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 design and evaluate the clinical application efficacy of a novel bilateral-separation endotracheal tube fixation device and provide references for clinical practice.Methods Using convenient sampling,60 patients from the Neurological Intensive Care Unit of a tertiary-level hospital in Zhengzhou were selected from May to December 2024.Patients were randomly divided into an experimental group(n=30)and a control group(n=30).The experimental group utilized the novel bilateral-separation endotracheal tube fixation device,while the control group employed traditional bandage fixation methods.Differences in fixation time,tube displacement,and intubation duration were compared between the 2 groups.Results The experimental group demonstrated significantly shorter tube fixation times compared to the control group(P＜0.05).However,no statistically significant differences were observed between the groups regarding intubation duration and tube displacement(P＞0.05).Conclusion The novel bilateral-separation endotracheal tube fixation device can reduce tube fixation time for patients in neurological intensive care and enhance nurse satisfaction.Despite not showing advantages in preventing tube displacement,the device still presents promising potential for broad clinical application.

Objective To define the operation scale of the biochemical test project based on the risk model,and design the statistical quality control(SQC)strategy by rationally adjusting the risk factors.Methods The σ(σ)values for the biochemistry test items were calculated based on the imprecision(CV)of internal quality control(IQC),external quality assessment(EQA)offset bias(Bias)and allowable total error(TEa)of CLIA 2019.By evaluating and adjusting the patient risk factors,designed the SQC for multiple test biochemical items representing high σ,medium σ and low σ categories.Results Clinical biochemistry testing items with different QC levels showed different σ performance,with values for P and K quality control levels 2 higher than level 1 and the remaining items all had very similar.18 projects for risk σ≥4.96:CK,LDH,GGT,AMY,AST,MG,TG,TBIL,FE,NA,UA,CREA,P,ALP,K,ALT and CA,respectively.Controlled with a QC program 13s N=2,run size was 179～1 000 samples.ALB,GLU,CL,TP and UREA need to achieve the expected operational scale by adjusting for risk factors.Conclusion The laboratory can combine program testing performance and patient safety goals,design SQC strategies for clinical biochemistry testing programs by rationally adjusting risk factors,apply as few SQC procedures for as much testing as possible,and align the laboratory workload and reporting interval with the number of patient samples.

Objective:To investigate the indications for prenatal diagnosis using copy number variation-sequencing (CNV-seq) and the abnormalities detected by the method.Methods:This retrospective analysis involved 17 994 singleton pregnant women who underwent prenatal CNV-seq at the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2022. These cases were divided into five groups based on the following indications for CNV-seq: abnormal fetal ultrasound findings, high-risk results indicated by non-invasive prenatal testing (NIPT) or Down's syndrome serological screening (Down's screening), adverse pregnancy history, and advanced maternal age. The proportions of cases with the indications for prenatal CNV-seq, the detection rates of abnormalities (numerical abnormalities of chromosomes, pathogenic/likely pathogenic CNV in structural abnormalities) in the five groups, and the distribution of these abnormalities were analyzed. Statistical analysis was performed using Chi-square test. Results:Among the 17 994 pregnant women, the women with abnormal fetal ultrasound findings, high-risk NIPT results, high-risk Down's screening results, adverse pregnancy history, and advanced maternal age accounted for 32.65% (5 875/17 994), 11.90% (2 142/17 994), 31.62% (5 690/17 994), 11.70% (2 105/17 994), and 12.13% (2 182/17 994), respectively. The detection rates of abnormalities in the five groups were 10.60% (623/5 875), 34.64% (742/2 142), 4.69% (267/5 690), 2.99% (63/2 105), and 3.67% (80/2 182), respectively. The overall detection rate of abnormalities was 9.86% (1 775/17 994). The cases with numerical abnormalities of chromosomes accounted for 68.79% (1 221/1 775), trisomy 21 was predominant (49.30%, 602/1 221). Chromosomal structural abnormalities were detected in 31.21% (554/1 775) of the cases with abnormalities, with 57.76% (320/554) harboring pathogenic CNVs and 42.24% (234/554) harboring likely pathogenic CNVs. The detection rate of chromosomal numerical abnormalities was higher than that of structural abnormalities in the abnormal fetal ultrasound group, NIPT high-risk group, and advanced maternal age group [6.81% (400/5 875) vs. 3.80% (223/5 875), χ2=53.10; 27.96% (599/2 142) vs. 6.68% (143/2 142), χ2=338.40; 2.43% (53/2 182) vs. 1.24% (27/2 182), χ2=8.61; all P<0.01]. A total of 416 microdeletions and 255 microduplications were detected in the 554 cases. The top three regions with the highest frequencies in microdeletions were Xp22.31 (12.74%, 53/416), 22q11.21 (7.93%, 33/416), and 17q12 (5.77%, 24/416); in microduplications, they were 22q11.21 (14.90%, 38/255), 17q12 (3.53%, 9/255), and 7q11.23 (3.53%, 9/255). Conclusions:Abnormal fetal ultrasound findings accounted for the highest proportion of prenatal diagnostic indications. The overall detection rate of abnormalities by CNV-seq is relatively high, especially in those with high-risk NIPT results as an indication for prenatal diagnosis. Among the chromosomal structural abnormalities detected in this study, the frequencies of Xp22.31 microdeletion and 22q11.21 microduplication are higher.

Forty adult male C57BL/6 mice were randomly divided into four groups:the control group,Salmonella typhimurium(S.typhimurium)(ST)group,phlorizin(PHZ)+S.typhimuri-um(ST)group,and PHZ(80 mg/kg)group,with 10 mice in each group.Morphological observa-tion,HE staining,ELISA,immunofluorescence and Western blot were performed,the results showed that PHZ significantly increased the cecal index,decreased the spleen index of S.typhi-murium-induced mice(P＜0.05),and reduce the pathological damage of cecum in mice.Mean-while,PHZ treatment also significantly reduced colonization of S.typhimurium in the cecum,spleen,mesenteric lymph nodes and liver(P＜0.05).The results of ELISA showed that PHZ treatment also significantly inhibited the S.ty phimurium-induced increase in the expression of IL-1β,INF-γ,TNF-a and IL-6 in the cecum of mice(P＜0.05).Immunofluorescence and Western blot results showed that PHZ significantly increased the protein expression levels of Occludin,Claudin-3,and ZO-1 in the cecal barrier of mice induced by S.typhimurium(P＜0.05).These results con-firmed that phlorizin could improve cecal inflammation and intestinal barrier damage induced by S.typhimurium in mice.

In the mid-20th century,internal mammary artery(IMA)ligation attracted attention for improving myocardial ischemia survival and relieving angina symptoms in animals,but was eliminated after sham-operation trials confirmed that its efficacy stemmed from a placebo effect.Recent advances in interventional techniques have led to the revival of distal IMA blockade,which has been shown to improve myocardial perfusion by modulating collateral circulation.Randomized controlled trials further showed that angina relief was significantly better in the blockade group than in the sham-operated group,especially in right coronary artery(RCA)and left anterior descending(LAD)lesions,but not in the ileocecal branch due to the lack of IMA collateral connections.Anatomy suggests that the internal mammary artery forms a natural collateral pathway to the RCA/LAD via the pericardial phrenic artery,which is the anatomic basis for its efficacy.Current technical limitations include incomplete occlusion,device-related complications,and insufficient evidence of long-term prognosis.Future studies are needed to optimize the design of occlusion devices,explore combined therapeutic strategies,and conduct controlled studies with conventional revascularization techniques.In this review,we systematically review the 100-year evolution of IMA occlusion,the paradigm shift from surgical ligation to precision intervention,analyze its anatomical and hemodynamic mechanisms,integrate evidence-based evidence and propose screening criteria for indications,and provide a new pathway for individualized treatment of high-risk patients who cannot tolerate coronary artery bypass grafting/percutaneous coronary intervention.

Traditional Chinese medicine(TCM)has been used for the control and prevention of infectious diseases for thousands of years.Due to its characteristics of multiple components and multiple targets,it shows promising therapeutic prospects in the field of anti-infection.Here,we provide a detailed introduction to the current application of various omics technologies,such as metabolomics,proteomics,genomics,and transcriptomics in the study of TCM's anti-infective properties.The application of omics technologies can help explore the active components and their targets in TCM that contribute to its anti-infective effects;elucidate the biosynthetic pathways of active components,aiding in the discovery of new active ingredients;and investigate the mechanisms by which TCM affects pathogenic microorganisms,as well as interpret the mechanisms of TCM's synergy with antibiotics.As more research findings are produced and validated,the role of TCM in addressing the global challenge of antimicrobial resistance will become increasingly prominent through the integration of multi-omics and multidisciplinary research methods in the future.

In the mid-20th century,internal mammary artery(IMA)ligation attracted attention for improving myocardial ischemia survival and relieving angina symptoms in animals,but was eliminated after sham-operation trials confirmed that its efficacy stemmed from a placebo effect.Recent advances in interventional techniques have led to the revival of distal IMA blockade,which has been shown to improve myocardial perfusion by modulating collateral circulation.Randomized controlled trials further showed that angina relief was significantly better in the blockade group than in the sham-operated group,especially in right coronary artery(RCA)and left anterior descending(LAD)lesions,but not in the ileocecal branch due to the lack of IMA collateral connections.Anatomy suggests that the internal mammary artery forms a natural collateral pathway to the RCA/LAD via the pericardial phrenic artery,which is the anatomic basis for its efficacy.Current technical limitations include incomplete occlusion,device-related complications,and insufficient evidence of long-term prognosis.Future studies are needed to optimize the design of occlusion devices,explore combined therapeutic strategies,and conduct controlled studies with conventional revascularization techniques.In this review,we systematically review the 100-year evolution of IMA occlusion,the paradigm shift from surgical ligation to precision intervention,analyze its anatomical and hemodynamic mechanisms,integrate evidence-based evidence and propose screening criteria for indications,and provide a new pathway for individualized treatment of high-risk patients who cannot tolerate coronary artery bypass grafting/percutaneous coronary intervention.

Traditional Chinese medicine(TCM)has been used for the control and prevention of infectious diseases for thousands of years.Due to its characteristics of multiple components and multiple targets,it shows promising therapeutic prospects in the field of anti-infection.Here,we provide a detailed introduction to the current application of various omics technologies,such as metabolomics,proteomics,genomics,and transcriptomics in the study of TCM's anti-infective properties.The application of omics technologies can help explore the active components and their targets in TCM that contribute to its anti-infective effects;elucidate the biosynthetic pathways of active components,aiding in the discovery of new active ingredients;and investigate the mechanisms by which TCM affects pathogenic microorganisms,as well as interpret the mechanisms of TCM's synergy with antibiotics.As more research findings are produced and validated,the role of TCM in addressing the global challenge of antimicrobial resistance will become increasingly prominent through the integration of multi-omics and multidisciplinary research methods in the future.

Purpose To explore the value of 5.0T MRI arterial spin labeling and morphological indexes for staging chronic kidney disease(CKD).Materials and Methods Ninety-five patients with CKD in Chongqing University Three Gorges Hospital from January to August 2024 were collected prospectively,all of whom underwent 5.0T MRI routine and arterial spin labeling examination with calculation of renal blood flow(RBF)and morphological evaluation.According to the estimated glomerular filtration rate(eGFR),the patients were categorized into early CKD group[eGFR 60-89 ml/(min?1.73 m2)]and intermediate-late CKD group[eGFR<59 ml/(min?1.73 m2)]and were further divided into stage 1-5.The differences in RBF between early and intermediate-late CKD patients were compared,and the differences in morphological indexes among different stages of CKD were also analyzed.Binary Logistic regression analysis was used to screen for independent influences on early or intermediate-late CKD staging.Receiver operating characteristic curve was used to evaluate the diagnostic efficacy of RBF values and morphological indexes for early CKD.RBF in CKD stages 1-5 were compared,with Bonferroni pairwise comparisons.The correlation between RBF values and both clinical and morphological indexes were also assessed.Results Whether in CKD stage 2 or 5,morphological factors affecting CKD staging were renal parenchymal signal,renal corticomedullary demarcation,renal volume and renal envelope(χ2=53.715,73.368,36.488,56.688,35.630,39.499,28.520,32.632,all P<0.001).In CKD stage 2,the independent influences screened by multivariate binary Logistic regression analysis were renal parenchymal signal(P<0.001)and renal corticomedullary demarcation(P=0.021).Both renal RBF values in early CKD were significantly higher than that in intermediate-late CKD(Z=-5.975,-5.885,both P<0.001).The areas under the curve for diagnosing early CKD using mean RBF of both kidneys,morphological indexes,and the combination of mean RBF with renal morphological indexes were 0.854,0.932 and 0.951,respectively.RBF values for both kidneys showed statistically significant differences among the five CKD stages(left:H=48.738;right:H=48.102,both P<0.001)and between non-adjacent stages(all P<0.05).Both kidneys RBF values showed a positive correlation with renal parenchymal signal and renal corticomedullary demarcation(left:r=0.600,0.503;right:r=0.550,0.504,both P<0.001).Conclusion The integration of arterial spin labeling and morphological assessment on 5.0T MRI enables a noninvasive and precise functional and morphological evaluation of early renal damage in CKD patients,providing a foundation for subsequent clinical CKD staging.