Associations of trajectories in body roundness index with incident cardiovascular disease: a prospective cohort study in rural China.

Aims: The body roundness index (BRI) has good predictive ability for both body fat and visceral adipose tissue. Longitudinal BRI trajectories can reveal the potential dynamic patterns of change over time. This prospective study assessed potential associations between BRI trajectories and incident cardiovascular disease (CVD) in rural regions of Northeast China. Methods: In total, 13,209 participants (mean age: 49.0 ± 10.3 years, 6,856 [51.9%] male) were enrolled with three repeated times of BRI measurements at baseline (2004-2006), 2008, and 2010, and followed up until 2017 in this prospective study. Using latent mixture model, the BRI trajectories were determined based on the data from baseline, 2008 and 2010. Composite CVD events (myocardial infarction, stroke, and CVD death combined) was the primary endpoint. Cox proportional-hazards models were used to analyze the longitudinal associations between BRI trajectories and incident CVD. Results: Three distinct BRI trajectories were identified: high-stable (n = 538), moderate-stable (n = 1,542), and low-stable (n = 11,129). In total, 1,382 CVD events were recorded during follow-up. After adjustment for confounders, the moderate-stable and high-stable BRI groups had a higher CVD risk than did the low-stable BRI group, and the HR (95%CI) were 1.346 (1.154, 1.571) and 1.751 (1.398, 2.194), respectively. Similar associations were observed between the trajectories of BRI and the risk of stroke and CVD death. The high-stable group was also significantly and independently associated with CVD, myocardial infarction, stroke, and CVD death in participants aged <50 years. Conclusion: BRI trajectory was positively associated with incident CVD, providing a novel possibility for the primary prevention of CVD in rural regions of China.

Rapid Preparation of Highly Stretchable and Fast Self-Repairing Antibacterial Hydrogels for Promoting Hemostasis and Wound Healing.

Hydrogel dressings have emerged as a vital resource in wound management, offering several advantages over conventional wound dressing materials. Their inherent biocompatibility, ability to replicate the native extracellular matrix, and capacity to provide an ideal environment for cell survival make them particularly valuable. Nevertheless, the mechanical properties of many hydrogel dressings are an area that warrants improvement, as it currently constrains their application range. This limitation is especially evident when skin wounds are addressed in highly active or easily scratched areas. In this study, we present the development of a highly stretchable self-repairing hydrogel by cross-linking poly(vinyl alcohol) (PVA) through dynamic boron ester bonds, coupled with the hydrogen bonding of carboxymethyl cellulose sodium (CMC) via an efficient one-pot method without adding any catalyst. This innovative PVA/CMC hydrogel exhibited remarkable antibacterial properties achieved through the incorporation of bergamot oil, which was dispersed in a ß-cyclodextrin solution. The hydrogel's elongation at the point of rupture reached an impressive 1910%, and it was capable of rapid self-healing in just 3 min upon bonding. Additionally, the hydrogel demonstrated excellent hemostatic properties, effectively mitigating blood loss and exudation. In vivo wound models have shown that PVA/CMC significantly expedites wound healing by reducing bacterial infections, inflammatory responses, and blood loss and by promoting collagen deposition. In summary, this research provides crucial insights into its potential as an advanced wound dressing material, particularly well-suited for addressing wounds in places with frequent activities or easy scratches.

Efficacy and mechanism study of cordycepin against brain metastases of small cell lung cancer based on zebrafish.

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive tumor with high brain metastasis (BM) potential. There has been no significant progress in the treatment of SCLC for more than 30 years. Cordycepin has shown the therapeutic potential for cancer by modulating multiple cellular signaling pathways. However, the effect and mechanism of cordycepin on anti-SCLC BM remain unknown. PURPOSE: In this study, we focused on the anti-SCLC BM effect of cordycepin in the zebrafish model and its potential mechanism. STUDY DESIGN AND METHODS: A SCLC xenograft model based on zebrafish embryos and in vitro cell migration assay were established. Cordycepin was administrated by soaking and microinjection in the zebrafish model. RNA-seq assay was performed to analyze transcriptomes of different groups. Geno Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to reveal the underlying mechanism. Real-time qPCR was used to verify the effects of cordycepin on the key genes. RESULTS: Cordycepin showed lower cytotoxicity in vitro compared with cisplatin, anlotinib and etoposide, but showed comparable anti-proliferation and anti-BM effects in zebrafish SCLC xenograft model. Cordycepin showed significant anti-SCLC BM effects when administrated by both soaking and microinjection. RNA-seq demonstrated that cordycepin was involved in vitamin D metabolism, lipid transport, and proteolysis in cellular protein catabolic process pathways in SCLC BM microenvironment in zebrafish, and was involved in regulating the expressions of key genes such as cyp24a1, apoa1a, ctsl. The anti-BM effect of cordycepin in SCLC was mediated by reversing the expression of these genes. CONCLUSION: Our work is the first to describe the mechanism of cordycepin against SCLC BM from the perspective of regulating the brain microenvironment, providing new evidence for the anti-tumor effect of cordycepin.

Cumulative exposure to elevated blood pressure better predicts cardiovascular disease risk in rural Chinese adults.

Background: Traditional risk estimations for cardiovascular disease (CVD) are based on current blood pressure (BP); however, whether cumulative exposure to elevated BP among rural individuals has additional prognostic value is unclear. We aimed to validate the association of cumulative BP with CVD occurrence and assess the prognostic value of cumulative BP in CVD risk prediction. Methods: A total of 13,057 participants who underwent three examinations from 2004 to 2010 were included in this rural epidemiological study and followed up until 2017. Cumulative BP was defined as the sum of the product of the average BP values between consecutive examinations and the time interval for each pair of successive tests prior to the follow-up period. CVD incidents that occurred during the follow-up period were noted and verified by qualified researchers. We used multivariate Cox models to assess the association of cumulative BP with CVD risk. The receiver operating characteristic curve was constructed to determine the predictive differentiation of single baseline BP measurements and cumulative BP values for CVD outcomes. Results: During the follow-up period, 1,312 participants underwent CVD incidents. We found that cumulative systolic BP (hazard ratio = 1.334, 95% confidence interval: 1.245, 1.430) and cumulative diastolic BP (hazard ratio = 1.253, 95% confidence interval: 1.168, 1.343) were associated with CVD incidence above and beyond that of the current BP. These stronger associations persisted for stroke, myocardial infarction, and CVD mortality. The area under the curve for the model increased significantly (p < 0.001) from 0.735 (0.720, 0.750) to 0.742 (0.728, 0.757) when integrating cumulative systolic BP instead of baseline systolic BP. Conclusion: Cumulative BP in Chinese rural adults showed a stronger association with CVD incidence than that of current BP. Furthermore, cumulative BP slightly improved the predictive performance for CVD. Our findings underline the incremental predictive value of cumulative BP in CVD risk assessment among Chinese rural adults.

Prognostic value of myocardial salvage index assessed by cardiovascular magnetic resonance in reperfused ST-segment elevation myocardial infarction.

Aims: Cardiovascular magnetic resonance (CMR) is a powerful tool to quantify the myocardial area at risk (AAR) and infarct size (IS), and evaluate the extent of myocardial salvage in acute ST-segment elevation myocardial infarction (STEMI). This study aimed to assess the prognostic value of myocardial salvage index (MSI) assessed by CMR in reperfused STEMI and investigate whether MSI could improve the predictive efficacy of the Global Registry of Acute Coronary Events (GRACE) risk score. Methods and results: About 104 consecutive patients who were hospitalized with first-time STEMI and received reperfusion therapy were prospectively enrolled. The primary endpoint was the incident of major adverse cardiovascular event (MACE) including all-cause mortality, non-fatal myocardial reinfarction and congestive heart failure within 36 months after the index event. Cox regression analysis was used to evaluate the prognostic association of MSI with MACE risk. About 21 (20.2%) patients developed MACE during the 3-year follow-up period, and patients with MSI < median had a higher incidence of MACE than those with MSI ≥ median [16 (30.8%) vs. 5 (9.6%), P = 0.007]. After adjusting all the parameters associated with MACE in univariate Cox analysis, MSI assessed by CMR remained independently significant as a predictor of MACE in multivariate Cox analysis (hazard ratio 0.963, 95% CI: 0.943-0.983; P < 0.001). Adding MSI to the GRACE risk score significantly increased the prognostic accuracy of the GRACE risk score (area under the curve: 0.833 vs. 0.773; P = 0.044), with a net reclassification improvement of 0.635 (P = 0.009) and an integrated discrimination improvement of 0.101 (P = 0.002). Conclusion: This study confirmed that MSI assessed by CMR had a good long-term prognostic value in reperfused STEMI and improve the prognostic performance of the GRACE risk score.

Association of isolated diastolic hypertension based on different guideline definitions with incident cardiovascular risk in a Chinese rural cohort.

The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline lowered the threshold (systolic blood pressure [SBP] <130 mm Hg and diastolic blood pressure [DBP] ≥80 mm Hg) for isolated diastolic hypertension (IDH), whereas the 2018 Chinese guideline still recommends the old threshold (SBP <140 mm Hg and DBP ≥90 mm Hg). This study aimed to investigate the association between IDH, as defined by both guidelines, and the risk of incident cardiovascular disease (CVD) in rural areas of northeast China. This prospective study included participants whose baseline data were collected between 2004 and 2006. The exclusion criteria were baseline CVD, incomplete data, and systolic hypertension. The primary end point was incident CVD, a composite end point including nonfatal myocardial infarction (MI), nonfatal stroke, and CVD death. Multivariate Cox models were used to evaluate the association of IDH with CVD risk. The authors analyzed 19 688 participants (7140 participants with IDH) according to the ACC/AHA guideline. Compared with normotensive participants, individuals with ACC/AHA-defined IDH were at a high risk of CVD (HR = 1.177, 95% CI: 1.035-1.339). A similar difference in CVD risk was noted when normotensive participants were compared with those with IDH, determined based on the 2018 Chinese guideline (HR = 1.218, 95% CI: 1.050-1.413). Similar results were found in participants who did not take antihypertensives at baseline. Moreover, IDH defined by either guideline was significantly associated with nonfatal MI. ACC/AHA-defined IDH was associated with a risk of CVD, implying that blood pressure management should be improved in rural areas of China.

Mechanism of hepatotoxicity of first-line tyrosine kinase inhibitors: Gefitinib and afatinib.

AIMS: Both gefitinib and afatinib are epidermal growth factor tyrosine kinase inhibitors (EGFR-TKI) in the treatment of non-small cell lung cancer (NSCLC). It has been reported that gefitinib and afatinib could cause hepatotoxicity during the clinic treatment, therefore it is critical to investigate their hepatotoxicity systematically. In this study, zebrafish (Danio rerio) were used as model animals to compare the hepatotoxicity and their toxic mechanism. MAIN METHODS: The zebrafish transgenic line [Tg (fabp10a: dsRed; ela3l:EGFP) was used in this study. After larvae developed at 3 days post fertilization (dpf), they were put into different concentrations of gefitinib and afatinib. At 6 dpf, the viability, liver area, fluorescence intensity, histopathology, apoptosis, transaminase reflecting liver function, the absorption of yolk sac, and the expression of relative genes were observed and analyzed respectively. KEY FINDINGS: Both gefitinib and afatinib could induce the larvae hepatotoxicity dose-dependently. Based on the liver morphology, histopathology, apoptosis and function assessments, gefitinib showed higher toxicity, causing more serious liver damage. Both gefitinib and afatinib caused abnormal expressions of genes related to endoplasmic reticulum stress (ERS) pathway and apoptosis. For example, jnk, perk, bip, chop, ire1, bid, caspase3 and caspase9 were up-regulated, while xbp1s, grp78, bcl-2/bax, and caspase8 were down-regulated. The hepatotoxicity difference of gefitinib and afatinib might be due to the different expression level of related genes.

End-of-life passenger vehicles recycling decision system in China based on dynamic material flow analysis and life cycle assessment.

China's automobile industry is developing rapidly, but the recycling rate of end-of-life vehicles has been low. In 2018, the recovery rate of end-of-life passenger vehicles was less than 18% of the scrapped amount. Dynamic material flow analysis can predict the amount of end-of-life passenger cars in China in the future, and analyze the flow of materials in recycling system. Life cycle assessment can be used to quantify greenhouse gas emissions. Therefore, this paper integrates these two methods into the model construction of recycling decision system. Meanwhile, sensitivity analysis of the important factors affecting the efficiency of the recovery system is carried out. Finally, the main recovery indexes of the system are predicted under three scenarios: low-speed, medium speed and high-speed development, which are set based on scrap volume, standard recovery rate, proportion of assembly into remanufacturing and carbon tax price. The research results show that in 2018, 656.9 kg/vehicle of iron, 150.2 kg/vehicle of aluminum and 7.9 kg/vehicle of copper are recovered from end-of-life passenger car in China, and the carbon emission during the recovery process is 651.1 kg of CO2eq/vehicle, with a total emission reduction of 3816.1 kgCO2eq/vehicle compared with the original production, and the economic benefit is about 5055.5 yuan/vehicle. The scenario prediction results show that by 2050, from the low-speed development scenario to the high-speed development scenario, the total amount of iron, aluminum and copper recovered rise from 3.96 million tons, 915 thousand tons and 46 thousand tons to 697 thousand tons, 1.61 million tons and 80 thousand tons respectively throughout the year. The carbon emission in the recovery process rise from 4.98 thousand tons to 9.32 million tons. Compared with the original production, the carbon emission reduction increases from 2.21 million tons to 38.3 million tons, the economic benefit increases from 58.9 billion yuan to 118.8 billion yuan, and the comprehensive benefit increases from 57 billion yuan to 111.6 billion yuan.

A systematical comparison of anti-angiogenesis and anti-cancer efficacy of ramucirumab, apatinib, regorafenib and cabozantinib in zebrafish model.

AIMS: Gastric cancer (GC) is one of the most common malignant tumors in the world. Anti-angiogenic therapy is a useful strategy for the treatment of advanced GC. This study was aimed to systemically compare the anti-angiogenesis, anti-cancer efficacy, as well as the safety of four known anti-angiogenic drugs, namely ramucirumab, apatinib, regorafenib and cabozantinib. MAIN METHODS: Anti-angiogenic effect was evaluated for the intersegmental vessels (ISVs) and subintestinal veins (SIVs) formation in the Tg (fli-1: EGFP) zebrafish embryos. Anti-cancer efficacy was tested for the in vivo cell proliferation in cell line derived tumor xenograft (CDX) model based on Tg (fli-1: EGFP) zebrafish embryos. KEY FINDINGS: All four drugs exhibited anti-angiogenic abilities and tumor inhibition effects in fli-1: EGFP transgenic zebrafish. Using zebrafish xenografted model, we found that effectiveness of ramucirumab in anti-GC-proliferation is better than apatinib, regorafenib and cabozantinib. The combination of anti-angiogenic drugs and cisplatin showed no significant benefit in tumors. Meanwhile, toxicity assay showed that all tested anti-angiogenic drugs could cause cardiovascular-related side effects. The therapeutic index (LD50/ED50) of cabozantinib is higher than apatinib and regorafenib, suggesting a potential as an anti-GC drug. SIGNIFICANCE: The comparison of GC-related anti-angiogenic drugs was first reported. It was found that cabozantinib had a potential as an anti-GC drug. Zebrafish model was an ideal animal model for the research of anti-angiogenic behaviors.