Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

Objective:To explore the predictive value of preoperative peripheral hematological parameters combined with clinicopathological features for cervical lymph node metastasis（CLNM） in patients with laryngeal squamous cell carcinoma（LSCC）, and to construct and validate a nomogram model for CLNM. Methods:A retrospective analysis was conducted on the clinical data of 264 LSCC patients who underwent surgical treatment and were pathologically confirmed, collected from the Second Affiliated Hospital of Shandong First Medical University and Taian 88 Hospital. Specifically, 161 patients from one hospital were allocated to the training cohort, while 103 patients from another hospital constituted the validation cohort. Based on postoperative pathological results, patients were categorized into CLNM-positive and CLNM-negative groups. The general clinical data, clinicopathological features, and hematological parameters of the two groups were analyzed and compared. A preoperative predictive model for CLNM was developed using logistic regression analysis, followed by validation and sensitivity analysis to evaluate the robustness of the model's predictive performance. Results:The results showed that there were significant differences in tumor location, tumor size, tumor differentiation, neutrophil percentage, lymphocyte count, lymphocyte percentage, c-reactive protein（CRP）, fibrinogen, neutrophil-to-lymphocyte ratio（NLR）, platelet-to-lymphocyte ratio（PLR）, systemic immune-inflammation index（SII）, systemic inflammation response index（SIRI）, and prognostic inflammatory index（PIV） between the CLNM-positive and CLNM-negative groups（P<0.05）. Lasso regression identified tumor location, clinical T stage, tumor size, tumor differentiation degree, red blood cell distribution width（RDW） -coefficient of variation（RDW-CV）, CRP, FIB, D-dimer, NLR, and lymphocyte-to-monocyte ratio（LMR） were the most predictive parameters. Multivariate logistic regression revealed that tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients（P<0.05）. A nomogram was constructed based on these five factors. The model demonstrated excellent discrimination, with a C-index of 0.837（95%CI 0.766-0.908） in the training cohort and 0.809（95%CI 0.698-0.920） in the validation cohort. Calibration curves and DCA curves in both cohorts confirmed the clinical utility of the model. Sensitivity analysis further supported the robustness of the results, showing good discrimination and calibration across different age and BMI subgroups. Conclusion:Tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients. The nomogram based on these variables exhibits strong discrimination, calibration, and clinical applicability, and may serve as a valuable tool for preoperative risk assessment and individualized treatment planning.
Humans ; Nomograms ; Laryngeal Neoplasms/blood* ; Retrospective Studies ; Lymphatic Metastasis ; Carcinoma, Squamous Cell/blood* ; Lymph Nodes/pathology* ; Male ; Female ; Middle Aged ; Neck ; C-Reactive Protein ; Aged ; Logistic Models ; Neutrophils ; Prognosis

Objective: To analyze the association of 24 h activity behaviors and physical health of primary school students, so as to provide a reference for promoting the physical health of children and adolescents. Methods: From May to June, 2023, by stratified random sampling method, 583 primary school students aged 7-12 were selected from Tianjin for physical health examination. ActiGraph GT3X+ was used to measure their 24 h activity behaviors for 7 d, and their mental health and 24 h activity behaviors were analyzed by gender and grade. LASSO regression was applied for assessing the impact of 24 h activity on their health. Results: The compliance rate of seated forward bending (93.12%) were higher in boys than girls (91.86%), and the differences were statistically significant ( χ 2=4.53, P <0.05). Sleep time ( β =0.06), light intensity physical activity (LPA) time ( β =0.11), and moderate to vigorous physical activity (MVPA) time ( β =0.14) were positively correlated with physical fitness, whereas sedentary behavior (SB) time ( β =-0.08) were negatively correlated with physical fitness, and MVPA time had a positive effect on physical health of children and adolescents, followed by LPA time; while sleep time also had a positive effect , and SB time had a negative effect ( P <0.05). Conclusions Primary school students are generally faced with low physical activity level and high SB time, and MVPA and LPA have a significant impact on physical health. Therefore, it is crucial to develop personalized and differentiated physical activity promotion policies and interventions for primary school students with different classmates and gender.

ObjectiveTo investigate risk factors for postoperative sore throat in patients with double-lumen endotracheal intubation. MethodsThe data used in this post-hoc analysis were prospectively collected from a randomized， controlled trial. Age from 18 to 65 years old， ASAI-Ⅲ patients undergoing general anesthesia with a double-lumen endotracheal tube were enrolled. The perioperative data collected retrospectively were as follows： gender， age， smoking history， endotracheal tube diameter， duration of endotracheal tube， dose of Sufentanil， use of Flurbiprofen Axetil， cough after extubation， etc..Dynamometer was applied to assess extubation force. According to occurrence of postoperative sore throat， patients were divided into two groups： those who experienced sore throats and those who did not. Comparative analysis and multivariate logistic regression analysis were performed to screen the risk factors. ROC curve was used for predicting the predictive value of risk factors. ResultsAmong the 163 patients ， 74 （45.4%） had postoperative sore throat vs 89 （54.6%） not had. Multivariate logistic regression showed female ［OR95%CI=3.83（1.73， 8.50）， P=0.000 1］ and extubation force ［OR95%CI=1.78（1.45， 2.17）， P＜0.001］ were independent risk factors for postoperative sore throat. AUC value showed the extubation force was 0.773［95%CI（0.701， 0.846）， P＜0.001］. Youden index was 0.447， and the cut-off valve of extubation force was 13N. ConclusionFemale and extubation force were risk factors for sore throat in patients with double lumen endotracheal intubation.

Objective:To investigate the mechanism of extract of ginkgo biloba (EGB) on mitochondrial autophagy in breast cancer cells MCF-7.Methods:Breast cancer MCF-7 cells were divided into four groups. EGB with mass concentrations of 40, 80, 120 mg/L was used to incubate breast cancer MCF-7 cells for 24 h or 48 h, as a low concentration group of EGB, a medium concentration group of EGB, and a high concentration group of EGB. Breast cancer MCF-7 cells without intervention were taken as control group. Cell proliferation was measured using MTT assay; Flow cytometry was used to detect cell apoptosis; Immunofluorescence assay was used to determine the contents of prostacyclin (P62), microtubule-associated protein light chain 3Ⅱ (LC3Ⅱ), and caspase-3; The levels of multidrug resistance-associated protein 1 (MRP1), multidrug resistance gene 1 (MDR1) and breast cancer resistance protein (BCRP) were identified by PCR; Western blotting was used to detect the expression of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK), p-ERK, and p-MAPK proteins in cells.Results:The results of MTT assay for cell proliferation showed that cell proliferation at 24 h in control group, EGB low, medium and high concentration groups were 0.95±0.14, 0.65±0.09, 0.51±0.07, 0.37±0.04, respectively, with a statistically significant difference ( F=43.13, P<0.001), cell proliferation at 48 h were 1.32±0.19, 0.54±0.08, 0.32±0.05, 0.15±0.02, respectively, with a statistically significant difference ( F=141.30, P<0.001). Compared with 24 h, cell proliferation was decreased in EGB low, medium and high concentration groups at 48 h (all P<0.05). Pairwise comparison showed that EGB treatment significantly decreased MCF-7 cell viability and cell proliferation was decreased in turn at 24 and 48 h in control group, low, medium, high EGB groups (all P<0.05). Flow cytometry analysis revealed that the apoptosis rates of MCF-7 cells in control group, EGB low, medium and high concentration groups were 2.12%±0.23%, 9.28%±0.45%, 15.17%±1.28% and 22.21%±2.32%, respectively, with a statistically significant difference ( F=128.80, P<0.001). Pairwise comparison showed that the apoptosis rate of control group, EGB low, medium and high concentration groups were increased in turn (all P<0.05). The results of immunofluorescence assay showed that the protein relative expression levels of P62 protein in MCF-7 cells of control group, EGB low, medium and high concentration groups were 3.34±0.52, 2.85±0.47, 2.02±0.18 and 1.08±0.21, respectively, with a statistically significant difference ( F=41.55, P<0.001). LC3Ⅱ protein relative expression levels were 0.24±0.05, 1.02±0.14, 1.47±0.26, 1.95±0.21, respectively, with a statistically significant difference ( F=94.82, P<0.001). The relative expression levels of caspase-3 protein were 0.25±0.03, 0.68±0.21, 1.12±0.17 and 1.65±0.23, respectively, with a statistically significant difference ( F=68.09, P<0.001). Pairwise comparison showed that LC3Ⅱ and caspase-3 protein expression levels were increased in turn in control group, EGB low, medium and high concentration groups, while P62 protein expression levels were decreased in turn (all P<0.05). The PCR experiment results showed that the MRP1 mRNA level of MCF-7 cells in control group, EGB low, medium and high concentration groups were 1.06±0.14, 0.83±0.18, 0.71±0.11, 0.52±0.08, respectively, with a statistically significant difference ( F=17.41, P<0.001). The mRNA levels of MDR1 were 1.14±0.17, 0.75±0.13, 0.60±0.09, 0.48±0.06, respectively, with a statistically significant difference ( F=34.40, P<0.001). BCRP mRNA levels were 1.09±0.11, 0.88±0.13, 0.69±0.07, 0.57±0.05, respectively, with a statistically significant difference ( F=34.13, P<0.001). Pairwise comparison showed that the levels of MRP1, MDR1 and BCRP mRNA were decreased in turn in control group, EGB low, medium and high concentration groups (all P<0.05). The results of Western blotting showed that the expression of ERK in MCF-7 cells in control group, EGB low, medium and high concentration groups were 2.54±0.38, 1.89±0.25, 1.55±0.21, 1.12±0.16, respectively, with a statistically significant difference ( F=31.18, P<0.001). MAPK expression were 2.47±0.34, 1.96±0.29, 1.63±0.27, 1.20±0.24, respectively, with a statistically significant difference ( F=20.90, P<0.001). p-ERK expression were 2.03±0.29, 1.74±0.21, 1.45±0.11, 1.18±0.24, respectively, with a statistically significant difference ( F=16.31, P<0.001). p-MAPK expression were 2.26±0.47, 1.90±0.41, 1.61±0.33, 1.35±0.16, respectively, with a statistically significant difference ( F=7.01, P=0.002). Pairwise comparison showed that the expressions of ERK, MAPK, p-ERK and p-MAPK in control group, EGB low, medium and high concentration groups were decreased in turn (all P<0.05) . Conclusion:EGB can inhibit the proliferation of breast cancer MCF-7 cells, promote the apoptosis of MCF-7 cells, decrease the expression of P62 protein, increase the expression of LC3Ⅱ and caspase-3 protein, induce mitochondrial autophagy.

Objectives:to analyze the efficacy of percutaneous coronary intervention(PCI)for complex left main(LM)lesions combined with chronic total occlusion(CTO)of the right coronary artery. Methods:Ninety patients with complex left main lesions hospitalized in Hunan Provincial People's Hospital from January 2019 to December 2022 were consecutively included.According to the coronary angiographic vascular lesions,patients were divided into complex left main lesions combined with right coronary artery CTO(observation group,n=30)and complex left main lesions without right coronary artery CTO(control group,n=60).The baseline clinical data,intraoperative conditions,angiographic results,and postoperative follow-up results of the patients were analyzed and compared between the two groups. Results:Fifty-eight(64.4%)out of the 90 patients were male.There was no statistically significant difference between the two groups in terms of baseline clinical data(all P>0.05),left main lesion condition(P=1.000),left main calcification condition(P=0.249),and preoperative TIMI flow grading(P=1.000).In the comparison between observation group and the control group,intraoperative occurrence of no-reflow(3.3%vs.5.0%,P=1.000),hypotension(10.0%vs.8.3%,P=1.000),pericardial effusion(3.3%vs.0%,P=0.333),the percentage of intravascular ultrasound(IVUS)use(86.7%vs.90.0%,P=0.635),and the use of circulatory assist device(P=0.699),and the proportion of intraoperative coronary spinning(26.7%vs.21.7%,P=0.597)were all similar between the two groups.The median follow-up time was 14.50(11.83,15.85)months,and the differences in the incidence of major adverse cardiovascular events(MACE)such as recurrent angina,acute myocardial infarction,rebleeding,readmission for heart failure,and cardiac death(31.0%vs.32.1%,P=1.000)were not statistically significant between the observation group and the control group. Conclusions:PCI revascularization may be a viable approach for elderly patients with complex LM lesions with multiple underlying disease,and combined right coronary artery CTO,intolerance and reluctance to CABG.

Objective:To analyze the effect of short collection time of digital positron emission tomography/computed tomography(PET/CT)on image quality,detected lesion and semi-quantitative parameters,and explore the feasibility of clinical application of short collection time of step by step collection mode.Methods:The digital PET/CT images of 63 subjects were retrospectively analyzed.All of them adopted PET/CT scan to conduct PET/CT examination for whole body according to the collection mode of step by step type and list-mode scan protocol.The reconstruction was implemented according to the different collection time of each bed,and they were divided into 90 s/bed group,60 s/bed group,45 s/bed group and 30 s/bed group.The 90s/bed was used as control group to compare the detection rate of the small lesion of each group("the shorter diameter of smaller radioactive concentration lesion of PET image and the lesion of CT image"was less than 0.5 cm)in PET images,and to measure the objective data of original tumor lesion,and to compare the maximum value(SUVmax),peak value(SUVpeak)and mean value(SUVmean)of standardized uptake value(SUV),noise(SD),metabolic tumor volume(MTV)and total lesion glycolysis(TLG).The signal-noise ratio(SNR),contrast noise ratio(CNR)and target-to-background ratio(TBR)were calculated and compared.The one-way analysis of variance(ANOVA test)was adopted to conduct comparison of inter groups for the image data of 4 groups.The Bland-Altman consistency test was adopted to analyze semi-quantitative parameters of intra group.The Likert 5 scores method was adopted to conduct subject evaluation for the quality of images.The Kappa test was adopted to evaluate the consistency of images.Results:The subjective scores of image quality of 4 groups were all≥3 points,and the consistency of image quality among the four groups was very well(Kappa=0.8,P<0.05).Compared with 90s/bed group,the detection rate of small lesions of other three groups were 100%.The differences of SUVmax,SUVpeak,SUVmean,SD,TLG and MTV of semi-quantitative indicators among 4 groups were not significant(P>0.05).There were significant differences in CNR,SNR and TBR of objective indicators of 18F-FDG PET image quality among 4 groups(F=31.741,34.199,12.021,P<0.001),respectively.There were no significant differences in noise between 60s/bed group and 90s/bed group,and between 45s/bed group and 90s/bed group,respectively.The noise of image of 30s/bed group appeared increase.The Bland-Altman consistent analysis of intra group basically was within 95%confidence interval(CI).Conclusions:The short collection time of step by step mode of digital PET/CT has very good clinical application.

Objective:To investigate the protective effect of lycopene on rats with cognitive dysfunction (CD) induced by sevoflurane anesthesia through endoplasmic reticulum stress (ERS).Methods:A rat CD model was established using sevoflurane anesthesia induction. SD rats were randomly divided into a sham operation group, model group, low-, high-dose (5 and 10 mg/kg) lycopene groups, and a lycopene + tunicamycin (10 mg/kg + 100 μg/kg) group, with 12 rats in each group. 5 and 10 mg of lycopene was dissolved in 1 ml of sodium carboxymethylcellulose to form a suspension, and 10 μg of clindamycin was dissolved in 1 and 2 ml of 0.1% dimethyl sulfoxide. Rats in the low-, high-dose lycopene groups were gavaged with 1 ml of lycopene suspension, respectively, and the rats in the lycopene + tunicamycin group were gavaged with 1 ml of lycopene suspension and received 1 ml intraperitoneal injection of clindamycin. The sham operation group and the model group received an equal amount of saline by gavage or intraperitoneal injection, respectively. The low-, high-dose lycopene groups received an equal amount of saline by intraperitoneal injection, both 1 time/d for 6 weeks. The Morris water maze test was used to determine the cognitive function of rats. HE staining was used to observe the morphological changes of rat hippocampal tissue. TUNEL staining was used to observe the apoptosis of neurons in rat hippocampal tissue. The ELISA method was used to detect the levels of brain-derived neurotrophic factor (BDNF) and S100 calcifying protein β (S100β) in hippocampal tissue. Western Blot was used to detect the levels of apoptosis-related proteins in rat hippocampal tissues, including the levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) with ERS marker glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and cysteinyl aspartate specific proteinase-12 (Caspase-12).Results:Compared with the model group, the escape latency, neuronal apoptosis rate, S100β level, GRP78, CHOP, Caspase-12, and Bax expression were decreased in the low-, high-dose lycopene groups on days 3, 4, and 5 (all P < 0.05), and the number of crossing platforms, BDNF level, and Bcl-2 expression were increased (all P < 0.05). With the increase of lycopene dose, the escape latency, neuronal apoptosis rate, S100β level, GRP78, CHOP, Caspase-12, and Bax expression were decreased in the high-dose lycopene group compared with the low-dose lycopene group on days 3, 4, and 5 (all P < 0.05), and the number of crossing platforms, BDNF level, and Bcl-2 expression were increased (all P < 0.05). Compared with the high-dose lycopene group, the escape latency, neuronal apoptosis rate, S100β level, GRP78, CHOP, Caspase-12, and Bax expression were increased in the lycopene + tunicamycin group on days 3, 4, and 5 (all P < 0.05), and the number of crossing platforms, BDNF level, and Bcl-2 expression were decreased (all P < 0.05). Hippocampal tissue neuronal loss and the inflammatory infiltration were both reduced in CD rats after lycopene intervention. The ERS activator tunicamycin attenuated the protective effect of lycopene on sevoflurane-induced CD rats. Conclusions:Lycopene may play a protective role against CD in rats anesthetized with sevoflurane by inhibiting ERS.