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1.
BMC Palliat Care ; 23(1): 136, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811953

RESUMO

BACKGROUND: An accurate perception of death risk is a prerequisite for advanced cancer patients to make informed end-of-life care decisions. However, there is to date no suitable scale to measure death risk perception. This study was to develop and psychometrically test the death risk perception scale (DRPS) for advanced cancer patients. METHODS: Process of instrument development and psychometric evaluation were used. First, qualitative research, a literature review, brainstorming, a Delphi study, and cognitive interviews were conducted to construct a pretest scale of death risk perception. Second, a scale-based survey was administered to 479 advanced cancer patients. Item, exploratory factor, and confirmatory factor analyses were employed to optimize the scale. The Cronbach's alpha was calculated as a reliability analysis. The validity analysis included construct, convergent, discriminant, and content validity values. RESULTS: A three-dimension, 12-item scale was developed, including deliberative, affective, and experiential risk perception. The confirmatory factor analysis supported the three-factor model with satisfactory convergent and discriminant validity levels. The Cronbach's alpha coefficient for internal consistency was 0.807 and scale-level content validity index was 0.98. CONCLUSIONS: The 12-item DRPS is a reliable and valid instrument for assessing the level of death risk perception in advanced cancer patients. More studies are needed to examine its structure and robustness prior to use.


Assuntos
Atitude Frente a Morte , Neoplasias , Percepção , Psicometria , Humanos , Psicometria/instrumentação , Psicometria/métodos , Neoplasias/psicologia , Neoplasias/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Inquéritos e Questionários , Reprodutibilidade dos Testes , Idoso , Adulto , Pesquisa Qualitativa , Medição de Risco/métodos , Medição de Risco/normas , Técnica Delphi , Análise Fatorial , Idoso de 80 Anos ou mais
2.
Cancer Lett ; 593: 216956, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38735381

RESUMO

Anti-CDK4/6 therapy has been employed for the treatment for head and neck squamous cell carcinoma (HNSCC) with CDK4/6 hyperactivation, but the response rate is relatively low. In this study, we first showed that CDK4 and CDK6 was over-expressed and conferred poor prognosis in HNSCC. Moreover, in RB-positive HNSCC, STAT3 signaling was activated induced by CDK4/6 inhibition and STAT3 promotes RB deficiency by upregulation of MYC. Thirdly, the combination of Stattic and CDK4/6 inhibitor results in striking anti-tumor effect in vitro and in Cal27 derived animal models. Additionally, phospho-STAT3 level negatively correlates with RB expression and predicts poor prognosis in patients with HNSCC. Taken together, our findings suggest an unrecognized function of STAT3 confers to CDK4/6 inhibitors resistance and presenting a promising combination strategy for patients with HNSCC.

3.
Cell Rep Med ; 5(5): 101519, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38692271

RESUMO

Osteosarcoma (OS) is the most common malignant bone tumor with a poor prognosis. Here, we show that the nuclear receptor RORγ may serve as a potential therapeutic target in OS. OS exhibits a hyperactivated oxidative phosphorylation (OXPHOS) program, which fuels the carbon source to promote tumor progression. We found that RORγ is overexpressed in OS tumors and is linked to hyperactivated OXPHOS. RORγ induces the expression of PGC-1ß and physically interacts with it to activate the OXPHOS program by upregulating the expression of respiratory chain component genes. Inhibition of RORγ strongly inhibits OXPHOS activation, downregulates mitochondrial functions, and increases ROS production, which results in OS cell apoptosis and ferroptosis. RORγ inverse agonists strongly suppressed OS tumor growth and progression and sensitized OS tumors to chemotherapy. Taken together, our results indicate that RORγ is a critical regulator of the OXPHOS program in OS and provides an effective therapeutic strategy for this deadly disease.


Assuntos
Neoplasias Ósseas , Mitocôndrias , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Osteossarcoma , Fosforilação Oxidativa , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Osteossarcoma/genética , Humanos , Fosforilação Oxidativa/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Linhagem Celular Tumoral , Animais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/tratamento farmacológico , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Ferroptose/genética , Ferroptose/efeitos dos fármacos , Camundongos Nus , Masculino , Proliferação de Células , Proteínas de Ligação a RNA
4.
Int J Nurs Stud ; 155: 104769, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38676992

RESUMO

BACKGROUND: Nursing care of colorectal cancer patients with stomas presents unique challenges, particularly during the transition from hospital to home. Early discharge programs can assist patients during this critical period. However, the effects of delivering a nurse-led discharge planning program remain under-studied. OBJECTIVE: Evaluate the effects of a nurse-led discharge planning on the quality of discharge education, stoma self-efficacy, readiness for hospital discharge, stoma quality of life, incidence of stoma complications, unplanned readmission rate, and length of stays. DESIGN: Assessor-blind parallel-arm randomized controlled trial with a repeated-measures design. SETTING(S): Participants were recruited from inpatients in the colorectal surgery unit of a university-affiliated hospital in Fujian, China. PARTICIPANTS: A total of 160 patients with colorectal cancer who received enterostomy surgery and were scheduled to be discharged to their homes. METHOD: Participants were randomly allocated to the experimental and control groups. The former received nurse-led discharge planning in addition to the usual discharge education, while the control group received only the usual discharge education. The program included an assessment, health education, stoma care, stoma support, discharge review, discharge medication and checklist integration, discharge referral, and post-hospital follow-up. Baseline data were collected prior to the intervention (T0). Data on the quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, and stoma quality of life were measured on the day of discharge from the hospital (T1). Patients' stoma self-efficacy and quality of life were repeat-measured 30 (T2) and 90 days post-discharge (T3). Data on stoma complications (T1, T2, T3), length of stays (T1), and unplanned readmission (T2, T3) were collected from medical records. RESULTS: Participants in the intervention group showed significant improvement in the quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, stoma quality of life, complications, and unplanned readmission, compared to the control group (p < 0.001). However, no statistically significant differences were observed in length of stays (p > 0.05). CONCLUSIONS: The program was effective for improving quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, and stoma quality of life, as well as for reducing complications and unplanned readmission among stoma patients. Integration of discharge planning into the usual process of care is recommended for clinical practice to facilitate a successful transition from hospital to home. REGISTRATION: This study was registered at the Chinese clinical trial registry (ChiCTR2200058756) on April 16, 2022, and participant recruitment was initiated in May 2022.


Assuntos
Neoplasias Colorretais , Alta do Paciente , Humanos , Neoplasias Colorretais/enfermagem , Neoplasias Colorretais/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estomas Cirúrgicos , China , Qualidade de Vida
5.
Palliat Support Care ; : 1-8, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38362710

RESUMO

BACKGROUND: Advanced cancer patients often experience existential distress (ED). However, the factors associated with ED remain unclear. This study investigated the current state of ED and identified the associated factors in Chinese patients with advanced cancer. METHODS: A cross-sectional study was conducted among 352 advanced cancer patients from 3 tertiary hospitals in Fujian, China. Participants were invited to complete the Existential Distress Scale, Number Rating Scale, Self-Perceived Burden Scale, Quality of Life Concerns in the End-of-Life Questionnaire, and Hospital Anxiety and Depression Scale. OBJECTIVES: This study aimed to investigate the level of existential distress among advanced cancer patients in China and identify the associated factors. RESULTS: A total of 352 advanced cancer patients were recruited for this study. The average score for ED was 8.48 ± 7.12 among the advanced cancer patients. Multiple regression showed that the associated factors included depression (ß = 0.32, p = 0.000), self-perceived burden (SPB) (ß = 0.18, p = 0.001), the presence of a spouse (ß = -0.10, p = 0.050), and reception of government subsidies (ß = 0.17, p = 0.001). The factors accounted for 30.1% of the total variance in ED (F = 8.472, p < 0.001). SIGNIFICANCE OF RESULTS: Among the advanced cancer patients queried, ED was found to be positively influenced by depression, SPB, and reception of government subsidies and negatively influenced by the presence of a spouse. Depression was the most important risk factor, and thus future ED interventions should target depression.

6.
Mol Ther ; 32(3): 749-765, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38310356

RESUMO

Approximately 80%-90% of hepatocellular carcinomas (HCC) occur in a premalignant environment of fibrosis and abnormal extracellular matrix (ECM), highlighting an essential role of ECM in the tumorigenesis and progress of HCC. However, the determinants of ECM in HCC are poorly defined. Here, we show that nuclear receptor RORγ is highly expressed and amplified in HCC tumors. RORγ functions as an essential activator of the matrisome program via directly driving the expression of major ECM genes in HCC cells. Elevated RORγ increases fibronectin-1 deposition, cell-matrix adhesion, and collagen production, creating a favorable microenvironment to boost liver cancer metastasis. Moreover, RORγ antagonists effectively inhibit tumor growth and metastasis in multiple HCC xenografts and immune-intact models, and they effectively sensitize HCC tumors to sorafenib therapy in mice. Notably, elevated RORγ expression is associated with ECM remodeling and metastasis in patients with HCC. Taken together, we identify RORγ as a key player of ECM remodeling in HCC and as an attractive therapeutic target for advanced HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Sorafenibe , Colágeno/metabolismo , Microambiente Tumoral
7.
Cancer Lett ; 586: 216612, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38211653

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is featured by notorious EGFR tyrosine kinase inhibitor (TKI) resistance attributable to activation of parallel pathways. The numerous phase I/II trials have rarely shown encouraging clinical outcomes of EGFR-TKIs during treatment in HNSCC patients with advanced tumors. A unique IL-6/STAT3 signaling axis is reported to regulate multiple cancer-related pathways, but whether this signaling is correlated with reduced EGFR-TKI responsiveness is unclear. Here, we found that STAT3 signaling is compensatorily upregulated after EGFR-TKI exposure and confers anti-EGFR therapy resistance during HNSCC therapy. Targeting STAT3 using small molecule inhibitors promotes complete recovery or sustained elimination of HNSCC tumors through combination with EGFR-TKIs both in vitro and in diverse animal models. Mechanistically, phosphorylated STAT3 was proven to enhance oncogenic autophagic flux, protecting cancer cells and preventing EGFR-TKI-induced tumor apoptosis. Thus, blockade of STAT3 signaling simultaneously disrupts several key interactions during tumor progression and remodels the autophagic degradation system, thereby rendering advanced HNSCC eradicable through combination with EGFR-TKI therapy. These findings provide a clinically actionable strategy and suggest STAT3 as a predictive biomarker with therapeutic potential for EGFR-TKI resistant HNSCC patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Animais , Humanos , Autofagia , Proteína Beclina-1/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Interleucina-6/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo
8.
J Med Chem ; 67(2): 1481-1499, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38227771

RESUMO

Nuclear receptor receptor-related orphan receptor γ (RORγ) is a ligand-dependent transcription factor and has been established as a key player in castration-resistant prostate cancers (CRPC) by driving androgen receptor (AR) overexpression, representing a potential therapeutical target for advanced prostate cancers. Here, we report the identification of the first-in-class RORγ covalent inhibitor 29 via the structure-based drug design approach following structure-activity relationship (SAR) exploration. Mass spectrometry assay validated its covalent inhibition mechanism. Compound 29 significantly inhibited RORγ transcriptional activity and remarkably suppressed the expression levels of AR and AR-targeted genes. Compound 29 also exhibited much superior activity in inhibiting the proliferation and colony formation and inducing apoptosis of the CRPC cell lines relative to the positive control 2 and noncovalent control 33. Importantly, it markedly suppressed the tumor growth in a 22Rv1 mouse tumor xenograft model with good safety. These results clearly demonstrate that 29 is a highly potent and selective RORγ covalent inhibitor.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Camundongos , Animais , Neoplasias de Próstata Resistentes à Castração/metabolismo , Proliferação de Células , Receptores Androgênicos/metabolismo , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
9.
IEEE J Biomed Health Inform ; 28(3): 1424-1435, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38127598

RESUMO

Colonoscopy is considered the best prevention and control method for colorectal cancer, which suffers extremely high rates of mortality and morbidity. Automated polyp segmentation of colonoscopy images is of great importance since manual polyp segmentation requires a considerable time of experienced specialists. However, due to the high similarity between polyps and mucosa, accompanied by the complex morphological features of colonic polyps, the performance of automatic polyp segmentation is still unsatisfactory. Accordingly, we propose a network, namely Cross-level Guidance and Multi-scale Aggregation (CGMA-Net), to earn a performance promotion. Specifically, three modules, including Cross-level Feature Guidance (CFG), Multi-scale Aggregation Decoder (MAD), and Details Refinement (DR), are individually proposed and synergistically assembled. With CFG, we generate spatial attention maps from the higher-level features and then multiply them with the lower-level features, highlighting the region of interest and suppressing the background information. In MAD, we parallelly use multiple dilated convolutions of different sizes to capture long-range dependencies between features. For DR, an asynchronous convolution is used along with the attention mechanism to enhance both the local details and the global information. The proposed CGMA-Net is evaluated on two benchmark datasets, i.e., CVC-ClinicDB and Kvasir-SEG, whose results demonstrate that our method not only presents state-of-the-art performance but also holds relatively fewer parameters. Concretely, we achieve the Dice Similarity Coefficient (DSC) of 91.85% and 95.73% on Kvasir-SEG and CVC-ClinicDB, respectively. The assessment of model generalization is also conducted, resulting in DSC scores of 86.25% and 86.97% on the two datasets respectively.


Assuntos
Benchmarking , Colonoscopia , Humanos , Processamento de Imagem Assistida por Computador
10.
Support Care Cancer ; 31(10): 614, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37801183

RESUMO

PURPOSE: Cancer patients undergoing chemotherapy are prone to suffering a higher incidence rate of depression, leading to poor quality of life. However, how cancer affects depression is unclear. This study aimed to examine whether the relationship between cognitive appraisal and depression is mediated by perceived stress and self-efficacy in cancer patients undergoing chemotherapy. METHODS: A total of 421 cancer patients undergoing chemotherapy participated in this cross-sectional survey. Cognitive appraisal of cancer, perceived stress, self-efficacy, and depression were measured with the Perceived Life Threat Scale, Perceived Stress Scale, General Self-efficacy Scale and Hospital Anxiety, and Depression Scale-Depression Scale, respectively. Path analysis was performed to analyze the mediating effects of perceived stress and self-efficacy on the relationship between cognitive appraisal of cancer and depression. RESULTS: Cognitive appraisal of cancer exerted direct (b = 0.066, SE = 0.020, p < 0.001, bias-corrected 95% CI = [0.027, 0.106]) and indirect (mediated by depression and insomnia) (b = 0.136, SE = 0.015, p < 0.001, bias-corrected 95% CI = [0.107, 0.167]) effects on depression. Perceived stress and self-efficacy were significant in mediating the relationship between cognitive appraisal of cancer and depression (b = 0.101, SE = 0.014, p < 0.001, bias-corrected 95% CI = [0.074, 0.132]; b = 0.021, SE = 0.006, p < 0.001, bias-corrected 95% CI = [0.006, 0.028], respectively). Additionally, a sequential mediating effect of perceived stress via self-efficacy was found, and the mediating effect size was 0.014 (p < 0.01, bias-corrected 95% CI = [0.010,0.034]). CONCLUSIONS: This study suggests that medical staff could prevent or relieve depression through improving self-efficacy or reducing perceived stress in cancer patients undergoing chemotherapy.


Assuntos
Neoplasias , Autoeficácia , Humanos , Estudos Transversais , Qualidade de Vida/psicologia , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Neoplasias/tratamento farmacológico , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Cognição
11.
BMC Genomics ; 24(1): 598, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37814244

RESUMO

BACKGROUND: Conus, a highly diverse species of venomous predators, has attracted significant attention in neuroscience and new drug development due to their rich collection of neuroactive peptides called conotoxins. Recent advancements in transcriptome, proteome, and genome analyses have facilitated the identification of conotoxins within Conus' venom glands, providing insights into the genetic features and evolutionary patterns of conotoxin genes. However, the underlying mechanism behind the extraordinary hypervariability of conotoxins remains largely unknown. RESULTS: We analyzed the transcriptomes of 34 Conus species, examining various tissues such as the venom duct, venom bulb, and salivary gland, leading to the identification of conotoxin genes. Genetic variation analysis revealed that a subset of these genes (15.78% of the total) in Conus species underwent positive selection (Ka/Ks > 1, p < 0.01). Additionally, we reassembled and annotated the genome of C. betulinus, uncovering 221 conotoxin-encoding genes. These genes primarily consisted of three exons, with a significant portion showing high transcriptional activity in the venom ducts. Importantly, the flanking regions and adjacent introns of conotoxin genes exhibited a higher prevalence of transposon elements, suggesting their potential contribution to the extensive variability observed in conotoxins. Furthermore, we detected genome duplication in C. betulinus, which likely contributed to the expansion of conotoxin gene numbers. Interestingly, our study also provided evidence of introgression among Conus species, indicating that interspecies hybridization may have played a role in shaping the evolution of diverse conotoxin genes. CONCLUSIONS: This study highlights the impact of adaptive evolution and introgressive hybridization on the genetic diversity of conotoxin genes and the evolution of Conus. We also propose a hypothesis suggesting that transposable elements might significantly contribute to the remarkable diversity observed in conotoxins. These findings not only enhance our understanding of peptide genetic diversity but also present a novel approach for peptide bioengineering.


Assuntos
Conotoxinas , Caramujo Conus , Animais , Conotoxinas/genética , Caramujo Conus/genética , Peptídeos/genética , Genoma , Genômica
12.
Chem Biol Interact ; 382: 110618, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37394161

RESUMO

Gastric cancer (GC) is a highly aggressive and deadly disease worldwide. Given the limitations of current treatments, it is crucial to discover more effective antitumor drugs. Here, we demonstrated that arthpyrone M (Art-M), a novel 4-hydroxy-2-pyridone alkaloid derived from the marine fungus Arthrinium arundinis, inhibited the proliferation, invasion and migration of GC both in vivo and in vitro. The underlying mechanism of Art-M in GC cells was explored by RNA-sequencing analysis, qRT-PCR and immunoblotting, which demonstrated that Art-M significantly suppressed the mTORC1 pathway by decreasing phosphorylated mTOR and p70S6K. Moreover, Art-M feedback increased the activities of AKT and ERK. Co-immunoprecipitation and immunoblotting analysis revealed that Art-M induced dissociation of Raptor from mTOR and promoted Raptor degradation, leading to the inhibition of mTORC1 activity. Art-M was identified as a novel and potent mTORC1 antagonist. Furthermore, Art-M enhanced GC cell sensitivity to apatinib, and the combination of Art-M and apatinib showed better efficacy in the treatment of GC. Taken together, these results demonstrate that Art-M is a promising candidate drug for the treatment of GC by suppressing the mTORC1 pathway.


Assuntos
Alcaloides , Antineoplásicos , Neoplasias Gástricas , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Fungos , Proteínas Proto-Oncogênicas c-akt/metabolismo
13.
Front Oncol ; 13: 1151321, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37377917

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is the leading cause of cancer-related mortality, primarily due to the abundance of cancer-associated fibroblasts (CAFs), depleted effector T cells, and increased tumor cell stemness; hence, there is an urgent need for efficient biomarkers with prognostic and therapeutic potential. Here, we identified BHLHE40 as a promising target for PDAC through comprehensive analysis and weighted gene coexpression network analysis of RNA sequencing data and public databases, taking into account the unique characteristics of PDAC such as cancer-associated fibroblasts, infiltration of effector T cells, and tumor cell stemness. Additionally, we developed a prognostic risk model based on BHLHE40 and three other candidate genes (ITGA2, ITGA3, and ADAM9) to predict outcomes in PDAC patients. Furthermore, we found that the overexpression of BHLHE40 was significantly associated with T stage, lymph node metastasis, and American Joint Committee on Cancer (AJCC) stage in a cohort of 61 PDAC patients. Moreover, elevated expression levels of BHLHE40 were validated to promote epithelial-mesenchymal transition (EMT) and stemness-related proteins in BXPC3 cell lines. Compared to the parent cells, BXPC3 cells with BHLHE40 overexpression showed resistance to anti-tumor immunity when co-cultured with CD8+ T cells. In summary, these findings suggest that BHLHE40 is a highly effective biomarker for predicting prognosis in PDAC and holds great promise as a target for cancer therapy.

14.
Clin Res Hepatol Gastroenterol ; 47(7): 102154, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37311519

RESUMO

BACKGROUND AND AIM: Autoimmune gastritis (AIG) is a prominent risk factor for pernicious anemia (PA) and gastric neoplasia. This study aimed to investigate the clinicopathological characteristics of AIG patients in China, with a focus on those who had positive anti-intrinsic factor antibodies (AIFA). METHODS: A total of 103 AIG patients who were diagnosed between January 2018 and August 2022 were reviewed in a large academic tertiary teaching hospital. Patients were divided into two groups based on the presence or absence of AIFA, and their serologic and histopathological characteristics were analyzed. RESULTS: The mean age of the 103 AIG patients was 54.16±11.92 years (range 23-79), with 69 (66.99%) being women. AIFA were present in 28.16% of patients. Patients with AIFA-positive had a higher risk of PA than those with AIFA-negative, as demonstrated by a larger mean corpuscular volume (MCV), lower hemoglobin level, and lower vitamin B-12 level (P<0.05). There were no statistically significant differences in gastric histopathology, gastrin level, and pepsinogen level when patients were divided into AIFA-positive and AIFA-negative group. Of the 103 cases, 34 (33.01%) were concomitant with other autoimmune diseases, with autoimmune thyroid diseases being the most common (25.24%, 26/103). Thyroid peroxidase antibody, which accounted for 45.45% (25/55), was the most prevalent thyroid antibody, followed by anti-thyroglobulin antibody (34.55%, 19/55), thyroid stimulating antibody (12.73%, 7/55), and thyrotropin receptor antibody (3.64%, 2/55). CONCLUSION: This study highlights the increased risk of severe anemia in AIFA-positive AIG patients, particularly for PA. Clinicians should consider the presence of AIFA as a warning sign for PA and prioritize early diagnosis and appropriate treatment to prevent serious complications.


Assuntos
Anemia Perniciosa , Doenças Autoimunes , Gastrite , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Estudos Retrospectivos , Gastrite/diagnóstico , Autoanticorpos , Doenças Autoimunes/complicações , Anemia Perniciosa/complicações
15.
Clin Res Hepatol Gastroenterol ; 47(2): 102076, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36623769

RESUMO

BACKGROUND: Crohn's disease (CD) is characterized by non-caseating intestinal granulomas. However, the reported detection rate of granulomas on endoscopy is low. This study aimed to analyze the differences in the detection rate of granulomas in different intestinal segments and lesions in Chinese patients with CD to improve the detection rate of granulomas in clinical practice. PATIENTS AND METHODS: 113 patients with CD were analyzed retrospectively. Patients were divided into two groups: those with (n = 51) and without granulomas (n = 62) on endoscopic biopsies. Clinical information was collected from the medical records, including age; erythrocyte sedimentation rate (ESR); C-reactive protein (CRP), albumin, and hemoglobin (Hb) levels; platelet count; disease course; sex; smoking history; related operation history; Montreal classification; and lesion location, size, and shape. RESULTS: The detection rates of granulomas in different lesion shapes were significantly different (P < 0.001), with those of longitudinal ulcers and circular ulcers being higher than those of erosion and irregular ulcers. We also found that the detection rates of granulomas in ascending colon and sigmoid colon were relatively higher than other segments of the intestine, however, the difference was not statistically significant (P = 0.716). Additionally, age, sex, smoking history, Montreal classification, related surgical history, disease course, and serum biochemical indicators (ESR; platelet count; and CRP, albumin, and Hb levels) were not significantly different between the two groups. CONCLUSIONS: The detection rate of granulomas in patients with CD is related to the morphology of the intestinal lesions. Meanwhile, lesion location may be correlated with the detection rate of granulomas.


Assuntos
Doença de Crohn , Humanos , Úlcera , Estudos Retrospectivos , População do Leste Asiático , Granuloma/diagnóstico , Granuloma/etiologia , Granuloma/patologia , Intestinos/patologia , Endoscopia Gastrointestinal , Proteína C-Reativa/análise
16.
Biomed Mater Eng ; 34(4): 319-330, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36502299

RESUMO

BACKGROUND: Myocardial infarction is a serious clinical disease with high mortality and poor prognosis. Cardiomyocytes (CMs) have limited regeneration abilities after ischemic injury. Their growth and differentiation can be enhanced by contact co-culture with stem cells. OBJECTIVE: The aim was to study the contact co-culture of Dil-labeled bone marrow mesenchymal stem cells (BMSCs) and CMs for inducing differentiation of CMs from stem cells for treating myocardial infarction. METHODS: After contact co-culture, the differentiation of BMSCs into CMs was analyzed qualitatively by detecting myocardial markers (cardiac troponin T and α-smooth muscle actin) using immunofluorescence and quantitatively using flow cytometry. To examine the mechanism, possible gap junctions between BMSCs and CMs were analyzed by detecting gap junction protein connexin 43 (C×43) expression in BMSCs using immunofluorescence. The functionality of gap junctions was analyzed using dye transfer experiments. RESULTS: The results revealed that BMSCs in contact with CMs exhibited myocardial markers and a significant increase in differentiation rate (P < 0.05); they also proved the existence and function of gap junctions between BMSCs and CMs. CONCLUSIONS: It was shown that contact co-culture can induce Dil-labeled BMSCs to differentiate into CM-like cells and examined the principle of gap junction-mediated signaling pathways involved in inducing stem cells to differentiate into cardiomyocytes.


Assuntos
Células-Tronco Mesenquimais , Infarto do Miocárdio , Ratos , Animais , Miócitos Cardíacos , Técnicas de Cocultura , Animais Recém-Nascidos , Células da Medula Óssea/metabolismo , Diferenciação Celular/fisiologia , Células Cultivadas
17.
Eur J Surg Oncol ; 49(3): 560-567, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36404253

RESUMO

PURPOSE: There is approximately 10%-50% of papillary thyroid carcinoma (PTC) patients with Hashimoto's thyroiditis (HT). In this research, we sought to better understand the role of HT in PTC progression as well as lymph node metastasis. METHODS: It is a retrospective and cross-sectional study, and 4131 PTC patients who underwent thyroidectomy were finally enrolled. Chi-square test, univariate and multivariate logistic regression analyses were employed to evaluate both the risk factors and the critical roles of HT during PTC metastasis. RESULT: In this cohort, 1555 patients (37.6%) were diagnosed with HT. According to multivariate analysis, male sex, high levels of TG and TPOAb, tumor extrathyroidal extension, maximum diameter >1 cm, and multifocality were independent risk factors for both central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). In addition, age <55 years and smoking were risk factors for CLNM, while CLNM was one of the risk factors for LLNM. Furthermore, HT was suggested a valuable protective factor for both CLNM and LLNM. In patients with HT, the total number of central lymph nodes was higher, while the positive rate was lower. Compared with those without HT, age and sex did not predict CLNM and LLNM in patients with HT. CONCLUSION: HT is considered a protective factor for both CLNM and LLNM in PTC. For patients with HT, surgeons should pay more attention to the preservation of parathyroid gland and the protection of recurrent laryngeal nerve due to less lymph node metastasis. Otherwise, radical operation is highly recommended.


Assuntos
Carcinoma Papilar , Doença de Hashimoto , Neoplasias da Glândula Tireoide , Humanos , Masculino , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/patologia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Metástase Linfática/patologia , Estudos Transversais , Carcinoma Papilar/patologia , Doença de Hashimoto/patologia , Linfonodos/patologia , Fatores de Risco , Biomarcadores
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Front Public Health ; 10: 980208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324466

RESUMO

Objectives: To understand the current status of smoking behavior among emergency physicians in China and to explore its determinants. Background: The emergency department is considered a more appropriate setting for tobacco interventions. However, the smoking behavior of emergency physicians can reduce the effectiveness of interventions for patient smoking behavior. Methods: From July to August 2018, we conducted a structured online questionnaire among Chinese emergency medicine physicians. We used descriptive analysis with binary logistic regression to analyze the current smoking status of Chinese emergency physicians and its determinants. Results: A total of 10,457 emergency physicians were included in this study. The prevalence of smoking among physicians was 25.35% (with 34.15 and 1.59% among male and female physicians, respectively). Results of logistic regression showed that postgraduate education (OR = 0.52, 95% CI: 0.41-0.66), chief-level title (OR = 0.79, 95% CI: 0.65-0.97), and regular exercise habits (OR = 0.83, 95% CI: 0.76-0.92) were associated with a lower risk of smoking behavior. However, being over 50 years old (OR = 1.71, 95% CI: 1.29-2.27), being fixed-term (OR = 1.25, 95% CI: 1.10-1.42), and having depressive symptoms (OR = 1.43, 95% CI: 1.28-1.61) were associated with a higher risk of smoking. Conclusion: The prevalence of smoking behavior among emergency physicians in China is high. Hospital management could reduce the incidence of smoking behavior among emergency physicians by strengthening smoking cessation training, paying attention to physicians' psychological health, reducing pressure on physicians in fixed-term positions, and encouraging physicians to develop regular exercise habits.


Assuntos
Médicos , Fumar , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Prevalência , Fumar/epidemiologia , Serviço Hospitalar de Emergência
20.
Front Genet ; 13: 990301, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36276934

RESUMO

Background: Disorders of CD274 and PDCD1LG2 contribute to immune escape in human cancers, and treatment with anti-programmed death receptor 1 (PD-1) has been widely used in recurrent or metastatic tumors. However, integrated studies considering CD274 and PDCD1LG2 across cancers remain limited. Materials and Methods: Differences in expression levels of CD274 and PDCD1LG2 were analyzed in diverse cancer types using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The clinical information and matched expression profiles of TCGA patients were obtained to determine the prognostic value of CD274 and PDCD1LG2. Moreover, correlations between CD274 and PDCD1LG2 and the immune signature were analyzed by exploring the TIMER2 and TISIDB databases. We also investigated correlations between CD274 and PDCD1LG2 and immunotherapeutic biomarkers, including mismatch repair (MMR), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA methylation. Results: Expression levels of CD274 and PDCD1LG2 varied across multiple cancer types. CD274 and PDCD1LG2 not only impacted the prognosis of patients with cancer but were associated with clinical characteristics (lymph node metastasis, tumor stage, and sex) in kidney renal papillary cell carcinoma, thyroid carcinoma, and some other cancer types. Typically, CD274 and PDCD1LG2 could be strongly correlated with macrophages, dendritic cells, neutrophils, and CD8+ T-cells. Furthermore, CD274 and PDCD1LG2 expression were associated with various immunosuppressive biomarkers, such as CTLA4, TIGIT, and LAG3. In addition, CD274 and PDCD1LG2 were significantly associated with MMR, TMB, MSI, and DNA methylation. Finally, enrichment analysis confirmed that CD274 and PDCD1LG2 were associated with numerous biological pathways, such as: "Activation of Immune Reactions" and "Epithelial-Mesenchymal Transition," suggesting that CD274 and PDCD1LG2 play crucial roles in cancer immunity and tumor metastasis. Conclusion: CD274 and PDCD1LG2 play critical roles in cancer progression and immune response and could serve as effective biomarkers to predict the prognosis and immune signature of cancer.

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