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1.
ESC Heart Fail ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38628024

RESUMO

AIMS: Recent years, several studies have suggested that abnormal baseline left ventricular (LV) function and structure are associated with left ventricular thrombus (LVT) formation. Despite this, most studies have given less attention to the potential role of left ventricular reverse remodelling (LVRR), that is, the improvement of LV function and structure, in resolving LVT. In this study, we aim to investigate the clinical characteristics, prognosis, and LVT resolution in patients with LVRR. METHODS AND RESULTS: This is a retrospective study conducted at The First Affiliated Hospital of Dalian Medical University. Our cohort consists of patients diagnosed with LVT between 1 November 2015 and 31 May 2020. Enrolled patients were categorized into two groups: LVRR and Failure of LVRR. The primary endpoints included LVT resolution and embolic events. A total of 84 patients were included in the study, with 59 patients in the LVRR group and 25 patients in the Failure of LVRR group. In our study, patients in the LVRR group experienced higher incidence of LVT resolution and a lower risk of embolic events. Multivariate logistic analysis revealed that Failure of LVRR was the only independent negative predictor for LVT resolution and positive predictor for embolic events. CONCLUSIONS: Patients with LVRR experience higher incidence of LVT resolution and have lower risk of embolic events, highlighting the significance of identifying and mitigating risk factors that contribute to abnormal LV function and structure in management of patients with LVT.

2.
J Mater Chem B ; 12(16): 3857-3880, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38563315

RESUMO

Immunotherapy is a therapeutic modality designed to elicit or augment an immune response against malignancies. Despite the immune system's ability to detect and eradicate neoplastic cells, certain neoplastic cells can elude immune surveillance and elimination through diverse mechanisms. Therefore, antitumor immunotherapy has emerged as a propitious strategy. Pyroptosis, a type of programmed cell death (PCD) regulated by Gasdermin (GSDM), is associated with cytomembrane rupture due to continuous cell expansion, which results in the release of cellular contents that can trigger robust inflammatory and immune responses. The field of nanomedicine has made promising progress, enabling the application of nanotechnology to enhance the effectiveness and specificity of cancer therapy by potentiating, enabling, or augmenting pyroptosis. In this review, we comprehensively examine the paradigms underlying antitumor immunity, particularly paradigms related to nanotherapeutics combined with pyroptosis; these treatments include chemotherapy (CT), hyperthermia therapy, photodynamic therapy (PDT), chemodynamic therapy (CDT), ion-interference therapy (IIT), biomimetic therapy, and combination therapy. Furthermore, we thoroughly discuss the coordinated mechanisms that regulate these paradigms. This review is expected to enhance the understanding of the interplay between pyroptosis and antitumor immunotherapy, broaden the utilization of diverse nanomaterials in pyroptosis-based antitumor immunotherapy, and facilitate advancements in clinical tumor therapy.


Assuntos
Antineoplásicos , Imunoterapia , Nanomedicina , Neoplasias , Piroptose , Piroptose/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Animais
3.
BMC Cancer ; 24(1): 359, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509485

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most frequent histological type of thyroid carcinoma. Although an increasing number of diagnostic methods have recently been developed, the diagnosis of a few nodules is still unsatisfactory. Therefore, the present study aimed to develop and validate a comprehensive prediction model to optimize the diagnosis of PTC. METHODS: A total of 152 thyroid nodules that were evaluated by postoperative pathological examination were included in the development and validation cohorts recruited from two centres between August 2019 and February 2022. Patient data, including general information, cytopathology, imprinted gene detection, and ultrasound features, were obtained to establish a prediction model for PTC. Multivariate logistic regression analysis with a bidirectional elimination approach was performed to identify the predictors and develop the model. RESULTS: A comprehensive prediction model with predictors, such as component, microcalcification, imprinted gene detection, and cytopathology, was developed. The area under the curve (AUC), sensitivity, specificity, and accuracy of the developed model were 0.98, 97.0%, 89.5%, and 94.4%, respectively. The prediction model also showed satisfactory performance in both internal and external validations. Moreover, the novel method (imprinted gene detection) was demonstrated to play a role in improving the diagnosis of PTC. CONCLUSION: The present study developed and validated a comprehensive prediction model for PTC, and a visualized nomogram based on the prediction model was provided for clinical application. The prediction model with imprinted gene detection effectively improves the diagnosis of PTCs that are undetermined by the current means.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/genética , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Nomogramas , Estudos Retrospectivos
4.
Biosci Rep ; 44(2)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38294290

RESUMO

Acute myelogenous leukemia (AML) is a common malignancy and is supposed to have the ability to escape host immune surveillance. The present study aimed to identify key genes in AML that may affect tumor immunity and to provide prognosis biomarkers of AML. The Cancer Genome Atlas (TCGA) dataset was screened for transcription factors (TFs) involved in immunity and influencing survival, combining Gene Expression Omnibus (GEO) data to validate the impact on patient survival. A prognostic signature was established using four transcription factors, and these genes play an important role in the immune system, with higher regulatory T cell (Treg) scores in high-risk patients compared with the low-risk group. Analysis of individual genes showed that STAT4 and Treg are closely related, which may be due to STAT4 transcribing related genes that affect immunity. STAT4 expression was positively correlated with the proportion of abnormal cells and promoted AML recurrence as verified by AML clinical patient samples. In addition, silencing of STAT4 significantly slowed down the proliferation capacity of HL60 cells. In conclusion, these findings suggest that STAT4 may be a potential biomarker for AML prognosis. As a key gene affecting the prognosis of AML patients, STAT4 has the potential to be a candidate diagnostic and prognostic biomarker for AML.


Assuntos
Leucemia Mieloide Aguda , Humanos , Prognóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Fatores de Transcrição , Fatores de Risco , Biomarcadores , Fator de Transcrição STAT4/genética
5.
Curr Protoc ; 3(12): e947, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38054948

RESUMO

The SIMBA (Simultaneous Imaging and Manipulation of genomic loci by Biomolecular Assemblies) system is an innovative CRISPR-based imaging technique that leverages dCas9-SunTag and FRB-mCherry-HP1α, with scFv-FKBP acting as a bridge. This powerful system enables simultaneous visualization and manipulation of genomic loci. The dCas9-SunTag fusion protein allows for precise targeting of specific genomic sites, and the FRB-mCherry-HP1α fusion protein facilitates the condensation of chromatin at the targeted loci. The scFv-FKBP bridge protein links dCas9-SunTag and FRB-mCherry-HP1α, ensuring efficient and specific recruitment of HP1α to the desired genomic loci. This integrated approach allows us to visualize and manipulate genomic regions of interest, opening up new avenues for studying genome organization, gene expression regulation, and chromatin dynamics in living cells. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Cloning of genetic constructs Basic Protocol 2: Transient transfection in mammalian cells and live-cell imaging Basic Protocol 3: Generation of SIMBA-expressing stable cell lines Basic Protocol 4: Manipulation of genomic loci using SIMBA.


Assuntos
Genômica , Rotulagem de Produtos , Animais , Cromatina/genética , Homólogo 5 da Proteína Cromobox , Fatores de Transcrição , Proteínas de Ligação a Tacrolimo , Mamíferos
6.
Int J Mol Sci ; 24(23)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38069270

RESUMO

Diabetic retinopathy (DR) is a leading cause of vision impairment in the working-age population worldwide. Various modes of photoreceptor cell death contribute to the development of DR, including apoptosis and autophagy. However, whether ferroptosis is involved in the pathogenesis of photoreceptor degeneration in DR is still unclear. High-glucose (HG)-stimulated 661W cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. The levels of intracellular iron, glutathione (GSH), reactive oxygen species (ROS), lipid peroxidation (MDA), and ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, FTH1, and NCOA4) were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. Our data showed the levels of iron, ROS, and MDA were enhanced and GSH concentration was reduced in HG-induced 661W cells and diabetic retinas. The expression of GPX4 and SLC7A11 was downregulated, while the expression of ACSL4, FTH1, and NCOA4 was upregulated in the 661W cells cultured under HG conditions and in the photoreceptor cells in diabetic mice. Furthermore, the administration of the ferroptosis inhibitor ferrostatin-1 (Fer-1) obviously alleviated ferroptosis-related changes in HG-cultured 661W cells and in retinal photoreceptor cells in diabetic mice. Taken together, our findings suggest that ferroptosis is involved in photoreceptor degeneration in the development of the early stages of DR.


Assuntos
3,4-Metilenodioxianfetamina , Diabetes Mellitus Experimental , Retinopatia Diabética , Ferroptose , Animais , Camundongos , Diabetes Mellitus Experimental/tratamento farmacológico , Espécies Reativas de Oxigênio , Retinopatia Diabética/tratamento farmacológico , Glutationa , Ferro , Fatores de Transcrição
7.
Medicine (Baltimore) ; 102(51): e36622, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38134113

RESUMO

RATIONALE: Gallbladder polyps are a general term for localized lesions in which the gallbladder wall protrudes into the gallbladder cavity, and benign lesions are common. Although current guidelines recommend cholecystectomy for gallbladder polyps ≥ 10 mm in size, the probability of finding cancer in postoperative pathological specimens is low. We should avoid unnecessary cholecystectomy and treat polyps with gallbladder preservation. Microwave ablation is safe and effective for the treatment of solid lesions, and can inactivates polyps while preserving gallbladder. Hence, we report a case of ultrasound-guided percutaneous microwave ablation of gallbladder polyps. PATIENT CONCERNS: A 72-year-old female patient had previously diagnosed a gallbladder polyp, but it was not taken seriously. Recently, the patient had occasional right upper abdominal discomfort and a desire to preserve gallbladder. DIAGNOSES: Ultrasound showed a medium hyperechoic papillary protrusion in the gallbladder without echo behind, and the changed position did not move. Contrast-enhanced ultrasound (CEUS) showed no malignant signs. The diagnosis was a gallbladder polyp. INTERVENTIONS: The bile is drained and the drainage tube is fixed under real-time ultrasound guidance, then the gallbladder cavity is flushed and filled. Saline was injected between the serous and mucosal layers of the gallbladder to form an "edema band" to protect the gallbladder wall. Then, ultrasound-guided biopsy of gallbladder polyps was performed and sent for histological examination. Finally, the microwave needle was inserted into the target area under real-time ultrasonic guidance, and ablation was performed for 3 minutes (20 W). Postoperative CEUS: No significant enhancement was observed in the lesion. OUTCOMES: Within 6 months of follow-up, the patient's gallbladder systolic function was normal, and there was no discomfort and no recurrence. The lesion reduction rate reached 100% at 1 week after surgery. LESSONS: Ultrasound guided percutaneous microwave ablation of gallbladder polyps not only preserves the gallbladder but also inactivates the polyps without affecting the systolic function of the gallbladder, which provides a new idea for the treatment of gallbladder polyps.


Assuntos
Doenças da Vesícula Biliar , Neoplasias da Vesícula Biliar , Pólipos , Feminino , Humanos , Idoso , Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/cirurgia , Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/cirurgia , Micro-Ondas/uso terapêutico , Doenças da Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/cirurgia , Doenças da Vesícula Biliar/patologia , Pólipos/diagnóstico por imagem , Pólipos/cirurgia , Ultrassonografia , Ultrassonografia de Intervenção
8.
Heliyon ; 9(10): e21059, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37916122

RESUMO

Background: Enhancing the diagnostic efficacy of early-stage lung cancer is crucial for improving prognosis. The objective of this study was to ascertain dependable exosomal miRNAs as biomarkers for the diagnosis of lung cancer. Methods: Exosomal miRNA candidates were identified through miRNA sequencing and subsequently validated in various case-control sets using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The correlation between the expression of exosomal miRNAs and the clinicopathological features of lung cancer was investigated. To assess the diagnostic efficacy of exosomal miRNAs for lung cancer, the receiver operating characteristic (ROC) curve analysis was conducted. The optimal cutoff value of exosomal miRNAs was determined in the testing cohort and subsequently confirmed in the validation cohort. Results: The results showed that the expression of exosomal miR-1290 was significantly elevated, while that of miR-29c-3p was significantly decreased in the plasma of lung cancer patients, especially in those with early-stage lung cancer, compared to individuals with benign lung conditions (P < 0.01). Exosomal miR-1290 and miR-29c-3p demonstrated superior diagnostic efficacy compared to conventional tumor biomarkers in distinguishing between lung cancer and benign lung diseases, as evidenced by their respective area under the curve (AUC) values of 0.934 and 0.868. Furthermore, exosomal miR-1290 and miR-29c-3p exhibited higher diagnostic efficiency in early-stage lung cancer than traditional tumor markers, with AUC values of 0.947 and 0.895, respectively. Notably, both exosomal miR-1290 and miR-29c-3p displayed substantial discriminatory capacity in distinguishing between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), as indicated by their respective AUC values of 0.810 and 0.842. Conclusions: The findings of this study provided evidence that exosomal miR-1290 and miR-29c-3p hold significant potential as biomarkers for the early detection of lung cancer, as well as for differentiating between NSCLC and SCLC.

9.
China CDC Wkly ; 5(41): 918-921, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37970070

RESUMO

The first indigenous incidence of Mpox (previously known as monkeypox) within Chinese mainland was documented in May 2023, with subsequent local and imported cases identified. A comprehensive understanding of the Mpox virus's (MPXV) characteristics within Beijing remains incomplete. In this study, 84 MPXV genomes from 82 local incidents and two imported instances, detected between May and July 2023, were analyzed. All MPXV strains fell within lineage C.1 of the West African clade, displaying limited genetic heterogeneity, encompassing 76-87 nucleotide substitutions and holding nucleotide identities between 99.996% and 100%. Phylogenetic exploration indicated that all genomes exhibited high homology to those presently prevalent in neighboring East Asian and Southeast Asian regions. Forty-six distinct haplotypes were identified among the strains, with 36.90% of genomes corresponding to four common haplotypes, suggesting repeated cross-regional introductions and restrained distribution via recurrent local transmission. These findings elucidate the genetic diversity and phylogenesis of MPXVs during their nascent transmission within Beijing and provide vital information to enhance future Mpox containment strategies.

10.
Am J Cancer Res ; 13(9): 4418-4433, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818057

RESUMO

Necroptosis is a new form of cell death. Since the discovery that long non-coding RNAs can affect the proliferation of lung adenocarcinoma, much has been learned about it, yet those of necroptosis-related long non-coding RNAs (NRlncRNAs) in lung adenocarcinoma (LUAD) remain enigmatic. This study aims to explore novel biomarkers and therapeutic targets for LUAD. The LUAD data was downloaded from The Cancer Genome Atlas, and necroptosis-related genes were retrieved from published literature. Co-expression analysis, univariate Cox analysis, least absolute shrinkage and selection operator regression analysis were used to identify necroptosis-related prognostic long non-coding RNAs. A comprehensive evaluation of tumor immunity for necrosis-related features was performed, and we identified a 9-NRlncRNA signature. Kaplan-Meier and Cox regression analyses confirmed that the signature was an independent predictor of LUAD outcome in the test and train sets (all P < 0.05). The areas of 1-, 2-, and 3-year overall survival under the time-dependent receiver operating characteristics (ROC) curve (AUC) were 0.754, 0.746, and 0.720, respectively. The GSEA results showed that 9 NRlncRNAs were associated with multiple malignancy-associated and immunoregulatory pathways. Based on this model, we found that the immune status and level of response to chemotherapy and targeted therapy were significantly different in the low-risk group compared with the high-risk group. qRT-PCR assay revealed that 9 NRlncRNAs were involved in the regulation of tumor cell proliferation and may affect the expression of programmed cell death 1 (PD1) and CD28 at human immune checkpoints. Our results indicated that the novel signature involving 9 NRlncRNAs (AL031600.2, LINC01281, AP001178.1, AL157823.2, LINC01290, MED4-AS1, AC026355.2, AL606489.1, FAM83A-AS1) can predict the prognosis of LUAD and are associated with the immune response. This will provide new insights into the pathogenesis and development of therapies for LUAD.

11.
Am J Cancer Res ; 13(9): 4478-4489, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818082

RESUMO

Globally, chronic obstructive pulmonary disease (COPD) is the cause of high morbidity and mortality, and constitutes a huge public health burden. Previous studies have reported that inflammation is closely related to COPD, but its potential mechanism is still unclear. Since the polarization of macrophages is involved in regulating inflammation, we assume that COPD changes the polarization of macrophages. To verify this, we investigated the relationship between the expression of S1PR1, HADC1, and inflammatory macrophages in COPD patients via flow cytometry, qRT-PCR, and western blot analysis. We found that macrophages of COPD individuals differentiated into M1 phenotype, and the expression of S1PR1 increased and HDAC1 decreased. S1PR1 also inhibits the expression of HDAC1, so S1PR1/HDAC1 signal regulates the polarization of macrophages. The results of the study put forward new ideas of the pathogenesis of COPD, and also proposed the possible treatment options.

12.
BMC Cancer ; 23(1): 785, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612615

RESUMO

PURPOSE: To compare the therapeutic efficacy and safety of microwave ablation (MWA) and lauromacrogol injection for ablation (LIA) for benign predominantly cystic thyroid nodules. MATERIALS AND METHODS: In this retrospective study, 85 patients with predominantly cystic thyroid nodules (PCTNs) who underwent microwave ablation (MWA) or lauromacrogol injection for ablation (LIA) between June 2019 and August 2022 at three hospitals were included in our research. Forty-six patients were treated with microwave ablation, and thirty-nine patients were treated with lauromacrogol injection for ablation. The baseline characteristics, nodal volume, volume reduction rate (VRR), and incidence of postoperative complications were compared between these two groups. RESULTS: After treatment, there were significant differences in the thyroid nodule volume and the volume reduction rate (VRR) at different follow-up times between the groups (p < 0.001). There were no significant differences in the nodal volume or the volume reduction rate (VRR) between the MWA group and the LIA group at 1, 3, 6, and 12 months (p > 0.05). Of note, no serious intraoperative or postoperative complications occurred in the corresponding group. CONCLUSION: MWA and LIA are very effective and safe strategies for the treatment of predominantly cystic thyroid nodules. However, LIA is more advantageous in that it is less expensive and has a shorter length of hospital stay than MWA.


Assuntos
Nódulo da Glândula Tireoide , Humanos , Polidocanol , Nódulo da Glândula Tireoide/cirurgia , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fator de Crescimento Transformador beta
13.
Clin Exp Med ; 23(8): 4401-4411, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37438568

RESUMO

Cancer has become a leading cause of death and disease burden worldwide, closely related to rapid socioeconomic development. However, the fundamental reason is the lack of comprehensive understanding of the mechanism of cancer, accurate identification of preclinical cancer, and effective treatment of the disease. Therefore, it is particularly urgent to study specific mechanisms of cancer and develop effective prediction and treatment methods. Long Pentraxin PTX3 is a soluble pattern recognition molecule produced by various cells in inflammatory sites, which plays a role as a promoter or suppressor of cancer in multiple tumors through participating in innate immune response, neovascularization, energy metabolism, invasion, and metastasis mechanisms. Based on this, this article mainly reviews the role of PTX3 in various cancers.


Assuntos
Proteína C-Reativa , Neoplasias , Humanos , Proteína C-Reativa/metabolismo , Imunidade Inata , Neoplasias/genética , Componente Amiloide P Sérico/genética
14.
Vaccine ; 41(32): 4700-4709, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37353454

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) is one of the most prevalent pathogens of bacterial keratitis. Bacterial keratitis is a major cause of blindness worldwide. The rising incidence of multidrug resistance of P. aeruginosa precludes treatment with conventional antibiotics. Herein, we evaluated the protective efficiency and explored the possible underlying mechanism of an X-ray inactivated vaccine (XPa) using a murine P. aeruginosa keratitis model. Mice immunized with XPa exhibit reduced corneal bacterial loads and pathology scores. XPa vaccination induced corneal macrophage polarization toward M2, averting an excessive inflammatory reaction. Furthermore, histological observations indicated that XPa vaccination suppressed corneal fibroblast activation and prevented irreversible visual impairment. The potency of XPa against keratitis highlights its potential utility as an effective and promising vaccine candidate for P. aeruginosa.


Assuntos
Infecções Oculares Bacterianas , Ceratite , Infecções por Pseudomonas , Animais , Camundongos , Pseudomonas aeruginosa , Raios X , Vacinas de Produtos Inativados/uso terapêutico , Ceratite/prevenção & controle , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Córnea/microbiologia , Córnea/patologia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/patologia , Infecções Oculares Bacterianas/prevenção & controle , Infecções por Pseudomonas/prevenção & controle , Camundongos Endogâmicos C57BL
15.
BMC Infect Dis ; 23(1): 270, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37131193

RESUMO

BACKGROUND: Noroviruses are a leading cause of acute gastroenteritis (AGE) worldwide. The geographical characteristics of norovirus outbreaks in Beijing and their influencing factors remain unknown. This study aimed to explore the spatial distributions, geographical characteristics, and influencing factors of norovirus outbreaks in Beijing, China. METHODS: Epidemiological data and specimens were collected through the AGE outbreak surveillance system in all 16 districts of Beijing. Data on spatial distribution, geographical characteristics, and influencing factors of norovirus outbreaks were analyzed using descriptive statistics methods. We measured spatial, geographical clustering of high- or low-value deviance from random distribution using Z-scores and P-values as statistical significance measures with Global Moran's I statistics and Getis-Ord Gi in ArcGIS. Linear regression and correlation methods were used to explore influencing factors. RESULTS: Between September 2016 and August 2020, 1,193 norovirus outbreaks were laboratory-confirmed. The number of outbreaks varied seasonally, typically peaking in spring (March to May) or winter (October to December). Outbreaks primarily occurred around central districts at the town level, and spatial autocorrelation was evident in both the entire study period and in individual years. Hotspots of norovirus outbreaks in Beijing were primarily found in contiguous areas between three central districts (Chaoyang, Haidian, Fengtai) and four suburban districts (Changping, Daxing, Fangshan, Tongzhou). The average population numbers, mean number of all schools, and mean number of kindergartens and primary schools for towns in central districts and hotspot areas were higher than those in suburban districts and non-hotspot areas respectively. Additionally, population numbers and densities of kindergartens and primary schools were influencing factors at the town level. CONCLUSIONS: Hotspots of norovirus outbreaks in Beijing were in contiguous areas between central and suburban districts with high populations, and high kindergarten and primary school densities were the likely driving forces. Outbreak surveillance needs to focus on contiguous areas between central and suburban districts with increased monitoring, medical resources, and health education.


Assuntos
Infecções por Caliciviridae , Norovirus , Humanos , Pequim/epidemiologia , China/epidemiologia , Surtos de Doenças , Escolaridade , Infecções por Caliciviridae/epidemiologia
16.
Front Immunol ; 14: 982180, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37114043

RESUMO

Glioblastomas (GBMs) are highly aggressive brain tumors that have developed resistance to currently available conventional therapies, including surgery, radiation, and systemic chemotherapy. In this study, we investigated the safety of a live attenuated Japanese encephalitis vaccine strain (JEV-LAV) virus as an oncolytic virus for intracerebral injection in mice. We infected different GBM cell lines with JEV-LAV to investigate whether it had growth inhibitory effects on GBM cell lines in vitro. We used two models for evaluating the effect of JEV-LAV on GBM growth in mice. We investigated the antitumor immune mechanism of JEV-LAV through flow cytometry and immunohistochemistry. We explored the possibility of combining JEV-LAV with PD-L1 blocking therapy. This work suggested that JEV-LAV had oncolytic activity against GBM tumor cells in vitro and inhibited their growth in vivo. Mechanistically, JEV-LAV increased CD8+ T cell infiltration into tumor tissues and remodeled the immunosuppressive GBM microenvironment that is non-conducive to immunotherapy. Consequently, the results of combining JEV-LAV with immune checkpoint inhibitors indicated that JEV-LAV therapy improved the response of aPD-L1 blockade therapy against GBM. The safety of intracerebrally injected JEV-LAV in animals further supported the clinical use of JEV-LAV for GBM treatment.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Glioblastoma , Vacinas contra Encefalite Japonesa , Vírus Oncolíticos , Animais , Camundongos , Glioblastoma/terapia , Imunoterapia , Microambiente Tumoral
17.
Front Immunol ; 14: 1046771, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936932

RESUMO

Hepatocellular carcinoma (HCC) is a high-incidence malignant tumor worldwide and lacks effective treatment options. Targeted drugs are the preferred recommendations for the systemic treatment of hepatocellular carcinoma. Immunotherapy is a breakthrough in the systemic treatment of malignant tumors, including HCC. However, either targeted therapy or immunotherapy alone is inefficient and has limited survival benefits on part of HCC patients. Investigations have proved that tyrosine kinase inhibitors (TKIs) have regulatory effects on the tumor microenvironment and immune response, which are potential sensitizers for immunotherapy. Herein, a combination therapy using TKIs and immunotherapy has been explored and demonstrated to improve the effectiveness of treatment. As an effective immunotherapy, adoptive T cell therapy in solid tumors is required to improve tumor infiltration and killing activity which can be possibly achieved by combination with TKIs.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Imunoterapia , Terapia Baseada em Transplante de Células e Tecidos , Microambiente Tumoral
18.
Front Med (Lausanne) ; 10: 1117204, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36993797

RESUMO

Purpose: To investigate changes in retinal circulation and the choroid in patients with acute myeloid leukemia (AML) in the acute and remission stages, to analyze the correlation between retinal circulation and laboratory parameters, and to assess risk factors associated with leukemic retinopathy. Methods: Forty-eight patients (93 eyes) with AML were enrolled and divided into two groups according to fundus examination findings: the retinopathy and no retinopathy groups. Patients underwent eye measurements before treatment and after remission. Macular vessel density (VD), perfusion density (PD), foveal avascular zone (FAZ), and choroidal thickness (ChT) were measured using optical coherence tomography angiography. Patients with healthy eyes were recruited as control participants. Results: Patients with leukemic retinopathy had higher measurements of white blood cells (WBCs), circulating blasts, fibrin degradation products, and cross-linked fibrin degradation products (D-dimer) and a lower hemoglobin (HB) count (p < 0.05). In the acute phase of the disease, the VD and PD were lower and the ChT was thicker in patients with AML than in controls (p < 0.05), irrespective of the presence of leukemic retinopathy; however, the patients were partially recovered in the remission stage. The VD was lower in patients with higher WBC (r = -0.217, p = 0.036), D-dimer (r = -0.279, p = 0.001), fasting blood glucose (FBG) (r = -0.298, p = 0.004) and triglyceride (r = -0.336, p = 0.001) levels. The FAZ area was negatively correlated with HB (r = -0.258, p = 0.012). Conclusion: Patients with AML appear to have subclinical retinal perfusion loss and choroidal thickening in the acute phase of the disease, but this is reversible. Injury to bone marrow function may cause a decrease in retinal perfusion. Leukemic retinopathy is associated with abnormal hematologic parameters and coagulopathy.

19.
Biomed Pharmacother ; 161: 114444, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36857912

RESUMO

Despite significant treatment advances, breast cancer remains the leading cause of cancer death in women. From the current treatment situation, in addition to developing chemoresistant tumours, distant organ metastasis, and recurrences, patients with breast cancer often have a poor prognosis. Aptamers as "chemical antibodies" may be a way to resolve this dilemma. Aptamers are single-stranded, non-coding oligonucleotides (DNA or RNA), resulting their many advantages, including stability for long-term storage, simplicity of synthesis and function, and low immunogenicity, a high degree of specificity and antidote. Aptamers have gained popularity as a method for diagnosing and treating specific tumors in recent years. This article introduces the application of ten different aptamer delivery systems in the treatment and diagnosis of breast cancer, and systematically reviews their latest research progress in breast cancer treatment and diagnosis. It provides a new direction for the clinical treatment of breast cancer.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Aptâmeros de Nucleotídeos/uso terapêutico , Sistemas de Liberação de Medicamentos , RNA , Terapia de Alvo Molecular
20.
Front Surg ; 10: 1106137, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36843997

RESUMO

Introduction: The objective of our study was to construct a preoperative prediction nomogram for the classical variant of papillary thyroid carcinoma (CVPTC) patients with a solitary lesion based on demographic and ultrasonographic parameters that can quantify the individual probability of high-volume (>5) lymph node metastasis (HVLNM). Materials and methods: In this study, a total of 626 patients with CVPTC from December 2017 to November 2022 were reviewed. Their demographic and ultrasonographic features at baseline were collected and analyzed using univariate and multivariate analyses. Significant factors after the multivariate analysis were incorporated into a nomogram for predicting HVLNM. A validation set from the last 6 months of the study period was conducted to evaluate the model performance. Results: Male sex, tumor size >10 mm, extrathyroidal extension (ETE), and capsular contact >50% were independent risk factors for HVLNM, whereas middle and old age were significant protective factors. The area under the curve (AUC) was 0.842 in the training and 0.875 in the validation set. Conclusions: The preoperative nomogram can help tailor the management strategy to the individual patient. Additionally, more vigilant and aggressive measures may benefit patients at risk of HVLNM.

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