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Linfoma de Células B Grandes Difuso , Neoplasias Primarias Múltiples , Humanos , Masculino , Anciano , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/genética , Linfoma de Células T/patología , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/genética , Intestino Delgado/patología , Ciclofosfamida/uso terapéutico , Vincristina/uso terapéutico , Doxorrubicina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Diagnóstico Diferencial , Prednisona/uso terapéuticoRESUMEN
The current version of Jing Xiao Chan Bao is believed to be the earliest medical book on gynecology remaining in China. It has three problems: formulae missing, lack of fluency in the text, and thus difficulties in proofreading and editing. These problems are still there because there are very few versions of Jing Xiao Chan Bao left in China and so it is difficult to do further studies to make comparisons. The Waseda University Library announced that the version they held was a handwritten. It provides a new version for further research of this book. This version was believed to be compiled and edited by Japanese scholars based on Medical Prescription Analogues (Yi Fang Lei Ju) and therefore appears to be similar to the South Song Dynasty version. Using archival research, it was found that in the version at Waseda University Library, the content organisation, the number of formulas, and the use of taboo words is different from those in the current version in China. In this sense, it is believed that this version is valuable and meaningful for archival and clinical research for traditional Chinese medicine.
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Medicina Tradicional China , China , Medicina Tradicional China/historia , Bibliotecas/historia , Universidades/historiaRESUMEN
BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.
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Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Mutación , Factores de Transcripción , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Masculino , Femenino , Persona de Mediana Edad , Factores de Transcripción/genética , Proteínas Cromosómicas no Histona/genética , Anciano , Proteína SMARCB1/genética , Adulto , Pronóstico , China , ADN Helicasas , Proteínas de Unión al ADN , Proteínas NuclearesRESUMEN
Objective: To investigate the characteristics of cytopenia and its impact on prognosis in patients with relapsed and refractory multiple myeloma (RRMM) after B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) immunotherapy therapy. Methods: Clinical data of 36 RRMM patients received BCMA CAR-T therapy at the First Affiliated Hospital of Nanjing Medical University from April 2017 to March 2023 were retrospectively collected. Among them, there were 17 males and 19 females, with an age [M (Q1, Q3)] of 62 (53, 67) years. The follow-up deadline was August 31, 2023, and the follow-up time [M (Q1, Q3)] was 33 (10, 30) months. The characteristics of cytopenia at different time points before lymphodepleting chemotherapy and after CAR-T cell infusion in all patients were analyzed. Kaplan-Meier method was used to compare the differences in progression-free survival (PFS) and overall survival (OS) in patients with different clinical characteristics. Single-cell sequencing analysis was used to analyze the changes in hematopoietic stem cells in three patients after CAR-T cell therapy. Results: The incidence of cytopenia after BCMA CAR-T cell therapy in 36 RRMM patients reached 100%. The incidence of neutropenia peaked on the 7th and 28th day after cell infusion with a biphasic pattern of change.Patients with all grade neutropenia reached 61.1% (22/36) and grade 3 or higher reached 33.3% (12/36) on the 7th day, while patients with all grade neutropenia reached 67.9% (19/28) and grade 3 or higher reached 28.6% (8/28) on the 28th day (P<0.001),respectively. The occurrence rate of lymphopenia reached a peak on the day of CAR-T cell infusion [97.2% (35/36) patients showed lymphopenia, while 80.6% (29/36) patients showed grade 3 or higher lymphopenia] (P<0.001).The incidence of all grade of thrombocytopenia and severe thrombocytopenia (grade 3 or higher) peaked on the 14th day after cell infusion, with the rates of 69.4% (25/36) and 30.6% (11/36) respectively, which had a prolonged duration(P<0.001). Even after 12 months, 40% (8/20) of patients still experienced thrombocytopenia.The incidence of anemia peaked on the 7th and 14th day after cell infusion, with a rate of 100% (36/36) (P<0.001). 50% (10/20) of patients still had anemia even 12 months after cell infusion. Kaplan-Meier survival analysis showed that patients with thrombocytopenia < grade 3 had undefined OS, while patients with thrombocytopenia ≥grade 3 had shorter OS [17 (95%CI: 2-32) months, χ2=4.154, P=0.042], indicating a poorer prognosis. However, there was no statistically significant difference in the relationship between other cytopenia and survival (all P>0.05). Single-cell sequencing analysis of bone marrow cells revealed decreased proliferation, increased apoptosis, and cell cycle arrest of hematopoietic stem cells after CAR-T cell infusion. Conclusions: All patients experienced varying degrees of cytopenia after receiving BCMA CAR-T cell infusion, and patients with thrombocytopenia ≥grade 3 had shorter OS and poorer prognosis.
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Citopenia , Linfopenia , Mieloma Múltiple , Neutropenia , Receptores Quiméricos de Antígenos , Trombocitopenia , Femenino , Humanos , Masculino , Anemia , Anticuerpos/uso terapéutico , Antígeno de Maduración de Linfocitos B/uso terapéutico , Mieloma Múltiple/terapia , Pronóstico , Receptores Quiméricos de Antígenos/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , AncianoRESUMEN
Objective: To investigate the therapeutic effect and prognostic value of oligoclonal bands (OB) in multiple myeloma (MM) patients after autologous stem cell transplant (ASCT). Methods: The data of 156 patients with MM who underwent ASCT after inductive treatment in the Department of Hematology, Jiangsu Provincial People's Hospital from December 2013 to February 2022 were retrospectively analyzed, including 91 males and 65 females. The median age was 56 (26, 71) years. Patients were divided into two groups according to OB formation after ASCT treatment, including OB group (n=60) and non-OB group (n=96). The last follow-up date was August 31, 2023, and the follow-up period was 42 (18, 117) months. The clinical baseline characteristics and efficacy of the two groups were compared. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups by Kaplan-Meier method. Cox risk regression modal was used to analyze the risk factors associated with prognosis. Results: There were no significant differences in age, type, stage, risk stratification, extramedullary disease (EMD), proportion of circulating plasma cells and induction therapy regimen between OB and non-OB groups (all P>0.05). The proportion of patients in OB group who achieved complete response (CR) or above after ASCT treatment was 93.3% (56/60), which was higher than that in non-OB group (80.2%, 77/96) (P=0.024). The negative rate of minimal residual disease (MRD) in OB group was 66.7% (40/60), which was higher than that in non-OB group (34.4%, 33/96) (P=0.001). The median PFS and OS in the OB group were not reached, and the median PFS and OS in the non-OB group were 28 (2, 80) months and 86 (2, 100) months, respectively. The PFS (P<0.001) and OS (P=0.017) of patients with OB were considerably longer. In the Cox multivariate analysis, OB was an independent prognostic factor for PFS in MM patients (HR=0.314, 95%CI: 0.153-0.644, P=0.002). Subgroup analysis showed that among high-risk patients with mSMART, the OS of patients in OB group was not reached, which was significantly better than that of non-OB group [71 (2, 90) months, P=0.046]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in standard risk group (not reached vs not reached, P=0.103). In those with EMD at diagnosis, patients with OB had significantly better OS than those with non-OB [not reached vs 47 (6, 74) months, P=0.037]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in those without EMD at diagnosis [not reached vs 86 (2, 100) months, P=0.130]. Conclusions: OB formation after ASCT treatment in MM patients is related to the efficacy and prognosis. OB formation can increase the negative MRD rate, prolong the OS and improve the prognosis, especially for newly diagnosed patients with extramedullary disease or patients with high-risk genetic characteristics.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Masculino , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Mieloma Múltiple/terapia , Mieloma Múltiple/diagnóstico , Resultado del Tratamiento , Bandas Oligoclonales/uso terapéutico , Estudios Retrospectivos , Trasplante Autólogo , Trasplante de Células MadreRESUMEN
Objective: To evaluate the prognostic value of Mayo MASS and R2-ISS staging systems in patients newly diagnosed with multiple myeloma (MM) . Methods: A total of 371 patients newly diagnosed with MM in Jiangsu Province Hospital were included in the study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was performed to detect cytogenetic abnormality. Clinical characteristics were combined to analyze the disease stage and evaluate the prognosis. Results: There were 37 (10.0%), 264 (71.0%), and 70 (18.8%) patients in R-ISS stage â , â ¡, and â ¢, respectively. The median progression-free survival (PFS) times were 37, 25, and 14 months (P<0.001). The median overall survival (OS) times were not reached (NR), 66, and 30 months (P<0.001). There were 71 (19.1%), 140 (37.7%), and 160 (43.2%) patients in Mayo MASS stages â , â ¡, and â ¢, and the median PFS times periods were 43, 27, and 19 months (P<0.001), and the median OS times were NR, NR, 35 months, respectively (P<0.001). There were, 23 (6.2%), 69 (18.6%), 222 (59.8%), and 57 (15.4%) patients in R2-ISS stages â , â ¡, â ¢, and â £, respectively. The median PFS times were 47, 31, 25, and 15 months (P=0.001), and the median OS times were NR, NR, 49, and 55 months, respectively (P<0.001) . Conclusion: Based on the R-ISS staging system, Mayo MASS, and R2-ISS prognostic staging system incorporated 1q21+, which allows a better stratification. However, the proportion of stage â ¢ patients in Mayo MASS and R2-ISS staging systems is relatively high, which is considered related to the high incidence of 1q21+ and ISS â ¢ in the Chinese population.
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Mieloma Múltiple , Humanos , Pronóstico , Mieloma Múltiple/diagnóstico , Hibridación Fluorescente in Situ , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
A concise review is given on the past two decades' results from laboratory experiments on collisionless magnetic reconnection in direct relation with space measurements, especially by the Magnetospheric Multiscale (MMS) mission. Highlights include spatial structures of electromagnetic fields in ion and electron diffusion regions as a function of upstream symmetry and guide field strength, energy conversion and partitioning from magnetic field to ions and electrons including particle acceleration, electrostatic and electromagnetic kinetic plasma waves with various wavelengths, and plasmoid-mediated multiscale reconnection. Combined with the progress in theoretical, numerical, and observational studies, the physics foundation of fast reconnection in collisionless plasmas has been largely established, at least within the parameter ranges and spatial scales that were studied. Immediate and long-term future opportunities based on multiscale experiments and space missions supported by exascale computation are discussed, including dissipation by kinetic plasma waves, particle heating and acceleration, and multiscale physics across fluid and kinetic scales.
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Objective: This study aimed to examine the relationship between low T3 syndrome (LT3S) and the prognosis of newly diagnosed multiple myeloma (NDMM) patients. Methods: A retrospective examination of 211 NDMM patients treated at the Department of Hematology, Jiangsu Provincial People's Hospital from July 2009 to December 2020 was performed, and all patients received thyroid function testing to determine if they had LT3S. We investigated the relationship between LT3S and clinical features, as well as its impact on MM prognosis. Results: Of the 211 patients, 119 were males, and 92 were females, with a median age of 60 (33-86) years. Patients with LT3S had significantly higher levels of ß(2)-microglobulin, C-reactive protein, and blood creatinine compared to those with normal T3 levels. They also had lower levels of hemoglobin, platelets, and serum albumin, as well as more advanced ISS stages (P<0.001) . Patients with LT3S had shorter progression-free survival (PFS) (16 months vs 30 months, P=0.003) and overall survival (OS) (57 months vs 75 months, P=0.004) than patients without LT3S. LT3S was found to be a standalone unfavorable factor in multivariate analysis, LT3S was an independent unfavorable factor in predicting both PFS (HR=2.114, 95% CI 1.271-3.516, P=0.004) and OS (HR=2.231, 95% CI 1.088-4.577, P=0.029) . Conclusions: Low T3 syndrome was an independent unfavorable prognostic predictor for NDMM.
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Síndromes del Eutiroideo Enfermo , Mieloma Múltiple , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Mieloma Múltiple/diagnóstico , Estudios Retrospectivos , PronósticoRESUMEN
Objective: To assess the efficacy of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of FLT3-ITD(+) acute myeloid leukemia (AML) with normal karyotype. Methods: The clinical data of FLT3-ITD(+) AML patients with normal karyotype in the First Affiliated Hospital of Nanjing Medical University from Jan 2018 to March 2021 were retrospectively analyzed. Results: The study included 49 patients with FLT3-ITD(+)AML, 31 males, and 18 females, with a median age of 46 (16-59) years old. All patients received induction chemotherapy, and 24 patients received sequential allo-HSCT (transplantation group) . The median follow-up time was 465 days, the one-year overall survival (OS) from diagnosis was (70.0 ± 7.4) %, and one-year disease-free survival (DFS) was (70.3±7.4) %. The one-year OS was significantly different between the transplantation group and the non-transplantation group [ (85.2 ± 7.9) % vs (52.6 ± 12.3) %, P=0.049]. but one-year DFS [ (84.7 ± 8.1) % vs (55.2 ± 11.9) %, P=0.061] was not. No significance was found in one-year OS between patients with low-frequency and high-frequency FLT3-ITD(+) (P>0.05) . There were 12 patients with high-frequency FLT3-ITD(+) in the transplantation and the non-transplantation groups, respectively. The one-year OS [ (68.8 ± 15.7) % in the transplantation group vs (26.2 ± 15.3) % in the non-transplantation group, P=0.027] and one-year DFS [ (45.5 ± 21.3) % in the transplantation group vs (27.8±15.8) % in the non-transplantation group, P=0.032] were significantly different between the two groups. Conclusion: Induction chemotherapy followed by allo-HSCT can enhance the prognosis of FLT3-ITD(+) patients, particularly those with FLT3-ITD high-frequency mutation.
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Quimioterapia de Inducción , Leucemia Mieloide Aguda , Trasplante Homólogo , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Femenino , Estudios Retrospectivos , Pronóstico , SobrevidaRESUMEN
Objective: This study aimed to investigate the influence of FGFR3 gene mutations on the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (NDMM) . Methods: A total of 198 patients with NDMM admitted to the Department of Hematology in Jiangsu Province Hospital between January 2016 and February 2023 were retrospectively analyzed. Next-generation sequencing and cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization were performed for all patients. The prognostic significance of FGFR3 mutation and clinical features were analyzed using the Log-rank test and Cox proportional hazards model. Results: Among 198 patients, 28 carried the FGFR3 gene mutation. These patients had significantly lower serum albumin levels, higher ß(2)-microglobulin levels, advanced Revised International Staging System stages, more frequent occurrence of t (4;14) , and shorter median progression-free survival (PFS) time (28 months vs 33 months, P=0.024) and overall survival (OS) time (54 months vs undefined, P=0.028) than patients without FGFR3 mutation. Additionally, patients carrying either FGFR3 mutation or t (4;14) had lower PFS (30 months vs 38 months, P=0.012) and OS (54 months vs undefined, P=0.017) than those without. The Cox proportional hazards model identified FGFR3 mutation as an independent risk factor for PFS and OS. Conclusion: FGFR3 gene mutation was an unfavorable independent prognostic predictor for NDMM.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Hibridación Fluorescente in Situ , Estudios Retrospectivos , Pronóstico , Mutación , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genéticaAsunto(s)
Neoplasias Trofoblásticas , Humanos , Femenino , Embarazo , Neoplasias Trofoblásticas/cirugíaRESUMEN
Magnetic reconnection has been observed in the transition region of quasi-parallel shocks. In this work, the particle-in-cell method is used to simulate three-dimensional reconnection in a quasi-parallel shock. The shock transition region is turbulent, leading to the formation of reconnecting current sheets with various orientations. Two reconnection sites with weak and strong guide fields are studied, and it is shown that reconnection is fast and transient. Reconnection sites are characterized using diagnostics including electron flows and magnetic flux transport. In contrast to two-dimensional simulations, weak guide field reconnection is realized. Furthermore, the current sheets in these events form in a direction almost perpendicular to those found in two-dimensional simulations, where the reconnection geometry is constrained.
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Objective: To investigate the longitudinal changes of white matter microstructural based on diffusion tensor imaging in parents who lost their only child without psychiatric disorders and its relationship with symptoms of posttraumatic stress disorder (PTSD). Methods: Parents who had who lost their only child and without psychiatric disorders in Jiangsu Province, from September 2016 to March 2017, were retrospectively collected (TENP group, 32). MRI scans were performed at baseline and at the end of 5-year follow-up, and the Clinician Administered PTSD Scales (CAPS) were used for assessing the severity of symptoms. Additionally, sex, age and education level matched healthy subjects were recruited as healthy controls (control group, 27) and underwent MRI scanning using the same protocol. The differences of fractional anisotropy (FA) values between TENP group and control group at baseline were analyzed by using Tract-based spatial statistics method, and the brain areas of lateral differences were used as the regions of interest for longitudinal follow-up analysis of TENP group. Partial correlation analysis was used to evaluate the relationship between FA values changes in longitudinal differences in brain regions and CAPS scores. Results: Compared with the control group, FA values of the right cingulate gyrus, Uncinate fasciculus, superior longitudinal fasciculus, corticospinal tract, Inferior fronto-occipital fasciculus, Inferior longitudinal fasciculus and forceps major in TENP group were decreased at baseline ((0.613±0.032) vs (0.631±0.034), (0.539±0.048) vs (0.563±0.045), (0.534±0.033) vs (0.558±0.039), (0.560±0.038) vs (0.580±0.030), (0.519±0.023) vs(0.549±0.024), (0.489±0.038) vs (0.518±0.027), (0.499±0.027) vs (0.533±0.032); all P<0.05). From baseline to follow-up, scores of trauma reexperience symptoms and avoidance/numbness symptoms were decreased ((5.2±2.8) vs (8.1±4.9), (4.0±3.2) vs (6.6±5.4); all P<0.05); FA values of the right corticospinal tract, Inferior fronto-occipital fasciculus, Inferior longitudinal fasciculus and forceps major were decreased ((0.523±0.049) vs (0.537±0.049), (0.568±0.052) vs (0.590±0.050), (0.540±0.063) vs (0.559±0.059), (0.520±0.059) vs (0.547±0.059); all P<0.05); The decrease of FA values of the right Inferior fronto-occipital fasciculus and right Inferior longitudinal fasciculus was negatively correlated with the decrease of avoidance/numbness symptoms scores (r=-0.458, -0.374, respectively, all P<0.05). Conclusions: The trauma of parents who lost their only child can result in impaired microstructural integrity of white matter. As the post-traumatic time goes by, parents who have lost their only child do not develop to PTSD and other psychiatric disorders, and the clinical symptoms are alleviated, the damage of the white matter microstructure continued to progress.
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Trastornos por Estrés Postraumático , Sustancia Blanca , Anisotropía , Encéfalo , Niño , Imagen de Difusión Tensora/métodos , Humanos , Hipoestesia , Hijo Único , Padres , Estudios RetrospectivosRESUMEN
Objective: To investigate the influence of the number of high-risk cytogenetic abnormalities (HRCA) on the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (MM) . Methods: A total of 360 patients with newly diagnosed MM admitted to Jiangsu Province Hospital between November 2013 and September 2020 were included in this study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was used to detect HRCA. Cytogenetic abnormalities were combined with clinical characteristics and outcomes for further analysis. Results: Among the 360 patients, 120 patients (33.3%) presented with no HRCAs, and 175 (48.6%) , 61 (16.9%) , and four (1.1%) patients had one, two, and three HRCA (s) , respectively. Patients were divided into three groups, including the no-HRCA group, one-HRCA group, and ≥two-HRCA group, according to the number of HRCAs. There were significant differences in the R-ISS stage, hemoglobin level, albumin level, and the proportion of bone marrow plasma cells among the three groups (P<0.05) . The COX proportional-hazards model identified extramedullary disease (P=0.018) , HRCA ≥ 2 (P=0.001) , and absence of autologous hematopoietic stem cell transplantation (P<0.001) as independent risk factors for progression free survival (PFS) and identified lactate dehydrogenase (LDH) level ≥ 220 U/L (P<0.001) , HRCA ≥2 (P=0.001) , and absence of autologous hematopoietic stem cell transplantation (P=0.005) as independent risk factors for overall survival (OS) . The median PFS was 28 months, 22 months, and 14 months (P=0.005) for the three cohorts, and their OS was not reached,60 months, and 30 months (P=0.001) , respectively. Conclusions: HRCA ≥ 2 is an independent risk factor for decreased survival in patients with newly diagnosed MM. More HRCAs result in heavier tumor burden, as well as a higher risk of disease progression and death.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Aberraciones Cromosómicas , Humanos , Hibridación Fluorescente in Situ , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Pronóstico , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
Under quasi-radial interplanetary magnetic fields (IMF), foreshock turbulence can have an impact on the magnetosheath and cusps depending on the location of the quasi-parallel shock. We perform three-dimensional simulations of Earth's dayside magnetosphere using the hybrid code HYPERS, and compare northward and southward quasi-radial IMF configurations. We study the magnetic field configuration, fluctuations in the magnetosheath and the plasma in the regions around the northern cusp. Under northward IMF with Earthward B x , there is a time-varying plasma depletion layer immediately outside the northern cusp. In the southward IMF case, the impact of foreshock turbulence and high-speed jets, together with magnetopause reconnection, can lead to strong density enhancements in the cusp.
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Objective: To investigate the in vitro inhibitory activity of a novel class â and â ¡b selective histone deacetylase (HDAC) inhibitor, purinostat mesylate (PM) , in diffuse large B-cell lymphoma and its mechanism. Methods: The 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide method was used to detect the effect of PM on cell proliferation. The effects of PM on cell cycle and apoptosis were detected by flow cytometry. The acetylation levels of HDAC substrate, cell cycle protein, apoptosis-related protein, and oncogene protein expression were detected by Western blot. Results: PM significantly inhibited the proliferation of lymphoma SUDHL-4 and SUDHL-6 cells and increased the acetylation levels of HDAC substrates H3, H4, and α-tubulin. In cell cycle experiments, PM induced G(0)/G(1) phase arrest in SUDHL-4 and SUDHL-6 cells. Western blot experiment showed that PM could significantly downregulate the expression of cyclin-dependent kinases Cdk2, Cdk4, Cdk6, cyclin D1, and cyclin E and upregulate the expression of CDK inhibitor protein p21. In the apoptosis experiment, PM could induce the apoptosis of SUDHL-4 and SUDHL-6 cells. Western blot experiment demonstrated that PM promoted endogenous apoptosis by activating caspase-3 kinase and affecting antiapoptotic protein Bcl-2. In addition, PM could downregulate the expression of oncogene marker proteins MYC, IKZF1, and IKZF3. Conclusion: PM has an efficient biological activity in vitro for diffuse large B-cell lymphoma, including double-hit lymphoma, and provides valuable experimental evidence for PM in clinical treatment.
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Inhibidores de Histona Desacetilasas , Linfoma de Células B Grandes Difuso , Humanos , Apoptosis , Proteínas de Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Histonas/farmacología , Histonas/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Mesilatos/farmacología , Mesilatos/uso terapéuticoAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Factor Estimulante de Colonias de Granulocitos , Etopósido/uso terapéutico , Ciclofosfamida/uso terapéutico , Células Madre Hematopoyéticas , Movilización de Célula Madre Hematopoyética , Trasplante Autólogo , Antígenos CD34RESUMEN
Objective: To study the risk factors associated with the hospital survival rate of elder patients with acute respiratory distress syndrome (ARDS) in Medical/Respiratory Intensive Care Units (MICUs/RICUs) by evaluating the prognosis, and therefore to provide insight into patient treatment strategy. Methods: Twenty MICUs/RICUs of 19 general hospitals in mainland China participated in the multicenter prospective cohort study carried out from Mar 1st, 2016 to Feb 28th, 2018. Patients who met the criteria of Berlin ARDS and older than 65 years were recruited. Baseline data, risk factors of ARDS, ventilator setup and prognosis data were collected from all patients. Univariant and multivariant regression analysis were conducted to analyze the factors associated with the prognosis. Results: 170 elder ARDS patients (age≥65 years) met the Berlin ARDS criteria, among whom 8.8% (15/170), 42.9% (73/170) and 48.2% (82/170) patients had mild, moderate and severe ARDS, respectively. The most common predisposing factor for elder ARDS was pneumonia, which was present in 134 patients (78.8%). 37.6% (64/170) patients were treated with noninvasive mechanical ventilation (NIV), but 43.8% (28/64) cases experienced treatment failure. 76.5% (130/170) patients were treated with invasive mechanical ventilation. All patients 80 years or older were given invasive mechanical ventilation. 51.8% (88/170) cases had complications of non-pulmonary organ failure. 61.8% (105/170) patients deceased during hospital stay. Multivariant logistic analysis showed that the independent risk factors for hospital survival rate in elder patients with ARDS were SOFA score (P=0.030, RR=0.725, 95% CI 0.543-0.969), oxygen index after 24 hours of ARDS diagnosis (P=0.030, RR=0.196, 95% CI 0.045-0.853), accumulated fluid balance within 7 days after diagnosis of ARDS (P=0.026, RR=1.000, 95% CI 1.000-1.000) and shock (P=0.034, RR=0.140, 95% CI 0.023-0.863). Conclusion: Among 20 ICUs, the high mortality rate of elder patients with ARDS was correlated with higher 24 hour SOFA score, lower 24 hour oxygen index after ARDS diagnosis, more positive fluid balance within 7 days and concomitant shock. The conservative fluid strategy within 7 days of ARDS diagnosis may benefit the elder ARDS patients.
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Síndrome de Dificultad Respiratoria , Anciano , Humanos , Pronóstico , Estudios Prospectivos , Respiración Artificial , Síndrome de Dificultad Respiratoria/epidemiología , Factores de RiesgoRESUMEN
Objective: To investigate sensitization rate of cow's milk in children, and explore its clinical features. Methods: This study enrolled a total of 818 patients under 18 years old with suspected food allergy who were admitted to the Allergy department in Beijing Shijitan Hospital during June 2018 to November 2020. The ImmunoCAP fluorescent enzyme-linked immunoassay system was used to quantify cow milk-specific immunoglobulin E (sIgE). Mild sensitization to cow's milk was defined as Radio-Allergo-Sorbent-Test (RAST) class 1, moderate sensitization was defined as class 2-3 and severe sensitization was class 4-6. Statistical methods such as χ2 test, independent sample t-test, one-way analysis of variance, and Spearman correlation analysis were used to retrospectively clarify differences of cow's milk sensitization rate between ages of children and elaborate its clinical features. Results: Overall sensitization rate of cow's milk reached 25.7% (210/818). Positive rate of cow milk sensitization (39.2%), cow milk sIgE levels [0.93 (0.52, 2.62)] kU/L, and moderate to severe sensitization rate (23.5%) were highest in infants aged between 0-3 years old. The sensitization rate and severity of sensitization declined with age. Most common clinical manifestation of cow milk sensitization was skin symptoms (50.0%), followed by respiratory symptoms (38.9%) and gastrointestinal symptoms (36.1%). Skin symptoms were the most common manifestation in 0-3 year-old group (47.3%), and respiratory symptoms were more common in 4-6 and 7-18 year-old groups (58.7%, 56.0%). Multiple-sensitization rate of patients with moderate to severe cow milk sensitization was 74.1%, most of which (70.4%) were co-sensitized by other food allergens, and 31.5% were co-sensitized by inhaled allergens. Conclusions: In population with age under 18 years old, infants aged between 0-3 years old suffered highest cow milk sensitization rate and increased sensitization severity. Then the severity decreased with age increasing. Patients with cow milk sensitization manifested skin symptoms most.