Objective To investigate the species of sandflies and the prevalence of Leishmania infections in sandflies from selected areas of northern and northwestern China, so as to provide insights into identification of leishmaniasis vectors and assessment of epidemiological trends of leishmaniasis in China. Methods Sandfly samples were collected from Mentougou District of Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County of Karamay District of Karamay City, Gaochang District of Turpan City in Xinjiang Uygur Autonomous Region from July 2023 to July 2024. Approximately 100 intact female sandfly samples were randomly selected from each site and the species of sandflies was identified according to morphological characteristics and molecular assays. Female sandflies originating from the same habitat were grouped into pools of 10 individuals. Leishmania infection was detected using polymerase chain reaction (PCR) assay targeting the internal transcribed spacer 1 (ITS-1) gene, and the prevalence of Leishmania infection was calculated in sandflies from different sampling sites using the minimum infection rate (MIR) method. In addition, positive amplicons were sequenced and subjected to phylogenetic analysis. Results A total of 6 155 sandflies were collected from different environments at sampling sites across the six aforementioned regions from July 2023 to July 2024. Phlebotomus chinensis (96.00%) was the dominant sandfly species in Mentougou District, Beijing Municipality, with a small proportion of Ph. sergenti (4.00%), and only Ph. chinensis was found in Xiangning County, Linfen City, Shanxi Province. Ph. wui was the only sandfly species detected in Ejin Banner, Alxa League, Inner Mongolia Autonomous Region, and Payzawat County, Kashgar City, Xinjiang Uygur Autonomous Region, and Ph. caucasicus (97.70%) was the dominant sandfly species in Karamay District, Karamay City, Xinjiang Uygur Autonomous Region, with a small proportion of Ph. wui (2.30%), while Ph. alexandri was the only species in Gaochang District, Turpan City, Xinjiang Uygur Autonomous Region. A total of 40, 60, 34, 18, 18, and 22 pools of sandfly samples were tested from Mentougou District in Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, Payzawat County in Kashgar City, Karamay District in Karamay City, and Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region, respectively. L. infantum was detected in Ph. chinensis samples from Mentougou District in Beijing Municipality, and Xiangning County of Linfen City in Shanxi Province, with MIR of 0.25% to 1.00%, and L. donovani was detected in Ph. wui from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region, with MIR of 0.56% to 0.88%; however, no Leishmania infection was detected in Ph. caucasicus from Karamay District in Karamay City or Ph. alexandri from Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region. Phylogenetic analysis showed that the Leishmania ITS-1 gene sequences obtained from Mentougou District in Beijing Municipality and Xiangning County in Linfen City of Shanxi Province were clustered into the same clade with the reference sequences of L. infantum ITS-1 gene, while the Leishmania ITS-1 gene sequences obtained from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region were clustered into the same clade with the reference sequences of L. donovani ITS-1 gene. Conclusions There are variations in sandfly species in selected areas of northern and northwestern China, and variations in the species of Leishmania infecting sandflies. Improved surveillance of sandfly vectors and targeted control strategies with adaptations to geographical features and leishmaniasis vectors are recommended.

AIM To study the chemical constituents from the buds of Aralia chinensis L.var.nuda Nakai and their in vitro anti-inflammatory activities.METHODS The 70％ethanol extract from the buds of A.chinensis var.nuda was isolated and purified by silica gel,Sephadex LH-20,ODS and semi-preparative HPLC,then the structures of compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as 4-(2,2-dibutoxyethyl)phenol(1),trans-linalool-3,7-oxide-6-O-β-D-glucopyranoside(2),2'-O-(9Z,12Z,15Z-octadecatrienoyl)glyceryl β-D-galactopyranoside(3),quercetin-3-O-β-D-glucopyranoside(3'→ O-3''')quercetin-3-O-β-D-galactopyranoside(4),syringaresinol-4'-O-β-D-glucopyranoside(5),p-hydroxybenzaldehyde(6),7α-hydroxystigmasterol 3-O-β-D-glucopyranoside(7),trans-p-hydroxy cinnamic acid methyl ester(8),funingensin A(9),3,4-dihydroxy-acetophenone(10),N-acetyltyramine(11),3,4-di-O-caffeoyl quinic acid(12),chlorogenic acid(13),aralia cerebroside(14),caffeic acid methyl ester(15),tetradecanoic acid(16).The IC50values of compounds 8,10,12 and 13 were(22.19±1.59),(35.25±1.30),(13.38±0.72),(15.73±1.16)μmol/L,respectively.CONCLUSION Compound 1 is a new compound,2-13 are isolated from genus Aralia for the first time.Compounds 8,10,12,13 exhibit significant in vitro anti-inflammatory activities.

Aim To explore the mechanism of Con-grong Shujing granule(CSGs)in the treatment of Par-kinson's disease(PD)by network pharmacology,mo-lecular docking and parallel reaction monitoring(PRM)technology.Methods The active components of CSGs and the target genes of Parkinson's disease were obtained through the database.The intersection targets of drugs and diseases were selected to construct the"drug-active ingredient-target"and protein interac-tion network.The intersection target genes were impor-ted into David database for GO and KEGG enrichment analysis,and the main components were docked with key targets.27 SD rats were randomly divided into the normal group(n=9),model group(n=9)and treat-ment group(n=9).On day 1,7 and 14 of treatment,PRM analysis was used to detect the changes in the specific peptides of key target proteins in the substantia nigra of rats.Results The main components of CSGs wereTanshialdehyde,Baicalein,Quercetin and Kaempferol.The most important targets for the treat-ment of PD were TP53,AKT1,EGFR,HSP90 AA1 and STAT3.KEGG analysis mainly enriched MAPK,PI3K-Akt and neurotrophic factor signaling pathway.The molecular docking between core components and core targets showed that the binding of drugs and targets had good activity.PRM analysis of key proteins found that the target peptide expression levels of ASK1,JNK1 and JNK3 were different among groups(P＜0.05).Con-clusion CSGs can alleviate ERS,inhibit apoptosis and play a neural protective role through the ASK1-JNK pathway.

AIM To study the chemical constituents from the buds of Aralia chinensis L.var.nuda Nakai and their in vitro anti-inflammatory activities.METHODS The 70％ethanol extract from the buds of A.chinensis var.nuda was isolated and purified by silica gel,Sephadex LH-20,ODS and semi-preparative HPLC,then the structures of compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as 4-(2,2-dibutoxyethyl)phenol(1),trans-linalool-3,7-oxide-6-O-β-D-glucopyranoside(2),2'-O-(9Z,12Z,15Z-octadecatrienoyl)glyceryl β-D-galactopyranoside(3),quercetin-3-O-β-D-glucopyranoside(3'→ O-3''')quercetin-3-O-β-D-galactopyranoside(4),syringaresinol-4'-O-β-D-glucopyranoside(5),p-hydroxybenzaldehyde(6),7α-hydroxystigmasterol 3-O-β-D-glucopyranoside(7),trans-p-hydroxy cinnamic acid methyl ester(8),funingensin A(9),3,4-dihydroxy-acetophenone(10),N-acetyltyramine(11),3,4-di-O-caffeoyl quinic acid(12),chlorogenic acid(13),aralia cerebroside(14),caffeic acid methyl ester(15),tetradecanoic acid(16).The IC50values of compounds 8,10,12 and 13 were(22.19±1.59),(35.25±1.30),(13.38±0.72),(15.73±1.16)μmol/L,respectively.CONCLUSION Compound 1 is a new compound,2-13 are isolated from genus Aralia for the first time.Compounds 8,10,12,13 exhibit significant in vitro anti-inflammatory activities.

Objective To investigate the mechanism of action of circ-0058063 regulating ERK/MAPK signaling pathway on ferroptosis in esophageal cancer cells.Methods EC9706 cells were randomly divided into the Control group,the si-NC group,the si-circ-0058063 group,and the si-circ-0058063+ISO group.qRT-PCR was used to detect the expression of circ-0058063 in esophageal cancer tissues and cells;CCK-8 and clone formation assay were used to detect the cell proliferation ability.The levels of Fe2+,malondialdehyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in cells were detected.Western blot was used to detect the ERK/MAPK signaling pathway and the expression of ferroptosis-related protein in cells.Results The expression level of circ-0058063 in esophageal cancer tissue was significantly higher than that in adjacent tissues(P<0.05);the expression level of circ-0058063 in human esophageal cancer cell EC9706 was significantly higher than that in human normal esophageal epithelial cell HEEC(P<0.05).Compared with the Control group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063 group were significantly reduced(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly increased(P<0.05).Compared with the si-circ-0058063 group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063+ISO group were significantly increased(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly decreased(P<0.05).Conclusion Knockdown of circ-0058063 can inhibit the proliferation of esophageal cancer cells and induce ferroptosis,and its mechanism of action may be related to the inhibition of ERK/MAPK signaling pathway activation.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Aim To investigate the effect of Shenqi Dihuang decoction(SQDH)on henoch-schonlein pur-pura nephritis(HSPN)rats by regulating AMPK/Sirt1/Nrf2 mediated ferroptosis and the possible mech-anism.Methods Thirty SD rats were randomly divid-ed into a control group(Control),HSPN group,SQDH low-dose group(SQDH-L,5.4 g·kg-1),SQDH high-dose group(SQDH-H,21.6 g·kg-1),and SQDH high-dose+AMPK inhibitor group(SQDH-H+CC,20 mg·kg-1),with six rats in each group.Except for the control group,all other groups of rats were injected intraperitoneally with ovalbumin and complete Freund's adjuvant to establish HSPN rat models.After the successful construction of the model,each group of rats was orally administered with the cor-responding dosage or physiological saline once a day for five weeks.HE staining was used to observe the his-topathological changes in renal tissues;immunohisto-chemistry(IHC)was employed to detect the deposition of IgA and IgG in renal tissues;serum biochemical pa-rameters of renal function and urinary protein levels were measured;commercial assay kits were utilized to determine oxidative stress markers and Fe2+levels in renal tissues;Western blot analysis was performed to assess ferroptosis-related proteins and the protein ex-pression of the AMPK/Sirt1/Nrf2 signaling pathway in renal tissues.Results Compared with the control group,the HSPN group showed significant pathological damage in kidney tissue,with significantly increased scores,increased deposition of IgA and IgG in kidney tissue,decreased serum total protein(TP)and albu-min(ALB),and average increases in serum creatinine(Cre),urea nitrogen(BUN),and urinary protein levels(P＜0.05).The levels of MDA,ROS,Fe2+,and ACSL4 protein expression in the kidney tissue sig-nificantly increased,while SOD activity,SLC7A11,GPX4,p-AMPK/AMPK,Sirt1,and Nrf2 protein ex-pression significantly decreased(P＜0.05).Com-pared with the HSPN group,the pathological damage to renal tissue was reduced,IgA and IgG deposition in renal tissue decreased,TP and ALB decreased,Cre,BUN,and urinary protein levels were all reduced(P＜0.05),and the levels of MDA,ROS,Fe2+,and ACSL4 protein expression in renal tissue were signifi-cantly reduced in each dose group of SQDH rats.SOD activity,SLC7A11,GPX4,p-AMPK/AMPK,Sirt1,and Nrf2 protein expression significantly increased(P＜0.05).Compared with the SQDH-H group,the AMPK inhibitor CC could inhibit the AMPK/Sirt1/Nrf2 signaling pathway induced ferroptosis and reverse the protective effect of SQDH on renal injury in HSPN rats.Conclusions SQDH can improve renal injury in HSPN rats,and its mechanism may be related to the activation of AMPK/Sirt1/Nrf2 signaling pathway to in-hibit ferroptosis.

Non-cystic fibrosis bronchiectasis(referred to as bronchiectasis)is a common chronic airway disease.Neutrophils have traditionally been considered to play a dominant role in the airway inflammation of bronchiectasis.However,it has been discovered that approximately 20％to 30％of bronchiectasis patients exhibited elevated eosinophil counts(Sputum eosinophil ratio＞3％or blood eosinophil count＞300/μl)in their sputum and blood samples,referred to as eosinophilic bronchiectasis(EB).Based on this novel discovery of the inflammatory phenotype,some scholars have advocated treating bronchiectasis as an"inflammatory disease"rather than an"infectious disease"in a novel therapeutic approach.This article reviews the discovery and the latest research advancements of EB,exploring its pathophysiological basis,clinical characteristics,and treatment,with the aim to facilitate the understanding and management of EB.

Objective To explore the effectiveness of drawing-based method in medical courses and their impact on students' learning habits,academic performance,and comprehensive competencies,in order to meet the demand for high-quality,interdisciplinary,and innovative talent,and provide theoretical support for integrating aesthetic education into medical training.Methods A questionnaire survey was conducted among medical students(n=310)at Dalian Medical University,covering the frequency of using drawing method and their effects on learning outcomes,innovation ability,and humanistic qualities.Data were analyzed using the Chi-square test and Fisher's exact test(P＜0.05).Results Totally 93.6％of students approved of using drawing method for learning medical courses,with 70.8％having developed a habit of drawing-based learning.Students with stronger drawing skills were more inclined to use drawing method and supported their application in teaching.The frequency of drawing-based learning was positively correlated with anatomy scores(P＜0.05).Students generally agreed that drawing method enhanced knowledge comprehension,learning interest,long-term memory,innovation ability,critical thinking,and humanistic qualities.However,students with weaker drawing skills perceived drawing method as potentially increasing learning burdens and being less efficient,but this perception significantly decreased with increased drawing frequency(P＜0.05).Conclusion Drawing methods are widely used in medical courses and effectively improve learning outcomes and comprehensive competencies.Drawing proficiency and frequency are key factors influencing students' acceptance and learning effectiveness.Future efforts should focus on promoting drawing method,strengthening students' drawing skills,and optimizing learning processes to deepen the integration of aesthetic education in medical training.

Objective:To investigate the predictive value of color Doppler ultrasound combined with electrocardio-gram for right heart dys function in patients with pulmonary heart disease(PHD).Methods:A total of 100 PHD patients admitted in Dongcheng Branch of First Affiliated Hospital of Anhui Medical University between January 2020 and December 2023 were retrospectively analyzed.According to results of 6min walking test(6MWT),pa-tients were divided into good right heart function group(n=64,≥350m)and right heart dysfunction group(n=36,＜350m).The indexes of cardiac color ultrasound[isovolumic relaxation time(IVRT),isovolumetric contraction time(IVCT)and right ventricular Tei index],ECG[24h mean R-R interval standard deviation(SDNN),normal R-R interval standard deviation per 5min(SDANN)and the ratio of low frequency components to high frequency components(LF/HF)]were compared between two groups.Receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of color Doppler ultrasound,ECG and their combination for right heart dys-function in PHD patients.Spearman correlation coefficient was used to analyze the association of color Doppler ul-trasound,ECG and their combination with right heart dysfunction in PHD patients.Results:Compared with those in good right heart function group,patients in right heart dysfunction group had significant higher IVRT[(120.64±14.08)ms vs.(97.87±10.93)ms],IVCT[(84.28±12.33)ms vs.(71.92±10.61)ms]and Tei index[(0.85±0.11)vs.(0.63±0.07)](P＜0.001 all),and significant lower SDNN[(75.52±12.58)ms vs.(85.58±11.75)ms],SDANN[(63.86±10.92)ms vs.(76.75±11.71)ms]and LF/HF[(1.33±0.19)vs.(1.84±0.27)](P＜0.001 all).ROC curve indicated that the AUC of color Doppler ultrasound combined ECG in diagnosing right heart dysfunction in PHD patients was 0.911(95％CI 0.838～0.959),which was significantly higher than those of color Doppler ultrasound[0.775(95％CI 0.681～0.853),Z=2.404,P=0.016]and ECG[0.688(95％CI 0.588～0.777),Z=3.968,P=0.001]alone.Spearman correlation analysis indicated that there was a significant positive correlation of color Doppler ultrasound(r=0.547),ECG(r=0.375)and their combination(r=0.810)with right heart dysfunction in PHD patients(P＜0.001 all),and the correlation between combined detection and right heart dysfunction in PHD patients was significantly higher.Conclusion:Color Doppler ultrasound combined with ECG possesses high diagnostic performance for right heart dysfunction in PHD patients.