Adverse events of direct factor Xa inhibitors: a disproportionality analysis of the FAERS database.

OBJECTIVES: Direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, commonly used direct oral anticoagulant (DOAC), are widely used to prevent and treat stroke and venous thromboembolic events in patients with atrial fibrillation (AF). This study aimed to assess and compare reports of adverse events associated with rivaroxaban, apixaban, and edoxaban, including hemorrhagic and non-hemorrhagic events. METHODS: Reporting odds ratio (ROR), proportional reporting ratio (PRR), Medications and Health Care Products Regulatory Agency (MHRA), and the information component (IC) were used to perform a risk assessment of adverse event reports in the FDA Adverse Event Reporting System (FAERS) database for the years 2018-2022. RESULTS: Combined with disproportionality analysis in different backgrounds, the salient risks of the three-factor Xa inhibitors varied. Rivaroxaban had the most significant risk of hemorrhage, apixaban had a higher incidence and risk of death, cardiac and cerebral adverse events, and edoxaban showed a more prominent risk in the kidneys and urinary system. CONCLUSION: Hemorrhage is a common risk with factor Xa inhibitors, with rivaroxaban being the most significant. Apixaban and edoxaban also showed significant association with non-hemorrhagic adverse events, and increased attention to non-hemorrhagic adverse events is needed in clinical use.

Effects of Drying Process and High Hydrostatic Pressure on Extraction of Antioxidant Ergothioneine from Pleurotus citrinopileatus Singer.

This study evaluated the effects of different drying techniques on the physicochemical properties of Pleurotus citrinopileatus Singer (P. citrinopileatus), focusing on the ergothioneine (EGT) contents. The P. citrinopileatus was subjected to natural ventilation drying (ND), freeze-drying (FD), and hot-air drying (HD). EGT was extracted using high-hydrostatic-pressure extraction (HHPE), and response surface methodology (RSM) was employed with four variables to optimize the extraction parameters. The crude EGT extract was purified by ultrafiltration and anion resin purification, and its antioxidant activity was investigated. The results showed that the ND method effectively disrupted mushroom tissues, promoting amino acid anabolism, thereby increasing the EGT content of mushrooms. Based on RSM, the optimum extracting conditions were pressure of 250 MPa, extraction time of 52 min, distilled water (dH2O) as the extraction solvent, and a 1:10 liquid-solid ratio, which yielded the highest EGT content of 4.03 ± 0.01 mg/g d.w. UPLC-Q-TOF-MSE was performed to assess the purity of the samples (purity: 86.34 ± 3.52%), and MS2 information of the main peak showed primary ions (m/z 230.1) and secondary cations (m/z 186.1050, m/z 127.0323) consistent with standard products. In addition, compared with ascorbic acid (VC), EGT showed strong free radical scavenging ability, especially for hydroxyl and ATBS radicals, at more than 5 mmol/L. These findings indicate that the extraction and purification methods used were optimal and suggest a possible synthetic path of EGT in P. citrinopileatus, which will help better explore the application of EGT.

Identification of C4BPA as biomarker associated with immune infiltration and prognosis in breast cancer.

Background: C4BPA is a gene that encodes the C4BP protein α chain and is involved in the complement system. C4BPA is regarded as a new biomarker for cancer, especially for non-small cell lung cancer and ovarian cancer. However, its role in breast cancer (BC) has not yet been determined. Methods: In this research, we used a bioinformatics approach to assess the prognostic significance of C4BPA in BC. Utilizing a variety of databases and analysis tools, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), R, STRING, and the Kaplan-Meier plotter, we specifically assessed the connection between C4BPA and BC. Results: C4BPA expression was markedly decreased in BC tissues compared to its expression in normal breast tissues (P<0.05). Additionally, a receiver operating characteristic (ROC) curve revealed that C4BPA has a significant capacity for prognostication and diagnostics. Additionally, C4BPA expression was linked to some immune infiltrating cells' functionality, according to gene set enrichment analysis (GSEA) and immune infiltration analysis. Low C4BPA expression was additionally related to poor progression-free interval (PFI) and overall survival (OS), according to the Kaplan-Meier method. We also found that C4BPA expression was independently connected to PFI and OS through Cox regression analysis. Finally, prognostic analysis of the various subgroups of breast invasive carcinoma (BRCA/BIC) in TCGA showed that patients with low C4BPA expression might have worse PFI and OS in patients with Luminal A compared to other BC subtypes. Conclusions: In conclusion, these results revealed that C4BPA could potentially act as a diagnostic biomarker for BC patients indicating unfavorable prognoses and offers valuable knowledge for creating therapeutics and prognostic indicators.

Ultrasound Detection of Fetal Palate Development in the Early Stages of the Second Trimester and Its Clinical Application.

OBJECTIVE: To establish normal values of palatal bone growth in fetuses at different gestational weeks in the early stages of the second trimester and to explore the clinical application value of the four-step ultrasound screening method for fetal cleft lip and palate. DESIGN: A prospective study of prenatal ultrasound screening. SETTING: Secondary maternal and child health institutions. PATIENTS: 300 fetuses of 12 to 20 +6 weeks gestation without cleft lip and/or palate; 8538 fetuses at high risk of cleft lip and palate with malformations or karyotypic abnormalities. INTERVENTIONS: None. MAIN OUTCOME MEASURES: palatomandibular diameter (PMD) and transverse palatal diameter was measured and establish their typical values. RESULTS: (1) There is a typical "superimposed line" sign in the median sagittal section of the typically developing fetal face from 12 to 20+6 weeks of gestation. (2) The PMD and hard palate transverse diameter of fetuses from 12 to 20+6 weeks of gestation increased linearly with time. (3) Among 8538 high-risk fetuses, 21 cases of cleft lip and palate were diagnosed by the four-step ultrasound screening method in the early stages of the second trimester. CONCLUSIONS: The median sagittal section of the typically developing fetal face in the early stages of the second trimester presents a typical "superimposed line" sign, and the PMD and transverse palatal diameter increase with time. The four-step ultrasound screening method for fetal cleft lip and palate in the early stages of the second trimester has high clinical application value.

Can the ultrasound microcystic pattern accurately predict borderline ovarian tumors?

OBJECTIVE: To investigate whether the ultrasound microcystic pattern (MCP) can accurately predict borderline ovarian tumors (BOTs). METHODS: A retrospective collection of 393 patients who met the inclusion criteria was used as the study population. Indicators that could well identify BOT in different pathological types of tumors were derived by multivariate unordered logistic regression analysis. Finally, the correlation between ultrasound MCP and pathological features was analyzed. RESULTS: (1) MCP was present in 55 of 393 ovarian tumors, including 34 BOTs (34/68, 50.0%), 16 malignant tumors (16/88, 18.2%), and 5 benign tumors (5/237, 2.1%). (2) Univariate screening showed significant differences (P < 0.05) in patient age, CA-125 level, ascites, > 10 cyst locules, a solid component, blood flow, and MCP among BOTs, benign ovarian tumors, and malignant ovarian tumors. (3) Multivariate unordered logistic regression analysis showed that the blood flow, > 10 cyst locules, and MCP were significant factors in identifying BOTs (P < 0.05). (4) The pathology of ovarian tumors with MCP showed "bubble"- or "fork"- like loose tissue structures. CONCLUSION: MCP can be observed in different pathological types of ovarian tumors and can be used as a novel sonographic marker to differentiate between BOTs, benign tumors and malignant tumors. MCP may arise as a result of anechoic cystic fluid filling the loose tissue gap.

Compounding warning letters to 503A facilities between 2017 and 2021.

BACKGROUND: The growing population demand and the epidemic lead of coronavirus disease 2019 have highlighted the critical importance of patient access to compounded formulations, including for special purposes such as pediatrics, geriatrics, and other uses. However, there are many potential risks, including quality issues and 503A facilities have not received valid prescriptions for individually-identified patients for a portion of the drug products they produce. OBJECTIVE: The aim is to analyze the (503A facilities) warning letters and identify the problem of compounding medicines not meeting the United States Pharmacopoeia specifications. METHODS: Content analysis and descriptive statistics methods were used to analyze the violations of compounding warning letters from 2017 to 2021. The content of warning letter violations was analyzed in terms of both the compounding environment and 503A facilities that did not received valid prescriptions for individually-identified patients for a portion of the drug products they produced. RESULTS: A total of 113 compounding warning letters (503A facilities, N = 112) from 2017 to 2021 were analyzed in this study. The percentage of 503A facilities involved in sterile compounding environmental issues was 79.46%, with facility design and environmental controls (73/89, 82.02%), cleaning and disinfecting the compounding area (59/89, 66.29%), and personnel cleansing and garbing (44/89, 49.44%) being the top 3 issues. Seventy-two (72/112, 64.29%) 503A facilities that did not received valid prescriptions for individually-identified patients for a portion of the drug products they produced. Fifty-one (51/72, 70.83%) of these warning letters were related to sterile environment issues, and 28 warning letters identified specific drugs that did not qualify for Section 503A exemptions. CONCLUSION: The warning letter of compounding drugs issued by Food and Drug Administration can be used as a learning tool for compounders. Compounders can learn from the experience and lessons, improve compounding operations and reduce mistakes.

Structural Characteristics and Emulsifying Properties of Soy Protein Isolate Glycated with Galacto-Oligosaccharides under High-Pressure Homogenization.

This study explored the Maillard reaction process during the glycation of soy protein isolate (SPI) with galacto-oligosaccharides (GOSs) under high-pressure homogenization (HPH) and its effects on the emulsifying properties of SPI. SPI-GOS glycation under moderate pressure (80 MPa) significantly inhibited the occurrence and extent of the Maillard reaction (p < 0.05), but homogenization pressures in the range of 80−140 MPa gradually promoted this reaction. HPH caused a decrease in the surface hydrophobicity of the glycated protein, an increase in the abundance of free sulfhydryl groups, unfolding of the protein molecular structure, and the formation of new covalent bonds (C=O, C=N). Additionally, the particle size of emulsions created with SPI-GOS conjugates was reduced under HPH, thus improving the emulsifying properties of SPI. A reduction in particle size (117 nm), enhanced zeta potential (−23 mV), and uniform droplet size were observed for the emulsion created with the SPI-GOS conjugate prepared at 120 MPa. The conformational changes in the glycated protein supported the improved emulsification function. All results were significantly different (p < 0.05). The study findings indicate that HPH provides a potential method for controlling glycation and improving the emulsifying properties of SPI.

Structural and Emulsifying Properties of Soybean Protein Isolate-Sodium Alginate Conjugates under High Hydrostatic Pressure.

Soybean protein isolate (SPI) is a kind of plant derived protein with high nutritional value, but it is underutilized due to its structural limitations and poor functionalities. This study aimed to investigate the effects of high hydrostatic pressure (HHP) treatment on SPI and sodium alginate (SA) conjugates prepared through the Maillard reaction. The physicochemical properties of the conjugate synthesized under 200 MPa at 60 °C for 24 h (SPI-SA-200) were compared with those of the conjugate synthesized under atmospheric pressure (SPI-SA-0.1), SPI-SA mixture, and SPI. The HHP (200 MPa) significantly hindered the Maillard reaction. This effect was confirmed by performing SDS-PAGE. The alterations in the secondary structures, such as α-helices, were analyzed using circular dichroism spectroscopy and the fluorescence intensity was determined. Emulsifying activity and stability indices of SPI-SA-200 increased by 33.56% and 31.96% respectively in comparison with the SPI-SA-0.1 conjugate. Furthermore, reduced particle sizes (356.18 nm), enhanced zeta potential (‒40.95 mV), and homogeneous droplet sizes were observed for the SPI-SA-200 emulsion. The present study details a practical method to prepare desirable emulsifiers for food processing by controlling the Maillard reaction and improving the functionality of SPI.

Effect of high hydrostatic pressure on solubility and conformation changes of soybean protein isolate glycated with flaxseed gum.

Soybean protein isolate (SPI) was incubated with flaxseed gum (FG) at 60 °C for 3 days under high hydrostatic pressure (HHP 0.1-300 MPa). Results showed improvement in solubility of SPI upon glycation with FG. The maximum solubility reached 86.84% when SPI-FG was treated at pH 8.0 and 200 MPa. The occurrence, degrees and sites of SPI-FG glycation suggested that moderate pressure (100 MPa) significantly promoted Maillard reactions, but higher pressures (greater than 200 MPa) suppressed these reactions. The secondary structure of the glycated proteins varied greatly with respect to α-helix and random coil contents and vibrations of the amide II band at 200 MPa. These microstructural changes increased the solubility over a broad pH range. The conformational changes in the glycated SPI supported the improved solubility of SPI-FG. Overall, HHP represents a potential method of controlling glycation to improve protein processability and expand their applicability in the food industry.

Effect of high-pressure processing enzymatic hydrolysates of soy protein isolate on the emulsifying and oxidative stability of myofibrillar protein-prepared oil-in-water emulsions.

BACKGROUND: Oil-in-water (O/W) emulsions are thermodynamically unstable and are easily oxidized. Recently, protein hydrolysates have been used to enhance the emulsifying and oxidative stability of emulsions. High-pressure processing (HPP) enzymatic hydrolysates of soy protein isolate have higher bioactivities. The objective of the study was to investigate the effects of various soy protein isolate hydrolysate (SPIH) concentrations obtained during different 4 h pressure treatments on improving the emulsifying and oxidative stability of myofibrillar protein (MP) emulsions. RESULTS: Emulsions with 4 mg mL-1 SPIH obtained at 200 MPa had the highest emulsifying activity index and emulsion stability index (P ≤ 0.05). This increase in emulsion stability was related to increased zeta potential and reduced average particle size. Optical microscopy and confocal laser scanning microscopy observations confirmed that emulsions with 4 mg mL-1 SPIH possessed relatively small oil droplets. The addition of SPIH obtained at 200 MPa significantly reduced thiobarbituric acid reactive substance values (P ≤ 0.05) of emulsions during 8 days of storage. Concurrently, the carbonyl content remained the lowest and the sulfhydryl content remained the highest, which indicated that the emulsions had higher protein oxidative stability. CONCLUSIONS: SPIH obtained under HPP could improve the emulsifying and oxidative stability of MP-prepared O/W emulsions.

Flavonoids from sea buckthorn inhibit the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages through the MAPK and NF-κB pathways.

Sea buckthorn has long been used as a functional food to regulate cholesterol, relieve angina, and diminish inflammation. Flavonoids are one of the main active components in sea buckthorn. We investigated the effects of sea buckthorn flavonoid (SF) treatment on two pathways that mediate inflammation, the mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways, to explore the anti-inflammatory activity of SFs in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The LPS-induced over-production of nitric oxide (NO) and prostaglandin E2 (PGE2) was inhibited by SFs through a mechanism related to the modulatory effects of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) genes. Additionally, SFs downregulated the production and mRNA expression of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß. Moreover, SFs inhibited the phosphorylation of the p38 and stress-activated protein kinase/jun amino-terminal kinase (SAPK/JNK) MAPK pathways, and they reduced the nuclear translocation of NF-κB to prevent its activation by blocking the phosphorylation and degradation of inhibitor protein of NF-κB α (IκB-α). Based on these findings, SFs may exert their inhibitory effects on inflammation by regulating the release of inflammatory mediators through the MAPK and NF-κB pathways. SFs highlight the potential benefits of using functional foods with anti-inflammatory actions to combat inflammatory diseases.