ObjectiveTo elucidate the correlation between alterations in digestion and absorption functions and hepatic deficiency states in aging rats based on the R-spondin1/Wnt3a signaling pathway， and reveal the intervention mechanism of Bugansan. MethodsForty-eight SPF-grade male SD rats were randomly assigned to six groups： blank control， model， low-， medium-， and high-dose （7.03， 14.06， 28.12 g·kg^-1， respectively） Bugansan， and vitamin E （suspension， 27 mg·kg^-1）， with 8 rats in each group. The rat model of aging was established by intraperitoneal injection of D-galactose （400 mg·kg^-1）， while the blank control group was injected with normal saline. Since the day of modeling， rats in intervention groups received corresponding agents by gavage， and those in blank control and model groups received an equal volume of normal saline （10 mL·kg^-1）. General biological features such as fur color， activity， body mass， water intake， and food intake were observed. Meanwhile， the content of malondialdehyde （MDA） and the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in the serum were measured to assess aging. Grip strength and the content of total bile acids （TBA） and the activity of α-amylase （AMY） in the serum were measured to evaluate hepatic deficiency states. The activity of β-galactosidase （β-gal） in the duodenum was measured to evaluate intestinal senescence. The levels of glucagon-like peptide-1 （GLP-1）， vasoactive intestinal peptide （VIP）， and D-xylose in the serum were determined to assess digestion and absorption functions of the small intestine. Hematoxylin-eosin staining was conducted to observe pathological changes of the duodenum to assess the small intestine damage. Immunohistochemical staining was employed to visualize the expression of B-cell-specific Moloney murine leukemia virus integration site 1 （Bmi1） and leucine-rich repeat-containing G protein-coupled receptor 5 （Lgr5） in the duodenal tissue. Moreover， Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to quantify the mRNA levels of Ki67， Bmi1， and Lgr5 to assess proliferation and regeneration of the small intestine. Additionally， the mRNA levels of R-spondin1， Wnt3a， β-catenin， and glycogen synthase kinase-3β （GSK-3β） and the protein levels of R-spondin1， Wnt3a， β-catenin， and phosphorylated GSK-3β （p-GSK-3β） in the duodenum were determined by Real-time PCR and Western blot， respectively， to analyze the mechanisms of intestinal digestion and absorption dysfunction in aging rats and the regulatory characteristics of Bugansan. ResultsCompared with blank control group， the model group showed decreases in body mass， water intake， food intake， grip strength， activities of SOD， GSH-Px， and AMY in the serum and content of GLP-1， VIP and D-xylose in the serum （P<0.05）， increases in the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）， reductions in villus length， villus width， crypt depth， and villi/crypt （V/C） value， down-regulated mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and up-regulated level of GSK-3β， phosphorylation （p）-GSK-3β （P<0.05）. Compared with the model group， Bugansan increased the body mass， water intake， food intake， grip strength， and activities of SOD， GSH-Px， and AMY and levels of GLP-1， VIP and D-xylose in the serum （P<0.05）， while decreasing the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）. Furthermore， Bugansan increased the villus length， villus width， crypt depth， and V/C value， up-regulated the mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and down-regulated the level of GSK-3β and p-GSK-3β （P<0.05）. ConclusionAging rats exhibit obvious impairments in digestion and absorption functions， accompanied by a state of hepatic deficiency. The traditional Chinese medicine approach of tonifying liver Qi effectively ameliorates aging-related changes by modulating the R-spondin1/Wnt3a signaling pathway to mitigate intestinal senescence and enhance digestion and absorption functions， ultimately contributing to the delay of aging.

Background::The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods::We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results::We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions::REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

In recent years,the number of Chest Pain Centers in China has increased rapidly.As of December 2023,there were 5 725 registered units of Chest Pain Centers nationwide,2 660 of which had passed the acceptance,and a total of 14.67 million patients with acute chest pain were treated.The Chest Pain Centers treated more than 3.18 million patients with acute chest pain in 2023,including more than 690 000 patients with acute myocardial infarction,and achieved positive results:significantly increasing the proportion of reperfusion therapy for ST-segment elevation myocardial infarction patients,ensuring the treatment of myocardial infarction patients in a short time,shortening the length of patient hospitalization,and reducing the hospitalization costs and mortality of patients.Through the construction of chest pain center,the treatment process was significantly optimized and the prognosis of patients was improved.At present,the construction and quality control of Chest Pain Centers still need to be further promoted.In some areas,the construction proportion of Chest Pain Centers and the level of diagnosis and treatment of chest pain need to be improved,patient delay is still an important challenge for the treatment of acute chest pain in China.

Objective:To explore the effectiveness of applying the ADDIE (analysis, design, develop, implement, evaluate) Model in clinical teaching for nursing interns in spine surgery department.Methods:Using a convenience sampling method, 44 nursing interns in the Department of Orthopedics at Peking Union Medical College Hospital were selected as the control group from July 2021 to May 2022, and were taught using traditional methods. From July 2022 to May 2023, 45 nursing interns were selected as the observation group, and a teaching team was formed to design a training program based on the five stages of the ADDIE instructional design model. This program was tailored to improve the overall clinical competence of the spinal surgery nursing interns. After training, the teaching effects were evaluated based on knowledge test scores, skills test scores, overall clinical competence, and teaching satisfaction.Results:After the training, the skills test scores in specialized nursing for the observation group were (94.87±1.10) points, higher than the control group's (93.98±1.41) points, with a statistically significant difference ( P<0.01). The observation group also scored higher than the control group in clinical judgment, organizational effectiveness, overall performance, and total score in the Mini-Clinical Evaluation Exercise, with statistically significant differences ( P<0.01). Additionally, the observation group reported higher satisfaction with the teaching plan and methods compared to the control group ( P<0.05) . Conclusions:Clinical teaching for spinal surgery nursing interns based on the ADDIE instructional design model can improve their specialized practical skills and overall clinical competence. The interns also expressed a high level of acceptance for this teaching design model.

AIM To study the Chemical constituents from Rhinacanthus nasutus(L.)Kurz and their in vitro antitumor and lipid-lowering activities.METHODS The ethyl acetate fraction from R.nasutus was isolated and purified by normal phase,reverse phase silica gel column and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro anti-tumor activity was determined by MTT assay,and the in vitro lipid-lowering activity was evaluated by oleic acid-induced HepG2 high-fat cell model.RESULTS Twenty compounds were isolated and identified as rhinacanthin A(1),rhinacanthin B(2),rhinacanthin C(3),rhinacanthin D(4),rhinacanthin E(5),rhinacanthin M(6),rhinacanthin N(7),rhinacanthin Q(8),rhinacanthin T(9),rhinacanthone(10),β-sitosterol(11),gallic acid(12),vanillic acid(13),syringic acid(14),lapachol(15),umbelliferone(16),sambucunlin A(17),17α,21-dihydroxy-1,4-pregnadiene-3,11,20-trione,21-acetate(18),1,8-dihydroxyanthraquinone(19),2,6-dimethoxy-1,4-benzoquinone(20).Compounds 3 and 7 inhibited the proliferation of HepG2,Hela,A549 and H22 tumor cells with IC50 values of(0.66±0.17)-(3.22±0.49)μmol/L in a time-and concentration-dependent manner.Compounds 3,7 and 9 had a lipid clearance rate of more than 50%in oleic acid-induced HepG2 high-fat cells.CONCLUSION Compounds 16-20 are isolated from this plant for the first time.Compounds 3 and 7 have good in vitro anti-tumor activities,and 3,7,9 have good in vitro lipid-lowering activities.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Objective To explore the mechanism of immediate effect regulated by acupuncture on acupoints in patients with migraine without aura(MwoA)during the interictal period.Methods A total of 28 MwoA patients were enrolled and resting-state functional magnetic resonance imaging(rs-fMRI)were performed at baseline and after acupuncture for 30 minutes.Paired t test was used to compare the differences of regional homogeneity(ReHo)and voxel-mirrored homotopic connectivity(VMHC)between two groups.Additionally,the correlation between the changes of rs-fMRI indexes and clinical scores was analyzed.Results In MwoA patients after acupuncture for 30 minutes,the mean regional homogeneity(mReHo)was decreased in the right lingual gyrus and right cere-bellum and was increased in the right middle frontal gyrus,while the z transformation voxel-mirrored homotopic connectivity(zVMHC)was significantly decreased in the bilateral cuneus compared with baseline.There was no significant correlation between imaging data and clinical scales.Conclusion Patients with MwoA after acupuncture for 30 minutes show abnormal ReHo and VMHC in multiple brain regions,which suggest that the mechanism of immediate effect may act through regulating pain-related brain regions.

Objective:To retrospectively analyze the anesthetic management characteristics of children undergoing resection of pheochromocytoma and paraganglioma (PPGL).Methods:The clinical data from patients undergoing resection of PPGL and confirmed histologically from January 1, 2010 to June 30, 2023 were retrospectively collected. The baseline characteristics, intraoperative conditions and postoperative complications were recorded.Results:The clinical data from 47 pediatric patients were analyzed. The overall incidence of hemodynamic instability events was 68% (32 cases). Lowering preoperative blood pressure to normal levels and the maximum diameter of tumor≥6 cm was helpful in reducing the incidence of the intraoperative hemodynamic instability events ( P<0.05). Postoperative hypotension developed in 7 cases, acute left heart failure in 1 case, arrhythmia in 1 case, adrenocortical insufficiency in 4 cases, and pulmonary infection in 13 cases. Conclusions:Thorough preoperative preparation, evidence-based anesthetic management, and meticulous postoperative vital sign monitoring can increase the perioperative safety for children undergoing resection of PPGL, thereby reducing the incidence of complications.

AIM:To observe the effect of acupuncture on adenosine A1 receptor(A1R)in the caudate puta-men(CPu)of complete Freund's adjuvant(CFA)rats,and to explore the potential mechanism of acupuncture in treat-ment of inflammatory pain.METHODS:Sixty-four 6～8-week-old male Wistar rats were randomly divided into saline group,model group(CFA group),CFA+manual acupuncture(MA)group,CFA+solvent dimethyl sulfoxide(DMSO)group,CFA+A1R agonist 2-chloro-N6-cyclopentyladenosine(CCPA)group,CFA+A1R antagonist 8-cyclopentyl-1,3-di-propylxanthine(DPCPX)group,CFA+MA+DMSO group and CFA+MA+DPCPX group.In MA groups,on the 2nd day af-ter modeling,the rats were needled at Zusanli points on both sides,30 min at a time,once per day,for 7 d.Pain threshold of plantar thermal radiation was used to observe the pain response of the rats.The content of cyclic adenosine monophos-phate(cAMP)in the CPu was detected by ELISA.The protein expression and phosphorylation levels of protein kinase A(PKA)and cAMP response element-binding protein(CREB)were detected by Western blot.The expression of A1R in the CPu was detected by immunofluorescence staining.RESULTS:Compared with saline group,CFA modeling signifi-cantly lowered the thermal pain threshold of the rats(P<0.01).Compared with CFA group,the thermal pain threshold of the rats in CFA+MA group and CFA+CCPA group was significantly increased(P<0.05 or P<0.01).Compared with CFA+ MA+DMSO group,the thermal pain threshold of the rats in CFA+MA+DPCPX group was decreased(P<0.05).Compared with CFA group,A1R protein relative expression level and positive cells in the CPu of the rats in CFA+MA group were in-creased(P<0.05 or P<0.01).Compared with saline group,cAMP content and p-CREB protein level in the CPu of the rats in CFA+MA group were decreased(P<0.05).Compared with CFA+DMSO group,cAMP content and p-CREB pro-tein level in CFA+MA+DMSO and CFA+CCPA groups were significantly decreased(P<0.01).Compared with CFA+MA+ DMSO group,the levels of cAMP,p-PKA and p-CREB in CFA+MA+DPCPX group were significantly increased(P<0.05 or P<0.01).CONCLUSION:Acupuncture on bilateral Zusanli can relieve inflammatory pain in CFA rats,and its mech-anism may be related to A1R/cAMP/p-CREB signaling pathway.

Objective:To explore the relationship between lipid metabolism molecules in plasma and carotid atherosclerotic plaques,traditional cardiovascular risk factors and possible dietary related factors.Methods:Firstly,among 1 312 community people from those who participated in a 10-year follow-up study of subclinical atherosclerosis cohort in Shijingshan District,Beijing,85 individuals with 2 or more carotid soft plaques or mixed plaques and 89 healthy individuals without plaques were selected according to the inclusive and the exclusive criteria(＜70 years,not having clinical cardiovascular disease and other diseases,etc.).Secondly,10 cases and 10 controls were randomly selected in the above 85 and 89 individuals respectively.Carotid plaques were detected using GE Vivid i Ultrasound Machine with 8L de-tector.Lipid metabolism molecules were detected by high performance liquid chromatography-mass spec-trometry.The detection indexes included 113 lipid metabolism molecules.Traditional cardiovascular risk factors were collected by unified standard questionnaires,and dietary related factors were collected by main dietary frequency and weight scale.The difference of lipid metabolism molecules between the case group and the control group was analyzed by Wilcoxin rank test.In the control group,the Spearman cor-relation method was used to analyze the correlation between statistically significant lipid metabolism molecules and traditional cardiovascular risk factors and dietary factors.Results:Among the 113 lipid metabolism molecules,53 lipid metabolism molecules were detected.C24∶0 sphingomyelin(SM),C22∶0/C24∶0 ceramide molecules,C18∶0 phosphoethanolamine(PE)molecules,and C18∶0/C18∶2(Cis)phosphatidylcholine(PC)were significantly higher in the carotid atherosclerotic plaque group than in the control group.The correlation analysis showed that C24∶0 SM was significantly positively correlated with low density lipoprotein cholesterol(LDL-C,r=0.636,P＜0.05),C18∶2(Cis)PC(DLPC)was sig-nificantly positively correlated with systolic pressure(r=0.733,P＜0.05),C18∶0 PE was significantly positively correlated with high sensitivity C-response protein(r=0.782,P＜0.01),C22∶0,C24∶0 ce-ramide and C18∶0 PE were negatively correlated with vegetable intake(r=-0.679,P＜0.05;r=-0.711,P＜0.05;r=-0.808,P＜0.01),C24∶0 ceramide was also negatively correlated with beans food intake(r=-0.736,P＜0.05)in the control group.Conclusion:The increase of plasma C24∶0 SM,C22∶0,C24∶0 ceramide,C18∶0PE,C18∶2(Cis)PC(DLPC),C18∶0PC(DSPC)may be new risk factors for human atherosclerotic plaques.These molecules may be related to blood lipid,blood pres-sure or inflammatory level and the intake of vegetables and soy products,but the nature of the association needs to be verified in a larger sample population.