GLP-1RAs caused gastrointestinal adverse reactions of drug withdrawal: a system review and network meta-analysis

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduce postprandial blood glucose, inhibit appetite, and delay gastrointestinal emptying. However, it is controversial that some patients are intolerant to GLP-1RAs.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials (RCTs) using GLP-1RAs with documented withdrawal due to gastrointestinal adverse reactions (GI AEs) from their inception to September 28, 2022. After extracting the information incorporated into the studies, a random-effects network meta-analysis was performed within a frequentist framework.Results64 RCTs were finally enrolled, which included six major categories of the GLP-1RA. The sample size of the GLP-1RAs treatment group was 16,783 cases. The risk of intolerable gastrointestinal adverse reactions of Liraglutide and Semaglutide was higher than that of Dulaglutide. Meanwhile, the higher the dose of the same GLP-1RA preparation, the more likely to cause these adverse reactions. These intolerable GI AEs were not significantly related to drug homology or formulations and may be related to the degree of suppression of the appetite center.ConclusionDulaglutide caused the lowest intolerable GI AEs, while Liraglutide and Semaglutide were the highest. For Semaglutide, the higher the dose, the more likely it is to drive GI AEs. Meanwhile, the risk of these GI AEs is independent of the different formulations of the drug. All these findings can effectively guide individualized treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359346, identifier CRD42022359346

Effect of Natural Nanostructured Rods and Platelets on Mechanical and Water Resistance Properties of Alginate-Based Nanocomposites

A series of biopolymer-based nanocomposite films were prepared by incorporating natural one-dimensional (1D) palygorskite (PAL) nanorods, and two-dimensional (2D) montmorillonite (MMT) nanoplatelets into sodium alginate (SA) film by a simple solution casting method. The effect of different dimensions of nanoclays on the mechanical, water resistance, and light transmission properties of the SA/PAL or MMT nanocomposite films were studied. The field-emission scanning electron microscopy (FE-SEM) result showed that PAL can disperse better than MMT in the SA matrix in the case of the same addition amount. The incorporation of both PAL and MMT into the SA film can enhance the tensile strength (TS) and water resistance capability of the film. At a high content of nanoclays, the SA/PAL nanocomposite film shows relatively higher TS, and better water resistance than the SA/MMT nanocomposite film. The SA/MMT nanocomposite films have better light transmission than SA/PAL nanocomposite film at the same loading amount of nanoclays. These results demonstrated that 1D PAL nanorods are more suitable candidate of inorganic filler to improve the mechanical and water resistance properties of biopolymers/nanoclays nanocomposites

Characterization and expression analysis of four members genes of flavanone 3-hydroxylase families from Chamaemelum nobile

Chamaemelum nobile is a traditional Chinese herbal medicine, whose secondary metabolites used in the pharmacology of Chinese medicine. Among them, the flavonoids have great research value. Flavanone 3-hydroxylase (F3H) is one of the core enzymes in the early steps of flavonoid biosynthesis. This study aimed to elucidate the structures, functions, and expression levels of F3H families from C. nobile. Four members of the F3H family were screened from C. nobile transcriptome data and performed bioinformatics analysis. Results showed that CnF3H1~4 had a high similarity with the other F3H plants, and all genes contained two conserved isopenicillin N synthase-like and oxoglutarate/iron-dependent dioxygenase domains. Further analysis revealed that the four CnF3H proteins contained some differences in binding sites. The results of secondary and 3-D structures displayed that the composition and proportion of the four CnF3H secondary structures were basically the same, and their 3D structures were consistent with the secondary structures. The phylogenetic tree displayed that CnF3H2, CnF3H3, and CnF3H4 were grouped with Asteraceae. The expression patterns of CnF3Hs in the roots, stems, leaves, and flowers of C. nobile were evaluated using the value of RPKM. The results indicated that CnF3Hs had significant difference in the expression of different tissues. Especially, CnF3H1~3 and CnF3H4 had the highest expression levels in the flowers and roots, respectively. Hence, CnF3Hs played a significant role in the flavonoid metabolism

Effects of 5-aminolevulinic Acid on the Photosynthesis, Antioxidant System, and α-Bisabolol Content of Matricaria recutita

Matricaria recutita is a widely used medicinal plant with broad pharmacological effects, and α-bisabolol is the main active ingredient of this plant. To improve its α-bisabolol content, M. recutita was sprayed with different concentrations (1.0, 2.0,and 4.0 mmol.L−1) of 5-aminolevulinic acid (ALA) or with water as a control to study the effects of ALA treatment on the photosynthesis, antioxidant system, and α-bisabolol content of M. recutita. Results showed that the photosynthetic rate, transpiration rate, stomatal conductance, intercellular CO2 concentration, soluble protein, total amino acids, soluble sugar, and α-bisabolol of M. recutita were significantly increased. Moreover, the activities of superoxide dismutase, peroxidase, and catalase of M. recutita were also enhanced by ALA treatment. Optimal results were obtained when the concentration of ALA was 2.0 mmol.L−1. Results showed that ALA treatment could improve the α-bisabolol content of M. recutita, and the underlying physiological mechanism was analyzed. ALA treatment was an effective measure for improving the medicinal value of M. recutita

Efficacy and Safety of Everolimus for Maintenance Immunosuppression of Kidney Transplantation: A Meta-Analysis of Randomized Controlled Trials

Background Conversion to everolimus is often used in kidney transplantation to overcome calcineurin inhibitor (CNI) nephrotoxicity but there is conflicting evidence for this approach. Objectives To investigate the benefits and harm from randomized clinical trials (RCTs) involving the conversion from CNI to everolimus after kidney transplantation. Methods Databases were searched up to March 2016. Two reviewers independently assessed trials for eligibility and quality, and extracted data. Results are expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). Results Eleven RCTs, with a total of 1,633 patients, met the final inclusion criteria. Patients converted to everolimus had improved renal function at 1 year posttransplant with an estimated glomerular filtration rate (eGFR) of 5.36 mL/min per 1.73 m2 greater than patients remaining on CNI (p = 0.0005) and the longer-term results (\u3e 1 year) of renal function was identical to that of 1 year. There was not a substantial difference in graft loss, mortality, and the occurrence of adverse events (AEs) or serious AEs. However, the risks of acute rejection and trial termination due to AEs with everolimus are respectively 1.82 and 2.63 times greater than patients staying on CNI at 1 year posttransplant (p = 0.02, p = 0.03, respectively). Further, those patients who converted to everolimus had a substantially greater risk of anemia, hyperlipidemia, hypercholesterolemia, hypokalemia, proteinuria, stomatitis, mouth ulceration, and acne. Conclusions Conversion from CNI to everolimus after kidney transplantation is associated with improved renal function in the first 5 years posttransplant but increases the risk of acute rejection at 1 year posttransplant and may not be well endured

Effects of post-harvest natural drying on seed quality and endogenous hormones of Camellia oleifera

Camellia oleifera Abel. (C. oleifera), one of the four woody oil-producing plants in the world produces edible oils with high percentage of unsaturated fatty acid content in seeds. The mature C. oleifera seeds continue to undergo a series of physiological changes after harvest. To this end, the dynamic changes in nutrients, oil content, fatty acid composition, and endogenous hormone content in C. oleifera seeds under different natural drying times after harvest were investigated. The content of soluble sugar and soluble protein of C. oleifera seeds increased with the extension of natural drying, especially soluble sugar content increased nearly 2-fold at 30 d after post-harvest natural drying compared with that of the control group. The content of oil reached a peak (23.6%) at 30 d after post-harvest natural drying. During the post-harvest natural drying process, the relative content of palmitic acid and oleic acid increased, while the relative content of palmitic acid and linoleic acid decreased. Furthermore, the levels of unsaturated fatty acids (oleic acid, linoleic acid, linolenic acid, and arachidonic acid) increased significantly with increasing natural drying time. The overall trend of endogenous hormones SA, SL, and ACC concentrations increased with the post-harvest natural drying process. Furthermore, the concentration of SA, SL, and ACC were positively correlated with oil content. Altogether, post-harvest natural drying for 30 days significantly promoted the anabolism of oil and improved the quality of C. oleifera seeds. These findings provide a scientific basis for reasonable post-harvest treatment to improve Camellia oil yield

Modeling the Impact of Tolling in Large-Scale Regional Networks: A Case Study for DVRPC

69A3551747111Recent years have witnessed a sharp decline in national highway trust fund that is primarily used to support infrastructure construction, expansion and retrofit. This is a challenging and critical issue for almost all states, including Pennsylvania. The primary reason is due to the decline of gas tax collected at gas pumps as a result of adaption of high fuel efficiency vehicles. The most recent and ongoing COVID-19 crisis adds additional burden to this lack of public funds for infrastructure, since the overall travel demand declines drastically. Most of states are currently evaluating the implications of tax loss, and proactively developing plan to collect funds in a more equitable and effective manner. The Pennsylvania Department of Transportation has lately given the green light for a proposal that could add tolls on an undetermined number of bridges, as a way to collect funding to support infrastructure. It imposes a challenge how to effectively and accurately evaluate the societal consequences of tolling of various forms, including social equity, congestion delay, emission, fuel use and potential toll revenue. In this research project, the study team aims to develop a large-scale multi-class network modeling and simulation framework, particularly for Delaware Valley Regional Planning Commission (DVRPC), that holistically models the spatio-temporal behaviors of private cars, ride-hailing cars, freight trucks, respectively. The result includes the prediction of travel time, travel delay, vehicle-mile-traveled and emissions for each of those vehicle classes and travel modes, either at road and intersection level or averaged at community level by time of day. Potential tolling strategies, such as locations and pricing, can be evaluated and deployed, with the trade-off among tolling revenue, system mobility and social equity

Association of vitamin D deficiency and subclinical diabetic peripheral neuropathy in type 2 diabetes patients

BackgroundDiabetic peripheral neuropathy (DPN) contributes to disability and imposes heavy burdens, while subclinical DPN is lack of attention so far. We aimed to investigate the relationship between vitamin D and distinct subtypes of subclinical DPN in type 2 diabetes (T2DM) patients.MethodsThis cross-sectional study included 3629 T2DM inpatients who undertook nerve conduction study to detect subclinical DPN in Zhongshan Hospital between March 2012 and December 2019. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25(OH)D) level < 50 nmol/L.Results1620 (44.6%) patients had subclinical DPN and they were further divided into subgroups: distal symmetric polyneuropathy (DSPN) (n=685), mononeuropathy (n=679) and radiculopathy (n=256). Compared with non-DPN, DPN group had significantly lower level of 25(OH)D (P < 0.05). In DPN subtypes, only DSPN patients had significantly lower levels of 25(OH)D (36.18 ± 19.47 vs. 41.03 ± 18.47 nmol/L, P < 0.001) and higher proportion of vitamin D deficiency (78.54% vs. 72.18%, P < 0.001) than non-DPN. Vitamin D deficiency was associated with the increased prevalence of subclinical DPN [odds ratio (OR) 1.276, 95% confidence interval (CI) 1.086-1.501, P = 0.003] and DSPN [OR 1. 646, 95% CI 1.31-2.078, P < 0.001], independent of sex, age, weight, blood pressure, glycosylated hemoglobin, T2DM duration, calcium, phosphorus, parathyroid hormone, lipids and renal function. The association between vitamin D deficiency and mononeuropathy or radiculopathy was not statistically significant. A negative linear association was observed between 25(OH)D and subclinical DSPN. Vitamin D deficiency maintained its significant association with subclinical DSPN in all age groups.ConclusionsVitamin D deficiency was independently associated with subclinical DSPN, rather than other DPN subtypes