International Journal of Medical Sciences最新文献

Prolonged exposure to high-intensity light can harm macula vision, particularly affecting the function of Müller cells and cone photoreceptors. Panax notoginseng saponins (PNS) have valuable pharmacological effects on cerebrovascular, neurological, and microcirculatory health. Notoginsenoside R1 (NGR1), derived from PNS, shows potential for treating vascular or ischemia-reperfusion-related retinal issues; however, its impact on cone cells and the functional vision profile is not well understood. This study aimed to explore the effect and efficacy of NGR1 on retinal photodamage in vivo in mice. In a mouse model, high-intensity light causes significant photoreceptor damage, increases the production of pro-inflammatory factors, promotes Müller cell gliosis, and remarkably reduces the content of M- and S-opsin in cones, resulting in the abnormal and dysfunctional mislocalization of cone-opsin protein trafficking. Our data demonstrated that NGR1 orally administered improved ERG amplitude, visual acuity, and visual contrast sensitivity function compared to the vehicle group. It also preserved S- and M-cone density, mitigated abnormal trafficking of cone opsin protein, inhibited Müller cell gliosis, and reduced retinal inflammation. Therefore, NGR1 may serve as a valuable traditional complementary therapeutic or nutraceutical component for enhancing functional vision and supporting the health of Müller and cone cells in the macula.

The relationship between coffee consumption and headache remains controversial. While caffeine has both analgesic and vasoconstrictive properties, excessive intake is associated with a higher prevalence of headache. This cross-sectional study investigated the association between coffee consumption and headache in a large Taiwanese cohort. Data were obtained from 27,109 participants aged 30-70 years from the Taiwan Biobank. Headache status and coffee consumption patterns, including type, frequency, and daily intake, were assessed via structured questionnaires. Multivariable logistic regression models were used to evaluate associations. Among participants, 19.7% reported headaches. Coffee consumption was significantly associated with increased odds of headache (odds ratio = 1.21; 95% confidence level= 1.14-1.29; p < 0.001). All coffee types, including black coffee, coffee with non-dairy creamer, and coffee with milk, were linked to elevated headache risk. Daily intake of one, two, or ≥ three cups was also associated with higher odds. Frequent coffee consumption (daily or weekly) is linked to higher odds of headache, whereas monthly consumption is not. Subgroup analyses revealed no significant associations between coffee consumption and headache in individuals aged ≥ 65 years or with diabetes, hypertension, depression, or a history of alcohol or tea consumption. These findings suggest that both the amount and frequency of coffee intake are associated with higher occurrence of headache, emphasizing the importance of personalized caffeine recommendations, particularly for individuals prone to headaches.

Nasopharyngeal carcinoma (NPC) exhibits a heterogeneous tumor immune microenvironment (TIME) shaped by chemokine signaling, yet the functional roles of tumor-derived chemokines remain elusive. This study integrates single-cell RNA sequencing (scRNA-seq) of NPC tissues with validation in 109 primary patient samples, revealing CXCL10 and CCL20 as tumor-secreted chemokines localized to distinct malignant epithelial subpopulations with antagonistic roles. CXCL10 correlates with prolonged progression-free survival (PFS) and enriches an immune-active TIME by recruiting CD8+ T cells and CD20+ B cells, whereas CCL20 associates with poor prognosis and immunosuppression through preferential recruitment of regulatory T cells (Tregs). Functional validation via in vitro chemotaxis assays and in vivo xenograft models demonstrates that CXCL10 overexpression suppresses tumor growth by enhancing effector immune cell infiltration, while CCL20 promotes Treg accumulation without impeding tumor progression. Mechanistically, Tregs in NPC exhibit elevated expression of co-inhibitory molecules (CTLA4, TIGIT) and engage B cells via CTLA4-CD86 signaling, potentially impairing antigen presentation. Multi-omics analysis of bulk RNA-seq, immunohistochemistry, and cell-cell communication further delineates the antagonistic interplay between CXCL10-driven immune activation and CCL20-mediated immunosuppression. Our findings establish CXCL10 and CCL20 as dual regulators of TIME polarization in NPC, offering prognostic biomarkers and therapeutic targets to rebalance antitumor immunity.

Background: Abdominal aortic aneurysm (AAA), characterized by pathological aortic dilation, carries high mortality in intensive care unit (ICU) settings. However, existing severity scores (e.g., SAPS III, SOFA) poorly capture AAA-specific mortality predictors. We aimed to develop a focused prognostic tool to improve short-term risk stratification in ICU-admitted AAA patients. Objective: To develop and validate a machine learning-based nomogram model using the Medical Information Mart for Intensive Care IV (MIMIC-IV; 2008-2019) and the eICU Collaborative Research Database (eICU-CRD; 2014-2015) for early mortality prediction (≤7 days) in critically ill patients with AAA, addressing limitations of conventional ICU scoring systems by integrating AAA-specific predictors and ensuring generalizability through external validation. Methods: Using two independent datasets from MIMIC-IV and eICU-CRD databases, we identified patients with AAA with complete ICU records and lab data within 24 hours of admission. Critical predictors were selected via a dual approach: least absolute shrinkage and selection operator (LASSO) regression to eliminate collinearity and support vector machine-recursive feature elimination (SVM-RFE) to rank feature importance. MIMIC-IV served as the training dataset, while eICU-CRD was used for external validation. A Cox regression-based nomogram was constructed using the training set and tested for 7-, 14-, and 28-day mortality prediction. Model performance was evaluated using area under the ROC curve (AUC), concordance index (C-index), calibration plots, and decision curve analysis. Results: Six key variables independently predicted mortality including age, sepsis, blood urea nitrogen (BUN), antihypertensive drug use, average percutaneous arterial oxygen saturation (SpO₂), and anion gap. The nomogram demonstrated optimal predictive accuracy for 7-day mortality (AUC: 0.730 [training] and 0.718 [validation]; C-indices: 0.717 and 0.731), with reduced performance for 14-day and 28-day outcomes. Calibration curves displayed strong agreement at both 7 and 14 days, and DCA indicated that the model provides significant clinical value. External validation in eICU-CRD mirrored these trends (7-day AUC: 0.723), supporting model generalizability. Conclusion: This multicohort-derived nomogram provides a simple yet reliable tool to predict early mortality (≤7 days) in critically ill AAA patients, which may guide time-sensitive interventions in critical care settings.

α-Tomatine is a steroidal glycoalkaloid found in immature tomatoes that has been shown to have multiple beneficial effects on health. However, its anti-inflammatory properties have been little investigated thus far. The aim of this study was to evaluate its potential anti-inflammatory properties and underlying molecular mechanisms in rat splenocytes in vitro and ex vivo. We measured the lipopolysaccharide (LPS)-stimulated secretion of inflammatory molecules by splenocytes to assess the anti-inflammatory effects of α-tomatine. The underlying mechanism was investigated via western blotting. Next, we verified the anti-inflammatory potential of α-tomatine in rat splenocytes ex vivo. Rats were subcutaneously injected with one of two dosages of α-tomatine for seven days. We then collected their splenocytes and used them to further investigate anti-inflammatory responses ex vivo. α-Tomatine reduced LPS-evoked TNF-α, IL-1β, and NO secretion in a dose-dependent manner in the splenocytes. It also suppressed the expression of phosphorylated p38, ERK, and NF-κB in vitro. Notably, in the ex vivo experimental model, α-tomatine strongly inhibited parts of the MAPK and NF-κB signaling pathways, resulting in reduced secretion of inflammatory molecules. These results revealed that α-tomatine exerted strong anti-inflammatory activities both in vitro and ex vivo. Further, its underlying mechanisms may be related to suppressing parts of the MAPK and NF-κB signaling pathways. We thus expect α-tomatine to be developed as a novel therapeutic candidate for the treatment of inflammation-related diseases.

Introduction: Academic qualification processes in medicine are an essential component of excellent research and teaching. In Germany, these qualification paths are characterized by heterogeneity in the regulations both between the federal states and between the faculties. This lack of uniformity in Germany stands in contrast to internationally established models with standardized and transparent career paths. In view of growing international mobility and increasing global competition, the need to reform academic careers in medicine in Germany is increasingly coming into focus. Methods: On the basis of a systematic analysis, higher education laws, doctoral, habilitation and appointment regulations of German medical faculties were examined for defined target criteria. This was followed by a literature search in Pubmed and Google Scholar databases as well as freely accessible documents on the qualification systems of other international universities. Results: The evaluation reveals considerable differences in the requirements, regulations and transparency of academic qualification levels in Germany. There is a lack of standardization processes in German regulations, particularly in the area of habilitation and extraordinary professorship. In an international comparison, there are clear differences between countries both in the existence of qualification levels and the qualification path to the qualification level. However, many countries have structured and transparent qualification levels with underlying tenure-track models or performance-oriented criteria. Conclusion: The results of the academic qualification structures in medicine show a need for reform of the German academic system in an international comparison. The introduction of transparent and structured career paths, based on systems already established in other countries (PhD model/tenure track system), would contribute to harmonization and the promotion of international comparability and mobility.

Heart failure with preserved ejection fraction (HFpEF) represents a complex clinical syndrome characterized by limited therapeutic options, which are largely due to its intricate pathophysiology. The role of mechanical stress is pivotal in maintaining cardiovascular homeostasis; conversely, its dysregulation may precipitate the progression of cardiovascular diseases. In HFpEF, both macroscopic structural alterations and intricate molecular processes might be influenced by mechanical stress. This review examines the potential associations between mechanical stress and HFpEF, exploring the pathophysiological underpinnings to the effects of mechanotransduction effectors on cardiac remodeling and the progression of heart failure, providing novel insights into the pathological mechanisms of HFpEF. Therapeutic strategies targeting these mechanotransduction effectors have shown promise in mitigating pathological cardiac remodeling in models of metabolic-associated heart failure, underscoring their potential as innovative treatments for HFpEF. Considering the clinical heterogeneity of HFpEF, it is imperative to pursue phenotype-specific personalized treatments to optimize therapeutic efficacy.

Periodontitis (PD) is a chronic inflammatory disease characterized by the accumulation of bacterial metabolites, sustained immune activation, and progressive loss of alveolar bone. Hyperbaric oxygen therapy (HBOT) has demonstrated anti-inflammatory and bone-reparative properties; however, its mechanistic effects in periodontitis remain underexplored. This study investigated whether HBOT mitigates periodontal bone loss and modulates bacterial, inflammatory, and osteoclastogenic pathways in a ligature-induced rat model. Sixty male Wistar rats underwent ligature placement for 28 days and were allocated into five groups (Sham, PD, PD+ natural recovery [RECOV], PD+early HBOT [EHBOT], PD+late HBOT [LHBOT]); HBOT was delivered as 100% oxygen at 2.0 ATA for 60 min/day. Gingival tissues were assessed for bacterial metabolites, lipoteichoic acid (LTA) and lipopolysaccharide (LPS), inflammatory cell infiltration, fibrotic integrity, and alveolar bone resorption. Cytokine and chemokine arrays were performed to evaluate cytokine-induced neutrophil chemoattractants, interleukin-1α, interleukin-1β, interleukin-1 receptor antagonist, LPS-induced chemokine CXCL5, thymus chemokine, tissue inhibitor of metalloproteinases-1, soluble intercellular adhesion molecule-1, and L-selectin. Ligature-induced periodontitis triggered robust inflammatory responses, elevated bacterial burden, increased receptor activator of nuclear factor kappa-B ligand (RANKL), and suppressed osteoprotegerin (OPG), promoting osteoclastogenesis and bone loss. Importantly, EHBOT produced more pronounced reductions in LTA/LPS and pro-inflammatory mediators and yielded greater preservation of trabecular microarchitecture than LHBOT or RECOV. HBOT overall significantly reduced LTA/LPS levels, suppressed inflammatory cytokines and adhesion molecules, and restored the RANKL/OPG balance in osteoblasts and osteocytes. Histological and micro-computed tomography analyses confirmed that HBOT preserved trabecular bone microarchitecture. These findings highlight the multi-targeted therapeutic potential of HBOT in suppressing inflammation, limiting immune cell infiltration, and preventing bone destruction, supporting its use as an adjunctive intervention for periodontitis and inflammatory bone disorders.

Objectives: Dietary patterns play a role associated with acute or chronic diseases. This study compared the correlation between dietary patterns and vitamin D status, using two methods for dietary pattern identification, related to gestational anemia among expectant mothers. Methods: In this cross-sectional study a total of 1502 expectant mothers aged > 15 years were recruited from the Nutrition and Health Survey data. Dietary patterns were discerned through principal component analysis (PCA) and reduced rank regression (RRR). Associations between dietary pattern scores, vitamin D, and anemia-related biomarkers were validated using linear and binomial logistic regression adjusted for sociodemographic and economic factors. Results: Two dietary patterns were identified: a plant and marine-based dietary pattern (PMDP) via PCA and a convenience food dietary pattern (CFDP) via RRR. PMDP was characterized by high intakes of plant and marine foods, while CFDP showed high intakes of canned and pickled foods. Risk estimation indicated that high PMDP intake was associated with 30% reduction in odds of vitamin D insufficiency, while moderate CFDP intake was linked to an increased risk of vitamin D insufficiency by 46%. Logistic regression analysis showed a positive association between CFDP and serum iron (β = 0.08; 95% CI: 0.05, 0.24), but a negative association with total iron binding capacity (β = -0.05; 95% CI: -0.44, -0.07). Conclusions: The PCA-derived dietary pattern effectively identifies eating patterns, while the RRR-derived dietary pattern has a better estimate for disease associations in a specific population. The RRR-derived dietary pattern provides valuable insights for dietary guidelines targeting vitamin D insufficiency.

Background: Glaucoma is a leading cause of irreversible blindness that is increasingly being linked to systemic metabolic disturbances. Metabolic syndrome (MetS) is a cluster of metabolic conditions that are associated with various ocular diseases, however the relationship between MetS and glaucoma remains insufficiently explored. This study aimed to investigate the associations between MetS and its components of central obesity, impaired glucose tolerance, high blood pressure, high blood triglycerides, and low high-density lipoprotein with glaucoma in a large Taiwanese population. Methods: A cross-sectional analysis was conducted using data from the Taiwan Biobank, encompassing 93,905 participants aged 40 years and older. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria, and glaucoma status was determined through self-reported diagnoses. Statistical analyses included logistic regression models adjusted for demographic and clinical variables. Results: The prevalence of MetS in the study population was 25.6%, and the association between MetS and glaucoma was significant (adjusted odds ratio [OR] = 1.15; 95% confidence interval [CI]: 1.02-1.30). A dose-response relationship was observed, with the risk of glaucoma increasing along with the number of MetS components, with a peak OR of 1.36 for individuals with four MetS components. Among the MetS components, impaired glucose tolerance showed the strongest association with glaucoma (OR = 1.17; 95% CI: 1.03-1.32). MetS was an independent risk factor for glaucoma, and the risk increased in parallel with the number of metabolic abnormalities. Conclusions: These findings show the importance of metabolic health in preventing glaucoma and suggest that targeted screening and early interventions may help to mitigate the risk of glaucoma in individuals with MetS.