To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents.

To investigate body composition and associated factors in adolescents undergoing long-term regular sports training.

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

Objective To explore the clinical application value of CT radiomics in predicting the grade of liver cancer and the prognosis after hepatectomy.Methods A retrospective selection was conducted on 385 liver cancer patients who underwent preoperative CT scans,and they were divided into training group(265 cases)and testing group(120 cases).The CT radiomics features were extracted and logistic regression was used to construct radiomics markers.A retrospective analysis was performed on 60 patients with liver cancer who underwent hepatectomy and regular follow-up.Results The area under the curve(AUC)of the radiomics signature in the train-ing group was 0.889.The AUC in the testing group was 0.941.For predicting prognosis after hepatectomy,the radiomics features with filter parameter of Filter 1.0 achieved optimal performance,with Dif.Scale1.2 being a good independent predictor of overall survival(OS).Conclusion CT radiomics has certain application value in predicting the grade of liver cancer and the prognosis after hepatectomy.

Objective To investigate the necessity of further surgery for patients with locally advanced esophageal squamous cell carcinoma following treatment with the programmed cell death-1 (PD-1) inhibitor combined with chemotherapy, and to assess its impact on survival. Methods Patients with stage ⅡA to ⅢB esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at our hospital from January 2020 to June 2022 were selected for this study. Based on whether they underwent surgery after receiving PD-1 inhibitor combined with chemotherapy, patients were divided into a surgery group and a non-surgery group. We compared the general clinical data, side effects, clinical complete response rates, progression-free survival (PFS), and overall survival (OS) between the two groups. Results A total of 58 patients were included in the study, comprising 45 males and 13 females, with an average age of (65.5±6.9) years. There were no statistical differences in general clinical data or adverse reactions between the two groups. Univariate analysis revealed that the objective response rate and surgery were significantly associated with PFS (P<0.05). Binary logistic regression analysis showed that surgery was the only independent risk factor for PFS (P=0.003). Kaplan-Meier survival analysis showed that the PFS and OS in the surgery group were significantly higher than those in the non-surgery group (HR=0.13, 95%CI 0.036 to 0.520, P＜0.001; HR=0.17, 95%CI 0.045 to 0.680, P=0.004). Conclusion After treatment with the PD-1 inhibitor combined with chemotherapy, patients with locally advanced esophageal squamous cell carcinoma still require surgical intervention to achieve improved PFS and OS.

Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.

Objective To evaluate cardiac involvement in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) using echocardiography combined with electrocardiography. Methods A retrospective analysis was performed on the detailed medical records of AAV patients treated in Jining First People’s Hospital between January 2020 and December 2024. Eighty patients were enrolled in the AAV group, and the risk of heart disease was compared between the AAV group and a control group with 80 subjects matched for age, sex, and cardiovascular disease risk factors. Results Electrocardiographic abnormalities were observed in 78.75% of patients in the AAV group, while significant electrocardiographic abnormalities only occurred in symptomatic patients in the control group. There were no differences in left atrial enlargement or interventricular septal thickening between the AAV group and the control group. The overall left ventricular systolic function in the AAV group was lower than that in the control group (8.75% vs. 0). The incidence of reduced diastolic function in the AAV group was significantly higher than that in the control group (37.5% vs. 15%). The incidence rates of tricuspid regurgitation, mitral regurgitation, aortic regurgitation, and pericardial effusion in the AAV group were significantly higher than those in the control group. Pericardial thickening, aortic stenosis, pulmonary hypertension, and rare periaortic granulomas were found in the AAV group, but not in the control group. Conclusion Echocardiography and electrocardiography are important examination methods for evaluating cardiac involvement in AAV. These methods have key roles in disease screening, diagnosis and treatment, follow-up, and prognosis judgment.

OBJECTIVE: To investigate the predictive value of oxygenation index (PaO₂/FiO₂) at intensive care unit (ICU) admission on 30-day mortality in patients with sepsis. METHODS: A retrospective study was conducted. Patients with sepsis who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to October 2023 were enrolled. The demographic information, comorbidities, sites of infection, vital signs and laboratory test indicators at the time of admission to the ICU, disease severity scores within 24 hours of admission to the ICU, treatment process and prognostic indicators were collected. According to the PaO₂/FiO₂ at ICU admission, patients were divided into Q1 group (PaO₂/FiO₂ of 4.1-16.4 cmHg, 1 cmHg ≈ 1.33 kPa), Q2 group (PaO₂/FiO₂ of 16.5-22.6 cmHg), Q3 group (PaO₂/FiO₂ of 22.7-32.9 cmHg), and Q4 group (PaO₂/FiO₂ of 33.0-94.8 cmHg). Differences in the indicators across the four groups were compared. Multifactorial Cox regression analysis was used to assess the relationship between PaO₂/FiO₂ and 30-day mortality of patients with sepsis. The predictive value of PaO₂/FiO₂, sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) on 30-day prognosis of patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve). RESULTS: A total of 1 711 patients with sepsis were enrolled, including 428 patients in Q1 group, 424 patients in Q2 group, 425 patients in Q3 group, and 434 patients in Q4 group. 622 patients died at 30-day, the overall 30-day mortality was 36.35%. There were statistically significant differences in age, body mass index (BMI), history of smoking, history of alcohol consumption, admission heart rate, respiratory rate, APACHE II score, SOFA score, Glasgow coma score (GCS), site of infection, Combined chronic obstructive pulmonary disease (COPD), blood lactic acid (Lac), prothrombin time (PT), albumin (Alb), total bilirubin (TBil), pH, proportion of mechanical ventilation, duration of mechanical ventilation, proportion of vasoactive medication used, and maximal concentration, length of ICU stay, hospital stay, incidence of acute kidney injury, in-hospital mortality, 30-day mortality among the four groups. Multivariate Cox regression analysis showed that after adjusting for confounding factors, for every 1 cmHg increase in PaO₂/FiO₂ at ICU admission, the 30-day mortality risk decreased by 2% [hazard ratio (HR) = 0.98, 95% confidence interval (95%CI) was 0.98-0.99, P < 0.001]. The 30-day mortality risk in the Q4 group was reduced compared with the Q1 group by 41% (HR = 0.59, 95%CI was 0.46-0.76, P < 0.001). The fitted curve showed that a curvilinear relationship between PaO₂/FiO₂ and 30-day mortality after adjustment for confounders. In the inflection point analysis, for every 1 cmHg increase in PaO₂/FiO₂ at PaO₂/FiO₂ < 28.55 cmHg, the risk of 30-day death in sepsis patients was reduced by 5% (HR = 0.95, 95%CI was 0.94-0.97, P < 0.001); when PaO₂/FiO₂ ≥ 28.55 cmHg, there was no statistically significant association between PaO2/FiO2 and the increase in the risk of 30-day death in sepsis (HR = 1.01, 95%CI was 0.99-1.02, P = 0.512). ROC curve analysis showed that the area under the curve (AUC) for the prediction of 30-day mortality by admission PaO₂/FiO₂ in ICU sepsis patients was 0.650, which was lower than the predictive ability of the SOFA score (AUC = 0.698) and APACHE II score (AUC = 0.723). CONCLUSION In patients with sepsis, PaO₂/FiO₂ at ICU admission is strongly associated with 30-day mortality risk, alerting healthcare professionals to pay attention to patients with low PaO₂/FiO₂ for timely interventions.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Retrospective Studies ; Prognosis ; Hospital Mortality ; Oxygen ; Male ; Predictive Value of Tests ; Female ; Middle Aged ; Aged

BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400 μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400 μmol/L cobalt nanoparticles and 25 μmol/L deferiprone),the deferiprone group(25 μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P＜0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factor α,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factor α,interleukin-1β,and interleukin-6)significantly decreased(P＜0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P＜0.05),while deferiprone inhibited this effect(P＜0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.

BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400 μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400 μmol/L cobalt nanoparticles and 25 μmol/L deferiprone),the deferiprone group(25 μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P＜0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factor α,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factor α,interleukin-1β,and interleukin-6)significantly decreased(P＜0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P＜0.05),while deferiprone inhibited this effect(P＜0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.