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 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.

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.

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.

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 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.

Objective To summarize the computed tomography (CT) and magnetic resonance imaging (MRI) features of IgG4-related pancreatitis.Methods The retrospective and descriptive study was conducted.The clinical data of 23 patients with IgG4-associated pancreatitis who were admitted to Sir Run Run Shaw Hospital of Zhejiang University School of Medicine from November 2012 to May 2018 were collected.There were 21 males and 2 females,aged from 45 to 83 years,with an average age of 63 years.Patients underwent upper abdominal enhanced CT and enhanced MRI examinations.Observation indicators:(1) imaging examination of the patients;(2) imaging characteristics on CT and MRI examinations;(3) follow-up.Follow-up using outpatient examination including laboratory and imaging examination was performed to detect clinical symptoms and signs once a month within 3 months postoperatively,once every 3 months within 3 months to 1 year postoperatively,once every 6 months with 1-2 years postoperatively,and once a year after 2 years postoperatively up to August 2018.Measurement data with skewed distribution were represented as M (range).Count data were described as absolute numbers.Results (1) Imaging examination of the patients:19 of 23 patients underwent upper abdominal enhanced CT combined with upper abdominal enhanced MRI scanning,3 underwent upper abdominal enhanced CT combined with upper abdominal MRI plain scanning,and 1 underwent only upper abdominal enhanced MRI scanning.(2) Imaging characteristics on CT and MRI examinations:pancreatic manifestations included 7 aspects.① Location of lesion and morphological classification:of 23 patients,17 were diffuse type,showing sausage-like appearance;4 were focal type,including 2 with mass in the pancreatic head and 2 with mass in the pancreatic body and tail;2 were multiple type,including 1 with mass in the pancreatic head,body and tail,and 1 with mass in the pancreatic body and tail.② Density of lesions on CT examination:of 23 patients,22 received CT plain scanning,including 10 with equal density and 12 with slightly low density;1 didn't receive CT plain scanning.③ Signal of lesions on MRI examination:on T1 weighted imaging,16 of 23 patients showed homogeneous slightly low signal,4 showed isointensity signal,2 showed mixed slightly low signal,and 1 showed slightly high signal.On T2 weighted imaging,21 of 23 patients showed homogeneous slightly high signal,1 showed isointensity signal,and 1 showed mixed slightly high signal.Of 23 patients,19 underwent diffuse weighted imaging (DWI) and 4 didn't undergo DWI.There were 17 patients with slightly high signal and 2 with high signal on DWI.On apparent diffusion coefficient imaging,10 patients showed slightly low signal,and 9 showed low signal intensity.④ Calcification:of 23 patients,2 had multiple calcifications including 1 of diffuse type with calcification located at pancreatic head,and 1 of focal type with calcification located at pancreatic body and tail;20 had no calcification;1 without CT plain scanning cannot be judged calcification.⑤ Enhancement pattern:23 patients showed progressive delayed enhancement of pancreatic lesions on enhancement scanning,homogeneous or heterogeneous enhancement in the arterial phase,and further enhancement in the portal venous phase and delayed phase (enhancement degree of focal type and multiple type was basically consistent with that of normal pancreas).⑥ Halo sign surrounding lesions:of 23 patients,7 had no halo sign,including 2 of diffuse type,3 of focal type,and 2 of multiple type;16 had halo sign (15 of diffuse type and 1 of focal type),including 11 with halo sign surrounding pancreatic body and tail,3 with halo sign surrounding whole pancreas,and 1 with halo sign posterior pancreatic body and tail,and 1 with halo sign anterior pancreatic head.⑦ The main pancreatic duct:14 of 23 patients had irregular stenosis of the main pancreatic duct,7 had mild dilatation of the main pancreatic duct,and 2 had no dilatation of the main pancreatic duct.Extra-pancreatic manifestations included 3 aspects.① Bile duct dilatation:10 of 23 patients had simple intra-hepatic and extra-hepatic bile duct dilatation,8 had no intrahepatic or extra-hepatic bile duct dilatation,and 5 had intra-pancreatic common duct stenosis with upstream bile duct dilatation.② Extra-pancreatic organ involvement:18 of 23 patients had extra-pancreatic organ involvement (5 with gall bladder involvement,4 with intra-hepatic and extra-hepatic bile duct and gall bladder involvement,3 with intra-hepatic and extra-hepatic bile duct involvement,1 with lung involvement,1 with spleen involvement,1 with common duct involvement,1 with kidney involvement,1 with lung and intra-hepatic and extra-hepatic bile duct involvement,1 with fibrosis of mesenteric root),and 5 had no extra-pancreatic organ involvement.③ Retroperitoneal lymph nodes:2 of 23 patients had enlarged retroperitoneal lymph nodes,21 had no enlarged retroperitoneal lymph nodes.(3) Follow-up:of 23 patients,19 were followed up for 3-74 months,with a median time of 22 months.Sixteen of 19 patients had various degrees of improvement in clinical symptoms,laboratory and imaging manifestations after standardized hormonotherapy,and 3 had no response to hormonotherapy.Conclusions CT and MRI examinations have important diagnostic value for IgG4-related pancreatitis.The pancreas mainly show diffuse swelling and halo sign surrounding lesions is a typical imaging characteristic.

Objective To investigate medication adherence and its influencing factors in community-based hypertensive patients in the Pearl River Delta of Guangdong Province, and lay the foundation for the development of targeted compliance interventions. Methods Between July 2015 and October 2016, a multi-stage cluster sampling method was used to conduct a community-based diagnostic survey in the Pearl River Delta region.A total of 1 829 community-based hypertension patients in this survey population were used to investigate medication adherence, the factors of which were derived through a multi-factor logistics regression analysis.Results The average medication-adherence score of hypertensive patients surveyed in this study was (4.6 ± 1.8), and patients with good medication adherence accounted for 62.82%(1 149/1 829).There were significant differences in medication adherence among patients according to their age, household registration types, marital status, level of education, employment status, medical payment methods,per capita monthly household income,drinking status,and family history of hypertension (P<0.05).Multivariate logistic regression analysis found that medication adherence was affected substantially by the type of household registration:local household types (OR= 0.537, 95% CI: 0.415-0.695); education level: college,bachelor and above (OR=2.139,95% CI:1.100-4.160); employment status: self-paying (OR=0.591, 95% CI: 0.376-0.930); and a family history of hypertension (OR= 1.279, 95% CI: 1.012-1.617).Conclusions It is necessary to pay more attention to medication adherence in patients with hypertension in communities.Given the influencing factors and characteristics illuminated by this study,it is suggested that various measures be taken to prevent and intervene in poor medication adherence, to improve the curative effect of hypertensive patients in communities.