Macrophage KLF15 prevents foam cell formation and atherosclerosis via transcriptional suppression of OLR-1.

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.

Prevalence, contemporary trends and associated factors of potentially inappropriate prescription of edoxaban in real-world clinical practice: A subanalysis of the SUNSHINE registry.

AIM: As the direct oral anticoagulant most recently approved in China, data pertaining to clinical edoxaban use are still scarce. This study investigated the prevalence of and contemporary trends in edoxaban prescription among Chinese patients as well as factors associated with its inappropriate use in a multicentre registry of patients treated in real-world clinical practice. METHODS: This real-world, prospective, multicentre and non-interventional study included 1005 inpatients treated with edoxaban. According to National Medical Products Administration and European Heart Rhythm Association guidelines, edoxaban therapy was determined to be appropriate or inappropriate in each case. RESULTS: The median patient age was 70.0 years (interquartile range 61.0-78.0 years) and 46.3% were women. Overall, 456 (45.4%) patients received inappropriate edoxaban therapy, and common issues included an inappropriately low dosage (183, 18.2%) or wrong drug selection (109, 10.8%), high dosage (73, 7.3%), unreasonable off-label use (49, 4.9%), contraindicated medication combinations (27, 2.7%) and incorrect administration timing (16, 1.6%). Several factors, such as age ≥75 years (odds ratio [OR] = 1.921, 95% confidence interval [CI] 1.355-2.723, P < 0.001), weight >60 kg (OR = 2.657, 95%CI 1.970-3.583, P < 0.001), severe renal insufficiency (OR = 1.988, 95% CI 1.043-3.790, P = 0.037), current anaemia (OR = 1.556, 95% CI 1.151-2.102, P = 0.004) and history of bleeding (OR = 2.931, 95% CI 1.605-5.351, P < 0.001) were associated with an increased risk of inappropriate edoxaban therapy, whereas factors associated with cardiovascular specialties, such as admission to a cardiovascular department (OR = 0.637, 95% CI 0.464-0.873, P = 0.005), dronedarone use (OR = 0.065, 95% CI 0.026-0.165, P < 0.001) and amiodarone use (OR = 0.365, 95% CI 0.209-0.637, P < 0.001) decreased this risk. CONCLUSION: In this real-world study, 45.4% of patients received an inappropriate treatment with edoxaban. Multiple clinical characteristics can help identify patients who should receive edoxaban. Further development and implantation of educational activities and management strategies are needed to ensure the correct use of edoxaban.

A review: The formation, prevention, and remediation of acid mine drainage.

In abandoned open-pit coal mines, surface water and groundwater form acidic waters with high concentrations of metal ions due to chemical interactions with ores such as pyrite, and the formation of acid mine drainage (AMD) is one of the major sources of pollution of world concern. For this reason, this paper reviews the formation mechanisms and influencing factors of AMD. It also describes the prediction, prevention, and remediation techniques for AMD, identifying key research gaps. It also discusses the current challenges and shortcomings faced globally in the management of AMD. The formation of AMD is mainly caused by the oxidation of pyrite in mines, but it is mainly influenced by history, climate, topography, and hydrogeology, making the formation mechanism of AMD extremely complex. Currently, the remediation technologies for AMD mainly include active treatment and passive treatment, which can effectively neutralize acidic wastewater. However, the prediction technology for AMD is blank, and the source treatment technology such as passivation and microencapsulation only stays in the experimental stage. This leads to the high cost of treatment technologies at this stage and the inability to identify potential risks in mines. Overall, this review provides remediation tools for AMD from predicting root causes to treatment. Geophysical technology is an effective method for predicting the motion path and pollution surface of AMD in the future, and resource recovery for AMD is a key point that must be paid attention to in the future. Finally, integrated treatment technologies that deserve further exploration need to be emphasized.

Simultaneous Determination of 108 Pesticide Residues in Three Traditional Chinese Medicines Using a Modified QuEChERS Mixed Sample Preparation Method and HPLC-MS/MS.

A rapid, efficient, simple, and high-throughput method for the simultaneous determination of 108 pesticide residues in three traditional Chinese medicines (TCMs) was established, comprising an improved QuEChERS method in combination with HPLC-MS/MS based on mixed samples. A quantity of 10 mL of acetonitrile was used as extraction solvent, and 10 mg of amino-modified multi-walled carbon nanotubes (MWCNTs-NH2) and 150 mg of anhydrous magnesium sulfate (MgSO4) were selected as sorbents for dispersive solid phase extraction. The performance of the method was verified according to the analytical quality control standards of SANTE/11813/2017 guidelines. With good linearity (R2 > 0.9984) in the range of 2−200 µg/L for all pesticides in the selected matrices, and good accuracy, precision, and high sensitivity, the recoveries were in the range of 70−120% for more than 95% of the pesticides, with a relative standard deviation (RSD) of less than 16.82% for all. The limit of detection (LOD) and limit of quantification (LOQ) of the method were 0.01−3.87 µg/kg and 0.07−12.90 µg/kg, respectively, for Fritillaria thunbergii Miq (F. thunbergii), Chrysanthemum Morifolium Ramat (C. morifolium), and Dendrobium officinale Kimura et Migo (D. officinale). The method was successfully applied to 60 batches of actual samples from different regions.

Prevalence, risk factors, and prediction of inappropriate use of non-vitamin K antagonist oral anticoagulants in elderly Chinese patients with atrial fibrillation: A study protocol.

Background: Atrial fibrillation (AF) is an arrhythmia that is prevalent globally, and its incidence grows exponentially with aging. Non-vitamin K antagonist oral anticoagulants (NOACs) have been developed in recent years, and it challenges the supremacy of warfarin for thromboembolism prophylaxis in AF. Nevertheless, there are limited data specifically evaluating the real-life use of NOACs in elderly patients with AF in China. Methods: This is a national, multicenter, non-interventional, cross-sectional study that enrolls patients with AF aged 75 years and above from 31 institutions across China. Data were collected using the Hospital Information System. The primary outcomes include (1) profiles of NOAC use in the elderly; (2) frequency of inappropriate NOAC use based on guidelines and approved labeling recommendations; (3) exploring potential risk factors related to NOACs inappropriate use; and (4) creating a prediction tool for inappropriate NOACs use. Conclusion: The results of this study reveal the prevalence, risk factors, and corresponding prediction tool of inappropriate NOACs use in older patients with AF in China, as well as provide valuable insights into the clinical application of NOACs in high-risk populations in the real-world setting. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT05361889.

Combination of puerarin and tanshinone IIA alleviates ischaemic stroke injury in rats via activating the Nrf2/ARE signalling pathway.

CONTEXT: Puerarin (Pue) and tanshinone IIA (Tan IIA) are often used in combination in the treatment of cerebrovascular diseases. OBJECTIVE: To investigate the neuroprotective effect and synergic mechanism of Pue-Tan IIA on the treatment of ischaemic stroke (IS). MATERIALS AND METHODS: IS was induced in rats by middle cerebral artery occlusion (MCAO). Rats were intraperitoneally injected with Pue (36 mg/kg), Tan IIA (7.2 mg/kg), or Pue-Tan IIA (36 and 7.2 mg/kg) for five times [30 min before ischaemia, immediately after reperfusion (0 h), 24, 48, and 72 h after reperfusion]. After administration, neurological function assessment and histological changes in the brain were performed. S-100ß and NSE levels were measured to determine the severity of brain injury. Oxidative stress parameters and inflammatory mediators were measured. The proteins involved in Nrf2/ARE signalling pathway were determined by qRT-PCR and western blot. RESULTS: After administration, the neurological function scores, infarct volume, S-100ß, and NSE levels were significantly reduced in MCAO rats, especially with Pue-Tan IIA treatment (p < 0.05). All treatments increased T-AOC, CAT, SOD, and GSH activities and reduced GSSG activity and MDA, TNF-α, IL-6, ICAM-1, and COX-2 levels in MCAO rats. Pue-Tan IIA significantly increased Nrf2 expression in the nucleus (1.81-fold) and decreased its expression in the cytoplasm (0.60-fold). Pue-Tan IIA significantly increased the expressions of HO-1 (1.87-fold) and NQO1 (1.76-fold) and decreased Keap1 expression (0.39-fold). DISCUSSION AND CONCLUSIONS: The combination of Pue and Tan IIA could alleviate ischaemic brain injury by activating Nrf2/ARE signalling pathway, providing an experimental basis for clinical applications.

Clinical Application of Early Warning Scoring Based on BiLSTM-Attention in Emergency Obstetric Preexamination and Triage.

Maternity is a special category of population and the criteria for emergency prescreening cannot be directly applied to adults. Therefore, a set of criteria for grading maternal conditions should be established. In this paper, we have combined the semantic analysis technique of BiLSTM-Attention neural network and fuzzy defect risk assessment method, to develop a hybrid approach, to preprocess the text of emergency obstetric prescreening information. Furthermore, we have used word2vec to characterize the word embedding vector and highlight the features related to the degree of defects of emergency obstetric prescreening information through the attention mechanism and obtain the semantic feature vector of the warning information. BiLSTM-Attention neural network has the dual advantages of extracting bidirectional semantic information and giving weight to important judgment information which has effectively improved the semantic understanding accuracy. Experimental tests and application analysis show that the judgment model which is based on proposed method has accurately classified and graded the defects of emergency obstetric prescreening alerts. Additionally, the accuracy and microaverage value are used as evaluation indexes.

Bromodomain and extra-terminal inhibitors emerge as potential therapeutic avenues for gastrointestinal cancers.

Gastrointestinal (GI) cancers, including colorectal cancer, pancreatic cancer, liver cancer and gastric cancer, are severe social burdens due to high incidence and mortality rates. Bromodomain and extra-terminal (BET) proteins are epigenetic readers consisting of four conserved members (BRD2, BRD3, BRD4 and BRDT). BET family perform pivotal roles in tumorigenesis through transcriptional regulation, thereby emerging as potential therapeutic targets. BET inhibitors, disrupting the interaction between BET proteins and acetylated lysines, have been reported to suppress tumor initiation and progression in most of GI cancers. In this review, we will demonstrate how BET proteins participate in the GI cancers progression and highlight the therapeutic potential of targeting BET proteins for GI cancers treatment.

Experimental Study on Bead on Plate (BOP) Welding of 6 mm Thick 9% Nickel Steel by Fiber Laser Welding.

Nine percent nickel steel has excellent properties in a cryogenic environment, so it has recently been used as a tank material for most LNG fuel-powered ships. However, 9% nickel steel causes arc deflection due to its tendency of magnetization during manual FCAW welding and the currently used filler metal is 10-25 times more expensive as a base metal compared to other materials, depending on manufacturers. Furthermore, the properties of its filler metal cause limitation in the welding position. To overcome these disadvantages, in this study, the tendency of penetration shape was analyzed through a fiber laser Bead on Plate (BOP) welding for 9% nickel steel with a thickness of 6 mm and a range of welding conditions for 1-pass laser butt welding of 6 mm thick 9% nickel steel with I-Groove were derived. Through this study, basic data capable of deriving optimal conditions for laser butt welding of 9% nickel steel with a thickness of 6 mm were obtained.

Suppression of microRNA-323-3p restrains vascular endothelial cell apoptosis via promoting sirtuin-1 expression in coronary heart disease.

AIMS: Coronary heart disease (CHD), a chronic inflammatory condition of vascular endothelial cells (VECs), poses a serious threat to human health. Previous studies have found that microRNAs (miRNAs) are closely related to the occurrence and development of cardiac diseases. Therefore, this study focused on the regulation by miR-323-3p on the progression of CHD. METHODS: Initially, we employed microarray-based gene expression profiling of CHD to identify differentially expressed miRNAs. Next, the expression of miR-323-3p and SIRT1 was detected by RT-qPCR in a rat model of CHD generated by feeding with a high-fat diet. The interaction between miR-323-3p and SIRT1 was identified using bioinformatics analysis and dual luciferase reporter gene assay. The expressions of miR-323-3p and SIRT1 were altered in CHD rats and vascular endothelial cells (VECs) to examine the specific effects on CHD. RESULTS: miR-323-3p was observed to be highly-expressed in blood samples from patients with CHD or with mild atherosclerosis and in the rat model of CHD. SIRT1 was a target gene of miR-323-3p, which could downregulate SIRT1 expression. miR-323-3p overexpression or SIRT1 inhibition resulted in increased apoptosis of VECs, elevated ac-p65 protein expression and ratio of ac-p65/p65, and upregulated expression of NF-κB signaling pathway-related proteins. Besides, miR-323-3p inhibition or SIRT1 upregulation in the CHD rat model was found to significantly alleviate symptoms and decrease levels of proteins related to the ac-p65 and NF-κB signaling pathways. CONCLUSION: Overall, the experimental data provide evidence that miR-323-3p suppression may restrain VEC apoptosis and prevent the resultant CHD progression via SIRT1-inactivatedNF-κB signaling pathway.

Bioinformatics analysis of immune infiltration in glioblastoma multiforme based on data using a methylation chip in the GEO database.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive and malignant tumor of the central nervous system. The study was to obtain the data of immune cell infiltration based on the data of a methylation chip in the GEO, and to clarify its prognostic significance for GBM. METHODS: The methylation data of glioblastoma was obtained by using the Illumina human methylation 450k BeadChip. The corrected expression was obtained by using edge R. Limma was used to correct the expression amount of the samples, and EpiDISH was used to translate the methylation expression data, so that the expression amount was transformed into the expression matrix of immune cells. The immune cells were then co-expressed, and the proportion and correlation of related immune cells was determined. The results of the cells in each of two groups were analyzed by enrichment and PCA mapping to establish the relevant differences. RESULTS: The data of GBM patients were obtained from the methylation chip of the GEO database. Patients were divided into a long-term (SNU-LTS) (21 cases), and short-term survival group (SNU-STS) (12 cases). There were 73 genes with significant individual differences between the two groups (P<0.05). EpiDISH was used to translate the methylation expression data into the expression matrix of immune cells, which showed that the highest proportion of cells in groups were mono cells, while Gran cells and CD8T appeared in a very small number of samples. The positive correlation between mono and B cells was the strongest, while the negative correlation between mono and Gran cells was the strongest. A violin chart shows that there was no significant difference in the infiltration degree of six kinds of immune cells between the two groups. Principal component analysis (PCA) showed that there was individual difference between the two groups, but the overall consistency was high. CONCLUSIONS: Data on tumor immune cell infiltration can be obtained by using a methylation chip in the GEO database. This not only extends the application abilities of methylation chips but provides obvious individual differences. The study of tumor immune infiltrating cells may pave the way for targeted therapy in the treatment of GBM.

The competition between the intrinsic and Rashba spin-orbit coupling and effects of correlations on Rashba SOC-driven transitions in the Kane-Mele model.

We investigate, firstly, the competition between the Rashba spin-orbit coupling (SOC) and the intrinsic SOC in Kane-Mele model. For the small intrinsic SOC, we investigate the effects of the Rashba SOC on the touching point of the valence and conduction bands when the ratio of the Rashba SOC to the intrinsic SOC is greater than classical value23. For the large intrinsic SOC, we find that the critical ratio of the two SOCs at which the band touching occurs decreases with the increasing intrinsic SOC and the locations of these touching points deviate from pointsKandK' of the Brillouin zone. Furthermore, effects of the Rashba SOC on these touching points are discussed in detail when the ratio is greater than the critical value. The Rashba SOC-driven topologically trivial and non-trivial transitions are also obtained in the first part of the work. Secondly, using the slave-rotor mean field method we investigate the influences of the correlation on the Rashba SOC-driven topologically trivial and non-trivial transitions in both the charge condensate and Mott regions. The topological Mott insulator with gapped or gapless spin excitations which arises from the interplay of the Rashba SOC and correlations is obtained in the work.

Appropriate Dosing Regimens of Non-Vitamin K Antagonist Oral Anticoagulants for Treatment of Patients With Non-Valvular Atrial Fibrillation: An Evidence-Based Consideration.

Patients with non-valvular atrial fibrillation (NVAF) exhibit a high risk of stroke, which is associated with high mortality. Thus, stroke prevention is crucial for the overall management of NVAF. Two categories of drugs, vitamin K antagonist warfarin and non-vitamin K antagonist oral anticoagulants (NOACs), are clinically used to prevent NVAF-related stroke. In some circumstances, NOACs are superior to warfarin. However, NOACs selection for NVAF patients is affected by many factors, including individual patient characteristics, comorbidities, risk factors, or laboratory variables. This article summarizes the discrepancy in NOACs management with emphasis on the dosing regimens and influencing factors, such as stroke risk, age, body weight, renal function, gastrointestinal bleeding (GIB) risk, and combination of antiplatelet therapy, in order to identify individual groups with particular clinical characteristics who may obtain more benefit from a certain dosing regimen of NOACs. Determination of a particular subset of patient populations for the appropriate dose regimen of NOACs will help to achieve desired clinical outcomes. Furthermore, to compensate clinical evidence, we should place more emphasis on the findings of current clinical trials and supplement real-world data.

Improved surface adhesion and wound healing effect of madecassoside liposomes modified by temperature-responsive PEG-PCL-PEG copolymers.

Madecassoside (MA) exhibits excellent therapeutic effects in wound healing and scar management. However, its high hydrophilic nature and low permeability through skin tissue limits its topical application. Liposomes are widely used to deliver drugs due to their high structural similarity and biocompatibility with cell membranes. However, normal liposome formulations are too fluid to maintain sufficient adhesion to the wound surface. In this study, in order to make an MA formulation conducive to topical administration, poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE), a biodegradable and temperature-responsive copolymer material, was synthesized and applied to improve the adhesion properties of MA liposomes. The mean particle size of the PECE-modified MA liposomes was 213.43±4.68 nm, and the zeta potential was -23.80±15.37 mV under the optimal conditions of EPC (egg yolk lecithin) to PECE at a mass ratio of 1:1. Additionally, PECE-modified MA liposomes maintained a hydrogel state for better adhesion until the temperature reached 43°C. Furthermore, the PECE-modified MA liposomes showed superior wound contraction effects relative to the MA liposomes in second-degree burn experiments using a rat model. These results indicated that PECE-modified MA liposomes have better surface adhesion performance and healing effects than unmodified MA liposomes.

ZJ01, a Small Molecule Inhibitor of the Kelch-Like ECH-Associated Protein 1-Nuclear Factor Erythroid 2-Related Factor 2 (Keap1-Nrf2) Protein-Protein Interaction, Reduces Hyperoxic Acute Lung Injury in a Mouse Model.

BACKGROUND Hyperoxic acute lung injury (ALI) is a complication of ventilation in patients with respiratory failure. Nuclear factor erythroid-2-related factor 2 (Nrf2) has an important role in ALI. Kelch-like ECH-associated protein 1 (Keap1) binds to Nrf2. ZJ01 is a small molecule inhibitor of Keap1-Nrf2 protein-protein interaction (PPI) that can reduce Keap1-induced inhibition of Nrf2. This study aimed to investigate the effects of ZJ01 and the heme oxygenase-1 (HO-1) inhibitor, zinc protoporphyrin IX (ZnPP IX), in a mouse model of hyperoxic ALI. MATERIAL AND METHODS C57BL/6J mice included five study groups: the room air+vehicle-treated group; the room air+ZJ01 group; the hyperoxia+vehicle-treated group; the hyperoxia+ZJ01 group; and the hyperoxia+ZJ01+ZnPP IX group. ZJ01, ZnPP IX, or vehicle were given 1 h after the hyperoxia challenge. The lungs from the mice were harvested at 72 h following the hyperoxia challenge. RESULTS Hyperoxia exposure for 72 h increased the activity of myeloperoxidase, the lung water content, the levels of tumor necrosis factor-alpha (TNF-alpha), and matrix metalloprotease-9 (MMP-9) in the vehicle-treated mice. ZJ01 treatment reduced hyperoxia-induced inflammation and increased the activation of Nrf2 and HO-1 compared with the vehicle-treated mice. Histology of the lungs showed that ZJ01 treatment reduced the changes of hyperoxia-induced ALI. Pretreatment with ZnPP IX reversed the beneficial effect of ZJ01. CONCLUSIONS ZJ01, a Keap1-Nrf2 PPI inhibitor, reduced hyperoxic ALI in a mouse model through the Nrf2/HO-1 pathway.

microRNA-132 inhibits cardiomyocyte apoptosis and myocardial remodeling in myocardial infarction by targeting IL-1ß.

The patients suffering from myocardial infarction (MI) undergo cardiac remodeling with the features of expanded myocardial infarct size and dilated left ventricle. Multiple microRNAs (miRNAs) are emerged as crucial modulators to participate in the remodeling process. This study is mainly intended to clarify the regulatory mechanism of miR-132 in the MI-induced myocardial remodeling. miR-132 low expression, while interleukin-1ß (IL-1ß) high expression was determined in MI by reverse-transcription quantitative polymerase chain reaction and ELISA assays. MI rats showed decreased cardiac function and increased cardiomyocyte apoptosis. Moreover, miR-132 and IL-1ß levels were altered in cardiomyocytes to explore their role in MI, with levels of proapoptotic or antiapoptotic proteins in MI together with cardiac function indexes observed. In addition, upregulation of miR-132, decreased levels of Bax and Cleaved Caspase-3, increased left ventricular ejection fraction, left ventricular fractional shortening, the maximum rate of rise or decrease of left ventricular pressure (±dp/dtmax ), and Bcl-2 level, which could be reversed by overexpressing IL-1ß. All in all, miR-132 inhibits cardiomyocyte apoptosis so as to ameliorate myocardial remodeling in rats with MI through IL-1ß downregulation. Thus, miR-132 is a potential candidate for the MI treatment.

Long non-coding RNA XIST promotes malignant behavior of epithelial ovarian cancer.

PURPOSE: This study aims to investigate the functional role of long non-coding RNA XIST in epithelial ovarian cancer (EOC). METHODS: Detection of XIST expression levels in EOC tissues and cell lines was done using qRT-PCR. The relationship between XIST expression and clinicopathological features of EOC patients was compared and analyzed. The cumulative survival rates were calculated using Kaplan-Meier. A Cox hazard model was used to identify risk factors for survival. Lastly, the effects of XIST on EOC cell were assessed in vitro. RESULTS: XIST was up-regulated in EOC tissues and cell lines. The expression of XIST was closely related to the tumor grade, distant metastasis, and FIGO stage in the EOC patients. The Cox regression analysis showed that high XIST expression was an independent predictor of prognosis in patients with EOC. In in vitro experiments, reducing XIST expression significantly suppressed cell proliferation, migration and invasion in EOC cells. CONCLUSION: XIST highly expressed in the EOC and plays a role in tumor promotion, which may be a potential target for the treatment of EOC.

Effects of Dehydration and Rehydration on Cognitive Performance and Mood among Male College Students in Cangzhou, China: A Self-Controlled Trial.

Water accounts for 75% of brain mass. Associations may exist between hydration and cognitive performance. The objective of this study was to investigate the effects of dehydration and rehydration on cognitive performance and mood. In this self-control trial, 12 men were recruited from a medical college in Cangzhou, China. After 12 h of overnight fasting, the participants took baseline tests at 8:00 AM on day 2. First morning urine and blood osmolality were analyzed to determine hydration state. Height, weight, and blood pressure were measured following standardized procedures. A visual analog scale for the subjective sensation of thirst was applied, and a profile of mood states questionnaire was applied. Tests were conducted for cognitive performance, including a test of digit span forward and backward, digit-symbol substitutions, dose-work, and stroop effects. Participants were required not to drink water for 36 h but were given three meals on day 3. On day 4, the same indexes were tested as a baseline test. At 8:30 AM, participants drank 1500 mL of purified water over 15 min. After a 1 h interval, the same measurements were performed. Compared with baseline test results, during the dehydration test, participants had lower scores of vigor (11.9 vs. 8.8, %, p = 0.007) and esteem-related affect (8.2 vs. 5.7, %, p = 0.006), lower total scores of digit span (14.3 vs. 13.3, %, p = 0.004), and higher error rates for dose-work (0.01 vs. 0.16, %, p = 0.005). Compared with the dehydration test scores, rehydration test scores showed that fatigue (4.3 vs. 2.1, %, p = 0.005) and total mood disturbance (TMD) (99.0 vs. 90.2, %, p = 0.008) improved, and scores of forward, backward, and total digit span increased (7.7 vs. 8.6, p = 0.014; 5.7 vs. 1.2, p = 0.019; 13.3 vs. 15.4, p = 0.001). Increases were also noted in correct number of digit symbol substitutions, reading speed, and mental work ability (70.8 vs. 75.4, p < 0.001; 339.3 vs. 486.4, n/min, p < 0.001; 356.1 vs. 450.2, p < 0.001), and reaction time decreased (30.2 vs. 28.7, s, p = 0.002). As a conclusion, dehydration had negative effects on vigor, esteem-related affect, short-term memory, and attention. Rehydration after water supplementation alleviated fatigue and improved TMD, short-term memory, attention, and reaction.

Comparative efficacy and safety of lipid-lowering agents in patients with hypercholesterolemia: A frequentist network meta-analysis.

BACKGROUND: The comparative efficacy and safety of PCSK9 inhibitors, statins, and ezetimibe to lower lipid levels in patients with hypercholesterolemia remain unknown. We aimed to investigate the benefits and harms of the lipid-lowering agents in these patients. METHODS: PubMed, Embase, and the Cochrane Library were searched from January 1, 2000 to June 1, 2018 for relevant randomized controlled trials (RCTs). Frequentist network meta-analysis was used to pool all estimates. Ranking probabilities were used to rank the comparative effects of all drugs against placebo. RESULTS: Eighty-four RCTs enrolled 246,706 patients were included. Most of the included were assessed as low risk of bias. The probabilities of PCSK9 inhibitors that ranked first in improving lipid outcomes were all 100%. The probability of statins that ranked first in reducing the risk of cardiovascular (CV) events was 60.6%, and the probability of PCSK9 inhibitor was 37.1%, while no significant difference of efficacy in reducing CV events was observed between the 2 agents (odds ratios [OR] 0.98, 95% CI 0.87-1.11). Statin ranked first in reducing all-cause and CV death. Compared with placebo, statins were associated with reduced risks of all-cause (OR 0.90, 95% CI 0.85-0.96) and CV death (OR 0.83, 95% CI 0.75-0.91) while PCSK9 inhibitors and ezetimibe were not. No agents caused adverse events (including neurocognitive events), except that statins therapy significantly increases the levels of alanine aminotransferase (ALT) (OR 1.89, 95% CI 1.42-2.51) and creatine kinase (CK) (OR 1.45, 95% CI 1.09-1.93) and the incidence of diabetes (OR 1.13, 95% CI 1.02-1.26). CONCLUSIONS: PCSK9 inhibitors were the most effective lipid-lowering agents in improving lipid levels. Furthermore, PCSK9 inhibitors achieved similar CV benefits like statins, while PCSK9 inhibitors were not associated with any increased risk of statin-related side-effects. Thus, PCSK9 inhibitors may also be recommended as promisingly first-line lipid-lowering treatment for patients with hypercholesterolemia, especially for these with statins intolerance or resistance.

The effect of gene therapy on postoperative recurrence of small hepatocellular carcinoma (less than 5cm).

To observe the curative effect of surgery combined with gene therapy on small hepatocellular carcinoma. Seventy-seven patients with small hepatocellular carcinoma (diameter < 5 cm) underwent surgical resection. The tumor located at the edge of the liver was treated by local excision or irregular hepatectomy. The tumor in the center of the liver was resected by hepatic lobectomy in order to ensure at least a 2-cm safety margin. Fifty-four patients underwent gene therapy (gene group) one or two times before operation, whereas 23 patients underwent surgery alone (control group) selected by themselves. The injectable gene was made of ADV-TK (adenovirus containing thymidine kinase suicide gene, with a concentration of 5 × 1012/ml). The prognosis of patients was analyzed by imaging twice a year. In the gene group, the 1-, 3-, and 5-year survival rates were 91.4, 63.6, and 52.1%. In the control group, the survival rates were 84.3, 54.4, and 32.6%, respectively. There was a significant difference in the overall survival rates between two groups. Factors associated with overall survival in univariate analysis included bilirubin, prothrombin activity, cirrhosis, and gene therapy (P < 0.05). In the multivariate analysis, it included cirrhosis, gene therapy, and bilirubin. The gene therapy hepatocellular carcinoma patients with a diameter < 5 cm could significantly reduce recurrence after operation. It was worthy of being popularized.