Current Medical Science最新文献

Objective: Glioma is a highly lethal tumor of the central nervous system (CNS) with limited therapeutic options. Recent evidence has highlighted the role of dysregulated alternative splicing in glioma progression. Although OY-TES-1 has been proposed as a potential therapeutic target, its splice isoforms have not been fully characterized. This study aimed to identify the clinically relevant splice variant of OY-TES-1 associated with glioma progression and to evaluate its potential as a target for innovative therapeutic strategies against this challenging disease.

Method: The potential splicing patterns of OY-TES-1, along with their relative frequency and correlation with patient survival, were analyzed via the TCGA SpliceSeq and OncoSplicing databases. RNA-Seq by expectation maximization (RSEM) values and clinicopathological data for all OY-TES-1 gene transcripts were downloaded from the UCSC Xena database, and Cox regression analysis was performed for both univariate and multivariate prognostic assessments. The expression of OY-TES-1 mRNA in glioma and normal brain tissues was detected via RT-PCR. The relationships between OY-TES-1 mRNA expression and the clinicopathological characteristics of glioma patients were analyzed via the χ² test. OY-TES-1-V5a was overexpressed in glioma cells through transient transfection with plasmids as well as stable transfection with lentivirus for further functional analysis. Glioma cell proliferation was assessed via the Cell Counting Kit-8 (CCK-8) assay. Migration and invasion abilities were evaluated via wound healing, Transwell, and Transwell Matrigel assays. Apoptosis was analyzed by flow cytometry.

Results: Bioinformatic analysis revealed four alternative splice variants of OY-TES-1 in glioma, among which OY-TES-1-V5a presented a relatively high percent spliced-in (PSI) value that was associated with significantly shorter overall survival. OY-TES-1-V5a was further identified as an independent prognostic risk factor for glioma patients, as its mRNA expression was significantly associated with Karnofsky performance status (KPS), tumor grade, and isocitrate dehydrogenase 1 (IDH1) mutation status. RT-PCR validation confirmed that OY-TES-1-V5a was overexpressed in glioma tissues compared with normal brain tissues. Functionally, forced expression of OY-TES-1-V5a enhanced glioma cell proliferation, migration, and invasion while suppressing apoptosis.

Conclusions: The OY-TES-1 splice variant V5a is highly expressed in glioma, is associated with poor prognosis, and actively drives malignant behavior, indicating its potential utility as a prognostic biomarker and a candidate target for therapeutic intervention.

Objective: Non-communicable diseases (NCDs), characterized by long duration, gradual progression, and high morbidity, have emerged as a fundamental threat to global public health. Furthermore, dramatic climate change may exacerbate existing trends that worsen the burden of NCDs. Therefore, this study aimed to systematically investigate the patterns and trends of NCDs attributed to nonoptimal temperatures from 1990 to 2021.

Methods: We utilized data from the Global Burden of Disease Study (GBD) 2021 to assess the temporal trends in age-standardized rates (ASR) of deaths and disability-adjusted life-years (DALYs) related to nonoptimal temperature-associated NCDs across 204 countries and territories from 1990 to 2021. Decomposition analysis was applied to quantify the contribution of key factors to this burden. The autoregressive integrated moving average (ARIMA) model was employed to predict trends over the next decade.

Results: Globally in 2021, NCDs attributable to high temperature (Hi-Tem) accounted for an estimated 302,464.7 deaths (95% uncertainty interval [UI]: 171,170.6, 472,625.3) and 6,947,660.6 DALYs (95% UI: 4,013,964.7, 10,611,801.7). The ASR of Hi-Tem-related NCDs deaths and DALYs increased by 35% and 34% between 1990 and 2021. Additionally, the global burden exhibited a significant declining trend in NCDs burden caused by low temperature (Lo-Tem), with 1,477,729.8 (95% UI: 1,316,829.3, 1,631,404.8) deaths and 27,797,533.3 (95% UI: 25,270,393.5, 30,766,299.9) DALYs in 2021. China and India had the highest number of deaths and DALYs for NCDs related to Hi-Tem and Lo-Tem. In 2021, the three leading causes of the NCDs burden attributable to nonoptimal temperature were ischemic heart disease, stroke, and chronic obstructive pulmonary disease. Men and older adults were consistently vulnerable to temperature, showing the greater burden of NCDs attributable to nonoptimal temperature, and aging would exacerbate this trend. The ARIMA model projected an increasing trend in Hi-Tem-related NCDs over the coming decade, while those related to Lo-Tem would show a downward trend.

Conclusion: The burden of NCDs associated with Hi-Tem has conspicuously increased in recent years compared to that associated with Lo-Tem, with significant diversity across age, sex, and socio-demographic index (SDI) levels. Therefore, public health strategies should prioritize tailored interventions for heterogeneous risk profiles across vulnerable populations, integrated with climate-resilient surveillance systems and real-time adaptive response mechanisms to mitigate projected climate-mediated exacerbations of NCD burden.

Familial hypercholesterolemia (FH) is a heritable condition that disrupts the body's ability to clear low-density lipoprotein cholesterol (LDL-C), commonly known as "bad cholesterol" from the bloodstream. This leads to persistently elevated LDL levels from birth, significantly increasing the risk of premature atherosclerosis and cardiovascular events, such as heart attack and stroke. This occurs due to variations in genes such as low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). The treatments that are available for FH include pharmacological interventions, microbiome-based treatments, molecular approaches, nanotechnology methods, surgical procedures, nutraceuticals, herbal therapy, yoga and physical fitness methods, along with lifestyle management. This review discusses the adverse effects associated with various conventional treatment methods for hypercholesterolemia and the need for a safe and effective approach for the treatment of this genetic condition. An integrated approach combining pharmacological, molecular, and lifestyle interventions has emerged as a pragmatic solution. Yoga and fitness-based therapies positively impact lipid profiles, offering non-pharmacological and holistic adjunctive options. This comprehensive approach addresses the multifaceted aspects of FH management, considering genetic factors, socioeconomic considerations, and individualized patient needs.

Prenatal depression is a prevalent mental health disorder that adversely affects maternal well-being and offspring health. Emerging evidence suggests that vitamin C (L-ascorbic acid), a key antioxidant, may influence this process through the regulation of DNA methylation (DNAm)-a critical epigenetic mechanism governing gene expression. This review summarizes current research on the role of vitamin C in modulating DNAm and explores its potential to mitigate the intergenerational impacts of prenatal depression. We analyze findings indicating that vitamin C may alleviate depressive symptoms and improve offspring health outcomes via epigenetic pathways. Furthermore, we highlight existing research gaps and propose future directions for investigation. By elucidating the interplay between vitamin C, epigenetic regulation, and prenatal depression, this article aims to provide novel insights for developing nutritional strategies to enhance maternal mental health and promote offspring well-being.

Objectives: This study aimed to investigate the association between laboratory biomarkers and short-term poor prognosis in patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and to develop a risk stratification model.

Methods: A retrospective analysis was conducted on clinical data from 117 EBV-HLH patients admitted to our hospital between June 2016 and December 2024. Patients were classified into poor prognosis (n = 48) and good prognosis (n = 69) groups based on 28-day outcomes. Potential predictors were screened by univariable logistic regression and receiver operating characteristic (ROC) curve analysis, and a composite laboratory-based risk scoring system was subsequently constructed.

Results: The poor prognosis group exhibited significantly higher levels of urea (UREA), direct bilirubin (DB), high-sensitivity cardiac troponin I (hscTnI), serum ferritin (Ferr), and prothrombin time (PT) than the good prognosis group did (all P < 0.05). ROC analysis determined the optimal cutoff values and corresponding odds ratios (ORs) for poor prognosis as follows: UREA (≥ 5.4 mmol/L, OR = 5.911), DB (≥ 10.0 μmol/L, OR = 2.524), hscTnI (≥ 7.4 pg/mL, OR = 2.747), Ferr (≥ 12,422 μg/L, OR = 2.366), and PT (≥ 14.1 s, OR = 3.221). A 0-5-point risk score model was constructed based on these thresholds. The incidence of poor prognosis increased progressively with the score: 23.08% (score 0-1), 27.59% (score 2), 45.00% (score 3), 66.67% (score 4), and 92.30% (score 5). Each 1-point increase in the score was associated with an OR of 1.915 for poor prognosis.

Conclusion: The composite risk scoring system incorporating UREA, DB, hscTnI, Ferr, and PT showed satisfactory predictive performance for short-term outcomes in EBV-HLH patients. A score of ≥3 identifies high-risk individuals who may benefit from intensified immunomodulatory therapy, thereby facilitating individualized and stratified clinical management.

Objective: Electroacupuncture (EA) has emerged as a clinically adopted complementary modality in the management of respiratory and digestive disorders. This investigation sought to elucidate the therapeutic potential of EA against sepsis-induced pulmonary and gastrointestinal injuries, with particular emphasis on delineating its multimodal mechanistical pathways.

Methods: Sepsis was induced in C57BL/6 mice by administeringting lipopolysaccharide (LPS) one hour after EA intervention at the Zusanli (ST36) and Tianshu (ST25) acupoints for eight days. Inflammatory responses and barrier function were evaluated in the lung and colon tissues. Hematoxylin and Eosin (H&E) staining was performed on lung tissues, while colon tissues were subjected to H&E staining, Wheat Germ Agglutinin-Fluorescein Isothiocyanate (WGA-FITC) staining, and Alcian Blue staining. Additionally, Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blotting were used to explore potential molecular mechanisms. Furthermore, 16S rRNA gene sequencing was employed to analyze changes in the gut microbiota.

Results: EA ameliorated both pulmonary injury and intestinal damage in septic mice. This protective effect was mediated through significant attenuation of pulmonary and intestinal inflammation, coupled with partial restoration of gut microbiota homeostasis. Specifically, EA inhibited the activation of Nod-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and mitogen-activated protein kinase (MAPK) pathways, and upregulated the transcription of lung barrier-related factors (MMP2, MMP9, Occludin) in the lung. In addition, EA improved inflammation and reduced damage to the intestinal mucosal barrier in the colon. This was accomplished by decreasing the expression of pro-inflammatory cytokines (IL-1β, TNF-α) and increasing the levels of mucin and glycoproteins. Furthermore, EA intervention altered the structure of the gut microbiota, resulting in a significant increase in the abundance of beneficial bacteria, such as Ruminococcaceae and Roseburia.

Conclusion: EA is a potential adjunct therapy for sepsis-related pulmonary and intestinal injury. The mechanism involves the inhibition of the NLRP3 inflammasome and remodeling of the gut microbiota.

Objective: The benefits of caffeine to human health have been widely reported, but the association between caffeine intake and mortality among patients with chronic kidney disease (CKD) has been rarely reported in large epidemiologic studies. This study aimed to investigate the association between caffeine intake and mortality among CKD patients.

Methods: Our study was conducted among non-dialysis CKD patients in the 2003-2016 National Health and Nutrition Examination Survey (NHANES). Weighted COX regression analysis was used to explore the linear relationship between caffeine intake and mortality among CKD patients (including all-cause mortality, as well as mortality due to cardiovascular disease, cancer, cerebrovascular disease, nephropathy, and influenza or pneumonia). Restricted cubic spline analysis was performed to explore the nonlinear relationship. Finally, threshold effects were analyzed through fitting a two-piecewise linear regression model.

Results: In a fully adjusted model, no significant linear association was found between caffeine intake and mortality. However, there was a U-shaped association between caffeine intake and all-cause mortality (inflection point: 277 mg). Moreover, there was a J-shaped association between caffeine intake and cardiovascular mortality (inflection point: 252 mg) and cancer mortality (inflection point: 79 mg).

Conclusion: All-cause mortality was reduced in CKD patients when caffeine intake was less than 277 mg (about 1.85 cups of Americano). However, excessive caffeine intake was associated with increased all-cause mortality, cardiovascular mortality and cancer mortality in this population.

Graphene quantum dots (GQDs) have emerged as promising nanomaterials in cancer therapy because of their unique physicochemical properties. This review comprehensively analyzes the roles of GQDs in cancer diagnostics and treatment, highlighting their biocompatibility, tunable photoluminescence, and surface functionalization capabilities. GQDs exhibit minimal toxicity, efficient cellular uptake, and favorable biodistribution, making them suitable for targeted drug delivery, photothermal therapy (PTT), and photodynamic therapy (PDT). Their intrinsic fluorescence also enables real-time bioimaging, supporting theranostic applications. This study explores their mechanisms of action, including reactive oxygen species (ROS) generation, heat-induced ablation, and pH-responsive drug release. GQDs have demonstrated efficacy across various cancers, such as breast, lung, brain, liver, and pancreatic cancers, through enhanced drug/gene delivery, biosensing, and image-guided therapy. Despite encouraging preclinical results, challenges related to toxicity profiling, standardization, regulatory frameworks, and scalability remain significant barriers to clinical translation. This review emphasizes the therapeutic versatility of GQDs and underscores the need for further research to overcome translational hurdles and realize their full potential in personalized cancer care.

Fibrotic diseases place a substantial burden on health and the economy, with limited treatment options. Therefore, effective therapeutic strategies are urgently needed. Emodin, a natural compound with diverse biological activities, has been demonstrated in multiple studies over recent years to have potential therapeutic effects on fibrotic diseases. This review aims to provide a comprehensive overview of the existing research on emodin's pharmacological effects and mechanisms in inhibiting fibrotic disease, with a focus on its therapeutic advantages and systemic mechanisms. Recent studies have shown that emodin plays a role in combating fibrotic diseases by suppressing the production of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α; it alleviates inflammation by inhibiting the NF-κB signaling pathway and preventing the degradation of IκB. Emodin also suppresses the activation of the MAPK pathway, enhances the expression of antioxidant enzymes, and influences the metabolism of the extracellular matrix (ECM). Thus, emodin is highlighted for its potential as an antifibrotic agent, and future research directions are proposed to deepen our understanding and develop novel treatment strategies for fibrotic diseases.

Objective: Bronchiolar adenoma (BA) is a peripheral pulmonary neoplasm characterized by a bilayered cell structure composed of basal cells and luminal cells. Owing to its low incidence and limited research data, clinicians and pathologists still have an insufficient understanding of this disease. This study aims to characterize the morphological, immunohistochemical, and genetic features of BA and its variants, and to determine whether BA can progress to a malignancy.

Methods: Among these 33 cases, 21 were histologically characterized by double-layered tumors with continuous basal cell layers. Six patients exhibited a partial classic bilayer, transitioning from a bilayer to a monolayer in certain lesion areas (mixed-type BAs). Six other BA-like tumors with monolayered components might represent the early stage of malignant transformation of BA. Next-generation sequencing analysis was conducted on 33 cases to elucidate the genetic spectrum.

Results: All the cellular components exhibited a relatively mild morphology. Immunohistochemical analysis revealed that basal cells coexpressed p40 and cytokeratin 5/6. Thyroid transcription factor 1 was expressed in the double-cell layer, which consists of ciliated columnar epithelial cells, basal cells, nonciliated columnar epithelial cells, and cuboidal epithelial cells. The pan-cancer gene panel was used to observe driver alterations in 9 of 21 classic bilayered BAs (43%), 2 of 6 mixed-type BAs (33%), and 3 of 6 monolayered BA-like lesions (50%). Genetically, monolayered BA-like lesions shared some alterations with classic BAs in mutational signatures, whereas NKX2-1 mutations were enriched only in monolayered BA-like lesions.

Conclusion: These findings underscore the histopathological and genetic characteristics of BA and its variants, suggesting that monolayered BA-like lesions have the potential to develop into lung adenocarcinoma. In the future, more cases should be recruited to further explore the malignant transformation of this specific entity via the multidimensional spectrum.