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

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.

AIM To explore the ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa(RP)and the possible mechanism.METHODS The RP transgenic mice(rd10)were randomly divided into the model group,the Leding group(0.15 g/kg)and the low and high dose Ziyin Mingmu Pills groups(4.50,9.00 g/kg),in contrast to the C57BL/6 mice of the normal group,with 12 mice in each group.The mice had their retinal pathological changes detected by HE staining;their visual function detected by electroretinogram(ERG);their fundus conditions and retinal thickness detected by optical coherence tomography(OCT);their retinal blood perfusion detected by laser speckle blood flow technique;their mRNA expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA detected by digital PCR;and their protein expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin detected by immunofluorescence staining.RESULTS Compared with the normal group,the model group displayed pathological changes in the fundus and retina and decreased amplitudes of ERG a wave and b wave(P＜0.01);decreased retinal thickness(P＜0.01);decreased retinal blood perfusion(P＜0.01);and decreased retinal expressions of Shh,Ptc,Smo,Gli1,N-myc,Cyclin mRNA and protein(P＜0.01).Compared with the model group,the groups intervened with Ziyin Mingmu Pills or Leding shared improved pathological changes in the fundus and retina tissue,and increased retinal thickness(P＜0.01);increased retinal blood flow(P＜0.01);increased amplitudes of ERG a wave and b wave(P＜0.01);and increased retinal Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA and protein expressions(P＜0.01).CONCLUSION Ziyin Mingmu Pills can improve the fundus pathological changes and visual function to delay RP in mice because of their efficacy in ameliorating retinal thickness and blood flow possibly by activating Shh signaling pathway.

AIM To study the chemical constituents from the branches and leaves of Toona ciliata Roem.var.pubescens(Franch.)Hand-Mazz.and their antitumor activities.METHODS The compounds were isolated and purified by silica gel,RP-18 reverse phase silica gel and semi-preparative HPLC,the structures of compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT method.RESULTS Fifteen compounds were isolated and identified as toonaolide D(1),toonaciliatin E(2),bourjotinolone A(3),(21R,23R)-epoxy-21α-ethoxy-24S,25-dihydroxyapotirucalla-7-en-3-one(4),(Z)-toonasterone C(5),(E)-toonasterone(6),3-epi-dyscusin C(7),(Z)-aglawone(8),(E)-volkendousin(9),8(14),15-isopimaradiene-2α,3α,19-triol(10),(-)-loliolide(11),cyclohexenone(12),pubinernoid A(13),quercetin-3-O-(4″-methoxy)-α-L-rahmnopyranosyl(14),5-hydroxymethyl-2-furancarboxaldehyde(15).The IC50 values of compounds 3 and 4 on K562 cells were 54.2 and 47.3 μmol/L,respectively,and the IC50 values on HEL cells were 47.3 and 61.1 μmol/L,respectively.CONCLUTION Compounds 4,7,10 and 11 are isolated from Toona genus for the first time,and compounds 2,15 are first isolated from this plant.Compounds 3 and 4 show weak antitumor activities.

This paper introduces a transfer learning approach based on regression models and demonstrates its application in the medical field through an example.Using data from the 2013-2014 U.S.National Health and Nutrition Examination Survey,the study investigates the association of sleep duration with depression levels and depressive disorder.It employs demographic characteristics and lifestyle factors as predictor variables to predict depression levels and depressive disorder across different racial groups.Compared to models built solely on target racial groups,transfer learning enhances the accuracy of estimating the effect of sleep duration in the target group and improves the prediction accuracy for depression levels and depressive disorder.The results illustrate that transfer learning effectively integrates source data to significantly improve estimation and prediction capabilities of target models,especially in situations with limited target data and heterogeneous data sources.

Objective To analyze the correlation between triglyceride glucose index (TyG) combined with different obesity indexes and new-onset ischemic stroke (IS) in 10 years in prediabetes population in Luzhou,Sichuan through cohort study. Methods A total of 2551 residents who participated in the epidemiological survey in Luzhou in 2011 and were diagnosed as having prediabetes were enrolled. According to the quartiles of baseline TyG-waist circumference (WC),TyG-waist to height ratio (WtHR),TyG-body mass index (BMI),and TyG-waist to hip ratio (WHR),they were divided into the 1st,2nd,3rd,and 4th quartiles groups (Q1,Q2,Q3,and Q4 groups). The incidence of new-onset IS in each group in 10 years was analyzed. The relationships between TyG-WC,TyG-WtHR,TyG-WHR and new-onset IS were analyzed by multivariate logistic regression. Results Among the 2551 prediabetes subjects enrolled in the study,123 died of various causes during the 10 years of non-intervention follow-up,with a mortality of 4.8％;142 had new-onset IS,with an incidence of 5.6％;and 224 had new-onset diabetes mellitus,including 22 also had new-onset IS,accounting for 9.8％. The quartile grouping analyses of TyG-WC and TyG-WtHR showed that the incidence of new-onset IS in prediabetes subjects over 10 years was Q4 group>Q3 group>Q2 group>Q1 group,with significant differences (P<0.05). The quartile grouping analysis of TyG-BMI showed that there was no significant difference in the incidence of new-onset IS (P>0.05). The quartile grouping analysis of TyG-WHR showed that the incidence of new-onset IS was Q3 group>Q4 group>Q2 group>Q1 group,with significant difference (P<0.05). Multivariate logistic regression analysis showed that TyG-WtHR was associated with new-onset IS in prediabetes subjects,either without adjusting any variable or after adjusting multiple factors. Conclusion TyG-WtHR is a risk factor of IS in prediabetes individuals. Enhancing management of prediabetes patients with high TyG-WtHR may reduce the risk of IS.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Objective To investigate the association between auditory processing and problem behaviors in preschool children,as well as the mediating role of executive function.Methods A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing,China from June to August 2021.They were evaluated using Preschool Auditory Processing Assessment Scale,Conners Parent Symptom Questionnaire,and Behavior Rating Inventory of Executive Functioning-Preschool version.Children with different demographic features were compared in the scores and the abnormality rates of auditory processing,problem behaviors,and executive function.The influencing factors of the total scores of auditory processing,problem behaviors,and executive function were evaluated using multiple linear regression analysis.Whether executive function was a mediating factor between auditory processing and executive function was examined.Results Sex and grade were the main influencing factors for the total score of auditory processing(P<0.05),and sex,grade,parental education level,and family economic status were the main influencing factors for the total scores of problem behaviors and executive function(P<0.05).The auditory processing score(rs= 0.458,P<0.05)and problem behavior score(rs=0.185,P<0.05)were significantly positively correlated with the executive function score,and the auditory processing score was significantly positively correlated with the problem behavior score(rs=0.423,P<0.05).Executive function played a partial mediating role between auditory processing and problem behaviors,and the mediating effect accounted for 33.44% of the total effect.Conclusions Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.[Chinese Journal of Contemporary Pediatrics,2024,26(2):174-180]

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.