A Comparative Analysis of ADRs under Obeticholic Acid and Ursodeoxycholic Acid in Cholestatic Liver Diseases Using the FAERS Database.

BACKGROUND: The objective of this study was to compare the safety profiles of OCA and UDCA for the treatment of PBC using the FDA Adverse Event Reporting System database. METHODS: We extracted reports for OCA from 2016 to 2023 and UDCA from 2004 to 2023. Demographic details, adverse events (AEs), and concomitant medications were analyzed using descriptive statistics and signal detection methods. RESULTS: The most common for OCA were pruritus (1345 cases, ROR 20.96) and fatigue (528 cases, ROR 3.46). UDCA was more frequently associated with hepatocellular carcinoma (22 cases, ROR 16.37) and type I hypersensitivity reactions (11 cases, ROR 12.77). OCA was also linked to a higher frequency of constipation (161 cases, ROR 3.92) and increased blood alkaline phosphatase levels (145 cases, ROR 44.27). CONCLUSION: This study reveals distinct safety profiles for OCA and UDCA in the treatment of PBC. OCA is associated with a higher frequency of pruritus, fatigue, constipation, and increased blood alkaline phosphatase levels, while UDCA is linked to hepatocellular carcinoma and type I hypersensitivity reactions. These findings support personalized treatment approaches based on individual patient characteristics.

Network pharmacological mechanism analysis and evidence-based medical validation of Dahuang Mudan Decoction in the treatment of acute pancreatitis.

BACKGROUND: Dahuang Mudan Decoction is commonly used in China for the treatment of acute pancreatitis. Nevertheless, the therapeutic efficacy of the drug remains a subject of debate, and its active ingredients and potential therapeutic targets remain to be determined. The present study used a network pharmacological approach to investigate the active ingredients and possible targets of the drug, and illustrated the clinical effectiveness of Dahuang Mudan Decoction in the treatment of acute pancreatitis by meta-analysis. METHODS: The present study investigated the active ingredients of the constituent herbs of Dahuang Mudan Decoction using the TCMID database. In order to further identify molecular targets, Swiss Target Prediction, OMIM and Genecards databases was be used. The present study used metascape database for gene ontology function enrichment analysis and Kyoto Genome Encyclopedia pathway enrichment analysis. A gene interaction network diagram was established for predicting the main targets and mechanism of action to Dahuang Mudan Decoction for acute pancreatitis. To further illustrate the validity of the gene targets and the clinical efficacy of the drug, 13 relevant studies were included for meta-analysis and analyzed using the Cochrane Collaboration's Review Manager 5.4 software. RESULT: After a thorough screening process, the present study identified three main components of Dahuang Mudan Decoction: kaempferol, quercetin and eupatin. These three major components have the potential to target 5 important proteins: AKT1, TNF-a, IL-6, TP53, HIF1A. In addition, pathway analyses by the Kyoto Genome Encyclopedia showed that Dahuang Mudan Decoction is active through the Pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, etc signaling pathway to act on acute pancreatitis. The results of meta-analysis showed that compared with the control group, the experimental group had superior performance in terms of overall treatment efficacy, reduction of hospital stays and inflammatory factor levels after treatment. CONCLUSION: In summary, network pharmacological studies have shown that Dahuang Mudan Decoction affects acute pancreatitis through different components, targets, and mechanisms. In addition, the meta-analysis study strongly supported the effectiveness of Dahuang Mudan Decoction in the treatment of acute pancreatitis.

Metabolic discrimination of rhizoma coptidis from different species using 1H NMR spectroscopy and principal component analysis.

Rhizoma coptidis, a broadly used medicinal plant, originates from the dried rhizomes of three species in Chinese pharmacopoeia, namely, Coptis chinensis Franch, Coptis deltoidea C. Y. Cheng et Hsiao, and Coptis teeta Wall. In this study, a novel approach using (1)H NMR spectroscopy combined with multivariate analysis was introduced to differentiate the three species and identify potential metabolic markers for better controlling the quality of rhizoma coptidis. A broad range of metabolites including alkaloids, sugars, organic acids, amino acids, and fatty acids present in rhizoma coptidis were detected by means of (1)H NMR spectroscopy. Principal component analysis (PCA) of the (1)H NMR data set showed a clear separation between all samples by PC1 and PC3, and some metabolites that could be responsible for the discrimination of the three species were identified. An analysis of variance (ANOVA) was performed to statistically verify the significance of differences in metabolite levels between species. By combining PCA and ANOVA, significantly higher contents of palmatine, coptisine, epiberberine, columbamine, and fatty acids together with lower contents of jateorrhizine were found in Coptis chinensis, whereas Coptis deltoidea and Coptis teetA showed the highest levels of sucrose and chlorogenic acid, respectively. This study indicates that metabolites of rhizoma coptidis vary with the species and the proposed method is suitable for metabolic fingerprinting analysis to check the genuine origin of rhizoma coptidis.

Development of Nomograms for Predicting Lymph Node Metastasis and Distant Metastasis in Newly Diagnosed T1-2 Non-Small Cell Lung Cancer: A Population-Based Analysis.

BACKGROUND: For different lymph node metastasis (LNM) and distant metastasis (DM), the diagnosis, treatment and prognosis of T1-2 non-small cell lung cancer (NSCLC) are different. It is essential to figure out the risk factors and establish prediction models related to LNM and DM. METHODS: Based on the surveillance, epidemiology, and end results (SEER) database from 1973 to 2015, a total of 43,156 eligible T1-2 NSCLC patients were enrolled in the retrospective study. Logistic regression analysis was used to determine the risk factors of LNM and DM. Risk factors were applied to construct the nomograms of LNM and DM. The predictive nomograms were discriminated against and evaluated by Concordance index (C-index) and calibration plots, respectively. Decision curve analysis (DCAs) was accepted to measure the clinical application of the nomogram. Cumulative incidence function (CIF) was performed further to detect the prognostic role of LNM and DM in NSCLC-specific death (NCSD). RESULTS: Eight factors (age at diagnosis, race, sex, histology, T-stage, marital status, tumor size, and grade) were significant in predicting LNM and nine factors (race, sex, histology, T-stage, N-stage, marital status, tumor size, grade, and laterality) were important in predicting DM(all, P< 0.05). The calibration curves displayed that the prediction nomograms were effective and discriminative, of which the C-index were 0.723 and 0.808. The DCAs and clinical impact curves exhibited that the prediction nomograms were clinically effective. CONCLUSIONS: The newly constructed nomograms can objectively and accurately predict LNM and DM in patients suffering from T1-2 NSCLC, which may help clinicians make individual clinical decisions before clinical management.

A Population-Based Study: How to Identify High-Risk T1-2 Esophageal Cancer Patients?

BACKGROUND: Due to individualized conditions of lymph node metastasis (LNM) and distant metastasis (DM), the following therapeutic strategy and diagnosis of T1-2 esophageal cancer (ESCA) patients are varied. A prediction model for identifying risk factors for LNM, DM, and overall survival (OS) of high-risk T1-2 ESCA patients is of great significance to clinical practice. METHODS: A total of 1,747 T1-2 ESCA patients screened from the surveillance, epidemiology, and end results (SEER) database were retrospectively analyzed for their clinical data. Univariate and multivariate logistic regression models were established to screen out risk factors for LNM and DM of T1-2 ESCA patients, while those of OS were screened out using the Cox regression analysis. The identified risk factors for LNM, DM, and OS were then subjected to the establishment of three nomograms, respectively. The accuracy of the nomograms was evaluated by depicting the calibration curve, and the predictive value and clinical utility were evaluated by depicting the clinical impact curve (CIC) and decision curve analysis (DCA), respectively. RESULTS: The age, race, tumor grade, tumor size, and T-stage were significant factors for predicting LNM of T1-2 ESCA patients (p < 0.05). The age, T-stage, tumor grade, and tumor size were significant factors for predicting DM of T1-2 ESCA patients (p < 0.05). The age, race, sex, histology, primary tumor site, tumor size, N-stage, M-stage, and surgery were significant factors for predicting OS of T1-2 ESCA patients (p < 0.05). The C-indexes of the three nomograms constructed by these factors were 0.737, 0.764, and 0.740, respectively, suggesting that they were clinically effective. CONCLUSIONS: The newly constructed nomograms can objectively and accurately predict the LNM, DM, and OS of T1-2 ESCA patients, which contribute to the individualized decision making before clinical management.

[Effect of different nutritional routes on the intestinal mucus barrier in scalded rats].

OBJECTIVE: To observe the effect of different nutritional routes of giving nutrition on the intestinal mucus barrier in severely scalded rats. METHODS: Wistar rats inflicted with 30% TBSA III degree scalding on the back were employed as the model and were randomly divided into 3 groups, i.e. control (C), parenteral nutrition (PN) and enteral nutrition (EN) groups. The rats in PN and EN groups were supplied with equal amount of nitrogen and calories and with equal volume of nutrition solution. The dynamic changes in the thickness of intestinal mucus layer and the contents of protein, hexose and acetylneuraminate in the mucus were examined. RESULTS: When compared with those in C group, the intestinal mucus layer became thinner and the contents of protein, hexose and acetylneuraminate in the mucus in both PN and EN groups decreased evidently after scalding. When compared between two nutritional groups, the thickness of intestinal mucus layer and the contents of the hexose and acetylneuraminate in the mucus in EN were much thicker and higher than those in PN group, while the mucus protein content exhibited no obvious difference between PN and EN groups. CONCLUSION: It was suggested that intestinal goblet cell synthesized and secreted less mucus after scalding in rats resulting in thinning of intestinal mucus layer and the change in mucus components. When compared with those in PN group, less injury to the intestinal goblet cells occurred and the intestinal mucus synthesis was less affected in EN group, and the components of intestinal mucus were maintained stable.