Five meroterpenoids, rhodonoids K-M (1-2), daurichromene E (3), and grifolins A-B (4-5), together with seven known compounds (6-12), were isolated from Rhododendron anthopogonoides. The chemical structures of these compounds were elucidated through comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ultraviolet (UV), infrared spectroscopy (IR), and nuclear magnetic resonance (NMR) data. Their absolute configurations were determined by comparing experimental electronic circular dichroism (ECD) spectra with computed values. Notably, compounds 1 and 3 demonstrated significant inhibitory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. These compounds markedly suppressed the mRNA expressions of inflammatory factors, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) while also down-regulating the protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2).
Mice ; Rhododendron/chemistry* ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Terpenes/isolation & purification* ; Molecular Structure ; Tumor Necrosis Factor-alpha/immunology* ; Cyclooxygenase 2/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Macrophages/immunology* ; Interleukin-6/immunology* ; Lipopolysaccharides ; Interleukin-1beta/immunology*

Objective:To analyze and identify the expression profiles of oxidative stress-related genes and circular RNAs(circRNAs)in ricin toxin(RT)-induced pyroptosis of mouse mononuclear macrophages(RAW264.7)using transcriptome sequencing and bioinformatics technology,and to preliminarily analyze their potential functions.Methods:The macrophages(RAW264.7 cells)were treated with RT to establish a cell pyroptosis model and divided into control group,40 μg·L-1 RT group,and 80 ng/mL RT group.Transmission electron microscope(TEM)was used to observe the morphology of the RAW264.7 cells in various groups;Western blotting method was used to detect the expression levels of the pyroptosis pathway-related proteins in the cells in various groups;80 μg·L-1 RT was selected for subsequent experiments.Transcriptome sequencing(RNA-Seq)was performed to obtain the circRNA and mRNA expression profiles in the RAW264.7 cells in control group and RT-treated group,followed by bioinformatics analysis.Results:Compared with control group,the cells in 40 and 80 μg·L-1 RT groups underwent morphological changes;the cells in RT groups showed obvious pyroptosis-like morphological changes,characterized by significant swelling of dying cells and the appearance of characteristic large bubbles on the plasma membrane.Compared with control group,the expression level of gasdermin DN-terminal fragment(GSDMD-N)protein in 40 and 80 μg·L-1 RT groups was increased(P<0.05);compared with 40 μg·L-1 RT group,the expression level of GSDMD-N protein in the cells in 80 μg·L-1 RT group was increased(P<0.05);therefore,the subsequent experiments used the RT concentration of 80 μg·L-1.A total of 2930 differentially expressed messenger RNAs(mRNAs)and 24 differentially expressed circRNAs were identified.The constructed circRNA-microRNA(miRNA)-mRNA competing endogenous RNA(ceRNA)regulatory network consisted of 7 circRNAs,12 miRNAs and 13 mRNAs.Gene Ontology(GO)functional enrichment analysis showed that in biological process(BP),the functions regulated by differentially expressed genes mainly included immune response and oxidative stress response;in cellular component(CC),differentially expressed genes were mainly localized to the external side of plasma membrane and cell leading edge;in molecular function(MF),they were mainly involved in transporter transmembrane activity and hormone receptor binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis showed that differentially expressed genes were mainly enriched in Toll-like receptor signaling pathway,Forkhead box O(FoxO)signaling pathway and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway.In the protein-protein interaction(PPI)network,the top 10 hub genes with the highest connectivity were screened by CytoHubba,including matrix metalloproteinase 9(MMP9),superoxide dismutase 2(SOD2),and v-src sarcoma viral oncogene homolog(Src).Conclusion:The expression profiles of oxidative stress-related genes and circRNAs in RAW264.7 cells are altered after RT treatment.The screened differentially expressed circRNAs and mRNAs may serve as potential targets to regulate RT-induced pyroptosis in RAW264.7 cells through oxidative stress pathways.

Objective To conduct a bibliometric and visual analysis of global literature on cardi-ovascular immune-related adverse events(irAEs)induced by immune checkpoint inhibitors(ICIs)in cancer treatment,and to explore the research status,hotspots,and future trends in this field.Meth-ods The Web of Science Core Collection(WOSCC)database was utilized to retrieve and screen rel-evant literature.CiteSpace software was employed for visual analysis of countries,institutions,au-thors,and keywords.Results A total of 1,350 articles were retrieved,with an annual increase in publication volume.The United States dominated in terms of national,institutional,and author contri-butions,while European countries and institutions demonstrated close collaborative networks.Keyword analysis and cited reference mapping revealed an evolution of research hotspots:from initial mechanistic investigations to monoclonal antibody applications,and subsequently to safety concerns.Current lre-search focuses on ICI monoconal antibody combination therapy for malignancies and cardiovascular irAEs,particularly fatal myocarditis,which has emerged as a prominent topic.Conclusion ICIs mon-oclonal antibody therapies and their associated cardiovascular irAEs,especially combination therapies and life-threatening myocarditis,represent key research frontiers.Investigations into drug combination strategies and fatal myocarditis may guide future research directions.

Objective:To compare the therapeutic efficacy of laparoscopic versus open hepatectomy based on three-dimensional image reconstruction in the treatment of hepatocellular carcinoma (HCC) in the central region of liver.Methods:Clinical data of 118 patients with HCC located in the central region of liver undergoing hepatectomy in the People's Hospital of Zhengzhou University from January 2020 to December 2023 were retrospectively analyzed, including 85 males and 33 females, aged (57.5±8.9) years old. According to surgical approach, patients were divided into two groups: the open surgery group ( n=66) and laparoscopic surgery group ( n=52). All patients underwent three-dimensional image reconstruction preoperatively to determine the tumor location and its relationship with the hepatic vessels. The operative duration, intraoperative blood loss, incidence of postoperative complications, postoperative hospital stay, and prognosis were compared between the groups. Results:Compared to open surgery, patients in laparoscopic group were younger [(55±9) years old vs. (59±8) years old], and experienced a longer operative time [212.5 (152.5, 262.3) min vs. 161.5 (135.8, 210.0) min] and a shorter postoperative hospital stay [11.0(9.0, 13.0) d vs. 13.0(11.0, 15.3) d] (all P<0.05). Postoperative pathology indicated that R0 resection was achieved in both groups. The incidence of postoperative complications were comparable between the two groups [34.6% (18/52) vs. 39.4% (26/66), χ2=0.28, P=0.594]. The 1-year and 3-year recurrence-free survivals were 69.7% and 53.0% in laparoscopic group, similar to those in open group (71.2% and 53.8%, respetctively, P=0.953). Conclusion:Laparoscopic hepatectomy based on three-dimensional image reconstruction is safe and feasible for HCC in central region in terms of clinical prognosis. Laparoscopic surgery is also associated with a shorter postoperative hospital stay.

Objective:To discuss the damage effect of vesicular stomatitis virus(VSV)on the vascular endothelial(VE)barrier,and to clarify its mechanism.Methods:The canine kidney cells were used to amplify VSV.The half tissue culture infective dose(TCID50)of VSV was determined using mouse brain endothelial tumor bEnd.3 cells,and subsequent experiment was conducted using 300 times the TCID50.The bEnd.3 cells were divided into infection 0 h group,infection 4 h group,infection 8 h group,and infection 12 h group for VE barrier damage experiments due to VSV infection.The bEnd.3 cells were also divided into control group,infection group,and correction group for experiments to inhibit the VSV replication and restore the VE barrier.The bEnd.3 cells were inoculated into Transwell chambers to construct an in vitro VE barrier model.Cell voltage resistance meter was used to detect the transepithelial resistance(TER)in various groups after the bEnd.3 cells were infected with VSV at different time points;fluorescein isothiocyanate-dextran leakage assay was used to detect the permeability coefficients of the cells in various groups;immunofluorescence staining was used to observe the localization changes of VE-cadherin,β-catenin,and phosphorylated β-catenin(p-β-catenin)in cytoskeleton and adherens junctions(AJs)of the bEnd.3 cells after VSV infection;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Wnt and β-catenin mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Wnt,β-catenin,and p-β-catenin proteins in the cells in various groups.Results:The TCID50 of VSV was 10-4.5·100 μL-1.TheTranswell chamber experiment results showed that compared with infection 0 h group,the TERs in the cells in the other groups were significantly decreased(P＜0.05),and the permeability coefficients were significantly increased(P＜0.05).The immunofluorescence staining results showed that compared with control group,the cytoskeleton of the bEnd.3 cells in infection group was disordered,the cell gaps was increased,the linear index of AJs was significantly decreased(P＜0.05),and β-catenin and p-β-catenin translocated from the cell membrane to the perinuclear area.The RT-qPCR results showed that compared with infection 0 h group,the expression levels of Wnt mRNA in the cells in the other groups were significantly decreased(P＜0.05),while the expression levels of β-catenin mRNA showed no statistically significant difference(P＞0.05).The Western blotting results showed that compared with infection 0 h group,the expression levels of Wnt protein in the cells in the other groups were significantly decreased(P＜0.05),the expression levels of β-catenin showed no statistically significant differences(P＞0.05),and the expression levels of p-β-catenin were significantly increased(P＜0.05).After inhibiting the VSV replication and correcting the low density lipoprotein receptor(LDLR)abnormalities,the Transwell chamber experiment results showed that compared with infection group,the TER in the cells in correction group was significantly increased(P＜0.05),and the permeability coefficient was significantly decreased(P＜0.05).The immunofluorescence staining results showed that compared with infection group,the gaps in the cells in correction group were reduced,and the perinuclear aggregation of β-catenin and p-β-catenin in the cells was restrained.The RT-qPCR results showed that compared with infection group,the expression level of Wnt mRNA in the cells in correction group was significantly increased(P＜0.05).The Western blotting results showed that compared with infection group,the expression level of Wnt protein in the cells in correction group was significantly increased(P＜0.05),the expression level of β-catenin showed no statistically significant difference(P＞0.05),and the expression level of p-P-catenin was significantly decreased(P＜0.05).Conclusion:VSV infection can cause the LDLR inactivation,reduce the expression level of Wnt protein,increase the phosphorylation level of β-catenin and cause its internalization,disrupt the stability of AJs,and ultimately lead to VE barrier damage.

Epilepsy is a chronic brain disease characterized by seizures， and is one of the most common nervous system diseases in clinic practice with the recurrent， transient， and refractory characteristics. Clinically， western medicine therapy is mainly adopted in the treatment of epilepsy， but it is not conducive to long-term use for patients on account of severe side effects， which can result in abnormalities in the digestive system， central nervous system， hematopoietic system， urinary system， and liver function to varying degrees. Syndrome differentiation is usually used for the treatment of epilepsy by traditional Chinese medicine （TCM）， which can avoid the side effects of western medicine treatment on the basis of improving patients' syndromes. The literature on TCM in the treatment of epilepsy in China and abroad indicates that the syndrome differentiation in TCM is often based on phlegm， blood stasis， wind， and deficiency， and the treatment methods include acupuncture， acupoint catgut embedding， moxibustion， Chinese medicine monomer， drug pair， and compound decoction. The various treatments of TCM play an important role in the comprehensive treatment of epilepsy through multiple channels and links， such as reducing the degree and number of seizures. This paper comprehensively summarized the clinical experience of TCM in the treatment of epilepsy， systematically expounded various treatment methods and ideas of TCM in the treatment of epilepsy， and deeply discussed the mechanism of TCM in the treatment of epilepsy， aiming to provide a theoretical basis for the clinical formulation of a reasonable individualized treatment plan for epilepsy and diversified ideas for the more effective treatment of epilepsy by TCM.

Worldwide, gastric cancer is the second leading cause of cancer deaths and the fifth most common malignant tumor. Gastric cancer is believed to be caused by a variety of factors, such as genetics, epigenetics, and environmental influences. Among the pathogenic factors, inflammation has been considered as one of the main risk factors for gastric cancer. There are currently limited ways to prevent gastric cancer. Although the combined application of aspirin and non-steroidal anti-inflammatory drugs can reduce the risk, it has great side effects and can easily cause gastric perforation or gastric bleeding. Therefore, an alternative plan is urgently needed. Curcumin is the yellow pigment in the rhizome of the plant turmeric. Current studies have found that curcumin has a protective effect on gastric mucosal damage caused by non-steroidal anti-inflammatory drugs, gastric mucosal damage in rats, and gastric mucosal damage caused by stress bleeding and Helicobacter pylori infection. Curcumin shows significant anti-inflammatory and anti-cancer activities by regulating DNA methylation, histone modification, nuclear factor erythrocyte 2 related factor 2 and other related signal pathways. In this article, the latest evidence of curcumin for epigenetic changes in gastric cancer and its potential contribution to gastric cancer were discussed.

Objective: To analyze epidemiological characteristics of campus bullying among primary and middle school students in central China to explore its relation with mental health problems, and to provide a reference for the campus bullying prevention. Methods: Stratified cluster sampling method was used to select primary and middle school 10 581 students from Anyang, Nanyang and Xinxiang cities of Henan Province, Middle School Students Mental Health Scale and the Self designed Scale of Adolescent Bullying Behavior were used to analyze the relationship between mental health problems with campus bullying behavior. Results: The total report rate of bullying penetrator was 12.5% among students in the three cities. Among primary and middle school students with mental health problems such as hostility, interpersonal stress, academic pressure and emotional imbalance, the detection rate of bullying behavior was 24.2%, 20.3%, 19.4% and 20.1%, respectively. The results of multivariate analysis showed that hostility symptoms ( OR =3.78, 95% CI =1.71-8.32), interpersonal stress ( OR =3.50, 95% CI = 1.62 -7.57), academic pressure ( OR = 1.62 , 95% CI =1.21-2.16) and emotional imbalance ( OR =2.80, 95% CI =1.41-5.56) showed a significant impact on campus bullying ( P <0.05). Conclusion Mental health problems of primary and middle school students are closely related to the occurrence of bullying behavior. It is necessary to pay attention to the mental health education of bullies and intervene bullying behaviors from the source.

Objective: To explore the associations between parental marital status with bullying and self injurious behavior among primary and secondary school students, and to provide intervention support for the prevention of self injurious behavior of primary and secondary school students. Methods: A total of 11 107 primary and secondary school students in Nanyang, Anyang and Xinxiang city from central China were selected using multistage clustering sampling method. A questionnaire survey regarding bullying was administered. Results: Report rate of bullying in boys (18.1%) was higher than that in girls (9.8%), while report rate of self injurious behavior in girls (3.9%) was higher than that in boys(3.2%)( χ 2=155.56, 4.64, P <0.05). The severity of bullying ( r =0.44) and types of bullying ( r =0.42) were positively correlated with self injurious behaviors( P <0.01), while parental marital status was negatively correlated with self injurious behavior( r=-0.11, P <0.01). Parental marital status negatively moderated the relationship between severity of bullying( β =-0.01), types ( β =-0.05) with self injurious behavior( P <0.01). Conclusion Parental marital status plays a moderating role in the association between bullying and self injurious behavior among primary and middle school students.The lower parental marital status, the higher rate of self injurious behavior among bullied children. Comparison of bullied rates among primary and secondary school students with different characteristics.

Objective:To investigate the value of tumor budding in the clinicopathology and prognosis of pancreatic neuroendocrine tumors.Methods:The Cliniccal data of 105 pancreatic neuroendocrine tumor patients underwent resection in Henan Provincial People's Hospital from Jan 2010 to Dec 2016 were retrospectively analyzed. Tumor budding was calculated through hematoxylin-eosin (HE) and immunohistochemical stained slides. Based on the receiver operating characteristic curve (ROC), the number of tumor budding ≥10 was defined as the high-grade budding group, and <10 as the low-grade budding group. Multiple analysis was performed to determine the relationship between tumor budding and clinicopathology as well as prognosis.Results:High-grade budding group was observed in 35 cases and low-grade group in 70. High-grade budding were more common in tumors with advanced T stage, high risk of lymphatic metastasis, preoperative liver metastasis, vascular invasion and postoperative recurrence (respectively χ 2=9.043, 4.286, 10.130, 12.090, 9.260, all P<0.05). Multivariate COX regression analysis showed that tumor budding ( P=0.018), tumor grade ( P=0.026), preoperative liver metastasis ( P=0.042), vascular invasion( P=0.048) was independent risk factors predicting poor prognosis. Conclusion:Tumor budding is highly correlated with clinicopathological parameters which reflect the aggressiveness of pancreatic neuroendocrine tumor, it is also an important prognostic factor.