Ginsenosides, including Rb 1 , Rb 2 , Rb 3 and Rc, belong to protopanaxadiol-type saponins in Panax ginseng C. A. Mey. Their contents are high in P. ginseng. They could inhibit oxidant stress, enhance immunity, lower blood sugar, resist tumor cells and facilitate other physiological activities. This study aimed to explore the interaction between ginsenosides Rb 1 , Rb 2 , Rb 3 and Rc and the intestinal flora of healthy people. It also sought to analyse the biotransformation products and pathways of these ginsenosides in in-vitro human intestinal bacteria and their effects on the diversity of human intestinal flora. Human intestinal bacteria were incubated with ginsenosides Rb 1 , Rb 2 , Rb 3 and Rc at 37 °C under anaerobic conditions. Samples were taken at different timepoints. The transformed products were identified by rapid high-resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. After 48 h of transformation, the transformed product of ginsenosides Rb 1 , Rb 2 , Rb 3 and Rc was ginsenoside compound K. The transformation rates were 83.5 %, 88.7 %, 85.6 %, and 84.2 %. 16S rRNA sequencing technology was applied to the bioinformatic analysis of faecal samples incubated for 48 h. Relative to the blank control, the relative abundance of Firmicutes and Proteobacteria significantly increased at the phylum level. Moreover, the relative abundance of Bacteroidetes significantly decreased in ginsenosides Rb 1 , Rb 2 , Rb 3 and Rc. At the genus level, the relative abundance of Escherichia significantly increased, whereas that of Dorea, Prevotella and Megasphaera significantly decreased in all groups. These results showed that Rb 1 , Rb 2 , Rb 3 and Rc could improve the structure and diversity of human intestinal flora and balance the metabolic process.

Protopanaxadiol (PPD)-type ginsenosides are the main ginsenosides in ginseng (Panax ginseng C. A. Meyer) with potential therapeutic effects on diseases related to intestinal flora imbalance. This study aimed to investigate the in vitro metabolism of protopanaxadiol ginsenosides in human intestinal flora and their effect on the flora. Rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF MS) was utilised for the transformation of ginsenoside constituents for sample identification. Using 16S rDNA gene sequencing technique, the effect of PPD-type ginsenosides on gut microflora was analysed based on the indices of microflora diversity and gut microflora. The sample was transformed for 6 h, and the metabolites were ginsenoside Rb1, Rc, Rb2, Rb3, CO, Gyp-IX, Gyp-XVII, CMc-1, F2, Rg3, CK, Rh2, and PPD. The metabolites were CK, Rh2, and PPD when the samples were transformed for 60 h. The intestinal microflora were subjected to high-throughput sequencing using the Illumina MiSeq 2500 sequencing platform. In comparison with the faecal sample from the blank group, the protopanaxadiol saponin group significantly increased the relative abundance of Firmicutes and significantly decreased Bacteroidetes and Proteobacteria at the phylum level, whereas it significantly increased the relative abundance of Prevotella_9, Faecalibacterium, and Dialister and significantly decreased Escherichia-Shigella, Dorea, and Lachnoclostridium at the genus level. This study provides a basis for the determination of the pharmacodynamic material basis and pharmacodynamic targets of PPD-type ginsenosides based on the intestinal flora.

Although diaphragmatic dysfunction is an important indicator of severity of illness and poor prognosis in ICU patients, there is no convenient and practical method to monitor diaphragmatic function. This study was designed to analyze diaphragmatic dynamic dysfunction by bedside ultrasound in septic patients and provide quantitative evidence to assess diaphragm function systematically. This prospective observational study was conducted from October 2019 to January 2021 in the Department of Respiratory and Critical Care Medicine. 74 patients suffered from sepsis were recruited and divided into two groups, sepsis group 1 (2 ≤ SOFA ≤ 5, n = 41) and sepsis group 2 (SOFA > 5, n = 33). 107 healthy volunteers were randomly recruited as the control group. In all participants, the diaphragmatic thickness and excursion were measured directly and the dynamic parameters including thickening fraction (TF), EQB/EDB, Contractile velocity, and area under diaphragmatic movement curve (AUDMC) were calculated by bedside ultrasound during quiet breathing (QB) and deep breathing (DB). Each parameter among three groups was analyzed separately by covariance analysis, which was adjusted by age, sex, body mass index, MAP, hypertension, and diabetes. First, contractile dysfunction occurred before diaphragmatic atrophy both in sepsis group 1 and sepsis group 2. Second, compared with the control group, the dynamic parameters showed significant decrease in sepsis group 1 and more obvious change in sepsis group 2, including TF, EQB/EDB. Third, the maximum contractile velocity decreased in sepsis group 1, reflecting the damage of intrinsic contraction efficiency accurately. Finally, per breathing AUDMC in two septic groups were lower than those in control group. However, per minute AUDMC was compensated by increasing respiratory rate in sepsis group 1, whereas it failed to be compensated which indicated gradual failure of diaphragm in sepsis group 2. Diaphragmatic ultrasound can be used to quantitatively evaluate the severity of sepsis patients whose contractile dysfunction occurred before diaphragmatic atrophy. As dynamic parameters, TF and EQB/EDB are early indicator associated with diaphragmatic injury. Furthermore, maximum contractile velocity can reflect intrinsic contraction efficiency accurately. AUDMC can evaluate diaphragmatic breathing effort and endurance to overcome resistance loads effectively.

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A new and practical protocol for the synthesis of medicinally privileged azolo­[1,3,5]­triazines by simply heating under air has been presented. The in situ generated N-azolo amidines from commercially available aromatic aldehydes and 3-aminoazoles with ammonium iodide undergo the second diamination to accomplish the [3 + 1 + 1 + 1] heteroannulation reaction. This convenient process is appreciated by high efficiency, broad substrate scope, gram-scale synthesis, and operational simplicity under reagent-free conditions.