Objective: To investigate the effect of integrin α5 on the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in periodontal ligament fibroblasts (PDLFs) within an inflammatory microenvironment. Methods: This study was approved by the Ethics Committee of Laboratory animals. After rat PDLFs were treated with LPS (0.5, 5, and 50 µg/mL) for 24 h, the primary medium was discarded and replaced with serum-free culture medium. After 24 h, the supernatant was collected and mixed with DMEM medium containing 10% exosome-free serum at a volume ratio of 1:1 to obtain conditioned medium (CM). The groups were labeled as the 0.5-CM, 5-CM, and 50-CM groups. In addition, PDLFs cultured in DMEM medium containing 10% exosome-free serum were considered the 0-CM group. PDLFs were cultured with the above CM. In the inhibitor group, PDLFs were cultured in 0-CM containing different concentrations of integrin α5 inhibitor ATN-161 (0, 0.025, 0.25, 2.5, 25, and 250 μg/mL). The effect of CM and integrin α5 inhibitor ATN-161 on cell viability was assessed using the CCK-8 assay. According to the CCK-8 results, in further inhibitor intervention experiments, PDLFs were cultured in 0-CM, 5-CM (without/with 25 μg/mL ATN-161), and 0-CM containing 25 μg/mL ATN-161, which were labeled as the 0-CM, 5-CM, ATN-161+5-CM, and ATN-161 groups, respectively. The expression changes of integrin α5 and NLRP3 were detected using Western blot and qRT-PCR techniques. For in vivo experiments, 24 rats were randomly divided into four groups (n=6). The control group contained healthy rats that received no treatment. The rats in the other three groups were injected with 40 µL of 0-CM containing 25 μg/mL ATN-161 or 5-CM (without or with 25 μg/mL ATN-161) on the palatal side of the left maxillary first molar every three days; these groups were classified as the ATN-161, 5-CM, and ATN-161+5-CM groups, respectively. On the 30th day, the left maxillary tissue of rats was used for Micro-CT, HE staining, and immunohistochemical detection. Results : The CCK-8 assay showed that CM, 25 μg/mL ATN-161, and ATN-161 concentrations below 25 μg/mL had no significant effect on cell viability at 12 h and 24 h (P > 0.05). 50-CM and 25 μg/mL ATN-161 significantly inhibited cell viability at 48 h (P < 0.05). For in vitro experiments, compared to the 0-CM group, both the protein and mRNA levels of integrin α5 and NLRP3 were significantly increased in rat PDLFs in the 5-CM group (P < 0.05). Intervention with 25 μg/mL ATN-161 significantly attenuated the enhancement of 5-CM on the expression of integrin α5 and NLRP3 (P < 0.05). For in vivo experiments, compared to the control group, alveolar bone resorption and periodontal inflammatory cell infiltration were significantly increased in the 5-CM and ATN-161+5-CM groups, and the expression of integrin α5 and NLRP3 was significantly increased (P < 0.01). However, compared to the 5-CM group, the ATN-161+5-CM group had less alveolar bone resorption and fewer periodontal inflammatory cells. Further, the expression of integrin α5 and NLRP3 was significantly reduced (P < 0.01). Conclusion In vitro and in vivo experiments showed that integrin α5 mediated NLRP3 expression in PDLFs under an inflammatory microenvironment. ATN-161 inhibited the expression of integrin α5, thus significantly downregulating the expression of NLRP3, which plays a role in inhibiting inflammation.

ObjectiveTo explore the molecular mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer （NSCLC） by inducing ferroptosis via poly（rC）-binding protein 1 （PCBP1）. MethodsThe serum containing Buzhong Yiqitang was prepared and cisplatin-resistant human non-small cell lung cancer （NSCLC） cells （A549/DDP） were cultured and randomly grouped as follows： Blank （10% blank serum）， model （10% blank serum+20 mg·L^-1 cisplatin）， Buzhong Yiqitang （10% serum containing Buzhong Yiqitang+20 mg·L^-1 cisplatin）， Fe-1 （10% blank serum+20 mg·L^-1 cisplatin+5 μmol·L^-1 Fe-1）， and Buzhong Yiqitang+Fe-1 （10% serum containing Buzhong Yiqitang+20 mg·L^-1 cisplatin+5 μmol·L^-1 Fe-1）. Firstly， PCR Array was used to screen ferroptosis-related genes regulated by Buzhong Yiqitang， and PCBP1 was identified as the target for studying the attenuation of cisplatin resistance by Buzhong Yiqitang. Subsequently， the median inhibitory concentration （IC₅₀） of cisplatin in each group was determined by the cell counting kit-8 （CCK-8） method and the resistance index （RI） was calculated. The ultrastructure of A549/DDP cells in each group was observed by transmission electron microscopy. The protein levels of PCBP1 and glutathione peroxidase 4 （GPX4） were determined by Western blot. The lipid reactive oxygen species （ROS） content in each group was determined by the C11-BODIRY 581/591 fluorescence probe. The ferrous ion assay kit was used to measure the ferrous ion content in each group. The malondialdehyde （MDA） assay kit was used to determine the MDA content in each group. ResultsCompared with model group， the IC₅₀ of cisplatin and the RI of A549/DDP cells decreased in the Buzhong Yiqitang group （P<0.05） but increased in the Fe-1 group （P<0.05）. The IC₅₀ of cisplatin and the RI of A549/DDP cells in the Buzhong Yiqitang+Fe-1 group were lower than those in the Fe-1 group （P<0.05）. Compared with the model group， the Buzhong Yiqitang group showed obvious mitochondrial ferroptosis， while the mitochondrial damage became less obvious after Fe-1 treatment. Compared with that in the Fe-1 group， the mitochondrial ferroptosis was aggravated after the intervention with Buzhong Yiqitang. Compared with blank group， the model group showed down-regulated expression levels of PCBP1 and GPX4 （P<0.05） and increased content of lipid ROS， ferrous ions， and MDA （P<0.05） in A549/DDP cells. Compared with model group， the Buzhong Yiqitang group showed down-regulated expression levels of PCBP1 and GPX4 （P<0.05） and increased content of lipid ROS， ferrous ions， and MDA （P<0.05）， while the Fe-1 group showed up-regulated expression levels of PCBP1 and GPX4 （P<0.05） and reduced content of lipid ROS， ferrous ions， and MDA （P<0.05）. Compared with the Fe-1 group， the Buzhong Yiqitang+Fe-1 group showed down-regulated expression levels of PCBP1 and GPX4 and increased content of lipid ROS， ferrous ions， and MDA （P<0.05）. ConclusionBuzhong Yiqitang attenuated cisplatin resistance in NSCLC by regulating PCBP1 to induce ferroptosis.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective:To explore the mediating effect of unhealthy lifestyle and depressive symptom on the associations between life course factors and aging health.Methods:The study included 6 217 participants (aged ≥45 years) from the China Health and Retirement Longitudinal Study (CHARLS). We used principal component analysis (PCA) and hierarchical clustering analysis (HCA) to divide participants into six subgroups based on 70 life course factors. Five key life course factors were identified based on correlation analysis and their contribution to aging health. Physiological dysregulation (PD) was calculated by using eight biomarkers in the 2015 CHARLS biomarker dataset. Linear regression, logistic regression, and mediation models were used to explore the complex associations of life course subgroups, key factors, unhealthy lifestyle, depression symptom with PD.Results:Life course subgroups were significantly associated with PD after adjusting chronological age and gender ( β: 0.08-0.17, all P<0.05). Life-course subgroups and key factors, including adverse experiences in adulthood and lower education level, were significantly associated with unhealthy lifestyle ( β: 0.04-0.52, all P<0.05). Life-course subgroups and key factors, including childhood trauma, parental health in childhood, adverse experiences in adulthood, and lower education level, were significantly associated with depression symptom ( OR: 1.16-4.76, all P<0.05). Mediation analysis showed that unhealthy lifestyle had partial mediating effect on the association of life course subgroups and key factors, including adverse experiences in adulthood, and lower education levels, with PD (3.1%-3.6%). Depression symptom had partial mediating effect on the association of life course subgroups and key factors, including childhood trauma, adverse experience in adulthood, and lower education level, with PD (6.0%-16.2%). Conclusions:Unhealthy lifestyle and depression symptom has partial mediating effect on the impact of life course factors on aging health. It is important to pay attention to these two modifiable factors while targeting childhood trauma and adverse experience in adulthood.

Background::Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI.Methods::TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t-test. Results::TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells. Conclusion::TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.

Objective:To explore the application of 3D visualisation technology combined with perforator flap transfer in reconstruction of soft tissue defects in traumatic hand and foot injury and explore the clinical outcomes.Methods:Between January 2021 and February 2023, a retrospective analysis was conducted in the Department of Emergency of the Affiliated Hospital of Jiangsu University and the Department of Sports Medical of Wuxi No. 9 People's Hospital, on the data of 12 patients (13 flaps) who received surgery of 3D visualisation technology combined with perforator flap transfer for soft tissue defects left by traumatic hand and foot injuries. The patients were 7 males and 5 females aged 45 [36.5, 55.8] years old. Nine patients had the defects in hand and 3 in foot, with 3 in the left and 9 in the right. The sizes of defects ranged from 8.0 cm×6.0 cm to 18.0 cm×17.0 cm. The time from injury to surgery was 13.5 [8.3, 20.8] days. Preoperative CTA scans of donor and recipient sites were performed, and the imaging data were processed for 3D image reconstruction and visualisation. A total of 13 flaps were designed and harvested, including 10 free anterolateral thigh perforator flaps (ALTPFs) and 3 pedicled perforator flaps of fibular artery containing fibular nerve nutrient vessel chains. The flap sizes ranged from 9.0 cm×6.0 cm to 20.0 cm×15.0 cm. Five of the donor sites were directly closed by suture and 8 by skin grafting. Monthly outpatient follow-ups were conducted for the first 3 months after surgery, and then the follow-up reviews were conducted through visits of outpatient clinic or reviewed via WeChat interviews. Information about the outcomes of the transferred flaps, complications and function recovery were recorded on all patients.Results:All 13 flaps were successfully harvested and transferred with the assistance of 3D visualisation technology. Preoperative location of perforator vessels was accurate and flap design was reasonable. The 3D visualisation provided an effective guidance for surgical manipulation. Twelve flaps survived completely after surgery. One flap that had partial necrosis healed after skin grafting. All patients were included in more than 6 months of postoperative follow-up, with a mean follow-up duration of 8.1 months±1.7 months. All flaps had good colour and texture. Four flaps that had swollen appearance received secondary thinning surgery with satisfactory outcomes. The recovery of 9 patients with hand injury was evaluated according to the Blood Circulation Elauation of Severed Finger Replantation Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association. At the final follow-up, the blood supply of flaps was excellent in 11 flaps and good in 2 flaps. Hand function was excellent in 2 hands, good in 4 hands and poor in 3 hands. Scores of American Orthopedic Foot and Ankle Societ(AOFAS) ankle-hindfoot was used for foot function evaluation and all 3 patients were in excellent. Of the postoperative complications, due to a haematoma beneath the flap, a local infection and a delayed fracture healing were occurred in 3 patients separately.Conclusion:The 3D visualisation technology assisted perforator flap transfer can achieve high-quality reconstruction of defects in hand and foot through precise preoperative flap design and simulated surgical incision, therefore it provides a better treatment outcomes for patients.

Objective To investigate the improvement effect and related mechanism of roxadustat on myocardial ischemia-reperfusion(I/R)injury in mice.Methods Twenty four male C57BL/6N mice were randomly divided into the sham operation group,the control group and the roxadustat group,with eight mice in each group.A mouse myocardial I/R model was established.The control group was given 100 μL saline injection containing 5%dimethyl sulfoxide by gavage.The roxadustat group was given 25 mg/kg roxadustat by gavage.The left anterior descending coronary artery of mice in both groups was ligated for 40 minutes,and then reperfusion for 24 hours to establish the myocardial I/R model.In the sham operation group,only the left anterior coronary artery was pierced without ligation.The area of myocardial infarction in mice was detected by triphenyltetrazolium chloride(TTC)staining.The apoptosis of mouse cardiomyocytes was detected by TdT-mediated dUTP nick and labeling(TUNEL)staining.The expression of apoptosis-related proteins bcl-2 associated X protein(Bax),Caspase3 and inflammatory cell markers F4/80 and myeloperoxidase(MPO)were detected by immunohistochemistry staining.The damage of myocardial cells was observed by hematoxylin-eosin(HE)staining.Results The area of myocardial infarction after myocardial I/R was reduced in the roxadustat group compared to the control group and the sham operation group(P＜0.05).The number of apoptotic cells was higher in the control group and the roxadustat group than that in the sham operation group,and the number of apoptotic cells was lower in the roxadustat group than that in the control group(P＜0.05).The expression levels of Bax and Caspase3 proteins in myocardial tissue were higher in the control group and the roxadustat group than those in the sham operation group,while those of the roxadustat group was lower than those of the control group(P＜0.05).The expression levels of F4/80 and MPO proteins in myocardial tissue were lower in the roxadustat group than those in the control group(P＜0.05).In the control group,the myocardial tissue arrangement was disordered,and there was an increase in interstitial vacuoles.Compared with the control group,the myocardial cells were arranged more neatly in the roxadustat group,and the interstitial vacuoles were reduced.Conclusion Roxadustat can reduce the myocardial infarction area after I/R injury,inhibit myocardial cell apoptosis,alleviate myocardial injury,reduce infiltration of myocardial macrophages and neutrophils,and reduce inflammatory injury.

ObjectiveTo elucidate the principles and methods of the Bayesian probabilistic linkage model， and to demonstrate the effect of applying the model in linking birth and death data. MethodsThrough the Shanghai birth and death registration system， data of 199 025 infants born in 2017 and 1 512 infants who died in 2017 and 2018 were collected. After cleaning the data， the data were divided into monthly blocks and fully linked. The Jaro-Winkler algorithm and Euclidean distance were employed to measure the similarity of fields for matching. A Bayesian probabilistic linkage model was constructed and the linking effect was evaluated using a confusion matrix. ResultsUsing the Bayesian probabilistic linkage model， the birth and death data of infants were effectively linked， revealing that 36.71% of infants who died in Shanghai were born outside the city， and the probability of infant death was 2.6‰. The confusion matrix of the test set showed a recall rate of 0.86， precision of 0.76， and an F-score of 0.81. ConclusionThe practical application of Bayesian probabilistic linkage demonstrates a good model performance， enabling the establishment of birth-death cohorts that more accurately reflect the true levels of infant mortality. Utilizing this technique to integrate data from different departments can effectively improve research efficiency in the field of public health.

Objective:Efficiency is a key factor in the sustainable operation of the medical insurance system.By measuring the current efficiency of the urban employee basic medical insurance system in 31 provinces in China from 2020 to 2021,it discovers possible problems,and provides reference suggestions for improving the efficiency of the system.Methods:Using the super efficiency SBM model based on unexpected output and the Malmquist index to measure the static and dynamic efficiency of employee medical in-surance in 31 provinces in China,and using Tobit regression analysis to analyze its influencing factors.Results:The overall compre-hensive efficiency of the national employee medical insurance operation is 0.826 in 2020 and 0.827 in 2021 respectively.The efficien-cy of employee medical insurance operation in the eastern region is significantly higher than that in the central and westem regions.Over 60％of provinces have inefficient operation of employee medical insurance.The overall total factor productivity of employee medical insurance operation is showing a downward trend,and the decline in technological progress is the main limiting factor.The level of economic development has a significant promotion effect on the efficiency of employee medical insurance operation,and the degree of population aging has a significant inhibitory effect on it.Conclusion:The efficiency of employee medical insurance opera-tion in China still needs to be improved,and there is a significant efficiency gap among different regions.Therefore,investment and attention should be increased in the central and western regions to bridge regional gaps and promote the equity development of medi-cal insurance.Therefore,the reform efforts should be continuously intensified to achieve technological progress.In addition,attention should also be paid to the driving role of economic development in the efficiency of employee medical insurance operation and the for-mulation of positive policies on population aging.

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.