OBJECTIVES: To investigate the effect of amentoflavone (AF) for alleviating lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and inhibiting NLRP3/ASC/Caspase-1 axis-mediated pyroptosis. METHODS: Female BALB/c mice were randomly divided into control group, LPS group, and AF treatment groups at low, moderate and high doses (n=12). ALI models were established by tracheal LPS instillation, and in AF treatment groups, AF was administered by gavage 30 min before LPS instillation. Six hours after LPS instillation, the mice were euthanized for examining lung tissue histopathological changes, protein levels in BALF, and MPO levels in the lung tissue. In the in vitro experiment, RAW264.7 cells were pretreated with AF, AC (a pyroptosis inhibitor), or their combination for 2 h before stimulation with LPS and ATP. The changes in cell proliferation and viability were detected using CCK-8 assay, and IL-1β, IL-6, IL-18, and TNF-α levels were determined with ELISA. Immunohistochemistry, immunofluorescence assay, and immunoblotting were used to detect the protein levels of NLRP3, ASC, cleaved caspase-1, and GSDMD N in rat lung tissues and the treated cells. RESULTS: In mice with LPS exposure, AF treatment significantly improved lung pathologies and edema, reduced protein levels in BALF and pulmonary MPO level, inhibited the high expression of NLRP3/ASC/Aspase-1 axis, reduced the expression of GSDMD N, and lowered the release of IL-1β, IL-6, IL-18, and TNF‑α. In RAW264.7 cells with LPS and ATP stimulation, AF pretreatment effectively reduced cell death, inhibited activation of the NLRP3/ASC/Aspase-1 axis, and reduced GSDMD N expression and the inflammatory factors. The pyroptosis inhibitor showed a similar effect to AF, and their combination produced more pronounced effects in RAW264.7 cells. CONCLUSIONS Amentoflavone can alleviate ALI in mice possibly by inhibiting NLRP3/ASC/Caspase-1 axis-mediated cell pyroptosis.
Animals ; Pyroptosis/drug effects* ; Acute Lung Injury/pathology* ; Mice ; Mice, Inbred BALB C ; Female ; Lipopolysaccharides ; Biflavonoids/pharmacology* ; RAW 264.7 Cells ; NLR Family, Pyrin Domain-Containing 3 Protein ; Caspase 1/metabolism* ; Lung

Due to the limited reliability of traditional self-completed questionnaire, the accuracy of measurement of physical behaviors (physical activity, sedentary behavior and sleep) is not high. With the development of technology, wearable devices (e.g. accelerometer) can be used for more accurate measurement of physical behaviors and have great application potential in large-scale research. However, the data of objective measurement of physical behaviors from large-scale cohort research in Asian populations is still limited. Between August 2020 and December 2021, the 3 rd resurvey of China Kadoorie Biobank (CKB) project used Axivity AX3 wrist triaxial accelerometer to collect the data of participants' daily activity and sleep status. A total of 20 370 participants from 10 study areas were included in the study, in whom 65.2% were women, and the age was (65.4±9.1) years. The participants' physical activity level varied greatly in different study areas. The objective measurement of participants' physical behaviors in CKB project has provided valuable resources for the description of 24-hour patterns of physical behaviors and evaluation of the health effect of physical activity, sedentary behavior and sleep as well as their association with diseases in the elderly in China.

Objective:To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors.Methods:This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels.Results:Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M ( Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) ( OR=1.23, 95% CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced ( OR=0.68, 95% CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95% CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95% CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95% CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95% CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions:Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.

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Objective:To explore the differences of physical activity levels between Chinese and British patients with cardiovascular disease (CVD) and its influencing factors.Methods:Based on the baseline survey of China Kadoorie Biobank (CKB) and United Kingdom Biobank (UKB), we identified the case and control group according to the self-reported disease history in the questionnaire. Metabolic equivalent of task, as the assessment of physical activity level, was graded according to the tertiles of specific ages and genders. Multiple logistic regression models were used to analyze the correlation between CVD status and physical activity levels.Results:We included 509 170 Chinese adults and 360 360 British adults in the analysis. After adjusting for multiple factors, we found a positive correlation between CVD patients and low physical activity levels in both CKB and UKB populations (CKB: OR=1.21, 95% CI:1.17-1.25; UKB: OR=1.24, 95% CI:1.20-1.28). There was a high correlation between the prevalence of CVD and low physical activity levels in males with CKB ( OR=1.33, 95% CI:1.27-1.40).Unlike the UKB population, as the length of CVD increased, the physical activity levels of CKB patients gradually approached that of the non-CVD population, and stroke was positively correlated with low physical activity levels ( OR=1.46, 95% CI:1.38-1.53). The decline in physical activity was more pronounced among CKB and UKB CVD patients with lower educational levels, current or former smokers or drinkers, and those with other chronic diseases. In CKB, there showed a high correlation between CVD disease and low physical activity levels in rural areas and non-retired populations. In UKB, there appeared a higher correlation between CVD disease and low physical activity levels in urban and non-working populations. Conclusions:The physical activity levels of CVD patients in both China and the UK were lower than that in non-CVD population. In addition to low-educated individuals, current or former smokers or drinkers, and those with other chronic diseases, it is critical to pay attention to the physical activity levels of rural, male, and non-retirees among Chinese patients.

Objective: To investigate the feasibility and the accuracy of the coronary CT angiography (CCTA)-derived Registry of Crossboss and Hybrid procedures in France, the Netherlands, Belgium and United Kingdom (RECHARGE) score (RECHARGE CCTA) for the prediction of procedural success and 30-minutes guidewire crossing in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Materials and Methods: One hundred and twenty-four consecutive patients (mean age, 54 years; 79% male) with 131 CTO lesions who underwent CCTA before catheter angiography (CA) with CTO-PCI were retrospectively enrolled in this study. The RECHARGE CCTA scores were calculated and compared with RECHARGECA and other CTA-based prediction scores, including Multicenter CTO Registry of Japan (J-CTO), CT Registry of CTO Revascularisation (CT-RECTOR), and Korean Multicenter CTO CT Registry (KCCT) scores. Results: The procedural success rate of the CTO-PCI procedures was 72%, and 61% of cases achieved the 30-minutes wire crossing. No significant difference was observed between the RECHARGE CCTA score and the RECHARGECA score for procedural success (median 2 vs. median 2, p = 0.084). However, the RECHARGE CCTA score was higher than the RECHARGE CA score for the 30-minutes wire crossing (median 2 vs. median 1.5, p = 0.001). The areas under the curve (AUCs) of the RECHARGE CCTA and RECHARGE CA scores for predicting procedural success showed no statistical significance (0.718 vs. 0.757, p = 0.655). The sensitivity, specificity, positive predictive value, and the negative predictive value of the RECHARGE CCTA scores of ≤ 2 for predictive procedural success were 78%, 60%, 43%, and 87%, respectively. The RECHARGE CCTA score showed a discriminative performance that was comparable to those of the other CTA-based prediction scores (AUC = 0.718 vs. 0.665–0.717, all p > 0.05). Conclusion The non-invasive RECHARGE CCTA score performs better than the invasive determination for the prediction of the 30-minutes wire crossing of CTO-PCI. However, the RECHARGECCTA score may not replace other CTA-based prediction scores for predicting CTO-PCI success.

Objective: To investigate the feasibility and the accuracy of the coronary CT angiography (CCTA)-derived Registry of Crossboss and Hybrid procedures in France, the Netherlands, Belgium and United Kingdom (RECHARGE) score (RECHARGE CCTA) for the prediction of procedural success and 30-minutes guidewire crossing in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Materials and Methods: One hundred and twenty-four consecutive patients (mean age, 54 years; 79% male) with 131 CTO lesions who underwent CCTA before catheter angiography (CA) with CTO-PCI were retrospectively enrolled in this study. The RECHARGE CCTA scores were calculated and compared with RECHARGECA and other CTA-based prediction scores, including Multicenter CTO Registry of Japan (J-CTO), CT Registry of CTO Revascularisation (CT-RECTOR), and Korean Multicenter CTO CT Registry (KCCT) scores. Results: The procedural success rate of the CTO-PCI procedures was 72%, and 61% of cases achieved the 30-minutes wire crossing. No significant difference was observed between the RECHARGE CCTA score and the RECHARGECA score for procedural success (median 2 vs. median 2, p = 0.084). However, the RECHARGE CCTA score was higher than the RECHARGE CA score for the 30-minutes wire crossing (median 2 vs. median 1.5, p = 0.001). The areas under the curve (AUCs) of the RECHARGE CCTA and RECHARGE CA scores for predicting procedural success showed no statistical significance (0.718 vs. 0.757, p = 0.655). The sensitivity, specificity, positive predictive value, and the negative predictive value of the RECHARGE CCTA scores of ≤ 2 for predictive procedural success were 78%, 60%, 43%, and 87%, respectively. The RECHARGE CCTA score showed a discriminative performance that was comparable to those of the other CTA-based prediction scores (AUC = 0.718 vs. 0.665–0.717, all p > 0.05). Conclusion The non-invasive RECHARGE CCTA score performs better than the invasive determination for the prediction of the 30-minutes wire crossing of CTO-PCI. However, the RECHARGECCTA score may not replace other CTA-based prediction scores for predicting CTO-PCI success.

Objective: To detect the expression of SVEP1, PKHD1 and P53 in primary liver cancer tissues by immunohistochemistry for predicting the recurrence of liver cancer. Methods: The clinical data of 103 patients with primary liver cancer who underwent surgical resection at Tianjin Medical University Cancer Institute and Hospital were gathered from January 2013 to January 2014 and analyzed retrospectively. Expression values of three different proteins were used to develop separate immunohistochemical scores for the prog-nosis of recurrence in patients. The patients were classified into either a high-risk or a low-risk group based on their immunohisto-chemical scores through ROC curve analysis. The difference in recurrence ratio between the two groups was then compared using the common research index of disease-free survival (DFS). Results: The median age of the total patients was 55 years (range 21-88 years), the median AFP level was 70.6 (range 1.03-718840.0) μg/L, the median CA19-9 level was 22.89 (range 0.6-1000.0) kU/L, and the medi-an tumor size was 4.5 (1.0-27.0) cm. The expression levels of SVEP1, PKHD1, and P53 in primary liver tumors were detected by immu-nohistochemistry and assigned separate immunohistochemical scores. The areas under the ROC curves of the immunohistochemical scores of SVEP1, PKHD1, and P53 were 0.861, 0.829, and 0.716, respectively. The critical values of SVEP1, PKHD1, and P53 were 4, 4, and 1 point, respectively (P<0.001). The three-year DFS rates among the SVEP1 high-risk (expression≤4 points) and low-risk groups (expression>4 points) were 4.1% and 51.7%, respectively. Similarly, the three-year survival rates among the PKHD1 high-risk (expres-sion≤4 points) and low-risk groups (expression>4 points) were 5.3% and 51.9%, respectively. The three-year DFS rates among the P53 high-risk (expression>1 point) and the low-risk group (expression≤1 point) were 6.3% and 27.3%, respectively. The survival differenc-es between all the pairs were statistically significant (P<0.001,<0.001, and 0.003 respectively). When PKHD1 was used in combination with SVEP1, the ROC curve had an area of 0.897 (P<0.001) with a sensitivity of 76.5% and a specificity of 94.4%. Conclusions: The accu-racy of P53 data for predicting primary liver cancer recurrence is insufficient and therefore it is not recommended for use. SVEP1 and PKHD1 data achieve sufficient accuracy for predicting the recurrence of primary liver cancer. Since SVEP1 data impart a higher specifici-ty and PKHD1 data impart a higher sensitivity to the prognosis scores, the combined use of the two markers is better than being used individually.

Objective To explore the relationship between plasma adiponectin, visfatin, leptin, and resistin levels, and the onset of colonic polyps in prediabetes subjects. Methods A total of 468 prediabetes subjects, who received colonoscopy examination, were enrolled in this study, including 248 cases of colon polyps (polyps group with prediabetes) and 220 cases without colonic mucosal lesions ( polyps-free group with prediabetes). According to the clinical characteristics of colonic polyps, colonic polyps patients with prediabetes were subdivided into single polyp group, multiple polyps group, low-risk polyps group, and high-risk polyps group, respectively. In addition, 108 subjects with normal glucose tolerance, who were matched with prediabetes subjects on gender and age, were selected as control group, and 46 cases of them were refered to polyps group with normal glucose tolerance and 62 cases were refered to polyps-free group with normal glucose. Plasma adiponectin, visfatin, leptin, and resistin levels were measured in all subjects, and related risk factors of colonic polyps in prediabetes patients were analyzed. Results Not only in normal glucose tolerance subjects, but also in prediabetes subjects, plasma visfatin levels in polyps group were significantly higher than those in polyps-free group (P＜0.05), and plasma adiponectin levels were significantly lower than those in polyps-free group [normal glucose tolerance (9.8±4.8 vs 13.3±3.9)mg/L, P＜0.05; prediabetes (5.6 ± 3.7 vs 9.2 ± 4.4)mg/L, P＜0.01], respectively. However, no significant difference in the plasma leptin and resistin levels were observed between polyps-free group and polyps group ( both P＞0. 05), respectively. In addition, in prediabetes subjects, plasma visfatin levels increased (P＜0.05) and adiponectin levels decreased significantly [(4.3 ± 2.6 vs 6.7 ± 3.9) mg/L, P＜0.05] in multiple polyps group than in single polyp group. Nevertheless, there were no significant differences in plasma leptin and resistin levels between two groups (both P＞0.05). Moreover, plasma adiponectin levels decreased significantly in high-risk polyps group with prediabetes than in low-risk polyps group with prediabetes[(3.7±2.9vs7.4±3.5)mg/L,P＜0.05].Meanwhile,noneofplasmavisfatin,leptin,andresistinlevels had shown significant difference between two groups (all P＞0.05). The multivariate logistic regression analysis found that adiponectin was an independent protective factor for colon polyps, multiple colon polyps and high-risk colon polyps. Conclusion The changes of plasma adiponectin levels might be associated with onset of colonic polyps in prediabetes.

Objective To compare the protective effect of double dose trimetazidine versus standard dose in patients with unstable angina and received PCI. Methods From September 2014 to June 2015,150 unstable angina pectoris patients who underwent PCI in our hospital were enrolled in this study. All the patients were randomized into two groups:the study group (patients given trimetazidine 40 mg tid 24 hours before operation) and the control group (patients given trimetazidine 20 mg tid 24 hours before operation). All patients received standard secondary prevention therapies of coronary heart disease. Comparison in the rates of angina pectoris attacks, ECG changes after PCI, levels of cardiac troponin I ( cTnI), myoglobin (Mb), creatine kinase isoenzyme ( CK-MB) and hs-CRP before and 12 hours after PCI was investigated between the 2 groups. Results Baseline data were comparable in the 2 groups. Rates of adverse drug reaction were lower in the control group, but the difference was not statistically significant (6. 7% vs. 2. 7% , P = 0. 439). There was no statistical difference between the two groups before PCI in terms of levels of cTNI and hs-CRP but was significantly lowered in the study group after PCI as compared to the control (both P < 0. 05 after PCI). The levels of CK-MB and Mb in the study group were lower than those in the control group after PCI, but the difference was not statistically significant. The rates of angina pectoris attacks and the changes in ST-T were less in the study group as compared to the control group without statistical significance. Conclusions Unstable angina pectoris patients receiving double dose of trimetazidine before PCI may enhance myocardial protection and reduce PCI related myocardial injury.