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Heterochromatin, a key component of the eukaryotic nucleus, is fundamental to the regulation of genome stability, gene expression and cellular functions. However, the factors and mechanisms involved in heterochromatin formation and maintenance still remain largely unknown. Here, we show that insulin receptor tyrosine kinase substrate (IRTKS), an I-BAR domain protein, is indispensable for constitutive heterochromatin formation via liquidâliquid phase separation (LLPS). In particular, IRTKS droplets can infiltrate heterochromatin condensates composed of HP1α and diverse DNA-bound nucleosomes. IRTKS can stabilize HP1α by recruiting the E2 ligase Ubc9 to SUMOylate HP1α, which enables it to form larger phase-separated droplets than unmodified HP1α. Furthermore, IRTKS deficiency leads to loss of heterochromatin, resulting in genome-wide changes in chromatin accessibility and aberrant transcription of repetitive DNA elements. This leads to activation of cGAS-STING pathway and type-I interferon (IFN-I) signaling, as well as to the induction of cellular senescence and senescence-associated secretory phenotype (SASP) responses. Collectively, our findings establish a mechanism by which IRTKS condensates consolidate constitutive heterochromatin, revealing an unexpected role of IRTKS as an epigenetic mediator of cellular senescence.
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RATIONALE: Warthin tumor (WT) is the second most common benign tumor in salivary gland. It has a slow growth rate and most frequently occurs in the parotid gland. Most patients present with an incidental finding of a painless mass inferior/anterior to the ear. Besides the epithelial component of the tumor, WT is characteristically associated with lymphoid stroma that is considered benign. While there have been a few reports of malignant transformation of the lymphoid components in WT, cases of WT concomitant with mantle cell lymphoma (MCL) are extremely rare. To the best of our knowledge, two cases have been described in the English literature. Herein, we report a case of WT concomitant with MCL in a 70-year-old female patient, and emphasize the importance of careful examination of lymphoid stroma in WT so that concurrent lymphoma is not missed. PATIENT CONCERNS: A 70-year-old Chinese woman with a 40-year history of cigarette smoking presented with a one year history of a right submaxillary mass with recent enlargement. DIAGNOSIS: Cervical ultrasound (US) and computed tomography (CT) scans of the neck revealed a well-circumscribed mass in the right parotid with a maximum diameter of 3.1 cm. Surgical resection of the mass was performed. Histopathological examination revealed a characteristic double-layer of neoplastic epithelium with prominent lymphoid stroma, suggesting WT. In addition, morphology and immunohistochemistry studies confirmed the coexistence of MCL. Thereafter, the final diagnosis of this case was WT concomitant with MCL. INTERVENTIONS: The patient was staged as stage I after clinical assessment. Due to the slow growth of parotid lesions, close observation was decided with periodic clinical and radiological monitoring. OUTCOMES: Currently, the patient demonstrates a stable disease by clinical evaluation. LESSONS: To the best of our knowledge, reported cases of WT concomitant with MCL are very rare. This case highlights the importance of a comprehensive assessment of the lymphoid stroma of WT to avoid missed diagnosis of a lymphoma component in a collision tumor.
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Adenolinfoma , Linfoma de Células del Manto , Neoplasias de la Parótida , Humanos , Linfoma de Células del Manto/patología , Linfoma de Células del Manto/complicaciones , Linfoma de Células del Manto/diagnóstico , Femenino , Anciano , Adenolinfoma/patología , Adenolinfoma/complicaciones , Adenolinfoma/cirugía , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/complicaciones , Glándula Parótida/patología , Glándula Parótida/diagnóstico por imagen , Glándula Parótida/cirugíaRESUMEN
Sugar serves as the primary energy source for mammals, with glucose metabolism facilitating energy acquisition in human cells. The proper functioning of intracellular glucose metabolism is essential for the maintenance of orderly and healthy physiological activities. Tumor cells, characterized by uncontrolled growth, exhibit dysregulated proliferation and apoptosis processes, leading to abnormal alterations in glucose metabolism. Specifically, tumor cells exhibit a shift towards aerobic glycolysis, resulting in the production of lactic acid that can be utilized as a metabolic intermediate for sustained tumor cell growth. This article provides a comprehensive overview of the enzymes involved in glucose metabolism and the alterations in gene expression that occur during tumor progression. It also examines the current research on targeting abnormal glucose metabolism processes for tumor treatment and discusses potential future directions for utilizing glucose metabolism as a therapeutic target.
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Cardiovascular disease is one of the diseases with the highest morbidity and mortality rates worldwide, and coronary artery bypass grafting (CABG) is a fast and effective treatment. More researchers are investigating in artificial blood vessels due to the limitations of autologous blood vessels. Despite the availability of large-diameter vascular grafts (Ø > 6 mm) for clinical use, small-diameter vascular grafts (Ø < 6 mm) have been a challenge for researchers to overcome in recent years. Vascular grafts made of polyvinyl alcohol (PVA) and PVA-based composites have excellent biocompatibility and mechanical characteristics. In order to gain a clearer and more specific understanding of the progress in PVA vascular graft research, particularly regarding the preparation methods, principles, and functionality of PVA vascular graft, this article discusses the mechanical properties, biocompatibility, blood compatibility, and other properties of PVA vascular graft prepared or enhanced with different blends using various techniques that mimic natural blood vessels. The findings reveal the feasibility and promising potential of PVA or PVA-based composite materials as vascular grafts.
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As a globally prevalent disease, obesity leads to many chronic diseases, so it is important to develop safe and effective treatments with fewer side effects and lasting weight loss. In this study, we developed a biodegradable hyaluronic acid microneedle patch loaded with polydopamine nanoparticles and mirabegron, which directly acted on subcutaneous white adipose tissue, and then induced browning of white adipose tissue through mild photothermal therapy. The approach showed excellent browning-promoting ability and biocompatibility. It is noteworthy that the weight of untreated mice increased by 9%, while the weight of obese mice decreased by nearly 19% after photothermal treatment. In addition, when mirabegron was used in combination with photothermal therapy, the weight loss of obese mice was more significant, with a weight loss of about 22%. This microneedle patch exhibited attractive potential for body slimming.
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Acetanilidas , Obesidad , Tiazoles , Animales , Ratones , Ratones Obesos , Obesidad/tratamiento farmacológico , Pérdida de Peso , Ratones Endogámicos C57BLRESUMEN
Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60%participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10%participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.
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RATIONALE: Atypical thymic carcinoid tumor is an exceedingly rare thymic neuroendocrine tumor derived from the cells of neuroendocrine system. Misdiagnosis or delayed diagnosis may result in disease progression to advanced stages and eventually leads to a poor prognosis. It is therefore necessary to make a correct diagnosis and provide an adequate treatment. PATIENT CONCERNS: A 33-year-old Chinese male presented with numbness in bilateral lower extremities and general fatigue for a month. Chest computed tomography revealed a superior anterior mediastinal mass. Thymoma was initially considered, given the location of the mass and radiographic presentation. DIAGNOSIS: Microscopic findings showed that the tumor cells are arranged in pseudoepitheliomatous growth or irregular nested growth pattern in a background of fibroconnective tissue, with focal infiltration into adipose tissue. The chrysanthemum-like structure or beam-like structure seen often in typical carcinoid tumor was not identified in this case. The tumor cells are spindled or oval, with focal active mitosis. The immunohistochemical staining showed strong positivity for CD56, CgA and Syn, positivity for CK, ACTH, and TTF-1, negativity for Vimentin, and ki67 labeled proliferation index was up to 10% in focal areas. According to the radiological and pathological findings, the diagnosis of atypical thymic carcinoid was made. INTERVENTIONS: The patient underwent surgical resection of the mass. OUTCOME: No recurrence or metastasis was identified during the follow up. LESSONS: Because of its low incidencen, onspecific clinical symptoms, tissue location, and radiological findings, atypical thymic carcinoid tumor may sometimes be misdiagnosed as thymoma. Attention should be paid to avoid misdiagnosis.
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Síndrome de ACTH Ectópico , Tumor Carcinoide , Timoma , Neoplasias del Timo , Masculino , Humanos , Adulto , Timoma/patología , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/etiología , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/cirugía , Tumor Carcinoide/complicaciones , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/cirugíaRESUMEN
Despite the therapeutic response of ferroptosis in various tumors, ferroptosis resistance has been found in numerous studies, significantly hindering the progress of ferroptosis anti-tumor therapy. Herein, we propose a metal-rich cascade nanosystem (Simvastatin-HMPB-Mn@GOx) combined with the dual-pathway regulation of ferroptosis resistance and photothermal therapy for efficient tumor combination therapy. The manganese-bonded hollow mesoporous Prussian blue (HMPB-Mn) serves as the photothermal agent and metal donor, and dissociates multivalent metal ions Mn2+, Fe3+ and Fe2+ to consume glutathione and amplify the Fenton reaction. Glucose oxidase (GOx) absorbed serves as the converter to provide hydrogen peroxide (H2O2) for the cascade Fenton reaction, causing a high burst of hydroxyl radicals (ËOH) and lipid peroxidation. Simvastatin innovatively acts as a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) inhibitor to decrease the expression of coenzyme Q10 (CoQ10) and glutathione peroxidase 4 (GPX4), eventually defeating ferroptosis resistance. The nanosystem acted in both classical and non-classical ferroptosis pathways and showed significant ferroptosis- and hyperthermia-induced anti-tumor efficacy both in vitro and in vivo. Thus, this study offers a promising way for ferroptosis and phototherapy to achieve complete tumor regression.
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Ferroptosis , Neoplasias , Humanos , Peróxido de Hidrógeno , Terapia Combinada , Metales , Neoplasias/tratamiento farmacológico , Glucosa OxidasaRESUMEN
Early detection of skin pathologies with current clinical diagnostic tools is challenging, particularly when there are no visible colour changes or morphological cues present on the skin. In this study, we present a terahertz (THz) imaging technology based on a narrow band quantum cascade laser (QCL) at 2.8 THz for human skin pathology detection with diffraction limited spatial resolution. THz imaging was conducted for three different groups of unstained human skin samples (benign naevus, dysplastic naevus, and melanoma) and compared to the corresponding traditional histopathologic stained images. The minimum thickness of dehydrated human skin that can provide THz contrast was determined to be 50 µm, which is approximately one half-wavelength of the THz wave used. The THz images from different types of 50 µm-thick skin samples were well correlated with the histological findings. The per-sample locations of pathology vs healthy skin can be separated from the density distribution of the corresponding pixels in the THz amplitude-phase map. The possible THz contrast mechanisms relating to the origin of image contrast in addition to water content were analyzed from these dehydrated samples. Our findings suggest that THz imaging could provide a feasible imaging modality for skin cancer detection that is beyond the visible.
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RATIONALE: Endometrioid adenofibroma is a benign epithelial neoplasm of the ovary, most of which are often unilateral. The symptoms of endometrioid adenofibroma are often nonspecific and misleading. Therefore, a full understanding of the characteristics, diagnosis, and treatment methods of this disease is of great importance. In this study, we report a 34-year-old woman who was found with an unidentified mass on the right ovary during the physical examination 3 years ago with nosymptoms or signs. PATIENT CONCERNS: A 34-year-old Chinese female was found with an unidentified 6 cm mass on the right ovary for 3 years that presented with no symptoms or signs. DIAGNOSIS: Pelvic ultrasound revealed a 6 cm cystic solid mixed mass on the right ovary. Through histological and immunohistochemical examinations, the tumor mass was finally diagnosed as endometrioid adenofibroma of ovary. INTERVENTIONS: To confirm the diagnosis, the ovarian tumor was laparoscopically resected. OUTCOMES: The patient returned to hospital after 3 months with no recurrence or postoperative complications. LESSONS: Endometrioid adenofibroma is a benign epithelial neoplasm of the ovary. Complete surgical resection is required and rare cases can recur. Postsurgical pathologic and immunohistochemical testing can confirm a diagnosis of endometrioid adenofibroma. It is important to understand of the key points of differential diagnosis of the disease due to the different prognosis and clinical treatment.
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Adenofibroma , Neoplasias Glandulares y Epiteliales , Neoplasias Ováricas , Femenino , Humanos , Adulto , Neoplasias Ováricas/patología , Neoplasias Glandulares y Epiteliales/diagnóstico , Diagnóstico Diferencial , Adenofibroma/diagnóstico , Adenofibroma/patología , Adenofibroma/cirugíaRESUMEN
Blood coagulation is the body's main defense to bleeding caused by trauma and is divided into endogenous and exogenous pathways. Calcium ions play a very important role in the process of blood coagulation, as the ions activate the many enzymes that are required for coagulation. In this paper, gelatin hemostatic membranes containing calcium ions were prepared by electrospinning. The fibers were characterized with scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. The biocompatibility and coagulation processes using the calcium ion-containing gelatin fibrous membranes were evaluated in vitro with dynamic whole-blood coagulation tests, hemolysis tests, coagulation time tests, and platelet adhesion tests. It was demonstrated that the calcium ion-containing gelatin membranes had lower hemolysis rates and shorter clotting times than commercially available hemostatic sponges and hemostatic gauzes. In vivo hemostasis experiments were also conducted on the tail vein and liver of mice. Animal experiments demonstrated that the incorporation of calcium ions into the electrospun gelatin membranes promoted platelet aggregation, ensured adhesion of the electrospun membrane to the wound and reduced the bleeding volume and hemostasis time. The composite calcium ion-gelatin electrospun membranes exhibited good in vivo and in vitro hemostatic abilities and accelerated blood clotting by stimulating the coagulation pathway to promote platelet aggregation at the wounds and the formation of mature blood clots for a new approach for acute trauma treatment.
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Hemostáticos , Nanofibras , Trombosis , Ratones , Animales , Gelatina/química , Cloruro de Calcio , Calcio/farmacología , Hemólisis , Hemostasis , Hemostáticos/farmacología , Hemostáticos/química , Hemorragia , Iones/farmacologíaRESUMEN
Aim To explore the effects of ethanol extraction of Dysosma versipellis on the proliferation and apoptosis of renal clear cell carcinoma OS-RC-2 cells and the underlying mechanism. Methods After treated with Dysosma versipellis, the proliferation of OS-RC-2 cells was detected by the CCK-8 assay and clone formation assay. The migration rate of cells was detected by thewound healing assay and Transwell assay. The level of ROS was detected by the reactive oxygen detection kit. The common targets between Dysosma versipellis and ROS were obtained by the network pharmacology. The above common targets were analyzed by KEGG. The apoptosis rate and cell cycle were detected by the flow cytometry, and the key proteins of MAPK signaling pathway and the levels of apoptosis related proteins were measured by Western blot. Results The results showed that Dysosma versipellis significantly inhibited the cell viability and migration ability of 0S-RC-2 cells, and up-regulated the level of ROS. Network pharmacology analysis showed a total of 165 common targets between Dysosma versipellis and ROS. KEGG analysis of the common targets revealed that there were significant changes in the MAPK signaling pathway. The results of Western blot showed that after treated with Dysosma versipellis, the protein level of JNK and the ratio of p-ERK/ERK were down-regulated. Besides, the protein level of caspase-9 and Bcl-2 declined, while the levels of cleaved caspase-9 and Bax were promoted. The flow cytometry results showed that Dysosma versipellis could significantly promote the apoptosis rate,down-regulate the cells in Gl-phase,while up-regulate the cells in G2/M-phase. The results of the rescue experiment showed that co-administration of NAC and Dysosma versipellis could significantly reverse the cell viability and apoptosis rate, the level of apop-totic related proteins, as well as the protein levels of MAPK pathway,when compared to treated with Dysosma versipellis alone in OS-RC-2. Conclusion In summary, Dysosma versipellis may inhibit the MAPK signaling pathway via the changes in ROS,further promoting apoptosis rate and decline cell proliferation in OS-RC-2 cell line.
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The use of morphology to diagnose invasive mould infections in China still faces substantial challenges, which often leads to delayed diagnosis or misdiagnosis. We developed a model called XMVision Fungus AI to identify mould infections by training, testing, and evaluating a ResNet-50 model. Our research achieved the rapid identification of nine common clinical moulds: Aspergillus fumigatus complex, Aspergillus flavus complex, Aspergillus niger complex, Aspergillus terreus complex, Aspergillus nidulans, Aspergillus sydowii/Aspergillus versicolor, Syncephalastrum racemosum, Fusarium spp., and Penicillium spp. In our study, the adaptive image contrast enhancement enabling XMVision Fungus AI as a promising module by effectively improve the identification performance. The overall identification accuracy of XMVision Fungus AI was up to 93.00% (279/300), which was higher than that of human readers. XMVision Fungus AI shows intrinsic advantages in the identification of clinical moulds and can be applied to improve human identification efficiency through training. Moreover, it has great potential for clinical application because of its convenient operation and lower cost. This system will be suitable for primary hospitals in China and developing countries.
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"Saccharum complex" is a hypothetical group of species, which is supposed to be involved in the origin of modern sugarcane, and displays large genomes and complex chromosomal alterations. The utilization of restricted parents in breeding programs of modern cultivated sugarcane has resulted in a genetic blockage, which controlled its improvement because of the limited genetic diversity. The use of wild relatives is an effective way to broaden the genetic composition of cultivated sugarcane. Due to the infrequent characterization of genomes, the potential of wild relatives is diffused in improving the cultivated sugarcane. To characterize the genomes of the wild relatives, the genome size and phylogenetic relationships among eight species, including Saccharum spontaneum, Erianthus arundinaceus, E. fulvus, E. rockii, Narenga porphyrocoma, Miscanthus floridulus, Eulalia quadrinervis, and M. sinensis were evaluated based on flow cytometry, genome surveys, K-mer analysis, chloroplast genome sequencing, and whole-genome SNPs analysis. We observed highly heterozygous genomes of S. spontaneum, E. rockii, and E. arundinaceus and the highly repetitive genome of E. fulvus. The genomes of Eulalia quadrinervis, N. porphyrocoma, M. sinensis, and M. floridulus were highly complex. Phylogenetic results of the two approaches were dissimilar, however, both indicate E. fulvus displayed closer relationships to Miscanthus and Saccharum than other species of Saccharum complex. Eulalia quadrinervis was more closely related to M. floridulus than M. sinensis; E. arundinaceus differ significantly from Miscanthus, Narenga, and Saccharum, but was relatively close to Erianthus. We proved the point of E. rockii and E. fulvus should not be classified as one genus, and E. fulvus should be classified as the Saccharum genus. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03338-5.
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Gliomas are the most common malignant tumor in the brain. As with other tumors, the progression of glioma depends on intra-tumoral angiogenesis. However, the effect of angiogenesis on gliomas is still not fully understood. In this study, we developed an angiogenesis pathway score using Gene Set Variation Analysis (GSAV) in R to assess the status of intra-glioma angiogenesis in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA mRNAseq_325, CGGA mRNA-array), and GSE16011 datasets. We found that the angiogenesis pathway score not only accurately predicted the prognosis of glioma patients, but also accurately distinguished the malignant phenotype and immune characteristics of gliomas. In addition, as an independent prognostic factor, the score could predict glioma sensitivity to radiotherapy and chemotherapy. In summary, we used the angiogenesis pathway score to reveal the relationship between glioma angiogenesis and the malignant phenotype, immune characteristics, and prognosis of glioma.
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Neoplasias Encefálicas , Glioma , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica , Glioma/patología , Humanos , PronósticoRESUMEN
The high therapeutic resistance of tumor is the primary cause behind tumor recurrence and incurability. In recent years, scientists have devoted themselves to find a variety of treatments to solve this problem. Herein, we propose a multi-hit strategy that is based on the biodegradable hollow mesoporous Prussian blue (HMPB)-based nanosystem for tumor-specific therapy that encapsulated the critical heat shock protein 90 (HSP90) inhibitor 17-dimethylamino-ethylamino-17-demethoxydeldanamycin (17-DMAG). The nanosystem was further modified using thermotropic phase transition material star-PEG-PCL (sPP) and hyaluronic acid (HA), which offers near infrared light (NIR) responsive release characteristic, as well as enhanced tumor cell endocytosis. Upon cell internalization of 17-DMAG-HMPB@sPP@HA and under 808 nm laser irradiation, photothermal-conversion effect of HMPB directly kills cells using hyperthermia, which further causes phase transition of sPP to trigger release of 17-DMAG, inhibits HSP90 activity and blocks multiple signaling pathways, including cell cycle, Akt and HIF pathways. Additionally, the down-regulation of GPX4 protein expression by 17-DMAG and the release of ferric and ferrous ions from gradual degradation of HMPB in the endogenous mild acidic microenvironment in tumors promoted the occurrence of ferroptosis. Importantly, the antitumor effect of 17-DMAG and ferroptosis damage were amplified using photothermal effect of HMPB by accelerating release of ferric and ferrous ions, and reducing HSP90 expression in cells, which induced powerful antitumor effect in vitro and in vivo. This multi-hit therapeutic nanosystem helps provide a novel perspective for solving the predicament of cancer treatment, as well as a promising strategy for design of a novel cancer treatment nanoplatform.
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AIMS: Myeloid neoplasms occur in the setting of chronic lymphocytic leukaemia (CLL)/CLL-like disease. The underlying pathogenesis has not been elucidated. METHODS: Retrospectively analysed 66 cases of myeloid neoplasms in patients with CLL/CLL-like disease. RESULTS: Of these, 33 patients (group 1) had received treatment for CLL/CLL-like disease, while the other 33 patients (group 2) had either concurrent diagnoses or untreated CLL/CLL-like disease before identifying myeloid neoplasms. The two categories had distinct features in clinical presentation, spectrum of myeloid neoplasm, morphology, cytogenetic profile and clinical outcome. Compared with group 2, group 1 demonstrated a younger age at the diagnosis of myeloid neoplasm (median, 65 vs 71 years), a higher fraction of myelodysplastic syndrome (64% vs 36%; OR: 3.1; p<0.05), a higher rate of adverse unbalanced cytogenetic abnormalities, including complex changes, -5/5q- and/or -7/7q- (83% vs 28%; OR: 13.1; p<0.001) and a shorter overall survival (median, 12 vs 44 months; p<0.05). CONCLUSIONS: Myeloid neoplasm in the setting of CLL/CLL-like disease can be divided into two categories, one with prior treatment for CLL/CLL-like disease and the other without. CLL-type treatment may accelerate myeloid leukaemogenesis. The risk is estimated to be 13-fold higher in patients with treatment than those without. The causative agent could be attributed to fludarabine in combination with alkylators, based on the latency of myeloid leukaemogenesis and the cytogenetic profile.
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Leucemia Linfocítica Crónica de Células B , Leucemia Mieloide , Síndromes Mielodisplásicos , Trastornos Mieloproliferativos , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Síndromes Mielodisplásicos/patología , Estudios RetrospectivosRESUMEN
Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a "disease-compound-target-pathway" network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD_(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.
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Medicamentos Herbarios Chinos , Neoplasias , Animales , Medicamentos Herbarios Chinos/farmacología , Plomo , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Ratas , Transducción de SeñalRESUMEN
INTRODUCTION: Infantile leukemia encompasses a heterogeneous group which needs stratifying for treatment selection. METHODS: We collected 78 cases of infantile leukemia and retrospectively analyzed their clinicopathological data. RESULTS: Infantile leukemia featured a ratio of acute myeloid leukemia (AML) to B-lymphoblastic leukemia (B-ALL) of 1:2, with a better survival for AML than B-ALL (median survival 36 vs 24 months). When stratified by age, "early" infantile B-ALL (2-6 months) showed a high rate of KMT2A rearrangement (100%), similar to the rate seen in congenital B-ALL (1 month) (100%) and higher than seen in "late" infantile B-ALL (≥7 months) (68%). The three categories of infantile B-ALL exhibited an age-dependent increase in survival (median survival 8.5, 24, and >24 months, respectively). The age-dependent survival benefit remained after excluding the cases negative for KMT2A rearrangement. Conversely, infantile AML lacked an age-dependent pattern of survival. CONCLUSION: The clinical outcome of infantile leukemia depends on the type of leukemia. Given the age-dependent survival, infantile B-ALL can be divided into three subcategories.
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Leucemia Mieloide Aguda/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Femenino , Reordenamiento Génico , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Lactante , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Masculino , Proteína de la Leucemia Mieloide-Linfoide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Estudios RetrospectivosRESUMEN
RATIONALE: Pulmonary artery intimal sarcoma is a rare tumor with exceptionally high mortality and easily misdiagnosed as pulmonary thromboembolism pulmonary thromboembolism (PTE) due to the nonspecific clinical presentation and symptom. Misdiagnosis or untimely diagnosis makes the disease progress to an advanced stage and eventually leads to a poor prognosis. PATIENT CONCERNS: A 37-year-old Chinese female presented with chest tightness and dyspnea for 3âmonths. Echocardiography and chest computed tomography revealed an intraluminal obstruction of the pulmonary arteries. Tests of serum tumor makers showed slight elevation for carbohydrate antigen-125, and α-fetoprotein. PTE was suspected according to the radiological and laboratory findings. DIAGNOSIS: Microscopic findings of the presumed thrombus showed prominent myxoid and edematous background with atypical spindled cells and curvilinear vascularity. Immunohistochemical staining demonstrated that the atypical spindled cells were positive for vimentin but negative for CK, S100, SMA, desmin, CD68, STAT6, CD34, ß-catenin, ALK-p80, p53, and MDM2. According to the radiological and pathological findings, the diagnosis of fibrosarcoma of pulmonary artery was made. INTERVENTIONS: The patient underwent surgical resection and the mass was excised as completely as possible. OUTCOME: Follow-up information showed no evidence of recurrence or metastasis after 3âmonths postresection. LESSONS: Because of the low incidence rate, nonspecific clinical symptoms, and radiological findings, primary fibrosarcoma of the pulmonary artery is commonly misdiagnosed as PTE. Pathological examination is necessary to confirm the diagnosis.