Fluoride-induced hypertension by regulating RhoA/ROCK pathway and phenotypic transformation of vascular smooth muscle cells: In vitro and in vivo evidence.

Fluoride exposure has been implicated as a potential risk factor for hypertension, but the underlying mechanisms remain unclear. This study investigated the role of the RhoA/ROCK signaling pathway in fluoride-induced hypertension. Male Wistar rats were divided into different groups and exposed to varying concentrations of sodium fluoride (NaF) or sodium chloride (NaCl) via drinking water. The rats' blood pressure was measured, and their aortic tissue was utilized for high-throughput sequencing analysis. Additionally, rat and A7r5 cell models were established using NaF and/or Fasudil. The study evaluated the effects of fluoride exposure on blood pressure, pathological changes in the aorta, as well as the protein/mRNA expression levels of phenotypic transformation indicators (a-SMA, calp, OPN) in vascular smooth muscle cells (VSMCs), along with the RhoA/ROCK signaling pathway (RhoA, ROCK1, ROCK2, MLC/p-MLC). The results demonstrated that fluoride exposure in rats led to increased blood pressure. High-throughput sequencing analysis revealed differential gene expression associated with vascular smooth muscle contraction, with the RhoA/ROCK signaling pathway emerging as a key regulator. Pathological changes in the rat aorta, such as elastic membrane rupture and collagen fiber deposition, were observed following NaF exposure. However, fasudil, a ROCK inhibitor, mitigated these pathological changes. Both in vitro and in vivo models confirmed the activation of the RhoA/ROCK signaling pathway and the phenotypic transformation of VSMCs from a contractile to a synthetic state upon fluoride exposure. Fasudil effectively inhibited the activities of ROCK1 and ROCK2 and attenuated the phenotypic transformation of VSMCs. In conclusion, fluoride has the potential to induce hypertension through the activation of the RhoA/ROCK signaling pathway and phenotypic changes in vascular smooth muscle cells. These results provide new insights into the mechanism of fluoride-induced hypertension.

The ischemia-enhanced myocardial infarction protection-related lncRNA protects against acute myocardial infarction.

Long non-coding RNA RP11-64B16.4 (myocardial infarction protection-related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.

Transcriptome and small RNA analysis unveils novel insights into the C4 gene regulation in sugarcane.

MAIN CONCLUSION: This study reveals miRNA indirect regulation of C4 genes in sugarcane through transcription factors, highlighting potential key regulators like SsHAM3a. C4 photosynthesis is crucial for the high productivity and biomass of sugarcane, however, the miRNA regulation of C4 genes in sugarcane remains elusive. We have identified 384 miRNAs along the leaf gradients, including 293 known miRNAs and 91 novel miRNAs. Among these, 86 unique miRNAs exhibited differential expression patterns, and we identified 3511 potential expressed targets of these differentially expressed miRNAs (DEmiRNAs). Analyses using Pearson correlation coefficient (PCC) and Gene Ontology (GO) enrichment revealed that targets of miRNAs with positive correlations are integral to chlorophyll-related photosynthetic processes. In contrast, negatively correlated pairs are primarily associated with metabolic functions. It is worth noting that no C4 genes were predicted as targets of DEmiRNAs. Our application of weighted gene co-expression network analysis (WGCNA) led to a gene regulatory network (GRN) suggesting miRNAs might indirectly regulate C4 genes via transcription factors (TFs). The GRAS TF SsHAM3a emerged as a potential regulator of C4 genes, targeted by miR171y and miR171am, and exhibiting a negative correlation with miRNA expression along the leaf gradient. This study sheds light on the complex involvement of miRNAs in regulating C4 genes, offering a foundation for future research into enhancing sugarcane's photosynthetic efficiency.

Advances in Fatigue Performance of Metal Materials with Additive Manufacturing Based on Crystal Plasticity: A Comprehensive Review.

Using metal additive manufacturing processes can make up for traditional forging technologies when forming complex-shaped parts. At the same time, metal additive manufacturing has a fast forming speed and excellent manufacturing flexibility, so it is widely used in the aerospace industry and other fields. The fatigue strength of metal additive manufacturing is related to the microstructure of the epitaxially grown columnar grains and crystallographic texture. The crystal plasticity finite element method is widely used in the numerical simulation of the microstructure and macro-mechanical response of materials, which provides a strengthening and toughening treatment and can reveal the inner rules of material deformation. This paper briefly introduces common metal additive manufacturing processes. In terms of additive manufacturing fatigue, crystal plasticity simulations are summarized and discussed with regard to several important influencing factors, such as the microstructure, defects, surface quality, and residual stress.

Relationship between bilirubin and systemic lupus erythematosus: A systematic review and meta-analysis.

AIMS: Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence worldwide. This study aimed to examine the correlation between serum bilirubin levels and SLE. METHODS: The Cochrane library, Embase, PubMed, and China National Knowledge Infrastructure (CNKI) databases were examined and assessed until March 2023. RevMan 5.3 software was utilized for the analysis of clinical trails. RESULTS: Five case-control studies were chosen and incorporated, examining the levels of serum bilirubin in patients with SLE compared to healthy individuals, as well as in active SLE patients versus inactive ones, in different sexes and in SLE patients with or without lupus nephritis (LN). The results of this meta-analysis demonstrated that serum bilirubin in healthy individuals were obviously increased compared to SLE patients (MD = 4.76; 95% CI, 3.15-6.38, p < .00001). Additionally, inactive SLE patients had higher levels of bilirubin than active SLE patients (MD = 3.15; 95% CI, 0.46-5.84, p = .02), and SLE patients without lupus nephritis had higher levels of serum bilirubin than those with lupus nephritis (MD = 4.91;95% CI, 2.87-6.95, p < .00001). Nevertheless, there were no disparities observed among SLE patients of varying sexes (MD = 0.34; 95% CI, -0.01 to 0.69, p = .06). CONCLUSION: The concentration of serum bilirubin may potentially be used as an indicator for estimating the advancement of SLE and reflecting the presence of kidney complications in individuals with SLE. Furthermore, more high quality studies were needed to identify these findings.

Effect of Strain Rate and Temperature on the Tensile Properties of Long Glass Fiber-Reinforced Polypropylene Composites.

Strain rate and temperature are influential factors that significantly impact the mechanical properties of long glass fiber-reinforced polypropylene composites. This study aims to investigate the tensile properties of these composites, analyzing the effects of temperature, strain rate, and their interplay on variables such as tensile stress, tensile strength, fracture stress, and fracture morphology through a series of comprehensive tensile experiments. The experimental results demonstrate a notable increase in both tensile strength and tensile fracture stress when the temperature is set at 25 °C, accompanied by strain rates of 10-4, 10-3, 10-2, and 10-1 s-1. Conversely, a significant decrease is observed in the aforementioned properties when the strain rate is fixed at 10-4, while varying temperatures of -25 °C, 0 °C, 25 °C, 50 °C, and 75 °C are applied. At lower temperatures, cracks manifest on the fracture surface, while matrix softening occurs at higher temperatures. Additionally, in the context of strain rate-temperature coupling, the decreasing trend of both tensile strength and tensile fracture stress decelerates as the temperature ranges from -25 °C to 75 °C at a strain rate of 10-1, compared to 10-4 s-1. These findings highlight the significant influence of both strain rate and temperature on high fiber content long glass fiber-reinforced polypropylene composites.

Multiple Metabolites Derived from Mushrooms and Their Beneficial Effect on Alzheimer's Diseases.

Mushrooms with edible and medicinal potential have received widespread attention because of their diverse biological functions, nutritional value, and delicious taste, which are closely related to their rich active components. To date, many bioactive substances have been identified and purified from mushrooms, including proteins, carbohydrates, phenols, and vitamins. More importantly, molecules derived from mushrooms show great potential to alleviate the pathological manifestations of Alzheimer's disease (AD), which seriously affects the health of elderly people. Compared with current therapeutic strategies aimed at symptomatic improvement, it is particularly important to identify natural products from resource-rich mushrooms that can modify the progression of AD. This review summarizes recent investigations of multiple constituents (carbohydrates, peptides, phenols, etc.) isolated from mushrooms to combat AD. In addition, the underlying molecular mechanisms of mushroom metabolites against AD are discussed. The various mechanisms involved in the antiAD activities of mushroom metabolites include antioxidant and anti-neuroinflammatory effects, apoptosis inhibition, and stimulation of neurite outgrowth, etc. This information will facilitate the application of mushroom-derived products in the treatment of AD. However, isolation of new metabolites from multiple types of mushrooms and further in vivo exploration of the molecular mechanisms underlying their antiAD effect are still required.

Evidence-based guideline for the prevention and management of perioperative infection.

BACKGROUND: We have updated the guideline for preventing and managing perioperative infection in China, given the global issues with antimicrobial resistance and the need to optimize antimicrobial usage and improve hospital infection control levels. METHODS: We conducted a comprehensive evaluation of the evidence for prevention and management of perioperative infection, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Revisions were made to the guidelines in response to feedback from the experts. RESULTS: There were 17 questions prepared, for which 37 recommendations were made. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the meta-analysis results, recommendations were graded using the Delphi method to generate useful information. CONCLUSIONS: This guideline provides evidence to perioperative antimicrobial prophylaxis that increased the rational use of prophylactic antimicrobial use, with substantial improvement in the risk-benefit trade-off.

Optimal clinical protocols for total-body 18F-FDG PET/CT examination under different activity administration plans.

BACKGROUND: Highly sensitive digital total-body PET/CT scanners (uEXPLORER) have great potential for clinical applications and fundamental research. Given their increasing sensitivity, low-dose scanning or snapshot imaging is now possible in clinics. However, a standardized total-body 18F-FDG PET/CT protocol is still lacking. Establishing a standard clinical protocol for total-body 18F-FDG PET/CT examination under different activity administration plans can help provide a theoretical reference for nuclear radiologists. METHODS: The NEMA image quality (IQ) phantom was used to evaluate the biases of various total-body 18F-FDG PET/CT protocols related to the administered activity, scan duration, and iterations. Several objective metrics, including contrast recovery (CR), background variability (BV), and contrast-to-noise ratio (CNR), were measured from different protocols. In line with the European Association of Nuclear Medicine Research Ltd. (EARL) guidelines, optimized protocols were suggested and evaluated for total-body 18F-FDG PET/CT imaging for three different injected activities. RESULTS: Our NEMA IQ phantom evaluation resulted in total-body PET/CT images with excellent contrast and low noise, suggesting great potential for reducing administered activity or shortening the scan duration. Different to the iteration number, prolonging the scan duration was the first choice for achieving higher image quality regardless of the activity administered. In light of image quality, tolerance of oncological patients, and the risk of ionizing radiation damage, the 3-min acquisition and 2-iteration (CNR = 7.54), 10-min acquisition and 3-iteration (CNR = 7.01), and 10-min acquisition and 2-iteration (CNR = 5.49) protocols were recommended for full-dose (3.70 MBq/kg), half-dose (1.95 MBq/kg), and quarter-dose (0.98 MBq/kg) activity injection schemes, respectively. Those protocols were applied in clinical practices, and no significant differences were observed for the SUVmax of large/small lesions or the SUVmean of different healthy organs/tissues. CONCLUSION: These findings support that digital total-body PET/CT scanners can generate PET images with a high CNR and low-noise background, even with a short acquisition time and low administered activity. The proposed protocols for different administered activities were determined to be valid for clinical examination and can maximize the value of this imaging type.

Multivariate models of commodity futures markets: a dynamic copula approach.

We apply flexible multivariate dynamic models to capture the dependence structure of various US commodity futures across different sectors between 2004 and 2022; particular attention is paid to the 2008 financial crisis and the COVID-19 pandemic. Our copula-based models allow for time-varying nonlinear and asymmetric dependence by integrating elliptical and skewed copulas with dynamic conditional correlation (DCC) and block dynamic equicorrelation (Block DECO). Flexible copula models that allow for multivariate asymmetry and tail dependence are found to provide the best performance in characterizing co-movements of commodity returns. We also find that the connectedness between commodities has dramatically increased during the financial distress and the COVID-19 pandemic. The impacts of the financial crisis appear to be more persistent than those of the pandemic. We apply our models to some risk management tasks in the commodity markets. Our results suggest that optimal portfolio weights based on dynamic copulas have persistently outperformed the equal-weighted portfolio, demonstrating the practicality and usefulness of our proposed models.

Palmitic Acid, A Critical Metabolite, Aggravates Cellular Senescence Through Reactive Oxygen Species Generation in Kawasaki Disease.

Coronary artery lesions (CALs) are severe complications of Kawasaki disease (KD), resulting in stenosis and thrombogenesis. Metabolomic profiling of patients' plasma could assist in elucidating the pathogenesis of CALs and identifying diagnostic biomarkers, which are imperative for clinical treatment. The metabolic profiles between KD patients with CALs and without CALs (non-coronary artery lesion, or NCAL, group) indicated the most significantly differentially expressed metabolite, palmitic acid (PA), showed the most massive fold change at 9.879. Furthermore, PA was proven to aggravate endothelial cellular senescence by increasing the generation of reactive oxygen species (ROS) in KD, and those two phenotypes were confirmed to be enriched among the differentially expressed genes between KD and normal samples from GEO datasets. Collectively, our findings indicate that cellular senescence may be one of the mechanisms of vascular endothelial damage in KD. PA may be a biomarker and potential therapeutic target for predicting the occurrence of CALs in KD patients. All things considered, our findings confirm that plasma metabolomics was able to identify promising biomarkers and potential pathogenesis mechanisms in KD. To conclude, Palmitic acid could be a novel target in future studies of CALs in patients with KD.

Docosahexaenoic Acid-Enhanced Autophagic Flux Improves Cardiac Dysfunction after Myocardial Infarction by Targeting the AMPK/mTOR Signaling Pathway.

Background and Purpose. Docosahexaenoic acid (DHA) is a type of polyunsaturated fatty acid enriched in cod liver oil and seaweed. It is necessary for the human body and has important functions, such as antioxidation and antiatherosclerosis activities. Long-term oral administration of DHA or the use of DHA at the initial stage of ischemia can increase the level of autophagy and exert a protective effect on neurological functions related to cerebral infarction. However, the effect of DHA on myocardial injury and cardiac insufficiency after myocardial infarction (MI) is unknown. This study was aimed at exploring whether DHA plays a protective role in AMI and its specific molecular mechanism. Experimental Method. In vitro cardiomyocyte hypoxia and in vivo MI injury models were used to determine the role of DHA in MI. Hypoxic injury induced damage in cultured neonatal mouse cardiomyocytes (NMCs). The C57BL/6J mouse MI model was established by permanent ligation of the left anterior descending branch. Main Results. DHA improved the cardiomyocyte viability of NMCs induced by hypoxia injury and reduced cell necrosis. DHA reduced infarct size, improved heart function, and reduced the degree of myocardial fibrosis in mice after MI. In addition, DHA enhanced autophagy flux and reduced apoptosis in vitro and in vivo. In addition, we found that chloroquine, an autophagy inhibitor, blocked the protective effect of DHA on cardiomyocyte apoptosis and cardiac dysfunction, indicating that DHA exerts cardioprotective effects in part by promoting autophagy flux. We also observed that DHA enhanced autophagy flux by activating the AMPK/mTOR signaling pathway. Conclusions and Significance. In conclusion, our findings indicate for the first time that DHA improves MI-induced cardiac dysfunction by promoting AMPK/mTOR-mediated autophagic flux.

[18F]FAPI-42 PET imaging in cancer patients: optimal acquisition time, biodistribution, and comparison with [68Ga]Ga-FAPI-04.

PURPOSE: [18F]FAPI-42 is a new fibroblast activation protein (FAP)-specific tracer used for cancer imaging. Here, we describe the optimal acquisition time and in vivo evaluation of [18F]FAPI-42 and compared intra-individual biodistribution, tumor uptake, and detection ability to [68Ga]Ga-FAPI-04. METHODS: A total of 22 patients with various types of cancer received [18F]FAPI-42 whole-body positron emission tomography/computed tomography (PET/CT). Among them, 4 patients underwent PET/CT scans, including an early dynamic 20-min, static 1-h, and static 2-h scans. The in vivo biodistribution in normal organs and tumor uptake were semiquantitatively evaluated using the standardized uptake value (SUV) and tumor-to-background ratio (TBR). Furthermore, both [18F]FAPI-42 and [68Ga]Ga-FAPI-04 PET/CT were performed in 12 patients to compare biodistribution, tumor uptake, and tumor detection ability. RESULTS: [18F]FAPI-42 uptake in the tumors was rapid and reached a high level with an average SUVmax of 15.8 at 18 min, which stayed at a similarly high level to 2 h. The optimal image acquisition time for [18F]FAPI-42 was determined to be 1 h postinjection. For tumor detection, [18F]FAPI-42 had a high uptake and could be clearly visualized in the lesions. Compared to [68Ga]Ga-FAPI-04, [18F]FAPI-42 had the same detectability for 144 positive lesions. In addition, [18F]FAPI-42 showed a higher SUVmax in liver and bone lesions (P < 0.05) and higher TBRs in liver, bone, lymph node, pleura, and peritoneal lesions (all P < 0.05). CONCLUSION: The present study demonstrates that the optimal image acquisition time of [18F]FAPI-42 is 1 h postinjection and that [18F]FAPI-42 exhibits comparable lesion detectability to [68Ga]Ga-FAPI-04. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100045757).

Post-interventional Evaluation and Follow-Up in Children With Patent Ductus Arteriosus Complicated With Moderate to Severe Pulmonary Arterial Hypertension: A Retrospective Study.

Background: Transcatheter closure is an important treatment for patent ductus arteriosus (PDA) complicated with moderate and severe pulmonary arterial hypertension (PAH). This report presents our experience with transcatheter closure of PDA complicated with moderate and severe PAH. Methods: The 49 cases of PDA complicated with moderate and severe PAH were collected in the Second Affiliated Hospital and Yuying Children's Hospital from January 2014 to December 2019 with transcatheter closure of PDA and follow-up. All patients were invited for transthoracic echocardiography, electrocardiogram, and thoracic radiography check-up. Results: Device implantation was successful in 48 of 49 patients (98.0%). Among them, 30 cases were in the PAH after defect correction (CD) group, and 19 examples were in the Non-PAH after defect correction (NCD) group. Pulmonary systolic pressure, left atrial diameter, and left ventricular end-diastolic diameter immediately after interventional therapy and 6 months later were lower than the pre-operative levels (p < 0.05). The incidence of the immediate residual shunt (RS) in this study was 34.9%, most of which were minimal amount shunt. RS disappeared in all patients within 1 year of therapy. Four patients had thrombocytopenia and one patient had left pulmonary artery stenosis. No other serious adverse event occurred during the follow-up period. The pressure gradient tricuspid valve regurgitation (PGTI) and the right heart catheterization (RHC) consistency points were 93.75% (15/16) and were within the 95% consistency limit by the Bland-Altman method. The Logistic regression analysis concluded that the pre-operative Pp/Ps and the narrowest diameter of PDA are risk factors for post-operative PAH (p < 0.05). The cut-off point of the pre-operative Pp/Ps and the narrowest diameter of PDA were calculated to be 0.595 and 4.75 mm, respectively. Conclusion: Interventional occlusion in children with PDA complicated with moderate and severe PAH is safe, effective, and has few complications. Targeted drug therapy has a good clinical effect. The narrowest diameter of PDA and the pre-operative Pp/Ps may be one of the risk factors of residual PAH after interventional therapy.

Individualized Experience With Percutaneous Transcatheter Closure of Multiple Atrial Septal Defects: A Single-Center Study.

Multiple atrial septal defects (ASDs) are one type of secundum ASD, most of which have an atrial septal aneurysm or long interdefect distance. In our retrospective single-center study, we reviewed different closure strategies for multiple ASDs. We analyzed 50 patients who underwent percutaneous transcatheter closure from May 2011 to July 2019. Information on the patients' characteristics, operation procedure, occluder selection, and complications was collected. According to the feature of the defects and device choice, multiple ASDs were divided into five groups. A successful operation was achieved in every patient. A total of 50 patients were implanted with 58 devices, with 26 patients implanted with a single standard ASD occluder (ASDO); six patients were implanted with double standard ASDOs, and only one patient was implanted with three standard ASDOs. There were 17 patients whose closure was made using the small-waist-big-edge ASDO. Seventy-six percent of the patients (38/50) had an immediate residual shunt. During the mean follow-up of 25.76 ± 22.53 months, the complete closure rate was 92%. Except for two patients with a transient atrioventricular block, individualized experience with percutaneous transcatheter closure for multiple ASDs was effective in a single-center study. After a mid- to long-term follow-up, the multiple ASDOs and small-waist-big-edge ASDO had no serious adverse events or complications.

Analysis of the impact of foreign direct investment on urbanization in China from the perspective of "circular economy".

Persisting in opening up and achieving coordinated development of economy, society, and ecology is China's major strategies for achieving sustainable urbanization. Ecological efficiency is a reasonable indicator to measure the development level of a circular economy. Therefore, using the statistical data of 30 provinces in China from 2004 to 2016, this paper uses the super-efficiency SBM model that considers undesired output to measure the eco-efficiency value, which is used to measure the level of circular economy development in each province. Based on this, a panel model is constructed to test the impact of circular economy and FDI on urbanization. The empirical results show that (1) there is a complex nonlinear relationship between the development of circular economy and the advancement of urbanization, and the shape of the curve varies with areas; (2) FDI under environmental regulation is conducive to promoting China's urbanization to achieve green, effective, and sustainable development; and (3) the development of the tertiary industry, human resources, innovation capabilities, and employment situation is conducive to promoting China's urbanization. Finally, based on the empirical results, this paper puts forward policy recommendations to achieve green, efficient, and intelligent development of Chinese cities by promoting the development of a circular economy and strengthening FDI screening.

The diagnostic role of AIM2 in Kawasaki disease.

Kawasaki disease (KD), a systemic vasculitis in children, may bring serious complications. However, the etiology of KD remains unclear. AIM2, an intracellular receptor, plays a vital role during the infection caused by a variety of pathogens. However, its role in KD remains unclear. The principal aim of the present research is to concentrate on the relation between AIM2 and KD. We detected the levels of AIM2, IL-18 and IL-1ß in all subjects by ELISA. The conventional inflammatory indices were detected in all subjects, such as WBC, HB, CRP and so on. The serum concentrations of AIM2, IL-18 and IL-1ß were notably upregulated in the KD group compared to the febrile group and healthy group, respectively. And the three indicators in the KD patients were greatly reduced after interpreted with IVIG. Furthermore, the expressions of IL-18 and IL-1ß were positively correlated with AIM2. Meanwhile, the cutoff value of serum AIM2 level for the diagnosis of KD was 541.90 ng/L with the specificity of 60% and sensitivity of 92.5%, compared to the febrile controls. And the area under curve (AUC) of AIM2 was 0.771. And no difference was observed in patients with CALs when compared with patients without CALs. The serum AIM2, IL-18 and IL-1ß might play a critical role during the progress of KD. AIM2 can be considered as a candidate indicator for Kawasaki disease diagnosis.

A Systematic Review of the Efficacy and Safety of Aspirin When Delivered at Different Medication Times for the Primary and Secondary Prevention of Cardiovascular and Cerebrovascular Diseases.

PURPOSE: Effective antiplatelet therapy can significantly reduce the incidence and mortality rate of cardiovascular and cerebrovascular diseases. Aspirin is widely used in the secondary prevention of cardiovascular and cerebrovascular diseases; however, there is widespread debate as to when patients should take an enteric-coated aspirin tablet on a daily basis. In the present study, we evaluated the efficacy and safety of different aspirin medication times (morning or before bedtime) in terms of the primary and secondary prevention of cardiovascular and cerebrovascular diseases using meta-analysis. METHODS: Studies with randomized control trials (RCT) or crossover trials regarding to the usage of aspirin (morning or before bedtime) for the primary or secondary prevention of cardiovascular and cerebrovascular diseases were searched in Medline, EMbase, Cochrane Library, CNKI, Wanfang Data, VIP Database and CBM. Review Manager 5 (RevMan 5, v5.3), a Cochrane systematic reviews software, was used to perform meta-analysis based on the recommendation of the Cochrane Handbook for risk assessment tools. RESULTS: Meta-analysis showed that taking low-dose aspirin tablets before bed reduced systolic and diastolic blood pressure compared with taking it in the morning. At the same time, the number of studies on platelet aggregation rate, C-reactive protein (CRP), serum nitric oxide (NO) or thromboxane B2 (TXB2) is too small to be reliable. However, there was a large heterogeneity across the studies. The quality of some studies was not high enough. CONCLUSION: Additional blood pressure benefits can be achieved by taking aspirin before bedtime, but it does not affect its antiplatelet effect and does not pose a higher risk of bleeding.

Development and progress of clinical trials of Coronavirus Disease 2019 antiviral drugs.

INTRODUCTION: We have summarized and analyzed the clinical trial registration status and the latest research progress of eight major antiviral drugs during the epidemic of Coronavirus Disease 2019 (COVID-19), which can provide reference methods for clinical formulation of the best antiviral treatment. AREAS COVERED: We used the generic names of 8 antiviral drugs as keywords to search and analyze the COVID-19-related clinical trials registered in Chinese Clinical Trial Registry and ClinicalTrials.gov. Then, we used the keywords to obtain and summarize their clinical research results related to COVID-19 in CNKI, WANFANG, CQVIP, and PubMed database. EXPERT OPINION: The registration system of clinical trials and the level of clinical trial design need to be further improved. At present, no specific drug has been found for the treatment of COVID-19, the efficacy of antiviral drugs mostly comes from small sample studies or retrospective studies, and the level of clinical evidence is low. Besides, multi-drug combination therapy may become a more effective treatment choice, but the drug interactions and adverse drug reactions also need to be closely monitored. In summary, the safety and efficacy of various antiviral drugs need to be confirmed by large samples and high-quality RCT studies.

Cost-Utility Analysis of four Chelation Regimens for ß-thalassemia Major: a Chinese Perspective.

OBJECTIVE: The Iron chelation is essential to prevent iron overload damage of vital organs, like heart, liver, and endocrine glands, in patients with transfusion-dependent thalassemia. The most common chelation regimens for ß-thalassemia major (ß-TM) patients used in China are a combination therapy of deferoxamine and deferiprone (DFO+DFP), deferoxamine (DFO) monotherapy, deferiprone (DFP) monotherapy and deferasirox (DFX) monotherapy. Such patients use iron chelators their whole lives, resulting in enormous treatment costs. This study analyses the cost-utility of these four regimens from the Chinese healthcare system perspective. METHODS: A Markov decision model was used over a 5-year time horizon and was populated using clinical data from a systematic literature review. We obtained utility data from local and previous research. Costs were estimated using Chinese national sources. RESULTS: From the base-case analysis results, DFP was the most cost-effective chelation regimen, followed by DFO, DFX, and DFO+DFP. DFP had 97.32%, 99.43%, and 58.04% likelihood of being cost-effective versus DFX, DFO+DFP, and DFO, respectively, at a payment threshold of 193,932.00 CNY/QALY (QALY, quality-adjusted life-year). CONCLUSIONS: DFP was the most cost-effective chelation regimen for ß-TM patients, followed by DFO, DFX, and DFO+DFP. Using DFP as the primary treatment regimen may potentially result in cost-savings and QALY gains for the Chinese healthcare system. To increase these benefits, the Chinese government should take measures to lower DFX and DFO drug costs, and Chinese clinicians should choose the cheaper DFX and DFO, increase the utility of DFO+DFP and reduce mortality and morbidity of DFP. Changes in influential parameters easily affect the results of DFX versus DFO+DFP and of DFP versus DFO; clinicians should focus on such parameters and adjust the regimens accordingly.