The causal relationship between sleep disturbances and the risk of frailty: a two-sample Mendelian randomization study.

OBJECTIVE: Adequate sleep is closely related to people's health. However, with increasing age, the quality of sleep worsens. At the same time, among elderly individuals, frailty is also a disturbing factor, which makes elderly individuals more vulnerable to negative factors. To explore the relationship between the two, we conducted this study. METHODS: In this paper, independent genetic variations related to insomnia, sleep duration and daytime sleepiness were selected as IVs, and related genetic tools were used to search published genome-wide association studies for a two-sample Mendelian randomization (TSMR) analysis. The inverse-variance weighted (IVW) method was used as the main Mendelian randomization analysis method. Cochran's Q test was used to test heterogeneity, MR‒Egger was used to test horizontal pleiotropy, and the MR-PRESSO test was used to remove outliers. RESULTS: According to our research, insomnia (OR = 1.10, 95% CI 1.03-1.17, P = 2.59e-97), long sleep duration (OR = 0.66, 95% CI 0.37-1.17, P = 0.02), short sleep duration (OR = 1.30, 95% CI 1.22-1.38, P = 2.23e-17) and daytime sleepiness (OR = 1.49, 95% CI 1.25-1.77, P = 0.96e-4) had a bidirectional causal relationship with frailty. CONCLUSIONS: Our research showed that there is a causal relationship between sleep disturbances and frailty. This result was obtained by a TSMR analysis, which involves the use of genetic variation as an IV to determine causal relationships between exposure and outcome. Future TSMR studies should include a larger sample for analysis.

Research on the Interaction Mechanism and Structural Changes in Human Serum Albumin with Hispidin Using Spectroscopy and Molecular Docking.

The interaction between human serum albumin (HSA) and hispidin, a polyketide abundantly present in both edible and therapeutic mushrooms, was explored through multispectral methods, hydrophobic probe assays, location competition trials, and molecular docking simulations. The results of fluorescence quenching analysis showed that hispidin quenched the fluorescence of HSA by binding to it via a static mechanism. The binding of hispidin and HSA was validated further by synchronous fluorescence, three-dimensional fluorescence, and UV/vis spectroscopy analysis. The apparent binding constant (Ka) at different temperatures, the binding site number (n), the quenching constants (Ksv), the dimolecular quenching rate constants (Kq), and the thermodynamic parameters (∆G, ∆H, and ∆S) were calculated. Among these parameters, ∆H and ∆S were determined to be 98.75 kJ/mol and 426.29 J/(mol·K), respectively, both exhibiting positive values. This observation suggested a predominant contribution of hydrophobic forces in the interaction between hispidin and HSA. By employing detergents (SDS and urea) and hydrophobic probes (ANS), it became feasible to quantify alterations in Ka and surface hydrophobicity, respectively. These measurements confirmed the pivotal role of hydrophobic forces in steering the interaction between hispidin and HSA. Site competition experiments showed that there was an interaction between hispidin and HSA molecules at site I, which situates the IIA domains of HSA, which was further confirmed by the molecular docking simulation.

Changes in frailty and depressive symptoms among middle-aged and older Chinese people: a nationwide cohort study.

BACKGROUND AND AIMS: The older people bears a severe burden of disease due to frailty and depressive symptoms, however, the results of association between the two in the older Chinese people have been conflicting. Therefore, this study aimed to investigate the developmental trajectories and interactions of frailty and depressive symptoms in the Chinese middle-aged and older adults. METHODS: The study used four waves of data from 2011, 2013, 2015 and 2018 in the China Health and Retirement Longitudinal Study (CHARLS) database, focused on middle-aged and older people ≥ 45 years of age, and analyzed using latent growth models and cross-lagged models. RESULTS: The parallel latent growth model showed that the initial level of depressive symptoms had a significant positive predictive effect on the initial level of frailty. The rate of change in depressive symptoms significantly positively predicted the rate of change in frailty. The initial level of frailty had a significant positive predictive effect on the initial level of depressive symptoms, but a significant negative predictive effect on the rate of change in depressive symptoms. The rate of change in frailty had a significant positive predictive effect on the rate of change in depressive symptoms. The results of the cross-lagged analysis indicated a bidirectional causal association between frailty and depressive symptoms in the total sample population. Results for the total sample population grouped by age and gender were consistent with the total sample. CONCLUSIONS: This study recommends advancing the age of concern for frailty and depressive symptoms to middle-aged adults. Both men and women need early screening and intervention for frailty and depressive symptoms to promote healthy aging.

Structural and signaling mechanisms of TAAR1 enabled preferential agonist design.

Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D3.32 for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design.

Novel insights from spatial transcriptome analysis in solid tumors.

Since its first application in 2016, spatial transcriptomics has become a rapidly evolving technology in recent years. Spatial transcriptomics enables transcriptomic data to be acquired from intact tissue sections and provides spatial distribution information and remedies the disadvantage of single-cell RNA sequencing (scRNA-seq), whose data lack spatially resolved information. Presently, spatial transcriptomics has been widely applied to various tissue types, especially for the study of tumor heterogeneity. In this review, we provide a summary of the research progress in utilizing spatial transcriptomics to investigate tumor heterogeneity and the microenvironment with a focus on solid tumors. We summarize the research breakthroughs in various fields and perspectives due to the application of spatial transcriptomics, including cell clustering and interaction, cellular metabolism, gene expression, immune cell programs and combination with other techniques. As a combination of multiple transcriptomics, single-cell multiomics shows its superiority and validity in single-cell analysis. We also discuss the application prospect of single-cell multiomics, and we believe that with the progress of data integration from various transcriptomics, a multilayered subcellular landscape will be revealed.

Activation of CTNNB1 by deubiquitinase UCHL3-mediated stabilization facilitates bladder cancer progression.

BACKGROUND: The catenin beta 1 gene (CTNNB1) plays a crucial role in the malignant progression of various cancers. Recent studies have suggested that CTNNB1 hyperactivation is closely related to the occurrence and development of bladder cancer (BCa). As a member of the deubiquitinating enzyme (DUB) family, ubiquitin C-terminal hydrolase L3 (UCHL3) is abnormally expressed in various cancers. In this study, we discovered that UCHL3 is a novel oncogene in bladder cancer, suggesting it is a promising target against bladder cancer. METHODS: We utilized CRISPR‒Cas9 technology to construct cell lines with UCHL3 stably overexpressed or knocked out. The successful overexpression or knockout of UCHL3 was determined using Western blotting. Then, we performed CCK-8, colony formation, soft agar and Transwell migration assays to determine the impact of the UCHL3 gene on cell phenotype. RNA-seq was performed with UCHL3-depleted T24 cells (established via CRISPR-Cas9-mediated genomic editing). We analyzed differences in WNT pathway gene expression in wild-type and UCHL3-deficient T24 cell lines using a heatmap and by gene set enrichment analysis (GSEA). Then, we validated the effect of UCHL3 on the Wnt pathway using a dual fluorescence reporter. We then analyzed the underlying mechanisms involved using Western blots, co-IP, and immunofluorescence results. We also conducted nude mouse tumor formation experiments. Moreover, conditional UCHL3-knockout mice and bladder cancer model mice were established for research. RESULTS: We found that the overexpression of UCHL3 boosted bladder cancer cell proliferation, invasion and migration, while the depletion of UCHL3 in bladder cancer cells delayed tumor tumorigenesis in vitro and in vivo. UCHL3 was highly associated with the Wnt signaling pathway and triggered the activation of the Wnt signaling pathway, which showed that its functions depend on its deubiquitination activity. Notably, Uchl3-deficient mice were less susceptible to bladder tumorigenesis. Additionally, UCHL3 was highly expressed in bladder cancer cells and associated with indicators of advanced clinicopathology. CONCLUSION: In summary, we found that UCHL3 is amplified in bladder cancer and functions as a tumor promoter that enhances proliferation and migration of tumor cells in vitro and bladder tumorigenesis and progression in vivo. Furthermore, we revealed that UCHL3 stabilizes CTNNB1 expression, resulting in the activation of the oncogenic Wnt signaling pathway. Therefore, our findings strongly suggest that UCHL3 is a promising therapeutic target for bladder cancer.

Comparative analysis of the gut microbiota of wild wintering whooper swans (Cygnus Cygnus), captive black swans (Cygnus Atratus), and mute swans (Cygnus Olor) in Sanmenxia Swan National Wetland Park of China.

The gastrointestinal microbiota, a complex ecosystem, is involved in the physiological activities of hosts and the development of diseases. Birds occupy a critical ecological niche in the ecosystem, performing a variety of ecological functions and possessing a complex gut microbiota composition. However, the gut microbiota of wild and captive birds has received less attention in the same region. We profiled the fecal gut microbiome of wild wintering whooper swans (Cygnus Cygnus; Cyg group, n = 25), captive black swans (Cygnus Atratus; Atr group, n = 20), and mute swans (Cygnus Olor; Olor group, n = 30) using 16S rRNA gene sequencing to reveal differences in the gut microbial ecology. The results revealed that the three species of swans differed significantly in terms of the alpha and beta diversity of their gut microbiota, as measured by ACE, Chao1, Simpson and Shannon indices, principal coordinates analysis (PCoA) and non-metricmulti-dimensional scaling (NMDS) respectively. Based on the results of the linear discriminant analysis effect size (LEfSe) and random forest analysis, we found that there were substantial differences in the relative abundance of Gottschalkia, Trichococcus, Enterococcus, and Kurthia among the three groups. Furthermore, an advantageous pattern of interactions between microorganisms was shown by the association network analysis. Among these, Gottschalkia had the higher area under curve (AUC), which was 0.939 (CI = 0.879-0.999), indicating that it might be used as a biomarker to distinguish between wild and captive black swans. Additionally, PICRUSt2 predictions indicated significant differences in gut microbiota functions between wild and captive trumpeter swans, with the gut microbiota functions of Cyg group focusing on carbohydrate metabolism, membrane transport, cofactor, and vitamin metabolism pathways, the Atr group on lipid metabolism, and the Olor group on cell motility, amino acid metabolism, and replication and repair pathways. These findings showed that the gut microbiota of wild and captive swans differed, which is beneficial to understand the gut microecology of swans and to improve regional wildlife conservation strategies.

Dyadic psycho-social interventions for stroke survivors and family caregivers: A systematic review and meta-analysis of randomized controlled trials.

AIMS AND OBJECTIVES: To describe dyadic psycho-social intervention measures and to evaluate their influence on stroke survivors and caregiver's functional independence, quality of life, depression, anxiety, self-efficacy and coping ability. BACKGROUND: Because of the importance of dyadic intervention and the seriousness of the psycho-social problems of stroke survivors and caregivers, understanding the influence of dyadic psycho-social interventions is vital. DESIGN: A systematic review and meta-analysis based on PRISMA guidelines. DATA SOURCES: Nine databases were systematically searched for randomized controlled trials submitted from 1910 to 4 July 2022. METHODS: The included papers were evaluated for quality, and quantitative data were standardly extracted and analysed by meta-analysis, followed by synthesis. The meta-analysis was carried out using Review Manager 5.4 software. RESULTS: Fifteen randomized controlled trials were included (n = 2190 for patients, and n = 1933 for caregivers). Study results showed that dyadic psycho-social interventions significantly alleviated the depressive symptoms of patients, obviously improved the ability to function independently of patients and more quickly alleviated the care burden of caregivers. CONCLUSIONS: This study provided moderate support for the benefits of dyadic psycho-social intervention in improving survivor and caregiver's functional independence, quality of life, depression, anxiety, self-efficacy and care burden. Nevertheless, due to limitations of the study, it was deemed necessary that this topic is studied further. RELEVANCE TO CLINICAL PRACTICE: This review suggests that dyadic psycho-social interventions should be considered as effective strategies for decreasing psycho-social problems of stroke survivors and caregivers, and provides evidence for the formulation of targeted intervention programs. The personalized implementation of such interventions should be the focus of clinical practice. NO PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public contribution.

Advances in spatial transcriptomics and related data analysis strategies.

Spatial transcriptomics technologies developed in recent years can provide various information including tissue heterogeneity, which is fundamental in biological and medical research, and have been making significant breakthroughs. Single-cell RNA sequencing (scRNA-seq) cannot provide spatial information, while spatial transcriptomics technologies allow gene expression information to be obtained from intact tissue sections in the original physiological context at a spatial resolution. Various biological insights can be generated into tissue architecture and further the elucidation of the interaction between cells and the microenvironment. Thus, we can gain a general understanding of histogenesis processes and disease pathogenesis, etc. Furthermore, in silico methods involving the widely distributed R and Python packages for data analysis play essential roles in deriving indispensable bioinformation and eliminating technological limitations. In this review, we summarize available technologies of spatial transcriptomics, probe into several applications, discuss the computational strategies and raise future perspectives, highlighting the developmental potential.

Bilateral Peutz-Jeghers-Associated Sex Cord Tumor With Annular Tubules Combined With Unilateral Adult Granulosa Cell Tumor: A Case Report.

Sex cord tumor with annular tubules (SCTATs) is a rare sex cord stromal tumor in the ovary. SCTAT combined with adult granulosa cell tumor (AGCT) is even rarer. Here, we report a unique case of ovarian tumors with mixed AGCT and SCTAT components. Due to the unusual coexistence, molecular testing was separately performed on each ovary. Both SCTAT and AGCT components were found to have STK11 germline mutation. Furthermore, the AGCT component had an additional FOXL2 somatic mutation. Based on medical history and molecular testing we conclude that the ovarian tumors were associated with Peutz-Jeghers syndrome (PJS). Thus, we present the first report of bilateral PJS-associated SCTAT combined with unilateral AGCT.

Relationships of Matrix Metalloproteinase 1 and a Tissue Inhibitor of Metalloproteinase to Collagen Metabolism in Haliotis discus hannai.

In response to physical, chemical, and/or biological stimuli, considerable tissue self-degradation occurs in abalone, causing severe post-harvest quality loss. During this process, the extracellular matrix (ECM) is greatly degraded by endogenous proteases. The main component of the ECM is collagen, primarily type I collagen. Although the activity of matrix metalloproteinases (MMPs), which can specifically degrade collagen, is precisely regulated by tissue inhibitors of MPs (TIMPs), indicating that MMPs and TIMPs play crucial roles in the regulation of tissue self-degradation, few studies have reported the interaction between MMPs and TIMPs. In this study, we reveal collagenases to participate in postmortem tissue self-degradation of Haliotis discus hannai by degrading type I collagen. The recombinant MMP-1 catalytic domain (rMMP1c) of abalone with high purity and enzyme activity is expressed using a prokaryotic expression system. The optimum temperature and pH for rMMP1c are 37 °C and 7.0, respectively. The thermal denaturation temperature of rMMP1c is 67.0 ± 0.9 °C. Ethylenediamine tetraacetic acid (EDTA) and 1,10-phenanthroline can completely inhibit rMMP1c activity, while Ba2+, Ca2+, and Mg2+ can significantly elevate it. TIMP is also expressed using HEK 293F cells. Recombinant TIMP (rTIMP) shows good inhibitory activity toward rMMP1c. Inhibition kinetics analyses reveal rTIMP to be a competitive inhibitor of rMMP1c. Biolayer interferometry reveals that rTIMP can effectively bind with rMMP1c, with an equilibrium dissociation constant value of 263 nM. rMMP1c effectively degrades type I collagen γ-ß-α chains in turn, and rTIMP can significantly inhibit rMMP1c degradation activity. These results provide a theoretical basis for the study of MMP and TIMP interaction and elucidate the possible mechanism for abalone tissue self-degradation.

Research progress of bile biomarkers and their immunoregulatory role in biliary tract cancers.

Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder carcinoma, originate from the biliary epithelium and have a poor prognosis. Surgery is the only choice for cure in the early stage of disease. However, most patients are diagnosed in the advanced stage and lose the chance for surgery. Early diagnosis could significantly improve the prognosis of patients. Bile has complex components and is in direct contact with biliary tract tumors. Bile components are closely related to the occurrence and development of biliary tract tumors and may be applied as biomarkers for BTCs. Meanwhile, arising evidence has confirmed the immunoregulatory role of bile components. In this review, we aim to summarize and discuss the relationship between bile components and biliary tract cancers and their ability as biomarkers for BTCs, highlighting the role of bile components in regulating immune response, and their promising application prospects.

Integrated strategy of network analysis prediction and experimental validation to elucidate the possible mechanism of compound Turkish gall ointment in treating eczema.

BACKGROUND: Compound Turkish gall ointment (CTGO) has a long history of being widely used as a folk medicine in Xinjiang for the treatment of eczema. CTGO is currently in the pre-investigational new drug application stage, but its pharmacological mechanisms of action have not yet been clarified. METHODS: First, a sensitive and reliable ultra-high performance liquid chromatography-Q exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) technique was established. Second, an integrative strategy of network analysis and molecular docking based on identified and retrieved ingredients was implemented to investigate the potential targets and pathways involved in the treatment of eczema with CTGO. Finally, Sprague-Dawley (SD) rats with eczema were prepared to verify the predicted results. The skin conditions of the rats were observed, evaluated, and scored. Skin tissues were observed by hematoxylin-eosin (HE) staining, and the levels of serum interferon-γ (IFN-γ) and interleukin-4 (IL-4) were determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κB p65), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: A total of 29 compounds were identified. We found 38 active components and 58 targets for the treatment of eczema, which included 118 signaling pathways related to inflammation, immunity, and apoptosis. CTGO significantly improved the skin surface and histopathological characteristics of eczema-affected rats, downregulated the expression of IL-4, TLR4, NF-κB (p65), IL-1ß, and TNF-α, and upregulated the expression level of IFN-γ. CONCLUSION: We predicted and validated our prediction that CTGO may be used to treat eczema by affecting the TLR4/NF-κB signaling pathway, which provides guidance for future experimental studies.

The construction of an artificial light-harvesting system with two-step sequential energy transfer based on supramolecular polymers.

An artificial light-harvesting system with two-step sequential energy transfer was constructed in aqueous media based on cyano-substituted p-phenylenevinylene derivative (PPTA) and bis-(p-sulfonatocalix[4]arenes) (BSC4) supramolecular polymers formed through host-guest interactions, in which two different fluorescent dyes, eosin Y (EY) and sulforhodamine (SR101), were employed as energy acceptors. The obtained artificial light-harvesting system can achieve an efficient two-step energy transfer process from PPTA-BSC4 to EY and then to SR101 with high energy-transfer efficiencies of up to 36.6% and 40.8%, respectively. More importantly, the harvested energy from the PPTA-BSC4 + EY + SR101 system can be used to promote the dehalogenation of α-bromoacetophenone with a yield of 89% in aqueous solution.

Synergistic Effect between Zr-MOF and Phosphomolybdic Acid with the Promotion of TiF4 Template.

Metal-Organic Framework (MOF) materials are often modified or functionalized, and then the crystal size and morphology of MOF materials are changed. In the process of preparing UiO-66 confined phosphomolybdic acid (PMA) composites (PU), the TiF4-modified PU (PMA + UiO-66) composite catalyst (TiF4-PU) was successfully synthesized by adding titanium tetrafluoride, and the catalytic desulfurization activity was excellent. Similarly, the reaction mechanism was investigated by means of infrared spectroscopy, Raman spectroscopy, XPS, and UV/Vis spectroscopy. The results show that the addition of TiF4 not only changes the appearance and color of the catalyst, but also changes the valence distribution of the elements in the catalyst. The number of oxygen vacancies in the MOF increases due to the addition of TiF4, and more electrons are transferred from the Zr-MOF to PMA to form more Mo5+, which improved the performance of oxidative desulfurization in comparison. Thus, a stronger strong metal-support interaction (SMSI) effect is observed for TiF4-modified PU catalysts. In addition, the quenching experiment of free radicals shows that ·OH radical is the main active substance in the oxidative desulfurization reaction over TiF4-PU catalyst.

Confined Heteropoly Blues in Defected Zr-MOF (Bottle Around Ship) for High-Efficiency Oxidative Desulfurization.

The Keggin-type polyoxometalates (POMs) are effective catalysts for oxidative desulfurization (ODS) and confining these POMs in metal-organic frameworks (MOFs) is a promising strategy to improve their performances. Herein, postsynthetic modification of POMs confined in MOFs by adding thiourea creates more unsaturated metal sites as defects, promoting ODS catalytic activity. Additional modification by confining 1-butyl-3-methyl imidazolium POMs in MOFs is performed to obtain higher ODS activity, owing to the affinity between electron-rich thiophene-based compounds and electrophilic imidazolium compounds. The ODS catalytic activities of four Zr-MOF-based composites (bottle around ship) including phosphomolybdate acid (PMA)/UiO-66, [Bmim]3 PMo12 O40 /UiO-66, PMA/Thiourea/UiO-66, and [Bmim]3 PMo12 O40 /Thiourea/UiO-66 are therefore investigated in detail. In order to explore the catalytic mechanism of these MOF composites, their microstructures and electronic structures are probed by various techniques such as X-ray diffraction, thermogravimetric analysis, Fourier transform infrared, Raman, scanning electron microscope, transmission electron microscope, BET, X-ray photoelectron spectroscopy, EPR, UV-vis, NMR spectra, and H2 -temperature-programmed reduction. The results reveal that phosphomolybdate blues and imidazolium phosphomolybdate blues with different Mo5+ /Mo6+ ratios with the Keggin structure are confined in defected UiO-66 for all four composites. This approach can be applied to design and synthesize other POMs/MOFs composites as efficient catalysts.

UCHL3 promotes ovarian cancer progression by stabilizing TRAF2 to activate the NF-κB pathway.

The inflammatory response plays an important role in carcinogenesis. However, the functional role and mechanism of the UCHL3-associated inflammatory response in ovarian cancer remain to be characterized. Here, we report that increased expression of UCHL3 facilitates tumourigenesis by targeting TRAF2 protein, thereby enhancing the inflammatory response. The expression of UCHL3 is elevated in ovarian cancer patients and is associated with an unfavourable prognosis. Genetic ablation of UCHL3 was found to markedly block ovarian cancer cell proliferation, viability and migration both in vitro and in vivo. Mechanistically, luciferase pathway screening results show that NF-κB signalling is clearly activated compared with other pathways. UCHL3 was found to activate NF-κB signalling by deubiquitinating and stabilizing TRAF2, leading to tumourigenesis. Our results indicate that highly expressed UCHL3 enhances inflammation by stabilizing TRAF2, which in turn facilitates tumourigenesis in ovarian cancer, and that UCHL3 is a potential target for ovarian cancer patients with increased inflammation.

Efficacy of ivabradine for heart failure: A protocol for a systematic review of randomized controlled trial.

BACKGROUND: Previous clinical trials have reported that ivabradine can effectively treat heart failure (HF). However, no systematic review has explored its efficacy and safety for HF. This systematic review will aim to evaluate the efficacy and safety of ivabradine for the treatment of patients with HF. METHODS: We will search the literature from the following electronic databases from inception to the January 31, 2019: Cochrane Central Register of Controlled Trials, EMBASE, MEDILINE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data. All randomized controlled trials (RCTs) of ivabradine for HF will be fully considered for inclusion without any restrictions. Additionally, grey literature including clinical trial registries, dissertations, and reference lists of included studies, conference abstracts will also be searched. Two researchers will review these literatures, extract data, and assess risk of bias of included RCTs separately. Data will be pooled by either fixed-effects model or random-effects model, and meta-analysis will be conducted if it is appropriate. RESULTS: The primary outcome is all-cause mortality. The secondary outcomes comprise of change in body weight, urine output, change in serum sodium, and all adverse events. CONCLUSIONS: The results of this study will summary provide up-to-dated evidence for assessing the efficacy and safety of ivabradine for HF. ETHICS AND DISSEMINATION: It is not necessary to acquire ethical approval for this systematic review, because no individual patient data will be used in this study. The results of this systematic review will be published through peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019120814.

A pilot study of the effect of ezetimibe for postprandial hyperlipidemia.

This study aimed to explore the feasible effect of ezetimibe for postprandial hyperlipidemia (PPHP).Sixty participants were included in this study. Of these, 30 subjects in the intervention group received ezetimibe, while the remaining 30 participants in the control group did not undergo ezetimibe. All patients in intervention group were treated for a total of 2 weeks. Primary endpoints consisted of serum levels of total cholesterol (Total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG). Secondary endpoints included apoB-48, remnant lipoprotein cholesterol (RLP-C), blood glucose, insulin, hemoglobin A1c (HbA1c), and monocyte chemotactic protein (MCP). All outcomes were measured before and after 2-week treatment.After 2-week treatment, participants in the intervention group did not show better outcomes in primary endpoints of Total-C, LDL-C, HDL-C, and TG; and secondary endpoints of apoB-48, RLP-C, blood glucose, insulin, HbA1c, and MCP, compared with subjects in the control group.The results of this study showed that ezetimibe may be not efficacious for participants with PPHP after 2-week treatment.