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BACKGROUND: The prognosis nutritional index (PNI) and the systemic inflammatory immunological index (SII) are characteristic indicators of the nutritional state and the systemic inflammatory response, respectively. However, there is an unknown combined effect of these indicators in the clinic. Therefore, the practicality of using the SII-PNI score to predict prognosis and tumor response of locally advanced gastric cancer (LAGC) following chemotherapy was the main focus of this investigation. METHODS: We retrospectively analyzed 181 patients with LAGC who underwent curative resection after neoadjuvant chemotherapy in a prospective study (NCT01516944). We divided these patients into tumour regression grade(TRG) 3 and non-TRG3 groups based on tumor response (AJCC/CAP guidelines). The SII and PNI were assessed and confirmed the cut-off values before treatment. The SII-PNI values varied from 0 to 2, with 2 being the high SII (≥ 471.5) as well as low PNI (≤ 48.6), a high SII or low PNI is represented by a 1 and neither is represented by a 0, respectively. RESULTS: 51 and 130 samples had TRG3 and non-TRG3 tumor responses respectively. Patients with TRG3 had substantially higher SII-PNI scores than those without TRG3 (p < 0.0001). Patients with greater SII-PNI scores had a poorer prognosis (p < 0.0001). The SII-PNI score was found to be an independent predictor of both overall survival (HR = 4.982, 95%CI: 1.890-10.234, p = 0.001) and disease-free survival (HR = 4.763, 95%CI: 1.994-13.903, p = 0.001) in a multivariate analysis. CONCLUSION: The clinical potential and accuracy of low-cost stratification based on SII-PNI score in forecasting tumor response and prognosis in LAGC is satisfactory.
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Terapia Neoadjuvante , Avaliação Nutricional , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/imunologia , Masculino , Feminino , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inflamação , Estado Nutricional , Estudos Prospectivos , Quimioterapia Adjuvante/métodosRESUMO
Intrauterine adhesion (IUA) is a common complication of surgical manipulation of the uterine cavity such as abortion. The pathology of IUA is characterized by fibrosis, but the pathogenesis is not fully understood. The function of Apelin-13 in IUA and related mechanisms were investigated in this study. The IUA rat model was established. The pathological changes and fibrosis degree of rat uterine tissues were detected by HE and Masson staining after intraperitoneal injection of Apelin-13. Epithelial-mesenchymal transition (EMT) of endometrial epithelial cells and endothelial-mesenchymal transition (EnMT) of vein endothelial cells were induced by TGF-ß1. Tube-forming assay using HUVEC was implemented to detect the effect of Apelin-13 upon angiogenesis. IHC staining, immunofluorescence staining, and Western blot were conducted to detect the expression levels of EMT markers, angiogenesis, and key proteins of the TGF-ß1/Smad signaling. Apelin-13 significantly alleviated IUA and fibrosis, and increased endometrial thickness and gland number in IUA rats. In addition, Apelin-13 significantly reversed EMT and EnMT induced by IUA modeling and TGF-ß1, promoted the tube-forming ability of HUVEC, and up-regulated the expression of angiogenesis-related proteins. Mechanistically, Apelin-13 significantly suppressed smad2/3 phosphorylation and inhibited the TGF-ß1/Smad signaling via its receptor APJ. Apelin-13 might alleviate IUA via repressing the TGF-ß1/Smad pathway and is expected to be a potent therapeutic option for the clinical treatment of IUA.
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Coix lacryma-jobi L. is a traditional medicinal plant in east Asia and is an important crop in Guizhou province, southwest China, where there are elevated levels of soil mercury and arsenic (As). Exposure to multiple potentially toxic elements (PTEs) may affect plant accumulation of metal(loid)s and food safety in regions with high geological metal concentrations. Field experiments were conducted to study the effects of PTEs on metal(loid) accumulation and physiological response of C. lacryma in different plant parts at three pollution levels. Total root length, number of root tips, number of branches, and number of root crosses increased with increasing pollution level, with increases in highly polluted areas of 44.2, 57.0, 79.6, and 97.2%, respectively, compared to lightly polluted areas. Under multi-element stress the activity of C. lacryma antioxidant oxidase showed an increase at low and medium PTE concentrations and inhibition at high concentrations. The As contents were all below the maximum limit of cereal food contaminants in China (GB 2762-2022, As < 0.5 mg kg-1). The stems had high Tl bioconcentration factors but the translocation factors from stem to grain were very low, indicating that the stems may be a key plant part restricting Tl transport to the grains. C. lacryma increased root retention and reduced the transport effect, thus reducing metal accumulation in the grains. C. lacryma adapted to PTE stress through root remodeling and enhanced antioxidant enzyme activities.
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Mineração , Poluentes do Solo , Poluentes do Solo/toxicidade , Poluentes do Solo/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Solo/química , China , Arsênio/toxicidade , Arsênio/metabolismo , Mercúrio/toxicidade , Mercúrio/metabolismo , Mercúrio/análiseRESUMO
BACKGROUND: Gastric cancer (GC) stands as a prevalent and challenging malignancy within the gastrointestinal tract. The potential of long non-coding RNAs (lncRNAs) as biomarkers and therapeutic targets in oncology has garnered immense research interest. This study aims to elucidate the relevance, biological roles, and mechanistic pathways of LncRNA HAGLR in the context of GC. METHODS: The assessments of cell proliferation, migration, and invasion were executed using CCK-8, wound healing, and Transwell assays. The interactions between HAGLR, miR-20a-5p, and E2F1 were appraised through luciferase reporter assays, fluorescence in situ hybridization (FISH), and RNA immunoprecipitation (RIP). A tumor xenograft model provided in vivo validation for in vitro findings. RESULTS: Elevated levels of HAGLR in GC cells and tissue specimens were linked to worse patient outcomes. The inhibition of HAGLR led to a decrease in GC cell proliferation, migration, and invasion, whereas its activation prompted contrary effects. The impact of HAGLR on cell migration and invasion was notably associated with epithelial-mesenchymal transition (EMT). Through bioinformatics, luciferase reporter assays, FISH, RIP, and Western blot analyses, it was revealed that HAGLR acts as a molecular sponge for miR-20a-5p, consequently augmenting E2F1 levels. CONCLUSIONS: The data suggest that the HAGLR/miR-20a-5p/E2F1 regulatory cascade is implicated in GC pathogenesis, offering a novel therapeutic avenue for GC management.
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Traumatic brain injury (TBI), a significant global health issue, is affecting â¼69 million annually. To better understand TBI's impact on brain function and assess the efficacy of treatments, this study uses a novel temporal-spatial cross-group approach with a porcine model, integrating resting-state functional magnetic resonance imaging (rs-fMRI) for temporal and arterial spin labeling for spatial information. Our research used 18 four-week-old pigs divided into three groups: TBI treated with saline (SLN, n = 6), TBI treated with fecal microbial transplant (FMT, n = 6), and a sham group (sham, n = 6) with only craniectomy surgery as the baseline. By applying machine learning techniques-specifically, independent component analysis and sparse dictionary learning-across seven identified resting-state networks, we assessed the temporal and spatial correlations indicative of treatment efficacy. Both temporal and spatial analyses revealed a consistent increase of correlation between the FMT and sham groups in the executive control and salience networks. Our results are further evidenced by a simulation study designed to mimic the progression of TBI severity through the introduction of variable Gaussian noise to an independent rs-fMRI dataset. The results demonstrate a decreasing temporal correlation between the sham and TBI groups with increasing injury severity, consistent with the experimental results. This study underscores the effectiveness of the methodology in evaluating post-TBI treatments such as the FMT. By presenting comprehensive experimental and simulated data, our research contributes significantly to the field and opens new paths for future investigations into TBI treatment evaluations.
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Ovarian cancer (OC) was the fifth leading cause of cancer death and the deadliest gynecological cancer in women. This was largely attributed to its late diagnosis, high therapeutic resistance, and a dearth of effective treatments. Clinical and preclinical studies have revealed that tumor-infiltrating CD8+T cells often lost their effector function, the dysfunctional state of CD8+T cells was known as exhaustion. Our objective was to identify genes associated with exhausted CD8+T cells (CD8TEXGs) and their prognostic significance in OC. We downloaded the RNA-seq and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD8TEXGs were initially identified from single-cell RNA-seq (scRNA-seq) datasets, then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were utilized to calculate risk score and to develop the CD8TEXGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in the risk groups were used to figure out the closely correlated pathways with the risk group. The role of risk score has been further explored in the homologous recombination repair deficiency (HRD), BRAC1/2 gene mutations and tumor mutation burden (TMB). A risk signature with 4 CD8TEXGs in OC was finally built in the TCGA database and further validated in large GEO cohorts. The signature also demonstrated broad applicability across various types of cancer in the pan-cancer analysis. The high-risk score was significantly associated with a worse prognosis and the risk score was proven to be an independent prognostic biomarker. The 1-, 3-, and 5-years ROC values, nomogram, calibration, and comparison with the previously published models confirmed the excellent prediction power of this model. The low-risk group patients tended to exhibit a higher HRD score, BRCA1/2 gene mutation ratio and TMB. The low-risk group patients were more sensitive to Poly-ADP-ribose polymerase inhibitors (PARPi). Our findings of the prognostic value of CD8TEXGs in prognosis and drug response provided valuable insights into the molecular mechanisms and clinical management of OC.
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Linfócitos T CD8-Positivos , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Prognóstico , RNA-Seq/métodos , Biomarcadores Tumorais/genética , Análise de Célula Única/métodos , Regulação Neoplásica da Expressão Gênica , Análise da Expressão Gênica de Célula ÚnicaRESUMO
Hemorrhagic shock/resuscitation (HS/R) can lead to acute kidney injury, mainly manifested as oxidative stress and inflammatory injury in the renal tubular epithelial cells, as well as abnormal autophagy and apoptosis. Sulforaphane (SFN), an agonist of the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) signaling pathway, is involved in multiple biological activities, such as anti-inflammatory, antioxidant, autophagy, and apoptosis regulation. This study investigated the effect of SFN on acute kidney injury after HS/R in mice. Hemorrhagic shock was induced in mice by controlling the arterial blood pressure at a range of 35-45 mmHg for 90 min within arterial blood withdrawal. Fluid resuscitation was carried out by reintroducing withdrawn blood and 0.9% NaCl. We found that SFN suppressed the elevation of urea nitrogen and serum creatinine levels in the blood induced by HS/R. SFN mitigated pathological alterations including swollen renal tubules and renal casts in kidney tissue of HS/R mice. Inflammation levels and oxidative stress were significantly downregulated in mouse kidney tissue after SFN administration. In addition, the kidney tissue of HS/R mice showed high levels of autophagosomes as observed by electron microscopy. However, SFN can further enhance the formation of autophagosomes in the HS/R + SFN group. SFN also increased autophagy-related proteins Beclin1 expression and suppressed P62 expression, while increasing the ratio of microtubule-associated protein 1 light chain 3 (LC3)-II and LC3-I (LC3-II/LC3-I). SFN also effectively decreased cleaved caspase-3 level and enhanced the ratio of anti-apoptotic protein B cell lymphoma 2 and Bcl2-associated X protein (Bcl2/Bax). Collectively, SFN effectively inhibited inflammation and oxidative stress, enhanced autophagy, thereby reducing HS/R-induced kidney injury and apoptosis levels in mouse kidneys.
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BACKGROUND: Carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) have both been applied intraoperatively to facilitate lymphatic mapping and postoperatively to sort lymph nodes (LNs) in gastric cancer patients. However, no study has compared the two tracers in gastric cancer patients. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted from January 2022 to March 2023. Patients with potentially resectable gastric cancer (cT1-4a N0/+ M0) were randomized to the CNSI or ICG group. RESULTS: This study enrolled 96 patients. Ninety patients were in the modified intention-to-treat population, including 46 patients (32 males and 14 females; mean [SD] age, 57.4 [9.4] years) in the CNSI group and 44 patients (31 males and 13 females; mean [SD] age, 60.8 [8.8] years) in the ICG group. The mean (SD) number of retrieved LNs was 69.8 (21.9) and 53.6 (17.2) in the CNSI and ICG groups, respectively (P<0.001). The mean (SD) number of retrieved micro-LNs was 19.9 (13.3) and 11.6 (9.9) in the CNSI and ICG groups, respectively (P=0.001). The mean (SD) number of metastatic LNs was 8.1 (11.9) and 5.2 (9.2) in the CNSI and ICG groups, respectively (P=0.19). CONCLUSIONS: Compared with ICG, CNSI can increase the number of LNs detected, especially micro-LNs. Both tracers have high diagnostic value for detecting metastatic LNs. CNSI-guided lymphography may be a superior method for improving the accuracy of LN dissection.
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Circular RNAs (circRNAs) have emerged as key regulators of cancer occurrence and progression, as well as promising biomarkers for cancer diagnosis and prognosis. However, the potential mechanisms of circRNAs implicated in lymph node (LN) metastasis of gastric cancer remain unclear. Herein, we identify a novel N6-methyladenosine (m6A) modified circRNA, circPAK2, which is significantly upregulated in gastric cancer tissues and metastatic LN tissues. Functionally, circPAK2 enhances the migration, invasion, lymphangiogenesis, angiogenesis, epithelial-mesenchymal transition (EMT), and metastasis of gastric cancer in vitro and in vivo. Mechanistically, circPAK2 is exported by YTH domain-containing protein 1 (YTHDC1) from the nucleus to the cytoplasm in an m6A methylation-dependent manner. Moreover, increased cytoplasmic circPAK2 interacts with Insulin-Like Growth Factor 2 mRNA-Binding Proteins (IGF2BPs) and forms a circPAK2/IGF2BPs/VEGFA complex to stabilize VEGFA mRNA, which contributes to gastric cancer vasculature formation and aggressiveness. Clinically, high circPAK2 expression is positively associated with LN metastasis and poor prognosis in gastric cancer. This study highlights m6A-modified circPAK2 as a key regulator of LN metastasis of gastric cancer, thus supporting circPAK2 as a promising therapeutic target and prognostic biomarker for gastric cancer.
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Adenosina , Metástase Linfática , RNA Circular , Proteínas de Ligação a RNA , Transdução de Sinais , Neoplasias Gástricas , Fator A de Crescimento do Endotélio Vascular , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Metástase Linfática/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Transdução de Sinais/genética , Camundongos , Masculino , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Prognóstico , Feminino , Camundongos NusRESUMO
The identification of readers, an important class of proteins that recognize modified residues at specific sites, is essential to uncover the biological roles of post-translational modifications. Photoreactive crosslinkers are powerful tools for investigating readers. However, existing methods usually employ synthetically challenging photoreactive warheads, and their high-energy intermediates generated upon irradiation, such as nitrene and carbene, may cause substantial non-specific crosslinking. Here we report dimethylsulfonium as a methyllysine mimic that binds to specific readers and subsequently crosslinks to a conserved tryptophan inside the binding pocket through single-electron transfer under ultraviolet irradiation. The crosslinking relies on a protein-templated σ-π electron donor-acceptor interaction between sulfonium and indole, ensuring excellent site selectivity for tryptophan in the active site and orthogonality to other methyllysine readers. This method could escalate the discovery of methyllysine readers from complex cell samples. Furthermore, this photo crosslinking strategy could be extended to develop other types of microenvironment-dependent conjugations to site-specific tryptophan.
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Lisina , Compostos de Sulfônio , Triptofano , Triptofano/química , Triptofano/análogos & derivados , Compostos de Sulfônio/química , Lisina/química , Lisina/análogos & derivados , Transporte de Elétrons , Raios Ultravioleta , Reagentes de Ligações Cruzadas/química , Processos Fotoquímicos , Humanos , Proteínas/químicaRESUMO
BACKGROUND: Optimal adjuvant chemotherapy after laparoscopic surgery in gastric cancer (GC) patients is still undefined. We aimed to evaluate the efficacy of S-1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (CAPOX) in patients with GC after laparoscopic gastrectomy. METHODS: A non-inferiority randomized controlled clinical trial was performed in China. Patients with advanced GC who underwent laparoscopic D2 gastrectomy were randomly assigned to receive SOX and CAPOX regimens. RESULTS: In total, 191 patients were screened between May 2018 and June 2019, and 140 (73.3%) were included in the modified intent-to-treat analysis (mITT), of whom 69 and 71 were assigned to the SOX and CAPOX groups, respectively. The SOX group had similar 3-year overall survival (OS) and disease-free survival to the CAPOX group. Subgroup analysis revealed significantly better OS in the SOX group for male patients ([HR] = 0.395; 95% [CI], 0.153-1.019; p = 0.045), age >60 (HR = 0.219; 95% [CI], 0.064-0.753; p = 0.016), tumors in the gastric antrum (HR = 0.273; 95% [CI], 0.076-0.981; p = 0.047), and moderately differentiated tumors (HR = 0.338; 95% [CI], 0.110-1.041; p = 0.041). There were no significant differences observed in terms of adverse events and recurrence patterns between the two groups. CONCLUSION: Adjuvant SOX was non-inferior to CAPOX treatments for patients with GC who underwent curative laparoscopic D2 gastrectomy. For male patients, aged >60 years, tumors in the gastric antrum, and moderately differentiated tumors, adjuvant SOX may achieve an improvement compared with CAPOX.
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Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Combinação de Medicamentos , Gastrectomia , Laparoscopia , Oxaliplatina , Ácido Oxônico , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Masculino , Gastrectomia/métodos , Feminino , Pessoa de Meia-Idade , Laparoscopia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Tegafur/uso terapêutico , Tegafur/administração & dosagem , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Quimioterapia Adjuvante/métodos , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Idoso , AdultoRESUMO
Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare and aggressive subtype of gastric cancer associated with poor prognosis. This study aimed to investigate the recurrent metastatic patterns and prognostic factors in AFPGC patients undergoing radical surgical resection. Data from 241 AFPGC patients diagnosed between January 2017 and January 2020 who underwent surgical resection were analyzed across multiple centers. Recurrence patterns, metastatic sites, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify risk factors for recurrent metastasis, overall survival (OS), and disease-free survival (DFS). There is an annual increase in the proportion of AFPGC cases, rising from 3.45% in 2017 to 7.88% in 2023. Higher serum AFP level was associated with increased likelihood of lymph node metastasis (P=0.006), deeper invasion depth (P=0.000) and greater tumor diameter (P=0.036). Independent predictors of recurrent metastasis included T4 infiltration, lymph node metastasis, tumor diameter >5 cm, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP levels. The 5-year OS and DFS rates were 36.5% and 34.2%, respectively, with poorer survival linked to higher preoperative AFP levels and postoperative increasing trend in AFP level. Independent risk factors for poor OS and DFS included T4 infiltration, lymph node metastasis, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP. Serum AFP level can serve as a potential predictive and prognostic biomarker. Identifying independent risk factors informs risk stratification and personalized treatment for AFPGC patients.
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OBJECTIVE: To establish nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of gastric cancer liver metastasis (GCLM) patients. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database for 5,451 GCLM patients diagnosed between 2010 and 2015 were analyzed. The cohort was divided into a training set (3,815 cases) and an internal validation set (1,636 cases). External validation included 193 patients from the Fourth Hospital of Hebei Medical University and 171 patients from the People's Hospital of Shijiazhuang City, spanning 2016-2018. Multivariable Cox regression analysis identified eight independent prognostic factors for OS and CSS in GCLM patients, including age, histological type, grade, tumor size, surgery, chemotherapy, bone metastasis, and lung metastasis. Two nomogram models were developed based on these factors and evaluated using time-dependent receiver operating characteristic curve analysis, calibration curves, and decision curve analysis. RESULTS: Internal validation showed that the nomogram models outperformed the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system in predicting 1-year, 2-year, and 3-year OS and CSS in GCLM patients (1-year OS: 0.801 vs. 0.593, P < 0.001; 1-year CSS: 0.807 vs. 0.598, P < 0.001; 2-year OS: 0.803 vs. 0.630, P < 0.001; 2-year CSS: 0.802 vs. 0.633, P < 0.001; 3-year OS: 0.824 vs. 0.691, P < 0.001; 3-year CSS: 0.839 vs. 0.692, P < 0.001). CONCLUSION: This study developed and validated nomogram models using SEER database data to predict OS and CSS in GCLM patients. These models offer improved prognostic accuracy over traditional staging systems, aiding in clinical decision-making.
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Introduction: Lymph node (LN) status is a vital prognostic factor for patients. However, there has been limited focus on predicting the prognosis of patients with late-onset gastric cancer (LOGC). This study aimed to investigate the predictive potential of the log odds of positive lymph nodes (LODDS), lymph node ratio (LNR), and pN stage in assessing the prognosis of patients diagnosed with LOGC. Methods: The LOGC data were obtained from the Surveillance, Epidemiology, and End Results database. This study evaluated and compared the predictive performance of three LN staging systems. Univariate and multivariate Cox regression analyses were carried out to identify prognostic factors for overall survival (OS). Three machine learning methods, namely, LASSO, XGBoost, and RF analyses, were subsequently used to identify the optimal LN staging system. A nomogram was built to predict the prognosis of patients with LOGC. The efficacy of the model was demonstrated through receiver operating characteristic (ROC) curve analysis and decision curve analysis. Results: A total of 4,743 patients with >16 removed lymph nodes were ultimately included in this investigation. Three LN staging systems demonstrated significant performance in predicting survival outcomes (P < 0.001). The LNR exhibited the most important prognostic ability, as evidenced by the use of three machine learning methods. Utilizing independent factors derived from multivariate Cox regression analysis, a nomogram for OS was constructed. Discussion: The calibration, C-index, and AUC revealed their excellent predictive performance. The LNR demonstrated a more powerful performance than other LN staging methods in LOGC patients after surgery. Our novel nomogram exhibited superior clinical feasibility and may assist in patient clinical decision-making.
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BACKGROUND: This study aimed to develop a novel six-gene expression biomarker panel to enhance the early detection and risk stratification of peritoneal recurrence and micrometastasis in locally advanced gastric cancer (LAGC). METHODS: We used genome-wide transcriptome profiling and rigorous bioinformatics to identify a six-gene expression biomarker panel. This panel was validated across multiple clinical cohorts using both tissue and liquid biopsy samples to predict peritoneal recurrence and micrometastasis in patients with LAGC. RESULTS: Through genome-wide expression profiling, we identified six mRNAs and developed a risk prediction model using 196 samples from a surgical specimen training cohort. This model, incorporating a 6-mRNA panel with clinical features, demonstrated high predictive accuracy for peritoneal recurrence in gastric cancer patients, with an AUC of 0.966 (95% CI: 0.944-0.988). Transitioning from invasive surgical or endoscopic biopsy to noninvasive liquid biopsy, the model retained its predictive efficacy (AUC = 0.963; 95% CI: 0.926-1.000). Additionally, the 6-mRNA panel effectively differentiated patients with or without peritoneal metastasis in 95 peripheral blood specimens (AUC = 0.970; 95% CI: 0.936-1.000) and identified peritoneal micrometastases with a high efficiency (AUC = 0.941; 95% CI: 0.874-1.000). CONCLUSIONS: Our study provides a novel gene expression biomarker panel that significantly enhances early detection of peritoneal recurrence and micrometastasis in patients with LAGC. The RSA model's predictive capability offers a promising tool for tailored treatment strategies, underscoring the importance of integrating molecular biomarkers with clinical parameters in precision oncology.
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Biomarcadores Tumorais , Perfilação da Expressão Gênica , Micrometástase de Neoplasia , Recidiva Local de Neoplasia , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Biópsia Líquida/métodos , Feminino , Micrometástase de Neoplasia/genética , Masculino , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Pessoa de Meia-Idade , Transcriptoma , IdosoRESUMO
Exposure to ozone (O3) and nitrogen dioxide (NO2) are related to pulmonary dysfunctions and various lung diseases, but the underlying biochemical mechanisms remain uncertain. Herein, the effect of inhalable oxidizing gas pollutants on the pulmonary surfactant (PS, extracted from porcine lungs), a mixture of active lipids and proteins that plays an important role in maintaining normal respiratory mechanics, is investigated in terms of the interfacial chemistry using in-vitro experiments; and the oxidative stress induced by oxidizing gases in the simulated lung fluid (SLF) supplemented with the PS is explored. The results showed that O3 and NO2 individually increased the surface tension of the PS and reduced its foaming ability; this was accompanied by the surface pressure-area isotherms of the PS monolayers shifting toward lower molecular areas, with O3 exhibiting more severe effects than NO2. Moreover, both O3 and NO2 produced reactive oxygen species (ROS) resulting in lipid peroxidation and protein damage to the PS. The formation of superoxide radicals (O2â¢-) was correlated with the decomposition of O3 and the reactions of O3 and NO2 with antioxidants in the SLF. These radicals, in the presence of antioxidants, led to the formation of hydrogen peroxide and hydroxyl radicals (â¢OH). Additionally, the direct oxidation of unsaturated lipids by O3 and NO2 further caused an increase in the ROS content. This change in the ROS chemistry and increased â¢OH production tentatively explain how inhalable oxidizing gases lead to oxidative stress and adverse health effects. In summary, our results indicated that inhaled O3 and NO2 exposure can significantly alter the interfacial properties of the PS, oxidize its active ingredients, and induce ROS formation in the SLF. The results of this study provide a basis for the elucidation of the potential hazards of inhaled oxidizing gas pollutants in the human respiratory system.
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Pulmão , Dióxido de Nitrogênio , Estresse Oxidativo , Ozônio , Surfactantes Pulmonares , Espécies Reativas de Oxigênio , Estresse Oxidativo/efeitos dos fármacos , Animais , Surfactantes Pulmonares/química , Suínos , Dióxido de Nitrogênio/química , Ozônio/química , Ozônio/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Antioxidantes/química , OxirreduçãoRESUMO
Background: Sepsis is a complex syndrome characterized by physiological, pathological, and biochemical abnormalities caused by infection. Its development is influenced by factors such as inflammation, nutrition, and immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and investigated its association with clinical prognosis of critically ill patients with sepsis. Methods: This retrospective observational study enrolled critically ill patients with sepsis who had an initial CRP, albumin, and lymphocyte data on the first day of ICU admission. All data were obtained from the Affiliated Hospital of Jiangsu University. The patients were divided into quartiles (Q1-Q4) based on their CALLY index. The outcomes included 30-/60-day mortality and acute kidney injury (AKI) occurrence. The association between the CALLY index and these clinical outcomes in critically ill patients with sepsis was evaluated using Cox proportional hazards and logistic regression analysis. Results: A total of 1,123 patients (63.0% male) were included in the study. The 30-day and 60-day mortality rates were found to be 28.1 and 33.4%, respectively, while the incidence of AKI was 45.6%. Kaplan-Meier analysis revealed a significant association between higher CALLY index and lower risk of 30-day and 60-day mortality (log-rank p < 0.001). Multivariate Cox proportional hazards analysis indicated that the CALLY index was independently associated with 30-day mortality [HR (95%CI): 0.965 (0.935-0.997); p = 0.030] and 60-day mortality [HR (95%CI): 0.969 (0.941-0.997); p = 0.032]. Additionally, the multivariate logistic regression model showed that the CALLY index served as an independent risk predictor for AKI occurrence [OR (95%CI): 0.982 (0.962-0.998); p = 0.033]. Conclusion: The findings of this study indicated a significant association between the CALLY index and both 30-day and 60-day mortality, as well as the occurrence of AKI, in critically ill patients with sepsis. These findings suggested that the CALLY index may be a valuable tool in identifying sepsis patients who were at high risk for unfavorable outcomes.
Assuntos
Proteína C-Reativa , Estado Terminal , Unidades de Terapia Intensiva , Linfócitos , Sepse , Humanos , Masculino , Feminino , Sepse/mortalidade , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Valor Preditivo dos Testes , Biomarcadores/sangue , Albumina Sérica/análise , Albumina Sérica/metabolismo , China/epidemiologiaRESUMO
BACKGROUND: The incidence of gastric cancer has significantly increased in recent years. Surgical resection is the main treatment, but the method of digestive tract reconstruction after gastric cancer surgery remains controversial. In the current study, we sought to explore a reasonable method of digestive tract reconstruction and improve the quality of life and nutritional status of patients after surgery. To this end, we statistically analyzed the clinical results of patients with gastric cancer who underwent jejunal interposition double-tract reconstruction (DTR) and esophageal jejunum Roux-en-Y reconstruction (RY). AIM: To explore the application effect of DTR in total laparoscopic radical total gastrectomy (TLTG) and evaluate its safety and efficacy. METHODS: We collected the relevant data of 77 patients who underwent TLTG at the Fourth Hospital of Hebei Medical University from October 2021 to January 2023. Among them, 35 cases were treated with DTR, and the remaining 42 cases were treated with traditional RY. After 1:1 propensity score matching, the cases were grouped into 31 cases per group, with evenly distributed data. The clinical characteristics and short- and long-term clinical outcomes of the two groups were statistically analyzed. RESULTS: The two groups showed no significant differences in basic data, intraoperative blood loss, number of lymph node dissections, first defecation time after operation, postoperative hospital stay, postoperative complications, and laboratory examination results on the 1st, 3rd, and 5th days after operation. The operation time of the DTR group was longer than that of the RY group [(307.58 ± 65.14) min vs (272.45 ± 62.09) min, P = 0.016], but the first intake of liquid food in the DTR group was shorter than that in the RY group [(4.45 ± 1.18) d vs (6.0 ± 5.18) d, P = 0.028]. The incidence of reflux heartburn (Visick grade) and postoperative gallbladder disease in the DTR group was lower than that in the RY group (P = 0.033 and P = 0.038). Although there was no significant difference in body weight, hemoglobin, prealbumin, and albumin between the two groups at 1,3 and 6 months after surgery, the diet of patients in the DTR group was better than that in the RY group (P = 0.031). CONCLUSION: The clinical effect of DTR in TLTG is better than that of RY, indicating that it is a more valuable digestive tract reconstruction method in laparoscopic gastric cancer surgery.
RESUMO
BACKGROUND: Surgical staplers have been widely used to facilitate surgeries, and this study aimed to examine the real-world effectiveness of a new powered stapling system with Gripping Surface Technology (GST) on intraoperative outcomes of gastrectomy for gastric cancer. METHOD: The data were extracted from the Fourth Hospital of Hebei Medical University's (FHHMU) medical records system. Participants (N = 121 patients) were classified into the GST (n = 59) or non-GST group (n = 62), based on the use of the GST system. The intraoperative outcomes such as bleeding were assessed by reviewing video records. T-tests, Chi-square tests, and Mann-Whitney-U tests were used to compare the baseline characteristics between groups. Multivariate logistic regression was conducted for adjusting outcomes to study the effect of variables. RESULTS: Compared with the non-GST group, the GST group had significantly lower risks for intraoperative bleeding, intraoperative anastomosis intervention rate, intraoperative suture, and intraoperative pression (aORs: 0.0853 (p < 0.0001), 0.076 (p = 0.0003), 0.167 (p = 0.0012), and 0.221 (p = 0.0107), respectively). The GST group also consumed one fewer cartridge than the non-GST group (GST:5 vs non-GST: 6, p = 0.0241). CONCLUSION: The use of the GST system was associated with better intraoperative outcomes and lower cartridge consumption in Chinese real-world settings.
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To develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of early-onset gastric cancer (EOGC) patients. A total of 1077 EOGC patients from the Surveillance, Epidemiology, and End Results (SEER) database were included, and an additional 512 EOGC patients were recruited from the Fourth Hospital of Hebei Medical University, serving as an external test set. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Based on these factors, two nomogram models were established, and web-based calculators were developed. These models were validated using receiver operating characteristics (ROC) curve analysis, calibration curves, and decision curve analysis (DCA). Multivariate analysis identified gender, histological type, stage, N stage, tumor size, surgery, primary site, and lung metastasis as independent prognostic factors for OS and CSS in EOGC patients. Calibration curves and DCA curves demonstrated that the two constructed nomogram models exhibited good performance. These nomogram models demonstrated superior performance compared to the 7th edition of the AJCC tumor-node-metastasis (TNM) classification (internal validation set: 1-year OS: 0.831 vs 0.793, P = 0.072; 1-year CSS: 0.842 vs 0.816, P = 0.190; 3-year OS: 0.892 vs 0.857, P = 0.039; 3-year CSS: 0.887 vs 0.848, P = 0.018; 5-year OS: 0.906 vs 0.880, P = 0.133; 5-year CSS: 0.900 vs 0.876, P = 0.109). In conclusion, this study developed two nomogram models: one for predicting OS and the other for CSS of EOGC patients, offering valuable assistance to clinicians.