Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective To explore the diagnosis and treatment strategies for elderly patients with ground-glass opacity (GGO). Methods The imaging features and postoperative pathological findings of the elderly patients with pulmonary GGO receiving surgery in our hospital from 2017 to 2019 were retrospectively analyzed. The patients were divided into an elderly patient group and a non-elderly patient group based on their age. Results Finally 575 patients were included in the study. There were 281 elderly patients, including 83 males and 198 females, with an average age of (67.0±5.3) years. There were 294 non-elderly patients, including 88 males and 206 females, with an average age of (49.1±7.3) years. Compared with the non-elderly patients, elderly GGO patients showed the following distinct clinical features: long observation time for lesions (P=0.001), high proportion of rough edges of GGO (P<0.001), significant pleural signs (P＜0.001) and bronchial signs (P＜0.001), and high proportion of type Ⅱ-Ⅳ GGO (P<0.001), lobectomy type (P=0.013), and invasive lesions reported in postoperative pathology (P<0.001). There was no statistical difference in the average hospital stay between the two groups (P=0.106). Multivariate logistic regression analysis showed that GGO diameter and GGO type were the main factors affecting the operation. Observation time, GGO diameter, GGO type and pleural signs were the main influencing factors for postoperative pathological infiltrative lesions. The cut-off value of GGO diameter in predicting infiltrating lesions was 10.5 mm in the elderly patients group. Conclusion The size and type of GGO are important factors in predicting invasive lesions and selecting surgical methods. Elderly patients with radiographic manifestations of type Ⅱ-Ⅳ GGO lesions with a diameter greater than 10.5 mm should be closely followed up.

Objective To systematically evaluate the effect of threshold inspiratory muscle training on pulmonary rehabilitation in postoperative lung cancer patients,with a focus on exploring the difference in efficacy under different interven-tion modes.Methods Randomized controlled trials on the effect of threshold inspiratory muscle training on pulmonary rehabilitation in postoperative lung cancer patients were retrieved from PubMed,Cochrane Library,Embase,Web of Science,CNKI,Wanfang data,VIP and China Biomedical Literature Database.Meanwhile,gray literature from ProQuest and clinicaltrials.gov was searched as supplements.The retrieval period was from the establishment of each data-base to May 9,2025.Cochrane 5.1.0 was used to evaluate the quality of literature,and a meta-analysis was per-formed using RevMan 5.4.Results Twelve studies involving 701 patients were included,all of which were of moderate to high quality.Threshold inspiratory muscle training could reduce the pulmonary complications of postoperative lung cancer patients(OR=0.45,95%CI 0.29 to 0.68,P<0.001),shorten the hospital stay(MD=-1.85,95%CI-3.29 to-0.42,P=0.010),improve the inspiratory muscle strength(MD=5.84,95%CI 0.96 to 10.71,P=0.020),enhance their ex-ercise endurance(SMD=0.40,95%CI 0.10 to 0.71,P=0.010),and did not increase the risk of pulmonary air leakage(OR=0.88,95%CI 0.47 to 1.63,P=0.680).Subgroup analysis revealed that shortening of hospital stay(MD=-2.98,95%CI-5.87 to-0.09,P=0.040)and the improvement in exercise endurance(SMD=0.57,95%CI 0.14 to 1.00,P=0.009)were significant only when threshold inspiratory muscle training was combined with aerobic exercise.However,standalone threshold inspiratory muscle training showed no statistical signifi-cance in these two outcomes.Conclusion Threshold inspiratory muscle training can effectively reduce postoperative pulmonary complications and im-prove inspiratory muscle strength in postoperative lung cancer patients with good safety.Threshold inspiratory muscle training could shorten hospital stay and improve exercise endurance only when combining with aerobic exercise.

Objective This study aimed to examine whether body mass index(BMI)was causally associated with blood transfusion reactions.Methods A two-sample Mendelian randomization(MR)analysis using the inverse variance weighted(IVW),MR-Egger regression,weighted median method(WME),weighted model method(WM),simple model method(SM)and simple median method(SM)was performed.Public genome-wide association study(GWAS)analysis was used as the data source,with summary statistical data sets of BMI(n=126 003;GWAS ID:ebi-a-GCST90095042)as the exposure variable and summary statistical data sets of transfusion reactions(n=199 451;GWAS ID:finn-b-ST19)as the outcome variable.The causal association between BMI and transfusion reactions was analyzed.Results 42 single nucleotide polymorphisms associated with transfusion reactions were identified by MR analysis.The IVW showed evidence to support the causal relationship between BMI and transfusion reactions(OR=0.29,95%CI=0.10～0.85).Nonetheless,the effect value β of the MR-Egger regression approach contrasts with that of IVW.The outcomes of the heterogeneity analysis,pleiotropy analysis,and sensitivity analysis indicated that P>0.05.Conclusion The results of MR analysis supported the possibility of a causal relationship between BMI and blood transfusion reactions,that is,the reduction of BMI will increase the risk of blood transfusion reactions.

Aim To study the role and mechanism of ML210 in glioma.Methods The cell viability was detected by CCK8 assay.The percentage of dead cells was detected by SYTOXstaining.The role of ferroptosis-signaling pathway in gliomas was detected bygenomics.Cell proliferation was observed by EdU staining and clone formation assay.Cell migration ability was detec-ted by scratch healing assay.The apoptosis was detec-ted by flow cytometry.Cell mitochondrial function was assesses by JC-1 staining.The mechanism of action of ML210 was detected by molecular docking coupled with immunoblotting assay(Western blot).The levels of ROS,MDA were observed by ELISA.Results Compared with the control group,ML210 treatment dose-dependently decreased glioma cell viability,in-hibited cell proliferation,migration,and increased cell apoptosis and mitochondrial dysfunction,which were reversed by ferroptosis antagonists.Gene microarray screening showed that 688 genes of the ferroptosissig-naling pathway were aberrant and 10 signaling path-ways were altered in gliomas.Molecular docking re-sults showed that ML210 binding to GPX4 significantly inhibited the protein expression level of GPX4 and pro-moted the elevation of ROS and MDA levels.Conclu-sions ML210 produces anti-glioma cells via GPX4-mediated ferroptosis pathway.

AIM To study the chemical constituents from Dictamni Cortex.METHODS The 70％ethanol extract from Dictamni Cortex was isolated and purified by HP-20 macroporous resin,silica gel,MCI,ODS and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Thirty-three compounds were isolated and identified as rutin(1),apigenin(2),catechin(3),hesperetin(4),leonuriside A(5),androsin(6),2-methoxy-4-acetylphenol-O-α-rhamnopyranosyl-(1"-6')-β-glucopyranoside(7),vanillic acid(8),gallic acid(9),4-hydroxybenzoic acid(10),benzoic acid(11),involcranoside B(12),benzyl β-D-glucopyranoside(13),bphenylethyl-rutinoside(14),1-bromonaphthalene(15),cimifugin(16),9(S),12(S),13(S)-trihydroxyoctadeca-10(E),15(Z)-dienoic acid(17),methyl-9,12,13-trihydroxyoctadeca-10,15-dienoate(18),7,8-dihydroxy-9,12(Z,Z)-octadecadienoic acid(19),vernolic acid(20),9,10(erythro)-dihydroxy-11 E-octadecadienoic acid methyl ester(21),(7Z,9E,13Z)-11-hydroxyhexadeca-7,9,13-trienoic acid(22),(7Z,10Z,14E,16Z,19Z)-13-hydroxydocosa-7,10,14,16,19-pentaenoic acid(23),(9E)-8,11,12-trihydroxyoctadecenoic acid methyl ester(24),n-hexanol-O-rutinoside(25),hexyl β-sophoroside(26),3-pentyl 6'-(3-hydroxy-3-methylglutaryl)-β-D-glucopyranoside(27),3-methylbut-3-enyl-6-O-β-D-glucopyranosyl-β-D-glucopyranoside(28),3-methyl-but-2-en-1-yl β-D-glucopyranoside(29),3-methylbutan-1-ol-β-D-glucopyranoside(30),pregnenolone(31),2-butoxytetrahydrofuran(32),psydrin(33).CONCLUSION Compounds 2-4,8-13,15-16,25-28 and 32-33 are isolated from Rutaceae family for the first time.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

Objective To explore the effect of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with unilateral upper limb mirror training on contralateral limb strength in patients with hemiplegia after ischemic stroke.Methods A total of 196 patients with hemiplegia after ischemic stroke were selected.All patients were divided into study group and control group via a random number table method,with 98 patients in each group.The control group received mirror training,while the study group received low-frequency rTMS treatment in addition to the control group.The neuroelectrophysiology,neurological function,limb motor function,and clinical efficacy of all patients were observed before and after treatment,and all patients were performed the resting-state functional MRI examination.A generalized estimating equation(GEE)model were used to analyze the improvement of contralateral limb strength.Results After treatment,the seed points in the study group showed a significant enhancement in connectivity with the whole brain function.The overall efficiency of the study group was significantly better than that of the control group.After treatment,the central motor conduction time(CMCT),neuron specific enolase(NSE),cortical latency(CL),and S100β of the two groups of patients were significantly reduced compared with before treatment,while the neurotrophin-3(NT-3),nerve growth factor(NGF),Fugl-Meyer assessment upper extremities(FMA-UE),Wolf motor function test(WMFT),modified Barthel index(MBI),and Berg balance scale(BBS)scores were significantly increased.Moreover,the study group showed a more significant improvement compared to the control group(P＜0.05).The GEE model analysis results showed that the improvement of contralateral limb strength in the study group was significantly better than that in the control group.Conclusion Low-frequency rTMS combined with unilateral upper limb mirror training can improve cortical excitability and upper limb motor function in hemiplegic patients after ischemic stroke,with good therapeutic effects.

Objective:To investigate the effects of moxibustion at Tianshu(ST25)acupoint on 5-fluorouracil(5-FU)-induced intestinal mucositis(IM)and its underlying mechanisms.Methods:Eighteen C57BL/6 male mice were randomly divided into four groups:normal control(NC),IM model(IM),moxibustion 15 min(MO 15 min),and moxibustion 30 min(MO 30 min).The IM model was established via intraperitoneal injection of 5-FU.Pathological changes in colon tissues were observed using hematoxylin and eosin(HE)staining.Protein expression levels of peroxisome proliferator-activated receptor alpha(PPARα),nuclear factor kappa-B(NF-κB),phosphorylated NF-κB(p-NF-κB),NOD-like receptor thermal protein domain associated protein 3(NLRP3),caspase-1,interleukin-1β(IL-1β),and interleukin-18(IL-18)were analyzed via Western blot,ELISA,and immunohistochemistry.Results:Compared with the NC group,the IM group showed significantly shortened colon length(P＜0.05),exhibited mucosal damage,inflammatory cell infiltration,and glandular disorder,along with upregulated protein expression of p-NF-κB,NLRP3,IL-1β,IL-18,and caspase-1(P＜0.05),and downregulated PPARα expression(P＜0.05).After moxibustion intervention,the MO 15 min group demonstrated increased intestinal length(P＜0.05),reduced pathological scores(P＜0.05),significantly downregulated expression of NLRP3,p-NF-κB,IL-1β,and IL-18(P＜0.05),and elevated PPARα expression(P＜0.05),while total NF-κB protein levels remained unchanged.Conclusion:Moxibustion at Tianshu(ST25)acupoint may alleviate 5-FU-induced intestinal mucosal inflammatory responses by activating PPARα to suppress the NF-κB/NLRP3 inflammasome signaling pathway.