Clinical and Experimental Medicine最新文献

Shift work, particularly night shifts, disrupts circadian rhythms and increases stroke risk. This manuscript explores the mechanisms connecting shift work with stroke, focusing on circadian rhythms, hypertension, and diabetes. The circadian system, controlled by different mechanisms including central and peripheral clock genes, suprachiasmatic nuclei (SCN), and pineal gland (through melatonin production), regulates body functions and responds to environmental signals. Disruptions in this system affect endothelial cells, leading to blood pressure issues. Type 2 diabetes mellitus (T2DM) is significantly associated with night shifts, with circadian disturbances affecting glucose metabolism, insulin sensitivity, and hormone regulation. The manuscript examines the relationship between melatonin, insulin, and glucose balance, highlighting pathways that link T2DM to stroke risk. Additionally, dyslipidemia, particularly reduced HDL-c levels, results from shift work and contributes to stroke development. High lipid levels cause oxidative stress, inflammation, and endothelial dysfunction, increasing cerebrovascular risks. The manuscript details the effects of dyslipidemia on brain functions, including disruptions in blood flow, blood-brain barrier integrity, and neural cell death. This comprehensive analysis emphasizes the complex interplay of circadian disruption, hypertension, diabetes, and dyslipidemia in increasing stroke risk among shift workers. Understanding these mechanisms is essential for developing targeted interventions to reduce stroke susceptibility and improve cerebrovascular health in this vulnerable population.

Pseudomonas aeruginosa bloodstream infections (PA BSIs) in adults, especially those complicated by sepsis, are associated with high rates of morbidity and mortality. Early identification of risk factors for both mortality and sepsis-induced coagulopathy (SIC) is critical to optimizing patient management and improving outcomes. We conducted a retrospective analysis of 118 adult patients diagnosed with PA BSIs at the Affiliated Hospital of Xuzhou Medical University from January 2022 to February 2024. Univariate analysis was employed to identify significant clinical factors, followed by multivariate stepwise logistic regression to determine independent predictors of mortality and SIC. Based on these findings, nomogram models were constructed and evaluated using the area under the receiver operating characteristic curve (AUC), Bootstrap resampling, and calibration plots to assess model performance. Empiric sensitive antibiotic therapy (ESAT) (OR = 0.039, P < 0.001), coronary artery disease (CAD) (OR = 10.315, P = 0.010), and invasive mechanical ventilation (OR = 3.926, P = 0.020) emerged as significant predictors of mortality. In contrast, elevated C-reactive protein (CRP) (OR = 1.011, P = 0.003), procalcitonin (PCT) (OR = 1.030, P = 0.005), and lower hemoglobin levels (OR = 0.963, P = 0.004) were independently associated with SIC. The AUC of mortality prediction model is 0.908, while the SIC prediction model yielded an AUC of 0.817. The predictive models developed in this study demonstrate early identification of mortality rates and SIC risk in PA BSI patients, which may have the potential to guide timely therapeutic interventions and improve clinical outcomes in this high-risk population.

Existing challenges in accurately diagnosing various rheumatic diseases (RDs) have stimulated the search for novel biomarkers to aid clinical evaluation and monitoring. We conducted a systematic review and meta-analysis of studies investigating the candidate biomarker endoglin (CD105), a transmembrane glycoprotein expressed in endothelial, myeloid, and lymphoid cells, in RD patients and healthy controls. We searched PubMed, Scopus, and Web of Science from inception to 10 August 2024 to identify relevant studies. We evaluated the risk of bias using the JBI Critical Appraisal Checklist and the certainty of evidence using GRADE (PROSPERO registration number: CRD42023581008). Overall, circulating endoglin concentrations were significantly higher in RD patients compared to controls (13 studies; standard mean difference, SMD = 0.64, 95% CI 0.13 to 1.14, p = 0.014; low certainty of evidence). The effect size of the between-group differences in endoglin concentrations was not significantly associated with age, male-to-female ratio, year of publication, number of participants, or mean RD duration. By contrast, the effect size was statistically significant in studies conducted in the European region (p = 0.033), involving patients with systemic sclerosis (p = 0.032), and measuring serum (p = 0.019). The results of this systematic review and meta-analysis suggest the potential pathophysiological role of endoglin in RDs. This, however, requires further investigation in prospective studies, particularly in patients with systemic sclerosis.

This study aims to analyze the differential expression of METTL14 in pancreatic cancer (PC) tissues and adjacent normal tissues, and its correlation with clinical outcomes. According to the inclusion and exclusion criteria, a total of 80 patients diagnosed in our hospital from January 2021 to January 2023 were chosen as research subjects. RTQ-PCR has detected the mRNA level expression of METTL14 in cancer and para-cancerous tissues. Immunohistochemistry was used to detect the protein expression of METTL14 in cancer and para-cancerous tissues. To compare the relationship between METTL14 expression and clinicopathological parameters in different PC patients. Kaplan-Meier survival analysis of the relationship between METTL14 expression in PC tissues and patient survival prognosis. The Multifactor COX model evaluates factors affecting the prognosis of PC. The expression level of METTL14 mRNA in PC tissues was 5.51 ± 0.35 (kDa), and the positive rate of METTL14 protein expression in PC tissues of all patients was 73.75 (59/80). Tumor location (P = 0.012), tumor differentiation degree (P = 0.028), tumor AJCC stage (P = 0.000), and lymph node metastasis (P = 0.000) were significantly related to the positive rate of METTL14 protein expression in PC tissue. Follow-up results showed that among 80 patients, 63 died. The three-year survival rate of the METTL14 positive group was 13.56% (8/59), and the three-year survival rate of the negative group was 42.86% (9/21). The difference in the three-year survival rate between METTL14 positive and negative expression groups was statistically significant (P = 0.031). Multivariate COX regression analysis results showed that METTL14 was positive (OR 2.797, 95% CI 1.233-5.877), tumor AJCC stage II-III (OR 1.628, 95% CI 1.435-3.859) and lymph node metastasis (OR 1.733, 95% CI 1.122-2.372) were substantive risk factors for poor prognosis in patients with PC. METTL14 expression increases in PC tissue, which is related to tumor AJCC stage, tumor differentiation, and lymph node metastasis, and can be evaluated in the survival prognosis of patients with PC.

Understanding the metastatic cascade is critical for the treatment and prevention of cancer-related death. Within a tumor, immune cells have the capacity to fuse with tumor cells to generate tumor-immune hybrid cells (THCs). THCs are hypothesized to be a subset of cancer cells with the capacity to enter circulation as circulating hybrid cells (CHC) and seed metastases. To understand the mechanism of THC metastasis, we investigated CHCs in peripheral blood from patients with stage IV colorectal cancer (CRC), as well as THCs in tissues of primary colorectal cancers and their liver metastasis sites using immunofluorescence, spatial proteomic, spatial transcriptomic, molecular classification, and molecular pathway analyses. Our findings indicated a high prevalence of CHCs and THCs in patients with stage IV CRC. THCs expressed CTLA4 in primary CRC lesions and correlated with upregulation of CD68, CD4, and HLA-DR in metastatic liver lesions, which is found in the consensus molecular subtype (CMS) 1 of primary CRC tissue. Pathway analysis of these genes suggested that THCs are associated with neutrophils due to upregulation of neutrophil extracellular trap signaling (NET) and neutrophil degranulation pathways. These data provide molecular pathways for the formation of THCs suggesting fusion with neutrophils, which may facilitate extravasation and metastatic seeding.

This study was to develop and validate a model for predicting who can benefit from multiple transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients.228 and 98 patients were included in the development and validation sets, respectively. The primary clinical endpoint was benefiting from consecutive multiple TACE treatments. Logistic regression analysis was used to screen the independent risk factors for the clinical endpoint. The independent risk factors were then used to construct the predictive model. The area under receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves were used to evaluate the predictive ability of the model.Multivariate Logistic regression analysis showed that complete envelope, hepatic lopes, tumor number, and alpha-fetoprotein (AFP) were independent risk factors for benefiting from multiple TACE in HCC patients. The area under the curve (AUC) of the model constructed by using independent risk factors in the development and validation sets was 0.843 (95% confidence interval [CI]: 0.784-0.902) and 0.828 (95%CI: 0.739-0.916), respectively. The calibration curves and clinical decision curves showed that the model had good predictive ability.The model established in this study has a good predictive effect on HCC patients who can benefit from multiple TACE.

Colorectal cancer is a leading cause of global mortality and presents a significant barrier to improving life expectancy. The primary objective of this study was to discern a unique differentially expressed gene (DEG) that exhibits a strong association with colorectal cancer. By achieving this goal, the research aims to contribute valuable insights to the field of translational medicine. We performed analysis of colorectal cancer microarray and the TCGA colon adenoma carcinoma (COAD) datasets to identify DEGs associated with COAD and common DEGs were selected. Furthermore, a pan-cancer analysis encompassing 33 different cancer types was performed to identify differential genes significantly expressed only in COAD. Then, comprehensively in-silico analysis including gene set enrichment analysis, constructing Protein-Protein interaction, co-expression, and competing endogenous RNA (ceRNA) networks, investigating the correlation between tumor-immune signatures in distinct tumor microenvironment and also the potential interactions between the identified gene and various drugs was executed. Further, the candidate gene was experimentally validated in tumoral colorectal tissues and colorectal adenomatous polyps by qRael-Time PCR. GUCA2A emerged as a significant DEG specific to colorectal cancer (|log2FC|> 1 and adjusted q-value < 0.05). Importantly, GUCA2A exhibited excellent diagnostic performance for COAD, with a 99.6% and 78% area under the curve (AUC) based on TCGA-COAD and colon cancer patients. In addition, GUCA2A expression in adenomatous polyps equal to or larger than 5 mm was significantly lower compared to smaller than 5 mm. Moreover, low expression of GUCA2A significantly impacted overall patient survival. Significant correlations were observed between tumor-immune signatures and GUCA2A expression. The ceRNA constructed included GUCA2A, 8 shared miRNAs, and 61 circRNAs. This study identifies GUCA2A as a promising prognostic and diagnostic biomarker for colorectal cancer. Further investigations are warranted to explore the potential of GUCA2A as a therapeutic biomarker.

Minimal residual disease (MRD) is of growing interest in light chain (AL) amyloidosis and is associated with higher rates of cardiac response. A new graded cardiac response criteria has been proposed for better assessment of cardiac improvement. We evaluated MRD status in 63 patients with cardiac AL amyloidosis using next generation flow cytometry (sensitivity ≥ 1*10^-5) within four cycles after treatment initiation and cardiac response kinetics. All patients were treated with first-line proteasome inhibitor (100%) and predominantly bortezomib (87.3%). The overall early MRD negative rates were 33.3%. Patients who achieved early MRD negativity were less likely to harbor t(11;14) (21.1% vs 57.5%, P = 0.009). The MRD negative rates amongst patients in hematologic complete response were 66.7% (14/21), and in very good partial response 29.2% (7/24). Early MRD negativity was associated with a higher likelihood of achieving ≥ cardiac partial response (≥ CarPR) (66.7% vs 38.1%, P = 0.032) and ≥ cardiac very good partial response (≥ CarVGPR) (38.1% vs 11.9%, P = 0.023) throughout first-line therapy. The cumulative incidence curve of achieving ≥ CarPR (P = 0.034) and ≥ CarVGPR (P = 0.026) showed significant difference between early MRD negative and positive group. After a median follow-up time of 27.2 months, the median progression free survival was longer in early MRD negative group (not reached vs 31.3 months, P = 0.033). Early MRD eradication in cardiac AL amyloidosis generated deeper and faster cardiac organ response.

Colorectal cancer (CRC) ranks among the most prevalent malignant tumors worldwide, with a multifactorial etiology encompassing genetic, environmental, and life-style factors, as well as the intestinal microbiota and its metabolome. These risk factors often work together in specific groups of patients, influencing how CRC develops and progresses. Importantly, alterations in the gut microbiota act as a critical nexus in this interplay, significantly affecting susceptibility to CRC. This review highlights recent insights into unmodifiable and modifiable risk factors for CRC and how they might interact with the gut microbiota and its metabolome. Understanding the mechanisms of these interactions will help us develop targeted, precision-medicine strategies that can adjust the composition of the gut microbiota to meet individual health needs, preventing or treating CRC more effectively.