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1.
Pathology ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39237383

RESUMEN

Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare and highly aggressive lymphoma with characteristic ALK rearrangements. Various fusion genes involving ALK have been demonstrated, but the influence of the ALK fusion partners on ALK protein expression and the genetic characteristics of ALK+ LBCL remain relatively unknown. In this study, we conducted an extensive clinicopathological and molecular analysis on seven cases of ALK+ LBCL to explore the correlation between ALK fusion genes and ALK protein expression, thereby enriching the genetic characteristics of this tumour. We integrated the findings from clinical, histopathological/immunophenotypic, and molecular studies, including three samples subjected to next-generation sequencing, and six cases underwent RNA-based ALK fusion gene detection. We identified five distinct types of ALK fusion genes, including CLTC, NPM1, PABPC1, SEC31A, and TFG. Notably, only the NPM1::ALK fusion showed nuclear and cytoplasmic ALK staining, and the remaining four fusion genes resulted in cytoplasmic ALK staining. Our analysis revealed that the CLTC::ALK fusion resulted in a unique cytoplasmic perinuclear Golgi zone focal granular heterogeneous staining pattern of ALK. Additionally, we identified six potentially clinically significant gene mutations, including TET2, CHD2, DTX1, KMT2D, LRP1B, and XPO1. Furthermore, in all cases, the absence of 5-hydroxymethylcytosine (5hmC) was observed. We present seven cases of ALK+ LBCL, discussing the correlation between fusion genes and ALK protein expression, and enhancing our understanding of the genetic attributes of this tumour. This study also shows the loss of 5hmC in nearly all seven ALK+ LBCL cases, independently of TET2 mutations.

2.
Int J Biol Sci ; 20(10): 3972-3985, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39113693

RESUMEN

Histone methyltransferase KMT2D is one of the most frequently mutated genes in diffuse large B-cell lymphoma (DLBCL) and has been identified as an important pathogenic factor and prognostic marker. However, the biological relevance of KMT2D mutations on tumor microenvironment remains to be determined. KMT2D mutations were assessed by whole-genome/exome sequencing (WGS/WES) in 334 patients and by targeted sequencing in 427 patients with newly diagnosed DLBCL. Among all 761 DLBCL patients, somatic mutations in KMT2D were observed in 143 (18.79%) patients and significantly associated with advanced Ann Arbor stage and MYC expression ≥ 40%, as well as inferior progression-free survival and overall survival. In B-lymphoma cells, the mutation or knockdown of KMT2D inhibited methylation of lysine 4 on histone H3 (H3K4), downregulated FBXW7 expression, activated NOTCH signaling pathway and downstream MYC/TGF-ß1, resulting in alterations of tumor-induced regulatory T cell trafficking. In B-lymphoma murine models established with subcutaneous injection of SU-DHL-4 cells, xenografted tumors bearing KMT2D mutation presented lower H3K4 methylation, higher regulatory T cell recruitment, thereby provoking rapid tumor growth compared with wild-type KMT2D via FBXW7-NOTCH-MYC/TGF-ß1 axis.


Asunto(s)
Proteína 7 que Contiene Repeticiones F-Box-WD , Linfoma de Células B Grandes Difuso , Mutación , Proteínas Proto-Oncogénicas c-myc , Linfocitos T Reguladores , Humanos , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Animales , Ratones , Femenino , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Masculino , Linfocitos T Reguladores/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Receptores Notch/metabolismo , Persona de Mediana Edad , Línea Celular Tumoral , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Transducción de Señal , Adulto , Progresión de la Enfermedad , Anciano
3.
Comput Struct Biotechnol J ; 23: 2883-2891, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39108678

RESUMEN

Crop pedigrees incorporate information on the kinship and genetic evolutionary history of breeding materials. Complete and accurate pedigree information is vital for effective genetic improvement of crops and maximal exploitation of heterosis in crop production. It is difficult for breeders to accurately extrapolate the selection of germplasm resources with missing genealogical information based on breeding experience. In this study, an algorithm called PidTools was developed, consisting of five sets of algorithms from three core modules, for accurate pedigree identification analysis. The algorithms and associated tools are suitable for all crops, for the reconstruction and visualization of a complete pedigree for breeding materials. The algorithm and tools were validated with the model crop maize. A genotype database was constructed using Maize6H-60K array data from 5791 maize inbred lines. The pedigree of the maize inbred line Jing72464 was identified without prior provision of any parental information. The pedigree information for Zheng58 was fully identified at the genome-wide scale. With regard to group identification, the parents of a doubled-haploid group were identified based on the genotyping data. The pedigree of 21 Dan340 derived lines were visualized using PidTools. The algorithms are incorporated into a user-friendly online analytical platform, PidTools-WS, with an associated customizable toolkit program, PidTools-CLI. These analytical tools and the present results provide useful information for future maize breeding. The PidTools online analysis platform is available at https://PidTools.plantdna.site/.

4.
Am J Surg Pathol ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39172106

RESUMEN

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare form of aggressive B-cell lymphoma with limited molecular information reported regarding interferon regulatory factor 4 (IRF4) status. Here, we presented 3 EBV-positive DLBCL cases with IRF4 rearrangement (EBV+DLBCL-IRF4-R) verified by fluorescence in situ hybridization (FISH). Three patients, including 1 male and 2 females (median age: 64 y; range: 45 to 68 y), had normal immune function. During a median follow-up of 12 months (range: 0 to 24 mo), 2 patients succumbed to the disease, and 1 patient achieved complete response. Three tumors were present in the mediastinum, stomach, and thalamus, respectively. All three tumors exhibited DLBCL morphology and were identified as the non-germinal center B-cell subtype, with EBV-encoded small RNA positivity ranging from 70% to 80%. RNA sequencing was able to identify RHOH and IGH as fusion partners of IRF4 in two cases. No MYC and BCL2 rearrangements were detected in 3 cases by FISH and RNA sequencing. Next-generation sequencing revealed a low mutation burden, and only IRF4 was recurrently mutated in two EBV+DLBCL-IRF4-R cases. Using the LymphGen 2.0 classifier, 1 case was classified as the MCD (including MYD88L265P and CD79B mutations) subtype. We report rare EBV+DLBCL-IRF4-R that may enhance our understanding of the diverse spectrum of large B-cell lymphoma.

5.
Cell Transplant ; 33: 9636897241259722, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38856035

RESUMEN

Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein-Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Trastornos Linfoproliferativos , Linfocitos T , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Trastornos Linfoproliferativos/etiología , Masculino , Femenino , Adulto , Linfocitos T/inmunología , Trasplante Homólogo/métodos , Trasplante Homólogo/efectos adversos , Adolescente , Niño , Persona de Mediana Edad , Adulto Joven , Ciclofosfamida/uso terapéutico
6.
Int J Immunopathol Pharmacol ; 38: 3946320241264369, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38886178

RESUMEN

Background: Typically, lymphatic tissue proliferative lesions include either benign lesions or lymphoma. However, not all lymphatic lesions can currently be accurately classified into one category, particularly in mucosal areas that are in contact with the external environment.Aims: To explore the morphology, immunophenotype, and molecular changes of Non-neoplastic B-cell predominant lymphoid proliferations (NBPLP) in pathological areas that are exposed to external surroundings which mimicked lymphoma.Methods and Results: 18 cases of Atypical lymphoid hyperplasia (AtLP)  were retrieved in this study. The biopsy samples were mucosal samples obtained from areas exposed to external surroundings, including intestines, urethra, cervix, tonsils, and tongue. Microscopically, there is a different level of B cell hyperplasia accompanied by morphological atypia. We categorized the morphology into 4 groups: type A (7/18), type B (3/18), type C (3/18), type D (5/18). Part of the AtLP was found positive for BCR gene rearrangement (6/15), and TCR gene rearrangement (1/4). The follow-up period ranged from 14.2 to 70 months. No evidence of lymphoma was found. Therefore, we diagnosed all of the presented cases as NBPLP. We illustrated the key differential points and provided valuable diagnostic experience on each subtype.Conclusions: Areas exposed to the external environment are commonly exposed to antigen and easily present with AtLP of NBPLP, accompanying with positive IGH rearrangement. Therefore, a comprehensive evaluation of macroscopic, morphology, immunophenotype, and molecular diagnostics is required to prevent the overdiagnosis of lymphoma.


Asunto(s)
Linfocitos B , Linfoma , Humanos , Femenino , Persona de Mediana Edad , Masculino , Linfocitos B/inmunología , Linfocitos B/patología , Linfoma/patología , Linfoma/diagnóstico , Linfoma/inmunología , Diagnóstico Diferencial , Adulto , Anciano , Proliferación Celular , Inmunofenotipificación
8.
Genes (Basel) ; 15(3)2024 02 25.
Artículo en Inglés | MEDLINE | ID: mdl-38540352

RESUMEN

Maize(Zea mays. L) is a globally important crop, and understanding its genetic diversity is crucial for plant breeding phylogenetic analyses and comparative genetics. While nuclear markers have been extensively used for mapping agriculturally important genes, they are limited in recognizing characteristics, such as cytoplasmic male sterility and reciprocal cross hybrids. In this study, we performed next-generation sequencing of 176samples, and the maize cultivars represented five distinct groups. A total of 89 single nucleotide polymorphisms (SNPs) and 11 insertion/deletion polymorphisms (InDels) were identified. To enable high-throughput detection, we successfully amplified and confirmed 49 SNP and InDel markers, which were defined as a Varietal Chloroplast Panel (VCP) using the Kompetitive Allele Specific PCR (KASP). The specific markers provided a valuable tool for identifying chloroplast groups. The verification experiment, focusing on the identification of reciprocal cross hybrids and cytoplasmic male sterility hybrids, demonstrated the significant advantages of VCP markers in maternal inheritance characterization. Furthermore, only a small subset of these markers is needed to provide useful information, showcasing the effectiveness of these markers in elucidating the artificial selection process of elite maize lines.


Asunto(s)
Genoma del Cloroplasto , Polimorfismo de Nucleótido Simple , Polimorfismo de Nucleótido Simple/genética , Mapeo Cromosómico , Marcadores Genéticos/genética , Zea mays/genética , Genotipo , Filogenia , Genoma de Planta/genética , Fitomejoramiento
9.
NPJ Precis Oncol ; 8(1): 76, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38538739

RESUMEN

Diffuse large B cell lymphoma (DLBCL) is an aggressive blood cancer known for its rapid progression and high incidence. The growing use of immunohistochemistry (IHC) has significantly contributed to the detailed cell characterization, thereby playing a crucial role in guiding treatment strategies for DLBCL. In this study, we developed an AI-based image analysis approach for assessing PD-L1 expression in DLBCL patients. PD-L1 expression represents as a major biomarker for screening patients who can benefit from targeted immunotherapy interventions. In particular, we performed large-scale cell annotations in IHC slides, encompassing over 5101 tissue regions and 146,439 live cells. Extensive experiments in primary and validation cohorts demonstrated the defined quantitative rule helped overcome the difficulty of identifying specific cell types. In assessing data obtained from fine needle biopsies, experiments revealed that there was a higher level of agreement in the quantitative results between Artificial Intelligence (AI) algorithms and pathologists, as well as among pathologists themselves, in comparison to the data obtained from surgical specimens. We highlight that the AI-enabled analytics enhance the objectivity and interpretability of PD-L1 quantification to improve the targeted immunotherapy development in DLBCL patients.

10.
Prev Med Rep ; 40: 102667, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38450207

RESUMEN

Background: Although workplace violence is prevalent in the healthcare system, the relationship between workplace violence, job satisfaction, and burnout among healthcare workers (HCWs) in mobile cabin hospitals in China during the COVID-19 pandemic has not yet been investigated. This study analyzes the mediating effects of perceived stress and work environment in the relationship between workplace violence, job satisfaction, and burnout. Methods: A cross-sectional study was conducted in December 2022 on 1,199 frontline HCWs working in mobile cabin hospitals in Chongqing, China, during the COVID-19 pandemic. Multiple linear regression and mediation analysis were performed. Results: A positive correlation was observed between workplace violence and burnout (r = 0.420, P < 0.01) and perceived stress (r = 0.524, P < 0.01), and a negative correlation was observed with job satisfaction (r = -0.254, P < 0.01). The perceived stress was positively correlated with burnout (r = 0.528, P < 0.01) and negatively with job satisfaction (r = -0.397, P < 0.01). Job satisfaction was negatively correlated with burnout (r = -0.300, P < 0.01). Perceived stress plays a significant mediating role between workplace violence and job burnout and between workplace violence and job satisfaction. The work environment has a significant moderating effect between workplace violence and job burnout and between workplace violence and job satisfaction. Conclusion: To reduce burnout among HCWs, hospital administrators should focus on reducing the incidence of workplace violence and perceived stress from work and on improving the work environment and job satisfaction.

11.
Signal Transduct Target Ther ; 9(1): 62, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448403

RESUMEN

Natural killer T cell lymphoma (NKTCL) is highly aggressive, with advanced stage patients poorly responding to intensive chemotherapy. To explore effective and safe treatment for newly diagnosed advanced stage NKTCL, we conducted a phase II study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab (NCT04096690). Twenty-two patients with a median age of 51 years (range, 24-74) were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days, followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days. The complete response and overall response rate after induction treatment were 59% (95%CI, 43-79%) and 68% (95%CI, 47-84%), respectively. With a median follow-up of 30 months, the 2 year progression-free and overall survival rates were 68% (95%CI, 45-83%) and 86% (95%CI, 63-95%), respectively. The most frequently grade 3/4 adverse events were neutropenia (32%, n = 7) and hypofibrinogenemia (18%, n = 4), which were manageable and led to no discontinuation of treatment. Tumor proportion score of PD-L1, peripheral blood high-density lipoprotein cholesterol, and apolipoprotein A-I correlated with good response, while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment. In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Asparaginasa , Linfoma , Células T Asesinas Naturales , Polietilenglicoles , Humanos , Receptor de Muerte Celular Programada 1 , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven
12.
Int J Surg Pathol ; 32(6): 1197-1203, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38166493

RESUMEN

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is rare in adults. The presence of intratumoral T lymphocytes and primitive rounded cells characterized this neoplasm. We report a 24-year-old Chinese man who developed EBV-SMT in the right adrenal gland with hepatitis B infection and autoimmune hemolytic anemia without a history of HIV infection, primary immune deficiency, organ transplantation, or malignant tumor. This patient had an unknown immunodeficient state. EBV-SMTs are commonly located in the liver, lung, and gastrointestinal tract but rarely in the adrenal gland. We reviewed 10 reported literature on EBV-SMT in the adrenal gland. It is imperative to distinguish EBV-SMT from conventional somatic smooth muscle tumors. The discovery of EBV-SMT forces the clinician to conduct a thorough evaluation of immune function and immune status surveillance, and these patients are vulnerable to subsequent malignant tumors.


Asunto(s)
Anemia Hemolítica Autoinmune , Infecciones por Virus de Epstein-Barr , Hepatitis B , Tumor de Músculo Liso , Humanos , Masculino , Tumor de Músculo Liso/patología , Tumor de Músculo Liso/diagnóstico , Tumor de Músculo Liso/virología , Anemia Hemolítica Autoinmune/diagnóstico , Anemia Hemolítica Autoinmune/patología , Anemia Hemolítica Autoinmune/inmunología , Anemia Hemolítica Autoinmune/complicaciones , Anemia Hemolítica Autoinmune/virología , Adulto Joven , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/patología , Hepatitis B/complicaciones , Hepatitis B/diagnóstico , Hepatitis B/virología , Herpesvirus Humano 4/aislamiento & purificación
13.
Prev Med Rep ; 37: 102554, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38174324

RESUMEN

To understand the level of post-traumatic growth (PTG) and influencing factors among front-line healthcare workers (HCWs) working in mobile cabin hospitals treating patients with Coronavirus Disease 2019 (COVID-19) under the Normalized Epidemic Prevention and Control Requirements adopted in China. A random sampling method was used to select 540 HCWs of the Chongqing-aid-Shanghai medical team from April to May 2022 as the study participants. Participants completed a general information questionnaire, the Post-traumatic Growth Inventory-Chinese version (PTGI-C), the Chinese version of the Connor-Davidson Resilience Scale (CD-RISC) and the Chinese Event Related Rumination Inventory (C-ERRI). Among the 540 included HCWs, 83.15 % were nurses and 78.89 % were women. The average scores for PTG (62.25 ± 16.73) and psychological resilience (64.22 ± 15.38) were at moderate levels, and the average score for rumination was low (21.62 ± 10.77). Pearson correlation analysis showed that CD-RISC and C-ERRI scores were positive with the PTGI-C score (r = 0.528, 0.316, P < 0.001). Multiple linear regression analysis identified psychological training or intervention during the COVID-19 epidemic (ß = 2.353, P = 0.044), psychological resilience (ß = 0.525, P < 0.001) and deliberate rumination (ß = 0.732, P < 0.001) as factors significantly associated with the PTG of front-line HCWs, which together explained 36.8 % of the total variance in PTG (F[5,539] = 63.866, P < 0.001). In general, psychological resilience and deliberate rumination can promote PTG among HCWs and can be improved by strengthening psychological training and interventions for HCWs working under the Normalized Epidemic Prevention and Control Requirements.

15.
Blood Adv ; 8(7): 1587-1599, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38170757

RESUMEN

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma with clinical and biological heterogeneity. The International Prognostic Index (IPI) shows great prognostic capability in the era of rituximab, but the biological signatures of IPI remain to be discovered. In this study, we analyzed the clinical data in a large cohort of 2592 patients with newly diagnosed DLBCL. Among them, 1233 underwent DNA sequencing for oncogenic mutations, and 487 patients underwent RNA sequencing for lymphoma microenvironment (LME) alterations. Based on IPI scores, patients were categorized into 4 distinct groups, with 5-year overall survival of 41.6%, 55.3%, 71.7%, and 89.7%, respectively. MCD-like subtype was associated with age of >60 years, multiple extranodal involvement, elevated serum lactate dehydrogenase (LDH), and IPI scores ranging from 2 to 5, whereas ST2-like subtype showed an opposite trend. Patients with EZB-like MYC+ and TP53Mut subtypes exhibited poor clinical outcome independent of the IPI; integrating TP53Mut into IPI could better distinguish patients with dismal survival. The EZB-like MYC-, BN2-like, N1-like, and MCD-like subtypes had inferior prognosis in patients with IPI scores of ≥2, indicating necessity for enhanced treatment. Regarding LME categories, the germinal center-like LME was more prevalent in patients with normal LDH and IPI scores of 0 to 1. The mesenchymal LME served as an independent protective factor, whereas the germinal center-like, inflammatory, and depleted LME categories correlated with inferior prognosis for IPI scores of 2 to 5. In summary, our work explored the biological signatures of IPI, thus providing useful rationale for future optimization of the IPI-based treatment strategies with multi-omics information in DLBCL.


Asunto(s)
Linfoma de Células B Grandes Difuso , Humanos , Persona de Mediana Edad , Pronóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Rituximab/uso terapéutico , Centro Germinal/patología , Microambiente Tumoral
16.
Cancer ; 130(8): 1246-1256, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-37941429

RESUMEN

BACKGROUND: Marginal zone lymphomas (MZLs) comprise a diverse group of indolent lymphoproliferative disorders; however, some patients develop histologic transformation (HT) with rapid progression to aggressive lymphoma. METHODS: Forty-three MZLs with HT (HT-MZLs), 535 MZLs, and 174 de novo diffuse large B-cell lymphomas (DLBCLs) without rearrangements of MYC, BCL2, and BCL6 were collected. Among these, 22 HT-MZLs, 39 MZLs, and 174 DLBCLs were subjected to 148-gene targeted exome sequencing. The clinicopathologic features of patients who had HT-MZL and their genetic alterations were compared with those of patients who had MZLs and DLBCLs. RESULTS: All 43 HT-MZLs corresponded to DLBCLs. No HT-MZLs harbored BCL2 and MYC and/or BCL6 rearrangements. Bone marrow involvement and higher levels of lactate dehydrogenase were significantly more common in HT-MZLs than in MZLs. Furthermore, upregulated BCL6, MUM1, C-MYC, and Ki-67 expression was observed more frequently in HT-MZLs than in MZLs. TBL1XR1 was the most frequently altered gene (63.6%) in HT-MZLs, followed by CCND3 (31.8%), CARD11, ID3, and TP53 (22.7%). A trend toward worse progression-free survival in patients with TBL1XR1 mutations was observed. Compared with MZLs and non-germinal center B-cell (GCB) type DLBCLs, significantly higher frequencies of TBL1XR1 and ID3 mutations were identified in HT-MZLs. PIM1 mutations frequently occurred in DLBCLs and were significantly associated with TBL1XR1 mutations but were mutated less in HT-MZLs that had TBL1XR1 mutations. CONCLUSIONS: The current findings reveal the clinicopathologic and genetic features of HT-MZLs, suggesting that these tumors might constitute a group distinct from MZL and de novo non-GCB type DLBCL. TBL1XR1 mutations may be considered a predictor of HT in MZL.


Asunto(s)
Linfoma de Células B de la Zona Marginal , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Supervivencia sin Progresión , Proteínas Proto-Oncogénicas c-bcl-2/genética
17.
Sci Rep ; 13(1): 22765, 2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-38123616

RESUMEN

This study aimed to investigate the clinical and social factors of delayed treatment for testicular torsion (TT) and to explore the risk factors of testicular excision in China. The clinical data of 1005 patients with TT who were admitted to 48 medical institutions in Chongqing city (China) from January 2012 to December 2021 were retrospectively analyzed. It was revealed that the misdiagnosis rates of non-senior (junior and middle) grade doctors and senior doctors were 25.1% and 9.6%, respectively. The proportion of TT patients who received timely treatment (within 6 h after onset of symptoms) was 23.8%. The results of the multivariable logistic regression analysis indicated that absent cremasteric reflex was a protective factor for delayed surgery of more than 6 h from onset of symptoms to surgery. Misdiagnosis, consultation with a non-urologist as the first consultant doctor, absence blood flow in color Doppler ultrasound, negative high-riding testis findings, the presence of fever, and non-manual detorsion were identified as risk factors associated with delayed surgery (more than 6 h from the onset of symptoms) for TT. Furthermore, misdiagnosis, non-urologist first-consultant doctor, absent blood flow in DUS, non-manual detorsion, fever, degree of cord twisting > 180, and the initial diagnosis in tertiary hospitals were risk factors for orchidectomy. Having TT on the right side, and the presence of nausea and vomiting were identified as protective factors for orchidectomy. Technical training in the diagnosis and treatment of TT should be extended to primary hospitals and doctors to significantly improve their accuracy in managing this condition.


Asunto(s)
Torsión del Cordón Espermático , Masculino , Humanos , Torsión del Cordón Espermático/diagnóstico , Torsión del Cordón Espermático/cirugía , Estudios Transversales , Diagnóstico Tardío , Estudios Retrospectivos , China/epidemiología
18.
Sci Bull (Beijing) ; 68(21): 2607-2619, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37798178

RESUMEN

Epstein-Barr virus (EBV) is the oncogenic driver of multiple cancers. However, the underlying mechanism of virus-cancer immunological interaction during disease pathogenesis remains largely elusive. Here we reported the first comprehensive proteogenomic characterization of natural killer/T-cell lymphoma (NKTCL), a representative disease model to study EBV-induced lymphomagenesis, incorporating genomic, transcriptomic, and in-depth proteomic data. Our multi-omics analysis of NKTCL revealed that EBV gene pattern correlated with immune-related oncogenic signaling. Single-cell transcriptome further delineated the tumor microenvironment as immune-inflamed, -deficient, and -desert phenotypes, in association with different setpoints of cancer-immunity cycle. EBV interacted with transcriptional factors to provoke GPCR interactome (GPCRome) reprogramming. Enhanced expression of chemokine receptor-1 (CCR1) on malignant and immunosuppressive cells modulated virus-cancer interaction on microenvironment. Therapeutic targeting CCR1 showed promising efficacy with EBV eradication, T-cell activation, and lymphoma cell killing in NKTCL organoid. Collectively, our study identified a previously unknown GPCR-mediated malignant progression and translated sensors of viral molecules into EBV-specific anti-cancer therapeutics.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfoma , Células T Asesinas Naturales , Humanos , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Proteómica , Linfoma/complicaciones , Células T Asesinas Naturales/patología , Microambiente Tumoral/genética
19.
Cancer Cell ; 41(10): 1705-1716.e5, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37774697

RESUMEN

We report the results of GUIDANCE-01 (NCT04025593), a randomized, phase II trial of R-CHOP alone or combined with targeted agents (R-CHOP-X) guided by genetic subtyping of newly diagnosed, intermediate-risk, or high-risk diffuse large B cell lymphoma (DLBCL). A total of 128 patients were randomized 1:1 to receive R-CHOP-X or R-CHOP. The study achieved the primary endpoint, showing significantly higher complete response rate with R-CHOP-X than R-CHOP (88% vs. 66%, p = 0.003), with overall response rate of 92% vs. 73% (p = 0.005). Two-year progression-free survival rates were 88% vs. 63% (p < 0.001), and 2-year overall survival rates were 94% vs. 77% (p = 0.001). Meanwhile, post hoc RNA-sequencing validated our simplified genetic subtyping algorithm and previously established lymphoma microenvironment subtypes. Our findings highlight the efficacy and safety of R-CHOP-X, a mechanism-based tailored therapy, which dually targeted genetic and microenvironmental alterations in patients with newly diagnosed DLBCL.

20.
Nurs Open ; 10(11): 7368-7381, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37705181

RESUMEN

AIM: To explore the job demands of healthcare workers (HCWs) working in mobile cabin hospitals in Shanghai and identify the influencing factors. DESIGN: The study had a cross-sectional design. METHODS: Using the convenience sampling method, we selected 1223 HCWs (medical team members) working in these mobile cabin hospitals during April-May 2022. The findings of the general information questionnaire and the hierarchy scale of job demands of HCWs working in mobile cabin hospitals were used for the investigation. RESULTS: The total score of job demands of the included HCWs was 132.26 ± 9.53; the average score of the items was 4.73 ± 0.34. Multivariate linear regression analyses showed that the following HCWs had significantly higher job demands: female HCWs and HCWs who received psychological training or intervention during the COVID-19 pandemic, were satisfied with the doctor/nurse-patient relationship, received support from family members/friends/colleagues, believed that the risk of working in mobile cabin hospitals was high, had adapted to the working environment of mobile cabin hospitals and had college/undergraduate level of education. They would benefit from increased social support and better training in terms of psychological coping mechanisms(both theoretical knowledge and applicable skills) and COVID-19 prevention,control and treatment abilities.

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