RESUMO
The popular formula Qiye Qingnian Powder, prescribed by Hua Tuo (BC145 - 208), is believed to "remove three kinds of worms, be conducive to the five main organs, keep fit, and prevent one's hair from turning gray". It is a representative formula in terms of "removing worms to prolong life" in traditional Chinese medicine. This paper focuses on "Qiye" in this formula, which plays an important role in removing worms, reviews its place in traditional Chinese medicine (TCM), Tibetan medicine, and Ayurvedic medicine and compares the concept of "removing worms" in Chinese and Ayurvedic medicine. It was found that the name and efficacy of Bhallataka in Ayurvedic medicine is related to "Qiye". It was also indicated that by comparing the concept of "worms" and the understanding of "removing worms" in traditional Chinese medicine and Ayurvedic medicine, in the theory of traditional medicines worms are the causative factor of diseases. Traditional Chinese medicine has rich connotations which involved medicinal concepts of Buddhism and Taoism and the idea of "removing worms to prolong life" is a unique contribution of traditional Chinese medicine to human health.
Assuntos
Ayurveda , Medicina Tradicional Chinesa , Ayurveda/história , Medicina Tradicional Chinesa/história , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/história , Humanos , PósRESUMO
BACKGROUND: Updated prevalence estimates along the continuum of Alzheimer's disease (AD) can foster a more nuanced and effective approach to managing AD within the current healthcare landscape. OBJECTIVES: This study aims to estimate the prevalence and severity distribution of dementia/AD (including mild, moderate, and severe stages) and all-cause mild cognitive impairment (MCI) in the United States using data from the Health and Retirement Study (HRS). DESIGN: Retrospective study. SETTING: Data from the bi-annual HRS surveys involving in-depth interviews of a representative sample of Americans aged >50 years. PARTICIPANTS: Dementia/AD and all-cause MCI patients from the 4 most recent HRS surveys (2014, 2016, 2018 and 2020). MEASUREMENTS: AD was identified based on diagnosis (self-report). Cognitive performance (modified Telephone Interview of Cognitive Status [TICS-m]) scores in the dementia/AD range were also captured; all-cause MCI was similarly identified using the TICS-m. Dementia/AD and MCI prevalence, as well as the distribution by dementia/AD stage (mild, moderate, or severe), were estimated. Sampling weights developed by HRS were applied to ensure the sample's representativeness of the target population and unbiased estimates for population parameters. RESULTS: Across the four HRS surveys, the total number of HRS respondents ranged from 15,000 to 21,000 (unweighted); 7,000 to 14,000 had TICS-m scores. The estimated prevalence of AD (all severity categories combined) in the 2014, 2016, 2018, and 2020 HRS surveys was 1.2%, 1.2%, 1.3% and 1.0%, respectively using the diagnosis-based approach; using the cognitive performance-based approach, 23-27% patients had scores in the dementia/AD ranges across the 4 surveys. The estimated prevalence of all-cause MCI was consistently 23% in each survey. In the 2020 survey, the distribution of mild, moderate, and severe disease stages was 34%, 45%, and 21%, respectively, in patients self-reporting an AD diagnosis, and 55%, 40%, and 5%, respectively in all patients meeting TICS-m threshold for dementia/AD. CONCLUSION: The prevalence of AD diagnosis based on self-report was approximately 1% across the 4 most recent HRS surveys and may reflect the proportion of patients who have actively sought healthcare for AD. Among HRS survey respondents with cognitive scores available, over 20% were in the dementia/AD range. The distribution of disease by stage differed for self-reported AD diagnosis vs dementia/AD based on cognitive scores. Discordance in estimates of dementia/AD and stage distributions underscores a need for better understanding of clinical practice patterns in AD diagnosis, use of clinical assessment tools, and severity classification in the United States. Accurate patient identification is needed, especially early in the AD disease continuum, to allow for timely and appropriate initiation of new anti-amyloid treatments.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Estados Unidos/epidemiologia , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/diagnóstico , Feminino , Idoso , Masculino , Prevalência , Estudos Retrospectivos , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/diagnóstico , Pessoa de Meia-Idade , Demência/epidemiologia , Demência/diagnóstico , Idoso de 80 Anos ou mais , Índice de Gravidade de Doença , Bases de Dados FactuaisRESUMO
Objective: To investigate the clinical characteristics and long-term prognostic factors of relapsed pediatric acute lymphoblastic leukemia (ALL). Methods: Clinical data including the age, time from initial diagnosis to relapse, relapse site, and molecular biological features of 217 relapsed ALL children primarily treated by the Chinese Children's Leukemia Group (CCLG)-ALL 2008 protocol in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between April 2008 and April 2015 were collected and analyzed in this retrospective cohort study. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. Results: The age at initial diagnosis of 217 relapsed patients was 5 (3, 7) years. There were 135 males and 82 females. The time from initial diagnosis to relapse of 217 children was 22 (10, 39) months. After relapse, 136 out of 217 children (62.7%) received treatment and the follow-up time was 65 (47, 90) months. The 5-year OS rate and EFS rate of the 136 relapsed children were (37±4) % and (26±4) %, respectively. The predicted 10-year OS rate and EFS rate were (35±5) % and (20±4) %, respectively. Univariate analysis showed that the 5-year OS rate in the group of patients with late relapse (43 cases) was significantly higher than those with very early (54 cases) and early relapse (39 cases) ((72±7)% vs. (16±5)%, (28±8)%, χ2=35.91, P<0.05), 5-year OS rate of the isolated extramedullary relapse group (20 cases) was significantly higher than isolated bone marrow relapse group (102 cases) and combined relapse group (14 cases) ((69±11)% vs. (31±5)%, (29±12)%, χ2=9.14, P<0.05), 5-year OS rate of high-risk group (80 cases) was significantly lower than standard-risk group (10 cases) and intermediate-risk group (46 cases) ((20±5)% vs. (90±10)%, (54±8)%, χ2=32.88, P<0.05). ETV6::RUNX1 was the most common fusion gene (13.2%, 18/136). The predicted 10-year OS rate of relapsed children with positive ETV6::RUNX1 was significantly higher than those without ETV6::RUNX1 (118 cases) ((83±9)% vs. (26±5)%, χ2=14.04, P<0.05). The 5-year OS for those accepted hematopoietic stem cell transplantation (HSCT) after relapse (42 cases) was higher than those without HSCT (94 cases) ((56±8)% vs. (27±5)%, χ2=15.18, P<0.05). Multivariate analysis identified very early/early relapse (HR=3.91, 95%CI 1.96-7.79; HR=4.15, 95%CI 1.99-8.67), bone marrow relapse including isolated bone marrow relapse and combined relapse (HR=6.50, 95%CI 2.58-16.34; HR=5.19, 95%CI 1.78-15.16), with ETV6::RUNX1 (HR=0.23, 95%CI 0.07-0.74) and HSCT after relapse (HR=0.24, 95%CI 0.14-0.43) as independent prognostic factors for OS (all P<0.05). Conclusions: Relapsed pediatric ALL mainly occurs very early and often affects bone marrow, which confer poor outcome. ETV6::RUNX1 is the most common genetic aberration with a favorable outcome. HSCT could rescue the outcome of relapsed children, though the survival rate is still poor.
RESUMO
Objective: To investigate the prognosis and related factors impacting renal response in newly diagnosed multiple myeloma (NDMM) patients with renal impairment. Methods: A total of 375 NDMM patients diagnosed at the Department of Hematology, the First Affiliated Hospital of Nanjing Medical University from August 2012 to April 2022 were retrospectively recruited. Patients were categorized into non-renal impairment group(n=273) and renal impairment group (n=102) according to renal function at initial diagnosis. All patients received≥2 cycles of bortezomib-based induction chemotherapy after admission. The hematological response included stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR) and stable disease (SD). The renal responses were defined as CR, PR, minor response (MR) and non-response (NR). General clinical data of the patients were collected, and patients were followed up by telephone. The follow-up deadline was December 3, 2022, and the median follow-up time [M (Q1, Q3)] was 42 (22, 61) months. Kaplan-Meier analysis was used to plot the survival curve. The log-rank test was utilized for inter-group comparisons. Multivariate logistic regression modeling facilitated the exploration of associated factors impacting renal response. Results: In the renal impairment group, there were 68 males and 34 females with a median age [M (Q1, Q3)] of 64 (58, 69) years. In the non-renal impairment group, there were 149 males and 124 females with a median age of 62 (54, 68) years. Compared with the renal impairment group, the age, lactate dehydrogenase and 24-hour urinary protein quantity were increased, the proportion of patients with light chain M protein and the proportion of patients at the DS-â ¢ stage, ISS-â ¢ stage and R-ISS-â ¢ stage were higher, the hemoglobin level and the proportion of patients receiving autologous hematopoietic stem cell transplantation were lower in the renal impairment group (all P<0.05). In 102 patients with renal impairment, renal responses of CR, PR, MR and NR were obtained in 53 (52.0%), 8 (7.9%), 18 (17.6%), 23 (22.5%) patients, respectively, and the overall response rate was 77.5% (79/102). Kaplan-Meier survival curve revealed that the median progression-free survival (PFS) was 24.0 (95%CI: 18.3-29.7) months in the renal impairment group, which was shorter than 31.0 (95%CI: 24.7-37.3) months in the non-renal impairment group (P=0.003). The median overall survival (OS) was 46.0 (95%CI: 36.5-55.5) months in the renal impairment group, which was shorter than 79.0 (95%CI: 59.9-98.1) months in the non-renal impairment group (P=0.002). Among the renal impairment group, patients with renal response of less than PR exhibited a median PFS of 19.0 (95%CI: 9.7-28.3) months, which was shorter than 28.0 (95%CI: 21.4-34.5) months for those achieving PR or better (P=0.048). The median OS was 31.0 (95%CI: 23.5-38.5) months in renal response with less than PR group, which was also worse than 57.0 (95%CI: 42.8-71.2) months for those who achieved PR or better (P=0.003). The results of multivariate logistic regression showed that hematological response achieving VGPR or better was a factor associated with renal response achieving PR (OR=4.20, 95%CI: 1.20-14.68, P=0.025). Conclusions: The prognosis of NDMM patients with renal impairment is poor. The hematological response with VGPR or better is related to the renal response achieving PR.
Assuntos
Mieloma Múltiplo , Insuficiência Renal , Humanos , Mieloma Múltiplo/complicações , Estudos Retrospectivos , Prognóstico , Bortezomib/uso terapêutico , Indução de Remissão , Rim/fisiopatologia , Quimioterapia de Indução , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
This article reported a case of an elderly female patient with diffuse lung lesions and multiple enlarged lymph nodes. In the early stages of diagnosis, many clues, obtained through cellular immunology and molecular biology tests on a variety of samples including blood and bronchoalveolar lavage fluid, pointed to the diagnosis of tuberculosis. At the same time, a peripheral lymph node biopsy was conducted, which led to the diagnosis of lymphoma coexisting with tuberculosis, a"dual-diagnosis". In the subsequent treatment, lymphoma therapy was actively pursued while the patient's tuberculosis infection was treated, with good results observed in the follow-up treatments. When diagnosing the disease, the differential diagnosis must be integrated into the overall disease process, and avoiding rigid adherence to a "unitary"diagnostic concept.
Assuntos
Linfonodos , Humanos , Feminino , Linfonodos/patologia , Diagnóstico Diferencial , Idoso , Pulmão/patologia , Pulmão/diagnóstico por imagem , Linfoma/diagnóstico , Linfoma/patologia , Tuberculose Pulmonar/diagnósticoRESUMO
Objective: To analyze the influence of operator's experience on the quality and success rate of root canal treatment with new nickel-titanium instruments, providing support for improving the success rate of root canal treatment with new nickel-titanium instruments in clinic. Methods: Cases of root canal treatment and non-surgical root canal retreatment with 6-12 months recall performed by residents (resident group) with experience of 1-3 years and endodontic specialists (specialist group) with experience of 5-7 years were collected from the electronic medical system of the Department of Endodontics, School of Stomatology, Capital Medical University, from September 2020 to August 2021. All cases were prepared by engine-driven glide path files and controlled memory nickel-titanium finishing files. Chi-square test and logistic regression were used to analyze the differences and influencing factors of complications, filling quality and success rate of root canal treatment between the two groups. Results: A total of 277 cases performed by 24 residents and 3 specialists were included, 169 in the resident group and 108 in the specialist group. The clinical incidence of flare-ups was significantly higher in the resident group [3.6% (6/169)] than in the specialist group [0(0/108)] (P=0.048). There were no significant differences in ledges, root canal transportations, perforations, or instrument separations between the two groups (P>0.05). The prevalence of satisfactory fillings was 62.7% (106/169) in the resident group, which was significantly lower than that in the specialist group [86.1% (93/108)] (P<0.05). The success rate of root canal treatment was 91.7% (155/169) and 94.4% (102/108) in the resident group and the specialist group, respectively, with no significant differences (χ2=0.73,P=0.392). Multivariate analysis showed that the success rate of root canal treatment was related to complications and quality of root fillings (P<0.05). Conclusions: Higher success rate of root canal treatment could be achieved by residents and endodontic specialists with engine-driven glide path files and controlled memory nickel-titanium files.
RESUMO
1. Abdominal fat deposition (AFD) is regulated by multiple intestinal tissues, and changes in the function of intestinal tissues are associated with AFD. Currently, integration of transcriptomic data across multiple intestinal tissues to explore excessive AFD has rarely been reported in broilers.2. In this study, a consensus gene co-expression network across the duodenum, jejunum, ileum and caecum of high- and low-abdominal fat broiler lines (HL and LL) was constructed using a publicly available transcriptomic data set. Combining the results of functional enrichment analyses and differential gene expression analyses, this investigated the genes and biological pathways across the four intestinal tissues that might influence AFD.3. In one expression module, NDUFA5, NDUFS6, NDUFA4, NDUFS4, ATP5H, ATP5J and ATP5C1 were significantly enriched in the oxidative phosphorylation pathway, with GPX2 and GSR significantly enriched in the glutathione metabolism pathway. These genes were significantly downregulated in the four intestinal tissues of the HL compared to LL chickens, which may be associated with AFD by increasing intestinal permeability.4. Lipid metabolism relevant genes were identified in other modules (ALDH7A1, ACSBG1, THEM4 and DECR1), which may be linked to AFD through regulation of lipid metabolism. Interestingly, in the first module, 12 genes were significantly enriched in the proteasome pathway and significantly downregulated in the four intestinal tissues in HL birds compared to LL birds, indicating a link between the proteasome and AFD.
RESUMO
Caries is an infectious disease in which the invasion of pathogens and their metabolites can activate the recognition and defense system of the pulpodentinal complex. In-depth understanding of the immune responses mediated by the pulpodentinal complex will help to estimate the real state of the dental pulp during the progression of caries and to take reasonable clinical treatment strategies, which can be more targeted and less invasive. Based on the physiology of the pulpodentinal complex, the present article introduce its immunocompetence and mechanism, reactive changes, clinical intervention and its significance during the caries progression, as to improve diagnostics as well as treatment strategies for caries.
Assuntos
Cárie Dentária , Polpa Dentária , Progressão da Doença , Cárie Dentária/imunologia , Humanos , Polpa Dentária/imunologiaRESUMO
Objective: To measure and compare the difference of personal attenuation rating (PAR) of the workers wearing foam earplugs before and after the training, and to evaluate the effect of ear protector wearing training on the noise protection. Methods: In February 2023, 94 workers exposed to noise in a machinery manufacturing factory were selected as subjects. The production noise in the workplace was measured and subjects were trained to wear earplugs. The PAR values of wearing 3M 1110 foam test earplugs were measured and recorded before and after the training by using the fit testing of hearing protection device. The differences between the actual PAR values with nominal values and the noise attenuation values in related standards were compared, and the protective effect of hearing protection device before and after training was evaluated. Results: The average age of the subjects was (36.76±11.48) years old, the average length of service was (16.34±11.64) years, and the average exposure time to noise was (15.67±11.64) years. The noise detection results of the subjects' posts were ranged from 80.1 to 94.3 dB (A). The results of subjects wore 3M 1110 foam test earplugs for fit testing showed that the binaural PAR value after training was (19.3±6.4) dB (A), which was significantly higher than that before training (11.1±7.4) dB (A) (t=13.31, P<0.001). After training, 11 people (11.70%) could reach the corrected noise reduction value (NRR value), 26 people (27.66%) could reach the standard of single noise reduction value (SNR value) ×0.6, and 84 people (89.36%) could reach the standard of (NRR-7) /2. The under protection rate of hearing protectors after training (7.45%) was significantly lower than that before training (45.74%), and the difference of different protection levels before and after training was statistically significant (χ(2)=40.83, P<0.001) . Conclusion: It is suggested that enterprises should use the fit testing instead of nominal value estimation to evaluate the noise reduction effect of hearing protection device. Special training on the selection and use of hearing protection device should be strengthened, so as to ensure that workers wear them correctly and improve the protective effect of hearing protection device.
Assuntos
Dispositivos de Proteção das Orelhas , Perda Auditiva Provocada por Ruído , Ruído Ocupacional , Exposição Ocupacional , Humanos , Ruído Ocupacional/prevenção & controle , Ruído Ocupacional/efeitos adversos , Adulto , Exposição Ocupacional/prevenção & controle , Perda Auditiva Provocada por Ruído/prevenção & controle , Masculino , Pessoa de Meia-Idade , Feminino , Local de TrabalhoRESUMO
POEMS syndrome is a rare plasma cell dysplasia. Its clinical manifestations include polyneuropathy, monoclonal protein, increased extravascular volume load, endocrinopathy, organomegaly and skin changes. The complex and atypical symptoms at presentation make early diagnosis challenging due to multiple system involvement. Peripheral neuropathy, limb numbness, is the most common initial symptom of this disease. However, case reports of increased extravascular volume load are rare. This article collected and analyzed the clinical data of two groups of patients with different initial symptoms (increased extravascular volume load and limb numbness). The clinical characteristics and treatment responses were summarized.
Assuntos
Síndrome POEMS , Humanos , Síndrome POEMS/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , IdosoRESUMO
BACKGROUND: LARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection. METHODS: Sequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome. RESULTS: Our study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer. CONCLUSIONS: Our study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , Neoplasias Retais , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Feminino , Masculino , Neoplasias Retais/patologia , Neoplasias Retais/metabolismo , Neoplasias Retais/genética , Neoplasias Retais/tratamento farmacológico , Quimioterapia Adjuvante , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Pessoa de Meia-Idade , Animais , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Proliferação de Células/efeitos dos fármacos , Receptor Notch1/metabolismo , Receptor Notch1/genética , Proteínas dos Microfilamentos/metabolismo , Proteínas dos Microfilamentos/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacosRESUMO
In recent years, the application of minimal residual disease (MRD) in solid tumors has gained widespread attention. MRD typically refers to the presence of residual cancer cells that remain undetectable by imaging after curative treatments, such as surgical resection. The presence of MRD post-surgery is significantly associated with an increased risk of tumor recurrence. In colorectal cancer, circulating tumor DNA (ctDNA) serves as an effective marker for assessing MRD, particularly in non-metastatic (stages I-III) colorectal cancer. As a real-time, accurate, and convenient biomarker, ctDNA can effectively predict tumor recurrence, guide postoperative adjuvant chemotherapy decisions, and provide crucial information for recurrence monitoring. The application prospects of ctDNA detection technology are vast, promising more precise and individualized treatment plans for colorectal cancer patients. This article comprehensively analyzes the progress in the application of ctDNA for detecting MRD in non-metastatic colorectal cancer patients, elaborates on its guiding role in clinical treatment decisions, and envisions the future development directions in this field.
Assuntos
DNA Tumoral Circulante , Neoplasias Colorretais , Neoplasia Residual , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , DNA Tumoral Circulante/sangue , Recidiva Local de Neoplasia , Biomarcadores Tumorais , Quimioterapia AdjuvanteRESUMO
Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [M (Q1, Q3)] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P>0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P=0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference (P=0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission (OR=0.126, 95%CI: 0.025-0.629). FLT3 mutation was not conducive to morphological remission (OR=5.832, 95%CI: 1.778-19.124) and negative MRD (OR=4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Compostos Bicíclicos Heterocíclicos com Pontes , Citarabina , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Criança , Masculino , Feminino , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Indução de Remissão , Adolescente , Daunorrubicina/administração & dosagem , Daunorrubicina/uso terapêutico , Quimioterapia de Indução , Mepesuccinato de Omacetaxina/administração & dosagem , Mepesuccinato de Omacetaxina/uso terapêutico , Estudos ProspectivosRESUMO
Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022. Methods: A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed. Results: â The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. â¡Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade â ¡-â £ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. â¢The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype (P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points (P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade â ¡-â £ (P<0.001, HR=5.94, 95% CI 3.50-10.10). â£The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% -80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively (P=0.690) . Conclusion: Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade â ¡-â £ acute gastrointestinal GVHD as independent risk factors affecting the patient's OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/terapia , Pessoa de Meia-Idade , Adulto , Masculino , Feminino , Prognóstico , Estudos Retrospectivos , Adolescente , Adulto Jovem , Idoso , Taxa de Sobrevida , Doença Enxerto-Hospedeiro/etiologiaRESUMO
OBJECTIVE: To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone (5-HDF), a compound extracted from Elsholtzia blanda Benth., against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action. METHODS: 5-HDF was extracted from Elsholtzia blanda Benth. using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses. In an A549 cell model of H1N1 influenza virus infection (MOI=0.1), the cytotoxicity of 5-HDF was assessed using MTT assay, and its effect on TRAIL and IL-8 expressions was examined using flow cytometry; Western blotting was used to detect the expression levels of inflammatory, apoptosis, and ferroptosis-related proteins. In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 µL H1N1 virus at the median lethal dose, the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight, lung index, gross lung anatomy and lung histopathology were observed. RESULTS: 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 µg/mL. In H1N1-infected A549 cells, treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65, lowered the expressions of IL-8, enhanced the expression of anti-ferroptosis proteins (SLC7A11 and GPX4), and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL. In H1N1-infected mice, treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies. CONCLUSION: 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis, inflammatory responses, and apoptosis via upregulating SLC7A11 and GPX4, inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK, and decreasing the expression of cleaved caspase3 and cleaved PARP.
Assuntos
Ferroptose , Flavonas , Inflamação , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Humanos , Células A549 , Camundongos , Animais , Ferroptose/efeitos dos fármacos , Flavonas/farmacologia , Apoptose/efeitos dos fármacos , Interleucina-8/metabolismo , Pulmão/patologia , Lamiaceae/química , Infecções por Orthomyxoviridae/tratamento farmacológico , Fator de Transcrição RelA/metabolismo , Caspase 3/metabolismoRESUMO
Objective: Exploring gene-age interactions associated with breast cancer prognosis based on epigenomic data. Methods: Differential expression analysis of DNA methylation was conducted using multiple independent epigenomic datasets of breast cancer from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The false discovery rate (FDR) method was used for multiple corrections, retaining differentially methylated sites with q-FDR≤0.05. A three-stage analytic strategy was implemented, using a multivariable Cox proportional hazards regression model to examine gene-age interactions. In the discovery phase, signals with q-FDR ≤ 0.05 were screened out using TCGA-BRCA database. In validation phaseâ , the interaction was validated using GSE72245 data, with criteria of P≤0.05 and consistent effect direction. In validation phaseâ ¡, the signals were further validated using GSE37754 and GSE75067 data. A prognostic prediction model was constructed by incorporating clinical indicators and interaction signals. Results: The three-stage analytic strategy identified a methylation site (cg16126280EBF1), which interacted with age to jointly affect the overall survival time of patients (interaction HR= 1.001 1,95%CI:1.000 7-1.001 5,P<0.001). Stratified analysis by age showed that the effect of hypermethylation of cg16126280EBF1 was completely opposite in younger patients (HR=0.550 5, 95%CI: 0.383 8-0.789 6, P=0.001) and older patients (HR=2.166 5, 95%CI: 1.285 2-3.652 2, P=0.004). Conclusions: The DNA methylation site cg16126280EBF1 exhibits an interaction with age, jointly influencing the prognosis of breast cancer in a complex association pattern. This finding contributes new population-based evidence for the development of age-specific targeted drugs.
Assuntos
Neoplasias da Mama , Metilação de DNA , Epigenômica , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Feminino , Prognóstico , Fatores Etários , Modelos de Riscos Proporcionais , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Bases de Dados Genéticas , Pessoa de Meia-IdadeRESUMO
Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10(8)/kg, and the number of CD34(+) cells was 3.29 (2.53-6.10) ×10(6)/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.