive for PD-L1 (p<0.001). Interestingly, BLS-type DLBCL more frequently showed activated B-cell phenotype (86.5% vs 65.2%, p=0.010), a high Ki-67 proliferative index (97.1% vs 63.3%, p<0.001), MYC overexpression (90.9% vs 56.2%, p=0.023), presence of haemophagocytic syndrome (86.5% vs 4.0%, p<0.001), and poorer overall survival (p<0.001) than DLBCL-NOS. These data suggest that the poor prognosis of BLS-type DLBCL may be explained by both extrinsic tumour microenvironment factors and intrinsic genetic factors of tumour cells, such as PD-L1-associated inactivation of anti-tumour immunity for the former, and MYC pathway activation-related aggressiveness for the latter.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Linfoma de Células B Grandes Difuso , Humanos , Antígeno B7-H1/metabolismo , Infecciones por Virus de Epstein-Barr/patología , Pronóstico , Herpesvirus Humano 4 , Linfoma de Células B Grandes Difuso/patología , Inmunoterapia , Microambiente Tumoral
15.
J Control Release ; 375: 1-19, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39208935

RESUMEN

Point-of-care ultrasound demonstrates significant potential in biomedical research due to its noninvasive, real-time visualization, cost-effectiveness, and other biological benefits. Ultrasound irradiation can precisely control the mechanical and physicochemical effects on pathogenic lesions, enabling real-time visualization, tunable tissue penetration depth, and therapeutic applications. This review summarizes recent advancements in ultrasound-enabled diagnostics and therapeutics, focusing on mechanochemical effects that can be directly integrated into biomedical applications. Additionally, the structure-functionality relationships of sonotheranostic nanoplatforms are systematically discussed, providing insights into the underlying biological effects. Finally, the limitations of current ultrasonic medicine are discussed, along with potential expansions to facilitate patient-centered translations.


Asunto(s)
Ultrasonografía , Humanos , Animales , Ultrasonografía/métodos , Sistemas de Atención de Punto , Terapia por Ultrasonido/métodos , Sistemas de Liberación de Medicamentos
16.
Am J Surg Pathol ; 48(11): 1425-1438, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38979928

RESUMEN

Burkitt lymphoma is characterized by high cell turnover and numerous cytoplasmic vacuoles that are demonstrated to be lipid droplets (LDs) decorated by adipophilin. By contrast, cytoplasmic vacuoles are variably observed in diffuse large B-cell lymphoma (DLBCL) and less well characterized. In this study, we first validated in DLBCL that cytoplasmic vacuoles are indeed LDs by Oil-red-O stain, Bodipy fluorescent stain, and electron microscopy. Second, in a cohort of DLBCL patients (n=52) we showed that LDs in effusional lymphoma cells were associated with a poorer prognosis ( P =0.029, log-rank test) and higher International Prognostic Index (IPI) score (94% vs. 66%, P =0.026) than those without. Moreover, using adipophilin as a surrogate marker for LDs, we found in another cohort of biopsy specimen (n=85) that expression of adipophilin by lymphoma cells predicted a poorer prognosis ( P =0.007, log-rank test) and higher IPI score (63% vs. 30%, P =0.005). In addition, whole exome sequencing of effusional DLBCL cells showed LD-positive DLBCL shared genetic features with the MCD ( MYD88 and CD79B mutations) subtype and highlighted OSBPL10 and CUBN as the most frequently mutated genes involved in lipogenesis. Whole transcriptome analysis by comparing effusional DLBCL cells with versus without LDs showed upregulation of EHHADH , SLC1A1 , CD96 , INPP4B , and RNF183 relevant for lymphoma lipogenesis and upregulation of epithelial-mesenchymal transition and KRAS signaling pathways. Higher expression of EHHADH and CD96 were validated in LD-positive clinical samples and LD-rich cell lines than LD-poor cells along with the known lipogenic gene, FASN . Our findings highlight the roles of LDs and adipophilin expression in DLBCL, suggest that these markers may predict prognosis and show that lipogenic genes may be potential therapeutic targets.


Asunto(s)
Biomarcadores de Tumor , Secuenciación de Nucleótidos de Alto Rendimiento , Gotas Lipídicas , Lipogénesis , Linfoma de Células B Grandes Difuso , Perilipina-2 , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/mortalidad , Gotas Lipídicas/metabolismo , Masculino , Lipogénesis/genética , Femenino , Perilipina-2/genética , Perilipina-2/análisis , Perilipina-2/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Persona de Mediana Edad , Pronóstico , Anciano , Adulto , Mutación , Valor Predictivo de las Pruebas , Acido Graso Sintasa Tipo I/genética , Acido Graso Sintasa Tipo I/metabolismo , Acido Graso Sintasa Tipo I/análisis , Anciano de 80 o más Años
18.
Artículo en Inglés | MEDLINE | ID: mdl-37801390

RESUMEN

Histopathological images provide the medical evidences to help the disease diagnosis. However, pathologists are not always available or are overloaded by work. Moreover, the variations of pathological images with respect to different organs, cell sizes and magnification factors lead to the difficulty of developing a general method to solve the histopathological image classification problems. To address these issues, we propose a novel cross-scale fusion (CSF) transformer which consists of the multiple field-of-view patch embedding module, the transformer encoders and the cross-fusion modules. Based on the proposed modules, the CSF transformer can effectively integrate patch embeddings of different field-of-views to learn cross-scale contextual correlations, which represent tissues and cells of different sizes and magnification factors, with less memory usage and computation compared with the state-of-the-art transformers. To verify the generalization ability of the CSF transformer, experiments are performed on four public datasets of different organs and magnification factors. The CSF transformer outperforms the state-of-the-art task specific methods, convolutional neural network-based methods and transformer-based methods. The source code will be available in our GitHub https://github.com/nchucvml/CSFT.

19.
Respirol Case Rep ; 11(6): e01165, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37249923

RESUMEN

Amiodarone is a commonly used antiarrhythmic agent but exhibits potential pulmonary toxicity. In this case series, we describe the clinical, radiographic, and histologic manifestations of three patients who developed interstitial lung disease (ILD) following amiodarone treatment for variable lengths of time with different dosages. The presentations on computed tomographic images and in pulmonary pathology differed among the three patients. All three had immediate discontinuation of amiodarone and received treatment with systemic corticosteroids. One patient eventually died from ventilator-associated pneumonia after an initial improvement. The other two patients recovered well but later experienced ILD recurrence following brief re-exposure to amiodarone. Through this case series, we aim to demonstrate the variable features of amiodarone-related ILD, and highlight the importance of timely amiodarone cessation and avoiding re-exposure to prevent the progression and recurrence of ILD.

20.
ERJ Open Res ; 9(1)2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36814554

RESUMEN

Background: Organising pneumonia (OP) has variable clinical and radiographic presentations and unstandardised treatments. Most patients with OP have favourable outcomes, but some develop respiratory insufficiency, experience recurrence or die. In this study we investigated the impact of computed tomographic (CT) patterns and extent of OP on the diagnostic and therapeutic management that patients received, and that on the therapeutic response and prognosis (particularly the risk of respiratory insufficiency and death). Methods: We retrospectively studied 156 patients with OP followed at our hospital between 2010 and 2021. The diagnosis was confirmed histologically and verified by multidisciplinary specialists. We performed Firth's logistic regression to determine the relationship between CT features and aetiologies, management and outcomes including the risk of severe disease (defined as the need for supplemental oxygen or mechanical ventilation). We conducted Kaplan-Meier analyses to assess survival differences. Results: Patients exhibiting multilobe involvement or mixed patterns, or both, were more likely to have secondary OP and receive immunosuppressants. Higher proportions of these patients experienced recurrence. Compared to patients with single-lobe involvement and single-pattern, they also had an enhanced risk of severe disease (the adjusted odds ratio for patients who simultaneously had multilobe involvement and mixed patterns was 27.64; 95% confidence interval 8.25-127.44). Besides, these patients had decreased survival probabilities. Conclusion: Different CT features of OP impact patients' management and prognosis. When treating patients with OP exhibiting multilobe involvement or mixed patterns, or both, it is important to identify the possible causative aetiology and follow closely for adverse outcomes.

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