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1.
Cancer Med ; 13(7): e7109, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38553942

RESUMO

BACKGROUND: The value of SyMRI-derived parameters from lumbar marrow for predicting early treatment response and optimizing the risk stratification of the Revised International Staging System (R-ISS) in participants with multiple myeloma (MM) is unknown. METHODS: We prospectively enrolled participants with newly diagnosed MM before treatment. The SyMRI of lumbar marrow was used to calculate T1, T2, and PD values and the clinical features were collected. All participants were divided into good response (≥VGPR) and poor response (

Assuntos
Mieloma Múltiplo , Humanos , Masculino , Feminino , Prognóstico , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/patologia , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Projetos Piloto , Estadiamento de Neoplasias , Imageamento por Ressonância Magnética , Estudos Retrospectivos
2.
J Cancer ; 15(8): 2110-2122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495508

RESUMO

Background: DHEA is a steroid hormone produced by the gonads, adrenal cortex, brain, and gastrointestinal tract. While the anti-obesity, anti-atherosclerosis, anti-cancer, and memory-enhancing effects of DHEA have been substantiated through cell experiments, animal studies, and human trials, the precise mechanisms underlying these effects remain unclear. Altered mitochondrial dynamics can lead to mitochondrial dysfunction, which is closely related to many human diseases, especially cancer and aging. This study was to investigate whether DHEA inhibits lung adenocarcinoma through the mitochondrial pathway and its molecular mechanism. Methods: Through animal experiments and cell experiments, the effect of DHEA on tumor inhibition was determined. The correlation between FASTKD2 expression and DHEA was analyzed by Western blot, Reverse transcription-quantitative PCR, Immunohistochemistry, and TCGA database. Results: In this study, DHEA supplementation in the diet can inhibit the tumor size of mice, and the effect of adding DHEA one week before the experiment is the best. DHEA limits the glycolysis process by inhibiting G6PDH activity, increases the accumulation of reactive oxygen species, and initiates apoptosis in the mitochondrial pathway of cancer cells. Conclusion: DHEA suppresses mitochondrial fission and promotes mitochondrial fusion by downregulating the expression of FASTKD2, thereby inhibiting tumor growth and prolonging the overall survival of lung adenocarcinoma patients, which also provides a new target for the prevention and treatment of lung adenocarcinoma.

3.
Ann Hematol ; 103(5): 1665-1673, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38326481

RESUMO

The aim of the study was to develop a new whole spinal MRI-based tumor burden scoring method in participants with newly diagnosed multiple myeloma (MM) and to explore its prognostic significance. We prospectively recruited participants with newly diagnosed MM; performed whole spinal MRI (sagittal FSE T1WI, sagittal IDEAL T2WI, and axial FLAIR T2WI) on them; and collected their clinical data, early treatment response, progression-free survival (PFS), and overall survival (OS). We developed a new tumor burden scoring method according to the extent of bone marrow infiltration in five MRI patterns. All participants were divided into good response and poor response groups after four treatment cycles. Univariate, multivariate analyses, and ROC were used to determine the performance of independent predictors. Thresholds for PFS and OS were calculated using X-tile, and their prognostic significance were assessed by Kaplan-Meier. The Kruskal-Wallis H test was used to compare the differences of tumor burden score between the revised International Staging System (R-ISS) stages. The new tumor burden scoring method was used in 62 participants (median score, 12; range, 0-18). The tumor burden score (OR 1.266, p = 0.002) was an independent predictor of poor response and the AUC was 0.838. Higher tumor burden scores were associated with shorter PFS (p = 0.002) and OS (p = 0.011). The tumor burden score was higher in R-ISS-III than in R-ISS-I and R-ISS-II (p = 0.016 and p = 0.006, respectively). The tumor burden score was an excellent predictor of prognosis and may serve as a supplemental marker for R-ISS.


Assuntos
Mieloma Múltiplo , Neoplasias da Coluna Vertebral , Humanos , Prognóstico , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/terapia , Projetos Piloto , Projetos de Pesquisa , Carga Tumoral , Estadiamento de Neoplasias , Imageamento por Ressonância Magnética , Estudos Retrospectivos
4.
Phys Chem Chem Phys ; 26(7): 6429-6435, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38317609

RESUMO

The electrical tree in grafted polypropylene (PP) is inhibited compared with that of pure PP. To understand the free radicals that are generated during the treeing process, we study the electron paramagnetic resonance (EPR) spectra. Additionally, to provide a clearer explanation of the suppression of electrical trees, this research uses electroluminescence (EL) and excitation computation. These methods help us to observe the movement of electrons and to understand the geometric and electronic structures involved. In pure PP, the energy required to excite the electrons is approximately the same as the band gap of PP while electrons are easier to be excited in grafted PP than in pure PP, because the band gap is narrower. As a result, though the electrical tree length is shorter in PP-g-MMA, the EPR signal is more intense because of the uneven distribution of electrons.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38372766

RESUMO

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a lethal hypovascular tumor surrounded by dense fibrosis. Albumin-bound paclitaxel and gemcitabine (AG) chemotherapy is the mainstay of PDAC treatment through depleting peritumoral fibrosis and killing tumor cells; however, it remains challenging due to the lack of a noninvasive imaging method evaluating fibrotic changes during AG chemotherapy. In this study, we developed a dual-modality imaging platform that enables noninvasive, dynamic, and quantitative assessment of chemotherapy-induced fibrotic changes through near-infrared fluorescence molecular imaging (FMI) and magnetic resonance imaging (MRI) using an extradomain B fibronectin (EDB-FN)-targeted imaging probe (ZD2-Gd-DOTA-Cy7). METHODS: The ZD2-Gd-DOTA-Cy7 probe was constructed by conjugating a peptide (Cys-TVRTSAD) to Gd-DOTA and the near-infrared dye Cy7. PDAC murine xenograft models were intravenously injected with ZD2-Gd-DOTA-Cy7 at a Gd concentration of 0.05 mmol/kg or free Cy7 and Gd-DOTA as control. The normalized tumor background ratio (TBR) on FMI and the T1 reduction ratio on MRI were quantitatively analyzed. For models receiving AG chemotherapy or saline, MRI/FMI was performed before and after treatment. Histological analyses were performed for validation. RESULTS: The ZD2-Gd-DOTA-Cy7 concentration showed a linear correlation with the fluorescence intensity and T1 relaxation time in vitro. The optimal imaging time was 30 min after injection of the ZD2-Gd-DOTA-Cy7 (0.05 mmol/kg), only half of the clinic dosage of gadolinium. Additionally, ZD2-Gd-DOTA-Cy7 generated a 1.44-fold and 1.90-fold robust contrast enhancement compared with Cy7 (P < 0.05) and Gd-DOTA (P < 0.05), respectively. For AG chemotherapy monitoring, the T1 reduction ratio and normalized TBR in the fibrotic tumor areas were significantly increased by 1.99-fold (P < 0.05) and 1.78-fold (P < 0.05), respectively, in the control group compared with those in the AG group. CONCLUSION: MRI/FMI with a low dose of ZD2-Gd-DOTA-Cy7 enables sensitive imaging of PDAC and the quantitative assessment of fibrotic changes during AG chemotherapy, which shows potential clinical applications for precise diagnosis, post-treatment monitoring, and disease management.

6.
Environ Toxicol ; 39(5): 3172-3187, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38348599

RESUMO

OBJECTIVE: Scutellaria baicalensis (SB) and Polygonatum Rhizoma (PR), two traditional Chinese medicines, are both known to suppress cancer. However, the mechanism and effect of combined treatment of them for lung cancer are rarely known. Investigating the combined effect of SB and PR (hereafter referred to as SP) in potential mechanism of lung cancer is required. This study was to evaluate the inhibitory effects of SP on A549 cell growth and to explore the underlying molecular mechanisms. METHODS: According to the theory of Chinese medicine and network pharmacology, in the in vivo experiment, a mouse model of carcinoma in situ was constructed, and lung carcinoma in situ tissues were collected for proteomics analysis, hematoxylin-eosin staining, and CK19 immunohistochemistry. In the in vitro experiment, lung cancer A549 cells at logarithmic growth stage were taken, and the inhibitory effect of SP on the proliferation of A549 cells was detected by CCK8 method. The expression of PON3 was detected by quantitative polymerase chain reaction and western blot. In addition, the effect of SP on the induction of apoptosis in A549 cells and the changes of membrane potential and reactive oxygen species (ROS) content were detected by flow cytometry. The changes of PON3 content in endoplasmic reticulum (ER) are observed by laser confocal microscopy, whereas the effects of SP on the expression of apoptosis-related proteins and ER stress-related proteins in A549 cells were examined by western blot. RESULT: By searching the Traditional Chinese Medicines of Systems Pharmacology (TCMSP) (https://www.tcmspe.com/index.php) database and SymMap database, the respective target genes of PR and SB were mapped into protein network interactions, and using Venn diagrams to show 38 genes in common between PR and SB and lung cancer, SP was found to play a role in the treatment of lung cancer. In vivo experiments showed that in a lung carcinoma in situ model, lung tumor tissue was significantly lower in the SP group compared with the control group, and PON3 was shown to be downregulated by lung tissue proteomics analysis. The combination of SP was able to inhibit the proliferation of A549 cells in a concentration-dependent manner (p < .0001). The expression levels of apoptosis-related proteins and ER stress proteins were significantly increased and the expression levels of PON3 and anti-apoptosis-related proteins were decreased in A549 cells. At the same time, knockdown of PON3 could inhibit tumor cell proliferation (p < .0001). The combination of different concentrations of SP significantly induced apoptosis in A549 cells (p < .05; p < .0001), increased ROS content (p < .01), and damaged mitochondrial membrane potential of A549 cells (p < .05; p < .0001), and significantly increased the expression levels of apoptosis-related proteins and ER stress proteins in lung cancer A549 cells. CONCLUSION: SP inhibits proliferation of lung cancer A549 cells by downregulating PON3-induced apoptosis in the mitochondrial and ER pathways.


Assuntos
Carcinoma in Situ , Neoplasias Pulmonares , Polygonatum , Animais , Camundongos , Humanos , Células A549 , Polygonatum/metabolismo , Scutellaria baicalensis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regulação para Baixo , Neoplasias Pulmonares/patologia , Apoptose , Proliferação de Células , Estresse do Retículo Endoplasmático , Proteínas de Choque Térmico/metabolismo , Linhagem Celular Tumoral
7.
Environ Toxicol ; 39(5): 2706-2716, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38240193

RESUMO

BACKGROUND: Previous studies have reported that inflammation, especially interleukin family members, plays an important role in the development of colorectal cancer (CRC). However, because of various confounders and the lack of clinical randomized controlled trial, the causal relationship between genetically predicted level of interleukin family and CRC risk has not been fully explained. OBJECTIVE: Bi-directional Mendelian randomization (MR) was conducted to investigate the causal association between interleukin family members and CRC. METHODS: Several genetic variables were extracted as instrumental variables (IVs) from summary data of genome-wide association studies (GWAS) for interleukin and CRC. IVs of interleukin family were obtained from recently published GWAS studies and the summary data of CRC was from FinnGen Biobank. After a series of quality control measures and strict screening, six models were used to evaluate the causal relationship. Pleiotropy, heterogeneity test, and a variety of sensitivity analysis were also used to estimate the robustness of the model results. RESULTS: Genetically predicted higher circulating levels of IL-2 (odds ratio [OR]: 0.76; 95% confidence interval [CI]: 0.63-0.92; p = .0043), IL-17F(OR: 0.78; 95% CI: 0.62-1.00; p = .015), and IL-31 (OR: 0.88; 95% CI: 0.79-0.98; p = .023) were suggestively associated with decreased CRC risk. However, higher level of IL-10 (OR: 1.40; 95% CI: 1.18-1.65; p = .000094) was causally associated with increased risk of CRC. Reverse MR results indicated that the exposure of CRC was suggestively associated with higher levels of IL-36α (OR: 1.23; 95% CI: 1.01-1.49; p = .040) and IL-17RD (OR: 1.22; 95% CI, 1.00-1.48; p = .048) and lower level of IL-13 (OR: 0.78; 95% CI: 0.65-0.95; p = .013). The overall MR results did not provide evidence for causal relationships between other interleukins and CRC (p > .05). CONCLUSION: We offer suggestive evidence supporting a potential causal relationship between circulating interleukins and CRC, underscoring the significance of targeting circulating interleukins as a strategy to mitigate the incidence of CRC.


Assuntos
Neoplasias Colorretais , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Interleucinas/genética , Interleucina-13 , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética
8.
Anal Bioanal Chem ; 416(6): 1375-1387, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38270633

RESUMO

As an important endogenous gasotransmitter, hydrogen sulfide (H2S) plays a critical role in various physiological functions and has been regarded as a biomarker of cancer due to its overexpression in cancer cells. In addition, the early stages of cancer are often accompanied by abnormalities in the intracellular microenvironments, and distinguishing between cancer cell/tissues and normal cell/tissues is of great significance to the accuracy of cancer diagnosis. However, deep insights into the simultaneous detection of H2S and viscosity/polarity variations in cancer cells/tissues are rarely reported. In this work, we designed and synthesized a mitochondria-targeting fluorescent probe PDQHS, which exhibits high selectivity for H2S with an emission peak around 632 nm and excellent response (17-fold) to viscosity/polarity beyond 706 nm. Meanwhile, PDQHS shows good biocompatibility and can specifically accumulate into mitochondria. Using PDQHS, the visual distinguishing of cancer cells from normal cells was achieved via dual-channel detection of H2S and viscosity/polarity. More importantly, PDQHS has been successfully applied to visualize endogenous and exogenous H2S in living cells and tumor tissue. Obviously, compared to the detection of a single biomarker, monitoring multiple biomarkers simultaneously through dual-channel response is conducive to amplifying the detection signal, providing a more sensitive and reliable imaging tool in the tumor region, which is beneficial for cancer prediction.


Assuntos
Sulfeto de Hidrogênio , Neoplasias , Humanos , Corantes Fluorescentes , Viscosidade , Células HeLa , Imagem Óptica , Biomarcadores , Neoplasias/diagnóstico por imagem
9.
Cancer Imaging ; 24(1): 15, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254185

RESUMO

BACKGROUND: To compare the diagnostic performance of Lung-RADS (lung imaging-reporting and data system) 2022 and PNI-GARS (pulmonary node imaging-grading and reporting system). METHODS: Pulmonary nodules (PNs) were selected at four centers, namely, CQ Center (January 1, 2018-December 31, 2021), HB Center (January 1, 2021-June 30, 2022), SC Center (September 1, 2021-December 31, 2021), and SX Center (January 1, 2021-December 31, 2021). PNs were divided into solid nodules (SNs), partial solid nodules (PSNs) and ground-glass nodules (GGNs), and they were then classified by the Lung-RADS and PNI-GARS. The sensitivity, specificity and agreement rate were compared between the two systems by the χ2 test. RESULTS: For SN and PSN, the sensitivity of PNI-GARS and Lung-RADS was close (SN 99.8% vs. 99.4%, P < 0.001; PSN 99.9% vs. 98.4%, P = 0.015), but the specificity (SN 51.2% > 35.1%, PSN 13.3% > 5.7%, all P < 0.001) and agreement rate (SN 81.1% > 74.5%, P < 0.001, PSN 94.6% > 92.7%, all P < 0.05) of PNI-GARS were superior to those of Lung-RADS. For GGN, the sensitivity (96.5%) and agreement rate (88.6%) of PNI-GARS were better than those of Lung-RADS (0, 18.5%, P < 0.001). For the whole sample, the sensitivity (98.5%) and agreement rate (87.0%) of PNI-GARS were better than Lung-RADS (57.5%, 56.5%, all P < 0.001), whereas the specificity was slightly lower (49.8% < 53.4%, P = 0.003). CONCLUSION: PNI-GARS was superior to Lung-RADS in diagnostic performance, especially for GGN.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , China
10.
Transpl Immunol ; 82: 101960, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38007171

RESUMO

PURPOSE: Allograft rejection is still the main cause of corneal transplantation failure. Therefore, we investigated the role of indoleamine 2,3-dioxygenase (IDO)-transfected bone marrow-derived mesenchymal stem cells (IDO-BMSCs) in corneal allograft rejection in rats. METHODS: IDO-BMSCs were constructed and co-cultured with CD4+CD24- T cells to detect their effects on the proliferation of CD4+CD25-T cells in vitro. A corneal allograft rat model was used to confirm our in vitro and in vivo observations. Therefore, IDO-BMSCs were injected directly into the recipient's conjunctiva on the day of corneal transplantation and on day 5 after operation. Corneal graft rejection indices, including corneal neovascularization, opacity, and edema, were measured for up to 14 days after transplantation. The recipients' cervical lymph nodes and peripheral blood were collected to test the role of IDO-BMSCs in immune cells using flow cytometry. RESULTS: The lentivirus-mediated IDO gene was successfully transfected into BMSCs, which stably secreted the IDO protein. The proliferation of CD4+CD25-T cells was significantly inhibited after their co-culture with IDO-BMSCs. Subconjunctival injection of IDO-BMSCs into corneal allografts of rats effectively reduced graft neovascularization, promoted allograft survival, and induced immune tolerance. Both CD4+ and CD8+ T cells in the local lymph nodes and peripheral blood, along with CD4+CD25-T cells in the local lymph nodes, were significantly reduced after transplantation. CONCLUSION: Our results suggest that IDO-BMSC treatment enhances the direct immunomodulatory effect of corneal allograft transplants in rats, promoting corneal allograft survival by inhibiting the proliferation of CD4+, CD8+, and CD4+CD25-T cells. Therefore, modification of BMSCs by lentivirus-mediated IDO gene transfection may provide a novel strategy for controlling corneal allograft rejection.


Assuntos
Transplante de Córnea , Células-Tronco Mesenquimais , Ratos , Animais , Linfócitos T CD8-Positivos , Medula Óssea/metabolismo , Rejeição de Enxerto , Sobrevivência de Enxerto , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Proliferação de Células
11.
J Gene Med ; 26(1): e3635, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37984993

RESUMO

BACKGROUND: Gastric cancer, marked by its heterogeneous nature, showcases various molecular subtypes and clinical trajectories. This research delves into the significance of metabolic and immune-driven pathways in gastric cancer, constructing a prognostic signature derived from differentially expressed metabolic and immune-correlated genes (DE-MIGs). METHODS: Metabolic and immune-associated gene were sourced from the GeneCards database. Differential expression analysis on the TCGA-STAD dataset was executed using the limma package, unveiling 51 DE-MIGs that underwent functional enrichment scrutiny. The LASSO Cox regression methodology guided the creation of the prognostic signature, and individual patient risk scores were determined. Assessment tools like CIBERSORT, ESTIMATE and ssGSEA were deployed to study the immune microenvironment, while mutation profiles, genomic stability, resistance to chemotherapy and immunotherapy responsiveness were scrutinized across distinct signature categorizations. RESULTS: Among the identified DE-MIGs, 26 were significantly tied to the overall survival of gastric cancer patients. The developed prognostic signature proficiently differentiated patients into high-risk and low-risk cohorts, with the latter showing markedly better outcomes. The study underscored the centrality of the immune microenvironment in influencing gastric cancer outcomes. Key pathways such as TGF-Beta, TP53 and NRF2 dominated the high-risk group, whereas the LRTK-RAS and WNT pathways characterized the low-risk group. Interestingly, the low-risk segment also manifested a heightened tumor mutation burden and enhanced susceptibility to immunotherapy. CONCLUSIONS: Our findings introduce a pivotal prognostic signature, rooted in DE-MIGs, that effectively segregates gastric cancer patients into distinct risk-based segments. Insights into the influential role of the immune microenvironment in gastric cancer progression pave the way for more refined therapeutic interventions.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Prognóstico , Imunoterapia , Mutação , Fatores de Risco , Microambiente Tumoral/genética
12.
Front Artif Intell ; 6: 1213620, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928449

RESUMO

Background: Due to the lower reliability of laboratory tests, skin diseases are more suitable for diagnosis with AI models. There are limited AI dermatology diagnostic models combining images and text; few of these are for Asian populations, and few cover the most common types of diseases. Methods: Leveraging a dataset sourced from Asia comprising over 200,000 images and 220,000 medical records, we explored a deep learning-based system for Dual-channel images and extracted text for the diagnosis of skin diseases model DIET-AI to diagnose 31 skin diseases, which covers the majority of common skin diseases. From 1 September to 1 December 2021, we prospectively collected images from 6,043 cases and medical records from 15 hospitals in seven provinces in China. Then the performance of DIET-AI was compared with that of six doctors of different seniorities in the clinical dataset. Results: The average performance of DIET-AI in 31 diseases was not less than that of all the doctors of different seniorities. By comparing the area under the curve, sensitivity, and specificity, we demonstrate that the DIET-AI model is effective in clinical scenarios. In addition, medical records affect the performance of DIET-AI and physicians to varying degrees. Conclusion: This is the largest dermatological dataset for the Chinese demographic. For the first time, we built a Dual-channel image classification model on a non-cancer dermatitis dataset with both images and medical records and achieved comparable diagnostic performance to senior doctors about common skin diseases. It provides references for exploring the feasibility and performance evaluation of DIET-AI in clinical use afterward.

13.
Front Immunol ; 14: 1242909, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37753069

RESUMO

Background: In order to investigate the impact of Treg cell infiltration on the immune response against pancreatic cancer within the tumor microenvironment (TME), and identify crucial mRNA markers associated with Treg cells in pancreatic cancer, our study aims to delve into the role of Treg cells in the anti-tumor immune response of pancreatic cancer. Methods: The ordinary transcriptome data for this study was sourced from the GEO and TCGA databases. It was analyzed using single-cell sequencing analysis and machine learning. To assess the infiltration level of Treg cells in pancreatic cancer tissues, we employed the CIBERSORT method. The identification of genes most closely associated with Treg cells was accomplished through the implementation of weighted gene co-expression network analysis (WGCNA). Our analysis of single-cell sequencing data involved various quality control methods, followed by annotation and advanced analyses such as cell trajectory analysis and cell communication analysis to elucidate the role of Treg cells within the pancreatic cancer microenvironment. Additionally, we categorized the Treg cells into two subsets: Treg1 associated with favorable prognosis, and Treg2 associated with poor prognosis, based on the enrichment scores of the key genes. Employing the hdWGCNA method, we analyzed these two subsets to identify the critical signaling pathways governing their mutual transformation. Finally, we conducted PCR and immunofluorescence staining in vitro to validate the identified key genes. Results: Based on the results of immune infiltration analysis, we observed significant infiltration of Treg cells in the pancreatic cancer microenvironment. Subsequently, utilizing the WGCNA and machine learning algorithms, we ultimately identified four Treg cell-related genes (TRGs), among which four genes exhibited significant correlations with the occurrence and progression of pancreatic cancer. Among them, CASP4, TOB1, and CLEC2B were associated with poorer prognosis in pancreatic cancer patients, while FYN showed a correlation with better prognosis. Notably, significant differences were found in the HIF-1 signaling pathway between Treg1 and Treg2 cells identified by the four genes. These conclusions were further validated through in vitro experiments. Conclusion: Treg cells played a crucial role in the pancreatic cancer microenvironment, and their presence held a dual significance. Recognizing this characteristic was vital for understanding the limitations of Treg cell-targeted therapies. CASP4, FYN, TOB1, and CLEC2B exhibited close associations with infiltrating Treg cells in pancreatic cancer, suggesting their involvement in Treg cell functions. Further investigation was warranted to uncover the mechanisms underlying these associations. Notably, the HIF-1 signaling pathway emerged as a significant pathway contributing to the duality of Treg cells. Targeting this pathway could potentially revolutionize the existing treatment approaches for pancreatic cancer.


Assuntos
Neoplasias Pancreáticas , Linfócitos T Reguladores , Humanos , Microambiente Tumoral/genética , Transcriptoma , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas
14.
Rev Esp Enferm Dig ; 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37350653

RESUMO

Gastrinoma, a common type of GEP-NENs, is often sporadic, rarely manifested as multiple endocrine neoplasia type 1 (MEN1). We described a rare case of MEN1-related gastrinomas in the stomach, duodenum and pancreas along with lymph node metastases. The female patient had a long history of recurrent abdominal pain and diarrhea. G1 neuroendocrine tumors were diagnosed by endoscopic biopsy in the pylorus, duodenal bulb and the neck of the pancreas successively. Her symptoms lessened and serum gastrin level decreased after surgery. This case will help us learn more about MEN1-associated patients who are confirmed with multiple neuroendocrine tumors.

15.
J Minim Invasive Gynecol ; 30(10): 805-812, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37247808

RESUMO

STUDY OBJECTIVE: To study the incidence of intrauterine adhesions (IUAs) after hysteroscopic myomectomy. Previous studies report a range of incidence for IUAs after hysteroscopic myomectomy. DESIGN: A retrospective review study. SETTING: An academic community hospital in the Boston metropolitan area. PATIENTS: Patients undergoing hysteroscopic myomectomy at our institution from January 2019 to February 2022. Patients were excluded if they did not have plans for future fertility or had a new diagnosis of cancer. INTERVENTIONS: All patients underwent hysteroscopic myomectomy using bipolar resectoscope without postoperative medical or barrier treatment. All procedures were performed by 1 of 4 fellowship-trained high-volume gynecologic surgeons with resident and fellow assistance. Incidence of postoperative IUAs was assessed and treated using second-look office hysteroscopy. MEASUREMENTS AND MAIN RESULTS: A total of 44 patients without preoperative IUAs underwent hysteroscopic myomectomy during our study period, and 4 patients (9.1%) developed new IUAs. Among 9 patients who were found to have preoperative IUAs and underwent concurrent hysteroscopic myomectomy and lysis of adhesions, we found a recurrence of IUAs in 5 patients (55.6%). We found the number, size, and deepest type of myoma removed were not correlated to an increased risk of new IUA formation. In addition, removing myomas on opposing walls during the same operation did not increase the incidence of new IUAs. CONCLUSION: Formation of IUAs after hysteroscopic myomectomy is a well-documented consequence. Our reported incidence of 9.1% of new IUAs that are not affected by the number, size, deepest type of myoma resected, and resection of myomas on opposing uterine walls contributes to the current literature. In addition, our finding of 55.6% of recurrent IUAs in patients undergoing both hysteroscopic myomectomy and lysis of adhesions highlights a high-risk population requiring additional study.


Assuntos
Mioma , Doenças Uterinas , Miomectomia Uterina , Neoplasias Uterinas , Gravidez , Humanos , Feminino , Miomectomia Uterina/efeitos adversos , Miomectomia Uterina/métodos , Incidência , Doenças Uterinas/cirurgia , Histeroscopia/efeitos adversos , Histeroscopia/métodos , Fertilidade , Mioma/complicações , Aderências Teciduais/epidemiologia , Aderências Teciduais/etiologia , Aderências Teciduais/cirurgia , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/complicações
16.
Eur Radiol ; 33(7): 4734-4745, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36723725

RESUMO

OBJECTIVES: This study aimed to develop and validate a predicting model for the histologic classification of solid lung lesions based on preoperative contrast-enhanced CT. METHODS: A primary dataset of 1012 patients from Tianjin Medical University Cancer Institute and Hospital (TMUCIH) was randomly divided into a development cohort (708) and an internal validation cohort (304). Patients from the Second Hospital of Shanxi Medical University (SHSMU) were set as an external validation cohort (212). Two clinical factors (age, gender) and twenty-one characteristics on contrast-enhanced CT were used to construct a multinomial multivariable logistic regression model for the classification of seven common histologic types of solid lung lesions. The area under the receiver operating characteristic curve was used to assess the diagnostic performance of the model in the development and validation cohorts, separately. RESULTS: Multivariable analysis showed that two clinical factors and twenty-one characteristics on contrast-enhanced CT were predictive in lung lesion histologic classification. The mean AUC of the proposed model for histologic classification was 0.95, 0.94, and 0.92 in the development, internal validation, and external validation cohort, respectively. When determining the malignancy of lung lesions based on histologic types, the mean AUC of the model was 0.88, 0.86, and 0.90 in three cohorts. CONCLUSIONS: We demonstrated that by utilizing both clinical and CT characteristics on contrast-enhanced CT images, the proposed model could not only effectively stratify histologic types of solid lung lesions, but also enabled accurate assessment of lung lesion malignancy. Such a model has the potential to avoid unnecessary surgery for patients and to guide clinical decision-making for preoperative treatment. KEY POINTS: • Clinical and CT characteristics on contrast-enhanced CT could be used to differentiate histologic types of solid lung lesions. • Predicting models using preoperative contrast-enhanced CT could accurately assessment of tumor malignancy based on predicted histologic types.


Assuntos
Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Pulmão/patologia , Curva ROC , Tomografia Computadorizada por Raios X/métodos
17.
Environ Sci Pollut Res Int ; 30(9): 24154-24167, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36334203

RESUMO

Ethylene oxide (EO) is a reactive epoxide. However, the association between EO exposure and the risk of developing asthma in humans is unknown. The aim of this study was to investigate the relationship between EO exposure and the risk of developing asthma in the general US population. In this cross-sectional study, data of 2542 patients from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016 were obtained and analyzed. Hemoglobin adducts of EO (HbEO) level be used as the main factor for predicting EO exposure. The association between the level of EO exposure and the risk of developing asthma was evaluated with logistic regression models and dose-response analysis curves of restricted cubic spline function. Mediation analysis and linear regression analysis were utilized to evaluate the association between EO exposure and inflammation indicators. According to the quartiles of HbEO level, the patients were divided into four groups. The results indicated that an increased HbEO level was associated with a higher risk of asthma onset. Compared with the lowest quartile, the odds ratio (OR) with the 95% confidence interval (CI) for the highest quartile was 1.960 (95% CI: 1.348-2.849, P = 0.003). After being adjusted for numerous potential confounders, the OR of quartile 4 relative to quartile 1 was 1.991 (95% CI: 1.359-2.916, P = 0.001). Consistent results were also obtained in most subgroup analyses and dose-response analysis curves. In addition, EO levels were positively correlated with the inflammatory indicators (P = 0.006 for WBC, P = 0.015 for lymphocyte, and P = 0.015 for neutrophil). This study revealed a positive correlation between the level of EO exposure and the risk of asthma in a representative US population. In addition, inflammatory response may prove to be a potential biological mechanism underlying EO-induced asthma.


Assuntos
Asma , Óxido de Etileno , Humanos , Inquéritos Nutricionais , Estudos Transversais , Compostos de Epóxi
19.
Cell Mol Biol (Noisy-le-grand) ; 69(15): 148-153, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38279465

RESUMO

The objective of this study was to explore the correlation between vaginal microecological imbalance and the expression of related inflammatory factors in pregnant women with group B streptococcus (GBS) infection and pregnancy outcomes. For this purpose, 100 GBS-positive pregnant women were recruited as the experimental group, and 100 GBS-negative pregnant women were recruited as the controls. The balance of vaginal microecology of pregnant women in different groups was compared. Results showed that the probability of vaginal microecological imbalance in the experimental group was much higher than against the controls. Fasting venous blood was drawn from the pregnant women in two groups. After centrifugation, the expression levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-1ß (IL-1ß) in serum were detected. It was found that the expression levels of IL-6, IL-1ß, and TNF-α in the experimental group were higher than against the controls. After delivery, it suggested that the incidence of premature delivery, neonatal infection, premature rupture of membranes, and other adverse childbirth in the experimental group was much higher in contrast to the controls, up to 87%. In conclusion, GBS infection can increase the incidence of vaginal microecological imbalance and the expression of serum inflammatory factors in pregnant women, and it can greatly raise the incidence of adverse pregnancy outcomes.


Assuntos
Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Recém-Nascido , Gravidez , Feminino , Humanos , Resultado da Gravidez , Gestantes , Interleucina-6 , Fator de Necrose Tumoral alfa , Streptococcus agalactiae , Infecções Estreptocócicas/epidemiologia , Inflamação
20.
J Transl Med ; 20(1): 545, 2022 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-36435788

RESUMO

BACKGROUND: This study aimed to analyze the clinical outcomes of blastocyst which undergo the preimplantation genetic testing (PGT) transplantation from frozen-thawed D5 and D6. In addition, the effect of blastocyst grade on clinical and neonatal outcomes was also investigated in this study. METHODS: The pregnancy and miscarriage rates of 1130 cycles of frozen embryo transfer, including 784 D5 frozen embryos and 346 D6 frozen embryos in the Reproductive Hospital of Shandong University from January to December 2020 were analyzed. Gardner blastocyst scoring was used for blastocyst evaluation. RESULTS: The pregnancy rate of D5 blastocyst was significantly higher, whereas the miscarriage rate of D5 blastocyst was lower, than that of D6 blastocyst tissue biopsy. No significant difference was observed in birth weight and low birth weight of D5 blastocyst and D6 blastocyst, preterm birth, gestational age, and neonatal sex. Frozen-thawed D5 blastocysts have higher pregnancy success rates and lower miscarriage rates compared to D6 blastocysts. CONCLUSION: Therefore, both blastocyst grade and embryo biopsy date must be considered when transferring frozen embryos.


Assuntos
Aborto Espontâneo , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Aborto Espontâneo/genética , Blastocisto , Transferência Embrionária , Testes Genéticos
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