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1.
Small Methods ; : e2400177, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38721966

RESUMO

This study addresses a crucial challenge in two-dimensional (2D) material-based electronic devices-inefficient heat dissipation across the van der Waals (vdW) interface connecting the 2D material to its three-dimensional (3D) substrate. The objective is to enhance the interfacial thermal conductance (ITC) of 2D/3D heterostructures without compromising the intrinsic thermal conductivities (κ) of 2D materials. Using 2D-MoS2/3D-GaN as an example, a novel strategy to enhance both the ITC across 2D/3D interface and κ of 2D material is proposed by introducing a controlled concentration (ρ) of vacancy defects to substrate's bottom surface. Molecular dynamics simulations demonstrate a notable 2.1-fold higher ITC of MoS2/GaN at ρ = 4% compared to the no-defective counterpart, along with an impressive 56% enhancement in κ of MoS2 compared to the conventional upper surface modification approaches. Phonon dynamics analysis attributes the ITC enhancement to increased phonon coupling between MoS2 and GaN, resulting from polarization conversion and hybridization of phonons at the defective surface. Spectral energy density analysis affirms that the improved κ of MoS2 directly results from the proposed strategy, effectively reducing phonon scattering at the interface. This work provides an effective approach for enhancing heat transfer in 2D/3D vdW heterostructures, promisingly advancing electronics' heat dissipation.

3.
Asian J Surg ; 47(4): 1734-1739, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38185563

RESUMO

OBJECTIVE: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. METHODS: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. RESULTS: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p < 0.001). CONCLUSION: In comparison to COT, ETGUA and SLEA demonstrate superiority in protecting neck muscles and preserving voice and swallowing function without compromising surgical safety or radicality.


Assuntos
Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Deglutição , Músculos do Pescoço/patologia , Endoscopia , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/cirurgia
4.
Aging (Albany NY) ; 16(1): 627-647, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38206305

RESUMO

BACKGROUND: Research has demonstrated that some tumor cells can transform into drug-tolerant persisters (DTPs), which serve as a reservoir for the recurrence of the disease. The persister state in cancer cells arises due to temporary molecular reprogramming, and exploring the genetic composition and microenvironment during the development of head and neck squamous cell carcinoma (HNSCC) can enhance our comprehension of the types of cell death that HNSCC, thus identifying potential targets for innovative therapies. This project investigated lipid-metabolism-driven ferroptosis and its role in drug resistance and DTP generation in HNSCC. METHODS: High levels of FSP1 were discovered in the tissues of patients who experienced relapse after cisplatin treatment. RNA sequencing indicated that a series of genes related to lipid metabolism were also highly expressed in tissues from these patients. Consistent results were obtained in primary DTP cells isolated from patients who experienced relapse. The Cancer Genome Atlas database confirmed this finding. This revealed that the activation of drug resistance in cancer cells is influenced by FSP1, intracellular iron homeostasis, and lipid metabolism. The regulatory roles of ferroptosis suppressor protein 1 (FSP1) in HNSCC metabolic regulation were investigated. RESULTS: We generated human oral squamous cell carcinoma DTP cells (HNSCC cell line) to cisplatin and observed higher expression of FSP1 and lipid-metabolism-related targets in vitro. The shFSP1 blockade attenuated HNSCC-DTP cell stemness and downregulated tumor invasion and the metastatic rate. We found that cisplatin induced FSP1/ACSL4 axis expression in HNSC-DTPC cells. Finally, we evaluated the HNSCC CSC-inhibitory functions of iFSP1 (a metabolic drug and ferroptosis inducer) used for neo-adjuvant chemotherapy; this was achieved by inducing ferroptosis in a patient-derived xenograft mouse model. CONCLUSIONS: The present findings elucidate the link between iron homeostasis, ferroptosis, and cancer metabolism in HNSCC-DTP generation and acquisition of chemoresistance. The findings may serve as a suitable model for cancer treatment testing and prediction of precision treatment outcomes. In conclusion, this study provides clinically oriented platforms for evaluating metabolism-modulating drugs (FSP1 inhibitors) and new drug candidates of drug resistance and ferroptotic biomarkers.


Assuntos
Carcinoma de Células Escamosas , Ferroptose , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Humanos , Camundongos , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Ferroptose/genética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Homeostase , Ferro/uso terapêutico , Metabolismo dos Lipídeos , Lipídeos , Recidiva Local de Neoplasia , Recidiva , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Microambiente Tumoral
5.
Exp Ther Med ; 27(2): 74, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38264426

RESUMO

Tumor vascular endothelial cells play a pivotal in the tumor microenvironment, influencing the proliferation, invasion, and metastasis of tumor progression. The present study investigated a novel method for inducing the transformation of breast cancer stem cells into endothelial cells, providing a cellular model investigating anti-angiogenic mechanisms in vitro. The breast cancer cell line MCF-7 was used, and the expression of CD133 was initially detected using flow cytometry. CD133+ breast cancer cells were purified using immunomagnetic bead sorting technology, yielding an MCF-7CD133+ subpopulation. The proliferation ability of these cells was assessed using an MTT assay, while their microsphere formation ability was evaluated using a microsphere formation assay. Post-transformation in an optimized endothelial cell culture medium, expression of endothelial cell markers CD31 and CD105 were detected using flow cytometry. Endothelial cell tube formation assays and DiI-labeled acetylated low-density lipoprotein (DiI-Ac-LDL) assays were employed to analyze the endothelial cell function of the MCF-7CD133+ cells. MDM2/CEN12 gene amplification was detected through fluorescence in situ hybridization (FISH). The MCF-7 breast cancer cell line exhibited 1.7±0.3% trace cells expressing the stem cell surface marker CD133. After anti-CD133 immunomagnetic bead sorting, MCF-7CD133+ and MCF-7CD133- subpopulation cells were obtained, with CD133 expression rates of 85.6±2.8 and 0.18±0.08%, respectively. MTT assay results demonstrated that, after 7 days, the proliferation rate of MCF-7CD133+ cells was significantly higher compared with MCF-7CD133- cells. MCF-7CD133+ subpopulation cells displayed strong stem cell characteristics, growing in suspension in serum-free media and forming tumor cell spheres. In contrast, MCF-7CD133- cells failed to form microspheres. After culturing cells in endothelial cell differentiation and maintenance media, the percentage of MCF-7CD133+ cells before and after endothelial cell culture was 0.3±0.16 and 81.4±8.37% for CD31+ cells and 0.2±0.08 and 83.8±7.24% for CD105+ cells, respectively. Vascular-like structure formation and Ac-LDL phagocytosis with red fluorescence in the tube formation assays confirmed endothelial cell function in the MCF-7CD133+ cells. FISH was used to verify MDM2/CEN12 gene amplification in the induced MCF-7CD133+ cells, indicating tumor cell characteristics. The modified endothelial cell transformation medium effectively induced differentiated tumor stem cells to express vascular endothelial cell markers and exhibit endothelial functions, ideal for in vitro anti-angiogenesis research.

6.
ACS Med Chem Lett ; 15(1): 21-28, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38229748

RESUMO

Oncogenic KRAS mutations were identified decades ago, yet the selective inhibition of specific KRAS mutant proteins represents an ongoing challenge. Recent progress has been made in targeting certain P-loop mutant proteins, in particular KRAS G12C, for which the covalent inhibition of the GDP state via the Switch II pocket is now a clinically validated strategy. Inhibition of other KRAS mutant proteins such as KRAS G13D, on the other hand, still requires clinical validation. The remoteness of the D13 residue relative to the Switch II pocket in combination with the solvent exposure and conformational flexibility of the D13 side chain, as well as the difficulties of targeting carboxylate residues covalently, renders this specific protein particularly challenging to target selectively. In this report, we describe the design and evaluation of potent and KRAS G13D-selective reversible inhibitors. Subnanomolar binding to the GDP state Switch II pocket and biochemical selectivity over WT KRAS are achieved by leveraging a salt bridge with D13.

7.
Int Immunopharmacol ; 126: 111309, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38048666

RESUMO

Choledochojejunostomy has been common surgical treatment of biliary tract disease. Scar formation at anastomotic often results in postoperative complications associated with bleak post-operative recovery, in which local inflammation may be a potential target to modulate local scar formation. This study investigated the effect of regulatory B10 cells on local scar formation through interleukin-10 signal pathway following Roux-en-Y choledochojejunostomy (RCJS) in a novel rat model. Sprague-Dawley (SD) rats with RCJS were randomly divided into blank group, experimental group, IL-10 blocking group, control group, and received different interventions and duration. Injected through dorsal vein of penis, rats in different groups were treated respectively according to scheme. These interventions were performed during surgery, on 1st day, and 2nd day after surgery. Related indexes, including blood examination, specimen tissue of anastomotic detection, were recorded and compared in different interventional groups. Rats in experimental groups had more rapid recovery in liver function and inflammatory index, and higher in IL-10 level. Flow cytometry analysis showed that rats in experimental groups had highest content of B10 cells and lowest content of CD4+CD25- T cells in peripheral blood. Wider anastomotic by macroscopical observation, and slighter proliferation of collagen fiber and smooth muscle fiber, lower α-SMA and TGF-ß1 levels by pathological staining were detected in experimental groups. Higher expression of the IL-10 gene and lower expression of TGF-ß1 at anastomotic were detected in experimental groups. B10 cells may relieve local inflammation of anastomotic following RCJS in rats through IL-10-dependent modulatory effect, and improve local scar formation.


Assuntos
Coledocostomia , Cicatriz , Masculino , Ratos , Animais , Fator de Crescimento Transformador beta1 , Ratos Sprague-Dawley , Interleucina-10 , Inflamação
8.
Eur Spine J ; 33(3): 1098-1108, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38153529

RESUMO

PURPOSE: This study aimed to establish a nomogram to predict the risk of venous thromboembolism (VTE), identifying potential risk factors, and providing theoretical basis for prevention of VTE after spinal surgery. METHODS: A retrospective analysis was conducted on 2754 patients who underwent spinal surgery. The general characteristics of the training group were initially screened using univariate logistic analysis, and the LASSO method was used for optimal prediction. Subsequently, multivariate logistic regression analysis was performed to identify independent risk factors for postoperative VTE in the training group, and a nomogram for predict risk of VTE was established. The discrimination, calibration, and clinical usefulness of the nomogram were separately evaluated using the C-index, receiver operating characteristic curve, calibration plot and clinical decision curve, and was validated using data from the validation group finally. RESULTS: Multivariate logistic regression analysis identified 10 independent risk factors for VTE after spinal surgery. A nomogram was established based on these independent risk factors. The C-index for the training and validation groups indicating high accuracy and stability of the model. The area under the receiver operating characteristic curve indicating excellent discrimination ability; the calibration curves showed outstanding calibration for both the training and validation groups. Decision curve analysis showed the clinical net benefit of using the nomogram could be maximized in the probability threshold range of 0.01-1. CONCLUSION: Patients undergoing spinal surgery with elevated D-dimer levels, prolonger surgical, and cervical surgery have higher risk of VTE. The nomogram can provide a theoretical basis for clinicians to prevent VTE.


Assuntos
Nomogramas , Tromboembolia Venosa , Humanos , Estudos Retrospectivos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Procedimentos Neurocirúrgicos , Pescoço , Fatores de Risco
9.
Int J Mol Sci ; 24(24)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38139175

RESUMO

Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer. While therapeutic innovations have made strides, radioresistance persists as a significant hindrance in OSCC treatment. Despite identifying numerous targets that could potentially suppress the oncogenic attributes of OSCC, the exploration of oncogenic protein kinases for cancer therapy remains limited. Consequently, the functions of many kinase proteins in OSCC continue to be largely undetermined. In this research, we aim to disclose protein kinases that target OSCC and elaborate their roles and molecular mechanisms. Through the examination of the kinome library of radiotherapy-resistant/sensitive OSCC cell lines (HN12 and SAS), we identified a key gene, the tyrosine phosphorylation-regulated kinase 3 (DYRK3), a member of the DYRK family. We developed an in vitro cell model, composed of radiation-resistant OSCC, to scrutinize the clinical implications and contributions of DYRK3 and phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS) signaling in OSCC. This investigation involves bioinformatics and human tissue arrays. We seek to comprehend the role of DYRK3 and PAICS signaling in the development of OSCC and its resistance to radiotherapy. Various in vitro assays are utilized to reveal the essential molecular mechanism behind radiotherapy resistance in connection with the DYRK3 and PAICS interaction. In our study, we quantified the concentrations of DYRK3 and PAICS proteins and tracked the expression levels of key pluripotency markers, particularly PPAT. Furthermore, we extended our investigation to include an analysis of Glut-1, a gene recognized for its linkage to radioresistance in oral squamous cell carcinoma (OSCC). Furthermore, we conducted an in vivo study to affirm the impact of DYRK3 and PAICS on tumor growth and radiotherapy resistance, focusing particularly on the role of DYRK3 in the radiotherapy resistance pathway. This focus leads us to identify new therapeutic agents that can combat radiotherapy resistance by inhibiting DYRK3 (GSK-626616). Our in vitro models showed that inhibiting PAICS disrupts purinosome formation and influences the survival rate of radiation-resistant OSCC cell lines. These outcomes underscore the pivotal role of the DYRK3/PAICS axis in directing OSCC radiotherapy resistance pathways and, as a result, influencing OSCC progression or therapy resistance. Our findings also reveal a significant correlation between DYRK3 expression and the PAICS enzyme in OSCC radiotherapy resistance.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/radioterapia , Neoplasias Bucais/metabolismo , Linhagem Celular Tumoral , Neoplasias de Cabeça e Pescoço/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas Tirosina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
10.
Int Immunopharmacol ; 125(Pt A): 111131, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38149572

RESUMO

BACKGROUND: Previous study found that supplements with active vitamin D3 alleviated experimental colitis. The objective of this study was to investigate the possible role of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a ketone synthase, on vitamin D3 protecting against experimental colitis. METHODS: HMGCS2 and vitamin D receptor (VDR) were measured in UC patients. The effects of vitamin D deficiency (VDD) and exogenous 1,25(OH)2D3 supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)-treated mice. DSS-induced oxidative stress and inflammation were analyzed in HT-29 cells. HMGCS2 was detected in 1,25(OH)2D3-pretreated HT-29 cells and mouse intestines. HMGCS2 was silenced to investigate the role of HMGCS2 in 1,25(OH)2D3 protecting against experimental colitis. RESULTS: Intestinal HMGCS2 downregulation was positively correlated with VDR reduction in UC patients. The in vivo experiments showed that VDD exacerbated DSS-induced colitis. By contrast, 1,25(OH)2D3 supplementation ameliorated DSS-induced colon damage, oxidative stress and inflammation. HMGCS2 was up-regulated after 1,25(OH)2D3 supplementation both in vivo and in vitro. Transfection with HMGCS2-siRNA inhibited antioxidant and anti-inflammatory effects of 1,25(OH)2D3 in DSS-treated HT-29 cells. CONCLUSION: 1,25(OH)2D3 supplementation up-regulates HMGCS2, which is responsible for 1,25(OH)2D3-mediated protection against oxidative stress and inflammation in DSS-induced colitis. These findings provide a potential therapeutic strategy for alleviating colitis-associated oxidative stress and inflammation.


Assuntos
Colite , Humanos , Camundongos , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/prevenção & controle , Inflamação/tratamento farmacológico , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Colecalciferol/uso terapêutico , Estresse Oxidativo , Sulfato de Dextrana/farmacologia , Camundongos Endogâmicos C57BL , Hidroximetilglutaril-CoA Sintase
11.
J Control Release ; 364: 718-733, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37944669

RESUMO

Adipose-derived mesenchymal stem cell-derived small extracellular vesicles (Ad-MSC-sEVs/AMEs) combined with scaffold materials are used in tissue-engineered bladders; however, the lack of retention leads to limited distribution of AMEs in the scaffold areas and low bioavailability of AMEs after bladder reconstruction. To improve retention of AMEs, we developed a novel strategy that modifies the surface charge of the bladder acellular matrix (BAM) via oxidative self-polymerization of dopamine-reducing graphene oxide (GO) and AMEs using ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD). We evaluated two BAM surface modification methods and evaluated the biocompatibility of materials and PPD and electrostatic adherence effects between PPD-modified AMEs and rGO-PDA/BAM in vivo and in vitro. Surface modification increased retention of AMEs, enhanced regeneration of bladder structures, and increased electrical conductivity of rGO-PDA/BAM, thereby improving bladder function recovery. RNA-sequencing revealed 543 miRNAs in human AMEs and 514 miRNAs in rat AMEs. A Venn diagram was used to show target genes of miRNA with the highest proportion predicted by the four databases; related biological processes and pathways were predicted by KEGG and GO analyses. We report a strategy for improving bioavailability of AMEs for bladder reconstruction and reveal that enriched miR-21-5p targets PIK3R1 and activates the PI3K/Akt pathway to promote cell proliferation and migration.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Ratos , Humanos , Animais , Engenharia Tecidual/métodos , Bexiga Urinária/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Matriz Extracelular/metabolismo , MicroRNAs/metabolismo
12.
Int J Med Sci ; 20(13): 1671-1678, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928871

RESUMO

Histamine receptor-1 (H1) antagonists like levocetirizine are frequently used nowadays to treat rhinitis patients who experience rhinorrhea and sneezing. The trachea may be affected by the H1 antagonist when it is used to treat nasal symptoms, either orally or through inhalation. The purpose of this study was to ascertain in vitro effects of levocetirizine on isolated tracheal smooth muscle. As a parasympathetic mimetic, methacholine (10-6 M) causes contractions in tracheal smooth muscle, which is how we tested effectiveness of levocetirizine on isolated rat tracheal smooth muscle. We also tested the drug's impact on electrically induced tracheal smooth muscle contractions. The impact of menthol (either before or after) on the contraction brought on by 10-6 M methacholine was also investigated. According to the results, the addition of levocetirizine at concentrations of 10-5 M or more caused a slight relaxation in response to methacholine's 10-6 M contraction. Levocetirizine could prevent spike contraction brought on by electrical field stimulation (EFS). As the concentration rose, it alone had a neglect effect on the trachea's basal tension. Before menthol was applied, levocetirizine might have also inhibited the function of the cold receptor. According to this study, levocetirizine might potentially impede the parasympathetic function of the trachea. If levocetirizine was used prior to menthol addition, it also reduced the function of cold receptors.


Assuntos
Cetirizina , Mentol , Ratos , Humanos , Animais , Cloreto de Metacolina/farmacologia , Mentol/farmacologia , Cetirizina/farmacologia , Cetirizina/uso terapêutico , Músculo Liso/fisiologia , Contração Muscular , Traqueia/fisiologia
14.
Diagnostics (Basel) ; 13(19)2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37835869

RESUMO

BACKGROUND: Correctly distinguishing mass-forming chronic pancreatitis (MFCP) from pancreatic cancer (PC) is of clinical significance to determine optimal therapy and improve the prognosis of patients. According to research, inflammation status in PC is different from that in MFCP. Mean platelet volume/platelet ratio (MPR) is a platelet-related inflammation index which has been proven to be valuable in the diagnosis and prognosis of various malignant cancers due to the change in mean platelet volume and platelet count under abnormal inflammatory conditions caused by tumors. Thus, we conducted this study to investigate the clinical value of MPR in distinguishing MFCP from PC. METHODS: We retrospectively analyzed the data of 422 patients who were suspected to have PC during imaging examination at our department from January 2012 to December 2021. Included patients were divided into the PC (n = 383) and MFCP groups (n = 39), according to their pathological diagnosis. Clinical data including MPR were compared within these two groups and the diagnostic value was explored using logistic regression. The ROC curve between MPR and PC occurrence was drawn and an optimal cut-off value was obtained. Propensity score matching was applied to match MFCP patients with PC patients according to their age and carbohydrate antigen 19-9 (CA19-9). Differences in MPR between groups were compared to verify our findings. RESULTS: The area under the ROC curve between MPR and PC occurrence was 0.728 (95%CI: 0.652-0.805) and the optimal cut-off value was 0.045 with a 69.2% sensitivity and 68.0% accuracy. For all the included patients, MPRs in the MFCP and PC groups were 0.04 (0.04, 0.06) and 0.06 (0.04, 0.07), respectively (p = 0.005). In patients with matching propensity scores, MPRs in the MFCP and PC groups were 0.04 (0.03, 0.06) and 0.06 (0.05, 0.08), respectively (p = 0.005). Multiple logistic regression in all included patients and matched patients confirmed MPR and CA19-9 as independent risk markers in distinguishing PC. Combining CA19-9 with MPR can increase the sensitivity and accuracy in diagnosing PC to 93.2% and 89.5%, respectively. CONCLUSION: MPR in PC patients is significantly higher than that in MFCP patients and may be adopted as a potential indicator to distinguish MFCP and PC. Its differential diagnosis capacity can be improved if combined with CA19-9.

16.
Ann Med ; 55(2): 2268112, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37824443

RESUMO

PURPOSE: This study aimed to develop a postoperative MRI-based fibrosis scoring system and to assess its correlation with anorectal function in locally advanced rectal cancer (LARC) cases administered neoadjuvant chemoradiotherapy (nCRT). METHODS: Pathologically confirmed LARC cases administered nCRT and radical resection were assessed retrospectively. Based on postoperative magnetic resonance imaging (MRI) findings, anastomotic fibrosis score (AFS) and perirectal fibrosis score (PFS) were determined to evaluate the extent of fibrosis. The Wexner continence score for anorectal function was obtained 2 years postoperatively and assessed for correlation with MRI fibrosis scores. The cases were divided into 2 groups by the median Wexner score. Univariable and multivariable analyses were adopted for building a nomogram model, whose diagnostic performance was estimated by receiver operating characteristic (ROC) and decision curve analyses (DCA). RESULTS: Finally, 144 patients with LARC were included in cohort 1 (training set). 52 patients were enrolled in cohort 2 (external validation set). Spearman correlation analysis indicated that AFS and PFS were positively correlated with the Wexner score. Univariable and multivariable analyses revealed age, tumor height, AFS, and PFS were independent predictors of anorectal function. The nomogram model achieved a good diagnostic performance, with AUCs of 0.800 and 0.827 in the training and validation sets, respectively; its predicting value was also confirmed by DCA. CONCLUSION: The present study showed AFS and PFS derived from postoperative MRI are positively correlated with Wexner score. In addition, the new scoring system was effective in predicting anorectal function in LARC cases administered nCRT.


Assuntos
Neoplasias Retais , Humanos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Terapia Neoadjuvante/métodos , Quimiorradioterapia/métodos , Resultado do Tratamento , Imageamento por Ressonância Magnética/métodos , Fibrose
17.
Front Psychiatry ; 14: 1235713, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37654993

RESUMO

Introduction: The effects of repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC) in patients with major depressive disorder (MDD) have been proved to have antidepressant effects. However, the absence of biomarkers to assess treatment response remains a challenge. This research aims to explore the relationship between frontal lobe activity, measured using near infrared spectroscopy (NIRS), and changes in symptoms among MDD patients following rTMS treatment. Methods: A total of 26 MDD patients underwent 20 sessions of 10 Hz rTMS targeting the left DLPFC. NIRS was used to measure frontal lobe activity during a verbal fluency test at baseline, after 10 rTMS sessions, and after 20 rTMS sessions. Responders were defined as individuals with more than a 50% reduction in symptoms based on the 21-item Hamilton Depression Rating Scale after 20 rTMS sessions. Results: Among the 14 responders, an increase in frontal lobe activity was significantly correlated with improvements in depressive symptoms following 10 (p = 0.0001) and 20 rTMS sessions (p = 0.007). Additionally, frontal lobe activity after 10 rTMS sessions was significantly associated with symptom improvement after 20 sessions (p = 0.001). These associations were not observed among non-responders. Conclusion: The findings from this study indicate distinct patterns of frontal lobe activity between responders and non-responders to rTMS treatment, suggesting that NIRS has the potential to serve as a biomarker for monitoring treatment response in MDD patients undergoing rTMS.

18.
J Affect Disord ; 341: 366-373, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37634818

RESUMO

BACKGROUND: To establish a clinically applicable neuroimaging-guided diagnostic support system that uses near-infrared spectroscopy (NIRS) for differential diagnosis at the individual level among major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SZ). METHODS: A total of 192 participants were recruited, including 40 patients with MDD, 38 patients with BPD, 65 patients with SZ, and 49 healthy individuals. We analyzed the spatiotemporal characteristics of hemodynamic responses in the frontotemporal cortex during a verbal fluency test (VFT) measured by NIRS to assess the accuracy of single-subject classification for differential diagnosis among the three psychiatric disorders. The optimal threshold of the frontal centroid value (54 seconds) was utilized on the basis of the findings of the Japanese study. RESULTS: The application of the optimal threshold of the frontal centroid value (54 seconds) allowed for the accurate differentiation of patients with unipolar MDD (72.5%) from BPD (78.9%) or SZ (84.6%). CONCLUSION: These results suggest that the NIRS-aided differential diagnosis of major psychiatric disorders can be a promising biomarker in Taiwan. Future multi-site studies are needed to validate our findings.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Esquizofrenia , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Bipolar/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Diagnóstico Diferencial , Espectroscopia de Luz Próxima ao Infravermelho
19.
Discov Nano ; 18(1): 96, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37505432

RESUMO

This article presents a new line tunneling dominating metal-semiconductor contact-induced SiGe-Si tunnel field-effect transistor with control gate (CG-Line SiGe/Si iTFET). With a structure where two symmetrical control gates at the drain region are given a sufficient negative bias, the overlap of the energy bands at the drain in the OFF-state is effectively suppressed, thus reducing the tunneling probability and significantly decreasing leakage current. Additionally, the large overlap area between the source and gate improves the gate's ability to control the tunneling interface effectively, improving the ON-state current and subthreshold swing characteristics. By using the Schottky contact characteristics of a metal-semiconductor contact with different work functions to form a PN junction, the need to control doping profiles or random doping fluctuations is avoided. Furthermore, as ion implantation is not required, issues related to subsequent annealing are also eliminated, greatly reducing thermal budget. Due to the different material bandgap characteristics selected for the source and drain regions, the probability of overlap of the energy bands in the source region in the ON-state is increased and that in the drain region in the OFF-state is reduced. Based on the feasibility of the actual fabrication process and through rigorous 2D simulation studies, improvements in subthreshold swing and high on/off current ratio can be achieved simultaneously based on the proposed device structure. Additionally, the presence of the control gate structure effectively suppresses leakage current, further enhancing its potential for low-power-consumption applications.

20.
Pancreas ; 52(2): e151-e162, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37523607

RESUMO

OBJECTIVES: This study aimed to develop a liver metastasis-related gene prognostic index (LMPI) for pancreatic ductal adenocarcinoma prognosis and therapy. METHODS: The Cancer Genome Atlas data set was used to identify liver metastasis-related hub genes via weighted gene coexpression network analysis. The core genes were identified to construct an LMPI by using the Cox regression method. An immune cell abundance identifier was applied to determine the immune cell abundance. RESULTS: A total of 78 hub liver metastasis-related genes in the black module were significantly enriched in complement and coagulation cascades, fat digestion and absorption, and the PPAR signaling pathway. Then, an LMPI was constructed on the basis of the 5 prognostic genes (MOGAT3, ASGR1, TRPM8, SGSM1, and LOC101927851). Patients with higher LMPI scores had poor overall survival, more co-occurring or mutually exclusive pairs of driver gene mutations, and less benefit from immunotherapy than patients with lower LMPI scores. In addition, a high correlation was also found between LMPI scores and immune infiltration, such as CD4 naive, CD8 T, cytotoxic T, T helper 2, follicular helper T, and natural killer cells. CONCLUSIONS: The core genes of the LMPI developed may be independent factors for predicting prognosis, immune characteristics, and immunotherapy efficacy in pancreatic ductal adenocarcinoma.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Prognóstico , Receptor de Asialoglicoproteína , Neoplasias Pancreáticas
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