Open Medicine最新文献

Objective: Endotoxin tolerance (ET) has been demonstrated to attenuate the inflammatory response in murine models of sepsis. This study seeks to elucidate the underlying mechanisms by which ET modulates inflammation in sepsis, with a particular focus on macrophage autophagy.

Methods: An in vivo sepsis model was generated using cecal ligation and perforation, while an in vitro model of inflammatory injury was induced via lipopolysaccharide (LPS) administration. ET was established through pretreatment with low-dose LPS. Subsequent analyses were conducted to assess the presence of the NLRP3 inflammasome, autophagic flux, and the expression levels of TRIM26.

Results: Heightened inflammation was observed in the TNF-α levels and various organs of the sepsis group; conversely, inflammation was reduced in the group receiving ET treatment. Upon stimulation with LPS, primary mouse peritoneal macrophages exhibited activation of the NLRP3 inflammasome and autophagy, accumulation of mitochondrial reactive oxygen species, compromised membrane potential, resulting in cell apoptosis, and decreased expression of TRIM26. ET was found to enhance autophagy, suppress the activation of NLRP3 inflammasomes, and upregulate the expression of TRIM26. Interestingly, modulation of autophagy levels either reversed or intensified the protective effects of ET on macrophages in vitro. Knockdown of TRIM26 using small interfering RNA (siRNA) resulted in increased NLRP3 inflammasome activation and accumulation of P62.

Conclusion: We reveal that ET restores the autophagic flux in macrophages, inhibit NLRP3 inflammasome activation, and mitigate inflammatory damage in septic mice, potentially through the regulation of TRIM26.

Background: For pediatric patients, there is still controversy regarding the anastomotic technique used for gastrointestinal construction. The study was to evaluate the continuous single-layer (CSL) intestinal anastomosis method compared with the two-layered interrupted anastomosis.

Methods: We retrospectively reviewed the medical records of the eligible patients following CSL anastomosis (n = 252) and interrupted double-layer (IDL) anastomosis (n = 196). The influences of CSL or IDL anastomosis on perioperative outcomes, including postoperative complications, anastomotic leakage, hospitalization cost, and postoperative hospital stay, were evaluated.

Results: No significant differences were found between the CSL and IDL groups in terms of anastomotic leakage or postoperative complications. CSL anastomosis was related to favorable clinical outcomes, including anastomotic time (11.6 ± 3.8 vs 24.3 ± 5.9 min, p < 0.001) and operative time (111.6 ± 48.6 vs 124.1 ± 54.2 min, p = 0.041). There was a decrease in inflammation variable (e.g., C-reactive protein) on postoperative day 5 (10.6 ± 5.8 vs 12.8 ± 6.6 mg/L, p = 0.032) in patients with CSL anastomoses compared to the IDL group.

Conclusions: The beneficial effects of CSL anastomosis in pediatric patients were demonstrated with respect to anastomotic time, length of postoperative recovery, and cost incurred.

Background: Intraperitoneal (IP) chemotherapy (IPC), including hyperthermic intraperitoneal chemotherapy (HIPEC), has emerged as a promising approach to control peritoneal metastases in gastrointestinal (GI) cancers. However, the safety profile and toxicity spectrum of IPC remain incompletely understood. This study aimed to evaluate the incidence of hematologic and biochemical adverse reactions following surgery with or without IPC and to compare the toxicity profiles of normothermic IPC and HIPEC. Additionally, potential risk factors for liver injury were investigated to guide clinical management.

Methods: In this retrospective cohort study, 449 patients with gastric or colorectal cancer undergoing surgical resection between January 2015 and September 2019 were analyzed. Patients were categorized into three groups: surgery alone (n = 171), surgery + normothermic IPC (IPC group, n = 82), and surgery + HIPEC (HIPEC group, n = 196). Baseline demographic and clinicopathological data, IPC details (including drug regimen, HIPEC technique [open vs closed], and perfusion duration), and postoperative laboratory toxicities were recorded. Hematologic toxicities (leucopenia, neutropenia, thrombocytopenia, and hemoglobin decline) and biochemical toxicities (liver and renal function abnormalities and D-dimer elevation) were graded according to CTCAE v5.0. Group comparisons were performed using χ ² or ANOVA tests. Due to a higher proportion of advanced-stage patients in the HIPEC group, stratified analyses were performed by clinical stage (I-II vs III-IV). Logistic regression was used to identify independent risk factors for liver injury in both IPC and HIPEC groups.

Results: Baseline characteristics were comparable across groups except for clinical stage, with the HIPEC group having a higher percentage of advanced-stage patients (79.6 vs 59.8%, P <0.05). Compared with the surgery-alone group, both IPC and HIPEC groups had significantly higher incidences of hemoglobin decline (25.7% vs 39.0% vs 49.0%, respectively; P <0.01), liver injury (37.4% vs 62.2% vs 60.7%, P <0.01), and D-dimer elevation (47.4% vs 68.3% vs 72.9%, P <0.01). In contrast, the incidences of leucopenia, neutropenia, and renal impairment were low (<12%) and did not differ significantly among groups. Thrombocytopenia was significantly more frequent in the HIPEC group than in the surgery-alone group (7.7 vs 2.9%, P = 0.046). Stratified analyses revealed no significant differences in adverse reaction rates between the IPC and HIPEC groups when adjusted by clinical stage. Multivariate logistic regression indicated that, in the IPC group, severe postoperative GI reactions ( ≥Grade II; OR, 3.72; 95% CI, 1.20-11.55; P = 0.023) and the use of a platinum plus docetaxel regimen (OR, 8.75; 95% CI, 1.78-43.12; P = 0.008) were independent predictors of l

Introduction: Advance care planning is a critical process that brings patients, their families, and healthcare providers together to set goals and outline preferences for future medical treatments, especially when chronic or terminal illnesses are involved. Recently, artificial intelligence has begun playing a key role in shared decision making, offering personalized recommendations based on detailed data analysis to help refine treatment decisions.

Objective: This review explores Artificial Intelligence's role in shared decision making, noting its potential to enhance treatment precision, reduce the workload for healthcare providers, and empower patients to engage more actively in their cares.

Methods: The systematic review was conducted using the The Preferred Reporting Items for a Systematic Review and Meta-Analysis Statement 2020 guidelines to ensure a comprehensive and transparent approach. We utilized the online tool Rayyan for screening and selection of relevant studies.

Results: The review highlights the importance of transparency and clinician involvement to ensure that artificial intelligence remains a supportive, rather than dominant, element in patient care. Emphasizing the human aspect of decision-making is essential, as is fostering a collaborative approach between artificial intelligence and healthcare professionals.

Conclusion: Artificial intelligence holds promise in transforming shared decision making, ongoing research must address these implementation challenges to secure its ethical and patient-centered use in healthcare.

Objectives: Demodex mite infestation is one of the most prevalent causes of blepharitis. This study was designed to evaluate whether Demodex blepharitis was related to novel inflammatory markers.

Methods: 89 patients with Demodex blepharitis and 76 age-matched participants without blepharitis enrolled in the study. Test parameters such as hemoglobin, albumin, neutrophil, lymphocyte, monocyte, platelet, WBC, CRP, HALP score, systemic immune-inflammation-index (SII), pan-immune-inflammation value (PIV), and Demodex density were evaluated.

Results: CRP values were numerically higher, and albumin levels were lower in the patient group, even though the differences between these levels in both groups were not statistically significant (p > 0.05). SII and PIV indices were shown to be numerically higher, and HALP score levels were statistically significantly lower in the patient group (p = 0.134, p = 0.319, p = 0.001). The ROC analysis was carried out, and the optimal cutoff point for the HALP score was designated using the formula of Youden's index. It was suggested that values below 504.8 for the HALP score can be used in the diagnosis of Demodex blepharitis with 66.5% of sensitivity and 78% of specificity.

Conclusions: CRP, SII, PIV, and specifically HALP scores, which are easy to obtain and easy to use in evaluating inflammation, may also be useful in assessing inflammation in Demodex blepharitis. Particularly, HALP scores may give clinicians the information about poor immune conditions and chronic inflammation in the patients.

Objective: Hypertrophic scars (HS) are a fibrotic proliferative disorder that results from an abnormal wound healing process, presenting significant challenges for clinical intervention. The primary characteristics of HS include excessive collagen deposition and angiogenesis. In recent years, the study of mesenchymal stem cells (MSCs) and their derived exosomes has emerged as a prominent area of research within the academic community. However, the therapeutic application of MSCs is impeded by several challenges, including immune rejection, sourcing limitations, ethical dilemmas, and difficulties related to the scalability of exosome production. Cell-free adipose extract (CEFAE), a novel bioproduct derived from adipose tissue, is rich in various active protein factors that are essential for MSCs and their exosomes. CEFAE presents several advantages, including low immunogenicity, non-tumorigenicity, and a high degree of clinical safety. However, the application of CEFAE in the prevention and treatment of scar formation has not been adequately validated through experimental studies.

Methods: This research established a rabbit ear scar model, establishing a control group, a low-concentration CEFAE group (L-CEFAE), and a high-concentration CEFAE group (H-CEFAE) to evaluate wound treatment. Observations of scar changes were conducted at 14 and 28 days post-treatment, supplemented by histological and immunohistochemical analyses.

Results: Histological analysis revealed that the H-CEFAE group achieved optimal outcomes, with the lowest collagen deposition, thinnest epidermal/dermal thickness, and the most orderly collagen alignment. Furthermore, the formation of new blood vessels in the H-CEFAE group showed a significant reduction over time, resulting in decreased blood supply, which is beneficial for suppressing scar tissue development. Quantification of COL I, COL III, and vascular endothelial growth factor also supports these results.

Conclusion: The findings indicated that high-concentration CEFAE has a beneficial preventive and therapeutic effect on scar proliferation. Furthermore, the study explored the potential mechanisms by which CEFAE inhibits scar proliferation, thereby providing novel therapeutic strategies for the prevention and management of clinical scars.

Background: Recent studies have highlighted that one of the main drivers for metastatic formation and resistance to the therapy are circulating tumor cells (CTCs) and cancer stem-like cells (CSCs). Measuring the CTCs has emerged as a non-invasive procedure for selecting the patients with higher risk of progression/relapse. However, still there are no methods enabling the identification of stem-like phenotype of the CTCs.

Methods: The image-based method was used for the identification of the circulating cancer stem-like cells (CCSCs) in metastatic breast cancer patients. The method was optimized using the CSCs established in the mammosphere culture of MCF-7 cells. Next the protocol was implemented to identify the CCSCs in samples collected from 60 patients.

Results: The recovery ratio for CCSCs identification using the established method was ∼60%. The CCSCs were identified as rare events accruing only in 2 patients out of 60, who participated in the study. Interestingly, the CCSCs were found only in CTC clusters. The analysis of SOX2 expression in formalin-fixed, paraffin-embedded material, revealed that the SOX2 expression was present in primary tumor samples.

Conclusion: The CCSCs presence was found to be a very rare event. The obtained results suggest that the CCSCs are mainly present in CTC clusters and stem-like reprograming of the cancer cells might occur early, in the primary tumor.

Purpose: The purpose of this study was to evaluate the risk and prognostic factors of stage IVB cervical cancer with brain metastasis from a population-based database, the Surveillance, Epidemiology and End Results (SEER).

Patients and methods: Cervical cancer patients initially diagnosed with brain metastasis between 2010 and 2019 were included in this study. The risk factors of developing brain metastasis were evaluated by logistic regression model with corresponding 95% confidence interval (95% CI). Survival analysis was performed through the Kaplan-Meier method, log-rank test, and Cox proportional hazards model.

Results: A total of 88 (88/25,476, 0.35%) cervical cancer patients initially diagnosed with brain metastasis between 2010 and 2019 were retrieved. Accompanied with lung, bone, or liver metastasis (all P < 0.001) was shown to be independent risk factors for developing brain metastasis. Patients with brain metastasis indicated a poor prognosis (P < 0.001, hazards ratio [HR] = 2.84, 95% CI = 1.71-4.72) with a 2.84-fold elevated risk of death compared with patients without brain metastasis. The median survival month for patients with brain metastasis was 6 months, which is much shorter compared with the lung (9 months) or liver (8.5 months) or bone (11 months) metastasis group. Along with lower tumor grade (P = 0.001, HR = 0.27, 95% CI = 0.09-0.76) and with bone metastasis (P = 0.007, HR = 2.74, 95% CI = 1.33-5.67) demonstrated poor overall survival outcomes in patients with brain metastasis, with a 3.7- and 1.33-fold higher risk of death, respectively. In terms of treatment modality, chemoradiotherapy tended to prolong the survival of stage IVB cervical cancer patients with brain metastasis (P = 0.001, HR = 0.17, 95% CI = 0.06-0.48), with an 83% reduction in the risk of death.

Conclusion: In conclusion, the prognosis of stage IVB cervical cancer patients with brain metastasis remains poor. Chemoradiotherapy may provide survival benefits, which deserves large-scale prospective clinical trials to confirm.

Introduction: Giant borderline ovarian tumours (GBOTs) are rare neoplasms that require meticulous management to prevent high-risk operative complications. The broader goal of this systematic review is to consolidate the existing knowledge on GBOTs by focusing on diagnostic approaches, differential diagnoses, and treatment strategies. Furthermore, the relationship between the clinical features of GBOTs and the types of diagnostic and therapeutic procedures implemented was determined.

Materials and methods: The publications were analysed for the following data: histopathological type of GBOT; patient's age; dimensions, weight, and/or volume of the tumour; levels and types of tumour markers determined; types of imaging tests performed; type of treatment applied.

Results: Twenty-one articles describing the clinical situation of 22 patients met the inclusion criteria for the systematic review. The mean age of the patients included in the analysis was 46.68 years (SD: 19.1 years); the youngest patient was 12, and the oldest was 76 years of age. In the analysed literature, patients most often (81.8%) had the mucinous type of GBOT. In the vast majority of cases (86.36%), based on the analysed literature, the surgical treatment method for the patients was laparotomy. In more than half of the patients (54.55%), the uterus was removed during surgical treatment. In the analysed literature, the hysterectomy procedure was not performed in patients under 40 years of age. Based on the analysed literature, it was found that if the CA 125 concentration in the blood serum of patients with mucosal tumours exceeded 40 U/mL, laparoscopy was not performed and the patients were treated using an open approach.

Conclusions: GBOTs are rare neoplasms that require meticulous management to prevent high-risk operative complications. Despite the diagnostic and therapeutic challenges posed by the large size and potential complications of these tumours, with proper medical care, patients can achieve successful outcomes and a good prognosis.

Objective: Peptide-encoding roles of lncRNAs are emerging in cancer biology. This study explores the function of the CCAT1-70aa peptide in hepatocellular carcinoma (HCC) and its underlying mechanisms.

Methods: Immunohistochemistry was used to detect CCAT1-70aa expression in HCC and adjacent tissues. An expression vector verified CCAT1's role in encoding CCAT1-70aa. Cell counting kit-8 and Transwell assays assessed the effects of CCAT1-70aa on HCC cell proliferation and invasion. Small-interfering RNAs (siRNAs) targeting CCAT1 were transfected into HCC cells to examine CCAT1-70aa expression. The role of the MAPK/ERK pathway was confirmed via Western blot and the ERK inhibitor FR180204.

Results: CCAT1-70aa was significantly upregulated in HCC tissues, correlating with tumor stage, serum alpha-fetoprotein levels, and vascular invasion. siRNA-mediated CCAT1 silencing reduced CCAT1-70aa expression, supporting that CCAT1-70aa is translated from lncRNA CCAT1. CCAT1-70aa, a 70-amino acid peptide, enhanced proliferation and invasion, activating the MAPK/ERK pathway, with its effects mitigated by ERK inhibition.

Conclusion: The CCAT1-70aa peptide is overexpressed in HCC and linked to aggressive tumor characteristics. It promotes proliferation and invasion via the MAPK/ERK pathway, providing insights for HCC diagnosis and treatment strategies.