Objective To investigate the clinical value of coronary computed tomography angiography(CCTA)based CT derived fractional flow reserve(CT-FFR)and ΔCT-FFR in improving the diagnostic efficiency for coronary abnormal hemodynamics in patients with severe calcification.Methods We retrospectively analyzed the clinical data of coronary artery disease(CAD)patients who underwent CCTA,CT-FFR,invasive coronary angiography(ICA)and FFR during hospitalization from January 2018 to June 2019 in Chinese PLA General Hospital.Severe calcification was defined as coronary artery calcium score(CACS)≥100 on single vessel level.A total of 107 CAD patients with 149 coronary arteries were included in the present study.The enrolled coronary arteries were assigned to CACS≥100 group(n=56)and CACS<100 group(n=93).CT-FFR was performed on the deep FFR platform based on machine learning(ML)algorithms and ΔCT-FFR was defined as CT-FFR difference between proximal and distal to the coronary lesion.The correlation and consistency between CT-FFR and FFR values were analyzed by Pearson and Bland-Altman methods.We attempted to analyze the incremental value of ΔCT-FFR for coronary functional evaluation,especial for coronary arteries with severe calcification,regarding FFR≤0.8 as the diagnostic gold standard.Comparison of receiver operating characteristic curves(ROC)between different diagnostic methods was presented by Delong test.Results Pearson and Bland-Altman analyses showed appreciable correlation(CACS≥100 group,r=0.71,P<0.01;CACS<100 group,r=0.73,P<0.01)and consistency(CACS≥100 group,Mean=-0.01,P=0.25;CACS<100 group,Mean=0,P=0.96)between CT-FFR and FFR values in both groups.FFR(0.80±0.08 vs.0.84±0.09,P=0.004)and CT-FFR(0.81±0.06 vs.0.85±0.06,P<0.001)levels were significant lower in CACS≥100 group than those in CACS<100 group,while ΔCT-FFR(0.14±0.06 vs.0.09±0.06,P<0.001)levels were significant higher in CACS≥100 group.Moreover,the diagnostic efficiency of CT-FFR in CACS≥100 group was inferior to that in CACS<100 group[AUC=0.792(95%CI 0.663-0.889)vs.AUC=0.929(95%CI 0.856-0.972),P=0.04],while it achieved significant improvement after ΔCT-FFR adjustment[AUC=0.876(95%CI 0.760-0.949)vs.AUC=0.792(95%CI 0.663-0.889),P=0.02]and was similar to that in CACS<100 group(P=0.37).Conclusion For coronary arteries with severe calcification,CT-FFR demonstrated significant incremental value in improving the diagnostic efficiency of coronary abnormal hemodynamics after ΔCT-FFR adjustment.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Objective:The main purpose of this study is to analyse the current situation and inequity status of children's medical security in China from the vision of children first.Methods:Using data from the China Family Panel Studies 2020 and based on the framework of universal health coverage cube,multivariate regression is used to analyse the differences in medical security between children and adults and among groups of children.Results:The participation rate of children in China is 80.96%,out-of-pocket ratios are 64.71%and 90.09%for inpatient and outpatient groups respectively.In terms of participation rate,insured children are less than that of adults(OR=0.434,P＜0.01);within children's groups,attending school(OR=2.075,P＜0.01)significantly increases children's participation rate,while left-behind by parent(s)(OR=0.791,P＜0.05)significantly decrease children's participation rate.With respect to service and cost coverage,children have higher out-of-pocket ratios compared to adults(β=0.066,P＜0.01);within children's groups,children eged 6 years and older have lower out-of-pocket medical expenses(β＜-0.316,P＜0.01),children with higher family income(β＜-0.022,P＜0.05),participated(β=-0.033,P＜0.01),and hospitalized(β=-0.270,P＜0.01)have lower out-of-pocket ratios.Conclusion:Double in equality exists in children's medical security in China.The level of children's health security in China is significantly lower than that of adults;within children's groups,children aged 0～5 years,not in school,left-behind by parent(s),and from lower-income families are more vulnerable.It is proposed to focus on increasing the participation rate of children through measures such as optimizing the contribution for children and launching family joint insurance.Policy design should also consider the needs of children and raise the level of children's benefits.Meanwhile,the focus should be on helping vulnerable groups in children,so as to ultimately achieve"children first"in health security.

Protein disulfide isomerase A6 (PDIA6) is closely related to inflammation and endoplasmic reticulum stress. To obtain the glycosyl derivatives of benzophenone polyphenols targeting PDIA6 with strong anti-inflammatory effects, twenty-five target glycosyl derivatives were synthesized by Friedel-Crafts acylation and deacetylation reaction, starting from the substituted benzophenone and α-bromoacetyl saccharide, and their interactions with PDIA6 were quantitatively investigated by bio-layer interferometry (BLI) technique. Their in vitro anti-inflammatory properties were also evaluated. The results showed that target compounds 4b, 10b, 17b, 18b, and 25b not only exhibit high affinity with PDIA6, but also present strong anti-inflammatory abilities. Above results suggest that this class of compounds can affect the signaling pathways related to inflammation by directly acting on PDIA6. In particular, such compounds exhibit the strong inhibitory effects on IL-1β and IL-6 release, suggesting the potential development prospect in the treatment of inflammatory diseases.

Objective:To explore the risk factors of coal workers' pneumoconiosis, reveal the molecular mechanism of pyroptosis in peripheral blood of coal workers' pneumoconiosis patients, and provide new strategies and potential diagnostic biomarkers for the treatment of the disease.Methods:From January 1, 2020 to December 31, 2022, workers with suspected occupational diseases who were diagnosed with coal workers' pneumoconiosis in the Third People's Hospital of Xinjiang Uygur Autonomous Region were included in the study, including 77 patients with coal workers' pneumoconiosis stage Ⅰ, 10 patients with stage Ⅱ, 6 patients with stage Ⅲ, and 49 workers with dust-free lung disease as the control group. General information of the subjects was collected, blood samples were collected for routine blood and blood biochemical results, and plasma levels of interleukin (IL) -1β and IL-18 were measured. Combined with the results of clinical examination, multi-factor ordered logistic regression analysis was carried out to evaluate the influencing factors of coal workers' pneumoconiosis. At the same time, the expression of pyroptosis related proteins in blood cells was detected to reveal the molecular mechanism of coal workers' pneumoconiosis.Results:All 142 subjects were male, with an average age of (51.65±6.31) years old and an average working age of (15.94±9.38) years. There were significant differences in smoking age ( F=4.95, P=0.003) and lunch break distribution ( H=8.84, P=0.031) among all groups. The hemoglobin content of stage Ⅰ patients was higher than that of stage Ⅱ patients, and the neutrophil percentage of stage Ⅲ patients was higher than that of the other 3 groups ( P<0.05). The levels of total bilirubin and indirect bilirubin in stage Ⅰ patients were higher than those in control group, while the erythrocyte sedimentation rate in stage Ⅱ patients was higher than that in the other 3 groups ( P<0.05). The levels of IL-18 and IL-1β in stage Ⅲ of coal workers' pneumoconiosis were higher than those in the other 3 groups ( P<0.05). Multiple logistic regression analysis showed that smoking age ( OR=1.03, 95% CI: 1.00-1.06) and IL-1β level ( OR=4.61, 95% CI: 1.59-13.32) were independent risk factors for coal workers' pneumoconiosis ( P<0.05). Compared with the control group, the expression levels of nucleotide-binding of oligomeric domain-like receptor protein 3 (NLRP3), Caspase-1, GSDMD, Caspase-4 and other proteins in stage Ⅲ of coal workers' pneumoconiosis were significantly increased ( P<0.05) . Conclusion:Smoking age is a risk factor for coal workers' pneumoconiosis, IL-1β may be a potential biomarker for the diagnosis of coal workers' pneumoconiosis, and pyroptosis may play a role in the development of peripheral inflammation of coal workers' pneumoconiosis.

Objective:To explore the risk factors of coal workers' pneumoconiosis, reveal the molecular mechanism of pyroptosis in peripheral blood of coal workers' pneumoconiosis patients, and provide new strategies and potential diagnostic biomarkers for the treatment of the disease.Methods:From January 1, 2020 to December 31, 2022, workers with suspected occupational diseases who were diagnosed with coal workers' pneumoconiosis in the Third People's Hospital of Xinjiang Uygur Autonomous Region were included in the study, including 77 patients with coal workers' pneumoconiosis stage Ⅰ, 10 patients with stage Ⅱ, 6 patients with stage Ⅲ, and 49 workers with dust-free lung disease as the control group. General information of the subjects was collected, blood samples were collected for routine blood and blood biochemical results, and plasma levels of interleukin (IL) -1β and IL-18 were measured. Combined with the results of clinical examination, multi-factor ordered logistic regression analysis was carried out to evaluate the influencing factors of coal workers' pneumoconiosis. At the same time, the expression of pyroptosis related proteins in blood cells was detected to reveal the molecular mechanism of coal workers' pneumoconiosis.Results:All 142 subjects were male, with an average age of (51.65±6.31) years old and an average working age of (15.94±9.38) years. There were significant differences in smoking age ( F=4.95, P=0.003) and lunch break distribution ( H=8.84, P=0.031) among all groups. The hemoglobin content of stage Ⅰ patients was higher than that of stage Ⅱ patients, and the neutrophil percentage of stage Ⅲ patients was higher than that of the other 3 groups ( P<0.05). The levels of total bilirubin and indirect bilirubin in stage Ⅰ patients were higher than those in control group, while the erythrocyte sedimentation rate in stage Ⅱ patients was higher than that in the other 3 groups ( P<0.05). The levels of IL-18 and IL-1β in stage Ⅲ of coal workers' pneumoconiosis were higher than those in the other 3 groups ( P<0.05). Multiple logistic regression analysis showed that smoking age ( OR=1.03, 95% CI: 1.00-1.06) and IL-1β level ( OR=4.61, 95% CI: 1.59-13.32) were independent risk factors for coal workers' pneumoconiosis ( P<0.05). Compared with the control group, the expression levels of nucleotide-binding of oligomeric domain-like receptor protein 3 (NLRP3), Caspase-1, GSDMD, Caspase-4 and other proteins in stage Ⅲ of coal workers' pneumoconiosis were significantly increased ( P<0.05) . Conclusion:Smoking age is a risk factor for coal workers' pneumoconiosis, IL-1β may be a potential biomarker for the diagnosis of coal workers' pneumoconiosis, and pyroptosis may play a role in the development of peripheral inflammation of coal workers' pneumoconiosis.

Takeda G protein-coupled receptor 5(TGR5)is a bile acid receptor located on the surface of cell membrane,widely distributed in many tissues and cells in the body,and can be directly activated by most bile acids in vivo.TGR5 plays an important role in various physiological and pathophysiological processes,including cellular Ca2+transport,oxidative stress,cell proliferation,inflammatory responses,and mitochondrial metabolism,thereby maintaining mitochondrial homeostasis and vascular endothelial function,and inhibiting the progression of cardiovascular diseases such as atherosclerosis,myocardial hypertrophy,and cardiac remodeling after myocardial infarction.Currently,with the gradual clinical application of numerous bile acid and bile acid derivatives drugs,it is necessary to further investigate the role of TGR5 in the cardiovascular system,which is an important basis for clinical application of these new drugs.This review discusses the relationship between TGR5 and cardiovascular system from five perspectives:TGR5's involvement in regulating macrophages,endothelial function,vascular smooth muscle cells,cardiomyocytes,and mitochondrial metabolism.It summarizes the recent research progress,aiming to provide the theoretical basis for TGR5 as a novel therapeutic target for cardiovascular diseases.

Objective To investigate the effect of microplastic(MPs)exposure on learning and memory in mice,and its mechanism by observing the protein expression of brain-derived neurotrophic factor(BDNF)/tyrosine receptor kinase B(TrkB)/N-methyl-D-aspartate receptor subtype 2B(NR2B)signaling pathway and neurogenesis.Methods Forty male C57BL/6 mice were randomly divided into control group(Ctrl)and microplastics exposure group(MPs).Mice in MPs group were treated with 0.3 mg/(kg·d)microplastics,administered by gavage at a volume of 200 μl for 30 consecutive days.Morris water maze test was used to evaluate the spatial learning and memory ability of mice.Western blotting was used to detect the protein levels of BDNF,TrkB and NR2B in hippocampus of mice.Immunofluorescent staining was used to observe the number of doublecortin(DCX)and neuronal nuclei antigen(NeuN)positive cells in the hippocampus of mice to evaluate hippocampal neurogenesis.Results Compared with the control group,the ability of learning and memory decreased significantly in MPs group mice(P＜0.01).The expression levels of BDNF,TrkB and NR2B in the hippocampus of MPs group mice were significantly lower than those of control group(P＜0.05).The number of DCX and NeuN positive cells in the hippocampus of MPs group was significantly lower than that of control group(P＜0.01).Conclusion MPs exposure induces learning and memory impairment which may be related to inhibiting BDNF/TrkB/NR2B signaling pathway and reducing hippocampal neurogenesis.

Objective To construct a mouse model of alcoholic liver fibrosis and explore the effect of supplementing exogenous thyroid hormone T3 on oxidative stress in liver.Methods Eighty mice were randomly divided into 6 groups,normal control group,alcoholic liver fibrosis(ALF)model group,and low concentration T3 intervention group(25 μg/kg),medium concentration T3 intervention group(50 μg/kg),high concentration T3 intervention group(100 μg/kg)and T3 control group(the concentration of T3 is 100 μg/kg).A model of mice alcoholic liver fibrosis was established by using alcoholic liquid feed combined with 31.5％ethanol gavage.From the sixth week,mice in the T3 intervention and T3 control group were injected with corresponding concentrations of T3 intraperitoneally for three weeks.Mice in the control and T3 control groups were fed with control liquid feed.The degree of mice liver injury and fibrosis was evaluated through the sirius red staining,Western blotting,and serum biochemical testing.The activity of superoxide dismutase(SOD),the content of glutathione(GSH)and malondialdehyde(MDA)in liver tissue were detected by ELISA,and the protein expressions of microtubule-associated protein light chain 3-Ⅱ(LC3-Ⅱ)and p62 were detected by immunohistochemistry and Western blotting.Results The liver structure and function in the ALF group were severely damaged,autophagy was inhibited,and the oxidative stress response was significantly enhanced compared with the control group.Compared with the ALF group,the recovery of liver functional and structure and autophagy were showed in the T3 intervention group,and SOD activity and GSH content in the liver increased in the low and medium concentrations of T3 intervention groups,while MDA content significantly decreased.In the high concentration T3 intervention group,it showed the same increase in SOD activity,a significant decrease in MDA content,while the content of GSH was lower than that in the control group,which was not different with the ALF group.Conclusion Appropriate supplementation of T3 could affect the occurrence and development of alcoholic liver fibrosis by restoring the liver autophagy to inhibit the oxidative stress response.

Aim To explore the role of Takeda G pro-tein-coupled receptor 5(TGR5)in the proliferation and migration of vascular smooth muscle cells(VSMCs)within the intimal layer of mice.Methods Mouse VSMCs were stimulated for proliferation and migration with PDGF-BB,followed by administration of INT-777 for activation of TGR5.CCK-8 assay and Ki-67 immunofluorescence staining were employed to eval-uate cell proliferation.The scratch assay was utilized to assess migration.Western blot analysis was conducted to monitor TGR5 protein expression.To further investi-gate the role of TGR5 in intimal hyperplasia in vivo,20 male wild-type C57BL/6J mice were randomly divided into four groups:sham group,carotid artery endothelial injury group,sham+UDCA(ursodeoxy-cholic acid,a TGR5 agonist)group,and carotid artery endothelial injury+UDCA group(n=5 in each group).After the establishment of endothelial injury model,mice were orally fed with regular maintenance feed containing 0.5％UDCA for 21 days.Subsequent-ly,samples were collected for Hematoxylin and Eosin(HE)staining to assess the neointimal hyperplasia.Immunofluorescence(IF)staining was used to exam-ine the proliferation of VSMCs within the carotid inti-ma.Results The specific activation of TGR5 marked-ly diminished cell viability,the proportion of Ki-67-positive cells,and slowed down the rate of wound-heal-ing.Notably,the specific activation of TGR5 increases the expression of UCP2 in cells and reduces the levels of reactive oxygen species(ROS).The inhibitory effect of TGR5 on VSMC proliferation and migration was neutralized upon the restoration of intracellular ROS level with H2O2.Activation of TGR5 was found to mitigate intimal thickening following carotid artery inju-ry.Conclusion TGR5 may inhibit the proliferation and migration of mouse VSMCs by attenuating intracel-lular oxidative stress.