Objective To investigate the effects of laparoscopic sleeve gastrectomy(LSG)on the cardiac structure and function in obese patients with heart failure(HF)and compare the efficacy of LSG across obese patients with different HF types.Methods This study included 33 obese patients with HF who underwent LSG.The clinical indicators were compared between before operation and 12 months after operation.Repeated measures analysis of variance was employed to evaluate the changes in echocardiographic parameters before operation and 3,6,and 12 months after operation.Patients were allocated into a HF with preserved ejection fraction group(n=17),a HF with mildly reduced ejection fraction group(n=5)and a HF with reduced ejection fraction(HFrEF)group(n=11)based on left ventricular ejection fraction(LVEF)before operation for subgroup analyses of the effects of LSG on the cardiac structure and function of obese patients with HF.The paired samples t-test was conducted to assess the degree of cardiac structural and functional alterations after LSG.Results The 33 patients included 69.7% males,with an average age of(35.3±9.9)years,and a body mass index(BMI)of(51.2±9.8)kg/m².The median follow-up was 9.0(5.0,13.3)months.Compared with the preoperative values,the postoperative BMI(P=0.002),body surface area(BSA)(P=0.009),waist circumference(P=0.010),hip circumference(P=0.031),body fat content(P=0.007),and percentage of patients with cardiac function grades Ⅲ-IV(P<0.001)decreased.At the 12-month follow-up left atrial diameter(P=0.006),right atrial long-axis inner diameter(RAD1)(P<0.001),right atrial short-axis inner diameter(RAD2)(P<0.001),right ventricular inner diameter(P=0.002),interventricular septal thickness at end-diastolic(P=0.002),and left ventricular end-diastolic volumes(P=0.004)and left ventricular end-systolic volumes(P=0.003) all significantly reduced compared with preoperative values.Additionally,left ventricular fractional shortening and LVEF improved(both P<0.001).Subgroup analyses revealed that cardiac structural parameters significantly decreased in the HF with preserved ejection fraction,HF with mildly reduced ejection fraction,and HFrEF subgroups compared with preoperative values.Notably,the HFrEF group demonstrated the best performance in terms of left atrial diameter(P=0.003),left ventricular inner diameter at end-diastole(P=0.008),RAD1(P<0.001),RAD2(P=0.004),right ventricular inner diameter(P=0.019),left ventricular end-diastolic volume(P=0.004)and left ventricular end-systolic volume(P=0.001),cardiac output(P=0.006),tricuspid regurgitation velocity(P=0.002),and pulmonary artery systolic pressure(P=0.001) compared to preoperatively.Postoperative left ventricular fractional shortening(P<0.001,P=0.003,P<0.001)and LVEF(P<0.001,P=0.011,P=0.001)became higher in all the three subgroups than the preoperative values.Conclusions LSG decreased the body weight,BMI,and BSA,improved the cardiac function grade,reversed the enlargement of the left atrium and left ventricle,reduced the right atrium and right ventricle,and enhanced the left ventricular systolic function.It was effective across obese patients with different HF types.Particularly,LSG demonstrates the best performance in improving the structures of both atria and ventricles in obese patients with HFrEF.
Humans ; Male ; Female ; Gastrectomy/methods* ; Heart Failure/complications* ; Adult ; Obesity/physiopathology* ; Laparoscopy ; Middle Aged ; Heart/physiopathology* ; Stroke Volume

Objective To compare the application effects of plankton multiplex polymerase chain reac-tion-capillary electrophoresis(PCR-CE),SYBR Green Ⅰ real-time quantitative PCR(qPCR)and microwave digestion-vacuum filtration-automated scanning electron microscopy(MD-VF-Auto SEM)in the diagnosis of drowning.Methods Lung,liver and kidney tissues from 212 drowned corpses and 30 non-drowned corpses were examined respectively by the three drowning-related plankton testing methods,and the detection rates of plankton in each tissue by three methods were compared.Results In drowned corpses,the total detection rates of PCR-CE,qPCR,and MD-VF-Auto SEM were 93.9%,96.2%,and 95.3%,respectively,with no statistically significant difference(P>0.05).The detection rate of lung tissue by MD-VF-Auto SEM(100%)was higher than those of PCR-CE and qPCR(P<0.05),and there was no significant difference in the detection rates of the three methods in liver or kidney tissues(P>0.05).In non-drowning corpses,a small number of diatoms(less than 10 cells/10 g)were detected by MD-VF-Auto SEM method,only in liver and kidney tissues,while the other two methods yielded negative results for all tissues.Conclusion All three methods have good efficacy in the examination of drowned corpses.The MD-VF-Auto SEM method directly observes diatom morpho-logical characteristics through scanning electron microscopy,and the qualitative and quantitative analy-ses are intuitive and accurate.It has great advantages in the examination of difficult degradation samples.The PCR-CE method and qPCR method have a low sample demand(0.5 g),are easy to operate and have short detection time(4-7 h).They are easy to be applied in the grassroots depart-ments and are suitable for the rapid determination of drowned corpses in routin cases.The combina-tion of the two DNA methods with the MD-VF-Auto SEM method can increase the detection rate of plankton,ensuring the reliability of examination results.This combined use is of significant importance in the application of drowning diagnosis.

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

A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

Objective To investigate the association of spleen volume with the risk of non-alcoholic fatty liver disease(NAFLD)as well as their causal relationship.Methods We included 90 NAFLD cases and 47 healthy controls who had received contrast-enhanced computed tomography(CT)scan of the abdomen at the Second Affiliated Hospital of Xi'an Jiaotong University from November 2022 to November 2023.We conducted three-dimensional reconstruction of the spleen through a deep learning network model using a two-stage coarse-to-fine segmentation approach.We compared the two groups using the two-sample t test or Mann-Whitney U test for continuous data and using the chi-square test for categorical data;evaluated the correlation between spleen volume and liver function indicators through Pearson correlation or Spearman rank correlation analyses;determined the factors influencing the development of NAFLD through multivariable Logistic regression analysis;and further assessed the casual relationship between spleen volume and NAFLD using the inverse variance-weighted two-sample Mendelian randomization(IVW-MR)method.Results Spleen volume was significantly larger in NAFLD cases than in controls(272.93±104.16 vs 204.37±81.20 cm3,P<0.001).The Spearman rank correlation analysis showed that spleen volume was positively correlated with the hepatic steatosis index(rs=0.422,P<0.001)and gamma-glutamyl transferase levels(rs=0.211,P=0.047)in patients with NAFLD.The multivariable Logistic regression analysis indicated that spleen volume was an independent risk factor for the development of NAFLD(odds ratio[OR]=1.01,95%confidence interval[CI]:1.00-1.02,P=0.049).The IVW-MR analysis detected a causal relationship between spleen volume and NAFLD(OR=1.16,95%CI:1.05-1.28,P=0.005).Conclusion Increased spleen volume may be a risk factor for the development and progression of NAFLD.Further studies are still needed to investigate the specific mechanism.

Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

Objective:To perform RHD gene detection on a blood sample with serological weak D phenotype.Methods:A specimen received by the People's Hospital of Zhijin County was serologically identified by the microcolumn gel method and saline method.RHD gene detection was conducted by the PCR-SSP method,and the full sequence determination of the 10 exons amplified was performed.The sequencing results were compared with the ISBT database to determine the genotype.Bioinformatics tool was used to predict the functional damage of mutant proteins,and Alphafold-3 was used for tertiary structural modeling of wild-type and mutant RhD proteins,and the structures of the two proteins were compared and analyzed to explore the reasons why mutations lead to weak serological manifestations.Results:The patient's genotype was identified as RHD*DV.5/RHD*01N.01 heterozygote,with the complete deletion of RHD genes on one chromosome,unable to express the D antigen.On the other chromosome,a G＞A mutation occurred at the 697th base of the 5th exon,resulting in a partial D phenotype.This mutation causes internal hydrogen bond changes at the 233 position of RhD protein,resulting in a change in the conformation of the protein,affecting binding to the corresponding antibody.Conclusion:The patient is a heterozygous mutant individual with RHD*DV.5/RHD*01N.01,exhibiting a partial D phenotype serologically.This variation is extremely rare and has been scarcely reported globally.