Association between acetaminophen administration and clinical outcomes in patients with sepsis admitted to the ICU: a retrospective cohort study.

Background: Sepsis, affecting over 30 million people worldwide each year, is a key mortality risk factor in critically ill patients. There are significant regional discrepancies in its impact. Acetaminophen, a common over-the-counter drug, is often administered to control fever in suspected infection cases in intensive care units (ICUs). It is considered generally safe when used at therapeutic levels. Despite its widespread use, there's inconsistent research regarding its efficacy in sepsis management, which creates uncertainties for ICU doctors about its possible advantages or harm. To address this, we undertook a retrospective cohort study utilizing the MIMIC-IV database to examine the correlation between acetaminophen use and clinical outcomes in septic patients admitted to the ICU. Methods: We gathered pertinent data on sepsis patients from the MIMIC-IV database. We used propensity score matching (PSM) to pair acetaminophen-treated patients with those who were not treated. We then used Cox Proportional Hazards models to examine the relationships between acetaminophen use and factors such as in-hospital mortality, 30-day mortality, hospital stay duration, and ICU stay length. Results: The data analysis involved 22,633 sepsis patients. Post PSM, a total of 15,843 patients were matched; each patient not receiving acetaminophen treatment was paired with two patients who received it. There was a correlation between acetaminophen and a lower in-hospital mortality rate (HR 0.443; 95% CI 0.371-0.530; p < 0.001) along with 30-day mortality rate (HR 0.497; 95% CI 0.424-0.583; p < 0.001). Additionally, it correlated with a decrease in the duration of hospitalization [8.4 (5.0, 14.8) vs. 9.0 (5.1, 16.0), p < 0.001] and a shorter ICU stay [2.8 (1.5, 6.0) vs. 3.1 (1.7, 6.5); p < 0.05]. Conclusion: The use of acetaminophen may lower short-term mortality in critically ill patients with sepsis. To confirm this correlation, future research should involve multicenter randomized controlled trials.

Metabolomic analysis to unravel the composition and dynamic variations of anthocyanins in bayberry-soaked wine during the maceration process.

In this work, we employed a global untargeted metabolomics technique to explore the intricate composition of anthocyanin constituents in bayberry wine and elucidate their alteration during the maceration process. Our analysis uncovered 20 distinct forms of anthocyanins in bayberry wine, including cyanidin-type, delphinidin-type, peonidin-type, malvidin-type, and other-type. 'Dongkui' (DK) bayberry wine was characterized by a predominance of glycoside forms of cyanidin-type and delphinidin-type anthocyanins, while 'Shuijing' (SJ) bayberry wine mainly contained other-type anthocyanins. Additionally, differential anthocyanins analyses conducted across various maceration periods demonstrated the different fate of the components in the wine, with a conspicuous decline in most glycosidic form anthocyanins. Moreover, correlation analysis revealed that the red hue of bayberry wine was primarily associated with cyanidin-3-O-glucoside, cyanidin-3-O-rhamnoside, delphinidin-3-O-arabinoside, and delphinidin-3-O-galactoside. This research contributes to our understanding of the anthocyanin composition and the dynamic variations in bayberry wine, opening avenues for further exploration and optimization of production techniques in the future.

Effects of alcoholic fermentation on the non-volatile and volatile compounds in grapefruit (Citrus paradisi Mac. cv. Cocktail) juice: A combination of UPLC-MS/MS and gas chromatography ion mobility spectrometry analysis.

Grapefruit has attracted much attention as a functional fruit, of which "Cocktail" is a special variety with low acidity. The present study aimed to investigate the effects of alcoholic fermentation on the non-volatile and volatile compounds of "Cocktail" grapefruit juice. To analyze, a non-targeted metabolomics method based on UPLC-MS/MS and volatiles analysis using GC-IMS were performed. A total of 1015 phytochemicals were identified, including 296 flavonoids and 145 phenolic acids, with noticeably increasing varieties and abundance following the fermentation. Also 57 volatile compounds were detected, and alcoholic fermentation was effective in modulating aromatic profiles of grapefruit juice, with terpenes and ketones decreasing, and alcohols increasing together with esters. Citraconic acid and ethyl butanoate were the most variable non-volatile and volatile substances, respectively. The results provide a wealth of information for the study of "Cocktail" grapefruit and will serve as a valuable reference for the large-scale production of grapefruit fermented juice in the future.

Effects of Poncirin, a Citrus Flavonoid and Its Aglycone, Isosakuranetin, on the Gut Microbial Diversity and Metabolomics in Mice.

Poncirin (PC) and its aglycone, isosakuranetin (IR), occur naturally in citrus fruits. This study aimed to explore the pathways behind the different health benefits of PC and IR by evaluating the effect of these two bioactive flavonoids on the gut microbial diversity and metabolomics of mice. The 16S rRNA gene sequencing was used to analyze the alteration of gut microbiota in mice after PC and IR intervention. The metabolic impact of PC and IR in mice were studied using a metabolomics approach based on LC-MS analysis. Results showed that, after 7 days intervention, PC and IR multiplied the abundance of Parabacteroides in mice's intestinal tracts by 1.2 and 1.0 times, respectively. PC increased the abundance of Bacteroides by 2.4 times. IR reduced the Allobaculum abundance by 1.0 time and increased Alloprevotella abundance by 1.5 times. When mice were given PC, their fecal acetic acid level increased by 1.8 times, while their isobutyric and isovaleric acid content increased by 1.2 and 1.3 times, respectively. Supplementation with IR had no significant effect on the content of short-chain fatty acids (SCFAs) in the feces of mice. The potential urine biomarkers of mice in the PC group were involved in the digestion and absorption of protein and carbohydrate, as well as the metabolism of amino acids, such as glycine, serine, threonine, tryptophan, D-arginine, D-ornithine, etc. IR mainly affected the amino acid metabolic pathways in mice, including taurine and hypotaurine metabolism, glutathione metabolism, histidine metabolism, D-glutamate metabolism, etc. This study provided valuable clues for future research on the health promoting mechanisms of PC and IR.

Involvement of phase II enzymes and efflux transporters in the metabolism and absorption of naringin, hesperidin and their aglycones in rats.

This study examined the effects of phase II metabolism and efflux transportation on the bioavailability of naringin, hesperidin, and their aglycones (naringenin and hesperetin) in rats. Results indicated naringin and hesperidin have a lower oral bioavailability than their aglycones. Of all the phase II enzymes tested, UDP-glucuronosyltransferase (UGT) 1A1, UGT1A2, UGT1A3, UGT1A7 and SULT sulfotransferase (SULT) 1B1 were of minor importance regarding the phase II metabolism of naringenin and hesperetin in the small intestine. Naringin, hesperidin, and their aglycones were all extensively metabolised in the liver. Naringin and hesperidin were more extensively transported by efflux transporters compared to their aglycones. Significant correlations between phase II enzymes and efflux transporters were detected. In conclusion, more extensive metabolism of naringin and hesperidin than their aglycones in the small intestine, and the interplay of phase II enzymes and efflux transporters in the small intestine explain the lower relative oral bioavailability of naringin and hesperidin than their aglycones.

Inhibitory effects of fermented Ougan (Citrus reticulata cv. Suavissima) juice on high-fat diet-induced obesity associated with white adipose tissue browning and gut microbiota modulation in mice.

In this study, Ougan juice (OJ) and lactic acid bacteria fermented Ougan juice (FOJ) were investigated individually for their capability of preventing obesity in high-fat diet (HFD)-fed C57BL/6J mice. After being administered with OJ or FOJ for 10 weeks, the body weight gain, hyperlipidemia, and gut microbiota dysbiosis of HFD-fed mice were examined. The results showed that OJ or FOJ supplementation inhibited weight gain, lowered fat accumulation, reduced liver steatosis, improved glucose homeostasis and insulin sensitivity, increased brown adipose tissue (BAT) activity, and promoted white adipose tissue (WAT) browning. Both OJ and FOJ additions increased the diversity of gut microbiota. OJ reduced the relative abundance of phylum Erysipelatoclostridiaceae and genus Erysipelatoclostridium and remarkably increased SCFA-producing bacteria Blautia, while FOJ reduced the ratio of Firmicutes to Bacteroidetes and enhanced the relative abundance of family Lactobacillaceae. Spearman's correlation analysis revealed that Akkermansia, Dubosiella, and Muribaculaceae were significantly negatively correlated with obesity-related indexes. In general, FOJ exhibited a better inhibitory effect on obesity than OJ, and the possible inhibitory mechanism lies in promoting WAT browning and increasing intestinal probiotics. This study provides the guidance for developing fermented Ougan juice as an obesity-inhibiting functional food.