This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

BACKGROUND:As a temporary matrix for new bone growth,the porous scaffold plays a key role in the process of bone repair.The structural design of porous scaffolds is a research priority in the process of bone repair.OBJECTIVE:To summarize traditional bone scaffolds(regular,uniform scaffolds)and bionic scaffolds(irregular,inhomogeneous scaffolds)in the field of bone tissue engineering research.METHODS:A computerized search was performed in the databases of CNKI,VIP,WanFang,Web of Science,Science Direct,PubMed,and EI.Literature published from January 2008 to March 2024 was selected.The search terms in Chinese included"bone tissue engineering,bionic scaffolds,bone trabeculae,traditional scaffolds,bone repair,triple-period minimal surfaces."The search terms in English were"bone tissue engineering,bionic scaffolds,bone trabeculae,traditional scaffolds,bone repair,TPMS."Finally,81 articles were included for review.RESULTS AND CONCLUSION:The structural design of bone scaffolds is the key to achieve bone repair and bone regeneration,and scaffold technology in bone tissue engineering has made remarkable progress.Traditional regular porous scaffolds are widely used due to their simple manufacturing process and good mechanical properties.However,these scaffolds often lack biological activity and are difficult to mimic the complex microenvironment of natural bone tissue,limiting their ability to promote cell proliferation and bone regeneration.On the contrary,bionic scaffolds provide a more suitable physiological microenvironment by mimicking the structural features of natural bone tissues,which promotes the proliferation and differentiation of osteoblasts,as well as the formation of new bone,and provides a new way of thinking for the effective treatment of bone defects.Despite the great potential of bionic scaffolds in theory,they still face many challenges in practical applications.Factors such as the scaffold's biocompatibility,bioactivity,and its long-term stability still need to be further verified through clinical trials.

Objective To explore the application of artificial intelligence quantitative analysis in the prognostic assessment of patients with connective tissue disease-associated interstitial lung disease(CTD-ILD).Methods A total of 67 patients with CTD-ILD were retrospectively selected.All subjects underwent high-resolution computed tomography(HRCT)scanning and were categorized into three groups,namely mild,moderate and severe groups,based on the results of pulmonary function tests.The survival rates of patients in each group were compared using Kaplan-Meier curves and analysis of variance.The univariate analysis was employed to assess the rela-tionships between artificial intelligence parameters and patient prognosis.Significant results were then incorporated into a multifacto-rial Cox regression model to construct the most accurate predictive model.Results A significant difference in survival rate was observed among the three groups(P<0.05).Univariate analysis revealed that the volume and percentage of lung infection in deceased patients were significantly greater than those in surviving patients,while the lung volume in deceased patients was significantly smaller than that in surviving patients.The analysis showed left lung volume and the percentage of lesion components CT value≤-750 HU as risk factors for prognosis,and the combination of these two factors as the most effective predictive model.Conclusion The artificial intelligence analysis system for lung lesions provides a new systematic and quantitative method for the prognostic assessment of CTD-ILD patients,which can be used for the prognostic assessment and follow-up of CTD-ILD patients.

Objective To explore the application of artificial intelligence quantitative analysis in the prognostic assessment of patients with connective tissue disease-associated interstitial lung disease(CTD-ILD).Methods A total of 67 patients with CTD-ILD were retrospectively selected.All subjects underwent high-resolution computed tomography(HRCT)scanning and were categorized into three groups,namely mild,moderate and severe groups,based on the results of pulmonary function tests.The survival rates of patients in each group were compared using Kaplan-Meier curves and analysis of variance.The univariate analysis was employed to assess the rela-tionships between artificial intelligence parameters and patient prognosis.Significant results were then incorporated into a multifacto-rial Cox regression model to construct the most accurate predictive model.Results A significant difference in survival rate was observed among the three groups(P<0.05).Univariate analysis revealed that the volume and percentage of lung infection in deceased patients were significantly greater than those in surviving patients,while the lung volume in deceased patients was significantly smaller than that in surviving patients.The analysis showed left lung volume and the percentage of lesion components CT value≤-750 HU as risk factors for prognosis,and the combination of these two factors as the most effective predictive model.Conclusion The artificial intelligence analysis system for lung lesions provides a new systematic and quantitative method for the prognostic assessment of CTD-ILD patients,which can be used for the prognostic assessment and follow-up of CTD-ILD patients.

BACKGROUND:As a temporary matrix for new bone growth,the porous scaffold plays a key role in the process of bone repair.The structural design of porous scaffolds is a research priority in the process of bone repair.OBJECTIVE:To summarize traditional bone scaffolds(regular,uniform scaffolds)and bionic scaffolds(irregular,inhomogeneous scaffolds)in the field of bone tissue engineering research.METHODS:A computerized search was performed in the databases of CNKI,VIP,WanFang,Web of Science,Science Direct,PubMed,and EI.Literature published from January 2008 to March 2024 was selected.The search terms in Chinese included"bone tissue engineering,bionic scaffolds,bone trabeculae,traditional scaffolds,bone repair,triple-period minimal surfaces."The search terms in English were"bone tissue engineering,bionic scaffolds,bone trabeculae,traditional scaffolds,bone repair,TPMS."Finally,81 articles were included for review.RESULTS AND CONCLUSION:The structural design of bone scaffolds is the key to achieve bone repair and bone regeneration,and scaffold technology in bone tissue engineering has made remarkable progress.Traditional regular porous scaffolds are widely used due to their simple manufacturing process and good mechanical properties.However,these scaffolds often lack biological activity and are difficult to mimic the complex microenvironment of natural bone tissue,limiting their ability to promote cell proliferation and bone regeneration.On the contrary,bionic scaffolds provide a more suitable physiological microenvironment by mimicking the structural features of natural bone tissues,which promotes the proliferation and differentiation of osteoblasts,as well as the formation of new bone,and provides a new way of thinking for the effective treatment of bone defects.Despite the great potential of bionic scaffolds in theory,they still face many challenges in practical applications.Factors such as the scaffold's biocompatibility,bioactivity,and its long-term stability still need to be further verified through clinical trials.

Objective:To investigate the correlation between pen-holding posture, grip strength and myopia.Methods:A cross-sectional study was performed.A total of 496 school-aged children in grades 1-6, who underwent eye examinations at Shenzhen Eye Hospital from November 2021 to May 2022 were consecutively enrolled as subjects.The subjects' age, grade, sex, refractive error and age of school enrollment were recorded.Subjects' grip strength and pen-holding posture were obtained with an electronic grip strength meter and a tool pen, and subjects were divided into correct pen-holding posture group and incorrect pen-holding posture group according to their pen-holding posture.Propensity scores for sex, grade, age at school entry, and grip strength in the two groups were matched using the nearest neighbor matching method.Multifactorial binary logistic regression analysis was performed with binocular myopia, monocular myopia, and emmetropia as dependent variables and grip strength, grade, refractive error, and pen-holding posture as independent variables.The correlation between grip strength and spherical equivalent was examined by Spearman rank correlation analysis and partial correlation analysis.This study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Shenzhen Eye Hospital (No.2022KYPJ032).Results:After matching propensity scores, there were 101 cases and 197 cases in the correct pen-holding posture group and incorrect pen-holding posture group, respectively.There was no statistical significance in sex, grade, age at enrollment, and grip strength between the two groups (all at P>0.05).Multinomial logistic regression results showed that using emmetropia as a reference, higher grade (4 versus 1∶7.601[1.307-44.206]; 5 versus 1∶4.392[1.039-18.562]), presence of anisometropia (21.366[5.750-79.397]) were relative risk factors for monocular myopia (all at P<0.05), and higher grade (3 versus 1∶4.389[1.783-10.800]); 4 versus 1∶15.398[3.267-72.574]; 5 versus 1∶7.447[2.232-24.851]; 6 versus 1∶6.462[2.116-19.734]) were relative risk factors for binocular myopia (all at P<0.05).Taking monocular myopia as a reference, higher grade (6 versus 1∶4.582[1.193-17.589]), presence of anisometropia (0.141[0.069-0.289]), and irregular pen-holding posture (2.608[1.340-5.075]) were associated factors for binocular myopia (all at P<0.05).According to partial correlation analysis, the spherical equivalent of the right eye of children with incorrect pen-holding posture was negatively correlated with the grip strength ( rs=-0.141, P=0.047). Conclusions:There is an association between pen-holding posture and myopia in school-aged children.Children with greater grip strength and incorrect pen-holding posture may have higher degrees of right eye refractive error.

Recent studies have shown that the formation of the primary cilium is associated with a specific cellular organelle known as the midbody remnant(MBR),which is a point-like organelle formed by shedding of the midbody at the end of mitosis.MBRs move along the cell surface close to the center body and regulate it to form primary cilia at the top of the centriole.Primary cilia can act as an organelle to inhibit tumorigenesis,and it is lost in a variety of tumors.Studies have shown that the accumulation of MBRs in tumor cells affects ciliogenesis;in addition,both MBRs and primary cilia are degraded in tumor cells through the autophagy pathway,and MBRs can also transfer tumor signaling pathway factors to primary cilia affecting tumorigenesis.In this article,the basic structure and the formation process of MBR and primary cilia are reviewed and the mechanism of MBRs regulating ciliogenesis is elaborated.The significance of MBR-mediated ciliogenesis in tumorigenesis and its potential as a target for cancer treatment are discussed.

ObjectiveTo explore the mechanism of Huanglian Jiedutang in inhibiting the pyroptosis mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes and alleviating the acute liver injury （ALI） induced by lipopolysaccharide （LPS） in the mouse model of sepsis. MethodFifty-four male C57BL/6 mice were randomized into blank， model， low- （3.08 g·kg^-1）， medium- （6.15 g·kg^-1）， and high-dose （12.30 g·kg^-1） Huanglian Jiedutang， and positive control （dexamethasone） groups （n=9）. The mice were administrated with Huanglian Jiedutang at different doses by gavage for 7 days， and then LPS （15 mg·kg^-1） was injected intraperitoneally for the modeling of sepsis. In the positive control group， dexamethasone （0.05 g·kg^-1） was injected intraperitoneally 1.5 h after modeling， and the mouse sepsis score （MSS） was recorded 12 h after modeling. The mice were sacrificed for the collection of blood and liver tissue samples. The levels of alanine transaminase （ALT） and aspartate transaminase （AST） were measured by a biochemical analyzer. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， IL-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the pathological changes in the liver tissue. The content of NLRP3 was observed by the immunofluorescence assay. The expression of apoptosis-associated speck-like protein containing CARD （ASC） was detected by immunohistochemistry. The protein levels of NLRP3， ASC， Caspase-1， and gasdermin D （GSDMD） in the liver tissue were determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to determine the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18. ResultCompared with the blank group， the model group showed elevated levels of ALT and AST （P<0.01） and risen levels of inflammatory cytokines in the serum （P<0.01）. In addition， the modeling resulted in edema and necrosis in the liver， and up-regulated the protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.01） and the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the drug intervention groups showed reduced content of inflammatory cytokines （P<0.01）， alleviated pathological damage in the liver tissue， and down-regulated protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.05，P<0.01） and mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05，P<0.01） in the liver tissue. ConclusionHuanglian Jiedutang can inhibit pyroptosis and reduce inflammation by inhibiting the activation of NLRP3 inflammasomes， thus demonstrating a therapeutic effect on acute liver injury in the mouse model of sepsis induced by LPS.

Objective:To explore the correlations of brain network functional connectivity (FC) alterations with cerebrospinal fluid (CSF) pathological biomarkers in patients with Alzheimer's disease (AD).Methods:A total of 39 patients with cognitive impairment, admitted to Department of Neurology, Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2020 to December 2022 were recruited; 23 patients were with AD and 16 with non-AD. Clinical data were compared between the 2 groups. Resting-state functional MRI (rs-fMRI) data were collected, and FC differences between brain networks and FC differences within brain networks were compared by independent component analysis. Correlations of FC differences between brain networks and FC differences within brain networks with concentrations of β-amyloid protein 1-42 (Aβ 1-42) and Tau protein in CSF were analyzed. Results:Compared with the non-AD group, AD group had significantly lower Aβ 1-42 in CSF ( P<0.05). Compared with those in the non-AD group, FC alterations between the left frontoparietal network (lFPN) and anterior default mode network (aDMN) and between the visual network (VN) and posterior cingulate cortex (PCC), as well as FC alterations in lFPN, were significantly increased in AD group ( P<0.05). Compared with those in the non-AD group, FC alterations between lFPN and cerebellar network (CEN), and FC alterations in aDMN, sensorimotor network (SMN) and VN were significantly decreased in AD group ( P<0.05). In AD group, FC in SMN was positively correlated with total Tau and phosphorylated-Tau181 in CSF ( P<0.05); FC between VN and PCC was positively correlated with total Tau in CSF ( P<0.05). CSF Aβ 1-42 was positively correlated with FC alterations in aDMN and VN, but negatively correlated with FC in FPN ( P<0.05). Conclusion:In AD patients, characteristic changes in FC within and between multiple brain networks are noted, which are related to changes of Tau protein and Aβ 1-42 in CSF.

Background Improper settings of outdoor smoking points in public places may increase the risk of secondhand smoke exposure among the population. Conducting research on air pollution in and around smoking spots and related influencing factors can provide valuable insights for optimizing the setting of outdoor smoking points. Objective To investigate the influence of the number of smokers at outdoor smoking points and the distance on the diffusion characteristics of surrounding air pollutants, in order to optimize the setting of outdoor smoking points. Methods Surrounding the exhibition halls in the China International Import Expo (CIIE), two outdoor smoking points were randomly selected, one on the first floor (ground level) and the other on the second floor (16 m above ground), respectively. At 0, 3, 6, and 9 m from the smoking points in the same direction, validated portable air pollutant monitors were used to measure the real-time fine particulate matter (PM_2.5) and carbon dioxide (CO₂) concentrations for consecutive 5 d during the exhibition, as well as the environmental meteorological factors at 0 m with weather meters including wind speed, wind direction, and air pressure. An open outdoor atmospheric background sampling point was selected on each of the two floors to carry out parallel sampling. Simultaneously, the number of smokers at each smoking point were double recorded per minute. The relationships between the number of smokers, distance from the smoking points, and ambient PM_2.5 and CO₂ concentrations were evaluated by generalized additive regression models for time-series data after adjustment of confounders such as temperature, relative humidity, and wind speed. Results The median numbers of smokers at smoking points on the first and second floors were 6 [interquartile range (IQR): 3, 9] and 9 (IQR: 6, 13), respectively. Windless (wind speed <0.6 m·s⁻¹) occupied most of the time (85.9%) at both locations. The average concentration of ambient PM_2.5 at the smoking points (0 m) [mean ± standard deviation, (106±114) μg·m⁻³] was 4.2 times higher than that of the atmospheric background [(25±7) μg·m⁻³], the PM_2.5 concentration showed a gradient decline with the increase of distance from the smoking points, and the average PM_2.5 concentration at 9 m points [(35±22) μg·m⁻³] was close to the background level (1.4 times higher). The maximum concentration of CO₂ [(628±23) μmol·mol⁻¹] was observed at 0 m, and its average value was 1.3 times higher than that of the atmospheric background [(481±40) μmol·mol⁻¹], and there was no gradient decrease in CO₂ concentration with increasing distance at 0, 3, 6, and 9 m points. The regression analyses showed that, taking smoking point as the reference, every 3 m increase in distance was associated with a decrease of ambient PM_2.5 by 24.6 [95% confidence interval (95%CI): 23.5, 25.8] μg·m⁻³ (23.2%) and CO₂ by 54.1 (95%CI: 53.1, 55.1) μmol·mol⁻¹ (8.6%). Every one extra smoker at the smoking point was associated with an average increase of PM_2.5 and CO₂ by 2.0 (95%CI: 1.7, 2.8) μg·m⁻³ and 1.0 (95%CI: 0.7，1.2) μmol·mol⁻¹, respectively. The sensitivity analysis indicated that, under windless conditions, the concentrations of PM_2.5 and CO₂ at the smoking points were even higher but the decreasing and dispersion characteristics remained consistent. Conclusion Outdoor smoking points could significantly increase the PM_2.5 concentrations in the surrounding air and the risks of secondhand smoke exposure, despite of the noticeable decreasing trend with increasing distance. Considering the inevitable poor dispersion conditions such as windless and light wind, outdoor smoking points are recommended to be set at least 9 m or farther away from non-smoking areas.