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1.
J Coll Physicians Surg Pak ; 34(6): 672-676, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840349

RESUMO

OBJECTIVE: To explore the preventive efficacy of antibiotics following surgical removal of the impacted mandibular third molars and screen the potential risk factors. STUDY DESIGN: A cohort trial. Place and Duration of the Study: Department of Oral and Maxillofacial Surgery, Zhejiang University School of Medicine, Stomatology Hospital, Hangzhou, China, from August 2021 to 2022. METHODOLOGY: Cases with impacted mandibular third molar were divided into two groups based on antibiotics use. The primary outcome variable post-operative infection, secondary clinical parameter analgesics intake, and other variables (the operative time, the history of pericoronitis, and wound closure) were documented. RESULTS: The post-operative infections occurred in 3.64% (n = 12) of the 330 cases (n = 330); 3.01% in the antibiotic group (n = 166) and 4.27% in the control group (n = 164, OR = 1.44, 95% CI: 0.49 to 4.06; p = 0.54). Concerning secondary outcome measures, the analgesics that the antibiotic group took was 5.40, and the control group took was 5.95 (95% CI = -0.21 to 1.30; p = 0.16). For those with post-operative infections, the average operative time was 22.83 minutes, whereas for those without post-operative infections it was 14.87 minutes (95% CI = -0.26 to 15.67; p = 0.04). When the operative time was greater than or equal to 15 minutes, it was related to more analgesics use (95% CI: -0.43 to 1.93; p <0.05), also was the history of pericoronitis (95% CI = 0.04 to 1.54; p = 0.04). CONCLUSION: Antibiotics are unnecessary for preventing post-operative infections or minimising analgesic requirements following extraction of the impacted mandibular third molars; operative time and pericoronitis showed a suppressive influence on post-operative recovery. KEY WORDS: Impacted molars, Antibiotics, Analgesics, Operative time, Pericoronitis.


Assuntos
Antibacterianos , Antibioticoprofilaxia , Dente Serotino , Infecção da Ferida Cirúrgica , Extração Dentária , Dente Impactado , Humanos , Dente Serotino/cirurgia , Masculino , Dente Impactado/cirurgia , Feminino , Extração Dentária/efeitos adversos , Adulto , Infecção da Ferida Cirúrgica/prevenção & controle , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Mandíbula/cirurgia , Adulto Jovem , China/epidemiologia , Duração da Cirurgia , Estudos de Coortes , Resultado do Tratamento
2.
Phytomedicine ; 131: 155758, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38843643

RESUMO

BACKGROUND: The adaptor protein apoptosis-associated speck-like protein (ASC) containing a caspase recruitment domain (CARD) can be activated through pyrin domain (PYD) interactions between sensors and ASC, and through CARD interactions between caspase-1 and ASC. Although the majority of ternary inflammasome complexes depend on ASC, drugs targeting ASC protein remain scarce. After screening natural compounds from Isatidis Radixin, we found that tryptanthrin (TPR) could inhibit NLRP3-induced IL-1ß and caspase-1 production, but the underlying anti-inflammatory mechanisms remain to be elucidated. PURPOSE: The purpose of this study was to determine the impact of TPR on the NLRP3, NLRC4, and AIM2 inflammasomes and the underlying mechanisms. Additionally, the efficacy of TPR was analysed in the further course of methionine- and choline-deficient (MCD)-induced NASH and lipopolysaccharide (LPS)-induced sepsis models of mice. METHODS: In vitro studies used bone marrow-derived macrophages to assess the anti-inflammatory activity of TPR, and the techniques included western blot, testing of intracellular K+ and Ca2+, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), co-immunoprecipitation, ASC oligomerization assay, surface plasmon resonance (SPR), and molecular docking. We used LPS-induced sepsis models and MCD-induced NASH models in vivo to evaluate the effectiveness of TPR in inhibiting inflammatory diseases. RESULTS: Our observations suggested that TPR could inhibit NLRP3, NLRC4, and AIM2 inflammasome activation. As shown in a mouse model of inflammatory diseases caused by MCD-induced NASH and LPS-induced sepsis, TPR significantly alleviated the progression of diseases. TPR interrupted the interactions between ASC and NLRP3/NLRC4/AIM2 in the co-immunoprecipitation experiment, and stable binding of TPR to ASC was also evident in SPR experiments. The underlying mechanisms of anti-inflammatory activities of TPR might be associated with targeting ASC, in particular, PYD domain of ASC. CONCLUSION: In general, the requirement for ASC in multiple inflammasome complexes makes TPR, as a novel broad-spectrum inflammasome inhibitor, potentially useful for treating a wide range of multifactorial inflammasome-related diseases.


Assuntos
Proteínas Adaptadoras de Sinalização CARD , Proteínas de Ligação ao Cálcio , Inflamassomos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Hepatopatia Gordurosa não Alcoólica , Quinazolinas , Animais , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Masculino , Proteínas de Ligação ao Cálcio/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Quinazolinas/farmacologia , Camundongos , Proteínas Reguladoras de Apoptose/metabolismo , Interleucina-1beta/metabolismo , Proteínas de Ligação a DNA/metabolismo , Caspase 1/metabolismo , Sepse/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Modelos Animais de Doenças
3.
Mol Cancer ; 23(1): 95, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720319

RESUMO

BACKGROUND: Dysregulation of immune surveillance is tightly linked to the development of metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC); however, its underlying mechanisms remain unclear. Herein, we aimed to determine the role of interleukin-21 receptor (IL-21R) in MASH-driven HCC. METHODS: The clinical significance of IL-21R was assessed in human HCC specimens using immunohistochemistry staining. Furthermore, the expression of IL-21R in mice was assessed in the STAM model. Thereafter, two different MASH-driven HCC mouse models were applied between IL-21R-deficient mice and wild type controls to explore the role of IL-21R in MASH-driven HCC. To further elucidate the potential mechanisms by which IL-21R affected MASH-driven HCC, whole transcriptome sequencing, flow cytometry and adoptive lymphocyte transfer were performed. Finally, flow cytometry, enzyme-linked immunosorbent assay, immunofluorescent staining, chromatin immunoprecipitation assay and western blotting were conducted to explore the mechanism by which IL-21R induced IgA+ B cells. RESULTS: HCC patients with high IL-21R expression exhibited poor relapse-free survival, advanced TNM stage and severe steatosis. Additionally, IL-21R was demonstrated to be upregulated in mouse liver tumors. Particularly, ablation of IL-21R impeded MASH-driven hepatocarcinogenesis with dramatically reduction of lipid accumulation. Moreover, cytotoxic CD8+ T lymphocyte activation was enhanced in the absence of IL-21R due to the reduction of immunosuppressive IgA+ B cells. Mechanistically, the IL-21R-STAT1-c-Jun/c-Fos regulatory axis was activated in MASH-driven HCC and thus promoted the transcription of Igha, resulting in the induction of IgA+ B cells. CONCLUSIONS: IL-21R plays a cancer-promoting role by inducing IgA+ B cells in MASH-driven hepatocarcinogenesis. Targeting IL-21R signaling represents a potential therapeutic strategy for cancer therapy.


Assuntos
Linfócitos B , Carcinoma Hepatocelular , Fígado Gorduroso , Imunoglobulina A , Neoplasias Hepáticas , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Linfócitos B/metabolismo , Linfócitos B/imunologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/etiologia , Regulação Neoplásica da Expressão Gênica , Imunoglobulina A/metabolismo , Subunidade alfa de Receptor de Interleucina-21/metabolismo , Subunidade alfa de Receptor de Interleucina-21/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Receptores de Interleucina-21/metabolismo , Receptores de Interleucina-21/genética
4.
J Cardiothorac Surg ; 19(1): 271, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702771

RESUMO

BACKGROUND: MicroRNA-200b-3p (miR-200b-3p) plays a pivotal role in inflammatory responses and is implicated in various inflammatory disorders. In this study, we aim to explore the role of miR-200b-3p in the inflammatory response in heart failure (HF). METHODS: Patients diagnosed with heart failure and age-matched healthy controls were studied. Peripheral blood samples from participants were collected for RNA-seq analysis to explore the expression profile of miR-200b-3p. The predictive value of miR-200b-3p and ZEB1 in the prognosis of heart failure was evaluated by analyzing the receiver operating characteristic (ROC) curve. Bioinformatics analysis and double luciferase reporter gene analysis were used to confirm the interaction between miR-200b-3p and ZEB1. Real-time quantitative polymerase chain reaction (QRT-PCR) was used to detect the expression levels of miR-200b-3p and ZEB1 in cardiopulmonary bypass. Additionally, the effects of miR-200b-3p on myocardial cell line (H9c2) injury were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: In the extracardiac circulation of HF patients, miR-200b-3p expression was significantly reduced, while ZEB1 levels were notably elevated. Analysis of the ROC curve revealed that miR-200b-3p and ZEB1 have predictive value in the prognosis of HF patients. The double luciferase reporter experiment demonstrated that miR-200b-3p binds to ZEB1 and inhibits its expression. Overexpression of miR-200b-3p demonstrated a remarkable ability to alleviate inflammation and inhibit the damage to myocardial cells in vivo. CONCLUSION: MiR-200b-3p can target and inhibit ZEB1, reducing the inflammatory reaction of myocardial cells. The miR-200b-3p/ZEB1 network may be helpful in preventing and treating HF.


Assuntos
Insuficiência Cardíaca , Inflamação , MicroRNAs , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Humanos , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , MicroRNAs/genética , Insuficiência Cardíaca/genética , Masculino , Inflamação/genética , Inflamação/metabolismo , Feminino , Pessoa de Meia-Idade , Regulação da Expressão Gênica
5.
Immunotherapy ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578121

RESUMO

Aim: The study aimed to assess the value of pretreatment peripheral blood neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), pan-immune-inflammation value (PIV) and systemic immune-inflammation index (SII) for predicting immunotherapy prognosis and efficacy in advanced gastric cancer (GC). Methods: A total of 84 advanced GC patients received immunotherapy were retrospectively collected. The optimal cut-off values were determined by receiver operating characteristic curves. The univariate and multivariate analysis investigated the effects of NLR, PLR, PIV and SII on patients prognosis. Results: NLR, PLR, PIV and SII had predictive value of efficacy. NLR ≥3.65 was an independent risk factor for worse outcomes. Conclusion: NLR, PLR, PIV and SII have predictive value of efficacy and NLR ≥3.65 suggests a poor prognosis following immunotherapy in advanced GC.


Immunotherapy can make gastric cancer patients live longer. However, not all patients live longer. We need simple, inexpensive and effective indicators to find patients who can live longer with immunotherapy. Routine blood test is common in our daily lives. Previous studies reported that some indicators in routine blood test can predict the prognosis and efficacy of surgery in gastric cancer patients. But it is not clear in immunotherapy for advanced gastric cancer patients. In our trial, we found that some indicators in routine blood test can help predict the effect of immunotherapy in patients with advanced gastric cancer and screen which patients will live longer with immunotherapy.

6.
RSC Adv ; 14(20): 13801-13807, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38681838

RESUMO

Near-infrared red (NIR) fluorescence imaging guide phototherapeutic therapy (PDT) has the advantages of deep tissue penetration, real-time monitoring of drug treatment and disease, little damage to normal tissue, low cytotoxicity and almost no side effects, and thus, it is attracting increasing research attention and is expected to show promising potential for clinical tumor treatment. The photosensitizer (PS), light source and oxygen are the three basic and important factors to construct PDT technology, and highly efficient PSs are still being passionately pursued because they determine the PDT efficiency. Ideal PSs should have properties such as good biocompatibility, deep tissue penetration, and highly efficient reactive oxygen species (ROS) generation despite the hypoxic environment. Therefore, pure organic type I PSs with NIR fluorescence have been receiving increasing attention due to their deep penetration and hypoxia resistance. However, reported NIR-active type I PSs usually require complex synthetic procedures, which presents a challenge for mass production. In this research work, based on the molecular design ideas of introducing the heavy atom effect and intramolecular charge transfer, we prepared three NIR-active type I PSs (TNZ, TNZBr, and TNZCHO) using a very simple method with one or two synthetic steps. Clear characterizations of photophysical properties, ROS performance tests, and fluorescent imaging of human umbilical vein endothelial (HUVE) cells and PDT treatment of HepG2 cells were carried out. The results revealed that the heavy atom and intramolecular charge transfer (ICT) effects could obviously enhance the ROS efficiency, and both PSs produce only type I ROS without any type II ROS (1O2) generation. The good NIR fluorescence brightness and type I ROS efficiency ensure satisfactory bioimaging and PDT outcomes. This research provides the possibility of preparing NIR-active type I PSs via mass production.

7.
J Clin Ultrasound ; 52(5): 566-574, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38538081

RESUMO

PURPOSE: To assess the predictive value of an ultrasound-based radiomics-clinical nomogram for grading residual cancer burden (RCB) in breast cancer patients. METHODS: This retrospective study of breast cancer patients who underwent neoadjuvant therapy (NAC) and ultrasound scanning between November 2020 and July 2023. First, a radiomics model was established based on ultrasound images. Subsequently, multivariate LR (logistic regression) analysis incorporating both radiomic scores and clinical factors was performed to construct a nomogram. Finally, Receiver operating characteristics (ROC) curve analysis and decision curve analysis (DCA) were employed to evaluate and validate the diagnostic accuracy and effectiveness of the nomogram. RESULTS: A total of 1122 patients were included in this study. Among them, 427 patients exhibited a favorable response to NAC chemotherapy, while 695 patients demonstrated a poor response to NAC therapy. The radiomics model achieved an AUC value of 0.84 in the training cohort and 0.83 in the validation cohort. The ultrasound-based radiomics-clinical nomogram achieved an AUC value of 0.90 in the training cohort and 0.91 in the validation cohort. CONCLUSIONS: Ultrasound-based radiomics-clinical nomogram can accurately predict the effectiveness of NAC therapy by predicting RCB grading in breast cancer patients.


Assuntos
Neoplasias da Mama , Gradação de Tumores , Neoplasia Residual , Nomogramas , Ultrassonografia Mamária , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Ultrassonografia Mamária/métodos , Adulto , Neoplasia Residual/diagnóstico por imagem , Valor Preditivo dos Testes , Idoso , Terapia Neoadjuvante , Mama/diagnóstico por imagem , Carga Tumoral , Radiômica
9.
Int J Surg ; 110(5): 2865-2873, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38329065

RESUMO

BACKGROUND: Radical inguinal lymph node dissection (rILND) is the most available treatment to cure penile cancer (PC) with limited inguinal-confined disease. However, guidelines regarding acceptable boundaries of rILND are controversial, and consensus is lacking. The authors aimed to standardize the surgical boundaries of rILND with definite pathological evidence and explore the distribution pattern of inguinal lymph nodes (ILNs) in PC. METHODS: A total of 414 PC patients from two centers who underwent rILND were enrolled. The ILN distribution was divided into seven zones anatomically for pathological examination. Student's t test and Kaplan-Meier survival analysis were used. RESULTS: ILNs displayed a funnel-shaped distribution with high density in superior regions. ILNs and metastatic nodes are present anywhere within the radical boundaries. Positive ILNs were mainly concentrated in zone I (51.7%) and zone II (41.3%), but there were 8.7% and 12.3% in inferior zones V and VI, respectively, and 7.1% in the deep ILNs. More importantly, a single positive ILN and first-station positive zone was detected in all seven regions. Single positive ILNs were located in zones I through VI in 40.4%, 23.6%, 6.7%, 18.0%, 4.5%, and 1.1%, respectively, and 5.6% presented deep ILN metastasis directly. CONCLUSIONS: The authors established a detailed ILN distribution map and displayed lymphatic drainage patterns with definite pathological evidence using a large cohort of PC patients. Single positive ILNs and first-station metastatic zones were observed in any region, even directly with deep ILN metastasis. Only rILND can ensure tumor-free resection without the omission of positive nodes.


Assuntos
Canal Inguinal , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Neoplasias Penianas , Humanos , Masculino , Neoplasias Penianas/cirurgia , Neoplasias Penianas/patologia , Excisão de Linfonodo/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Canal Inguinal/cirurgia , Canal Inguinal/patologia , Linfonodos/patologia , Linfonodos/cirurgia , Adulto , Estudos de Coortes
10.
Scand J Gastroenterol ; 59(6): 722-729, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38362884

RESUMO

OBJECTIVE: To explore the effects of pretreatment peripheral blood panimmune-inflammation value (PIV), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) on the efficacy and prognostic value of immunotherapy in patients with inoperable advanced or locally advanced oesophageal squamous cell carcinoma (ESCC). METHODS: Clinical data of 107 inoperable advanced or locally advanced ESCC patients were retrospectively analysed between May 2019 and August 2023, the receiver operating characteristic curves (ROCs) of PIV, SII, NLR, and PLR in patients prior to immunotherapy were plotted, and their optimal cutoff values were determined. The risk factors were determined by univariate and multivariate analyses in groups based on the optimal cut-off values. RESULTS: Peripheral blood PIV, SII and PLR before immunotherapy had predictive value for the optimal efficacy of immunotherapy in patients with inoperable advanced or locally advanced ESCC; patients with PIV ≥415.885, SII ≥834.295 and NLR ≥3.740 had a low objective response rate (ORR), disease control rate (DCR), a short progression-free survival (PFS) and overall survival (OS) after immunotherapy (p < 0.05). Patient tumour stage, distant lymph node metastasis, lung metastasis, liver metastasis, PIV, SII, and NLR were risk factors affecting PFS and OS (p < 0.05). Tumour stage and SII were independent risk factors affecting PFS and OS (p < 0.05). CONCLUSION: In patients with inoperable advanced or locally advanced ESCC, peripheral blood PIV, SII, and NLR have predictive value for immunotherapy outcome, SII is an independent risk factor affecting the survival prognosis, and SII ≥834.295 suggests a poor prognosis from immunotherapy.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Imunoterapia , Neutrófilos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/sangue , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Idoso , Prognóstico , Imunoterapia/métodos , Curva ROC , Valor Preditivo dos Testes , Adulto , Linfócitos , Plaquetas , Estadiamento de Neoplasias , Contagem de Linfócitos , Contagem de Plaquetas , Inflamação/sangue , Fatores de Risco
11.
Artigo em Chinês | MEDLINE | ID: mdl-38297867

RESUMO

Objective:Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) play important roles in the poor prognosis of different inflammatory and neoplastic diseases, but their effects on postoperative recurrence of chronic rhinosinusitis(CRS) are unknown. The aim of this study was to investigate the correlation between preoperative NLR and PLR and the risk of postoperative recurrence in CRS. Methods:Clinical data were collected from patients with CRS who underwent initial functional endoscopic sinus surgery from October 2018 to February 2022 at our institution. Follow-up was until February 2023, and the study endpoint was defined as patient postoperative recurrence or follow-up time up to date. The optimal preoperative NLR and PLR threshold values were obtained based on subject work curve analysis, and they were divided into high and low level subgroups, respectively, and the clinical characteristics and postoperative recurrence rates of patients were compared between groups; patients were divided into non-recurrent CRS and recurrent CRS according to their postoperative recurrence, and Kaplan-Meier survival curves and logistic regression analysis were performed to explore the correlation between NLR and PLR and CRS The correlation between NLR and PLR and postoperative recurrence was investigated by Kaplan-Meier survival curve and logistic regression analysis. Results:A total of 630 patients with CRS were included, including 382 and 140 patients with high NLR and high PLR, respectively. The postoperative recurrence rates of CRS patients in the high NLR and high PLR groups were significantly higher than those in the low NLR and low PLR groups(P<0.05). The recurrent CRS had higher NLR and PLR levels and higher proportion of high NLR and high PLR than the non-recurrent CRS(P<0.05), and similarly the duration of recurrent CRS and the rate of allergic rhinitis with recurrence were significantly higher than the non-recurrent CRS(P<0.05). Kaplan-Meier survival curves showed that postoperative CRS was significantly higher in the high NLR and high PLR groups compared with the low NLR and low PLR groups. recurrence was significantly higher(P<0.05). In addition, logistic regression analysis showed that high NLR, high PLR, disease duration, and combined allergic rhinitis were significantly associated with an increased risk of postoperative recurrence of CRS(P<0.05). Conclusion:Both high preoperative NLR and high PLR are independent risk factors for postoperative recurrence of CRS, and they are expected to be new indicators for postoperative prognostic assessment and risk stratification of CRS patients. In addition, disease duration and comorbid allergic rhinitis were significantly associated with the risk of postoperative recurrence of CRS.


Assuntos
Rinite Alérgica , Rinossinusite , Humanos , Neutrófilos , Contagem de Plaquetas , Plaquetas , Linfócitos , Prognóstico , Estudos Retrospectivos
12.
Mol Biomed ; 5(1): 6, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342791

RESUMO

Cancer is associated with a high degree of heterogeneity, encompassing both inter- and intra-tumor heterogeneity, along with considerable variability in clinical response to common treatments across patients. Conventional models for tumor research, such as in vitro cell cultures and in vivo animal models, demonstrate significant limitations that fall short of satisfying the research requisites. Patient-derived tumor organoids, which recapitulate the structures, specific functions, molecular characteristics, genomics alterations and expression profiles of primary tumors. They have been efficaciously implemented in illness portrayal, mechanism exploration, high-throughput drug screening and assessment, discovery of innovative therapeutic targets and potential compounds, and customized treatment regimen for cancer patients. In contrast to conventional models, tumor organoids offer an intuitive, dependable, and efficient in vitro research model by conserving the phenotypic, genetic diversity, and mutational attributes of the originating tumor. Nevertheless, the organoid technology also confronts the bottlenecks and challenges, such as how to comprehensively reflect intra-tumor heterogeneity, tumor microenvironment, tumor angiogenesis, reduce research costs, and establish standardized construction processes while retaining reliability. This review extensively examines the use of tumor organoid techniques in fundamental research and precision medicine. It emphasizes the importance of patient-derived tumor organoid biobanks for drug development, screening, safety evaluation, and personalized medicine. Additionally, it evaluates the application of organoid technology as an experimental tumor model to better understand the molecular mechanisms of tumor. The intent of this review is to explicate the significance of tumor organoids in cancer research and to present new avenues for the future of tumor research.


Assuntos
Neoplasias , Organoides , Medicina de Precisão , Humanos , Organoides/patologia , Organoides/efeitos dos fármacos , Medicina de Precisão/métodos , Neoplasias/patologia , Neoplasias/genética , Neoplasias/tratamento farmacológico , Animais , Microambiente Tumoral
13.
J Reconstr Microsurg ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38176431

RESUMO

BACKGROUND: Deep circumflex iliac artery (DCIA)-vascularized iliac graft transposition is a method for treating femoral head osteonecrosis but with inconsistent efficacy. We aim to improve the method of this surgery by recommending the optimal location of the iliac pedicle to satisfy the vascular length for transposition and the blood supply of the vascularized iliac graft. METHODS: The DCIA and its surrounding tissues were assessed on computed tomography angiography images for 100 sides (left and right) of 50 patients. The length of the vascular pedicle required for transposition and the length of the pedicle at different iliac spine positions were compared. The diameter and cross-sectional area of the DCIA and the distance between the DCIA and iliac spine were measured at different points to assess blood supply. We also compared differences in sex and left-right position. RESULTS: The diameter and cross-sectional area of the DCIA gradually decreased after crossing the anterior superior iliac spine (ASIS), and it approached the iliac bone. However, when the DCIA was 4 cm behind the ASIS (54 sides, 54%), it coursed posteriorly and superiorly away from the iliac spine. The vascular length of the pedicle was insufficient to transpose the vascularized iliac graft to the desired position when it was within 1 cm of the ASIS. The vascular length requirement was satisfied, and the blood supply was sufficient when the pedicle was positioned at 2 or 3 cm. CONCLUSION: To obtain a satisfactory pedicle length and sufficient blood supply, the DCIA pedicle of the vascularized iliac graft should be placed 2 to 3 cm behind the ASIS. The dissection of DCIA has slight differences in sex and left-right position due to anatomical differences.

14.
BMC Surg ; 24(1): 4, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166900

RESUMO

BACKGROUND: Corpus callosum glioblastoma (ccGBM) is a specific type of GBM and has worse outcomes than other non-ccGBMs. We sought to identify whether en-bloc resection of ccGBMs based on T2-FLAIR imaging contributes to clinical outcomes and can achieve a satisfactory balance between maximal resection and preservation of neurological function. METHODS: A total of 106 adult ccGBM patients (including astrocytoma, WHO grade 4, IDH mutation, and glioblastoma) were obtained from the Department of Neurosurgery in Nanfang Hospital between January 2008 and December 2018. The clinical data, including gender, age, symptoms, location of tumor, involvement of eloquent areas, extent of resection (EOR), pre- and postoperative Karnofsky Performance Status (KPS) scales, and National Institute of Health stroke scale (NIHSS) scores were collected. Propensity score matching (PSM) analysis was applied to control the confounders for analyzing the relationship between the en-bloc technique and EOR, and the change in the postoperative KPS scales and NIHSS scores. RESULTS: Applying the en-bloc technique did not negatively affect the postoperative KPS scales compared to no-en-bloc resection (P = 0.851 for PSM analysis) but had a positive effect on preserving or improving the postoperative NIHSS scores (P = 0.004 for PSM analysis). A positive correlation between EOR and the en-bloc technique was identified (r = 0.483, P < 0.001; r = 0.720, P < 0.001 for PSM analysis), indicating that applying the en-bloc technique could contribute to enlarged maximal resection. Further survival analysis confirmed that applying the en-bloc technique and achieving supramaximal resection could significantly prolong OS and PFS, and multivariate analysis suggested that tumor location, pathology, EOR and the en-bloc technique could be regarded as independent prognostic indicators for OS in patients with ccGBMs, and pathology, EOR and the en-bloc technique were independently correlated with patient's PFS. Interestingly, the en-bloc technique also provided a marked reduction in the risk of tumor recurrence compared with the no-en-bloc technique in tumors undergoing TR, indicating that the essential role of the en-bloc technique in ccGBM surgery (HR: 0.712; 95% CI: 0.535-0.947; P = 0.02). CONCLUSIONS: The en-bloc technique could contribute to achieving an enlarged maximal resection and could significantly prolong overall survival and progression-free survival in patients with ccGBMs.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Adulto , Humanos , Glioblastoma/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Corpo Caloso/cirurgia , Corpo Caloso/patologia , Neoplasias Encefálicas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Procedimentos Neurocirúrgicos/métodos
15.
J Nanobiotechnology ; 22(1): 11, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38167103

RESUMO

The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has had a profound impact on the global health and economy. While mass vaccination for herd immunity is effective, emerging SARS-CoV-2 variants can evade spike protein-based COVID-19 vaccines. In this study, we develop a new immunization strategy by utilizing a nanocarrier, dendritic mesoporous silica nanoparticle (DMSN), to deliver the receptor-binding domain (RBD) and conserved T-cell epitope peptides (DMSN-P-R), aiming to activate both humoral and cellular immune responses in the host. The synthesized DMSN had good uniformity and dispersion and showed a strong ability to load the RBD and peptide antigens, enhancing their uptake by antigen-presenting cells (APCs) and promoting antigen delivery to lymph nodes. The DMSN-P-R vaccine elicited potent humoral immunity, characterized by highly specific RBD antibodies. Neutralization tests demonstrated significant antibody-mediated neutralizing activity against live SARS-CoV-2. Crucially, the DMSN-P-R vaccine also induced robust T-cell responses that were specifically stimulated by the RBD and conserved T-cell epitope peptides of SARS-CoV-2. The DMSN demonstrated excellent biocompatibility and biosafety in vitro and in vivo, along with degradability. Our study introduces a promising vaccine strategy that utilizes nanocarriers to deliver a range of antigens, effectively enhancing both humoral and cellular immune responses to prevent virus transmission.


Assuntos
COVID-19 , Nanopartículas , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , Epitopos de Linfócito T , Vacinação , Anticorpos Neutralizantes , Peptídeos , Anticorpos Antivirais
17.
J Clin Ultrasound ; 52(2): 144-151, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37991026

RESUMO

PURPOSE: To explore the value of ultrasound (US) characteristics in diagnosing breast fibromatosis (BF) and evaluate their differences from breast carcinoma. METHODS: A total of 121 patients with BF (n = 24, 29 lesions) or invasive ductal carcinoma (IDC) (n = 97, 102 lesions) of the breast were included. Their clinical and US findings were recorded and analyzed. RESULTS: The mean age of BF was younger than that of IDC (28.75 ± 5.55 vs. 50.19 ± 9.87, p < 0.001). The mean size of the BF was smaller than that of IDC (2.09 ± 0.91 vs. 2.71 ± 1.20, p = 0.011). Compared to IDC, BF had more frequency of posterior echo attenuation (p < 0.001), less frequency of peripheral hyperechoic halo (p = 0.002), calcification (p = 0.001), US reported axillary lymph node positive (p = 0.025), and grade 2-3 vascularity (p < 0.001). The Breast Imaging Reporting and Data System categorized BF at a lower level than IDC (p < 0.001). After adjusting for age, the peripheral hyperechoic halo, posterior echo feature, and vascularity could independently identify the differences between these two entities. CONCLUSION: Some differences were observed between BF and IDC in terms of patient age, lesion size, and US characteristics.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Humanos , Feminino , Carcinoma Ductal de Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Mama/diagnóstico por imagem , Mama/patologia , Ultrassonografia , Linfonodos/patologia , Estudos Retrospectivos
19.
Scand J Gastroenterol ; 59(3): 304-315, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37978827

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related death. Immunotherapy is one of the new options for cancer treatment. This study aimed to develop an immune-related signature associated with CRC. METHODS: We performed differential analysis to screen out the differentially expressed genes (DEGs) of The Cancer Genome Atlas-Colorectal Cancer (TCGA-CRC) datasets. Weighted gene co-expression network analysis (WGCNA) was performed to obtain the key module genes associated with differential immune cells. The candidate genes were obtained through overlapping key DEGs and key module genes. The univariate and multivariate Cox regression analyses were adopted to build a CRC prognostic signature. We further conducted immune feature estimation and chemotherapy analysis between two risk subgroups. Finally, we verified the expression of immune-related prognostic genes at the transcriptional level. RESULTS: A total of 61 candidate genes were obtained by overlapping key DEGs and key module genes associated with differential immune cells. Then, an immune-related prognostic signature was built based on the three prognostic genes (HAMP, ADAM8, and CD1B). The independent prognostic analysis suggested that age, stage, and RiskScore could be used as independent prognostic factors. Further, we found significantly higher expression of three prognostic genes in the CRC group compared with the normal group. Finally, real-time polymerase chain reaction verified the expression of three genes in patients with CRC. CONCLUSION: The prognostic signature comprising HAMP, ADAM8, and CD1B based on immune cells was established, providing a theoretical basis and reference value for the research of CRC.


Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Humanos , Prognóstico , Microambiente Tumoral/genética , Expressão Gênica , Perfilação da Expressão Gênica , Neoplasias Colorretais/genética , Proteínas de Membrana , Proteínas ADAM
20.
Cell Rep Med ; 5(1): 101343, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38154462

RESUMO

Parastomal hernia (PSH) is a common complication in patients receiving ileal conduit urinary diversion after radical cystectomy. In this randomized controlled clinical trial, we validate our previous finding that extraperitonealization of ileal conduit decreases incidence of PSH. In total, 104 consecutive patients undergoing radical cystectomy at Sun Yat-sen University Cancer Center are randomized 1:1 to receive either modified (extraperitonealized) ileal conduit (n = 52) or conventional ileal conduit (n = 52). Primary endpoint is incidence of radiological PSH during follow-up. Incidence of radiological PSH is lower in the modified group than in the conventional group (11.5% vs. 28.8%; p = 0.028) after a median follow-up of 32 months, corresponding to a hazard ratio of 0.374 (95% confidence interval: 0.145-0.965, p = 0.034) in the modified conduit group. The results support our previous finding that extraperitonealization of the ileal conduit is effective for reducing risk of PSH in patients receiving ileal conduit diversion.


Assuntos
Neoplasias da Bexiga Urinária , Derivação Urinária , Humanos , Cistectomia , Hérnia/etiologia , Incidência , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/efeitos adversos , Derivação Urinária/métodos
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