Effect of Pulsatilla decoction on vulvovaginal candidiasis in mice. Evidences for its mechanisms of action.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common infection that affects the female reproductive tract. Pulsatilla decoction (PD), a traditional Chinese herbal medicine, is a classic and effective prescription for VVC. However, its mechanism of action remains unclear. PURPOSE: This study aimed to evaluate the efficacy and potential mechanism of action of the n-butanol extract of Pulsatilla decoction (BEPD) in VVC treatment. METHODS: High performance liquid chromatography (HPLC) was used to detect the main active ingredients in BEPD. A VVC-mouse model was constructed using an estrogen-dependent method to evaluate the efficacy of BEPD in VVC treatment. Fungal burden and morphology in the vaginal cavity were comprehensively assessed. Candida albicans-induced inflammation was examined in vivo and in vitro. The effects of BEPD on the Protein kinase Cδ (PKCδ) /NLR family CARD domain-containing protein 4 (NLRC4)/Interleukin-1 receptor antagonist (IL-1Ra) axis were analyzed using by immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and reverse transcription-quantitative polymerase chain reaction (qRT-PCR). RESULTS: BEPD inhibited fungal growth in the vagina of VVC mice, preserved the integrity of the vaginal mucosa, and suppressed inflammatory responses. Most importantly, BEPD activated the "silent" PKCδ/NLRC4/IL-1Ra axis and negatively regulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, thereby exerting a therapeutic efficacy on VVC. CONCLUSIONS: BEPD effects on mice with VVC were dose-dependent. BEPD protects against VVC by inhibiting inflammatory response and NLRP3 inflammasome via the activation of the PKCδ/NLRC4/IL-1Ra axis. This study revealed the pharmacological mechanism of BEPD in VVC treatment and provided further evidence for the application of BEPD in VVC treatment.

Capture of CO2 during the Electrolysis Process and Its Utilization in Supercapacitor Materials.

With climate change and environmental issues, the emissions of CO2 and its greenhouse effect have become a focal point. At present, the utilization of CO2 includes its synthesis into chemicals and fuels such as methane, methanol, and CO. CO2 utilization can be achieved through carbon capture and storage technologies, which involve capturing CO2 from industrial emissions and storing it to reduce the CO2 concentration in the atmosphere. However, these CO2 capture and utilization technologies still face challenges, such as technical immaturity and high costs. One of the CO2 capture and utilization technologies is the production of energy storage materials. In this study, CO2 captured by molten salt was used as the carbon source, and TiO2 nanotube arrays were used as precursors. Titanium carbide nanotube arrays(TiC-NTAs)with high specific surface area and high conductivity were prepared by electrolysis. Afterward, the electrochemical energy storage performance of TiC in different electrolytes was tested. The results show that reducing the ionic radius of the electrolyte is conducive to increasing the area-specific capacitance of the device and that the degradation of the cycle life of the quasi-solid supercapacitor may be caused by an increase in the internal resistance due to the loss of water from the electrolyte. This study provides a reference value for the low-temperature synthesis of nanometal carbides and the selection of electrolytes.

Effect of the Pulsatilla decoction n-butanol extract on vulvovaginal candidiasis caused by Candida glabrata and on its virulence factors.

Vulvovaginal candidiasis (VVC) caused by Candida glabrata (C. glabrata) is more persistent and resistant to treatment than when caused by Candida albicans (C. albicans) and has been on the rise in recent years. The n-butanol extract of Pulsatilla Decoction (BEPD) has been shown to be effective in treating VVC caused by C. glabrata, but the underlying mechanism of action remains unclear. In this study, the experimenter conducted in vitro and in vivo experiments to explore the effects of BEPD on the virulence factors of C. glabrata, as well as its efficacy, with a focus on possible immunological mechanism in VVC caused by C. glabrata. The contents of Anemoside B4, Epiberberine, Berberine, Aesculin, Aesculetin, Phellodendrine and Jatrorrhizine in BEPD, detected by high-performance liquid chromatography, were 31,736.64, 13,529.66, 105,143.72, 19,406.20, 4952.67, 10,317.03, 2489.93 µg/g, respectively. In vitro experiments indicated that BEPD moderately inhibited the growth of C. glabrata, its adhesion, and biofilm formation, and affected the expression of efflux transporters in the biofilm state. In vivo experiments demonstrated that BEPD significantly reduced vaginal inflammatory manifestation and the release of proinflammatory cytokines and LDH in mice with VVC caused by C. glabrata. Moreover, it inhibited the Phosphorylation of EGFR, ERK, P38, P65, and C-Fos proteins. The results suggested that although BEPD moderately inhibits the growth and virulence factors of C. glabrata in vitro, it can significantly reduce vaginal inflammation by down-regulating the EGFR/MAPK signaling pathway in mice with VVC infected by C. glabrata.

An integrated approach for studying the metabolic profiling of herbal medicine in mice using high-resolution mass spectrometry and metabolomics data processing tools.

Analysis of exposure to traditional Chinese medicine (TCM) in vivo based on mass spectrometry is helpful for the screening of effective ingredients of TCM and the development of new drugs. The method of screening biomarkers through metabolomics technology is a nontargeted research method to explore the differential components between two sets of biological samples. By taking this advantage, this study aims to takes Forsythia suspensa, which is a TCM also known as Lian Qiao (LQ), as the research object and to study its in vivo exposure by using metabolomics technology. By comparing the significant differences between biological samples before and after administration, it could be focused on the components that were significantly upregulated, where a complete set of analysis strategies for nontargeted TCM in vivo exposure mass spectrometry was established. Furthermore, the threshold parameters for peak extraction, parameter selection during statistical data analysis, and sample concentration multiples in this method have also been optimized. More interestingly, by using the established analysis strategy, we found 393 LQ-related chemical components in mice after administration, including 102 prototypes and 291 LQ-related metabolites, and plotted their metabolic profiles in vivo. In short, this study has obtained a complete mass spectrum of LQ exposure in mice in vivo for the first time, which provides a reference for research on the active ingredients of LQ in vivo. More importantly, compared with other methods, the analysis strategy of nontargeted exposure of TCM in vivo-based mass spectrometry, constructed by using this research method, has good universality and does not require self-developed postprocessing software. It is worth mentioning that, for the identification and characterization of trace amounts of metabolites in vivo, this analysis strategy has no discrimination and has a detection capability similar to that of highly exposed components.

Toxic metabolites and metabolic soft spots of celastrol based on glutathione metabolic capture and high-resolution mass spectrometry.

BACKGROUND: Celastrol is known as one of the most medicinally valuable compounds. However, the pharmaceutical application of celastrol is significantly limited due to high toxicity, while there are few reports on the mechanism of toxicity. METHODS: This study searched for possible toxic metabolites through phase I in vitro metabolism and glutathione capture experiments. Then in vivo metabolism experiments in mice and rats were conducted to look for metabolites in vivo. Finally, mice in vivo toxicity experiment was conducted to verify the toxicity of different doses of celastrol to mice. RESULTS: In the in vivo and in vitro metabolism experiments, we found 7 phase I metabolites in vitro, 9 glutathione conjugation metabolites in vitro, and 20 metabolites in vivo. The metabolic soft points of celastrol could be the quinone methyl structure at C3-OH and C6. In vivo toxicity experiments show that celastrol causes weight loss, diarrhea, gastrointestinal tract and liver inflammation in mice. CONCLUSIONS: This study analyzed the metabolites and possible metabolic soft spots of celastrol, and its hepatotoxicity and gastrointestinal toxicity were demonstrated through in vivo studies for the first time. The results might provide an important basis for potential structural modification to increase the druggability of celastrol.

Preparation of VZrHfNbTa High-Entropy Alloy-Based High-Temperature Oxidation-Resistant Coating and Its Bonding Mechanism.

Ultra-high Temperature Oxidation-Resistant Alloys (UTORAs) have received a lot of attention due to the increased research demand for deep space exploration around the world. However, UTORAs have the disadvantages of easy oxidation and chalking. So, in this study, a UTORAs is prepared by hot-press sintering on VZrHfNbTa (HEA: High Entropy Alloys can generally be defined as more than five elements by the equal atomic ratio or close to the equal atomic ratio alloying, the mixing entropy is higher than the melting entropy of the alloy, generally forming a high entropy solid solution phase of a class of alloys.) a substrate coated with hafnium. The bonding mechanism, resistance to high-temperature oxidation, and hardness of the sample tests are carried out. The results show that zirconium in the matrix will diffuse into the hafnium coating during the high-temperature sintering process and form the HfZr alloy transition layer, the coating thickness of the composite is about 120 µm, and the diffusion distance of zirconium in the hafnium coating is about 60 µm, this transition layer chemically combines the hafnium coating and the HEA substrate into a monolithic alloy composite. The results of high-temperature oxidation experiments show that the oxidation degree of the hafnium-coated VZrHfNbTa composite material is significantly lower than that of the VZrHfNbTa HEA after oxidation in air at 1600 °C for 5 h. The weight gain of the coated sample after oxidation is 56.56 mg/cm2, which is only 57.7% compared to the weight gain of the uncoated sample (98.09 mg/cm2 for uncoated), and the surface of the uncoated HEA shows obvious dents, oxidation, and pulverization occurred on the surface and interior of the sample. In contrast, the coated composite alloy sample mainly undergoes surface oxidation sintering to form a dense HfO2 protective layer, and the internal oxidation of the hafnium-coated VZrHfNbTa composite alloy is significantly lower than that of the uncoated VZrHfNbTa HEA.

Liposomal doxorubicin and free doxorubicin in vivo quantitation method developed on CE-LIF and its application in pharmacokinetic analysis.

As a novel drug delivery system, liposomes were used to improve pharmacokinetics/pharmacodynamics (PK/PD) characters, minimize toxicity, and enhance drug-target selectivity. However, heterogeneity of drug releasing process and liposome itself challenged traditional pharmaceutical analytical techniques, especially in vivo pharmacokinetic studies. In this study, a novel liposomal doxorubicin (L-DOX) pharmacokinetic analysis strategy was developed with capillary electrophoresis coupled with laser-induced fluorescence (CE-LIF) detector. The background electrolyte (BGE) system was composed of borate and sodium dodecyl sulfate (SDS), which was optimized to successfully achieve simultaneous online separation and quantitative analysis of free DOX and liposome-encapsulated DOX. The method was applied to the in vivo pharmacokinetic study of L-DOX in rats. The results showed that the concentration of total DOX (T-DOX) was gradually decreasing, while the concentration of L-DOX was relatively stable, with a concentration of 31.6 ± 4.8 µg/mL within 24 h. It was the first time to achieve liposomal drugs in vivo analysis with CE-LIF. CE-LIF was proved as potential rapidly real-time analytical methods for liposomal drugs in vivo occurrence monitoring.

Comparing postoperative analgesia of bilateral serratus anterior plane block and thoracic paravertebral block for children following the Nuss procedure: protocol for a randomised, double-blind, non-inferiority clinical trial.

INTRODUCTION: The Nuss procedure, despite being a minimally invasive surgery, is regarded as one of the most painful surgical procedures in children, and postoperative pain control remains a major clinical issue in this population. Thoracic paravertebral nerve block (TPVB) is reported as excellent pain relief for the Nuss procedure despite its challenging performance and associated adverse effects. Serratus anterior plane block (SAPB) is a simplified and effective method for managing thoracic pain as an alternative to TPVB. However, whether SAPB can provide analgesia comparable with that provided by the TPVB approach in children undergoing the Nuss procedure is unknown. METHODS AND ANALYSIS: This will be a prospective, randomised, double-blind, single-centre, non-inferiority trial that will enrol children aged 7-16 years subjected to the Nuss operation for pectus excavatum. In total, 74 paediatric patients will be randomly assigned to either the SAPB or TPVB group after general anaesthesia to receive ultrasound-guided regional nerve blocks (0.25% ropivacaine 2.5 mg/kg). The primary outcome will be the assessment of postoperative pain intensity at predetermined time points. The secondary outcomes will include assessing intraoperative opioid intake, consumption of analgesics within 24 hours postoperatively, time of first use of rescue analgesics, extubation time, perioperative adverse events and plasma ropivacaine concentrations across the block groups. Demographic and clinical characteristics (eg, pectus severity and the number of bars used) of the patients will be recorded. All data will be collected by investigators who are blinded to the treatment. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Ethics Committee on Biomedical Research of the West China Hospital of Sichuan University (2021-1275). During the period of the study, all procedures will be conducted following the principles of the Declaration of Helsinki. The results of the trial will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: ChiCTR2200056596.

Global Xenobiotic Profiling of Rat Plasma Using Untargeted Metabolomics and Background Subtraction-Based Approaches: Method Evaluation and Comparison.

BACKGROUND: Global xenobiotic profiling (GXP) is to detect and structurally characterize all xenobiotics in biological samples using mainly liquid chromatography-high resolution mass spectrometry (LC-HRMS) based methods. GXP is highly needed in drug metabolism study, food safety testing, forensic chemical analysis, and exposome research. For detecting known or predictable xenobiotics, targeted LC-HRMS data processing methods based on molecular weights, mass defects and fragmentations of analytes are routinely employed. For profiling unknown xenobiotics, untargeted and LC-HRMS based metabolomics and background subtraction-based approaches are required. OBJECTIVE: This study aimed to evaluate the effectiveness of untargeted metabolomics and the precise and thorough background subtraction (PATBS) in GXP of rat plasma. METHODS: Rat plasma samples collected from an oral administration of nefazodone (NEF) or Glycyrrhizae Radix et Rhizoma (Gancao, GC) were analyzed by LC-HRMS. NEF metabolites and GC components in rat plasma were thoroughly searched and characterized via processing LC-HRMS datasets using targeted and untargeted methods. RESULTS: PATBS detected 68 NEF metabolites and 63 GC components, while the metabolomic approach (MS-DIAL) found 67 NEF metabolites and 60 GC components in rat plasma. The two methods found 79 NEF metabolites and 80 GC components with 96% and 91% successful rates, respectively. CONCLUSION: Metabolomics methods are capable of GXP and measuring alternations of endogenous metabolites in a group of biological samples, while PATBS is more suited for sensitive GXP of a single biological sample. A combination of metabolomics and PATBS approaches can generate better results in the untargeted profiling of unknown xenobiotics.

Nilaparvata lugens ERR2 regulates moulting and ovary development is related to hormone signalling.

The nuclear receptor (NR) superfamily is one of the largest groups of transcription factors in living organisms. Oestrogen related receptor (ERR) is a class of nuclear receptors closely related to oestrogen receptors (ERs). In this study, the Nilaparvata lugens (N. lugens) ERR2 (NlERR2) was cloned, and the expression of NlERR2 was detected by qRT-PCR to explore the distribution of NlERR2 during development and in different tissues. Using RNAi and qRT-PCR, the interaction between NlERR2 and related genes of the 20-hydroxyecdysone (20E) and juvenile hormone (JH) signalling pathways was studied. The results showed that topical application of 20E and juvenile hormone III (JHIII) affected the expression of NlERR2, and NlERR2 could affect the expression of genes related to 20E and JH signalling pathways. Furthermore, NlERR2 and JH/20E hormone signalling-related genes affect moulting and ovarian development. NlERR2 and NlE93/NlKr-h1 affect the transcriptional expression of Vg-related genes. In summary, NlERR2 is related to hormone signalling pathways, which is also related to the expression of Vg and Vg related genes. Brown planthopper is one of the most important rice pests. This study provides an important basis for mining new targets for pest control.

[Mechanism of Shenling Baizhu Powder in alleviation of ulcerative colitis in mice based on high-throughput transcriptome sequencing].

High-throughput transcriptome sequencing was used to study the mechanism of Shenling Baizhu Powder(SLBZP) in the alleviation of the dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) in mice. The mouse model of DDS-induced UC was treated with SLBZP by gavage. The changes in general state, disease activity index(DAI), and colon length were observed. The hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissues of mice. Enzyme-linked immunosorbent assay(ELISA) was used to determine the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1ß, IL-6, IL-4, and IL-10 in the serum and tissues of mice. The differentially expressed genes in the control group, the model group, and the SLBZP group were analyzed by high-throughput transcriptome sequencing, and the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were conducted on the differentially expressed genes. The results showed that after intragastric administration of SLBZP, the symptoms of diarrhea and bloody stool were improved, and the disease active index(DAI) score was reduced. SLBZP effectively reduced the inflammatory cell infiltration and goblet cell loss in the colonic mucosal tissue, reduced the levels of TNF-α, IL-1ß, IL-6 in the serum and colon tissue, and increased the levels of IL-4 and IL-10 in the serum and colon tissue. There were 25 differential genes in SLBZP vs the model group, which were significantly enriched in immune response, immune system process, immunoglobulin production, and other biological processes. KEGG pathway analysis showed that the differential genes were enriched in signaling pathways such as neomycin, kanamycin, and gentamicin biosynthesis, cytokine-cytokine receptor interaction, primary immunodeficiency, and IgA synthesis of the intestinal immune network. This study shows that SLBZP may alleviate UC through immune regulation.

The efficacy of negative pressure wound therapy after hepatopancreatobiliary surgery: A systematic review and meta-analysis.

Objective: To evaluate the comparative influence of NPT and standard surgical dressing administration on incidence risk for surgical site infections, complications, and hospital re-admission after hepatopancreatobiliary surgery. Methods: Five databases were systematically searched according to PRISMA guidelines. These databases included Web of Science, MEDLINE, CENTRAL, EMBASE, and Scopus for eligible studies published prior to March 2021. With eligible studies, we conducted a random-effects meta-analysis to evaluate comparative outcomes such as superficial surgical infection, deep surgical infection, seroma incidence, hematoma incidence, and hospital re-admission in patients receiving NPT or standard surgical dressings after hepatopancreatobiliary surgery. Results: The search strategy yielded 963 studies, with six studies meeting inclusion criteria. Odds of superficial surgical site infection (OR: 1.58), deep surgical site infection (1.43), seroma complication (1.64), hematoma complication (0.40) were insignificantly different between patients receiving NPT and standard surgical dressing. The odds of hospital re-admission rate (2.37), however, were elevated in patients receiving standard surgical dressing relative to those receiving NPT. Conclusion: This meta-analysis shows that NPT usage slightly reduces risk of hospital readmission as compared to standard surgical dressing. We did not observe any significant effect of NPT on superficial, deep surgical infections, seroma, and haematoma outcomes following hepatopancreatobiliary surgery. These findings may aid clinicians in stratifying risk and selecting treatment strategy in patients undergoing hepatopancreatobiliary surgery.

Causal effect of serum 25-hydroxyvitamin D levels on low back pain: A two-sample mendelian randomization study.

Background: Previous observational studies have suggested the involvement of 25-hydroxyvitamin D [25(OH)D] in chronic pain. However, whether the 25(OH)D is a novel target for management, the causality remains unclear. Methods: A two-sample Mendelian randomization (MR) study was conducted to identify the causal association between 25(OH)D and low back pain (LBP). The primary analysis was revealing causality from serum 25(OH)D level (n = 417,580) on LBP (21,140 cases and 227,388 controls). The replicated analysis was performing MR estimates from circulating 25(OH)D concentration (n = 79,366) on LBP experienced last month (118,471 cases and 343,386 controls). Inverse variance weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results. Results: IVW estimation indicated strong evidence that higher serum 25(OH)D levels exerted a protective effect on LBP (OR = 0.89, 95% CI = 0.83-0.96, p = 0.002). Similar trends were also found in replicate analysis (OR = 0.98, 95% CI = 0.96-1.00, p = 0.07). After meta-analysis combining primary and replicated analysis, the causal effect is significant (p = 0.03). Sensitivity analysis supported that the MR estimates were robust. Conclusion: In our MR study, genetically increased serum 25(OH)D levels were associated with a reduced risk of LBP in the European population. This might have an implication for clinicians that vitamin D supplements might be effective for patients with LBP in clinical practice.

Interleukin-17 as a potential therapeutic target for chronic pain.

Chronic pain remains to be a clinical challenge and is recognized as a major health problem with varying impacts on quality of life. Currently, the first-line therapy for chronic pain is opioids, which are often accompanied by unwanted psychoactive side effects. Thus, new and effective treatments for chronic pain are urgently needed and eagerly pursued. Inflammatory cytokines, especially interleukin-17 (IL-17), are reportedly potential therapeutic targets owing to their pivotal role in chronic pain from the neuroinflammation perspective. Recently, substantial evidence confirmed that IL-17 and IL-17 receptors (IL-17Rs) were increased in neuropathic, inflammatory, and cancer pain models. Notably, IL-17/IL-17R antibodies also reportedly relieve or cure inflammatory- and pain-related diseases. However, existing studies have reported controversial results regarding IL-17/IL-17Rs as potential therapeutic targets in diverse animal models of chronic pain. In this review, we present a summary of published studies and discuss the evidence, from basic to clinical to research, regarding the role and mechanism of action between IL-17 and diverse kinds of chronic pain in animal models and clinical patients. Furthermore, we evaluated IL-17-based therapy as a potential therapeutic strategy for inflammatory- and pain-related disease. Importantly, we also discussed clinical trials of IL-17/IL-17R targeting monoclonal antibodies. Overall, we found that IL-17 is a potential therapeutic target for chronic pain from the perspective of neuroinflammation.

Myocarditis complicated by massive right ventricular thrombus and extensive pulmonary embolism: A case report.

An intracardiac thrombus may develop as a consequence of myocarditis, and in rare cases, a dominantly right ventricular thrombus develops, which may impair cardiac function and even cause life-threatening cardiovascular events. We report a 24-year-old man presented with recurrent episodes of palpitation and precordial discomfort after catching a cold 2 months ago. Transthoracic echocardiography (TTE) and computed tomography pulmonary angiogram (CTPA) revealed a mass attached to the apex of the right ventricle and extensive bilateral pulmonary artery emboli. There was no indication where the thrombi originated from in this young patient without any underlying disease except myocarditis. Pulmonary endarterectomy and embolectomy of pulmonary arteries and right ventricle were performed. Postoperative pathological results confirmed the presence of fibrinous necrosis and hemosiderin deposition. The formation of an intraventricular thrombus is closely related to myocarditis, which can affect individuals of all ages, but especially young people. Thus, patients with myocarditis should be closely monitored and followed up because of the increased risk of extensive thrombosis.

The Function of Nilaparvata lugens (Hemiptera: Delphacidae) E74 and Its Interaction With ßFtz-F1.

Drosophila E74 is an early gene located in the polytene chromosome 74EF puff position. E74 controls the production of late genes, indicating that it plays a crucial role in this cascade model. Nilaparvata lugens E74 is closely related to Diaphorina citri, Bemisia tabaci, and Laodelphax striatellus. After downregulating E74, molting, and nymphal mortality were increased, and ovarian development was delayed. Moreover, the expression of Vg was reduced at the transcriptional level, as measured by qRT-PCR, and the content of Vg protein was reduced, as detected by Western blotting. After downregulating E74, the expression of hormone-related genes, including Tai, ßFtz-F1, Met, Kr-h1, UspA, UspB, E93, and Br, was changed. The expression of E74 was significantly decreased after downregulating hormone-related genes. When the expression of E74 and ßFtz-F1 was downregulated together, nymph mortality and molting mortality were higher than those when E74 or ßFtz-F1 was downregulated alone. Thus, E74 probably interacts with ßFtz-F1 at the genetic level. In summary, this study showed that E74 plays a crucial role in the development, metamorphosis and reproduction of N. lugens, possibly via the interaction with ßFtz-F1 at the genetic level. This study provides a basis for the development of new target-based pesticides and new methods for the effective control of N. lugens.

Integrated approach toward absorption, distribution, metabolism, and excretion of Xiaoke pills in zebrafish based on UPLC-HRMS and DESI-MS techniques.

Traditional Chinese medicine (TCM) has been used in clinical settings for over 2000 years in China. The study of the absorption, distribution, metabolism, and excretion (ADME) of TCM in vivo could be beneficial for the discovery of the active components in TCM. However, the conventional strategies used for ADME research are based on rodent models and have the characteristics of lengthy experimental periods, complex processes, and extensive data processing, which make it difficult to perform rapid analyses and high-throughput ADME screening of the medicinal components of TCM. In this study, an integrated high-throughput research strategy for the in vivo ADME analysis of TCM was established based on a zebrafish model. Accordingly, a combination of ultra-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS), desorption electrospray ionization-mass spectrometry (DESI-MS) imaging, and in-house non-targeted precise-and-thorough background-subtraction (PATBS) data post-processing techniques were successfully applied for the analysis of the metabolism of zebrafish exposed to Xiaoke pills. A total of 49 compounds related to Xiaoke pills (including 13 prototypical components and 36 metabolites) were detected in zebrafish. In total, 32 of them, including puerarin, daidzein, deoxyschizandrin, formononetin, and glibenclamide, which have been identified to have hypoglycemic activity in our previous studies and are phase I and phase II metabolites resulting from the hydroxylation, demethylation, glucuronidation, sulfation, and glycosylation of the prototypical components in vivo, were found in rats treated with Xiaoke pills. Furthermore, the overall distribution of the known compounds in zebrafish exposed to Xiaoke pills was explored using DESI-MS. In summary, this study provides a practical approach for the high-throughput screening of the active components of TCM using a zebrafish model.

Exploration of Q-Marker of Rhubarb Based on Intelligent Data Processing Techniques and the AUC Pooled Method.

Rhubarb, as a traditional Chinese medicine, has several positive therapeutic effects, such as purging and attacking accumulation, clearing heat and purging fire, cooling blood, and detoxification. Recently, Rhubarb has been used in prescriptions for the prevention and treatment of COVID-19, with good efficacy. However, the exploration of effective quantitative approach to ensure the consistency of rhubarb's therapeutic efficacy remains a challenge. In this case, this study aims to use non-targeted and targeted data mining technologies for its exploration and has comprehensively identified 72 rhubarb-related components in human plasma for the first time. In details, the area under the time-concentration curve (AUC)-pooled method was used to quickly screen the components with high exposure, and the main components were analyzed using Pearson correlation and other statistical analyses. Interestingly, the prototype component (rhein) with high exposure could be selected out as a Q-marker, which could also reflect the metabolic status changes of rhubarb anthraquinone in human. Furthermore, after comparing the metabolism of different species, mice were selected as model animals to verify the pharmacodynamics of rhein. The in vivo experimental results showed that rhein has a positive therapeutic effect on pneumonia, significantly reducing the concentration of pro-inflammatory factors [interleukin (IL)-6 and IL-1ß] and improving lung disease. In short, based on the perspective of human exposure, this study comprehensively used intelligent data post-processing technologies and the AUC-pooled method to establish that rhein can be chosen as a Q-marker for rhubarb, whose content needs to be monitored individually.