European Journal of Medical Research最新文献

Background: Ischemic brain injury results in high disability due to neuroinflammation and oxidative stress, and M1/M2 polarization of glial cells plays a key role in neuroinflammation. This research explored the protective effect of Catalpalactone on middle cerebral artery occlusion (MCAO)-induced brain injury and its underlying regulation mechanism in rats.

Methods: The ischemic lesions were induced by the MCAO, and the oxygen and glucose deprivation/reoxygenation (OGD/R) was used for BV2 microglial cell induction. The polarization of glial cells was determined via immunohistochemistry staining assessment. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) assays were used for the glycolysis and oxidative phosphorylation test. After that, the cell counting kit-8 (CCK-8) for cell viability test and flow cytometry for apoptosis and phosphorylation analysis were performed. Furthermore, a co-culture model of BV2 and PC12 cells was used for the purpose of exploring the effects of Catalpalactone on the interaction and of microglia and neurons in ischemic brain injury. Finally, the Modified Neurological Severity Score (mNSS) analysis was used for the analysis on the neurological function.

Results: After MCAO induction, the infiltration of microglial cells were significantly increased in the injury area, and its M1 phenotype was enhanced (up-regulated Cd86). In vitro, the OGD/R-induced BV2 microglial cell also exhibited the increasing M1 phenotype with higher glycolysis activity, but lower oxidative phosphorylation through the activating JAK-SATA signaling pathway. Finally, we determined that 15 μM Catalpalactone optimally induces M2 microglial polarization with increased cell viability and decreased apoptosis in the OGD/R-induced BV2 cell model, while also reducing mNSS scores and improving neurological function in the MCAO rat model.

Conclusion: We clarified the underlying mechanism of Catalpalactone treatment for ischemic lesions through promoting M2 microglial cells phenotype.

Atrial fibrillation (AF) poses a serious health threat to human health and causes various adverse effects. It is currently the most common type of arrhythmia in adults. Long-term AF induces a series of heart-remodeling events, including mainly cardiac structural remodeling and electrical remodeling, which further exacerbates AF. The oxidative stress has been shown to play a role in inducing myocardial remodeling and the progression of AF. Recent studies have shown that ferroptosis occurs in the myocardium of patients with AF, which exacerbates oxidative stress and may constitute a new mechanism for the progression of AF. However, it is unknown to us how ferroptosis is involved in the initiation and maintenance of AF, so the purpose of this review is to elucidate the possible underlying mechanism of ferroptosis exacerbating AF. We reviewed the latest studies on myocardial ferroptosis and AF and speculate that the lipid peroxidation products isolevuglandins (IsoLGs), which are produced during myocardial ferroptosis, may be involved in the progression of AF through two pathways: (1) IsoLGs inhibit the degradation of myocardial collagen, worsening myocardial fibrosis; and (2) IsoLGs promote the occurrence of amyloidosis in the myocardium and increase the risk of AF. Consequently, we aim to prevent the progression of atrial fibrillation by either suppressing the production of IsoLGs or enhancing their clearance process to inhibit ferroptosis in the myocardium, improving the prognosis of patients with AF.

Background: Dysregulation of long non-coding RNA H19 (lncRNA H19) is involved in cervical cancer (CC) progression. This study aims to unveil the specific role and relevant mechanism of lncRNA H19 in CC.

Methods: The expression of lncRNA H19 in CC cells was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). CC cells were transfected with sh-H19, followed by cell proliferation, apoptosis, migration and invasion were examined. After location of H19 in cells using fluorescence in Situ Hybridization (FISH), target microRNAs (miRNAs) and genes associated with lncRNA H19 were predicted using bioinformatics analysis and validated by dual-luciferase reporter assay. Finally, the specific role of lncRNA H19 in CC was explored in vivo.

Results: The upregulation of lncRNA H19 was observed in CC cells. LncRNA H19 knockdown inhibited the proliferation, migration, and invasion of CC cells, and remarkably promoted CC cell apoptosis. LncRNA H19 was localized in the nucleus and interacted with miR-140 that was downregulated in CC cells. MiR-140 inhibition reversed the effects of lncRNA H19 knockdown on CC cell development. MiR-140 targets ALDH1A1, and lncRNA H19 knockdown decreased the ALDH1A1 expression, which was rescued by miR-140 inhibition. In vivo experiments also shown that reduction of lncRNA H19 diminishes tumor growth via targeting the miR-140/ALDH1A1 axis.

Conclusion: LncRNA H19 promotes the malignant progression of CC through targeting miR-140/ALDH1A1 axis.

The significance of m6A modifications in several biological processes has been increasingly recognized, particularly in the context of cancer. For instance, m6A modifications in gastric cancer (GC) have been significantly implicated in tumor progression, metastasis, and treatment resistance. GC is characterized by the differential expression of m6A regulators. High expression writers such as METTL3 and WTAP are associated with poor prognosis and aggressive clinical features. Conversely, low expression of METTL14 is linked to worse clinical outcomes, whereas elevated levels of demethylases, such as FTO and ALKBH5, correlate with better survival rates. These m6A regulators influence several cellular biological functions, including proliferation, invasion, migration, glycolysis, and chemotherapy resistance, thereby affecting tumor growth and therapeutic outcomes. The assessment of m6A modification patterns and the expression profiles of m6A-related genes hold substantial potential for improving the clinical diagnosis and treatment of GC. In this review, we provide an updated and comprehensive summary of the role of m6A modifications in GC, emphasizing their molecular mechanisms, clinical significance, and translational applications in developing novel diagnostic and therapeutic strategies.

Background: The medial approach for minimally invasive harvesting of a deep circumflex iliac artery (DCIA) flap is described for reconstruction of the jaw. The associated preservation of the crest of the ilium prevents the raising of the abdominal internal oblique muscle (IO) in a standard fashion. However, reconstructive surgery of composite mandibular defects includes bone and soft tissue. To achieve this goal, we combined this technique with a new perforator-based raising of the IO for reconstruction of intraoral soft tissue.

Methods: In this study, we present eight cases of patients with composite mandibular defects who underwent the myo-osseous DCIA flap procedure with an IO perforator. Virtual surgical planning was employed to preplan the size and configuration of the graft. Cutting guides were made using CAD/CAM technology. The surgical procedure followed the described medial approach for minimally invasive harvesting, leaving the iliac crest, spine, and skin intact. In addition, we completely cut and isolated the IO with its sole attachment being the ascending branch of the DCIA. We used either a surgical guide with a slot to lead through both the transverse branch of the bone and the ascending branch of the IO or a surgical guide consisting of 2 parts.

Results: In all instances, the flap successfully survived with a 100% success rate. There were no signs of infection, wound opening, or bleeding in either patient. Furthermore, the patients did not exhibit permanent complications related to the donor site. The internal oblique perforator flap exhibited remarkable integration in all patients and underwent rapid transformation. Notably, the flap developed keratinized mucosa (KM) that closely resembled the attached gingiva.

Conclusion: Our study demonstrated the effectiveness of a medial approach for harvesting a newly designed more flexible chimeric myo-osseous deep circumflex iliac artery flap. By incorporating virtual surgical planning and custom-made cutting guides for obtaining deep circumflex iliac artery flaps through the medial route along with an internal oblique perforator flap, we have established a highly promising method for the rehabilitation of patients with composite mandibular defects. This approach not only improves functional outcomes, but also enhances aesthetic results to maintain patients' quality of life.

Objectives: The aim of this study is to construct a nomogram for predicting subsequent early pregnancy loss in women with a history of pregnancy loss, which may increase well-being and the capacity for managing reproductive options.

Materials and methods: We conducted a retrospective analysis of medical records from women with a history of pregnancy loss at the Reproductive Medicine Center of Lanzhou University Second Hospital between January 2019 and December 2022. A cohort of 718 patients was selected for the study. We structured our data into a training set of 575 cases (80% of the cohort) and a test set of 143 cases (20%). To identify significant predictors, we applied a stepwise forward algorithm guided by the Akaike Information Criterion (AIC) to the training set. Model validation was conducted using the test set. For the validation process, we employed various methods to assess the predictive power and accuracy of the model. Receiver Operating Characteristic (ROC) curves provided insights into the model's ability to distinguish between outcomes effectively. Calibration curves assessed the accuracy of the probability predictions against actual outcomes. The clinical utility of the model was further evaluated through Decision Curve Analysis, which quantified the net benefits at various threshold probabilities. In addition, a nomogram was developed to visually represent the risk factors.

Results: Among the 36 candidate variables initially considered, 10 key predictors were identified through logistic regression analysis and incorporated into the nomogram. These selected variables include age, education, thrombin time (TT), antithrombin III (AT-III), D-dimer levels, 25-hydroxy Vitamin D, immunoglobulin G(IgG), complement components C4, anti-cardiolipin antibody (ACA) and lupus anticoagulant (LA). In addition, based on clinical experience, the number of previous pregnancy losses was also included as a predictive variable. The prediction model revealed an area under the curve (AUC) of approximately 0.717 for the training set and 0.725 for the validation set. Calibration analysis indicated satisfactory goodness-of-fit, with a Hosmer-Lemeshow test yielding a χ2 value of 7.78 (p = 0.55). Decision curve analysis confirmed the clinical utility of the nomogram. Internal validation confirmed the robust performance of the predictive model.

Conclusions: The constructed nomogram provides a valuable tool for predicting subsequent early pregnancy loss in women with a history of pregnancy loss. This nomogram can assist clinicians and patients in making informed decisions regarding the management of pregnancy and improving clinical outcomes.

Trial registration: This study was registered in the Chinese Clinical Trial Registry under the registration number ChiCTR2000039414 on October 27, 2020. The registration was done retrospectively.

Background: RNA editing is recognized as a crucial factor in cancer biology. Its potential application in predicting the prognosis of colon adenocarcinoma (COAD) remains unexplored.

Methods: RNA editing data of COAD patients were downloaded from the Synapse database. LASSO regression was used to construct the risk model and verified by the receiver operating characteristic (ROC) curve. GO and KEGG enrichment analyses were performed to delineate the biological significance of the differentially expressed genes. Finally, differential analysis and immunohistochemistry were used to verify the expression of adenosine deaminase 1 (ADAR1).

Results: We evaluated a total of 4079 RNA editing sites in 514 COAD patients from Synapse database. A prognostic signature was constructed based on five genes were significantly associated with the prognosis of COAD patients including GNL3L, NUP43, MAGT1, EMP2, and ARSD. Univariate and multivariate Cox regression analysis revealed that RNA editing-related genes (RERGs)-related signature was an independent risk factor for COAD. Moreover, Experimental evidence shows that ADAR1 is highly expressed in colon adenocarcinoma and silencing ADAR1 can inhibit cancer cell proliferation.

Conclusion: We established a prognostic model based on five RERGs with strong predictive value. This model not only serves as a foundation for a novel prognostic tool but also facilitates the identification of potential drug candidates for treating COAD.

Background: Some evidence highlights individuals lacking an adequate level of vitamins may experience heightened susceptibility to post-anesthesia complications. The current study summarized the previous evidence assessing the impact of deficient vitamin levels on complications and outcomes following anesthesia.

Methods: A comprehensive search in scientific English databases was conducted from January 2000 to January 2024. The inclusion and exclusion criteria were applied, the full-texts were thoroughly analyzed, and the risk-of-bias was assessed.

Results: A multitude of 1322 published articles were discovered based on search strategy and 14 eligible papers were enrolled. The mean age of patients was 39.3 years and the majority were male. Patients with vitamin B12 deficiency experienced both neurological and hematologic consequences post-anesthesia. Delirium was observed among patients lacking sufficient levels of vitamin D, and those deficient in vitamin K presented symptoms indicative of epidural hematoma. Post-anesthesia consequences were manifested with a delay, ranging from hours to days following the anesthesia procedure in vitamin K and B12 deficiency, while patients deficient in vitamin C and B1 experienced an acute onset of symptoms during surgery. Significantly, a notable proportion (42%) had pre-existing risk factors for vitamin deficiency prior to the surgery, while 35% of the risk-factors for vitamin deficiency were diagnosed after the surgery. There was a wide range of complete or partial recovery periods following surgical intervention, spanning over a few days up to several months according to the severity of symptoms.

Conclusions: Based on the evidence from the reviewed studies, this study robustly suggests that serum vitamins level before surgery should be measured among patients who are at risk of vitamin deficiency or have some related clinical symptoms.

The objective of this study was to conduct a comprehensive comparison of the effects of hip and knee strengthening training in patients with patellofemoral pain (PFP). A meta-analysis was conducted to investigate the effects of these two types of strengthening training on patients' lower limb biomechanics, knee pain and function. The aim was to evaluate the effectiveness of the two training modalities and provide evidence-based recommendations for the rehabilitation of patients with PFP. A total of 12 studies were identified through a search of the Web of Science, EBSCO, and PubMed databases. The selected studies comprised nine randomized controlled trials (RCTs), one comparative controlled trial (CCTs) and two cohort studies (CSs), with a total of 1,066 patients. The quality of the included studies was evaluated via the PEDro scale, and a meta-analysis was conducted via Stata18 software. The results show that both types of strengthening training positively impact pain reduction and improved knee function in PFP patients. Moderate evidence from meta-analyses indicated that hip strengthening training (SMD = -1.740, 95%; CI -2.212 to -1.267, P < 0.001) was more effective than knee strengthening training (SMD = -1.302, 95%; CI -1.75 to -0.86, P < 0.001) in reducing pain (VAS). Similarly, Strong evidence suggests that hip strengthening training (SMD = 1.205, 95%; CI 0.968 to 1.443, P < 0.001) was significantly more effective than knee strengthening training (SMD = 1.023, 95%; CI 0.722 to 1.325, P < 0.001) in improving knee function (AKPS). Additionally, moderate evidence suggests that hip strengthening training significantly increased hip abductor strength (SMD = 0.848, 95%; CI 0.508-1.187, P < 0.001) and external rotator strength (SMD = 0.780, 95%; CI 0.416-1.145, P < 0.001), while strong evidence suggests that knee strengthening training did not significantly enhance knee extensor strength (SMD = 0.212, 95%; CI -0.014 to 0.439, P = 0.066). Therefore, clinicians should use hip strengthening as one of the primary training interventions when treating patients with PFP.