AIM:To explore the mechanism of doxorubicin/copper(DOX/Cu)complex induced copper death in hepatocellular carcinoma cells.METHODS:Human hepatocellular carcinoma cell line Huh7 was treated with DOX/Cu 0,2.5,4,7.5,10 and 12.5 μmol/L.The cell viability was detected by CCK-8 method.The cell proliferation level was observed by laser microscopy and proliferation kit.The cell invasion ability was determined by cell scratch assay.The flow cytometry was used to de-tect intracellular reactive oxygen species(ROS)and copper ion levels.And the western blot was used to detect intracellular iron-sulfur cluster proteins expression levels.RESULTS:With the increase of DOX/Cu concentration,cell viability,cell prolifera-tion and invasion ability decreased gradually.The copper ion chelating agent(TTM)can significantly restore the effects of DOX/Cu on cell viability.After DOX/Cu treatment,intracellular copper ion and ROS levels related to coproptosis were significantly increased,accompanied by the loss of iron-sulfur cluster proteins.CONCLUSION:DOX/Cu can inhibit hepatocellular carcinoma cells through cuproptosis.

AIM:To explore the mechanism of doxorubicin/copper(DOX/Cu)complex induced copper death in hepatocellular carcinoma cells.METHODS:Human hepatocellular carcinoma cell line Huh7 was treated with DOX/Cu 0,2.5,4,7.5,10 and 12.5 μmol/L.The cell viability was detected by CCK-8 method.The cell proliferation level was observed by laser microscopy and proliferation kit.The cell invasion ability was determined by cell scratch assay.The flow cytometry was used to de-tect intracellular reactive oxygen species(ROS)and copper ion levels.And the western blot was used to detect intracellular iron-sulfur cluster proteins expression levels.RESULTS:With the increase of DOX/Cu concentration,cell viability,cell prolifera-tion and invasion ability decreased gradually.The copper ion chelating agent(TTM)can significantly restore the effects of DOX/Cu on cell viability.After DOX/Cu treatment,intracellular copper ion and ROS levels related to coproptosis were significantly increased,accompanied by the loss of iron-sulfur cluster proteins.CONCLUSION:DOX/Cu can inhibit hepatocellular carcinoma cells through cuproptosis.

Background Ozone (O₃) pollution has gradually become a primary problem of air pollution in recent years. Conducting epidemiological studies on the correlation between O₃ concentration variation and risk of cardiovascular and cerebrovascular diseases can provide reference data for O₃ risk assessment and related policy making. Objective To quantitatively evaluate the effects of O₃ exposure on mortalities of cardiovascular and cerebrovascular diseases among residents in Minhang District, Shanghai. Methods Data of mortalities of cardiovascular and cerebrovascular diseases, air pollutants, and meteorological factors in Minhang District of Shanghai from January 1, 2016 to December 31, 2021 were collected. Associations between O₃ concentration and the mortalities due to total cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke were analyzed by generalized additive models with a quasi Poisson distribution with different lag patterns, such as current day effect (lag0), single-day lag effects (lag1-lag3), and cumulative lag effects (lag01-lag03). The subgroup analyses of age, sex, and season were conducted. Furthermore, temperature was divided into low, middle, and high levels based on the 25th percentile (P₂₅) and the 75th percentile (P₇₅) to perform hierarchical analyses. Increased excess risks (ER) of death from target diseases caused by a 10 µg·m⁻³ increase in daily maximum 8 h concentration of O₃ (O₃-8 h) and their 95% confidence intervals (CI) were used to indicate the effects of O₃. Results The associations between O₃ and the risks of death from cardiovascular and cerebrovascular diseases were statistically significant at lag2, lag3, lag02, and lag03 (P<0.05), with the greatest effect size observed at lag03. The ER values of death from cardiovascular and cerebrovascular diseases in general population, male residents, and people aged 65 years and older, from coronary heart disease in male residents, and from stroke in general population increased by 1.02% (95%CI: 0.36%, 1.69%), 1.40% (95%CI: 0.47%, 2.34%), 0.87% (95%CI: 0.19%, 1.55%), 1.96% (95%CI: 0.49%, 3.44%), and 1.02% (95%CI: 0.07%, 1.98%) for a 10 µg·m⁻³ increase in O₃-8 h concentration at lag03, respectively. During the warm season (from April 1 to September 30), the ER values of death from cardiovascular and cerebrovascular diseases and coronary heart disease per 10 µg·m⁻³ increase in O₃ were 1.18% (95%CI: 0.33%, 3.33%) and 2.69% (95%CI: 0.39%, 5.03%), while the O₃ effect was only statistically significant on cardiovascular and cerebrovascular diseases during the cold season (from October 1 to March 31 next year). At the middle and high temperature levels, the ER values of death from cardiovascular and cerebrovascular diseases increased by 1.63% (95%CI: 0.32%, 2.96%) and 1.14% (95%CI: 0.17%, 2.12%) respectively. The two-pollutant models showed similar results after including other pollutants (carbon monoxide, nitrogen dioxide, sulfur dioxide, fine particulate matter, or inhalable particulate matter). Conclusion Ambient O₃ pollution may increase the mortality risks of cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke in Minhang District of Shanghai.

Objective:To investigate the role and mechanisms of SOCS3 protein in IL-10 inhibiting the expression of inflam-matory factors in Chlamydia-infected cells.Methods:The activation of STAT3 protein were examined in Chlamydia-infected cells by Western blot,and the activation of p38 and ERK1/2 were also examined in infected cells treated with socs3 siRNA.The expression of socs3 gene was examined in Chlamydia-infected cells treated with IL-10 or Stattic by RT-PCR.IL-6 and IL-12 were measured in infect-ed cells treated with socs3 siRNA using ELISA kits.Results:Socs3 expression was up-regulated by IL-10 through activation of STAT3 protein.IL-6 and IL-12 induced by Chlamydia were down-regulated by IL-10 through induction of socs3.The activation of p38 and ERK1/2 signalling pathways were inhibited by SOCS3.Conclusion:IL-10 inhibits the production of pro-inflammatory cytokines through induction of SOCS3 and inhibition p38 and ERK1/2 signalling pathways.

Objective:To investigate the efficacy and safety of dual antiplatelet therapy (DAPT) in patients with minor ischemic stroke (MIS) and tiny unruptured intracranial aneurysm (UIA).Methods:Patients with MIS and tiny UIA admitted to the Department of Neurology, Weifang People's Hospital from October 1, 2022 to February 29, 2024 were included retrospectively. MIS was defined as baseline National Institutes of Health Stroke Scale (NIHSS) score ≤3. Tiny UIA was defined as UIA with a diameter of ≤3 mm. According to the antiplatelet therapy regimen, the patients were divided into an aspirin alone group and an aspirin+clopidogrel DAPT group. The main outcome measure was the clinical outcome at 90 days after onset. The modified Rankin Scale (mRS) score 0-1 was defined as a good outcome and >1 was defined as a poor outcome. Secondary outcome measures included aneurysm rupture, cerebral hemorrhage, and recurrence of cerebral ischemic events. Multivariate logistic regression analysis was used to identify the independent influencing factors for poor outcome. Results:A total of 183 patients with MIS and tiny UIA were included, including 108 males (59.0%), median aged 68 years (interquartile range, 61-73 years). All the UIAs were solitary. The mRS score of all patients before onset was 0; 152 patients (83.1%) had good outcome at 90 days after onset, 31 (16.9%) had poor outcome, and no UIA occurred rupture bleeding. Of the 94 patients (51.4%) who received aspirin monotherapy, 14 patients (14.9%) experienced recurrent cerebral ischemic events during follow-up, and 73 (77.7%) had good outcome. Of the 89 patients (48.6%) who received DAPT, 5 (5.6%) experienced recurrent ischemic events during follow-up, and 79 (88.8%) had good outcome. The recurrence rate of cerebral ischemic events in the aspirin group was significantly higher than that in the DAPT group ( χ2=4.227, P=0.040), while the good outcome rate was significantly lower than that in the DAPT group ( χ2=4.006, P=0.045). Multivariate logistic regression analysis showed that baseline NIHSS score was an independent risk factor for poor outcome (odds ratio 4.597, 95% confidence interval 1.864-11.339; P=0.001), while DAPT was an independent protective factor for good outcome (odds ratio 0.265, 95% confidence interval 0.079-0.892; P=0.032). Conclusion:Compared with aspirin monotherapy, the short-term combination of aspirin and clopidogrel in patients with MIS and tiny UIA may improve the outcome, reduces the recurrence of cerebral ischemic events, and has good safety.

Objective To explore the application and effect of a pulmonary rehabilitation exercise program in patients with moderate to severe COPD based on the Information-Motivation-Behavior Skill(IMB)Model.Methods The convenience sampling method was adopted to select patients with moderate to severe COPD admitted to the department of respiratory and critical care medicine in a tertiary A hospital in Yantai City from October 2021 to February 2022.They were randomly divided into an intervention group(32 cases)and a control group(31 cases).The intervention group was treated with the pulmonary rehabilitation exercise program based on the IMB model on the basis of routine nursing,while the control group was treated with routine nursing.The degree of dyspnea,exercise endurance,quality of life,pulmonary rehabilitation exercise compliance,self-management ability and lung function were compared between the 2 groups before and 6 months after the intervention.Results After intervention,the degree of dyspnea,exercise endurance,quality of life,pulmonary rehabilitation exercise compliance and self-management ability were significantly different between the 2 groups(P＜0.05).There was no statistically significant difference in lung function between the 2 groups after intervention(P＞0.05).Conclusion The pulmonary rehabilitation program based on IMB model can effectively alleviate the symptoms of dyspnea in patients with moderate to severe COPD,improve exercise endurance,improve pulmonary rehabilitation exercise compliance and self-management ability,and improve the patients'quality of life.

Objective:To study the correlation of bone metabolism biomarkers between newborn twins and their mothers during pregnancy.Methods:From January 1, 2018 to June 30, 2022, newborn twins with mild symptoms admitted to the neonatal department of our hospital were retrospectively reviewed. The clinical data of the twins and their mothers were collected, including bone metabolism biomarkers of the twins within 3 d after birth and their mothers within last month during pregnancy. The twins were assigned into different groups according to gestational age(GA), birth weight(BW), the relationship between BW and GA(appropriate for GA(AGA),small for GA(SGA) and large for GA(LGA), birth season, gender, and the mothers' age, ethnicity, pre-delivery body mass index (BMI), gestational BMI increase, number of births and chorionic properties. The correlations of bone metabolism biomarkers between the twins and their mothers were analyzed.Results:A total of 302 pairs of twins were included. The incidence of insufficient or deficient serum 25-(OH)D 3 was 97.4% among the mothers, and 87.7% among the twins. The levels of blood phosphorus ( r=0.262, P<0.001) and 25-(OH)D 3 ( r=0.239, P=0.002) in mothers were positively correlated with the twin with larger BW. No significant differences existed in 25-(OH)D 3 between genders, AGA,SGA and LGA, birth season, and mothers' age, ethnicity, pre-delivery BMI, gestational BMI increase and chorionic properties( P>0.05). 25-(OH)D 3 in the twins were positively correlated with BW and 25-(OH)D 3 of mothers before delivery ( P<0.05) and negatively correlated with number of births ( P<0.05). Conclusions:In most mothers and their newborn twins, 25-(OH)D 3 are insufficient or deficient. The levels of blood phosphorus and 25-(OH) D 3 are correlated between the newborns and their mothers. The lower the BW of the newborn, the more times the mother give birth and the lower the mother's pre-delivery 25-(OH)D 3 level, the lower the newborn's 25-(OH)D 3 level.

Objective:To design a lung nodule detection algorithm based on the improved YOLOv7 model.Methods:Firstly, in the PAFPN structure, a lightweight upsampling operator CARAFE is introduced to improve the lung nodule detection accuracy. Then an enhanced small-scale detection layer is added to enhance the detection performance for small-target lung nodules, while the number of trained parameters can be reduced and the model complexity can be lowered. An enhanced small-scale detection layer is added to the YOLOv5 model algorithm while comparing it with the original YOLOv5 model algorithm, the original YOLOv7 model algorithm, and the improved YOLOv7 model algorithm in terms of the total loss of the training set of the improvement points, while ensuring that the parameter indexes remain unchanged. The original YOLOv7 model algorithm and the improved YOLOv7 model algorithm are used to process the 2 test set images and compare them with other classical lung nodule detection algorithms Mask R-CNN, YOLOv3, YOLOv5s and YOLOv7.Results:Compared with the original YOLOv5 model algorithm, the improved YOLOv5 model algorithm with the addition of an enhanced small-scale detection layer has a 1.3% increase in precision, a 3.5% increase in recall, a 3.1% increase in mean average precision (mAP), a 25.3% decrease in parameters amount, and a decrease in the complexity of the network; whereas the improved YOLOv7 model algorithm has a 1.8% increase in mAP, a 28.3% decrease in parameters amount, and the model complexity decreased by 5 G. Adding the enhanced small-scale detection layer with replacement of the special diagnostic fusion network as a lightweight up-sampling operator CARAFE algorithm can minimize the total loss of the model during the training process. The original YOLOv7 model algorithm is more accurate but still has missed detections and false positives. When reasoning about image 1, the original YOLOv7 model has a missed detection. And when reasoning about image 2, the original YOLOv7 model has a false positive. The improved YOLOv7 model is well improved in both missed detection and false positives. Compared with the classical model algorithm, the precision, recall, and mAP of the improved YOLOv7 model algorithm were 91.7%, 89.1%, and 93.5%, respectively.Conclusions:The improved YOLOv7 model has stronger feature expression ability and uses fewer parameters, which can effectively improve the detection precision of lung nodules.

Ginsenoside Rb1, the effective constituent of ginseng, has been demonstrated to play favorable roles in improving the immunity system. However, there is little study on the osteogenesis and angiogenesis effect of Ginsenoside Rb1. Moreover, how to establish a delivery system of Ginsenoside Rb1 and its repairment ability in bone defect remains elusive. In this study, the role of Ginsenoside Rb1 in cell viability, proliferation, apoptosis, osteogenic genes expression, ALP activity of rat BMSCs were evaluated firstly. Then, micro-nano HAp granules combined with silk were prepared to establish a delivery system of Ginsenoside Rb1, and the osteogenic and angiogenic effect of Ginsenoside Rb1 loaded on micro-nano HAp/silk in rat calvarial defect models were assessed by sequential fluorescence labeling, and histology analysis, respectively. It revealed that Ginsenoside Rb1 could maintain cell viability, significantly increased ALP activity, osteogenic and angiogenic genes expression. Meanwhile, micro-nano HAp granules combined with silk were fabricated smoothly and were a delivery carrier for Ginsenoside Rb1. Significantly, Ginsenoside Rb1 loaded on micro-nano HAp/silk could facilitate osteogenesis and angiogenesis. All the outcomes hint that Ginsenoside Rb1 could reinforce the osteogenesis differentiation and angiogenesis factor's expression of BMSCs. Moreover, micro-nano HAp combined with silk could act as a carrier for Ginsenoside Rb1 to repair bone defect.
Alginates/pharmacology* ; Animals ; Bone Regeneration ; Cell Differentiation ; Durapatite/pharmacology* ; Ginsenosides ; Osteogenesis ; Rats ; Silk/pharmacology* ; Tissue Scaffolds

Objective:Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods:We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results:In the analysis,average levels of indoor PM with aerodynamic diameters＜2.5 μm(PM2.5)decreased significantly by 59.2％(from 59.6 to 24.3 μg/m3,P＜0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by-84.6％(95％confidence interval[CI]:-90.7 to-78.6),growth differentiation factor-15 by-48.1％(95％CI:-31.2 to-25.6),osteoprotegerin by-65.4％(95％CI:-56.5 to-18.7),interleukin-4 by-46.6％(95％CI:-62.3 to-31.0)and myeloperoxidase by-60.3％(95％CI:-83.7 to-3.0),respectively.Conclusion:Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable popu-lations at risks.