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 To analyze the relationship between 15 immunophenotypes of peripheral blood T cells and age and gender in healthy adults in the Dalian area. Methods A total of 277 healthy adults admitted to the physical examination center of the Second Affiliated Hospital of Dalian Medical University from October 2022 to June 2023 were selected as the research subjects,including 154 males and 123 females. They were divided into three groups according to age:young group(18～44 years,n=103),middle-aged group(45～60 years,n=114) and old age group(>60 years,n=60). Flow cytometry was used to determine immunophenotypes of T cells,including the absolute count and proportion of na?ve cells (N),central memory (CM),effector memory (EM),terminal effector memory (TEM),activation (HLA-DR+) and senescence (CD28-) CD4+and CD8+T cells,and the differences of them among age and gender were analyzed. Spearman correlation analysis was also used to evaluate the correlation between age and immunophenotypes of T cells. Results Compared with the young group,the absolute count and proportion of CD8+TEM,CD4+HLA-DR+,CD8+HLA-DR+and CD8+CD28-T lymphoaytes cells were increased in the middle-aged group and old age group (Z=2.009～6.607),while the absolute count and proportion of CD8+N T cells were decreased in the middle-aged group (Z=5.574～7.999) and old age group,and the differences were statistically significant (all P<0.05),respectively. Compared with the female group,the absolute count and proportion of CD8+CM,CD8+HLA-DR+and CD8+CD28-T cells were increased in the female group (Z=2.945～6.131),while the absolute count and proportion of CD3+,CD4+and CD8+N T cells were decreased in the male group (Z=2.075～4.225),and the differences were statistically significant(all P<0.05),respectively. Spearman correlation analysis showed that age was positively correlated with the absolute count and proportion of CD4+CM,CD4+HLA-DR+,CD4+CD28-,CD8+TEM,CD8+HLA-DR+and CD8+CD28-T lymphocytes cells (r=0.125～0.479,all P<0.05),while negatively correlated the absolute count and proportion of CD4+N and CD8+N T lymphocytes cells (r=-0.538～-0.148,all P<0.05). Conclusion The 15 immunophenotypes of peripheral blood T lymphocytes cells in healthy adults from Dalian area are affected by age and gender,so it is necessary to establish a suitable local reference interval to provide a more accurate reference for immune function assessment.

Objective To investigate the predictive value of the diagnostic model constructed by CT radiomics combined with clin-ical and CT features for the P53 mutation status in lung adenocarcinoma.Methods The data of 177 patients with lung adenocarcinoma were retrospectively collected,including 75 cases of P53 mutant type and 102 cases of wild type.They were randomly divided into training cohort(n=123)and validation cohort(n=54)in a 7∶3 ratio.The region of interest(ROI)was delineated using MaZda software,and the features were screened using the least absolute shrinkage and selection operator(LASSO).The predictive model was devel-oped based on logistic regression analysis,and its diagnostic efficacy was evaluated.Results There were statistically significant differences in lesion diameter,maximum solid component diameter,lobulation sign,and lymph node metastasis between the two groups in the training cohort(P＜0.05).The area under the curve(AUC)in the training cohort of the radiomics score model,clinical imaging feature model,and combined model were 0.778,0.759,and 0.817,and the AUC in the validation cohort were 0.668,0.722,and 0.783,respectively.The clinical decision curve suggested that the combined model demonstrated superior clinical net benefits.Conclusion The combined model constructed by CT radiomics,lesion diameter,and lymph node metastasis has better predictive value for the P53 mutation status in lung adenocarcinoma.

Objective:To investigate the feasibility and safety of laparoscopic purse- string suture clamps combined with multi-functional seal caps for esophagojejunal Roux-en-Y anastomosis during total laparoscopic radical total gastrectomy (TLTG).Methods:This was a retrospective descriptive study of 42 patients with primary gastric malignancies who underwent TLTG at the First Affiliated Hospital of Nanjing Medical University that utilized laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis between May, 2024 and January, 2025. The cohort included 33 males and 9 females, with a mean age of (67.7 ±9.5) years and a mean body mass index (BMI) of (23.9±2.9) kg/m 2. The American Society of Anesthesiologists (ASA) physical status classifications were I - II in 40 patients and III in 2 patients, and all patients were definitively diagnosed preoperatively via gastroscopy, dual-energy CT, and/or MRI. Tumor locations included the gastroesophageal junction (GEJ) in 28 cases (Siewert type II - III), the upper third of the stomach in 12 cases, and the middle third in 2 cases. The median distance of esophageal invasion was 1.3 cm, though in 10 cases this was ≥2 cm. Preoperative TNM staging was I-II in 17 patients and III in 25 patients. Surgical outcomes including operative time, anastomosis time, intraoperative blood loss, pathological results, and postoperative recovery were retrospectively analyzed. Results:All 42 operations were successful. The mean operative time was(212.5±26.4) minutes, and the average time from multi-functional seal cap placement to completion of the esophagojejunal anastomosis was (54.2±7.5) minutes. Mean intraoperative blood loss was (79.9±21.3) ml. Postoperative pathology confirmed R0 resection in all specimens, with a mean proximal esophageal margin distance of (2.1±1.6) cm. Furthermore, (51.9±15.1) lymph nodes on average were harvested from each patient; the mean time to oral intake was (149.5±41.4) hours; and the mean hospital stay was (11.3±5.4) days. Postoperative complications occurred in 6 patients: anastomotic leakage ( n=2), residual intra-abdominal infection ( n=1), pulmonary infection ( n=3), and Clavien-Dindo grade III or higher complications occurred in 2 patients. No recurrence, mortality, or anastomosis-related complications were observed within a median follow-up of 5.8 months (range 3.5-11.2). Conclusion:We find the application of the laparoscopic purse-string suture clamps and multi-functional seal caps for esophagojejunal anastomosis in TLTG to be safe and feasible, with satisfactory short-term outcomes.

AIM: To investigate the correlation between fundus blood flow parameters and carotid artery ultrasound blood flow parameters in patients with hypertensive retinopathy(HRP).METHODS: A total of 50 patients(22 left eyes and 28 right eyes)with HRP admitted to our hospital from June 2021 to June 2023 were retrospectively included as the experimental group, and 50 healthy physical examination subjects(22 left eyes and 28 right eyes)during the same period were included as the healthy group. Pearson correlation was used to analyze the correlation between fundus blood flow parameters and carotid artery ultrasound blood flow parameters.RESULTS: The AUC values of fundus blood flow parameters and carotid artery ultrasound blood flow parameters and their combined diagnosis of HRP were 0.853, 0.844 and 0.935, respectively. Pearson correlation analysis showed that carotid systolic peak blood flow velocity was negatively correlated with foveal avascular zone(FAZ)area, FAZ circumference and non-circularity index, and positively correlated with macular vascular density(all P<0.05). The end-diastolic blood flow velocity was positively correlated with FAZ area and macular vascular density(all P<0.05). The internal carotid artery resistance index was positively correlated with FAZ area(P<0.05).CONCLUSION: The combination of fundus blood flow parameters and carotid artery ultrasound blood flow parameters in the diagnosis of HRP has good application value in the diagnosis of HRP.

Osteoporosis is a common senile bone metabolism disease， clinically characterized by decreased bone mass， destruction of bone microstructure， increased bone fragility， and easy fracture. It tends to occur in the elderly and postmenopausal women， seriously threatening the quality of life and physical and mental health of the elderly. At present， the treatment of osteoporosis is mainly based on oral western medicines， such as calcium， Vitamin D， and bisphosphonates. Still， there are drawbacks such as a long medication cycle and many adverse reactions. In recent years， due to the advantages of multi-component， multi-pathway， and multi-target， some traditional Chinese medicines and effective ingredients can regulate the osteogenic and osteoclastic differentiation process in both directions and are widely used in the prevention and treatment of osteoporosis. Hippophae rhamnoides is a commonly used herbal medicine， and its fruits are rich in flavonoids， polyphenols， fatty acids， vitamins， and trace elements， which have been proven to have a good anti-osteoporosis effect. Isorhamnetin is the main effective ingredient of Hippophae rhamnoides fruits， which has many pharmacological effects such as anti-inflammation， anti-oxidative stress， anti-aging， and anti-tumor. Studies have shown that isorhamnetin can participate in the regulation of bone metabolism and has a good anti-osteoporosis effect. However， the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis have not been systematically summarized. Therefore， this paper reviewed the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis by referring to relevant literature to provide more basis for the development and application of isorhamnetin.

Osteoporosis is a systemic metabolic disease characterized by decreased bone mass, leading to an increased risk of fractures. Although osteoporosis in children and adolescents is rare, its incidence in younger populations is showing an increasingly notable trend. The diagnostic criteria for osteoporosis in children and adolescents include a bone mineral density(BMD) Z-score of≤-2.0 accompanied by a significant fracture history, defined as two or more long bone fractures before the age of 10, three or more long bone fractures before the age of 19, or the presence of low-energy vertebral compression fractures even in the absence of low BMD. The genetic causes and underlying mechanisms of pediatric osteoporosis remain largely unknown, requiring further research to elucidate the molecular pathways involved. Such advances could help reduce the disease′s impact on growth and development and improve the quality of life in affected children and adolescents.

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

Objective To analyze the relationship between 15 immunophenotypes of peripheral blood T cells and age and gender in healthy adults in the Dalian area. Methods A total of 277 healthy adults admitted to the physical examination center of the Second Affiliated Hospital of Dalian Medical University from October 2022 to June 2023 were selected as the research subjects,including 154 males and 123 females. They were divided into three groups according to age:young group(18～44 years,n=103),middle-aged group(45～60 years,n=114) and old age group(>60 years,n=60). Flow cytometry was used to determine immunophenotypes of T cells,including the absolute count and proportion of na?ve cells (N),central memory (CM),effector memory (EM),terminal effector memory (TEM),activation (HLA-DR+) and senescence (CD28-) CD4+and CD8+T cells,and the differences of them among age and gender were analyzed. Spearman correlation analysis was also used to evaluate the correlation between age and immunophenotypes of T cells. Results Compared with the young group,the absolute count and proportion of CD8+TEM,CD4+HLA-DR+,CD8+HLA-DR+and CD8+CD28-T lymphoaytes cells were increased in the middle-aged group and old age group (Z=2.009～6.607),while the absolute count and proportion of CD8+N T cells were decreased in the middle-aged group (Z=5.574～7.999) and old age group,and the differences were statistically significant (all P<0.05),respectively. Compared with the female group,the absolute count and proportion of CD8+CM,CD8+HLA-DR+and CD8+CD28-T cells were increased in the female group (Z=2.945～6.131),while the absolute count and proportion of CD3+,CD4+and CD8+N T cells were decreased in the male group (Z=2.075～4.225),and the differences were statistically significant(all P<0.05),respectively. Spearman correlation analysis showed that age was positively correlated with the absolute count and proportion of CD4+CM,CD4+HLA-DR+,CD4+CD28-,CD8+TEM,CD8+HLA-DR+and CD8+CD28-T lymphocytes cells (r=0.125～0.479,all P<0.05),while negatively correlated the absolute count and proportion of CD4+N and CD8+N T lymphocytes cells (r=-0.538～-0.148,all P<0.05). Conclusion The 15 immunophenotypes of peripheral blood T lymphocytes cells in healthy adults from Dalian area are affected by age and gender,so it is necessary to establish a suitable local reference interval to provide a more accurate reference for immune function assessment.