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1.
Clin Chim Acta ; 560: 119732, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38772522

RESUMO

AIM: Our study focuses on the microbial and metabolomic profile changes during the adenoma stage, as adenomas can be considered potential precursors to colorectal cancer through the adenoma-carcinoma sequence. Identifying possible intervention targets at this stage may aid in preventing the progression of colorectal adenoma (CRA) to malignant lesions. Furthermore, we evaluate the efficacy of combined microbial and metabolite biomarkers in detecting CRA. METHODS: Fecal metagenomic and serum metabolomic analyses were performed for the discovery of alterations of gut microbiome and metabolites in CRA patients (n = 26), Colorectal cancer (CRC) patients (n = 19), Familial Adenomatous Polyposis (FAP) patients (n = 10), and healthy controls (n = 20). Finally, analyzing the associations between gut microbes and metabolites was performed by a Receiver Operating Characteristic (ROC) curve. RESULTS: Our analysis present that CRA patients differ significantly in gut microflora and serum metabolites compared with healthy controls, especially for Lachnospiraceae and Parasutterella. Its main metabolite, butyric acid, concentrations were raised in CRA patients compared with the healthy controls, indicating its role as a promoter of colorectal tumorigenesis. α-Linolenic acid and lysophosphatidylcholine represented the other healthy metabolite for CRA. Combining five microbial and five metabolite biomarkers, we differentiated CRA from CRC with an Area Under the Curve (AUC) of 0.85 out of this performance vastly superior to the specificity recorded by traditional markers CEA and CA199 in such differentiation of these conditions. CONCLUSIONS: The study underlines significant microbial and metabolic alterations in CRA with a novel insight into screening and early intervention of its tumorigenesis.

2.
Phys Med Biol ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38670143

RESUMO

OBJECTIVE: Photon-counting micro-computed tomography (micro-CT) is a major advance in small animal preclinical imaging. Small molecule- and nanoparticle-based contrast agents have been widely used to enable the differentiation of liver tumors from surrounding tissues using photon-counting micro-CT. However, there is a notable gap in the application of these market-available agents to the imaging of breast and ovarian tumors using photon-counting micro-CT. Herein, we have used photon-counting micro-CT to determine the effectiveness of these contrast agents in differentiating ovarian and breast tumor xenografts in live, intact mice. Approach. Nude mice carrying different types of breast and ovarian tumor xenografts (AU565, MDA-MB-231 and SKOV-3 human cancer cells) were injected with ISOVUE-370 (a small molecule-based agent) or Exitrone Nano 12000 (a nanoparticle-based agent) and subjected to photon-counting micro-CT. To improve tumor visualization using photon-counting micro-CT, we developed a novel color visualization method, which changes color tones to highlight contrast media distribution, offering a robust alternative to traditional material decomposition methods with less computational demand. Main results. Our in vivo experiments confirm the effectiveness of this color visualization approach, showing distinct enhancement characteristics for each contrast agent. Qualitative and quantitative analyses suggest that Exitrone Nano 12000 provides superior vasculature enhancement and better quantitative consistency across scans, while ISOVUE-370 delivers a more comprehensive tumor enhancement but with significant variance between scans due to its short blood half-time. Further, a paired t-test on mean and standard deviation values within tumor volumes showed significant differences between the AU565 and SKOV-3 tumor models with the nanoparticle-based contrast agent (p-values < 0.02), attributable to their distinct vascularity, as confirmed by immunohistochemical analysis. Significance. These findings underscore the utility of photon-counting micro-CT in non-invasively assessing the morphology and anatomy of different tumor xenografts, which is crucial for tumor characterization and longitudinal monitoring of tumor progression and response to treatments. .

3.
Clin Chim Acta ; 558: 117899, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38574942

RESUMO

Acute myeloid leukemia (AML) is a hematologic malignancy with a high recurrence rate and poor long-term prognosis. DNA excision repair systems, such as base excision repair (BER) and nucleotide excision repair (NER), play a major role in maintaining genomic stability and integrity. Further intensive investigations are necessary to uncover additional AML prognosis loci. In this study, we analyzed 16 candidate SNPs within NER and BER pathways in AML patients. Our results showed the GT/GG genotype of the XPC rs2228001 polymorphism was significantly associated with WBC count in dominant models (OR = 0.41, 95 % CI = 0.18-0.96, p = 0.039). Additionally, the rs25487 and rs3213245 SNPs in the XRCC1 gene, in both co-dominant and dominant models, were significantly associated with PLT count in AML (p < 0.05). The GG genotype of rs1130409 in APEX1 was more prone to adverse cytogenetics in both the codominant and recessive models (p < 0.05). Furthermore, the GA genotypes of ERCC8 rs158572 in codominant model was significantly correlated with refractory group (p < 0.05). ERCC8 rs158572 and XRCC1 rs3213245 in both codominant and dominant models were significantly correlated with the MRD positivity (p < 0.05). Kaplan-Meier analysis revealed an link between overall survival (OS) and the co-dominant, dominant, and recessive models of rs2228001 in XPC. Additionally, patients with the GG and GT/GG genotype in the co-dominant, dominant model and recessive model in XPC rs2228001 exhibited significantly longer survival (p < 0.05). Multivariate Cox analyses indicated that rs2228001 in both co-dominant and dominant models were independent favorable factors impacting patient OS (OR < 1). Our findings suggest that genetic polymorphisms in DNA excision repair pathway genetic polymorphisms contribute to the chemosensitivity and prognosis of acute myeloid leukemia.


Assuntos
Reparo do DNA , Leucemia Mieloide Aguda , Polimorfismo de Nucleotídeo Único , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Reparo do DNA/genética , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Adulto , Idoso , Adulto Jovem , Adolescente , Reparo por Excisão
4.
Artigo em Inglês | MEDLINE | ID: mdl-38442048

RESUMO

Grading laryngeal squamous cell carcinoma (LSCC) based on histopathological images is a clinically significant yet challenging task. However, more low-effect background semantic information appeared in the feature maps, feature channels, and class activation maps, which caused a serious impact on the accuracy and interpretability of LSCC grading. While the traditional transformer block makes extensive use of parameter attention, the model overlearns the low-effect background semantic information, resulting in ineffectively reducing the proportion of background semantics. Therefore, we propose an end-to-end network with transformers constrained by learned-parameter-free attention (LA-ViT), which improve the ability to learn high-effect target semantic information and reduce the proportion of background semantics. Firstly, according to generalized linear model and probabilistic, we demonstrate that learned-parameter-free attention (LA) has a stronger ability to learn highly effective target semantic information than parameter attention. Secondly, the first-type LA transformer block of LA-ViT utilizes the feature map position subspace to realize the query. Then, it uses the feature channel subspace to realize the key, and adopts the average convergence to obtain a value. And those construct the LA mechanism. Thus, it reduces the proportion of background semantics in the feature maps and feature channels. Thirdly, the second-type LA transformer block of LA-ViT uses the model probability matrix information and decision level weight information to realize key and query, respectively. And those realize the LA mechanism. So, it reduces the proportion of background semantics in class activation maps. Finally, we build a new complex semantic LSCC pathology image dataset to address the problem, which is less research on LSCC grading models because of lacking clinically meaningful datasets. After extensive experiments, the whole metrics of LA-ViT outperform those of other state-of-the-art methods, and the visualization maps match better with the regions of interest in the pathologists' decision-making. Moreover, the experimental results conducted on a public LSCC pathology image dataset show that LA-ViT has superior generalization performance to that of other state-of-the-art methods.

5.
Zhongguo Gu Shang ; 37(3): 319-26, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38515423

RESUMO

Acetabular quadrilateral plate injury has become a hot spot and focus in the field of orthopaedic trauma and pelvic floor function in recent years. Although there are five fracture types,they are all based on fracture morphology,without considering the pulling force of ligaments,joint capsular and muscles. A perfect classification needs to describe the displacement of bone mass in three-dimensional space to better guide reduction and fixation. The seven incision and exposure methods are still the traditional open-eye surgery,and how to protect the criss-crossing vascular neural network and pelvic organs is still the focus. Quadrilateral defect causes dislocation of artificial hip joint,and quantitative evaluation of quadrilateral defect volume and revision techniques are still a hot topic. In this paper,the viewpoints of three-dimensional network structure of acetabular pelvic vascular anatomy,anatomical surgical target channel and fixation anchor point of acetabular fracture reduction are proposed to design new techniques for accurate and minimally invasive surgical operations,in order to realize the requirements of rapid orthopedic rehabilitation.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Fraturas da Coluna Vertebral , Humanos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Acetábulo/cirurgia , Acetábulo/lesões , Fraturas do Quadril/cirurgia , Placas Ósseas
6.
Leukemia ; 38(5): 1057-1071, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38424136

RESUMO

Most forms of chemotherapy for acute myeloid leukemia (AML) are often ineffective in eliminating leukemic stem cells (LSCs), as their underlying mechanisms remain unclear. Here, we have identified circFAM193B, which regulates the redox biology of LSCs and is associated with unfavorable outcomes in AML patients. In vitro and in vivo assays suggested that circFAM193B significantly inhibits LSCs chemotherapy resistance and AML progression. Knockdown circFAM193B enhances mitochondrial OXPHOS function and inhibits the accumulation of reactive oxygen species and lipid peroxidation mediated by chemotherapy, which protects AML cells from oxidative stress-induced cell death. Mechanistically, circFAM193B physically interacts with arginine methyltransferase PRMT6 catalytic domain and enhances the transcription efficiency of key lipid peroxidation factor ALOX15 by decreasing H3R2me2a modification. In summary, we have identified circFAM193B was downregulated in LSCs to promote the survival of LSC by modulating energy metabolism and the redox balance in the postchemotherapy persistence of LSC. Our studies provide a conceptual advance and biological insights regarding the drug resistance of LSCs via circRNA mediated PRMT6-deposited methylarginine signaling.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda , Peroxidação de Lipídeos , Células-Tronco Neoplásicas , Proteínas Nucleares , Proteína-Arginina N-Metiltransferases , Humanos , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Camundongos , Animais , Estresse Oxidativo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo
7.
Free Radic Biol Med ; 213: 36-51, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38215892

RESUMO

Short-chain fatty acids (SCFAs), particularly propionate and butyrate, have been reported in many cancers. However, the relationship between propionate and acute myeloid leukemia (AML) remains unclear. Additionally, Acyl-CoA synthetase long chain family member 4 (ACSL4) has been reported to regulate immunity in solid tumors, but there are still many gaps to be filled in AML. Here, we discovered the underlying mechanism of propionate and ACSL4-mediated ferroptosis for immunotherapy. Our results showed that the level of propionate in the AML patients' feces was decreased, which was correlated to gut microbiota dysbiosis. Moreover, we demonstrated that propionate suppressed AML progression both in vivo and in vitro. In mechanism, propionate induced AML cells apoptosis and ferroptosis. The imbalance of reactive oxygen species (ROS) and redox homeostasis induced by propionate caused mitochondrial fission and mitophagy, which enhanced ferroptosis and apoptosis. Furthermore, ACSL4-mediated ferroptosis caused by propionate increased the immunogenicity of AML cells, induced the release of damage-associated molecular patterns (DAMPs), and promoted the maturation of dendritic cells (DCs). The increased level of immunogenicity due to ferroptosis enable propionate-based whole-cell vaccines to activate immunity, thus further facilitating effective killing of AML cells. Collectively, our study uncovers a crucial role for propionate suppresses AML progression by inducing ferroptosis and the potential mechanisms of ACSL4-mediated ferroptosis in the regulation of AML immunity.


Assuntos
Ferroptose , Leucemia Mieloide Aguda , Humanos , Propionatos/farmacologia , Mitofagia , Apoptose , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia
8.
bioRxiv ; 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38260707

RESUMO

Photon-counting micro computed tomography (micro-CT) offers new potential in preclinical imaging, particularly in distinguishing materials. It becomes especially helpful when combined with contrast agents, enabling the differentiation of tumors from surrounding tissues. There are mainly two types of contrast agents in the market for micro-CT: small molecule-based and nanoparticle-based. However, despite their widespread use in liver tumor studies, there is a notable gap in research on the application of these commercially available agents for photon-counting micro-CT in breast and ovarian tumors. Herein, we explored the effectiveness of these agents in differentiating tumor xenografts from various origins (AU565, MDA-MB-231, and SKOV-3) in nude mice, using photon-counting micro-CT. Specifically, ISOVUE-370 (a small molecule-based agent) and Exitrone Nano 12000 (a nanoparticle-based agent) were investigated in this context. To improve tumor visualization, we proposed a novel color visualization method for photon-counting micro-CT, which changes color tones to highlight contrast media distribution, offering a robust alternative to traditional material decomposition methods with less computational demand. Our in vivo experiments confirm its effectiveness, showing distinct enhancement characteristics for each contrast agent. Qualitative and quantitative analyses suggested that Exitrone Nano 12000 provides superior vasculature enhancement and better quantitative consistency across scans, while ISOVUE-370 gives more comprehensive tumor enhancement but with a significant variance between scans due to its short blood half-time. This variability leads to high sensitivity to timing and individual differences among mice. Further, a paired t-test on mean and standard deviation values within tumor volumes showed significant differences between the AU565 and SKOV-3 tumor models with the nanoparticle-based (p-values < 0.02), attributable to their distinct vascularity, as confirmed by immunohistochemistry. These findings underscore the utility of photon-counting micro-CT in non-invasively assessing the morphology and anatomy of different tumor xenografts, which is crucial for tumor characterization and longitudinal monitoring of tumor development and response to treatments.

10.
Clin Chim Acta ; 554: 117789, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38246208

RESUMO

Gene mutations are a pivotal component of the pathogenesis of MDS, and they hold profound prognostic significance for predicting treatment responses and survival outcomes. However, reports about mutation patterns in Chinese MDS patients are limited. In this study, we analyzed the genetic mutation of 23 genes in 231 patients with MDS using next-generation sequencing (NGS) technology, and explored the characteristics of gene mutations in MDS patients and their associations with clinical outcomes, survival, and transformation outcomes. Our results showed that 68.83% patients had at least one gene mutation, and the most common mutations were ASXL1 (21.65%), SF3B1 (17.32%), U2AF1 (16.02%), TET2 (14.72%) and TP53 (8.66%). We also showed that the genetic mutations of TP53, U2AF1 and DNMT3A are independent risk factors for death in patients with MDS, and the ETV6 gene mutation was an independent risk factor for the transformation of MDS patients to AML through the univariate and multivariate Cox regression analysis model. Additionally, the study developed a risk score based on gene mutation data that demonstrated robust predictive capability and stability for the overall survival of MDS patients. Our research provided a strong theoretical basis for the establishment of personalized treatment and prognostic risk assessment models for Chinese MDS patients.


Assuntos
Síndromes Mielodisplásicas , Humanos , Fator de Processamento U2AF/genética , Mutação , Prognóstico , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Fatores de Transcrição/genética
11.
Autophagy ; 20(3): 541-556, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37733919

RESUMO

Sorafenib is the most widely used first-line drug for the treatment of the advanced hepatocellular carcinoma (HCC). Unfortunately, sorafenib resistance often limits its therapeutic efficacy. To evaluate the efficacy of artesunate against sorafenib-resistant HCC and to investigate its underlying pharmacological mechanisms, a "sorafenib resistance related gene-ART candidate target" interaction network was constructed, and a signaling axis consisting with artesunate candidate target AFAP1L2 and sorafenib target SRC, and the downstream FUNDC1-dependent mitophagy was identified as a major contributor to the sorafenib resistance and a potential way of artesunate to mitigate resistance. Notably, our clinical data demonstrated that AFAP1L2 expression in HCC tissues was markedly higher than that in adjacent non-cancerous liver tissues (P < 0.05), and high AFAP1L2 expression was also significantly associated with an unfavorable overall survival of HCC patients (P < 0.05). Experimentally, AFAP1L2 was overexpressed in sorafenib resistant cells, leading to the activation of downstream SRC-FUNDC1 signaling axis, further blocking the FUNDC1 recruitment of LC3B to mitochondria and inhibiting the activation of mitophagy, based on both in vitro and in vivo systems. Moreover, artesunate significantly enhanced the inhibitory effects of sorafenib on resistant cells and tumors by inducing excessive mitophagy. Mechanically, artesunate reduced the expression of AFAP1L2 protein, suppressed the phosphorylation levels of SRC and FUNDC1 proteins, promoted the FUNDC1 recruitment of massive LC3B to mitochondria, and further overactivated the mitophagy and subsequent cell apoptosis of sorafenib resistant cells. In conclusion, artesunate may be a promising strategy to mitigate sorafenib resistance in HCC via exacerbating AFAP1L2-SRC-FUNDC1 axis-dependent mitophagy.Abbreviations: AFAP1L2, actin filament associated protein 1 like 2; ANOVA, analysis of variance; ANXA5, annexin V; ART: artesunate; CETSA, cellular thermal shift assay; CI: combination index; CO-IP: co-immunoprecipitation; CQ: chloroquine; CT, computed tomography; [18F]-FDG, fluoro-2-D-deoxyglucose F18; FUNDC1: FUN14 domain containing 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HCC, hepatocellular carcinoma; H&E Staining: hematoxylin - eosin staining; HepG2R, sorafenib resistant HepG2; IF, immunofluorescence; IHC, immunohistochemistry; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; miR, microRNA; mRNA: messenger RNA; OE, overexpression; OS, overall survival; PET, positron emission tomography; qRT-PCR: quantitative real-time PCR; sh, short hairpin; shNC: negative control shRNA; shAFAP1L2: short hairpin AFAP1L2; SORA, sorafenib; SPR, surface plasmon resonance; SRC, SRC proto-oncogene, non-receptor tyrosine kinase; SUV, standardized uptake value; TEM, transmission electron microscopy; TOMM20: translocase of outer mitochondrial membrane 20.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sorafenibe/farmacologia , Mitofagia/genética , Artesunato/farmacologia , Artesunato/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Autofagia , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo
12.
Heart Surg Forum ; 26(5): E478-E484, 2023 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-37920094

RESUMO

BACKGROUND: Ventricular septal rupture (VSR) following myocardial infarction (MI) is a rare but lethal complication. We analyzed the long-term results and risk factors for survival in the treatment of VSR. METHODS: From January 2012 to December 2021, 115 consecutive patients with post-MI VSR were admitted to our hospital. Depending on different treatment methods patients were divided into following three groups: medical, transcatheter intervention, and surgical repair. During the study, relevant clinical data, operation-related conditions, and follow-up data were analyzed. The Kaplan-Meier method and log-rank test were used to determine the cumulative incidence of mortality. The independent risk factors for patient mortality were evaluated by multivariate logistic regression. RESULTS: The mean follow-up time was 43.4 ± 34.7 months. The overall in-hospital, 30-day, and long-term mortality rates were 24.3%, 38.3%, and 51.3%, respectively. In the medical group, the in-hospital and 30-day mortality rates were 46.7 % (21/45) and 82.2 % (37/45), respectively, with only three patients alive at follow-up. In the transcatheter intervention group, 30-day and long-term mortality rates were 12% and 28%, respectively. In the surgical repair group, 30-day and long-term mortality rates were 8.9% and 22.2%, respectively. Compared with the surgery-group patients, patients with transcatheter intervention had a longer time from VSR to intervention. Logistic regression analysis revealed that age, previous infarction, Killip class, serum creatinine, Troponin T, N-terminal pro-B-type natriuretic peptide, and medical strategy were risk factors for all-cause mortality. CONCLUSIONS: The 30-day and long-term outcomes of patients treated with surgical repair and transcatheter intervention were significantly better than medically treated patients.


Assuntos
Infarto do Miocárdio , Ruptura do Septo Ventricular , Humanos , Seguimentos , Ruptura do Septo Ventricular/diagnóstico , Ruptura do Septo Ventricular/etiologia , Ruptura do Septo Ventricular/cirurgia , Estudos Retrospectivos , Infarto do Miocárdio/cirurgia , Fatores de Risco , Resultado do Tratamento
13.
J Cancer Res Clin Oncol ; 149(19): 17307-17318, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37819582

RESUMO

PURPOSE: Stem cells are known to play an important role in tumor treatment and many of them have shown tumor-suppressing ability in different cancers; however, whether hematopoietic stem cells (HSCs) have growth-inhibiting effects on leukemia cells has not been fully evaluated. Herein, we aimed to demonstrate the growth-restraining function of HSCs in acute leukemia treatment. METHODS: Cell fusion experiment was conducted by PEG-1500. The viability, proliferation, apoptosis and differentiation of leukemia cells were evaluated by cell counting, CCK-8 and flow cytometry analysis. The morphological changes were imaged using a fluorescence microscope. The expression of genes was detected by quantitative reverse transcription PCR (qRT-PCR). RESULTS: We observed that HSCs and their lytic extracts had the capability to suppress leukemia cells proliferation, promote apoptosis and especially induce acute myelogenous leukemia (AML) cells differentiation, which might have an effect on differentiation therapy to leukemia especially AML treatment. The expression levels of Bcl-2, Survivin decreased and Bax increased following HSCs extracts treatment. Furthermore, the expression of inflammatory cytokines also changed in AML cells which might have to do with the mechanism of HSCs/extracts suppressing effect. CONCLUSION: HSCs and their extracts can suppress the proliferation of leukemia cells and enhance the differentiation of AML cells and using the extracts of HSCs might be a probable therapeutic option for acute leukemia.


Assuntos
Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/patologia , Diferenciação Celular , Proliferação de Células , Apoptose/genética
14.
Biomark Res ; 11(1): 89, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798791

RESUMO

Mitochondria are energy-generated organelles and take an important part in biological metabolism. Mitochondria could be transferred between cells, which serves as a new intercellular communication. Mitochondrial transfer improves mitochondrial defects, restores the biological functions of recipient cells, and maintains the high metabolic requirements of tumor cells as well as drug resistance. In recent years, it has been reported mitochondrial transfer between cells of bone marrow microenvironment and hematological malignant cells play a critical role in the disease progression and resistance during chemotherapy. In this review, we discuss the patterns and mechanisms on mitochondrial transfer and their engagement in different pathophysiological contexts and outline the latest knowledge on intercellular transport of mitochondria in hematological malignancies. Besides, we briefly outline the drug resistance mechanisms caused by mitochondrial transfer in cells during chemotherapy. Our review demonstrates a theoretical basis for mitochondrial transfer as a prospective therapeutic target to increase the treatment efficiency in hematological malignancies and improve the prognosis of patients.

15.
Orthop Surg ; 15(11): 2855-2863, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37740552

RESUMO

BACKGROUND: Iliosacral screw insertion by computer-assisted navigation gradually became the main technique in some hospitals, but the expensive price limited the extensive application. But other techniques such as 3D printed template was used to place iliosacral screw as novel method. This study was to compare the efficiency of percutaneous iliosacral screw placement by using patient-specific template and computer-assisted navigation. METHODS: Total of 58 patients from September 2017 to September 2021 with sacral injury were treated operatively with percutaneous screw technique, which was selected for this retrospective analysis and divided into two groups (template and computer-assisted navigation). There were 31 patients in template group and 27 patients in computer-assisted navigation group. The surgical details (operation time, blood loss, number of screw placements, and number of fluoroscopies), complications, radiographic and clinical results were recorded. The quality of reduction was assessed by the Matta scoring system. T-test and rank-sum test was used in this study. RESULTS: Operation time in template group was less (33.97 ± 16.61 < 60.31 ± 11.46 min, p < 0.01), but the preoperative preparation time was more (6.35 ± 1.60 > 5.41 ± 1.58, p < 0.05). The quality of reduction in both groups was no difference (p = 0.352). A patient was complicated with gluteal vessel injury in operation in navigation group, which was treated with ligation, but the same injury was not observed in template group. The related surgical data of patient with gluteal injury was ignored in statistical analysis. CONCLUSION: Both of the two techniques could improve surgical efficiency, the operation time in template was less than computer-assisted navigation group, but the preoperative preparation time was more.


Assuntos
Fraturas Ósseas , Cirurgia Assistida por Computador , Humanos , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas/métodos , Estudos Retrospectivos , Parafusos Ósseos , Cirurgia Assistida por Computador/métodos , Impressão Tridimensional , Computadores
16.
Orthop Surg ; 15(9): 2400-2409, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37435882

RESUMO

OBJECTIVE: Posterior wall (PW) fractures were sometimes associated in both-column acetabular fractures. How to evaluate pre-operatively the necessity for the performance of the posterior approach was an issue to be solved. In order to solve this issue, the computer-assisted virtual surgery technique was used to evaluate if the involved PW in both-column acetabular fractures (BACF) should be managed through posterior approach and verify the feasibility of this method. METHODS: Data of a consecutive cohort of 72 patients with both-acetabular fractures from January 2012 to January 2020 was collected for retrospective study, of which 44 patients had concomitant acetabular PW fractures, and patients without PW fractures were labeled as the BCAF group. Computer-assisted virtual surgery technique was performed pre-operatively to evaluate the necessity for performance of posterior approach in 44 patients, and posterior approach was required if more than 3 mm of displacement was still present in the reduced 3D model. The 23 patients without treatment through posterior approach were labeled as the BCAF-PW- group, and the 21 patients with treatment through posterior approach were labeled as the BCAF-PW+ group. Operation-related and post-operative parameters were recorded. The quality of reduction and functional outcomes were assessed by the Matta scoring system and modified Merle d'Aubigné and Postel scoring system. The measurement data were analyzed using the t-test of independent samples and rank-sum test of ranked data between every two groups. Also, the one-way analysis of variance (ANOVA) was used to analyze data between the three groups. RESULTS: Comparing operation-related and post-operative parameters in the three groups, some PW fractures in both-column acetabular fractures could be ignored, and which could be evaluated pre-operatively for necessity of an additional posterior approach. Operative time (271.2 ± 32.8 mins) and intra-operative blood loss (1176.7 ± 211.1 mL) were significantly higher in the BCAF-PW+ group. The excellent/good of reduction (25/28 of the BCAF group, 21/23 of the BCAF-PW- group, 19/21 of the BCAF-PW+ group) and functional outcomes (24/28 of the BCAF group, 18/23 of the BCAF-PW- group, 18/21 of the BCAF-PW+ group) of three groups were similar. The incidence of complications, such as deep vein thrombosis (4/28 of the BCAF group >3/23 of the BCAF-PW- group >1/21 of the BCAF-PW+ group) and injury of lateral femoral cutaneous nerve (3/23 of the BCAF-PW- group >2/28 of the BCAF group >0/21 of the BCAF-PW+ group), was no significant difference. CONCLUSION: The partial both-column acetabular fractures with PW involvement could be managed through a single anterior approach without another posterior approach by evaluation of computer-assisted virtual surgery technique.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Fraturas da Coluna Vertebral , Humanos , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Acetábulo/cirurgia , Acetábulo/lesões , Resultado do Tratamento , Fraturas do Quadril/cirurgia , Fraturas Ósseas/cirurgia , Computadores
17.
PLoS One ; 18(6): e0286123, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37319275

RESUMO

The high spatial and temporal resolution of dynamic contrast-enhanced MRI (DCE-MRI) can improve the diagnostic accuracy of breast cancer screening in patients who have dense breasts or are at high risk of breast cancer. However, the spatiotemporal resolution of DCE-MRI is limited by technical issues in clinical practice. Our earlier work demonstrated the use of image reconstruction with enhancement-constrained acceleration (ECA) to increase temporal resolution. ECA exploits the correlation in k-space between successive image acquisitions. Because of this correlation, and due to the very sparse enhancement at early times after contrast media injection, we can reconstruct images from highly under-sampled k-space data. Our previous results showed that ECA reconstruction at 0.25 seconds per image (4 Hz) can estimate bolus arrival time (BAT) and initial enhancement slope (iSlope) more accurately than a standard inverse fast Fourier transform (IFFT) when k-space data is sampled following a Cartesian based sampling trajectory with adequate signal-to-noise ratio (SNR). In this follow-up study, we investigated the effect of different Cartesian based sampling trajectories, SNRs and acceleration rates on the performance of ECA reconstruction in estimating contrast media kinetics in lesions (BAT, iSlope and Ktrans) and in arteries (Peak signal intensity of first pass, time to peak, and BAT). We further validated ECA reconstruction with a flow phantom experiment. Our results show that ECA reconstruction of k-space data acquired with 'Under-sampling with Repeated Advancing Phase' (UnWRAP) trajectories with an acceleration factor of 14, and temporal resolution of 0.5 s/image and high SNR (SNR ≥ 30 dB, noise standard deviation (std) < 3%) ensures minor errors (5% or 1 s error) in lesion kinetics. Medium SNR (SNR ≥ 20 dB, noise std ≤ 10%) was needed to accurately measure arterial enhancement kinetics. Our results also suggest that accelerated temporal resolution with ECA with 0.5 s/image is practical.


Assuntos
Neoplasias da Mama , Imageamento por Ressonância Magnética , Feminino , Humanos , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste/farmacocinética , Seguimentos , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos
18.
Cancer Med ; 12(14): 14960-14978, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37329186

RESUMO

BACKGROUND: Though immunological abnormalities have been proven involved in the pathogenesis of lymphoma, the underlying mechanism remains unclear. METHODS: We investigated 25 single nucleotide polymorphisms (SNPs) of 21 immune-related genes and explored their roles in lymphoma. The genotyping assay of the selected SNPs was used by the Massarray platform. Logistic regression and Cox proportional hazards models were used to analyze the associations of SNPs and the susceptibility of lymphoma or clinical characteristics of lymphoma patients. In addition, Least Absolute Shrinkage and Selection Operator regression was used to further analyze the relationships with the survival of lymphoma patients and candidate SNPs, and the significant difference between genotypes was verified by the expression of RNA. RESULTS: By comparing 245 lymphoma patients with 213 healthy controls, we found eight important SNPs related to the susceptibility of lymphoma, which were involved in JAK-STAT, NF-κB and other functional pathways. We further analyzed the relationships between SNPs and clinical characteristics. Our results showed that both IL6R (rs2228145) and STAT5B (rs6503691) significantly contributed to the Ann Arbor stages of lymphoma. And the STAT3 (rs744166), IL2 (rs2069762), IL10 (rs1800871), and PARP1 (rs907187) manifested a significant relationship with the peripheral blood counts in lymphoma patients. More importantly, the IFNG (rs2069718) and IL12A (rs6887695) were associated with the overall survival (OS) of lymphoma patients remarkably, and the adverse effects of GC genotypes could not be offset by Bonferroni correction for multiple comparison in rs6887695 especially. Moreover, we determined that the mRNA expression levels of IFNG and IL12A were significantly decreased in patients with shorter-OS genotypes. CONCLUSIONS: We used multiple methods of analysis to predict the correlations between lymphoma susceptibility, clinical characteristics or OS with SNPs. Our findings reveal that immune-related genetic polymorphisms contribute to the prognosis and treatment of lymphoma, which may serve as promising predictive targets.


Assuntos
Linfoma , Humanos , Genótipo , Linfoma/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Modelos de Riscos Proporcionais , Predisposição Genética para Doença , Estudos de Casos e Controles
19.
Mol Biol Rep ; 50(8): 6601-6610, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37344641

RESUMO

BACKGROUND: Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but their clinical and prognostic relevance in acute myeloid leukemia (AML) have rarely been reported. METHODS: A total of 368 newly diagnosed non-M3 AML patients were included in this study. Next generation sequencing including four SF genes was performed on the genomicDNA. The clinical features and survival were analyzed using statistical analysis. RESULTS: We found that 64 of 368 patients harbored SF mutations. The SF mutations were much more frequently found in older or male patients. SRSF2 mutations were shown obviously co-existed with IDH2 mutation. The level of measurable residual disease after first chemotherapy was higher in SF-mutated patients compared to that in SF-wild patients, while the complete remission rate was significantly decreased. And the overall survival of SF-mutated patients was shorter than that of SF-wild patients. Moreover, our multivariable analysis suggests that the index of male, Kit mutation or ZRSR2 mutation was the independent risk factor for overall survival. SRSF2mut was associated with older age, higher proportion of peripheral blasts or abnormal cell proportion by flow cytometry. CONCLUSION: SF mutation is a distinct subgroup of AML frequently associated with clinic-biological features and poor outcome. SRSF2mut could be potential targets for novel treatment in AML.


Assuntos
Leucemia Mieloide Aguda , Spliceossomos , Humanos , Masculino , Idoso , Spliceossomos/genética , Prognóstico , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de RNA/genética , Leucemia Mieloide Aguda/genética , Mutação/genética
20.
Clin Case Rep ; 11(5): e7374, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37215975

RESUMO

Key Clinical Message: A 23-year-old male with a tumor in the eye socket was characterized by multimodal images, including ultrasonography, computed tomography, and magnetic resonance imaging. After admission, surgical resection of the tumor was performed and superficial angiomyxoma was confirmed. Two years later, this tumor recurred in the same location. Abstract: Superficial angiomyxoma (SAM) is a rare benign neoplasm composed mostly of myxoid material that can affect many parts of the body in middle-aged patients. Only a few case reports have involved imaging, which is extremely insufficient. Here, we present a case of SAM in the eye socket evaluated by imaging, including ultrasonography, computed tomography, and magnetic resonance imaging. The patient underwent surgical resection, and the diagnosis of SAM was confirmed. During the postoperative follow-up, the tumor recurred in the same location without metastasis 2 years later.

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