Patients receiving maintenance hemodialysis (MHD) experience a high mortality burden, with cardiovascular disease remaining a major cause of death. This study aimed to evaluate the association between adjunctive hemoperfusion combined with conventional hemodialysis (HD + HP) and long-term survival outcomes in patients receiving MHD. This single-center retrospective cohort study was conducted at Shanghai Changhai Hospital. Patients with end-stage renal disease who received MHD between January 2015 and December 2023 were retrospectively identified from the center’s hemodialysis records. Among the 640 eligible patients, 419 (65.5

The first chemical and biological investigation on Anoectochilus xingrenensis, a closely related species of A. roxburghii, revealed that the crude polysaccharide of A. xingrenensis (AXP) displayed significant anti-rheumatoid arthritis (RA) effects against collagen-induced arthritis (CIA) in rats. X21, a new polysaccharide with a molecular weight of 2.71 × 104 Da, was purified as a major fraction from AXP and characterized as a heteroglycan backbone consisting of →4)-β-D-Galp-(1→, →4)-α-D-Glcp-(1→, and →4,6)-α-D-Glcp-(1→, and with a terminal residue of α-D-Manp-(1→. Pharmacological study demonstrated that X21 significantly reduced the arthritis score, increased the body weight, alleviated articular bone destruction, and decreased the levels of pro-inflammatory factors in the serum of CIA rats. Moreover, 16S rRNA sequencing indicated that X21 could restore the gut microbiota of RA rats by decreasing the relative abundance of Lactobacillus and increasing that of Roseburia, leading to increased levels of short chain fatty acids. In addition, X21 significantly suppressed macrophage M1 polarization and promoted M2 polarization both in vitro and in vivo, potentially by down-regulating the expressions of p-p65, p-IκB, p-JNK and p-p38 in NF-κB and MAPK pathways and up-regulating that of p-STAT6 in JAK/STAT pathway, respectively. Our study suggests that X21 from A. xingrenensis could be regarded as a promising drug candidate and prebiotic for RA treatment.

Sepsis-induced myocardial injury (SIMI) commonly occurs as a complication of severe sepsis and septic shock. This research aims to explore the function of miR-222-3p inhibition in SIMI and its possible regulatory mechanisms. A rat SIMI model was established using the cecal ligation and puncture method. In vitro experiments were conducted using lipopolysaccharide (LPS) to induce myocardial injury in H9C2 cells. miR-222-3p and MEGF9 expression were determined using qRT-PCR. Myocardial injury, inflammatory response, and oxidative stress indicators were detected using the ELISA and biochemical colorimetric assays. Cell viability and apoptosis were assessed using the CCK-8 method and flow cytometry. The interaction between miR-222-3p and MEGF9 was verified through a luciferase reporter gene assay. In the serum of rats with sepsis and LPS-induced H9C2 cells, miR-222-3p exhibited high expression, while MEGF9 was lowly expressed. Inhibition of miR-222-3p alleviated myocardial injury, inflammatory response, and oxidative stress in sepsis rats and LPS-induced cells, as evidenced by reduced CK-MB, cTnI, LDH, IL-6, IL-1β, TNF-α, and MDA level, and enhanced SOD activity. Inhibition of miR-222-3p increased LPS-induced cell viability and diminished apoptosis. miR-222-3p targeted MEGF9. Inhibiting MEGF9 expression could reverse the protective role of miR-222-3p suppression on LPS-induced myocardial injury. This study’s results indicate that miR-222-3p exacerbates SIMI reactions by targeting and inhibiting MEGF9 expression. It is possible that miR-222-3p functions as a potential therapeutic target for SIMI.

Objective Maintenance hemodialysis (MHD) patients face a high risk of mortality. This study aimed to identify factors associated with mortality and assess the survival benefit of hemodialysis combined with hemoperfusion (HD + HP) using HA130/KHA80 cartridges in MHD patients. Methods A single-center retrospective cohort study was conducted at Shanghai Changhai Hospital, enrolling 640 MHD patients treated from January 2015 to December 2023. Clinical data were extracted from electronic medical records and hemodialysis management systems. Patients were stratified into HD alone (n = 419) and HD + HP (n = 221) groups. Univariate and multivariate logistic regression were used to identify factors associated with all-cause mortality. Time-dependent Cox regression (with HP as a time-varying covariate) was applied to evaluate the association between HP exposure and mortality. Propensity score matching (1:1, caliper width = 0.02) was performed based on sex, age, primary renal disease, vascular access, and comorbidities, yielding 173 balanced patients per group. Simon–Makuch curves and Mantel–Byar tests were used for survival analysis. Results Diabetic kidney disease (DKD) was the most common primary renal disease (30.9%). The overall all-cause mortality rate was 54.4%, and cardiovascular disease was the leading cause of death (32.8%). Exploratory logistic regression identified older age, higher red blood cell distribution width (RDW), DKD, and elevated creatine kinase-MB (CK-MB) as factors associated with increased all-cause mortality, while higher chloride (Cl), total protein (TP), prealbumin (PAB), hemoglobin (HB), and HD + HP therapy were associated with lower mortality (all P < 0.05). As the primary analytical approach for time-to-event outcomes, time-dependent Cox regression showed that HP exposure was associated with a 25% reduction in all-cause mortality after adjustment for confounders (HR = 0.75; 95% CI: 0.58–0.98; P = 0.03). After propensity score matching, HD + HP significantly reduced both all-cause mortality (31.2% vs 64.2%) and cardiovascular mortality compared with HD alone (Mantel–Byar test: P = 0.032 and P = 0.003, respectively). Conclusion Cardiovascular disease is the leading cause of death in MHD patients. HD + HP therapy is associated with a reduced risk of all-cause and cardiovascular mortality in MHD patients, supporting its potential as a strategy to improve survival in this high-risk population.

Introduction Haemodialysis (HD) is an essential treatment for end-stage renal disease patients to improve their quality of life. However, conventional HD may not effectively remove medium and large molecules and protein-bound toxins, leading to the occurrence of various complications. Haemoadsorption (HA), on the other hand, can address this limitation. Therefore, a multicentre, open-label, randomised, parallel controlled study will be conducted to compare HA combined with HD (HAHD) with HD alone in maintenance haemodialysis (MHD) patients. The primary endpoint is the change in serum β2-MG, PTH and CRP values.Methods and analysis We plan to enrol 410 MHD patients from 10 participating medical centres in Shanghai. Patients will experience a 4-week washout period and a 52-week observation period. After the washout period, the eligible patients will be randomised in a 1:1 ratio to the two groups: the control group, 3 times/week conventional HD treatment; and the experiment group, 3 times/week conventional HD treatment+1 time/week HA treatment. The baseline and follow-up data at 0, 4, 12, 24, 36 and 52 weeks were collected from both groups, including the following: medical history, routine physical examination, dialysis regimen, laboratory tests, dialysis adequacy as defined by standard Kt/V, chest X-ray, ECG, cardiac ultrasound and three scales. Comorbidities, combined medications and adverse events will also be captured. The primary outcomes will include change in serum β2-MG, PTH and CRP values. Secondary outcomes will include change values for serum protein-bound toxins, improvement in patient quality of life, sleep disturbance and pruritus.Ethics and dissemination The protocol has been approved by the Ethics Committees of 10 participating medical centres. Shanghai Changhai Hospital Ethics Committee will oversee the study. The results will be presented at national and international academic meetings, and publications will be submitted to peer-reviewed journals.Trial registration number NCT05639010.

Aims/Background Hypertension (HT) is a prevalent medical condition showing an increasing incidence rate in various populations over recent years. Long-term hypertension increases the risk of the occurrence of hypertensive nephropathy (HTN), which is also a health-threatening disorder. Given that very little is known about the pathogenesis of HTN, this study was designed to identify disease biomarkers, which enable early diagnosis of the disease, through the utilization of high-throughput untargeted metabolomics strategies. Methods The participants of this study were patients admitted to The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, who were randomly divided into three groups: Normal group (n = 11), HT group (n = 10), and HTN group (n = 12). Urine exosomes were extracted, purified, and subjected to untargeted metabolomics analysis. Differential metabolites and their significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified. The least absolute shrinkage and selection operator (LASSO) regression analysis was then employed to establish a diagnostic model for early-stage HTN. Finally, logistic regression and receiver operating characteristic (ROC) curve analysis were performed to identify biomarkers related to early HTN. Results Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed significant differences in the metabolic profiles of the three patient groups. Compared to subjects of the Normal group, the HT and HTN groups exhibited significantly upregulated and downregulated profiles of differential metabolites, respectively. LASSO regression analysis results indicated that 4-hydroxyphenylacetic acid, bilirubin, uracil, and iminodiacetic acid are potential biomarkers for HTN or HT. Conclusion With untargeted metabolomics analysis, we successfully identified differential metabolites in HTN. A further LASSO regression analysis revealed that four key metabolites, namely 4-hydroxyphenylacetic acid, bilirubin, uracil, and iminodiacetic acid, hold promise for the diagnosis of early-stage HTN.

INTRODUCTION:The study aimed to evaluate the stability and compatibility of diverse antibiotics in 7.5% icodextrin peritoneal dialysis (PD) solution, subjected to various temperatures over a span of 14-day period. METHODS:Antibiotics, namely, amikacin, imipenem, ciprofloxacin, vancomycin, and cefazolin, were incorporated into 7.5% icodextrin solution and subsequently stored at various temperature and period. The concentrations of these antibiotics were measured using high-performance liquid chromatography. Stability of antibiotics is defined as the remaining drug concentration >90% of the initial one throughout the test period. RESULTS:Ciprofloxacin and amikacin were demonstrated stable for a period of 14 days in icodextrin solution across all tested temperatures. Amikacin retained over 90% of its initial concentration when combined with either vancomycin, cefazolin, or ciprofloxacin at various temperatures for 14 days. In combination with amikacin, ciprofloxacin maintained stability for 14 days at all tested temperatures, while vancomycin maintained stability for 14 days at both 4°C and 25°C, and 7 days at 37°C. Cefazolin, however, only exhibited stability for 8 h at 37°C and 7 days at both 4°C and 25°C. The stability of imipenem in icodextrin solution was notably low, remaining stable for a maximum 6 h at 4°C. CONCLUSION:Ciprofloxacin, amikacin, as well as combinations of amikacin and vancomycin, amikacin and cefazolin, amikacin and ciprofloxacin, can be added to icodextrin solution for treatment of PD-associated peritonitis because they maintain stability for a minimum of 7 days at the temperatures of 4°C and 25°C, and 8 h at 37°C.

The aim of the current study was to investigate the relationship between environmental factors and metabolic gene genotypes related to semen quality. A total of 341 men were recruited and classified into normal or abnormal semen quality groups according to the World Health Organization’s 2010 criteria. Alcohol and tobacco use among men was self-reported. Pb (lead), As (arsenic), Ti (titanium), and Zn (zinc) metal elements in seminal plasma were measured using inductively coupled plasma mass spectrometry (ICP-MS). The ALDH2 rs671 and GSTP1 rs1695 polymorphism were detected using high-resolution melting (HRM) PCR. Individual environmental factors, including smoking, drinking, and exposure to Pb, As, Ti, or Zn, did not significantly associate with the risk of semen abnormalities. The ALDH2 GA/AA mutation genotype increased the risk of semen abnormalities in smoking males (AOR = 1.27; 95

BACKGROUND:Chronic inflammation is well recognized as a key factor related to renal function deterioration in patients with diabetic kidney disease (DKD). Neutrophil extracellular traps (NETs) play an important role in amplifying inflammation. With respect to NET-related genes, the aim of this study was to explore the mechanism of DKD progression and therefore identify potential intervention targets. METHODS:Hub NET-related DEGs were screened via differential expression analysis and three machine learning methods, namely, LASSO, SVM-RFE and random forest. Consensus clustering was performed to analyze NET-related subtypes in DKD patients. KEGG enrichment analysis, GSEA, GSVA, ssGSEA and ESTIMATE were conducted to explore the molecular features of DKD patient subtypes. Leveraging single-nucleus RNA-seq datasets, the "scissor" and "bisqueRNA" algorithms were applied to identify the composition of renal cell types in DKD patient subtypes. Soft clustering analysis was performed to obtain gene groups with similar expression patterns during the development and progression of DKD. The correlations between hub NET-related DEGs and clinical parameters were mined from the Nephroseq V5 database. The core gene among the hub NET-related DEGs was selected by calculating semantic similarity. "Cellchat" algorithm, immunostaining, ELISA and flow cytometry were performed to explore the expression and function of the core gene. The Drug-Gene Interaction Database (DGIdb) was searched to identify candidate drugs. RESULTS:Six hub NET-related DEGs, namely, ACTN1, ITGB2, IL33, HRG, NFIL3 and CLEC4E, were identified. On the basis of these 6 genes, DKD patients were classified into 2 clusters. Cluster 1 patients, with higher NET scores, were evidently more immune-activating than those of cluster 2. Markedly increased numbers of immune cells, fibroblasts and proinflammatory proximal tubular cells were observed in cluster 1 but not in cluster 2. Cluster 1 also represented a more clinically advanced disease state. Among the 6 hub NET-related DEGs, the mRNA expression of ACTN1, ITGB2, IL33 and HRG was correlated with the eGFR. By semantic similarity analysis, IL33 was considered a central gene among the 6 genes. Cell-cell communication analysis further indicated that intercellular interactions via IL-33 were enhanced in DKD. Serum IL-33 concentration was negatively correlated with eGFR. IHC staining revealed that IL-33 expression was upregulated in the tubular epithelium in DKD patients. Supernatants from inflammatory tubular epithelial cells can increase MPO in neutrophils, whereas addition of anti-IL-33 antibody attenuated this phenotype. CONCLUSIONS:We identified 2 distinct NET-related subtypes in DKD patients, in which one subgroup was apparently more inflammatory and associated with a more severe clinical state. A significantly increased level of IL-33 in this inflammatory patient subgroup may play a role in aggravating inflammation via the IL-33-ST2 axis.

Renal injury, a prevalent clinical outcome with multifactorial etiology, imposes a substantial burden on society. Currently, there remains a lack of effective management and treatments. Extensive research has emphasized the diverse biological effects of natural polysaccharides, which exhibit promising potential for mitigating renal damage. This review commences with the pathogenesis of four common renal diseases and the shared mechanisms underlying renal injury. The renoprotective roles of polysaccharides in vivo and in vitro are summarized in the following five aspects: anti-oxidative stress effects, anti-apoptotic effects, anti-inflammatory effects, anti-fibrotic effects, and gut modulatory effects. Furthermore, we explore the structure-activity relationship and bioavailability of polysaccharides in relation to renal injury, as well as investigate their utility as biomaterials for alleviating renal injury. The clinical experiments of polysaccharides applied to patients with chronic kidney disease are also reviewed. Broadly, this review provides a comprehensive perspective on the research direction of natural polysaccharides in the context of renal injury, with the primary aim to serve as a reference for the clinical development of polysaccharides as pharmaceuticals and prebiotics for the treatment of kidney diseases.

Object: The association between magnesium depletion score (MDS) and kidney stone disease (KSD) remains unknown. This study was designed to investigate the association of MDS with KSD in adults. Methods: A total of 19,654 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES). The MDS was calculated by assessing four aspects, including alcohol assumption, renal function, and use of diuretics and proton pump inhibitor. Multivariable logistic regressions were performed to explore the associations between MDS and the prevalence of KSD. Linear correlations were conducted explore the relationship of testosterone with MDS. Results: In the multivariable logistic regressions with full adjustment for confounding variables, the odds ratio of MDS associating with KSD was 1.28 (95% CI: 1.04-1.58, P = 0.022) in total population, and 1.70 (95% CI: 1.16-2.50, P=0.007) in female participants. Besides, compared to the lowest MDS, the highest MDS was associated with a lower testosterone (beta = -16.39, P=0.009) after full adjustment in non-menopause women. Conclusion: This study highlighted a positive correlation of high MDS with KSD in female population, which may be associated low level of serum testosterone.

Lung cancer is the second most common malignant tumor worldwide. The problem of drug resistance in lung cancer leads to treatment failure and recurrence in more than 90% of cancer patients. Thus, developing chemical probes that can observe drug-resistant lung cancer cells in real-time and eliminate them is of great interest. However, such tools that can simultaneously probe drug-resistant lung cancer cells and therapeutic modes of action have not yet been developed. In this work, we reported a fluorescent prodrug that can be activated in cancer cell lysosomes to release amonafide (ANF) and aniline mustard, where the fluorescent signal of ANF (lambda ex/ lambda em = 405/570-620 nm) can be tracked by super-resolution imaging in live cancer cells. With imaging studies, we found that this new fluorescent prodrug uniquely displays an autophagy-driven ferroptosis-inducing effect, accompanied by the accumulation of intracellular ferrous ions and lipid peroxidation. More importantly, the fluorescent prodrug exhibits potential anti-proliferative activity, especially against drug-resistant A549R lung cancer cells (IC50, -3 mu M), better than the positive control drug cisplatin (IC50, -27 mu M). This work indicates that the development of fluorescent prodrugs as autophagy-driven ferroptosis inducers may represent a viable approach for targeting drug-resistant cancer cells.

Previous researches indicate that tryptophan metabolism is critical to allergic inflammation and that indoleamine 2,3-dioxygenase 1 (IDO1), as a key enzyme, is known for its immunosuppressive properties. Therefore, we are aimed to explore whether tryptophan metabolism, especially IDO1, influences allergic asthma and clarify specific mechanism. With the analysis of clinical data, exploration in cell experiments, and verifying in HDM-induced asthma mice models, we finally found that in allergic asthma, low level of T1 cytokines along with high level of T2 cytokines inhibited the expression of IDO1 in airway epithelium, hampering the kynurenine pathway in tryptophan metabolism and decreasing the level of intracellular kynurenine (Kyn). As an endogenous ligand of aryl hydrocarbon receptor, Kyn regulated the expression of cystathionine-g-lyase g- lyase (CTH). Notably, in asthma models, enhancing either IDO1 or H2S 2 S relieved asthma, while inhibiting the activity of CTH exacerbated it. IDO1-Kyn-CTH pathway could be a potential target for treatment for allergic asthma.

Rationale:The present understanding of the cellular characteristics and communications in crystal nephropathy is limited.Here, molecular and cellular studies combined with single-cell RNA sequencing (scRNA-seq) were performed to investigate the changes in cell components and their interactions in glyoxylate-induced crystallized kidneys to provide promising treatments for crystal nephropathy.Methods: The transcriptomes of single cells from mouse kidneys treated with glyoxylate for 0, 1, 4, or 7 days were analyzed via 10× Genomics, and the single cells were clustered and characterized by the Seurat pipeline.The potential cellular interactions between specific cell types were explored by CellChat.Molecular and cellular findings related to macrophage-to-epithelium crosstalk were validated in sodium oxalate (NaOx)-induced renal tubular epithelial cell injury in vitro and in glyoxylate-induced crystal nephropathy in vivo.Results: Our established scRNA atlas of glyoxylate-induced crystalline nephropathy contained 15 cell populations with more than 40000 single cells, including relatively stable tubular cells of different segments, proliferating and injured proximal tubular cells, T cells, B cells, and myeloid and mesenchymal cells.In this study, we found that Mrc1 + macrophages, as a subtype of myeloid cells, increased in both the number and percentage within the myeloid population as crystal-induced injury progresses, and distinctly express IGF1, which induces the activation of a signal pathway to dominate a significant information flow towards injured and proliferating tubule cells.IGF1 promoted the repair of damaged tubular epithelial cells induced by NaOx in vitro, as well as the repair of damaged tubular epithelial cells and the recovery of disease outcomes in glyoxylate-induced nephrolithic mice in vivo. Conclusion:After constructing a cellular atlas of glyoxylate-induced crystal nephropathy, we found that IGF1 derived from Mrc1 + macrophages attenuated crystal nephropathy through promoting renal tubule cell proliferation via the AKT/Rb signaling pathway.These findings could lead to the identification of potential therapeutic targets for the treatment of crystal nephropathy.

Myocardial ischemia-reperfusion injury (MIRI) significantly worsens the outcomes of patients with cardiovascular diseases. Dexmedetomidine (Dex) is recognized for its cardioprotective properties, but the related mechanisms, especially regarding metabolic reprogramming, have not been fully clarified. A total of 60 patients with heart valve disease are randomly assigned to Dex or control group. Blood samples are collected to analyze cardiac injury biomarkers and metabolomics. In vivo and vitro rat models of MIRI are utilized to assess the effects of Dex on cardiac function, lactate production, and mitochondrial function. It is found that postoperative CK-MB and cTNT levels are significantly lower in the Dex group. Metabolomics reveals that Dex regulates metabolic reprogramming and reduces lactate level. In Dex-treated rats, the myocardial infarction area is reduced, and myocardial contractility is improved. Dex inhibits glycolysis, reduces lactate, and improves mitochondrial function following MIRI. Lactylation proteomics identifies that Dex reduces the lactylation of Malate Dehydrogenase 2（MDH2), thus alleviating myocardial injury. Further studies reveal that MDH2 lactylation induces ferroptosis, leading to MIRI by impairing mitochondrial function. Mechanistic analyses reveal that Dex upregulates Nuclear Receptor Subfamily 3 Group C Member 1（NR3C1) phosphorylation, downregulates Pyruvate Dehydrogenase Kinase 4 (PDK4), and reduces lactate production and MDH2 lactylation. These findings provide new therapeutic targets and mechanisms for the treatment for MIRI.

Background Finding a simple, effective and rapid diagnostic method to improve the diagnosis of gastroesophageal reflux-induced chronic cough (GERC) is indicated. Our objective was to determine the diagnostic value of the pepsin concentration in saliva and induced sputum for GERC. Methods 171 patients with chronic cough were enrolled. The diagnosis and treatment followed the chronic cough diagnosis and treatment protocol. Saliva and induced sputum were collected, and the pepsin concentration was determined using Peptest. A Gastroesophageal Reflux Diagnostic Questionnaire (GerdQ) was completed. The diagnostic value of the pepsin concentration in saliva and induced sputum for GERC was analysed and compared. Results The salivary pepsin concentration predicted GERC with an area under the receiver operating characteristic curve (AUC) of 0.845. The optimal cut-off value was 76.10 ng·mL −1 , the sensitivity was 83.58% and the specificity was 82.69%. The pepsin concentration in the induced sputum supernatant for GERC had an AUC of 0.523. When GerdQ was used for GERC diagnosis, the AUC was 0.670 and the diagnostic value of salivary pepsin was better compared to GerdQ (DeLong test, p=0.0008). Salivary pepsin had a comparable diagnostic value to GerdQ (AUC 0.779 versus 0.826; p=0.4199) in acidic GERC. Salivary pepsin had superior diagnostic value compared to GerdQ (AUC 0.830 versus 0.533; p<0.0001) in non-acidic GERC. Conclusions A salivary pepsin concentration >76.10 ng·mL −1 is of good diagnostic value for GERC, especially in non-acidic GERC. The pepsin concentration in induced sputum has a low diagnostic value.

Cistanche tubulosa (CT), a well-known TCM, has always been processed with rice wine for the treatment of kidney-yang deficiency syndrome (KYDS) since time immemorial. In order to explore the effect of processing on the efficacy and metabolites of CT in vivo, a comprehensive method using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was established for the analysis of the altered endogenous metabolites in response to the intervention of the raw and processed CT in KYDS model, and the metabolites of the absorbed compounds in rats after gastric perfusion. It was showed that CT could improve KYDS, and the effect of processed product was more significant. A total of 47 differential metabolites were identified in urine. Pathway analysis proved that purine metabolism, alanine, aspartate and glutamate metabolism, and citrate cycle were the main pathways. Furthermore, 53 prototypes and 48 metabolites have been detected in rats. This was the first systematic research focus on the metabolites of raw and processed CT in vivo, which could provide a scientific basis for explaining the increasing efficiency of the processed CT. Moreover, it provides a valuable strategy for analyzing the chemical components and metabolites of other traditional Chinese medicine prescriptions.

Cryptotanshinone (CPT), a major biological active ingredient extracted from root of Salvia miltiorrhiza (Danshen), has shown several pharmacological activities. However, the effect of CPT on radiation-induced lung fibrosis (RILF) is unknown. In this study, we explored the protective effects of CPT on RILF from gut-lung axis angle, specifically focusing on the bile acid (BA)-gut microbiota axis. We found that CPT could inhibit the process of epithelial mesenchymal transformation (EMT) and suppress inflammation to reduce the deposition of extracellular matrix in lung fibrosis in mice induced by radiation. In addition, 16S rDNA gene sequencing and BAs-targeted metabolomics analysis demonstrated that CPT could improve the dysbiosis of gut microbiota and BA metabolites in RILF mice. CPT significantly enriched the proportion of the beneficial genera Enterorhabdus and Akkermansia, and depleted that of Erysipelatoclostridium, which were correlated with increased intestinal levels of several farnesoid X receptor (FXR) natural agonists, such as deoxycholic acid and lithocholic acid, activating the FXR pathway. Taken together, these results suggested that CPT can regulate radiation-induced disruption of gut microbiota and BAs metabolism of mice, and reduce the radiation-induced lung inflammation and fibrosis. Thus, CPT may be a promising drug candidate for treating RILF.

Danggui Buxue Decoction (DBD), consisting of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (Huangqi, HQ) and Angelica sinensis (Oliv.) Diels (Danggui, DG), is a traditional Chinese medicine (TCM) formula with the function of tonifying Qi and promoting blood. In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to comprehensively identify the chemical constituents in DBD and those entering into the rat serum after gastric perfusion. A combination of the UNIFI platform and Global Natural Product Social molecular networking (GNPS) was used to analyze the chemical composition of DBD. As a result, 207 compounds were unambiguously or tentatively identified including 60 flavonoids, 38 saponins, 35 organic acids, 26 phthalides, 12 phenylpropanoids, 11 amino acids and 25 others. Furthermore, a total of 80 compounds, including 29 prototype components and 51 exogenous metabolites, were detected in the serum of rats. Phase I reactions (oxidation, reduction, and hydration), phase II reactions (methylation, sulfation, and glucuronidation), and their combinations were the main metabolic pathways of DBD. The results provided fundamental information for further studying the pharmacological mechanisms of DBD, as well as its quality control research.

Ophiopogonis Radix, also known as "Maidong" (MD) in China, is frequently sulfur-fumigated (SF) in the pretreatment process of MD to improve the appearance and facilitate preservation. However, the process leads to changes in chemical composition, so it is essential to develop an approach to identify the chemical characteristics between nonfumigated and sulfur-fumigated products. This paper provided a practical method based on UPLC-QTOF-MS combined Global Natural Products Social Molecular Networking (GNPS) with multivariate statistical analysis for the characterization and discrimination of MD with different levels of sulfur fumigation, high concentration sulfur fumigation (HS), low concentration sulfur fumigation (LS) and without sulfur fumigation (WS). First, a number of 98 compounds were identified in those MD samples. Additionally, the results of Principal component analysis (PCA) and Orthogonal partial least-squares-discriminant analysis (OPLS-DA) demonstrated that there were significant chemical differences in the chemical composition of MD with different degrees of SF. Finally, fourteen and sixteen chemical markers were identified upon the comparison between HS and WS, LS and WS, respectively. Overall, these results can be able to discriminate MD with different levels of SF as well as establish a solid foundation for further quality control and pharmacological research.