OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland （HMG）. METHODS Female SD rats were divided into control group and HMG group according to body weight， with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling， two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid （calculated by crude drug） intragastrically， once a day， for 7 consecutive days. Blood samples were collected before the first administration （0 h）， and at 5， 15， 30 minutes and 1， 2， 4， 8， 12， 24 hours after the last administration， respectively. Using chlorzoxazone as the internal standard， the plasma concentrations of ferulic acid， paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve （AUC0－24 h， AUC0－∞）， mean residence time （MRT0－∞）， half-life （t1/2）， peak time （tmax）， peak concentration （cmax）] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group， the AUC0－24 h， AUC0－∞ and cmax of ferulic acid in the HMG group were significantly increased （P＜0.05）； the AUC0－24 h， AUC0－∞ ， MRT0－∞ ， t1/2 and cmax of paeoniflorin increased， but there was no significant difference between 2 groups （P＞0.05）； the AUC0－24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged （P＜0.05）. C ONCLUSIONS In HMG model rats， the exposure of ferulic acid， paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase， and the retention time of rosmarinic acid is significantly prolonged.

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

Objective To determine the scores of patients with a confirmed diagnosis of drug-induced liver injury(DILI)using Roussel Uclaf Causality Assessment Method(RUCAM),Maria&Victorino assessment scale,and Revised Electronic Causality Assessment Method(RECAM),to compare the accuracy of the three scales in diagnosis,and to investigate their clinical significance in the diagnosis of DILI.Methods A total of 98 patients with a confirmed diagnosis of DILI who were hospitalized in Peking University First Hospital from January 2011 to December 2022 were enrolled,with liver biopsy results supporting DILI and a clear history of medication.Clinical data were collected from all subjects,and the above causality assessment scales were used for scoring.The chi-square test was used to analyze the diagnostic accuracy of the causality assessment scales,and the weighted kappa coefficient was used to analyze the consistency between the three scales.Results For all patients with DILI enrolled,RECAM had the highest accuracy,with a significant difference compared with RUCAM(χ2=5.667,P=0.017).RUCAM and RECAM had moderate consistency in diagnosis(κw=0.469),while RECAM and Maria&Victorino scale had poor consistency(κw=0.156).For the patients with acute DILI,RECAM,RUCAM,and Maria&Victorino scales had a diagnostic inconsistency rate of 3.7%,11.1%,and 42.6%,respectively;for the patients with hepatocellular type DILI,the three scales of a diagnostic inconsistency rate of 8.9%,21.4%,and 62.5%,respectively;for the patients with cholestasis type or mixed type DILI,the three scales of a diagnostic inconsistency rate of 10.0%,22.5%,and 47.5%,respectively.Conclusion The use of RECAM and RUCAM scales in acute DILI can improve diagnostic rate,and for hepatocellular type DILI and DILI with the clinical manifestation of cholestasis(cholestasis type DILI and mixed type DILI),the use of RECAM and RUCAM scales can also improve diagnostic rate.The selection of causality assessment scales with a relatively high accuracy based on the course and clinical classification of the disease may help to further improve clinical diagnostic rate.

The aim of the present study was to investigate the protective mechanism of Forsythia suspensa extracts(FSE)on S.aureus-induced inflammatory injury of rat mammary epithelial cells.Fifty lactating rats were selected and randomly divided into five groups with 10 rats each:the blank control group(the fourth pair of mammary glands were injected with saline),the model group(the fourth pair of mammary glands were injected with 100 pL of S.aureus bacterial solution),the high-dose group(the fourth pair of mammary glands were injected with S.aureus bacterial solu-tion for 24 h,and then the rats were administered by gavage of 3.750 g/(kg·d)FSE for 1-7 d),the medium-dose group(24 h after the fourth pair of mammary injections,the rats were adminis-tered by gavage 1.875 g/(kg·d)FSE for 1-7 d),and in the low-dose group(24 h after the fourth pair of mammary injections,the rats were administered by gavage 0.935 g/(kg·d)FSE for 1-7 d),blood samples were collected 24 h after the last administration of the drug and then the rats were executed.The results showed that the mammary tissue of the model group was severely dam-aged,and the mRNA expression of IKKβ,MyD88,NF-κB,and TLR4 was significantly increased in the mammary tissue(P＜0.05).The relative expression of IKKβ,MyD88,NF-κB,and TLR4 pro-teins in the mammary tissue of the model group was significantly decreased(P＜0.05)by medium and high doses of FSE compared with the model group.Therefore,FSE may play an anti-inflammatory role by inhibiting the Toll-like signaling pathway to improve S.aureus-induced inflammatory re-sponse in rat mammary epithelial cells and decrease the expression of the downstream pathway proteins IKKβ,MyD88,NF-κB,and TLR4.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Aim To explore the mechanism of action of the active ingredients of Callerya nitida var.hirsutissima corresponding to the target gene in the treatment of triple-negative breast cancer(TNBC), using network pharmacology, molecular docking technology and in vitro experimental verification.Methods Based on literature research and combined with database screening, the main active components of Callerya nitida var.hirsutissima and the related targets of TNBC were obtained.Intersection genes were found to construct a protein interaction(PPI)network diagram, and core targets were screened according to the size of the correlation.A core target interaction network model of "Traditional Chinese Medicine-Ingredients-Targets-Disease" was constructed.The intersection targets were analyzed for gene GO function and KEGG pathway enrichment analysis.Finally, molecular docking and in vitro experimental verification of the selected components and the target were carried out.Results A total of 38 active components of Callerya nitida var.hirsutissima were collected, as well as 388 related potential targets, 3 919 TNBC targets, and 277 Callerya nitida var.hirsutissima therapeutic targets for TNBC.It mainly acted on multiple targets such as PIK3R1, PIK3CA, MAPK1, AKT1, SRC, etc.In in vitro experiments, it could be seen that the chloroform fraction of Callerya nitida var.hirsutissima and the monomer compounds luteolin and betulin had certain inhibitory effects on cell proliferation.All groups could inhibit the expression of VEGFA, AKT, PIK3CA, CDK1, CDK4 within the range of administration concentration.Conclusions Based on network pharmacology and molecular docking methods, this study explores the possible targets and signaling pathways of Callerya nitida var.hirsutissima in the treatment of TNBC, and conducts in vitro verification experiments to further verify the prediction of network pharmacology.

Objective: To understand the prevalence of chronic kidney disease (CKD) and related factors in adults in Anhui province based on the data of Chinese Chronic Diseases and Nutrition Surveillance program (2018) in Anhui. Methods: Multi-stage stratified cluster random sampling was used to select participants aged ≥18 years. Moreover, questionnaire survey, body measurements and laboratory tests were conducted. The complex weighting method was used to estimate the prevalence of CKD in residents with different characteristics, and complex sampling data logistic regression model was used for multivariate analysis to identify related risk factors. Results: A total of 7 181 participants were included. The overall prevalence of CKD was 11.06% in adults in Anhui, and the prevalence was 12.49% in women and 9.59% in men (P<0.05). The moderate, high and very high risk for CKD progression were 8.66%, 2.02% and 0.38%, respectively. Multivariate analysis showed that age (OR=1.03, 95%CI: 1.00-1.05), BMI (OR=1.05, 95%CI: 1.01-1.09), being woman (OR=1.38,95%CI: 1.22-1.55), hypertension (OR=2.50, 95%CI: 1.76-3.56), diabetes (OR=2.28, 95%CI: 1.51-3.43), dyslipidemia (OR=1.26, 95%CI: 1.11-1.43) and hyperuricemia (OR=2.16, 95%CI: 1.68-2.78) were risk factors for CKD. Conclusion: The prevalence of CKD in adults in Anhui was relatively high and age, gender, BMI, hypertension, diabetes, dyslipidemia and hyperuricemia were found to be associated with the prevalence of CKD. To prevent CKD and its complications, attention should be paid to the management of related risk factors, including overweight and obesity, hypertension, diabetes, dyslipidemia and hyperuricemia.
Adult ; Male ; Female ; Humans ; Adolescent ; Cross-Sectional Studies ; Prevalence ; Hyperuricemia/epidemiology* ; Renal Insufficiency, Chronic/epidemiology* ; Hypertension/epidemiology*

The Leguminosae perennial vines of Callerya and Millettia have many species and wide distribution， not only can be used for medicines， but also they have ornamental and insecticidal effects. With increasing demand for Spatholobi Caulis， and the reserves of wild medicinal materials are on the verge of exhaustion， resulting in the increasing number of mixtures and substitutes in the market， which makes it urgent to study the origin of Spatholobi Caulis. By referring to related literature， there are three major origins of Spatholobi Caulis， including Callerya， Millettia and Spatholobus. Callerya is separated from Millettia， they are divided and united for many times， now the official website of Flora of China has accepted the revision of them as two genera. This paper intends to compare the chemical components and pharmacodynamic effects of Callerya and Millettia， aiming to explore the similarities and differences between the two genera， so as to determine the rationality and necessity of separating Callerya from Millettia. After comparing， it was found that the chemical composition and pharmacodynamic effects of the two genera were different， which supported the separation of Callerya from Millettia， and it was not recommended to mix use of them.

Network pharmacology and the mouse model of viral pneumonia caused by influenza virus FM_1 were employed to explore the main active components and the mechanism of Pulsatilla chinensis against the inflammatory injury of influenza virus-induced pneumonia. The components and targets of P. chinensis were searched from TCMSP, and the targets associated with influenza virus-induced pneumonia were searched from GeneCards. The common targets between P. chinensis and influenza virus-induced pneumonia were identified with Venn diagram established in Venny 2.1. The herb-component-disease-target(H-C-D-T) network was constructed by Cytoscape 3.7.2. The above data were imported into STRING for PPI network analysis. Gene Ontology(GO) enrichment and KEGG pathway enrichment were performed with DAVID. BALB/cAnN mice were infected with the influenza virus FM_1 by nasal drip to gene-rate the mouse model of pneumonia. Immunohistochemistry was adopted to the expression profiling of inflammatory cytokines in the lung tissues of mice in the blank group, model group, and P. chinensis group 1, 3, 5, and 7 days after infection. The pathological changes of lung and trachea of mice in blank group, model group, and P. chinensis group were observed with light microscope and scanning electron microscope at all the time points. The network pharmacological analysis indicated that 9 compounds of P. chinensis were screened out, with a total of 57 targets, 22 of which were overlapped with those of influenza virus-induced pneumonia. A total of 112 GO terms(P<0.05) were enriched, including 81 terms of biological processes, 11 terms of cell components, and 20 terms of molecular functions. A total of 53 KEGG signaling pathways(P<0.05) were enriched, including TNF signaling pathway, influenza A signaling pathway, NF-κB signaling pathway, MAPK signaling pathway and other signaling pathways related to influenza/inflammation. In the P. chinensis group, the expression of TNF-α and IL-1 in the lung tissue was down-regulated on the 3 rd day after infection, and that of IL-6 in the lung tissue was down-regulated on the 5 th day after infection. Light microscopy and scanning electron microscopy showed that P. chinensis significantly alleviated the pathological damage of lung and trachea compared with the model group. This study reflects the multi-components, multi-targets, and multi-pathways of P. chinensis against influenza virus-induced pneumonia. P. chinensis may reduce the production of proinflammatory cytokines and mediators and block the pro-inflammatory signaling pathways to alleviate viral pneumonia, which provides reference for future research.
Animals ; Drugs, Chinese Herbal ; Mice ; Network Pharmacology ; Orthomyxoviridae ; Pneumonia/genetics* ; Pulsatilla