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Acute myeloid leukemia (AML) can manifest as de novo AML (dn-AML) or secondary AML (s-AML), with s-AML being associated with inferior survival and distinct genomic characteristics. The underlying reasons for this disparity remain to be elucidated. In this multicenter study, next-generation sequencing (NGS) was employed to investigate the mutational landscape of AML in 721 patients from June 2020 to May 2023.Genetic mutations were observed in 93.34% of the individuals, with complex variations (more than three gene mutations) present in 63.10% of them. TET2, ASXL1, DNMT3A, TP53 and SRSF2 mutations showed a higher prevalence among older individuals, whereas WT1 and KIT mutations were more commonly observed in younger patients. BCOR, BCORL1, ZRSR2, ASXL1 and SRSF2 exhibited higher mutation frequencies in males. Additionally, ASXL1, NRAS, PPMID, SRSF2, TP53 and U2AF1 mutations were more common in patients with s-AML, which PPM1D was more frequently associated with therapy-related AML (t-AML). Advanced age and hyperleukocytosis independently served as adverse prognostic factors for both types of AML; however, s-AML patients demonstrated a greater number of monogenic adverse prognostic factors compared to dn-AML cases (ASXL1, PPM1D, TP53 and U2AF1 in s-AML vs. FLT3, TP53 and U2AF1 in dn-AML). Age and sex-related gene mutations suggest epigenetic changes may be key in AML pathogenesis. The worse prognosis of s-AML compared to dn-AML could be due to the older age of s-AML patients and more poor-prognosis gene mutations. These findings could improve AML diagnosis and treatment by identifying potential therapeutic targets and risk stratification biomarkers.
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BACKGROUND: The immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is crucial for preventing infections and relapse and enhancing graft-versus-tumor effects. B cells play an important role in humoral immunity and immune regulation, but their reconstitution after allo-HSCT has not been well studied. METHODS: In this study, we analyzed the dynamics of B cells in 252 patients who underwent allo-HSCT for 2 years and assessed the impact of factors on B-cell reconstitution and their correlations with survival outcomes, as well as the development stages of B cells in the bone marrow and the subsets in the peripheral blood. RESULTS: We found that the B-cell reconstitution in the bone marrow was consistent with the peripheral blood (p = 0.232). B-cell reconstitution was delayed by the male gender, age >50, older donor age, the occurrence of chronic and acute graft-versus-host disease, and the infections of fungi and cytomegalovirus. The survival analysis revealed that patients with lower B cells had higher risks of death and relapse. More importantly, we used propensity score matching to obtain the conclusion that post-1-year B-cell reconstitution is better in females. Meanwhile, using mediation analysis, we proposed the age-B cells-survival axis and found that B-cell reconstitution at month 12 posttransplant mediated the effect of age on patient survival (p = 0.013). We also found that younger patients showed more immature B cells in the bone marrow after transplantation (p = 0.037). CONCLUSION: Our findings provide valuable insights for optimizing the management of B-cell reconstitution and improving the efficacy and safety of allo-HSCT.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Feminino , Humanos , Masculino , Transplante Homólogo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/epidemiologia , Linfócitos B , RecidivaRESUMO
BACKGROUND: Abnormally expressed BCR/ABL protein serves as the basis for the development of chronic myeloid leukaemia (CML). The F-actin binding domain (FABD), which is a crucial region of the BCR/ABL fusion protein, is also located at the carboxyl end of the c-ABL protein and regulates the kinase activity of c-ABL. However, the precise function of this domain in BCR/ABL remains uncertain. METHODS: The FABD-deficient adenovirus vectors Ad-BCR/ABLâ³FABD, wild-type Ad-BCR/ABL and the control vector Adtrack were constructed, and 32D cells were infected with these adenoviruses separately. The effects of FABD deletion on the proliferation and apoptosis of 32D cells were evaluated by a CCK-8 assay, colony formation assay, flow cytometry and DAPI staining. The levels of phosphorylated BCR/ABL, p73, and their downstream signalling molecules were detected by western blot. The intracellular localization and interaction of BCR/ABL with the cytoskeleton-related protein F-actin were identified by immunofluorescence and co-IP. The effect of FABD deletion on BCR/ABL carcinogenesis in vivo was explored in CML-like mouse models. The degree of leukaemic cell infiltration was observed by WrightâGiemsa staining and haematoxylin and eosin (HE) staining. RESULTS: We report that the loss of FABD weakened the proliferation-promoting ability of BCR/ABL, accompanied by the downregulation of BCR/ABL downstream signals. Moreover, the deletion of FABD resulted in a change in the localization of BCR/ABL from the cytoplasm to the nucleus, accompanied by an increase in cell apoptosis due to the upregulation of p73 and its downstream proapoptotic factors. Furthermore, we discovered that the absence of FABD alleviated leukaemic cell infiltration induced by BCR/ABL in mice. CONCLUSIONS: These findings reveal that the deletion of FABD diminished the carcinogenic potential of BCR/ABL both in vitro and in vivo. This study provides further insight into the function of the FABD domain in BCR/ABL.
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Apoptose , Proliferação de Células , Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Animais , Humanos , Camundongos , Apoptose/genética , Actinas/metabolismo , Carcinogênese/genética , Domínios Proteicos , Linhagem Celular TumoralRESUMO
INTRODUCTION: DNA methylation regulates gene transcriptional functions in the pathogenesis of malignant diseases. In prostate cancer, several tumor suppressors are known to be tumor specifically methylated. METHODS: In this study, 450K methylation data and mRNA expression data were accessed from The Cancer Genome Atlas-Prostate Adenocarcinoma database and analyzed bioinformatically. Methylation-specific PCR was used to examine the methylation condition in AOX1 promoter. qRT-PCR was applied to measure the mRNA expression of AOX1. Western blot was employed to detect the expressions of AOX1 and the EMT associated proteins. Transwell and scratch healing assays were used to examine the invasive and migratory abilities of the prostate cancer cells respectively. RESULTS: AOX1 was lowly expressed and hypermethylated in the prostate cancer tissues and cells. Also, AOX1 was downregulated at protein level in prostate cancer cells. Knocking down AOX1 could promote cell migration and invasion in the prostate cancer cells. By using a DNA methylation inhibitor, 5-AzadC was found to promote the expression of AOX1 and reverse the promoting effects of short interfering RNA against AOX1 on cell migration and invasion. CONCLUSION: This study suggested that DNA methylation and low AOX1 level might be biomarkers for prostate cancer.
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Metilação de DNA , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Movimento Celular/genética , Próstata/patologia , RNA Mensageiro , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Aldeído Oxidase/genética , Aldeído Oxidase/metabolismoRESUMO
PURPOSE: To investigate the safety and efficacy of ultrasound-guided renal access and tract dilation using balloon dilators, as well as to identify suitable patients for this technique. METHODS: Consecutive patients undergoing ultrasound-guided PCNL using balloon dilators between December 2019 and June 2020 in seven large medical centers from China were prospectively enrolled. Demographic and perioperative parameters of the patients were collected. Logistic regression analysis was used to analyze factors that would affect the success rate of tract establishment using ultrasound-guided renal access and balloon dilation. RESULTS: A total of 170 patients were included in this study, among whom, 91.18% of the (155/170) patients had a successful tract establishment under ultrasound guidance on the first attempt. The stone-free rate was 83.5% and postoperative complications occurred in 14 patients (8.23%). In univariate analysis, history of ipsilateral surgery (p = 0.026), and stone diameter (p = 0.01) were significantly associated with tract establishment failure, while a larger width of the target calyx (p = 0.016) and the presence of hydronephrosis (p = 0.001) were significantly associated with a successful tract establishment. In multivariate analysis, only hydronephrosis in target calyx (p = 0.027) was a favorable factor for successful tract establishment, and the history of ipsilateral renal surgery (p = 0.012) was the only independent risk factor for failure of tract establishment. CONCLUSION: It was safe and effective to establish percutaneous renal access with balloon dilation under whole-process ultrasound monitoring during PCNL. Furthermore, patients with a hydronephrotic target calyx and without history of ipsilateral renal surgery were most suited to this technique. Trial registration CHiCTR1800014448.
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Hidronefrose , Cálculos Renais , Nefrostomia Percutânea , Dilatação/métodos , Humanos , Hidronefrose/diagnóstico por imagem , Hidronefrose/cirurgia , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Nefrostomia Percutânea/métodos , Decúbito Ventral , Ultrassonografia de IntervençãoRESUMO
Objective: To evaluate the modified Zhang's 'three-level' technique of retroperitoneal laparoscopic adrenalectomy (RLA) to treat adrenal lesions for patients with BMI of 25-30 Kg/m2. Methods: A retrospective analysis was performed in all patients with BMI of 25-30 Kg/m2 in our hospital from January 2014 to December 2019. Those who underwent laparoscopic adrenal surgery were divided into two groups on the basis of the technique used: the Zhang's technique (the ZT group) and the modified technique (the MT group). Results: Herein, 170 operations were included (ZT, 91 patients; MT, 79 patients). RLA was successfully performed in all of them. Compared with the ZT group patients, the MT group patients showed shorter operation time (p = 0.007), lesser intraoperative blood loss (p = 0.023), shorter operation time, earlier postoperative diet recovery (p < 0.001), shorter postoperative drainage time (p < 0.001) and shorter postoperative hospitalization period (p = 0.001). It was also worth noting that the unplanned total adrenalectomy rate was significantly less in the MT group than in the ZT group (0% vs. 10.8%, p = 0.020). There was no significant difference in the complications between the two groups (3.3% vs. 2.5%, p = 0.567). Conclusions: We found that MT was a beneficial retroperitoneal laparoscopic treatment for adrenal lesions in patients who had a BMI of 25-30 Kg/m2. It may provide a reference for the treatment of adrenal surgical diseases in such patients.
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Doenças das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Laparoscopia/métodos , Sobrepeso/complicações , Doenças das Glândulas Suprarrenais/complicações , Adrenalectomia/efeitos adversos , Adulto , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Índice de Massa Corporal , Feminino , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Espaço Retroperitoneal/cirurgia , Estudos RetrospectivosRESUMO
Recent evidence suggests that serum secreted frizzled-related protein (SFRP) 4 may affect ß-cell function. In a cross-sectional clinical study, 56 subjects with type 2 diabetes mellitus (T2DM), 52 subjects with impaired glucose tolerance (IGT) and 42 normal glucose tolerance (NGT) subjects were enrolled to investigate the relationship between SFRP4 levels and the first-phase of glucose-stimulated insulin secretion, glucose metabolism and inflammation. Intravenous glucose tolerance tests were conducted, and acute insulin response (AIR), the area under the curve of the first-phase (0-10 min) insulin secretion (AUC), and the glucose disposition index (GDI) were calculated. The serum levels of SFRP4, IL-1ß, plasma glucose, serum lipid, and glycated hemoglobin (HbA1c) were measured. Levels of serum SFRP4 and IL-1ß in the T2DM group and IGT group were significantly higher than those in the NGT group (P < 0.01). The AIR, AUC and GDI between the three groups showed a progressive decrease from the NGT to IGT groups with the lowest value in the T2DM groups (P < 0.01). The serum SFRP4 levels were negatively correlated with AIR, AUC, GDI and HOMA-ß (P < 0.01) and were positively correlated with fasting plasma glucose, HbA1c, hs-CRP, and IL-1ß (P < 0.01). Our study provides evidence that the concentrations of serum SFRP4 in T2DM and IGT subjects were increased and were correlated closely with glycose metabolic disorder, the first-phase of glucose-stimulated insulin secretion and chronic low-grade inflammation. SFRP4 may participate in the development of type 2 diabetes mellitus.
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Diabetes Mellitus Tipo 2/sangue , Intolerância à Glucose/sangue , Glucose/farmacologia , Insulina/sangue , Proteínas Proto-Oncogênicas/sangue , Adulto , Glicemia/metabolismo , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina/fisiologia , Interleucina-1beta/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Introduction: The incidence of renal tumours is increasing annually, and imaging alone cannot meet the diagnostic needs. Aim: This single-centre study aimed to evaluate the predictors of diagnostic imaging-guided percutaneous renal mass biopsy (PRMB), its accuracy and safety, and subsequent changes to the treatment plan. Material and methods: We retrospectively collected the clinical data of patients who had undergone PRMB. The diagnosis rate, pathological data, and complications were analysed. Potential predictors of a diagnostic PRMB were evaluated using logistic regression analysis. Changes to the treatment plan due to PRMB results were also analysed. Results: A total of 158 patients were included in this study. The univariate analysis showed that higher tumour diameter (OR = 1.223, 95% CI: 1.018-1.468, p = 0.031) and number of biopsy cores ≥ 2 (OR = 6.125, 95% CI: 2.006-18.703, p = 0.001) were significantly associated with diagnostic biopsy, and multivariate analysis results showed that higher tumour diameter (OR = 1.215, 95% CI: 1.008-1.463, p = 0.041) was an independent predictor of diagnostic biopsy. A nomogram including tumour diameter and number of biopsy cores was constructed to predict diagnostic biopsy. Compared with postoperative pathology, the concordance between biopsy and postoperative pathology at identifying malignancies, histologic type, and histologic grade were 100% (47/47), 85.1% (40/47), and 54.1% (20/37), respectively. The treatment plans of 15 patients (9.5%) changed based on the PRMB results. Fourteen patients (8.9%) had minor complications (Clavien-Dindo classification < 2). Conclusions: Our results suggest that tumour diameter was an independent predictor of diagnostic biopsy. Furthermore, PRMB can be accurately and safely performed and may guide clinical decision-making for patients with renal tumours.
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The aim of this study is to evaluate the ability of infrared wavenumber of calculus to predict postoperative infection in patients with upper urinary tract calculus (UUTC), and to establish a predictive model based on this. From March 2018 to March 2023, 480 UUTC patients from Fujian Provincial Hospital were included in this study. The infrared-wavenumbers related infection score (IR-infection score) was constructed by univariate analysis, multicollinearity screening, and Lasso analysis to predict postoperative infection. Continually, the Delong test was used to compare the predictive power between the IR-infection score and traditional indicators. Afterward, we performed urine metagene sequencing and stone culture to prove the correlation between calculus toxicity and IR-infection score. Finally, logistic regression was used to build a nomogram. IR-infection score composed of four independent wavenumbers could precisely predict postoperative infection (AUCvalidation cohort = 0.707) and sepsis (AUCvalidation cohort = 0.824). IR-infection score had better predictive ability than commonly used clinical indicators. Moreover, metagenomics sequencing and calculus culture confirmed the correlation between IR-infection score and calculus toxicity (all P < 0.05). The nomogram based on the IR-infection score had high predictive power (all AUCs > 0.803). Our study first developed a novel infrared spectroscopy marker and nomogram, which can help urologists better predict postoperative infection in UUTC patients.
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Complicações Pós-Operatórias , Espectrofotometria Infravermelho , Cálculos Urinários , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Cálculos Urinários/cirurgia , Adulto , Infecções Urinárias/diagnóstico , Idoso , Biomarcadores/urina , Fatores de Risco , Medição de Risco/métodosRESUMO
Objectives: The modified three-level technique for retroperitoneal laparoscopic adrenalectomy (RLA) has proven beneficial in the treatment of adrenal lesions in patients with BMI≥25 Kg/m2. This paper aims to summarize our institution's seven-year experience using this technique for all patients with Adrenal Lesions ≤ 6cm. Patients and methods: Between January 2016 and December 2022. The patients underwent laparoscopic adrenal surgery were categorized into Zhang's technique (ZT) (Three-level Technique) group and modified technique (MT) group. The fundamental characteristics and perioperative data were analyzed, with statistical significance set at p<0.05. Results: In total, 731 patients were stratified into two groups: ZT (n=448) and MT (n=283). Statistically significant distinctions were not detected between the two groups regarding sex, BMI, tumor location, tumor size, tumor type, or American Society of Anesthesiologists (ASA) score (p>0.05). The MT group demonstrated superior outcomes compared to the ZT group in terms of operative time, estimated blood loss, drainage volume, diet recovery time, complication rates, and postoperative hospitalization duration (p<0.05). 17 (4.34%) in the ZT group required unplanned adrenalectomy, while there was none in MT group (P<0.05). Conclusion: MT retroperitoneal laparoscopic adrenalectomy has demonstrated its benefits in the treatment of adrenal lesions across all patients with adrenal lesions ≤ 6cm, serving as a valuable point of reference for the surgical management of adrenal diseases. Patient summary: We have made modifications to the classic retroperitoneal laparoscopic adrenalectomy and achieved superior surgical outcomes, resulting in a procedure known as modified retroperitoneal laparoscopic adrenalectomy. This technique is suitable for both obese individuals and the general population with adrenal lesions ≤ 6cm.
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Neoplasias das Glândulas Suprarrenais , Laparoscopia , Humanos , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Adrenalectomia/métodos , Espaço Retroperitoneal/cirurgia , Espaço Retroperitoneal/patologia , Laparoscopia/métodosRESUMO
BACKGROUND: Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes, especially in older AML patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer drug because it selectively induces the extrinsic apoptosis of tumor cells without affecting normal cells. However, clinical trials have shown that the responses of patients to TRAIL are significantly heterogeneous. It is necessary to explore predictable biomarkers for the preselection of AML patients with better responsiveness to TRAIL. Here, we investigated the critical role of tumor protein p53 inducible nuclear protein 2 (TP53INP2) in the AML cell response to TRAIL treatment. METHODS: First, the relationship between TP53INP2 and the sensitivity of AML cells to TRAIL was determined by bioinformatics analysis of Cancer Cell Line Encyclopedia datasets, Cell Counting Kit-8 assays, flow cytometry (FCM) and cell line-derived xenograft (CDX) mouse models. Second, the mechanisms by which TP53INP2 participates in the response to TRAIL were analyzed by Western blot, ubiquitination, coimmunoprecipitation and immunofluorescence assays. Finally, the effect of TRAIL alone or in combination with the BCL-2 inhibitor venetoclax (VEN) on cell survival was explored using colony formation and FCM assays, and the effect on leukemogenesis was further investigated in a patient-derived xenograft (PDX) mouse model. RESULTS: AML cells with high TP53INP2 expression were more sensitive to TRAIL in vitro and in vivo. Gain- and loss-of-function studies demonstrated that TP53INP2 significantly enhanced TRAIL-induced apoptosis, especially in AML cells with nucleophosmin 1 (NPM1) mutations. Mechanistically, cytoplasmic TP53INP2 maintained by mutant NPM1 functions as a scaffold bridging the ubiquitin ligase TRAF6 to caspase-8 (CASP 8), thereby promoting the ubiquitination and activation of the CASP 8 pathway. More importantly, simultaneously stimulating extrinsic and intrinsic apoptosis signaling pathways with TRAIL and VEN showed strong synergistic antileukemic activity in AML cells with high levels of TP53INP2. CONCLUSION: Our findings revealed that TP53INP2 is a predictor of responsiveness to TRAIL treatment and supported a potentially individualized therapeutic strategy for TP53INP2-positive AML patients.
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Apoptose , Compostos Bicíclicos Heterocíclicos com Pontes , Sinergismo Farmacológico , Leucemia Mieloide Aguda , Sulfonamidas , Ligante Indutor de Apoptose Relacionado a TNF , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Animais , Camundongos , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Apoptose/efeitos dos fármacos , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Linhagem Celular Tumoral , Nucleofosmina , Ensaios Antitumorais Modelo de Xenoenxerto , Citoplasma/metabolismo , Feminino , Proteínas NuclearesRESUMO
Introduction: Upper urinary tract epithelial carcinoma (UTUC) and bladder cancer are both sources of urinary epithelial cell. In our previous study of asymptomatic bladder tumors, we found that most of these tumors could be resected through the urethra without radical surgery. This study analyzed the treatment strategies for asymptomatic UTUC. Aim: To investigate the clinicopathological features and surgical methods of these patients, thus choosing appropriate surgical treatment. Material and methods: 136 patients with UTUC were recruited, of whom 21 patients with asymptomatic UTUC were group A, and 115 UTUC patients with hematuria or low back pain were group B. The clinicopathological features, oncologic outcomes, and surgical methods of patients were evaluated. Results: Radical resection was the main surgical treatment which was included (group A 80.95%, group B 90.43%). Other patients were treated with kidney-retaining surgery. No statistically significant difference was observed in the pathological stage and grade between groups A and B (p > 0.05). During a median follow-up period of 44.3 months, tumor-specific mortality of group A was 7.14%, and that of group B was 5.10%. In the same period, 106 patients with asymptomatic bladder tumor were recruited: 31 patients of them had asymptomatic bladder urothelial carcinoma. The asymptomatic UTUC group had a higher stage and grade of clinicopathological features than the asymptomatic bladder urothelial carcinoma group (p < 0.001). Conclusions: The principle of asymptomatic UTUC treatment is the same as that of symptomatic UTUC. Risk stratification should be carried out according to clinical staging and other parameters, and the corresponding surgical treatment should be selected.
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PURPOSE: The morphology of bone marrow cells is essential in identifying malignant hematological disorders. The automatic classification model of bone marrow cell morphology based on convolutional neural networks shows considerable promise in terms of diagnostic efficiency and accuracy. However, due to the lack of acceptable accuracy in bone marrow cell classification algorithms, automatic classification of bone marrow cells is now infrequently used in clinical facilities. To address the issue of precision, in this paper, we propose a Dual Attention Gates DenseNet (DAGDNet) to construct a novel efficient, and high-precision bone marrow cell classification model for enhancing the classification model's performance even further. METHODS: DAGDNet is constructed by embedding a novel dual attention gates (DAGs) mechanism in the architecture of DenseNet. DAGs are used to filter and highlight the position-related features in DenseNet to improve the precision and recall of neural network-based cell classifiers. We have constructed a dataset of bone marrow cell morphology from the First Affiliated Hospital of Chongqing Medical University, which mainly consists of leukemia samples, to train and test our proposed DAGDNet together with the bone marrow cell classification dataset. RESULTS: When evaluated on a multi-center dataset, experimental results show that our proposed DAGDNet outperforms image classification models such as DenseNet and ResNeXt in bone marrow cell classification performance. The mean precision of DAGDNet on the Munich Leukemia Laboratory dataset is 88.1%, achieving state-of-the-art performance while still maintaining high efficiency. CONCLUSION: Our data demonstrate that the DAGDNet can improve the efficacy of automatic bone marrow cell classification and can be exploited as an assisting diagnosis tool in clinical applications. Moreover, the DAGDNet is also an efficient model that can swiftly inspect a large number of bone marrow cells and offers the benefit of reducing the probability of an incorrect diagnosis.
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Leucemia , Redes Neurais de Computação , Humanos , Algoritmos , Leucemia/patologia , Células da Medula Óssea/patologiaRESUMO
This study aimed to analyze the infection risk factors for transurethral resection of the prostate (TURP) and establish predictive models to help make personalized treatment plans. Our study was designed one-center and retrospectively enrolled 1169 benign prostatic hyperplasia (BPH) patients. Risk factors were explored for postoperative infection. A TURP-postoperative infection (TURP-PI) model with infection prediction values was created. The improved-TURP-PI (I-TURP-PI) model, including extra new factors (pathogens species), was also built to see whether it could optimize the prediction abilities. At last, we developed a nomogram for better clinical application. Operation time, preoperative indwelling urinary catheter (PIUC), and positive preoperative urine culture were independent risk factors (all P < 0.05). Interestingly, pathogens species in pre-surgery urine (PEnterococcus faecium = 0.014, PPseudomonas aeruginosa = 0.086) were also independent risk factors. Patients with positive Enterococcus faecium (37.50%) were most likely to have postoperative infection. We built two models with AUCTURP-PI = 0.709 (95% CI 0.656-0.763) and AUCI-TURP-PI = 0.705 (95% CI 0.650-0.760). The nomogram could help improve the prediction ability. To our knowledge, our study is the first to use pathogen species in urine before surgery as risk factors for infection prediction after TURP. TURP-PI and I-TURP-PI models have essential roles in predicting patients' postoperative infections and in better postoperative antibiotic decision-making.
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Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Ressecção Transuretral da Próstata/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Próstata/cirurgia , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fatores de RiscoRESUMO
To explore the clinical significance and prognosis of acute myeloid leukemia (AML) patients with WT1 mutations.In total, the clinical data of 269 adult patients with non-M3 AML were considered retrospectively. From these patients, 153 carried WT1 mutation whereas 116 were negative. WT1 mutation positive patients were further divided into WT1 low expression and high expression groups base on the expression level of WT1 by qPCR at diagnosis (cut off: 170500). Survival and therapeutic effect analysis were performed for the above patients with different interfering factors such as co-mutations, the extent of WT1 log reduction and the chemotherapy regimens. Patients with high WT1 expression have higher rate of relapse. We can accurately identify patients with inferior outcomes when we take the following factors into consideration: the WT1 expression level at diagnosis; different prognostic factors including co-mutations (especially NPM1 and FLT3-ITD); the log reduction of WT1 after induction therapy and the risk of stratification. Idarubicin + Cytarabine (IA) regimen could reduce the expression level of WT1 after treatment, and Allo-HSCT played an important role in improving the prognosis of patients with WT1 high expression and patients with WT1 negativity. Among the relapsed patients, there existed a rising trend of WT1-MRD in advance than MFC-MRD and that of patients with continuous complete remission (CR). Different clinical background should be taken into consideration when we judge the prognosis and therapeutic effect of patients with WT1 mutations. In addition, WT1 may be an optional MRD marker, which needs regular monitoring.
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Relevância Clínica , Leucemia Mieloide Aguda , Adulto , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Prognóstico , Estudos Retrospectivos , Proteínas WT1/genética , Proteínas WT1/metabolismoRESUMO
BACKGROUND: Myeloid neoplasms (MN) tend to relapse and deteriorate. Exploring the genomic mutation landscape of MN using next-generation sequencing (NGS) is a great measure to clarify the mechanism of oncogenesis and progression of MN. METHODS: This multicenter retrospective study investigated 303 patients with MN using NGS from 2019 to 2021. The characteristics of the mutation landscape in the MN subgroups and the clinical value of gene variants were analyzed. RESULTS: At least one mutation was detected in 88.11% of the patients (267/303). TET2 was the most common mutation in the cohort, followed by GATA2, ASXL1, FLT3, DNMT3A, and TP53. Among patients with myeloid leukemia (ML), multivariate analysis showed that patients aged ≥60 years had lower overall survival (OS, p = 0.004). Further analysis showed TET2, NPM1, SRSF2, and IDH1 gene mutations, and epigenetic genes (p < 0.050) presented significantly higher frequency in older patients. In patients with myelodysplastic syndrome (MDS) and myelodysplastic neoplasms (MPN), univariate analysis showed that BCORL1 had a significant impact on OS (p = 0.040); however, in multivariate analysis, there were no factors significantly associated with OS. Differential analysis of genetic mutations showed FLT3, TP53, MUC16, SRSF2, and KDM5A mutated more frequently (p < 0.050) in secondary acute myeloid leukemia (s-AML) than in MDS and MPN. TP53, U2AF1, SRSF2, and KDM5A were mutated more frequently (p < 0.050) in s-AML than in primary AML. KDM5A was observed to be restricted to patients with s-AML in this study, and only co-occurred with MUC16 and TP53 (2/2, 100%). Another mutation was MUC16, and its co-occurrence pattern differed between s-AML and AML. MUC16 mutations co-occurred with KDM5A and TP53 in 66.7% (2/3) of patients with s-AML and co-occurred with CEBPA in 100% (4/4) of patients with AML. CONCLUSIONS: Our results demonstrate different genomic mutation patterns in the MN subgroups and highlight the clinical value of genetic variants.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Transtornos Mieloproliferativos , Humanos , Idoso , Nucleofosmina , Estudos Retrospectivos , Relevância Clínica , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , China/epidemiologia , Prognóstico , Proteína 2 de Ligação ao Retinoblastoma/genéticaRESUMO
Objective: The aim of this study is to evaluate a potential successful strategy for treating large renal hilar angiomyolipoma (RHAML) during the procedure of laparoscopic nephron-sparing surgery (NSS). Methods: The total study population includes 12 patients with large RHAMLs who underwent laparoscopic NSS in the Department of Urology of Fujian Provincial hospital and People's Hospital of Zhejiang, ranging from January 2016 to March 2020. The perioperative variables, intraoperative procedures, and postprocedure complications were all recorded. Three months later, all patients returned to the hospital to check their postoperative recovery by reviewing the computed tomography urography (CTU) image. In the follow-up, patients were asked to have their review by CT or color doppler ultrasound every year. Results: Laparoscopic NSS was successfully performed in all patients. The average operation time was 113.33 ± 33.39â min; the intraoperative blood loss was about 137.50 ± 91.17â ml; the warm ischemia time was 25.25 ± 4.88â min; the drainage tube extubation time was 4.58 ± 2.07 days; and the hospital stay time was 6.42 ± 1.78 days. The average follow-up time was 14.58 ± 9.18 months. After 3 months, all CTU images showed an unobstructed urinary tract in the patient, and no tumor recurrence was found. In addition, no patients had renal atrophy and urine extravasation during follow-up. Conclusions: Laparoscopic NSS for RHAML is complex and technically demanding, but good surgical design and operation can achieve satisfactory surgical results. Modified laparoscopic NSS was a beneficial technique and may provide a reference for treating patients with RHAML.
RESUMO
To compare the applicability of 14 equations of estimating glomerular filtration rate (eGFR) before and after nephron-sparing surgery (NSS) for renal function assessment of patients with renal tumors. Preoperative and postoperative GFR is measured by emission computed tomography (ECT) with 99mTc-DTPA as an imaging agent as reference GFR (rGFR) to compare with all formulas. Spearman correlation analysis and Bland-Altman agreement analysis were used to evaluate the correlation between rGFR and eGFR1 to 14 before and after surgery. A total of 50 cases including 22 males and 28 females were included. The results of preoperative eGFR1-14 correlated with rGFR (P < 0.05). The calculation results of all estimation formulas have a significant correlation with preoperative GFR. Preoperative MDRD-I, CKD-EPI SCysC, and FAS Scr-SCysC have good consistency. The CG formula has the highest precision and FAS Scr-SCysC has the highest accuracy. A total of 30 patients followed up after surgery, and postoperative rGFR correlated with CG, CKD-EPI, FAS, and BIS formulas (P < 0.05). But postoperative rGFR has no significant correlation with MDRD and Schwartz (P > 0.05). Postoperative CKD-EPI Scr-SCysC has best consistency, and FAS Scr-SCysC has the highest accuracy and precision. Our data suggest that eGFR equations evaluated by both serum creatinine (Scr) and cystatin C (SCysC) is not necessarily better than those evaluated by one of them alone. Among all enrolled equations, FAS Scr-SCysC is the best one to evaluate postoperative GFR in patients with renal tumors.
Assuntos
Neoplasias Renais , Insuficiência Renal Crônica , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Rim/fisiologia , Rim/cirurgia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Masculino , Néfrons/cirurgia , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/cirurgiaRESUMO
To study the relationship between preoperative urine culture, bacterial species and infection after percutaneous nephrolithotomy in patients with upper urinary tract stones, and summarize the clinical characteristics of different bacterial infections. From January 2014 and January 2020, 963 patients with upper urinary tract stones who underwent PCNL in the department of urology of Fujian provincial hospital were included in the study. Information included the patient's age, gender, weight, diabetes, chronic disease history, urine routine, preoperative urine culture results, stone size, number of stones, hydronephrosis level, operation time, body temperature, heart rate, blood pressure, breathing rate, hemoglobin, serum creatinine, bilirubin, platelets and whether there was preoperative infection were recorded. 141 patients (14.6%) had a positive urine culture before surgery, and 7 of them had multiple bacterial infections. The most common pathogenic bacteria was Escherichia coli, followed by Enterococcus and Klebsiella pneumoniae. A total of 74 cases (7.7%) of 963 patients with infection after PCNL occurred, 24 cases (32.4%) of infected patients progressed to urinary septic shock. Univariate analysis shown that the probability of infection in patients with long operation time and positive urine culture was significantly higher, and the difference was statistically significant. Further multivariate logistic regression analysis shown that positive urine culture before operation and long operation time were independent risk factors for infection after PCNL. Among the 29 patients with septic shock, 18 cases (62.1%) had a positive urine culture before surgery. The incidence (43.9%) of postoperative infection in Escherichia coli positive patients was significantly higher than that in the negative group, and the difference was statistically significant. The rate of patients with Escherichia coli infection progressing to septic shock was 9 cases (60%). 2 patients with Enterococcus faecium infection and 2 patients with Klebsiella pneumoniae infection all progressed to septic shock. The age of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 58.53 ± 11.73 years, 76.5 years and 74 years.The body temperature of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 39.10 ± 0.25 °C, 39.45 °C and 38.65 °C. The highest pct value of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 80.62 ± 31.45 ng/mL, 24.32 ng/mL and 8.45 ng/mL. The nitrite positive rate of patients with post-PCNL infection caused by Escherichia Coli, Enterococcus faecium and Klebsiella pneumoniae were 64.51%, 16.6% and 0. Postoperative infection of PCNL is significantly correlated with positive preoperative urine culture, and positive preoperative urine culture is an independent risk factor for postoperative infection. The most common pathogen of postoperative infection of PCNL is Escherichia coli, followed by Enterococcus and Klebsiella pneumoniae. Patients with Escherichia coli infection are often positive for nitrite before surgery, mainly manifested by high fever, and PCT is significantly increased (often exceeded 100 ng/ml). Enterococcus faecium and Klebsiella pneumoniae infections mostly occur in elderly patients and often progress to septic shock. Patients with Enterococcus faecium infection have a high fever, and the PCT value is significantly higher (often exceeded 20 ng/ml). Patients with Klebsiella pneumoniae infection have a moderate fever, and the PCT value generally does not exceeded 10 ng/ml. Long operation time is another independent risk factor for PCNL infection.
Assuntos
Infecções Bacterianas , Enterococcus faecium , Infecções por Escherichia coli , Cálculos Renais , Nefrolitotomia Percutânea , Choque Séptico , Cálculos Urinários , Idoso , Infecções Bacterianas/etiologia , Escherichia coli , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Cálculos Renais/etiologia , Klebsiella pneumoniae , Masculino , Pessoa de Meia-Idade , Nefrolitotomia Percutânea/efeitos adversos , Nitritos , Estudos Retrospectivos , Choque Séptico/etiologiaRESUMO
Acute myeloid leukemia (AML) is a rapidly progressing and often fatal hematopoietic malignancy. Venetoclax (VEN), a recent FDA-approved BCL-2 selective inhibitor, has high initial response rates in elderly AML patients, but the majority of patients eventually acquire resistance. Multiple studies have demonstrated that the female sex is associated with better outcomes in patients with AML, which are predominantly attributed to estrogen signaling. As a novel membrane estrogen receptor, G protein-coupled estrogen receptor (GPER)-mediated-rapid estrogen effects have attracted considerable attention. However, whether targeting GPER enhances the antileukemic activity of VEN is unknown. In this study, we first demonstrated that GPER expression was dramatically reduced in AML cells owing to promoter hypermethylation. Furthermore, pharmacological activation of GPER by G-1 combined with VEN resulted in synergistic antileukemic activity in vitro and in vivo. Mechanistically, G-1/VEN combination synergistically triggered concurrent mitochondria-related apoptosis and gasdermin E (GSDME)-dependent pyroptosis by activating p38-MAPK/myeloid cell leukemia 1 (MCL-1) axis. Importantly, leukemic pyroptosis heightened CD8+ T cell immune function by releasing interleukin (IL)-1ß/18 into the tumor microenvironment. Our study corroborates that GPER activation shows a synergistic antileukemic effect with VEN, making it a promising therapeutic regimen for AML.