OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

Objective To investigate the relationship between nuclear factor(NF)-κB signaling pathway and gender differences in alcoholic liver fibrosis. Methods C57BL/6 N mice at 7-8 weeks of age were randomly divided into: male normal group, male model group, female normal group and female model group of 20 mice each. The normal group was fed with control liquid diet for 8 weeks, and the model group was fed with alcoholic liquid diet for 8 weeks combined with 31.5% ethanol gavage (5g/kg twice a week) to establish an alcoholic liver fibrosis model. The mice were executed at the end of 8 weekends, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, estradiol (E

Cardiovascular diseases(CVDs)are a leading factor driving mortality worldwide.Iron,an essential trace mineral,is important in numerous biological processes,and its role in CVDs has raised broad discussion for decades.Iron-mediated cell death,namely ferroptosis,has attracted much attention due to its critical role in cardiomyocyte damage and CVDs.Furthermore,ferritinophagy is the upstream mechanism that induces ferroptosis,and is closely related to CVDs.This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy,and the regulatory pathways and molecular targets involved in ferritinophagy,and to determine their roles in CVDs.Furthermore,we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs.Collectively,this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

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.

Objective To investigate the effect of osimertinib combined with aspirin on the survival pe-riod of the advanced lung adenocarcinoma patients with epidermal growth factor receptor(EGFR)mutation.Methods Sixty lung adenocarcinoma patients with EGFR mutation in advanced non-small cell lung cancer(NSCLC)first diagnosed in Banan District Second People's Hospital of from August 2020 to October 2021 were selected as the study subjects and divided into the observation group and control group by the random number table method,30 cases in each group.The observation group adopted osimertinib combined with aspi-rin,and the control used osimertinib merely.The overall response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS)and the adverse reactions occurrence were compared between the two groups.Results ORR and DCR after 3,6,12 months medication in the observation group were higher than those in the control group,but the differences were not statistically significant(P＞0.05).Compared with the control group,PFS and OS in the observation group were longer,and the differences were statistically significant[14.9(11.8,17.2)m vs.10.5(8.9,12.5)m;24.1(19.5,27.4)m vs.18.1(16.1,21.1)m,P＜0.05].In addition,PFS and OS in male and female patients with brain metastasis,EGER19 and 21 ex-on mutation in the observation group were longer than those in the control group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in overall and≥Ⅲ degree adverse reactions between the two groups(P＞0.05).Conclusion Osimertinib combined with aspirin could prolong PFS and OS of the advanced lung adenocarcinoma patients with EGFR mutation without increasing the risk of adverse reactions.

Objective To explore the value of serum microRNAs-145(miR-145)and P53 antibody detection in the evaluation of therapeutic effect and prognosis in the treatment of breast cancer with Long Bei Xiaoyao Powder.Methods Ninety cases of breast cancer patients admitted to Beijing Aerospace General Hospital from January 2020 to January 2021 were selected as the study subjects.The patients were randomly divided into an observation group and a control group by random number table method,with 45 cases in each group.All of the patients in the two groups received individualized comprehensive treatment,and additionally the observation group was treated with Long Bei Xiaoyao Powder.The course of treatment covered three months.Real-time fluorescence quantitative polymerase chain reaction(PCR)method was used to detect serum miR-145 expression level,and enzyme-linked immunosorbent assay(ELISA)was used to detect serum P53 antibody expression level.The differences in the pre-and post-treatment expression levels of serum miR-145 and P53 antibodies in the two groups were compared,the relationship between the serum miR-145 and P53 antibody expression level and the poor prognosis of the patients in the observation group was explored by logistic regression analysis,and receiver operating characteristic curve(ROC)was drawn to analyze the value of the serum miR-145 and P53 antibody detection in the prediction of poor prognosis in the observation group.Results(1)After treatment,the detection value of serum miR-145 in the two groups of patients showed an increasing trend(P＜0.05),while that of the P53 antibody showed a decreasing trend(P＜0.05).The intergroup comparison showed that the detection value of serum miR-145 in the observation group was significantly higher than that of the control group,while the detection value of P53 antibody was significantly lower than that of the control group,the differences being all statistically significant(P＜0.05).(2)In the observation group,the detection value of serum miR-145 in the patients with good prognosis was significantly higher than that in the patients with poor prognosis,and the detection value of serum P53 antibody in the patients with good prognosis was significantly lower than that in the patients with poor prognosis,the differences being all statistically significant(P＜0.05).(3)Logistic regression analysis showed that high expression of miR-145 was a protective factor for the patients with poor prognosis in the observation group,and high expression of P53 antibody was a risk factor for the patients with poor prognosis in the observation group(P＜0.05).(4)The area under the ROC curve(AUC)for the prediction of prognosis of the patients in the observation group by the combination of serum miR-145 and P53 antibody was the largest(0.877,95%CI:0.769-0.985),and its sensitivity and specificity were 93.75%and 93.10%,respectively,with statistically significant differences(P＜0.05).Conclusion Low expression of serum miR-145 and high expression of serum P53 antibody are presented in the breast cancer patients with poor prognosis,and Long Bei Xiaoyao Powder exerts satisfactory therapeutic effect in treating breast cancer,which is conducive to enhancing the expression level of serum miR-145 and reducing the expression level of serum P53 antibody.

Objective To observe the application effect of family-centered diversified extended services in treating retinopathy (ROP) of premature infants. Methods A total of 100 premature infants with ROP were selected and randomly divided into control group and observation group, with 50 cases in each group. The control group received routine nursing services, while the observation group received family-centered diversified extended services. The compliance of parents of infants, ocular parameters of infants, the 20-item Measure of Processes of Care (MPOC-20) score by parents and the Chinese version of Parenting Sense of Competence Scale (C-PSOC) score were compared between the two groups. Results The compliance of parents in the observation group was significantly better than that in the control group (P<0.05); one month after intervention, the decrease of intraocular pressure, the anterior chamber angle at 500 μm from the scleral spur (ACA500), central anterior chamber depth (CACD), and anterior chamber angle opening distance at 500 μm from the scleral spur (AOD500) in the observation group were significantly greater than those in the control group (P<0.05); after intervention, the MPOC-20 and C-PSOC scores of parents in the observation group were significantly higher than those in the control group (P<0.05). Conclusion Family-centered diversified extended services can improve the compliance of parents in participating in treatment and their satisfaction degree with nursing services, improve ocular conditions in ROP children, enhance parents′ sense of parenting competence, and have a positive effect on the prognostic recovery of ROP patients.

Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.
Animals ; Autism Spectrum Disorder ; Macaca mulatta ; Disease Models, Animal ; Behavior, Animal ; Macaca fascicularis ; Male ; Humans