International Journal of Medical Sciences最新文献

Limbal niche cells (LNCs) possess embryonic stem cell (ESC) characteristics, expressing ESC markers such as Sox2, Nanog, and Oct4; stromal characteristics, expressing neurocrest markers such as CD90; and have angiogenic potential expressing angiogenesis markers such as CD34. In addition, these cells can be induced into adipocytes, chondrocytes, and osteocytes, indicating that they are valuable adult stem cells. However, how these cells may be appropriately passaged and maintained, what signaling pathways are necessary for such regeneration, and how the cells can be used for the treatment of various diseases caused by stem cell deficiency, such as limbal stem cell deficiency, remain unclear. Herein, we summarize the most recent advances in limbal niche research, with emphasis on the regeneration of adult limbal progenitors and their mechanisms, to promote cell-based therapy for various eye diseases due to stem cell deficiency or malfunction. Such a strategy may also provide a platform for stem cell therapy for other similar human diseases worldwide.

Background and purpose: High-dose-rate endobronchial brachytherapy (HDR-BTE) is an effective technique for the treatment of malignant tracheobronchial tumors. Although two-dimensional (2D) planning provides limited dosimetric information and does not accurately assess the relationship between the catheter and the tumor or the dose delivered to organs at risk (OARs), it continues to be used because it ensures adequate PTV coverage, is associated with low toxicity, and minimizes the risk of catheter displacement by avoiding patient transfer to the CT simulation room.

Patient and methods: An 83-year-old patient with 2D HDR-BTE for tracheal recurrence of previously resected lung adenocarcinoma was analyzed and compared with four simulated 3D plans based on catheter position relative to the tumor volume, while keeping the active length and prescribed dose constant.

Results: The favorable oblique scenario achieved the best PTV coverage (D90: 9.05 Gy; V100: 100%), although with highest V150 (96.47%) and homogeneity index (IH: 5.14). The unfavorable oblique and posterior positions significantly reduced coverage (V100: 51.4% and 61.29%, respectively). The esophagus was the most sensitive organ, showing the highest doses in the posterior orientation of the catheter. The contralateral lung and heart received low doses; while the aorta showed higher doses in the favorable oblique scenario due to the location of the PTV.

Conclusions: Catheter orientation in HDR-BTE has a significant impact on PTV coverage and the dose delivered to critical organs. Despite the trend toward 3D planning, there is no direct clinical evidence comparing the two techniques.

In orthopedic surgery, the most performed manipulation is bone drilling. One significant problem related to this manipulation is the overheating which causes thermal osteonecrosis. By reports the drill speed is the main factor responsible for heat generation and contributes up to 78% to temperature rise during bone drilling. Therefore, the aim of this work is to develop and implement drilling speed control approach to control the temperature rise in drilling area and prevent overheating of bone tissue. During drilling, a real-time drill bit tip temperature estimation is calculated based on data from a non-contact temperature sensor and information from the robot control system. This way, temperature feedback during drilling process is realized. Further, on the base of modified PI controller the target speed depending on the increase in the drill bit tip temperature is calculated. Applying the drill speed control approach, the experimental results showed a decrease in the maximum temperature on the drill bit tip during drilling by up to 13 °C was observed, and the temperature rise was limited to 65-70 °C, with values above 65 °C lasting less than 2 s. The novelty of this work is the realization of temperature feedback and drill speed control approach during drilling process. Applying them in a robotic bone drilling process, the temperature increase in the instrument-bone area was significantly limited, the critical temperature values at which thermal osteonecrosis occurs were not reached, and that substantially reduces the likelihood of thermal osteonecrosis during drilling.

The tumor mechanical microenvironment (TMME) is a critical regulator of cancer initiation, progression, metastasis, and therapeutic response. Beyond biochemical signaling, physical cues such as matrix stiffness, solid stress, interstitial fluid flow, and extracellular matrix (ECM) architecture regulate tumor-cell behavior, stromal remodeling, abnormal vascular proliferation and leakage, immune interactions, and drug resistance. However, conventional in vitro and in vivo models remain limited in recapitulating the dynamic, heterogeneous, and coupled mechanical features of native tumors. Tumor organoids, particularly patient-derived tumor organoids (PDOs), have emerged as physiologically relevant and experimentally tractable platforms for modeling tumor mechanics, as they preserve key aspects of tumor architecture, cellular heterogeneity, and genetic background while enabling precise experimental manipulation and high-throughput analysis. This review summarizes recent advances in modeling the TMME in tumor organoids. We first discuss major mechanical features of the tumor microenvironment (TME). We then discuss current strategies for recreating these features in organoid models, including stiffness-defined matrices, engineered ECMs, microfluidic platforms, mechanical actuation systems, multicellular co-culture models, and three-dimensional (3D) bioprinting. We also highlight their applications in mechanistic studies, disease modeling, and drug testing. Finally, we discuss current limitations including the overemphasis on stiffness-based design, limited reproducibility and standardization, and insufficient preservation of tumor spatial heterogeneity and mechanical gradients. We further outline future directions toward controllable, standardized, and patient-specific organoid platforms through advances in engineered matrices, microfluidics, automation, and computational analysis. By shifting from single-parameter modeling to systems-level reconstruction of the TMME, tumor organoid models are becoming increasingly powerful platforms for mechanistic discovery and therapeutic evaluation.

Aims: Our study aimed to determine whether incorporating social determinants of health (SDOH) improves cross-sectional classification of prevalent diagnosed diabetes and to quantify the extent to which model performance is attributable to variables that may occur downstream of diabetes diagnosis.

Methods: We analyzed data from the 2023 Behavioral Risk Factor Surveillance System (BRFSS) as the development cohort and the 2024 BRFSS as an independent temporal validation cohort. Analyses were restricted to adults aged 35 years or older residing in states that administered the SDOH module. The outcome was self-reported diagnosed diabetes. Before model development, 30% of the 2023 sample was reserved as a test set. Imputation, encoding, feature processing, and hyperparameter tuning were performed within nested cross-validation. Histogram-based gradient boosting and penalized logistic regression were evaluated across six pre-specified nested predictor specifications. Final models were applied unchanged to the 2024 cohort without refitting, re-tuning, or threshold recalibration. Performance estimates incorporated BRFSS survey weights.

Results: The development cohort comprised 179,752 adults (weighted prevalence 16.97%) and the validation cohort 161,092 (18.07%). Discrimination ranged from 0.75 to 0.81 across algorithms, with gradient boosting and penalized logistic regression indistinguishable (0.811 versus 0.808). The full model achieved an area under the receiver operating characteristic curve (AUROC) of 0.811 (95% CI 0.801 - 0.822) and transported to the validation cohort with a calibration slope of 1.040. Adding nine SDOH items changed discrimination by 0.006 (95% CI 0.004 - 0.008), with maximum net benefit gain under 0.003; discrimination rose from 0.743 to 0.811 only when healthcare utilization and comorbidity measures were added. Several SDOH nonetheless showed robust adjusted associations, including food insecurity (OR 1.27 - 1.39) and supplemental nutrition assistance program receipt (OR 1.34, 95% CI 1.11 - 1.61). At a fixed threshold, sensitivity ranged from 0.62 to 0.89 across age groups.

Conclusions: SDOH were independently associated with prevalent diagnosed diabetes but provided little incremental value beyond demographic, behavioral, and healthcare access measures, a finding that was consistent across consecutive survey cycles. Most of the observed discrimination was attributable to healthcare utilization and comorbidity variables that may plausibly reflect consequences of an established diagnosis rather than characteristics preceding disease recognition.

Early detection and intervention can prevent the onset and progression of type 2 diabetes mellitus (T2DM); however, achieving early diagnosis and accurate prediction remains challenging. Metabolomics, a potent diagnostic tool in systems biology, makes it possible to systematically identify important biomarkers linked to type 2 diabetes, which provides vital proof for risk assessment and early diagnosis. This review summarizes research advances in metabolomics for T2DM prediction and early detection since 2010 by incorporating both the reported prospective and cross-sectional metabolic evidence, with a focus on putative biomarkers and their metabolic characteristics identified across diverse biological samples. Furthermore, it highlights the unique advantages of metabolomics in T2DM early warning, aiming to offer novel insights for future research on personalized prevention and early diagnostic strategies.

In this study, we designed a novel 'metformin-coated nanoselenium nanocomposite' (Met+SeNP) to leverage the synergistic potential of both agents delivered via a single nanoplatform, aiming to restore metabolic and hormonal homeostasis in a letrozole-induced PCOS rat model. Met+SeNP was synthesized via a redox reaction of sodium selenite and ascorbic acid in the presence of metformin, creating a stable metformin-functionalized selenium nanocomposite. The particles were characterized using UV-Vis spectroscopy, SEM, and EDX. Female Sprague-Dawley rats were divided into five groups: Healthy, PCOS (letrozole-induced), Metformin (300 mg/kg), SeNP (0.4 mg/kg), and Met+SeNP (nanocomposite dose, SeNP 0.4 mg/kg + Metformin 300 mg/kg). The nanocomposite treatment most effectively minimized weight gain (39.36% vs. PCOS controls), normalized HOMA-IR, and restored circulating LH, estrogen, and testosterone levels. Histopathological evaluation demonstrated a marked reduction in cystic follicles and recovery of corpus luteum formation following Met+SeNP therapy. Immunohistochemical analysis further revealed that Met+SeNP robustly reversed PCOS-induced suppression of INR, IRS-1, and IRS-2 expression in both liver and skeletal muscle tissues. In addition, the nanocomposite significantly improved serum ALT, AST, and ALP levels while maintaining normal urea and creatinine concentrations, supporting hepatic protection and systemic safety. The metformin-functionalized SeNP nanocomposite represents a promising potent therapeutic strategy for PCOS-associated metabolic dysfunction, outperforming monotherapies in restoring insulin signaling, endocrine balance, and tissue integrity.

Background: Based on previous studies showing that frailty is associated with postoperative adverse events in older patients undergoing various surgical procedures, older patients with frailty may be more vulnerable to POCD. This study was designed to evaluate the effect of frailty on postoperative cognitive dysfunction (POCD) in aged rats undergoing general anaesthesia.

Methods: Male Sprague-Dawley rats aged 18 months were allocated to Control and Frailty groups according to hind limb immobilisation using aluminium splints. Before and after general anaesthesia, Y-maze test for cognitive function and frailty status were evaluated. Frailty, including muscle atrophy, assessed by quadriceps weight, was further evaluated by measuring glutathione peroxidase 4 (GPX4) and threonine.

Results: Twenty rats were enrolled and evenly allocated between the two groups, with no dropouts. There was no significant difference in the alternation ratio in the Y maze test between the groups before general anaesthesia; however, a significant difference was observed two days after general anaesthesia (65% ± 37% in the Control group vs 29% ± 28% in the Frailty group, p = 0.01). Body weight was similar between the groups throughout the study. By contrast, quadriceps weight was significantly lower in the Frailty group [2.4 (2.3-2.6) g vs 2.0 (1.7-2.3) g, p = 0.0001]. GPX4 and threonine levels in the quadriceps were also significantly lower in the Frailty group.

Conclusion: Frailty was significantly associated with POCD. Prevention of frailty may be important for reducing the risk of POCD.

Evidence suggests that the degree of insulin resistance in pregnancy (IRiP) seems to affect pregnancy outcomes regardless of the presence of gestational diabetes. A physiological moderate increase in IRiP is a protective factor for fetal development, but excessive enhancement can lead to maternal metabolic disorders and placental dysfunction, increasing the risk of gestational diabetes and adverse pregnancy outcomes, as well as having adverse effects on the long-term health of the offspring. This review briefly explores the key factors influencing IRiP, including pregnancy-specific and non-pregnancy-specific factors. It also discusses the assessment methods for insulin resistance that can be implemented during pregnancy and the increased probabilities of adverse effects on both the mother and the offspring, such as preeclampsia or eclampsia, neonatal hypoglycemia, and the risk of obesity and metabolic diseases in the offspring in the future. Finally, the intervention strategies were briefly described, such as in terms of diet, exercise, and medication, etc. This provides a basis and insights for the management and research of IRiP.

Background: Gastroesophageal reflux disease (GERD) is a common gastrointestinal condition associated with significantly impaired quality of life. While tea consumption has been associated with various health benefits, its relationship with GERD remains controversial. The aim of this study was to evaluate the relationship between the prevalence of GERD and tea consumption, including the type, drinking frequency and daily intake of tea, in a large Taiwanese cohort.

Methods: The type of tea was categorized as fully fermented, semi-fermented, and non-fermented; frequency and daily intake were recorded. Standardized self-reported questionnaires were used to record GERD status. Multivariable logistic regression was used to examine the association between tea consumption and GERD.

Results: Of the 27,119 participants, 4706 (17.4%) had GERD and 22,413 did not. A significant association was found between habitual tea consumption and a low prevalence of GERD (odds ratio [OR], 0.843; 95% confidence interval [CI], 0.779 - 0.911; p < 0.001) compared to non-drinkers. However, this association was only identified for semi- and non-fermented teas (OR, 0.832; 95% CI, 0.765 - 0.905; p < 0.001), but not fully fermented tea. Daily consumption of 1-2 cups (350-700 mL) (OR, 0.881 and 0.765, respectively) was significantly associated with a low prevalence of GERD, however drinking more than 3 cups per day was not significantly associated with GERD prevalence. Furthermore, drinking tea every day (OR, 0.847) was significantly associated with a low prevalence of GERD, while only drinking tea weekly or monthly was not.

Conclusion: The consumption of semi-fermented and non-fermented tea was associated with a low prevalence of GERD, but the association depended on the frequency and quantity of consumption. Further studies are needed to investigate the biological mechanisms of different types of tea and establish interventional strategies for those at high risk of GERD.