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Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageâ ¡, 33(53.2%)patients in stage â ¢ and 18(29.1%)patients in stage â £. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B , Humanos , Estudos Retrospectivos , Criança , Linfoma de Células B/tratamento farmacológico , China , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adolescente , Feminino , Masculino , Proteínas Proto-Oncogênicas c-bcl-6/genética , Estudos de Coortes , Proteínas Proto-Oncogênicas c-bcl-2/genética , Pré-Escolar , Hibridização in Situ Fluorescente , Resultado do Tratamento , Proteínas Proto-Oncogênicas c-myc/genéticaRESUMO
Objective: To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope. Methods: This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan-Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope. Results: A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group (HR=11.66, 95%CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions: ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.
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Síncope , Humanos , Idoso , Síncope/diagnóstico , Síncope/etiologia , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Eletrocardiografia Ambulatorial/métodos , Eletrocardiografia Ambulatorial/instrumentação , Eletrocardiografia/métodos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/complicaçõesRESUMO
Echinococcosis is a common zoonotic disease in livestock; the type with the highest incidence is cystic echinococcosis (CE). In clinical management, patients with CE of the liver in which the cyst wall is calcified have been found to have better prognoses than those without calcification. In this study, we collected calcified and uncalcified cyst wall tissue from patients with hepatic CE and observed significant changes in the expression of 2336 messenger ribonucleic acids (mRNAs), 178 long noncoding RNAs (lncRNAs), 210 microRNAs (miRNAs), and 33 circular RNAs (circRNAs) using high-throughput sequencing (HTS). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed RNAs (DERNAs: DEmRNAs, DElncRNAs, DEmiRNAs, and DEcircRNAs) were performed to explore these RNAs' potential biological functions and signaling pathways. Ultimately, the results of hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining confirmed the correlation between calcification and apoptosis of the cyst wall. In summary, this study was an initial exploration of the molecular-biological mechanism underlying spontaneous calcification of the hydatid cyst wall, and it provides a theoretical basis for exploring new targets for drug treatment in CE.
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Biologia Computacional , Humanos , Calcinose/genética , Calcinose/parasitologia , Transcriptoma , Equinococose/parasitologia , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , MicroRNAs/genética , Equinococose Hepática/parasitologia , Adulto , Feminino , Pessoa de Meia-Idade , RNA Circular/genéticaRESUMO
Objective: To investigate the effects of the epidermal growth factor receptor(EGFR) inhibitor Gefitinib on airway inflammation and airway remodelling in asthmatic C57BL/6 mice, and to analyze its possible mechanisms. Methods: Male C57BL/6 mice, aged 6-8 weeks, were randomly assigned into five groups: Group A (control group), Group B (asthma group), Group C (asthma+20 mg/kg gefitinib group), Group D (asthma+40 mg/kg gefitinib group), and Group E (40 mg/kg gefitinib group), with seven mice per group. Mice were sensitized by intraperitoneal injection of a mixture of 0.2 ml solution containing OVA and Al(OH)3 [20 µg OVA+2 mg Al(OH)3 dissolved in 0.2 ml of physiological saline] at Day 0 and 14. Starting from Day 25 to 31, Group B, C, and D were challenged with nebulization of 1% OVA solution (8 ml) to induce asthma, once a day for approximately 40 minutes, with continuous aerosolization for 7 days. Group C and D were given 0.2 ml of Gefitinib dissolved in 0.5% carboxymethylcellulose sodium (CMCNa) by gavage half an hour before challenging, and Group E was simultaneously given with 0.2 ml of Gefitinib dissolved in 0.5% CMCNa only. Group A and B were given an equivalent volume of 0.5% CMCNa by gavage. After 24 h of final challenge, the bronchoalveolar lavage fluid (BALF) was prepared for the determination of total cell count and eosinophil count. The levels of total immune globulin E (IgE) in serum and interleukin (IL)-4, IL-5 and IL-13 in BALF and lung tissue homogenates were measured by ELISA. The mRNA expression levels of IL-4, IL-5, IL-13 in lung were measured. Immunohistochemistry and Western blot experiments were used to detect the expression levels of EGFR in lung tissues. Results: In Group B, the level of total IgE in serum, total cell count, eosinophil count, the levels of IL-4, IL-5, IL-13 in BALF and the phosphorylation of EGFR and its downstream activation in lung were higher than those in Group A (all P<0.05). The levels of total IgE in serum [(261.32±44.38) ng/ml, (194.09±52.39) ng/ml vs (1 023.70±105.51) ng/ml], total cell count [(23.70±4.08)×105/ml, (14.92±4.06)×105/ml vs (35.36±6.30)×105/ml], eosinophil count [(108.00±13.69)×104/ml, (67.00±17.28)×104/ml vs (147.86±20.06)×104/ml], IL-4 [(36.42±4.48) pg/ml, (30.45±8.12) pg/ml vs (58.72±7.17) pg/ml], IL-5 [(16.20±4.62) pg/ml, (13.38±5.14) pg/ml vs (23.46±5.38) pg/ml], IL-13 [(18.45±7.28) pg/ml, (14.33±7.70) pg/ml vs (104.12±24.66) pg/ml] in BALF of Group C and D were lower than those in Group B (all P<0.05). The levels of IL-4, IL-5, and IL-13 as well as their mRNA levels in the lung tissue of Group C and D were lower than those in Group B (all P<0.05). In Group C and D, the positive expression rate of phosphorylated epidermal growth factor receptor (p-EGFR) in lung tissue [(40.53±6.80)%, (23.60±4.42)% vs (70.78±5.36)%], p-EGFR/EGFR (61.68±7.48, 51.13±5.19 vs 105.90±11.66), phosphorylated extracellular regulated protein kinase (p-Erk)/extracellular regulated protein kinase (Erk) (75.28±7.11, 47.54±4.83 vs 98.76±4.71), and phosphorylated protein kinase B (p-Akt)/protein kinase B (Akt) (96.24±5.40, 68.52±2.73 vs 103.30±4.52) was lower than those of Group B (all P<0.05). There was no statistically significant difference in the relevant indicators between Group A and E (all P>0.05). Conclusion: Gefitinib may alleviate airway inflammation and airway remodeling in asthmatic mice by inhibiting EGFR phosphorylation and affecting the activation of downstream Erk and Akt.
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Remodelação das Vias Aéreas , Asma , Gefitinibe , Camundongos Endogâmicos C57BL , Animais , Asma/tratamento farmacológico , Asma/metabolismo , Camundongos , Gefitinibe/farmacologia , Remodelação das Vias Aéreas/efeitos dos fármacos , Masculino , Líquido da Lavagem Broncoalveolar , Inflamação , Interleucina-4/metabolismo , Quinazolinas/farmacologia , Receptores ErbB/metabolismo , Ovalbumina , Pulmão/metabolismo , Pulmão/patologia , Interleucina-5/metabolismo , Interleucina-13/metabolismo , Eosinófilos , Modelos Animais de DoençasRESUMO
Objective: To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies. Methods: A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed. Results: A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common. Conclusions: Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.
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Anormalidades Múltiplas , Ductos Paramesonéfricos , Anormalidades Urogenitais , Útero , Vagina , Humanos , Feminino , Estudos Retrospectivos , Anormalidades Urogenitais/epidemiologia , Útero/anormalidades , Vagina/anormalidades , Ductos Paramesonéfricos/anormalidades , Incidência , Anormalidades Múltiplas/epidemiologia , Transtornos 46, XX do Desenvolvimento Sexual/epidemiologia , Rim/anormalidades , Colo do Útero/anormalidades , Colo do Útero/patologia , Genitália Feminina/anormalidades , China/epidemiologia , Anormalidades Congênitas/epidemiologia , AdultoRESUMO
Objective: To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC. Methods: In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients). The patients had all received TMFP after completing standard nCRT. The variables studied included (1) clinicopathological characteristics; (2) clinical complete remission (cCR) and efficacy of TMFP in determining pCR after NCRT in LARC patients; and (3) hospital attended, sex, age, clinical T- and N-stages, distance between the lower margin of the tumor and the anal verge, baseline and post-radiotherapy serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 concentrations, chemotherapy regimen, use of immunosuppressants with or without radiotherapy, radiation therapy dosage, interval between surgery and radiotherapy, surgical procedure, clinical T/N stage after radiotherapy, cCR, pathological results of TMFP, puncture method (endoscopic or percutaneous), and number and timing of punctures. Single-factor and multifactorial logistic regression analysis were used to determine the factors affecting pCR after NCRT in LARC patients. A prediction model was constructed based on the results of multivariat analysis and the performance of this model evaluated by analyzing subject work characteristics (ROC), calibration, and clinical decision-making (DCA) curves. pCR was defined as complete absence of tumor cells on microscopic examination of the surgical specimens of rectal cancer (including lymph node dissection) after NCRT, that is, ypT0+N0. cCR was defined according to the Chinese Neoadjuvant Rectal Cancer Waiting Watch Database Study Collaborative Group criteria after treatment, which specify an absence of ulceration and nodules on endoscopy; negative rectal palpation; no tumor signals on rectal MRI T2 and DWI sequences; normal serum CEA concentrations, and no evidence of recurrence on pelvic computed tomography/magnetic resonance imaging. Results: Of the 110 patients, 45 (40.9%) achieved pCR after nCRT, which was combined with immune checkpoint inhibitors in 34 (30.9%). cCR was diagnosed before puncture in 38 (34.5%) patients, 43 (39.1%) of the punctures being endoscopic. There were no complications of puncture such as enterocutaneous fistulae, vaginal injury, prostatic injury, or presacral bleeding . Only one (2.3%) patient had a small amount of blood in the stools, which was relieved by anal pressure. cCR had a sensitivity of 57.8% (26/45) for determining pCR, specificity of 81.5% (53/65), accuracy of 71.8% (79/110), positive predictive value 68.4% (26/38), and negative predictive value of 73.6% (53/72). In contrast, the sensitivity of TMFP pathology in determining pCR was 100% (45/45), specificity 66.2% (43/65), accuracy 80.0% (88/110), positive predictive value 67.2% (45/67), and negative predictive value 100.0% (43/43). In this study, the sensitivity of TMFP for pCR (100.0% vs. 57.8%, χ2=24.09, P<0.001) was significantly higher than that for cCR. However, the accuracy of pCR did not differ significantly (80.0% vs. 71.8%, χ2=2.01, P=0.156). Univariate and multivariate logistic regression analyses showed that a ≥4 cm distance between the lower edge of the tumor and the anal verge (OR=7.84, 95%CI: 1.48-41.45, P=0.015), non-cCR (OR=4.81, 95%CI: 1.39-16.69, P=0.013), and pathological diagnosis by TMFP (OR=114.29, the 95%CI: 11.07-1180.28, P<0.001) were risk factors for pCR after NCRT in LARC patients. Additionally, endoscopic puncture (OR=0.02, 95%CI: 0.05-0.77, P=0.020) was a protective factor for pCR after NCRT in LARC patients. The area under the ROC curve of the established prediction model was 0.934 (95%CI: 0.892-0.977), suggesting that the model has good discrimination. The calibration curve was relatively close to the ideal 45° reference line, indicating that the predicted values of the model were in good agreement with the actual values. A decision-making curve showed that the model had a good net clinical benefit. Conclusion: Our predictive model, which incorporates TMFP, has considerable accuracy in predicting pCR after nCRT in patients with locally advanced rectal cancer. This may provide a basis for more precisely selecting individualized therapy.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Biópsia/métodos , Antígeno Carcinoembrionário/sangue , Resultado do Tratamento , Adulto , IdosoRESUMO
AIM: To assess the performance of diffusion-relaxation correlation spectrum imaging (DR-CSI) in the characterization of parotid gland tumors. MATERIALS AND METHODS: Twenty-five pleomorphic adenomas (PA) patients, 9 Warthin's tumors (WT) patients and 7 malignant tumors (MT) patients were prospectively recruited. DR-CSI (7 b-values combined with 5 TEs, totally 35 diffusion-weighted images) was scanned for pre-treatment assessment. Diffusion (D)-T2 signal spectrum summating all voxels were built for each patient, characterized by D-axis with range 0â¼5 × 10-3 mm2/s, and T2-axis with range 0â¼300ms. With boundaries of 0.5 and 2.5 × 10-3 mm2/s for D, all spectra were divided into three compartments labeled A (low D), B (mediate D) and C (high D). Volume fractions acquired from each compartment (VA, VB, VC) were compared among PA, WT and MT. Diagnostic performance was assessed using receiver operating characteristic analysis and area under the curve (AUC). RESULTS: Each subtype of parotid tumors had their specific D-T2 spectrum. PA showed significantly lower VA (8.85 ± 4.77% vs 20.68 ± 10.85%), higher VB (63.40 ± 8.18% vs 43.05 ± 7.16%), and lower VC (27.75 ± 8.51% vs 36.27 ± 11.09) than WT (all p<0.05). VB showed optimal diagnostic performance (AUC 0.969, sensitivity 92.00%, specificity 100.00%). MT showed significantly higher VA (21.23 ± 12.36%), lower VB (37.09 ± 6.43%), and higher VC (41.68 ± 13.72%) than PA (all p<0.05). Similarly, VB showed optimal diagnostic performance (AUC 0.994, sensitivity 96.00%, specificity 100.00%). No significant difference of VA, VB and VC was found between WT and MT. CONCLUSIONS: DR-CSI might be a promising and non-invasive way for characterizing parotid gland tumors.
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Adenolinfoma , Adenoma Pleomorfo , Imagem de Difusão por Ressonância Magnética , Neoplasias Parotídeas , Humanos , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Imagem de Difusão por Ressonância Magnética/métodos , Adulto , Idoso , Adenoma Pleomorfo/diagnóstico por imagem , Adenoma Pleomorfo/patologia , Estudos Prospectivos , Adenolinfoma/diagnóstico por imagem , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/patologia , Sensibilidade e Especificidade , Idoso de 80 Anos ou maisRESUMO
AIM: This study aimed to reveal the unique microenvironment of peri-implantitis through single-cell analysis. MATERIALS AND METHODS: Herein, we performed single-cell RNA sequencing (scRNA-seq) of biopsies from patients with peri-implantitis (PI) and compared the results with healthy individuals (H) and patients with periodontitis (PD). RESULTS: Decreased numbers of stromal cells and increased immune cells were found in the PI group, which implies a severe inflammatory infiltration. The fibroblasts were found to be heterogeneous and the specific pro-inflammatory CXCL13+ sub-cluster was more represented in the PI group, in contrast to the PD and H groups. Furthermore, more neutrophil infiltration was detected in the PI group than in the PD group, and cell-cell communication and ligand-receptor pairs revealed most neutrophils were recruited by CXCL13+ fibroblasts through CXCL8/CXCL6-CXCR2/CXCR1. Notably, our study demonstrated that the unique microenvironment of the PI group promoted the differentiation of monocyte/macrophage lineage cells into osteoclasts, which might explain the faster and more severe bone resorption in the progression of PI than PD. CONCLUSIONS: Collectively, this study suggests a unique immune microenvironment of PI, which may explain the differences between PI and PD in the clinic. These outcomes will aid in finding new specific and effective treatments for PI.
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AIM: To investigate whether the Vesical Imaging-Reporting and Data System (VI-RADS) could be used to develop a new non-invasive preoperative grade-prediction system to partially predict high-grade bladder cancer (HG-BC). MATERIALS AND METHODS: The present study enrolled 89 primary BC patients prospectively from March 2022 to June 2023. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of VI-RADS for predicting HG-BC and muscle-invasive bladder cancer (MIBC) in the entire group. In the low VI-RADS (≤2) group, the decision tree-based method was used to obtain significant predictors and construct the decision-tree model (DT model). The performance of the DT model and low VI-RADS scores for predicting HG-BC was determined using ROC, calibration, and decision curve analyses. RESULTS: At a cut-off of ≥3, the specificity and positive predictive value of VI-RADS for predicting HG-BC in the entire group was 100%, and the area under the ROC curve (AUC) was 0.697. Among 65 patients with low VI-RADS scores, the DT model showed an AUC of 0.884 in predicting HG-BC compared to 0.506 for low VI-RADS scores. Calibration and decision curve analyses showed that the DT model performed better than the low VI-RADS scores. CONCLUSION: Most VI-RADS scores ≥3 correspond to HG-BCs. VI-RADS could be used as a grouping imaging biomarker for a pathological grade-prediction procedure, which in combination with the DT model for low VI-RADS (≤2) populations, would provide a potential preoperative non-invasive method of predicting HG-BC.
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Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Biomarcadores , Árvores de Decisões , Imageamento por Ressonância Magnética/métodos , Estudos RetrospectivosRESUMO
AIM: To develop a radiomics signature applied to magnetic resonance imaging (MRI)-images to predict cytogenetic abnormalities in multiple myeloma (MM). MATERIALS AND METHODS: Patients with newly diagnosed MM were enrolled retrospectively from March 2019 to September 2022. They were categorised into the high-risk cytogenetics (HRC) group and standard-risk cytogenetics (SRC) group. The patients were allocated randomly at a ratio of 7:3 into training and validation cohorts. Volumes of interest (VOI) was drawn manually on fat suppression T2-weighted imaging (FS-T2WI) and copied to the same location of the T1-weighted imaging (T1WI) sequence. Radiomics features were extracted from two sequences and selected by reproducibility and redundant analysis. The least absolute shrinkage selection operation (LASSO) algorithm was applied to build the radiomics signatures. The performance of the radiomics signatures to distinguish HRC with SRC was evaluated by ROC curves. The area under the curve (AUC), specificity, and sensitivity were also calculated. RESULTS: A total of 105 MM patients were enrolled in this study. The four and 11 most significant and relevant features were selected separately from T1WI and FS-T2WI sequences to build the radiomics signatures based on the training cohort. Compared to the T1WI sequence, the radiomics signature based on the FS-T2WI sequence achieved better performance with AUCs of 0.896 and 0.729 in the training and validation cohorts respectively. A sensitivity of 0.833, specificity of 0.667, and Youden index of 0.500 were achieved for the FS-T2WI radiomics signature in the validation cohort. CONCLUSIONS: The radiomics signature based on MRI provides a non-invasive and convenient tool to predict cytogenetic abnormalities in MM patients.
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Medula Óssea , Mieloma Múltiplo , Humanos , Medula Óssea/diagnóstico por imagem , Aberrações Cromossômicas , Imageamento por Ressonância Magnética/métodos , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/genética , Radiômica , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
PURPOSE: Obesity is the main driving factor for comorbidities in Prader-Willi syndrome (PWS) patients due to overeating behaviors. The gut microbiota has been implicated in the etiology of obesity and associated comorbidities. The purpose of the present study was to characterize the fecal microbiota in Chinese patients with PWS and compare it to that of patients with obesity as well as healthy controls. METHODS: We conducted a cross-sectional study with 35 PWS patients (PWS), 35 patients with obesity (OB), and 35 healthy controls (HC). Metagenomic sequencing was performed in stool samples. RESULTS: The composition of the fecal microbiota in PWS patients differed from that of participants in the OB and HC groups. It was characterized by increased Akkermansia Eubacterium, Eubacterium rectale, and Roseburia intestinalis and decreased Parabacteroides and Phascolarctobacterium. Additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was lower in PWS patients than in patients with obesity. Spearman rank correlation analysis showed that Achromobacter, Acidiphilium, Xylophilus, and Frisingicoccus were significantly negatively correlated with HOMA-IR. CONCLUSION: The composition of the gut microbiota in Chinese PWS patients differed from that in patients with obesity, which might contribute to higher insulin sensitivity in PWS patients.
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Microbioma Gastrointestinal , Resistência à Insulina , Síndrome de Prader-Willi , Criança , Humanos , Estudos Transversais , ObesidadeRESUMO
Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.
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Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Síndromes Mielodisplásicas , Segunda Neoplasia Primária , Humanos , Estudos Retrospectivos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/terapia , Prognóstico , Síndromes Mielodisplásicas/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Indução de Remissão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Parasite-derived non-coding RNAs (ncRNAs) not only contribute to life activities of parasites, and microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) may generate a competitive endogenous RNA (ceRNA) regulatory network with host miRNAs and mRNAs via extracellular vesicles, thereby participating in infection and pathogenic processes. This article presents an overview of characterizing ncRNAs derived from parasites and the cross-species regulatory role of parasite-derived ncRNAs in host gene expression and its underlying mechanisms.
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MicroRNAs , Parasitos , Animais , Redes Reguladoras de Genes , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Circular/genética , RNA Endógeno CompetitivoRESUMO
[This corrects the article DOI: 10.3389/fped.2020.00136.].
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To investigate the relationship between male semen parameters and sperm DNA fragment index with age. Adopt cross-sectional sampling survey design, 3 203 male patients who visited the Department of Reproductive Andrology in the Third Affiliated Hospital of Zhengzhou University from January 2019 to June 2021 were selected as subjects. Age range is 18-57 years, with the median age of 30 years. Through quartile regression analysis, the correlation between age and different male semen parameters and DNA fragment index (DFI) was presented. The study population was divided into ≤30 years old group and >30 years old group, and the correlation between age and semen volume, sperm concentration, total sperm count, progressive motility, total motility, percentage of normal sperm and DFI level were compared and analyzed. The results showed that there were significant differences in progressive motility, total motility and DFI level among different age groups (χ2=-4.608, -4.604, -7.719,P all <0.05), but there was no significant difference in semen volume, sperm concentration, total sperm count and percentage of normal sperm (χ2=-1.712, -1.203, -0.149, -0.175,P all >0.05). In the>30 years old age group, there was a very weak negative correlation between male age and semen volume, progressive motility and total motility (r=-0.137, -0.101 and -0.056, P all <0.05). There was a very weak positive correlation between male age and sperm concentration and sperm DFI level (r=0.061, 0.190, P all <0.05), while there was no correlation between male age and total sperm count and percentage of normal sperm (r=-0.018, -0.016,P all >0.05). In conclusion, with the increase of age, especially after the age of 30, semen volume, progressive motility and total motility decreased, while sperm concentration and DFI level increased, and semen quality decreased.
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Infertilidade Masculina , Sêmen , Humanos , Masculino , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Análise do Sêmen , Estudos Transversais , Infertilidade Masculina/genética , Motilidade dos Espermatozoides , Fragmentação do DNA , Espermatozoides , Contagem de Espermatozoides , DNARESUMO
Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
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Anemia de Fanconi , Masculino , Feminino , Humanos , Criança , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/genética , Quebra Cromossômica , Estudos Retrospectivos , Éxons , China/epidemiologiaRESUMO
Deep learning (DL) methods further promote the development of quantitative structure-activity/property relationship (QSAR/QSPR) models by dealing with complex relationships between data. An acetylcholinesterase inhibitory toxicity model of ionic liquids (ILs) was established using a convolution neural network (CNN) combined with support vector machine (SVM), random forest (RF) and multilayer perceptron (MLP). A CNN model was proposed for feature self-learning and extraction of ILs. By comparing with the model results through feature engineering (FE), the model regression results based on the CNN model for feature extraction have been substantially improved. The results showed that all six models (FE-SVM, FE-RF, FE-MLP, CNN-SVM, CNN-RF, and CNN-MLP) had good prediction accuracy, but the results based on the CNN model were better. The hyperparameters of six models were optimized by grid search and the 10-fold cross validation. Compared with the existing models in the literature, the model performance has been further improved. The model could be used as an intelligent tool to guide the design or screening of low-toxicity ILs.
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Líquidos Iônicos , Líquidos Iônicos/toxicidade , Estrutura Molecular , Acetilcolinesterase , Relação Quantitativa Estrutura-Atividade , Redes Neurais de ComputaçãoRESUMO
AIM: To explore the possibility of discriminating minimal residual disease (MRD) status in multiple myeloma (MM) based on magnetic resonance imaging (MRI) and identify optimal machine-learning methods to optimise the clinical treatment regimen. MATERIALS AND METHODS: A total of 83 patients were analysed retrospectively. They were divided randomly into training and validation cohorts. The regions of interest were segmented and radiomics features were extracted and analysed on two sequences, including T1-weighted imaging (WI) and fat saturated (FS)-T2WI, and then radiomics models were built in the training cohort and evaluated in the validation cohort. Clinical characteristics were calculated to build a traditional model. A combined model was also built using the clinical characteristics and radiomics features. Classification accuracy was assessed using area under the curve (AUC) and F1 score. RESULTS: In the training cohort, only the bone marrow (BM) infiltrate ratio (p=0.005) was retained after univariate and multivariable logistic regression analysis. In T1WI, the linear support vector machine (SVM) achieved the best performance compared to other classifiers, with AUCs of 0.811 and 0.708 and F1 scores of 0.792 and 0.696 in the training and validation cohorts, respectively. Similarly, in FS-T2WI sequence, linear SVM achieved the best performance with AUCs of 0.833 and 0.800 and F1 score of 0.833 and 0.800. The combined model constructed by the FS-T2WI-linear SVM and BM infiltrate ratio outperformed the traditional model (p=0.050 and 0.012, Delong test), but showed no significant difference compared with the radiomics model (p=0.798 and 0.855). CONCLUSION: The linear SVM-based machine-learning method can offer a non-invasive tool for discriminating MRD status in MM.
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OBJECTIVE: To evaluate the clinical outcomes of immature teeth treated with regenerative endodontic procedures with an over-36-month review, to identify potential contributing factors of root deve-lopment, and to provide new reference for long-time prognosis of regenerative endodontic procedures. METHODS: We recruited teeth that had undergone regenerative endodontic procedures at the Department of Pediatric Dentistry in Peking University School and Hospital of Stomatology from January 2013 to June 2017 and had a follow-up period of more than 36 months.Clinical and radiographic records were collected.We evaluated the treatment outcomes and summarized different patterns of root development.Changes in root length, root canal wall thickness were compared between preoperative and recall radiographs.A statistical analysis was performed using software SPSS 22.0 to identify potential contributing factors of root development. RESULTS: In this study, 84 teeth were recruited and the mean follow-up period was (44.7±19.3) months.The longest follow-up period was 81 months.Sixty-eight teeth (81.0%) were clinical success with bony healing, and 55 teeth (80.9%) gained the continued root development.Forty teeth completed root development with apical closure.The rate of the apical closure reached 58.8%.Twenty-four teeth gained normal root morphology with the increasing of root length and canal wall thickness and apical closure.The rate of continued root development was 92.5% in teeth with broken central cusp and 58.3% in teeth with trauma, which was statistically significant (P < 0.05).There was a statistically significant difference (P < 0.05) between the root development rates of teeth with different induced bleeding heights (orifice/middle/tip of the root)(92.9%/81.0%/63.2%). CONCLUSION: Most of the teeth treated with regenerative endodontic procedures achieved continued root development with an over 36-month follow-up.However, the patterns of root development were different.The morphology of some teeth were close to the physiological state.Etiology and the height of induced bleeding are two factors significantly associated with the rate of the continued development root.