Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

OBJECTIVE:Elevated blood pressure increases the risk of cardiovascular diseases.Isometric exercise training has been shown to significantly reduce resting blood pressure,but the factors influencing its effectiveness remain unclear,and specific application guidelines are yet to be established.This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis,explore its moderating factors,and provide evidence-based recommendations based on its dose-response relationship.METHODS:Following the PRISMA guidelines,a systematic search was conducted in PubMed,Embase,Cochrane Library,Scopus,and Web of Science databases using keywords"Isometric exercise training,""Systolic blood pressure,"and"Diastolic blood pressure,"covering literature up to September 2024.Randomized controlled trials involving isometric exercise training and resting blood pressure were included.Three independent researchers performed literature screening and data extraction,assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework.Main effect pooling,publication bias assessment,subgroup,and regression analysis were conducted using R software(version 4.3.4).RESULTS:A total of 28 articles(comprising 32 randomized controlled trials)involving 977 participants were included.(1)Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure(MD=-8.01,95％CI=-9.22 to-6.80,P＜0.01,I2=18.20％,low evidence grade)and diastolic blood pressure(MD=-3.46,95％CI=-4.64 to-2.28,P＜0.01,I2=0％,moderate evidence grade)compared to no exercise.(2)Subgroup analysis results revealed significant influences of gender,health status,exercise modality,frequency,intensity,duration,sets per session,rest duration,and baseline blood pressure on the main effects for both systolic(P＜0.01)and diastolic blood pressure(P＜0.05).(3)Regression analysis results did not show any significant influencing factors,but body mass index(β=-4.11,P=0.091)showed a significant negative trend on the main effect for systolic blood pressure.(4)No significant publication bias was observed in the meta-analysis results(P＞0.05).CONCLUSION:(1)Isometric exercise training significantly lowers systolic(low evidence grade)and diastolic(moderate evidence grade)blood pressure with clinically meaningful thresholds.(2)Participant characteristics(gender,health status,baseline blood pressure,and body mass index)and isometric exercise training protocols(modality,frequency,intensity,duration,cycle,sets per session,and rest duration)influence its antihypertensive effects.(3)The article recommends the optimal blood pressure management prescription:three sessions per week,with four sets per session,each set lasting 2 minutes with a 2-minute rest,at an intensity of 95％HRpeak using isometric wall squat exercises;the intervention period can be adjusted around a 6-week node.Future high-quality research is urgently needed to further validate and support these conclusions.

OBJECTIVE:Elevated blood pressure increases the risk of cardiovascular diseases.Isometric exercise training has been shown to significantly reduce resting blood pressure,but the factors influencing its effectiveness remain unclear,and specific application guidelines are yet to be established.This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis,explore its moderating factors,and provide evidence-based recommendations based on its dose-response relationship.METHODS:Following the PRISMA guidelines,a systematic search was conducted in PubMed,Embase,Cochrane Library,Scopus,and Web of Science databases using keywords"Isometric exercise training,""Systolic blood pressure,"and"Diastolic blood pressure,"covering literature up to September 2024.Randomized controlled trials involving isometric exercise training and resting blood pressure were included.Three independent researchers performed literature screening and data extraction,assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework.Main effect pooling,publication bias assessment,subgroup,and regression analysis were conducted using R software(version 4.3.4).RESULTS:A total of 28 articles(comprising 32 randomized controlled trials)involving 977 participants were included.(1)Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure(MD=-8.01,95％CI=-9.22 to-6.80,P＜0.01,I2=18.20％,low evidence grade)and diastolic blood pressure(MD=-3.46,95％CI=-4.64 to-2.28,P＜0.01,I2=0％,moderate evidence grade)compared to no exercise.(2)Subgroup analysis results revealed significant influences of gender,health status,exercise modality,frequency,intensity,duration,sets per session,rest duration,and baseline blood pressure on the main effects for both systolic(P＜0.01)and diastolic blood pressure(P＜0.05).(3)Regression analysis results did not show any significant influencing factors,but body mass index(β=-4.11,P=0.091)showed a significant negative trend on the main effect for systolic blood pressure.(4)No significant publication bias was observed in the meta-analysis results(P＞0.05).CONCLUSION:(1)Isometric exercise training significantly lowers systolic(low evidence grade)and diastolic(moderate evidence grade)blood pressure with clinically meaningful thresholds.(2)Participant characteristics(gender,health status,baseline blood pressure,and body mass index)and isometric exercise training protocols(modality,frequency,intensity,duration,cycle,sets per session,and rest duration)influence its antihypertensive effects.(3)The article recommends the optimal blood pressure management prescription:three sessions per week,with four sets per session,each set lasting 2 minutes with a 2-minute rest,at an intensity of 95％HRpeak using isometric wall squat exercises;the intervention period can be adjusted around a 6-week node.Future high-quality research is urgently needed to further validate and support these conclusions.

Purpose: In this study, the neural communication patterns between hypothalamic structures and cortical areas in girls diagnosed with central precocious puberty (CPP) were explored. Endocrine profiles were incorporated to clarify the pathophysiological interactions between cerebral networks and hormonal regulation. The hypothalamus was designated as the key focus area for connectivity analysis. Methods: Fifty-seven girls (37 CPP, 20 non-CPP) were recruited from the Pediatric Development Clinic at the Second Affiliated Hospital of Anhui Medical University. The collected data included demographic information, gonadotropin-releasing hormone stimulation tests, and magnetic resonance imaging scans. Hypothalamic functional connectivity (FC) was analyzed using predefined region of interest coordinates, and correlations between hormone levels and FC values were assessed. Results: Compared to the non-CPP group, the CPP group exhibited elevated baseline follicle-stimulating hormone (FSH), baseline luteinizing hormone (LH), peak FSH, peak LH, and peak LH/FSH ratios. Patients with CPP exhibited enhanced neural synchronization linking the right lateral hypothalamic effector zone to the right superior frontal gyrus (displaying a borderline significant correlation with peak LH concentrations), concurrent with diminished functional coupling of the right lateral hypothalamic efferent to the right fusiform/supramarginal gyri. The left lateral hypothalamic projections demonstrated amplified connectivity with the right cuneus. No FC differences were observed in the medial hypothalamus. Conclusion Abnormal lateral hypothalamus FC patterns were identified in CPP girls and were particularly linked to peak LH levels. The findings offer novel insights into the neuroendocrine mechanisms underlying CPP.

ObjectiveTo systematically quantify the multidimensional effect of virtual reality-based exergaming (VREG) on health outcomes among individuals with cognitive impairment under the framework of the International Classification of Functioning, Disability and Health (ICF). MethodsMeta-analysis was conducted in accordance with the PRISMA statement. PubMed, Cochrane Library, Embase, Scopus, Web of Science, CNKI, Wanfang Data and VIP were researched for randomized controlled trials (RCTs) investigating VREG for cognitive impairment, with the search deadline set on February 1, 2026. The Cochrane Risk of Bias 2.0 tool was adopted to evaluate the methodological quality of included studies. A three-level meta-analytic model was implemented with R 4.4.2. The GRADE framework was further used to rate the certainty of pooled evidence. ResultsA total of 22 RCTs were included. VREG might improve global cognitive function (SMD = 0.69, 95%CI 0.11 to 1.28, P = 0.022), memory (SMD = 0.47, 95%CI 0.07 to 0.87, P = 0.023), attention (SMD = 0.62, 95%CI 0.23 to 1.01, P = 0.004), executive function (SMD = 0.42, 95%CI 0.09 to 0.75, P = 0.013), balance (SMD = 0.54, 95%CI 0.07 to 1.00, P = 0.027), muscle strength (SMD = 0.63, 95%CI 0.37 to 0.88, P = 0.001), mobility (SMD = 0.29, 95%CI 0.04 to 0.54, P = 0.024) and quality of life (SMD = 0.29, 95%CI 0.03 to 0.56, P = 0.029). No significant effect was observed for depressive symptoms, comprehensive physical fitness and fall risk (all P > 0.05). Subgroup and meta-regression analyses indicated that session duration < 45 minutes produced the largest improvement in attention (SMD = 0.95, 95%CI 0.55 to 1.34, P < 0.001); intervention cycles of twelve to 24 weeks were optimal for mobility (SMD = 0.85, 95%CI 0.44 to 1.25, P < 0.001); age negatively correlated to balance improvement (β = -0.11, 95%CI -0.20 to -0.02, P = 0.020), suggesting less intervention benefits among older participants. ConclusionVREG is an effective non-pharmacological intervention to improve multidimensional physical and mental health in people with cognitive impairment. Protocols featuring short single sessions with long-term duration should be prioritized.

Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

Subtype classification of age-related macular degeneration (AMD) based on optical coherence tomography (OCT) images serves as an effective auxiliary tool for clinicians in diagnosing disease progression and formulating treatment plans. To improve the classification accuracy of AMD subtypes, this study proposes a keypoint-based, attention-enhanced residual network (KPA-ResNet). The proposed architecture adopts a 50-layer residual network (ResNet-50) as the backbone, preceded by a keypoint localization module based on heatmap regression to outline critical lesion regions. A two-dimensional relative self-attention mechanism is incorporated into convolutional layers to enhance the representation of key lesion areas. Furthermore, the network depth is appropriately increased and an improved residual module, ConvNeXt, is introduced to enable comprehensive extraction of high-dimensional features and enrich the detail of lesion boundary contours, ultimately achieving higher classification accuracy of AMD subtypes. Experimental results demonstrate that KPA-ResNet achieves significant improvements in overall classification accuracy compared with conventional convolutional neural networks. Specifically, for the wet AMD subtypes, the classification accuracies for inactive choroidal neovascularization (CNV) and active CNV reach 92.8% and 95.2%, respectively, representing substantial improvement over ResNet-50. These findings validate the superior performance of KPA-ResNet in AMD subtype classification tasks. This work provides a high-accuracy, generalizable network architecture for OCT-based AMD subtype classification and offers new insights into integrating attention mechanisms with convolutional neural networks in ophthalmic image analysis.
Tomography, Optical Coherence/methods* ; Humans ; Macular Degeneration/diagnostic imaging* ; Neural Networks, Computer

Objective To analyze the influencing factors of poor incision healing in postoperative patients with breast cancer.Methods The clinical data of 150 patients with breast cancer diagnosed by the Department of Nail Milk surgery of the Fifth affiliated Hospital of Xinjiang Medical University from January 2016 to December 2023 were retrospectively analyzed.According to the postoperative wound healing,the patients were divided into two groups:good healing group(n=94)and poor healing group(n=56).The general data,operation-related data and clinicopathological characteristics of the two groups were collected for univariate analysis,and the single-factor indexes with statistical significance were analyzed by multivariate Logistic analysis to screen the risk factors of poor incision healing after operation.The statistically significant indexes of regression analysis were analyzed by receiver operating characteristic(ROC)curve to further explore its predictive value in poor incision healing after breast cancer operation.Results The data of the two groups were compared and analyzed.Multivariate Logistic regression analysis showed that BMI,diabetes,age,axillary lymph node dissection and hemoglobin were independent risk factors for poor incision healing(P＜0.05).ROC curve analysis of independent risk factors showed that when the age was more than 57.5,the area under the curve(AUC)was 0.635,the sensitivity was 55.4％,the specificity was 68.1％,and the critical value was 57.5.When BMI＞24.9 kg/m2,the area under the curve(AUC)was 0.735,the sensitivity was 87.5％,the specificity was 61.7％,and the critical value was 24.9(P＜0.001).When hemoglobin＜101.5 g/L,the area under the curve(AUC)was 0.829,the sensitivity was 57.1％,the specificity was 94.7％,and the critical value was 101.5 g/L(P＜0.001).Conclusion BMI,diabetes,hemoglobin,age and axillary lymph node dissection are independent risk factors for poor wound healing after breast cancer operation.When BMI＞24.9 kg/m2,age＞57.5 years old and hemoglobin＜101.5 g/L,it can predict the occurrence of poor incision healing in patients with breast cancer.

Objective To analyze the influencing factors of poor incision healing in postoperative patients with breast cancer.Methods The clinical data of 150 patients with breast cancer diagnosed by the Department of Nail Milk surgery of the Fifth affiliated Hospital of Xinjiang Medical University from January 2016 to December 2023 were retrospectively analyzed.According to the postoperative wound healing,the patients were divided into two groups:good healing group(n=94)and poor healing group(n=56).The general data,operation-related data and clinicopathological characteristics of the two groups were collected for univariate analysis,and the single-factor indexes with statistical significance were analyzed by multivariate Logistic analysis to screen the risk factors of poor incision healing after operation.The statistically significant indexes of regression analysis were analyzed by receiver operating characteristic(ROC)curve to further explore its predictive value in poor incision healing after breast cancer operation.Results The data of the two groups were compared and analyzed.Multivariate Logistic regression analysis showed that BMI,diabetes,age,axillary lymph node dissection and hemoglobin were independent risk factors for poor incision healing(P＜0.05).ROC curve analysis of independent risk factors showed that when the age was more than 57.5,the area under the curve(AUC)was 0.635,the sensitivity was 55.4％,the specificity was 68.1％,and the critical value was 57.5.When BMI＞24.9 kg/m2,the area under the curve(AUC)was 0.735,the sensitivity was 87.5％,the specificity was 61.7％,and the critical value was 24.9(P＜0.001).When hemoglobin＜101.5 g/L,the area under the curve(AUC)was 0.829,the sensitivity was 57.1％,the specificity was 94.7％,and the critical value was 101.5 g/L(P＜0.001).Conclusion BMI,diabetes,hemoglobin,age and axillary lymph node dissection are independent risk factors for poor wound healing after breast cancer operation.When BMI＞24.9 kg/m2,age＞57.5 years old and hemoglobin＜101.5 g/L,it can predict the occurrence of poor incision healing in patients with breast cancer.